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Sample records for human pineal gland

  1. Neuropeptide Y in the adult and fetal human pineal gland.

    PubMed

    Møller, Morten; Phansuwan-Pujito, Pansiri; Badiu, Corin

    2014-01-01

    Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally.

  2. The pineal gland.

    PubMed

    Paquette, H

    2000-04-01

    The pineal gland is located posterior to the midbrain and is the site of melatonin production. Research on pineal gland function in neonates is very limited. This article will discuss pineal gland development and the possible relationship between melatonin production and sudden infant death syndrome. Further research on pineal gland function is needed in order to establish its significance for the neonate.

  3. The pineal gland - Its possible roles in human reproduction

    NASA Technical Reports Server (NTRS)

    Brzezinski, Amnon; Wurtman, Richard J.

    1988-01-01

    The paper discusses the role of the pineal gland in controlling mammalian reproduction, with particular attention given to the role of melatonin in polyestrus mammals, like humans and laboratory rodents. Evidence is cited indicating the influence of melatonin production and blood content on the age of puberty, the timing of the ovulatory cycle, gonadal steriodogenesis, and patterns of reproductive behavior. It is suggested that abnormal patterns of melatonin might be associated with amenorrhea, anovulation, unexplained infertility, premature menopause, and habitual abortions.

  4. The pineal gland in human beings: relevance to pediatrics.

    PubMed

    Cavallo, A

    1993-12-01

    Several facts suggest that the pineal gland must have a significant role in human beings: the presence of melatonin secretion from infancy to old age; a circadian secretory pattern similar to that found in animal species in which this gland has well-defined functions; its responsiveness to light; and the presence of melatonin receptors in the hypothalamus. Despite the importance of the pineal gland and melatonin in the reproductive activity of all nonprimate vertebrate species studied, the relationship of melatonin secretion to the activity of the hypothalamic-pituitary-gonadal axis in human beings remains presumptive. Some data suggest a possible pineal-reproductive connection throughout the human lifespan, but new research approaches are needed for a better definition of this connection during normal development and in disorders of the reproductive axis. In addition, recent studies that have applied strictly defined techniques to unravel the masking effects of various behavioral and environmental factors suggest that the pineal gland and melatonin have a fundamental role in the regulation of the human biologic clock. Melatonin concentrations in blood or urine may become a useful marker of the circadian rhythm in disorders of rhythms. Moreover, administration of melatonin in physiologic or pharmacologic doses may have an important application in suppression of the hypothalamic-pituitary-gonadal axis as a contraceptive, and in therapy for disorders of biologic rhythms. Among the latter, of particular interest to the pediatric population will be the potential application of melatonin treatment in establishing or reestablishing circadian rhythms in infants and children maintained for long periods under artificial light conditions, as encountered in intensive care units, and in the treatment of sleep and other rhythm disorders associated with developmental delay or blindness. Further research and approval by the U.S. Food and Drug Administration will be required

  5. Association of mast cells with calcification in the human pineal gland.

    PubMed

    Maślińska, Danuta; Laure-Kamionowska, Milena; Deręgowski, Krzysztof; Maśliński, Sławomir

    2010-01-01

    Increased pineal calcifications and decreased pineal melatonin biosynthesis, both age related, support the notion of a pineal bio-organic timing mechanism. The role of calcification in the pathogenesis of pineal gland dysfunction remains unknown but the available data document that calcification is an organized, regulated process, rather than a passive aging phenomenon. The cellular biology and micro-environmental conditions required for calcification remain poorly understood but most studies have demonstrated evidence that mast cells are strongly implicated in this process. The aim of the present study was to examine the phenotype of mast cells associated with early stages and with the progressive development of calcification in the human pineal gland. The study was performed on pineal samples of 170 fetuses and children whose brains were autopsied and diagnosed during 1998-2002. The representative cerebral and pineal specimens were stained with haematoxylin and eosin or the von Kossa staining technique and for the distribution of mast cell tryptase, mast cell chymase, histamine H4 receptor and vascular network using biotinylated Ulex europaeus agglutinin. Tryptase mast cells were found in all stages of pineal gland development independently of the presence of local tissue lesions. All of them were always localized in the close vicinity of the blood vessels and expressed immunoreactivity to histamine H4 receptor antibody. Immunolocalization of mast cells by chymase antibody (and following dual immunostaining with both chymase and tryptase antibodies) demonstrated that these cells were few in number and were located in the subcapsular region of the gland. In our study, all functional mast cells that underwent activation and were co-localized with deposits of calcium did not contain chymase. All of them were stained with tryptase and represent the MC-T phenotype. Tryptase mast cells and extracellular tryptase were often associated with areas of early and more

  6. Association of mast cells with calcification in the human pineal gland.

    PubMed

    Maślińska, Danuta; Laure-Kamionowska, Milena; Deręgowski, Krzysztof; Maśliński, Sławomir

    2010-01-01

    Increased pineal calcifications and decreased pineal melatonin biosynthesis, both age related, support the notion of a pineal bio-organic timing mechanism. The role of calcification in the pathogenesis of pineal gland dysfunction remains unknown but the available data document that calcification is an organized, regulated process, rather than a passive aging phenomenon. The cellular biology and micro-environmental conditions required for calcification remain poorly understood but most studies have demonstrated evidence that mast cells are strongly implicated in this process. The aim of the present study was to examine the phenotype of mast cells associated with early stages and with the progressive development of calcification in the human pineal gland. The study was performed on pineal samples of 170 fetuses and children whose brains were autopsied and diagnosed during 1998-2002. The representative cerebral and pineal specimens were stained with haematoxylin and eosin or the von Kossa staining technique and for the distribution of mast cell tryptase, mast cell chymase, histamine H4 receptor and vascular network using biotinylated Ulex europaeus agglutinin. Tryptase mast cells were found in all stages of pineal gland development independently of the presence of local tissue lesions. All of them were always localized in the close vicinity of the blood vessels and expressed immunoreactivity to histamine H4 receptor antibody. Immunolocalization of mast cells by chymase antibody (and following dual immunostaining with both chymase and tryptase antibodies) demonstrated that these cells were few in number and were located in the subcapsular region of the gland. In our study, all functional mast cells that underwent activation and were co-localized with deposits of calcium did not contain chymase. All of them were stained with tryptase and represent the MC-T phenotype. Tryptase mast cells and extracellular tryptase were often associated with areas of early and more

  7. A survey of molecular details in the human pineal gland in the light of phylogeny, structure, function and chronobiological diseases.

    PubMed

    Stehle, Jörg H; Saade, Anastasia; Rawashdeh, Oliver; Ackermann, Katrin; Jilg, Antje; Sebestény, Tamás; Maronde, Erik

    2011-08-01

    The human pineal gland is a neuroendocrine transducer that forms an integral part of the brain. Through the nocturnally elevated synthesis and release of the neurohormone melatonin, the pineal gland encodes and disseminates information on circadian time, thus coupling the outside world to the biochemical and physiological internal demands of the body. Approaches to better understand molecular details behind the rhythmic signalling in the human pineal gland are limited but implicitly warranted, as human chronobiological dysfunctions are often associated with alterations in melatonin synthesis. Current knowledge on melatonin synthesis in the human pineal gland is based on minimally invasive analyses, and by the comparison of signalling events between different vertebrate species, with emphasis put on data acquired in sheep and other primates. Together with investigations using autoptic pineal tissue, a remnant silhouette of premortem dynamics within the hormone's biosynthesis pathway can be constructed. The detected biochemical scenario behind the generation of dynamics in melatonin synthesis positions the human pineal gland surprisingly isolated. In this neuroendocrine brain structure, protein-protein interactions and nucleo-cytoplasmic protein shuttling indicate furthermore a novel twist in the molecular dynamics in the cells of this neuroendocrine brain structure. These findings have to be seen in the light that an impaired melatonin synthesis is observed in elderly and/or demented patients, in individuals affected by Alzheimer's disease, Smith-Magenis syndrome, autism spectrum disorder and sleep phase disorders. Already, recent advances in understanding signalling dynamics in the human pineal gland have significantly helped to counteract chronobiological dysfunctions through a proper restoration of the nocturnal melatonin surge.

  8. The pineal gland from development to function.

    PubMed

    Sapède, Dora; Cau, Elise

    2013-01-01

    The pineal gland is a small neuroendocrine organ whose main and most conserved function is the nighttime secretion of melatonin. In lower vertebrates, the pineal gland is directly photosensitive. In contrast, in higher vertebrates, the direct photosensitivity of the pineal gland had been lost. Rather, the action of this gland as a relay between environmental light conditions and body functions involves reception of light information by the retina. In parallel to this sensory regression, the pineal gland (and its accessory organs) appears to have lost several functions in relation to light and temperature, which are important in lower vertebrate species. In humans, the functions of the pineal gland overlap with the functions of melatonin. They are extremely widespread and include general effects both on cell protection and on more precise functions, such as sleep and immunity. Recently, the role of melatonin has received a considerable amount of attention due to increased cancer risk in shift workers and the discovery that patients suffering from neurodegenerative diseases, autism, or depression exhibit abnormal melatonin rhythms.

  9. Dynamics in enzymatic protein complexes offer a novel principle for the regulation of melatonin synthesis in the human pineal gland.

    PubMed

    Maronde, Erik; Saade, Anastasia; Ackermann, Katrin; Goubran-Botros, Hany; Pagan, Cecile; Bux, Roman; Bourgeron, Thomas; Dehghani, Faramarz; Stehle, Jörg H

    2011-08-01

    Time of day is communicated to the body through rhythmic cues, including pineal gland melatonin synthesis, which is restricted to nighttime. Whereas in most rodents transcriptional regulation of the arylalkylamine N-acetyltransferase (Aanat) gene is essential for rhythmic melatonin synthesis, investigations into nonrodent mammalian species have shown post-transcriptional regulation to be of central importance, with molecular mechanisms still elusive. Therefore, human pineal tissues, taken from routine autopsies were allocated to four time-of-death groups (night/dawn/day/dusk) and analyzed for daytime-dependent changes in phosphorylated AANAT (p31T-AANAT) and in acetyl-serotonin-methyltransferase (ASMT) expression and activity. Protein content, intracellular localization, and colocalization of p31T-AANAT and ASMT were assessed, using immunoblotting, immunofluorescence, and immunoprecipitation techniques. Fresh sheep pineal gland preparations were used for comparative purposes. The amount of p31T-AANAT and ASMT proteins as well as their intracellular localization showed no diurnal variation in autoptic human and fresh sheep pineal glands. Moreover, in human and sheep pineal extracts, AANAT could not be dephosphorylated, which was at variance to data derived from rat pineal extracts. P31T-AANAT and ASMT were often found to colocalize in cellular rod-like structures that were also partly immunoreactive for the pinealocyte process-specific marker S-antigen (arrestin) in both, human and sheep pinealocytes. Protein-protein interaction studies with p31T-AANAT, ASMT, and S-antigen demonstrated a direct association and formation of robust complexes, involving also 14-3-3. This work provides evidence for a regulation principle for AANAT activity in the human pineal gland, which may not be based on a p31T-AANAT phosphorylation/dephosphorylation switch, as described for other mammalian species.

  10. Descartes and the pineal gland in animals: a frequent misinterpretation.

    PubMed

    Finger, S

    1995-01-01

    René Descartes presented a number of reasons for his choice of the pineal gland as a logical place for the soul to interact with the physical machinery of the body. It is often stated that one of his reasons was that he believed animals do not have pineal glands, whereas humans alone possess a soul and this small structure. This is a misinterpretation of Descartes. The philosopher knew that barnyard and other animals possess pineal glands, having seen this with his own eyes. His point was that the pineal is unique in humans only because of a special function - acting as the seat for the rational soul. PMID:11619024

  11. Descartes and the pineal gland in animals: a frequent misinterpretation.

    PubMed

    Finger, S

    1995-01-01

    René Descartes presented a number of reasons for his choice of the pineal gland as a logical place for the soul to interact with the physical machinery of the body. It is often stated that one of his reasons was that he believed animals do not have pineal glands, whereas humans alone possess a soul and this small structure. This is a misinterpretation of Descartes. The philosopher knew that barnyard and other animals possess pineal glands, having seen this with his own eyes. His point was that the pineal is unique in humans only because of a special function - acting as the seat for the rational soul.

  12. Lymphopoiesis in the chicken pineal gland

    SciTech Connect

    Cogburn, L.A.; Glick, B.

    1981-10-01

    Pineal lymphoid development was studied in two breeds of chickens from hatching until sexual maturity. No lymphocytes were found in the pineal prior to 9 days of age (da). Lymphocytes migrate through the endothelium of venules into the pineal stroma. Lymphoid tissue reached its maximal accumulation in 32-da pineal glands of both breeds. At this age, the New Hampshire (NH) breed had a larger proportion of lymphoid volume to total pineal volume (32%) than did pineal glands from White Leghorn (WL) chickens (18%).

  13. Circadian regulation of pineal gland rhythmicity.

    PubMed

    Borjigin, Jimo; Zhang, L Samantha; Calinescu, Anda-Alexandra

    2012-02-01

    The pineal gland is a neuroendocrine organ of the brain. Its main task is to synthesize and secrete melatonin, a nocturnal hormone with diverse physiological functions. This review will focus on the central and pineal mechanisms in generation of mammalian pineal rhythmicity including melatonin production. In particular, this review covers the following topics: (1) local control of serotonin and melatonin rhythms; (2) neurotransmitters involved in central control of melatonin; (3) plasticity of the neural circuit controlling melatonin production; (4) role of clock genes in melatonin formation; (5) phase control of pineal rhythmicity; (6) impact of light at night on pineal rhythms; and (7) physiological function of the pineal rhythmicity.

  14. Analysis of the human, bovine and rat 33-kDa proteins and cDNA in retina and pineal gland.

    PubMed

    Abe, T; Nakabayashi, H; Tamada, H; Takagi, T; Sakuragi, S; Yamaki, K; Shinohara, T

    1990-07-16

    A monoclonal antibody (mAb) was produced against a bovine retinal 33-kDa protein. Several clones of 33-kDa protein were isolated from each library of cDNA from human, bovine and rat retinas and rat pineal gland by mAb screening and by hybridization with cDNA probes. Each of the four cDNA sequences was determined and amino acid (aa) sequences were deduced from the nucleotide sequences. The latter were nearly identical in rat retina and rat pineal gland (99.6%) and were similar in human, bovine and rat retina (more than 87%). Each of these cDNAs had one long ORF and encoded 245 or 246 aa. The deduced aa sequences in rat retina and rat pineal gland were virtually identical and the sequences in human, bovine and rat retina were highly homologous (more than 88%). The predicted Mr for each of these proteins was 28,246 in the human, 28,176 in bovine, 28,143 in rat retina, and 28,129 in rat pineal gland. Each of the sequences has a putative site for phosphorylation by A kinase; we have confirmed that the putative site is Ser73. These results show that the 33-kDa proteins in the retina and pineal gland have the same sequences and the same phosphorylation site and suggest that the functional role of this protein is the same in the retina and pineal gland.

  15. Pineal and Pituitary Glands

    MedlinePlus

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  16. Circadian clock system in the pineal gland.

    PubMed

    Fukada, Yoshitaka; Okano, Toshiyuki

    2002-02-01

    The pineal gland is a neuroendocrine organ that functions as a central circadian oscillator in a variety of nonmammalian vertebrates. In many cases, the pineal gland retains photic input and endocrinal-output pathways both linked tightly to the oscillator. This contrasts well with the mammalian pineal gland equipped only with the output of melatonin production that is subject to neuronal regulation by central circadian oscillator located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Molecular studies on animal clock genes were performed first in Drosophila and later developed in rodents. More recently, clock genes such as Per, Cry, Clock, and Bmal have been found in a variety of vertebrate clock structures including the avian pineal gland. The profiles of the temporal change of the clock gene expression in the avian pineal gland are more similar to those in the mammalian SCN rather than to those in the mammalian pineal gland. Avian pineal gland and mammalian SCN seem to share a fundamental molecular framework of the clock oscillator composed of a transcription/translation-based autoregulatory feedback loop. The circadian time-keeping mechanism also requires several post-translational events, such as protein translocation and degradation processes, in which protein phosphorylation plays a very important role for the stable 24-h cycling of the oscillator and/or the photic-input pathway for entrainment of the clock. PMID:11890455

  17. An historical view of the pineal gland and mental disorders.

    PubMed

    López-Muñoz, F; Molina, J D; Rubio, G; Alamo, C

    2011-08-01

    Since Classical Antiquity numerous authors have linked the origin of some mental disorders to physical and functional changes in the pineal gland because of its attributed role in humans as the connection between the material and the spiritual world. The pineal organ was seen as a valve-like structure that regulated the flow of animal spirits through the ventricular system, a hypothesis that took on more vigour during the Middle Ages and the Renaissance. The framework for this theory was "the three cells of the brain", in which the pineal gland was even called the "appendix of thought". The pineal gland could also be associated with the boom, during this period, of certain legends about the "stone of folly". But the most relevant psychopathological role of this organ arrived with Descartes, who proposed that it was the seat of the human soul and controlled communications between the physical body and its surroundings, including emotions. After a period of decline during which it was considered as a mere vestigial remnant of evolution, the link between the pineal gland and psychiatric disorders was definitively highlighted in the 20th century, first with the use of glandular extracts in patients with mental deficiency, and finally with the discovery of melatonin in 1958. The physiological properties of melatonin reawakened interest in the relationship between the pineal gland and mental disorders, fundamentally the affective and sleep disorders, which culminated in the development of new pharmacological agents acting through melatonergic receptors (ramelteon and agomelatine).

  18. [Morphofunctional and molecular bases of pineal gland aging].

    PubMed

    Khavinson, V Kh; Lin'kova, N S

    2012-01-01

    The review analyzed morphology, molecular and functional aspects of pineal gland aging and methods of it correction. The pineal gland is central organ, which regulates activity of neuroimmunoendocrine, antioxidant and other organisms systems. Functional activity of pineal gland is discreased at aging, which is the reason of melatonin level changing. The molecular and morphology research demonstrated, that pineal gland hadn't strongly pronounced atrophy at aging. Long-term experience showed, that peptides extract of pineal gland epithalamin and synthetic tetrapeptide on it base epithalon restored melatonin secretion in pineal gland and had strong regulatory activity at neuroimmunoendocrine and antioxidant organism systems.

  19. Classification of the venous architecture of the pineal gland by 7T MRI.

    PubMed

    Cho, Zang-Hee; Choi, Sang-Han; Chi, Je-Gun; Kim, Young-Bo

    2011-10-01

    Magnetic resonance imaging (MRI) at 7.0 Tesla (7T) can show many details of anatomical structures with unprecedented resolution and contrast. In this report, we describe for the first time the unexpected wide variation in pineal gland structure, as visualized by MR images obtained with 7T in a group of healthy young volunteers. A total of 34 volunteers (22 men and 12 women) were enrolled in the study. Their 7T MR images revealed such wide variations in pineal gland shape that it led us to attempt to classify the patterns seen in these pineal glands. Indeed, they were successfully correlated with a previous human cadaver study of venous structures by Tamaki et al., who classified the venous structures of the pineal gland into three categories. This is the first human in vivo pineal vein imaging study using 7T MRI. Pineal venous imaging may permit the early diagnosis of a pineal tumor.

  20. [Characteristics of the pineal gland and thymus relationship in aging].

    PubMed

    Lin'kova, N S; Poliakova, V O; Kvetnoĭ, I M; Trofimov, A V; Sevost'ianova, N N

    2011-01-01

    The review presents the interference between thymus and pineal gland during their involution. The research data of thymus peptides influence on pineal gland and pineal peptides on thymus are summarized. Analysis of these data showed that pineal peptides (Epithalamin, Epitalon) had more effective geroprotective effect on thymus involution in comparison with geroprotective effect of thymic peptides (Thymalin, Thymogen) on involution of pineal gland. The key mechanisms of pineal peptides effect on thymus dystrophy is immunoendocrine cooperation, which is realized as transcription's activation of various proteins.

  1. Unique Case Report of Pineal Gland Metastasis From Bladder Carcinoma.

    PubMed

    Li, Jun; Wang, Ping; Wang, Bin

    2016-05-01

    Pineal metastasis is uncommon and most metastatic pineal lesions are asymptomatic. To our knowledge the herein reported case is the first in which the pineal gland was confirmed as the metastatic site of a bladder carcinoma.The patient reported in this case is a 59-year-old man who suffered from headache and delirium for 4 days after surgical treatment for removal of a bladder carcinoma 1 year ago. Magnetic resonance imaging (MRI) revealed a solid tumor involving the pineal gland with significant enhancement.The patient underwent surgical treatment for removal of the neoplastic lesion in the pineal gland. Histopathological examination confirmed invasion of the pineal gland by metastatic urothelial carcinoma.This case highlighted that the presence of pineal lesions in patient with known malignancy should raise suspicion of metastatic involvement.

  2. Unique Case Report of Pineal Gland Metastasis From Bladder Carcinoma

    PubMed Central

    Li, Jun; Wang, Ping; Wang, Bin

    2016-01-01

    Abstract Pineal metastasis is uncommon and most metastatic pineal lesions are asymptomatic. To our knowledge the herein reported case is the first in which the pineal gland was confirmed as the metastatic site of a bladder carcinoma. The patient reported in this case is a 59-year-old man who suffered from headache and delirium for 4 days after surgical treatment for removal of a bladder carcinoma 1 year ago. Magnetic resonance imaging (MRI) revealed a solid tumor involving the pineal gland with significant enhancement. The patient underwent surgical treatment for removal of the neoplastic lesion in the pineal gland. Histopathological examination confirmed invasion of the pineal gland by metastatic urothelial carcinoma. This case highlighted that the presence of pineal lesions in patient with known malignancy should raise suspicion of metastatic involvement. PMID:27149501

  3. Pineal Gland Lymphoma: Case Report and Literature Review.

    PubMed

    Gupta, Akshya; Johnson, Mahlon; Hussain, Ali

    2015-01-01

    A 65-year-old male presented to our institution with acute-onset headache. Imaging studies demonstrated a mass in the region of the pineal gland, with subsequent histopathology findings being consistent with large B cell lymphoma. The patient was treated with methotrexate, but ultimately did not survive. Primary central nervous system (CNS) lymphoma rarely involves the pineal gland, but should be considered in the differential diagnosis of pineal gland tumors in the appropriate clinical setting.

  4. Pineal Gland Lymphoma: Case Report and Literature Review

    PubMed Central

    Gupta, Akshya; Johnson, Mahlon; Hussain, Ali

    2015-01-01

    A 65-year-old male presented to our institution with acute-onset headache. Imaging studies demonstrated a mass in the region of the pineal gland, with subsequent histopathology findings being consistent with large B cell lymphoma. The patient was treated with methotrexate, but ultimately did not survive. Primary central nervous system (CNS) lymphoma rarely involves the pineal gland, but should be considered in the differential diagnosis of pineal gland tumors in the appropriate clinical setting. PMID:26605125

  5. GABAergic signaling in the rat pineal gland.

    PubMed

    Yu, Haijie; Benitez, Sergio G; Jung, Seung-Ryoung; Farias Altamirano, Luz E; Kruse, Martin; Seo, Jong Bae; Koh, Duk-Su; Muñoz, Estela M; Hille, Bertil

    2016-08-01

    Pinealocytes secrete melatonin at night in response to norepinephrine released from sympathetic nerve terminals in the pineal gland. The gland also contains many other neurotransmitters whose cellular disposition, activity, and relevance to pineal function are not understood. Here, we clarify sources and demonstrate cellular actions of the neurotransmitter γ-aminobutyric acid (GABA) using Western blotting and immunohistochemistry of the gland and electrical recording from pinealocytes. GABAergic cells and nerve fibers, defined as containing GABA and the synthetic GAD67, were identified. The cells represent a subset of interstitial cells while the nerve fibers were distinct from the sympathetic innervation. The GABAA receptor subunit α1 was visualized in close proximity of both GABAergic and sympathetic nerve fibers as well as fine extensions among pinealocytes and blood vessels. The GABAB 1 receptor subunit was localized in the interstitial compartment but not in pinealocytes. Electrophysiology of isolated pinealocytes revealed that GABA and muscimol elicit strong inward chloride currents sensitive to bicuculline and picrotoxin, clear evidence for functional GABAA receptors on the surface membrane. Applications of elevated potassium solution or the neurotransmitter acetylcholine depolarized the pinealocyte membrane potential enough to open voltage-gated Ca(2+) channels leading to intracellular calcium elevations. GABA repolarized the membrane and shut off such calcium rises. In 48-72-h cultured intact glands, GABA application neither triggered melatonin secretion by itself nor affected norepinephrine-induced secretion. Thus, strong elements of GABA signaling are present in pineal glands that make large electrical responses in pinealocytes, but physiological roles need to be found.

  6. Cytologic features of the normal pineal gland on squash preparations.

    PubMed

    Murro, Diana; Alsadi, Alaa; Nag, Sukriti; Arvanitis, Leonidas; Gattuso, Paolo

    2014-11-01

    As primary pineal lesions are extremely rare, many surgical pathologists are unfamiliar with normal pineal cytologic features. We describe cytologic features of the normal pineal gland in patients of varying ages and identify common diagnostic pitfalls. We performed a retrospective review of pineal gland biopsies performed at our institution, where approximately 30,000 surgical specimens are accessioned yearly, for the last 23 years. Only two pineal gland biopsies were found. Although both cases were initially diagnosed as low-grade gliomas on frozen section, the final diagnosis was benign pineal tissue based on light microscopy and immunohistochemistry results. Additionally, we performed squash preparations of five normal pineal gland autopsy specimens with Papanicolaou and Diff-Quik® (Dade Behring, Newark, DE) stains. Infant preparations were highly cellular smears composed of numerous, uniform, single cells with indistinct cytoplasm, small round-to-oval nuclei, fine chromatin, and absent nucleoli and calcifications. The vague microfollicular pattern mimicked a pineocytoma and the fine fibrillary background mimicked a glial neoplasm. Young adult smears were similar; however, microcalcifications were present with fewer background single cells. Older patients had much less cellular smears composed of small clusters of cells with fusiform-to-spindle nuclei, a fine chromatin pattern, and indistinct cytoplasmic borders. There were fewer background single cells and more microcalcifications. The cytologic features of the native pineal gland vary with age. Normal pineal tissue can be confused with a pineocytoma or low-grade glioma. Familiarity with normal pineal gland cytological features will help to avoid a potential misdiagnosis.

  7. Symptomatic glial cysts of the pineal gland.

    PubMed

    Fain, J S; Tomlinson, F H; Scheithauer, B W; Parisi, J E; Fletcher, G P; Kelly, P J; Miller, G M

    1994-03-01

    Small asymptomatic cysts of the pineal gland represent a common incidental finding in adults undergoing computerized tomography or magnetic resonance (MR) imaging or at postmortem examination. In contrast, large symptomatic pineal cysts are rare, being limited to individual case reports or small series. The authors have reviewed 24 cases of large pineal cysts. The mean patient age at presentation was 28.7 years (range 15 to 46 years); 18 were female and six male. Presenting features in 20 symptomatic cases included: headache in 19; nausea and/or vomiting in seven; papilledema in five; visual disturbances in five (diplopia in three, "blurred vision" in two, and unilateral partial oculomotor nerve palsy in one); Parinaud's syndrome in two; hemiparesis in one; hemisensory aberration in one; and seizures in one. Four lesions were discovered incidentally. Magnetic resonance imaging typically demonstrated a 0.8- to 3.0-cm diameter mass (mean 1.7 cm) with homogeneous decreased signal intensity on T1-weighted images, increased signal intensity on T2-weighted images, and a distinct margin. Hydrocephalus was present in eight cases. The cysts were surgically excised via an infratentorial/supracerebellar approach (23 cases) or stereotactically biopsied (one case). Histological examination revealed a cyst wall 0.5 to 2.0 mm thick comprised of three layers: an outer fibrous layer, a middle layer of pineal parenchymal cells with variable calcification, and an inner layer of hypocellular glial tissue often exhibiting Rosenthal fibers and/or granular bodies. Evidence of prior hemorrhage, mild astrocytic degenerative atypia, and disorganization of pineal parenchyma were often present. Postoperative follow-up review in all 24 cases (range 3 months to 10 years) revealed no complications in 21, mild ocular movement deficit in one, gradually resolving Parinaud's syndrome in one, and radiographic evidence of a postoperative venous infarct of the superior cerebellum with ataxia of 1 week

  8. [Participation of pineal gland in antistressor activity of adaptogenic drugs].

    PubMed

    Arushanian, É B; Beĭer, É V

    2015-01-01

    Chronic stress produces some morphological changes in rats, including thymus weight reduction, adrenal hypertrophy, and peptic ulcers in stomach. Repeated administration of phytoadaptogenic drugs (ginseng and bilobil) decreased these stress-induced disorders. The antistressor activity of drugs was attenuated upon by removal of the pineal gland. Histochemical and morphometric investigation of pineal tissues in stressed animals showed that that the pharmacological effect was accompanied by increasing functional activity of the pineal gland. It is suggested that pineal mobilization may participate in antistressor activity of phytoadaptogenic drugs.

  9. [Participation of pineal gland in antistressor activity of adaptogenic drugs].

    PubMed

    Arushanian, É B; Beĭer, É V

    2015-01-01

    Chronic stress produces some morphological changes in rats, including thymus weight reduction, adrenal hypertrophy, and peptic ulcers in stomach. Repeated administration of phytoadaptogenic drugs (ginseng and bilobil) decreased these stress-induced disorders. The antistressor activity of drugs was attenuated upon by removal of the pineal gland. Histochemical and morphometric investigation of pineal tissues in stressed animals showed that that the pharmacological effect was accompanied by increasing functional activity of the pineal gland. It is suggested that pineal mobilization may participate in antistressor activity of phytoadaptogenic drugs. PMID:25826867

  10. The pineal gland and the menstrual cycle.

    PubMed

    Sandyk, R

    1992-04-01

    The menstrual cycle reflects the expression of a cyclical process involving the interaction between the hypothalamic-pituitary axis and the ovaries. This complex process requires an integrated neural and humoral control mechanism. It is now well established that a hypothalamic "transducer" located in the medial basal hypothalamus integrates neural and humoral information and translates it into an oscillatory signal which eventually results in the release of the gonadotropin releasing hormone (GnRH), triggering the secretion of gonadotropins from the pituitary gland. Recent animal studies indicate that melatonin influences the functions of the hypothalamic-pituitary-gonadal axis by modifying the firing frequency of the hypothalamic GnRH pulse generator. Consequently, the pineal gland, through the action of melatonin, may exert an important modulatory effect on the mechanisms controlling menstrual cyclicity. Furthermore, abnormal melatonin functions may be involved in the pathogenesis of several disorders of the menstrual cycle including some forms of hypothalamic amenorrhea such as exercise and malnutrition-induced amenorrhea. Consideration of pineal melatonin functions provides a new dimension into the understanding of the neuroendocrine mechanisms governing the cyclical phenomena of the female reproductive system.

  11. Cytologic features of the normal pineal gland of adults.

    PubMed

    Jiménez-Heffernan, José A; Bárcena, Carmen; Agra, Carolina; Asunción, Alfonso

    2015-08-01

    It is well known that the histology of normal pineal gland may resemble not only pineal tumors but also gliomas, owing to its cellularity which is much greater than that of normal white or gray matter. Our recent experience with a case in which part of a normal gland was submitted for intraoperative consultation, together with the scarcity of cytologic descriptions, led us to perform a cyto-histologic correlation study. In addition to the intraoperative case, we collected five pineal glands from consecutive adult autopsies. During the squash procedure, we often noted the presence of calcified grains. Smears were hypercellular, distributed in tissue fibrillary fragments and as numerous single cells, with crystalline structures. Pineal gland cells (pineocytes) were large, round, epithelioid with ill-defined cytoplasms and moderate nuclear pleomorphism. Spindle cells with greater fibrillary quality were less common. One of the most remarkable findings seen in all cases was the presence of cytoplasmic pigment. Histological evaluation and immunohistochemical staining confirmed that the tissue was normal pineal gland. The histology showed a characteristic lobular aspect and frequent corpora arenacea. The pigment seen cytologically was also encountered in histology and corresponded to lipofuscin. Cytologic features of the pineal gland are peculiar when compared to other normal structures of the central nervous system. These features correlate closely with what is seen on histology. In an adequate clinical context, and in combination with frozen sections, cytology allows a specific recognition of the pineal gland during intraoperative pathologic consultations.

  12. Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging.

    PubMed

    Paltsev, Michael A; Polyakova, Victoria O; Kvetnoy, Igor M; Anderson, George; Kvetnaia, Tatiana V; Linkova, Natalia S; Paltseva, Ekaterina M; Rubino, Rosa; De Cosmo, Salvatore; De Cata, Angelo; Mazzoccoli, Gianluigi

    2016-03-15

    Deficits in neuroendocrine-immune system functioning, including alterations in pineal and thymic glands, contribute to aging-associated diseases. This study looks at ageing-associated alterations in pineal and thymic gland functioning evaluating common signaling molecules present in both human and animal pinealocytes and thymocytes: endocrine cell markers (melatonin, serotonin, pCREB, AANAT, CGRP, VIP, chromogranin А); cell renovation markers (p53, AIF, Ki67), matrix metalloproteinases (MMP2, MMP9) and lymphocytes markers (CD4, CD5, CD8, CD20). Pineal melatonin is decreased, as is one of the melatonin pathway synthesis enzymes in the thymic gland. A further similarity is the increased MMPs levels evident over age in both glands. Significant differences are evident in cell renovation processes, which deteriorate more quickly in the aged thymus versus the pineal gland. Decreases in the number of pineal B-cells and thymic T-cells were also observed over aging. Collected data indicate that cellular involution of the pineal gland and thymus show many commonalities, but also significant changes in aging-associated proteins. It is proposed that such ageing-associated alterations in these two glands provide novel pharmaceutical targets for the wide array of medical conditions that are more likely to emerge over the course of ageing.

  13. Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging.

    PubMed

    Paltsev, Michael A; Polyakova, Victoria O; Kvetnoy, Igor M; Anderson, George; Kvetnaia, Tatiana V; Linkova, Natalia S; Paltseva, Ekaterina M; Rubino, Rosa; De Cosmo, Salvatore; De Cata, Angelo; Mazzoccoli, Gianluigi

    2016-03-15

    Deficits in neuroendocrine-immune system functioning, including alterations in pineal and thymic glands, contribute to aging-associated diseases. This study looks at ageing-associated alterations in pineal and thymic gland functioning evaluating common signaling molecules present in both human and animal pinealocytes and thymocytes: endocrine cell markers (melatonin, serotonin, pCREB, AANAT, CGRP, VIP, chromogranin А); cell renovation markers (p53, AIF, Ki67), matrix metalloproteinases (MMP2, MMP9) and lymphocytes markers (CD4, CD5, CD8, CD20). Pineal melatonin is decreased, as is one of the melatonin pathway synthesis enzymes in the thymic gland. A further similarity is the increased MMPs levels evident over age in both glands. Significant differences are evident in cell renovation processes, which deteriorate more quickly in the aged thymus versus the pineal gland. Decreases in the number of pineal B-cells and thymic T-cells were also observed over aging. Collected data indicate that cellular involution of the pineal gland and thymus show many commonalities, but also significant changes in aging-associated proteins. It is proposed that such ageing-associated alterations in these two glands provide novel pharmaceutical targets for the wide array of medical conditions that are more likely to emerge over the course of ageing. PMID:26943046

  14. Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging

    PubMed Central

    Paltsev, Michael A.; Polyakova, Victoria O.; Kvetnoy, Igor M.; Anderson, George; Kvetnaia, Tatiana V.; Linkova, Natalia S.; Paltseva, Ekaterina M.; Rubino, Rosa; De Cosmo, Salvatore; De Cata, Angelo; Mazzoccoli, Gianluigi

    2016-01-01

    Deficits in neuroendocrine-immune system functioning, including alterations in pineal and thymic glands, contribute to aging-associated diseases. This study looks at ageing-associated alterations in pineal and thymic gland functioning evaluating common signaling molecules present in both human and animal pinealocytes and thymocytes: endocrine cell markers (melatonin, serotonin, pCREB, AANAT, CGRP, VIP, chromogranin A); cell renovation markers (p53, AIF, Ki67), matrix metalloproteinases (MMP2, MMP9) and lymphocytes markers (CD4, CD5, CD8, CD20). Pineal melatonin is decreased, as is one of the melatonin pathway synthesis enzymes in the thymic gland. A further similarity is the increased MMPs levels evident over age in both glands. Significant differences are evident in cell renovation processes, which deteriorate more quickly in the aged thymus versus the pineal gland. Decreases in the number of pineal B-cells and thymic T-cells were also observed over aging. Collected data indicate that cellular involution of the pineal gland and thymus show many commonalities, but also significant changes in aging-associated proteins. It is proposed that such ageing-associated alterations in these two glands provide novel pharmaceutical targets for the wide array of medical conditions that are more likely to emerge over the course of ageing. PMID:26943046

  15. Is postmenopausal osteoporosis related to pineal gland functions?

    PubMed

    Sandyk, R; Anastasiadis, P G; Anninos, P A; Tsagas, N

    1992-02-01

    There is currently considerable interest in the pathogenesis of postmenopausal osteoporosis, which is the most common metabolic bone disease. Osteoporosis affects approximately 20 million persons in the United States, 90% of whom are postmenopausal women. Although there is evidence that estrogen deficiency is an important contributory factor, the pathogenesis of osteoporosis is multifactorial and presently poorly understood. There is evidence that pineal melatonin is an anti-aging hormone and that the menopause is associated with a substantial decline in melatonin secretion and an increased rate of pineal calcification. Animal data indicate that pineal melatonin is involved in the regulation of calcium and phosphorus metabolism by stimulating the activity of the parathyroid glands and by inhibiting calcitonin release and inhibiting prostaglandin synthesis. Hence, the pineal gland may function as a "fine tuner" of calcium homeostasis. In the following communication, we propose that the fall of melatonin plasma levels during the early stage of menopause may be an important contributory factor in the development of postmenopausal osteoporosis. Consequently, plasma melatonin levels taken in the early menopause could be used as an indicator or perhaps as a marker for susceptibility to postmenopausal osteoporosis. Moreover, light therapy, administration of oral melatonin (2.5 mg at night) or agents which induce a sustained release of melatonin secretion such as 5-methoxypsoralen, could be useful agents in the prophylaxis and treatment of postmenopausal osteoporosis. Finally, since application of external artificial magnetic fields has been shown to synchronize melatonin secretion in experimental animals and humans, we propose that treatment with artificial magnetic fields may be beneficial for postmenopausal osteoporosis. PMID:1305608

  16. Pineal Gland Volume Assessed by MRI and Its Correlation with 6-Sulfatoxymelatonin Levels among Older Men.

    PubMed

    Sigurdardottir, Lara G; Markt, Sarah C; Sigurdsson, Sigurdur; Aspelund, Thor; Fall, Katja; Schernhammer, Eva; Rider, Jennifer R; Launer, Lenore; Harris, Tamara; Stampfer, Meir J; Gudnason, Vilmundur; Czeisler, Charles A; Lockley, Steven W; Valdimarsdottir, Unnur A; Mucci, Lorelei A

    2016-10-01

    The pineal gland produces the hormone melatonin, and its volume may influence melatonin levels. We describe an innovative method for estimating pineal volume in humans and present the association of pineal parenchyma volume with levels of the primary melatonin metabolite, 6-sulfatoxymelatonin. We selected a random sample of 122 older Icelandic men nested within the AGES-Reykjavik cohort and measured their total pineal volume, their parenchyma volume, and the extent of calcification and cysts. For volume estimations we used manual segmentation of magnetic resonance images in the axial plane with simultaneous side-by-side view of the sagittal and coronal plane. We used multivariable adjusted linear regression models to estimate the association of pineal parenchyma volume and baseline characteristics, including 6-sulfatoxymelatonin levels. We used logistic regression to test for differences in first morning urinary 6-sulfatoxymelatonin levels among men with or without cystic or calcified glands. The pineal glands varied in volume, shape, and composition. Cysts were present in 59% of the glands and calcifications in 21%. The mean total pineal volume measured 207 mm(3) (range 65-536 mm(3)) and parenchyma volume 178 mm(3) (range 65-503 mm(3)). In multivariable-adjusted models, pineal parenchyma volume was positively correlated with 6-sulfatoxymelatonin levels (β = 0.52, p < 0.001). Levels of 6-sulfatoxymelatonin did not differ significantly by presence of cysts or calcification. By using an innovative method for pineal assessment, we found pineal parenchyma volume to be positively correlated with 6-sulfatoxymelatonin levels, in line with other recent studies.

  17. Pineal Gland Volume Assessed by MRI and Its Correlation with 6-Sulfatoxymelatonin Levels among Older Men.

    PubMed

    Sigurdardottir, Lara G; Markt, Sarah C; Sigurdsson, Sigurdur; Aspelund, Thor; Fall, Katja; Schernhammer, Eva; Rider, Jennifer R; Launer, Lenore; Harris, Tamara; Stampfer, Meir J; Gudnason, Vilmundur; Czeisler, Charles A; Lockley, Steven W; Valdimarsdottir, Unnur A; Mucci, Lorelei A

    2016-10-01

    The pineal gland produces the hormone melatonin, and its volume may influence melatonin levels. We describe an innovative method for estimating pineal volume in humans and present the association of pineal parenchyma volume with levels of the primary melatonin metabolite, 6-sulfatoxymelatonin. We selected a random sample of 122 older Icelandic men nested within the AGES-Reykjavik cohort and measured their total pineal volume, their parenchyma volume, and the extent of calcification and cysts. For volume estimations we used manual segmentation of magnetic resonance images in the axial plane with simultaneous side-by-side view of the sagittal and coronal plane. We used multivariable adjusted linear regression models to estimate the association of pineal parenchyma volume and baseline characteristics, including 6-sulfatoxymelatonin levels. We used logistic regression to test for differences in first morning urinary 6-sulfatoxymelatonin levels among men with or without cystic or calcified glands. The pineal glands varied in volume, shape, and composition. Cysts were present in 59% of the glands and calcifications in 21%. The mean total pineal volume measured 207 mm(3) (range 65-536 mm(3)) and parenchyma volume 178 mm(3) (range 65-503 mm(3)). In multivariable-adjusted models, pineal parenchyma volume was positively correlated with 6-sulfatoxymelatonin levels (β = 0.52, p < 0.001). Levels of 6-sulfatoxymelatonin did not differ significantly by presence of cysts or calcification. By using an innovative method for pineal assessment, we found pineal parenchyma volume to be positively correlated with 6-sulfatoxymelatonin levels, in line with other recent studies. PMID:27449477

  18. Neuroendocrine mediated effects of electromagnetic-field exposure: Possible role of the pineal gland

    SciTech Connect

    Wilson, W.B.; Stevens, R.G.; Anderson, L.E. )

    1989-01-01

    Reports from recent epidemiological studies have suggested a possible association between extremely low frequently (ELF; including 50- or 60-Hz) electric- and magnetic-field exposure, and increased risk of certain cancers, depression, and miscarriage. ELF field-induced pineal gland dysfunction is a possible etiological factor in these effects. Work in our laboratory and elsewhere has shown that ELF electromagnetic-field exposure can alter the normal circadian rhythm of melatonin synthesis and release in the pineal gland. Consequences of reduced or inappropriately timed melatonin release on the endocrine, neuronal, and immune systems are discussed. Laboratory data linking ELF field exposure to changes in pineal circadian rhythms in both animal and humans are reviewed. The authors suggest that the pineal gland, in addition to being a convenient locus for measuring dyschronogenic effects of ELF field exposure, may play a central role in biological response to these fields via alterations in the melatonin signal.

  19. The originality of Descartes' theory about the pineal gland.

    PubMed

    Lokhorst, G J; Kaitaro, T T

    2001-03-01

    René Descartes thought that the pineal gland is the part of the body with which the soul is most immediately associated. Several prominent historians (such as Soury, Thorndike and Sherrington) have claimed that this idea was not very original. We re-examine the evidence and conclude that their assessment was wrong. We pay special attention to the thesis about the pineal gland which Jean Cousin defended in January, 1641.

  20. Occurrence of Pineal Gland Tumors in Combined Chronic Toxicity/Carcinogenicity Studies in Wistar Rats.

    PubMed

    Treumann, Silke; Buesen, Roland; Gröters, Sibylle; Eichler, Jens-Olaf; van Ravenzwaay, Bennard

    2015-08-01

    Pineal gland tumors are very rare brain lesions in rats as well as in other species including humans. A total of 8 (out of 1,360 examined) Wistar rats from 3 different combined chronic toxicity/carcinogenicity or mere carcinogenicity studies revealed pineal gland tumors. The tumors were regarded to be spontaneous and unrelated to treatment. The morphology and immunohistochemical evaluation led to the diagnosis malignant pinealoma. The main characteristics that were variably developed within the tumors were the following: cellular atypia, high mitotic index, giant cells, necrosis, Homer Wright rosettes, Flexner-Wintersteiner rosettes and pseudorosettes, positive immunohistochemical reaction for synaptophysin, and neuron-specific enolase. The pineal gland is not a protocol organ for histopathological examination in carcinogenicity studies. Nevertheless, the pineal gland can occasionally be encountered on the routine brain section or if it is the origin of a tumor protruding into the brain, the finding will be recorded. Therefore, although known to be a rare tumor in rats, pineal neoplasms should be included in the list of possible differential diagnoses for brain tumors, especially when the tumor is located in the region of the pineal body.

  1. Pineal gland volume in primary insomnia and healthy controls: a magnetic resonance imaging study.

    PubMed

    Bumb, Jan M; Schilling, Claudia; Enning, Frank; Haddad, Leila; Paul, Franc; Lederbogen, Florian; Deuschle, Michael; Schredl, Michael; Nolte, Ingo

    2014-06-01

    Little is known about the relation between pineal volume and insomnia. Melatonin promotes sleep processes and, administered as a drug, it is suitable to improve primary and secondary sleep disorders in humans. Recent magnetic resonance imaging studies suggest that human plasma and saliva melatonin levels are partially determined by the pineal gland volume. This study compares the pineal volume in a group of patients with primary insomnia to a group of healthy people without sleep disturbance. Pineal gland volume (PGV) was measured on the basis of high-resolution 3 Tesla MRI (T1-magnetization prepared rapid gradient echo) in 23 patients and 27 controls, matched for age, gender and educational status. Volume measurements were performed conventionally by manual delineation of the pineal borders in multi-planar reconstructed images. Pineal gland volume was significantly smaller (P < 0.001) in patients (48.9 ± 26.6 mm(3) ) than in controls (79 ± 30.2 mm(3) ). In patients PGV correlated negatively with age (r = -0.532; P = 0.026). Adjusting for the effect of age, PGV and rapid eye movement (REM) latency showed a significant positive correlation (rS  = 0.711, P < 0.001) in patients. Pineal volume appears to be reduced in patients with primary insomnia compared to healthy controls. Further studies are needed to clarify whether low pineal volume is the basis or the consequence of functional sleep changes to elucidate the molecular pathology for the pineal volume loss in primary insomnia.

  2. [Single mechanism of remodelling extracellular matrix in thymus and pineal gland at aging].

    PubMed

    Lin'kova, N S; Poliakova, V O; Kvetnoĭ, I M

    2011-01-01

    The expression of matrix metalloproteinase 2 and 9 in thymus and pineal gland has been verified. These data demonstrate single mechanism of remodelling extracellular matrix in thymus and pineal gland at aging.

  3. Rhythmic control of endocannabinoids in the rat pineal gland.

    PubMed

    Koch, Marco; Ferreirós, Nerea; Geisslinger, Gerd; Dehghani, Faramarz; Korf, Horst-Werner

    2015-01-01

    Endocannabinoids modulate neuroendocrine networks by directly targeting cannabinoid receptors. The time-hormone melatonin synchronizes these networks with external light condition and guarantees time-sensitive and ecologically well-adapted behaviors. Here, the endocannabinoid arachidonoyl ethanolamide (AEA) showed rhythmic changes in rat pineal glands with higher levels during the light-period and reduced amounts at the onset of darkness. Norepinephrine, the essential stimulus for nocturnal melatonin biosynthesis, acutely down-regulated AEA and other endocannabinoids in cultured pineal glands. These temporal dynamics suggest that AEA exerts time-dependent autocrine and/or paracrine functions within the pineal. Moreover, endocananbinoids may be released from the pineal into the CSF or blood stream.

  4. A new identified complication of intracystic hemorrhage in a large pineal gland cyst.

    PubMed

    Mehrzad, Raman; Mishra, Suprav; Feinstein, Alexander; Ho, Michael G

    2014-01-01

    Pineal gland cysts are typically asymptomatic, benign cysts most commonly found incidentally in adults. In rare cases, a large pineal gland cyst can be complicated by intracystic hemorrhage, which could then manifest with neurological symptoms. We report a new complication of intracystic hemorrhage in a large pineal gland cyst in a 40-year-old man with new onset seizures.

  5. The pineal gland and the clinical course of multiple sclerosis.

    PubMed

    Sandyk, R

    1992-01-01

    Clinical, epidemiological, biochemical, immunological, and radiological studies suggest that the pineal gland may be implicated in the pathophysiology of multiple sclerosis (MS). The following communication is concerned with the association among MS, pregnancy, the postpartum period, and melatonin secretion and illustrates, based on a clinical case report, the influence of the pineal gland on the clinical course of MS. This association is noteworthy since MS may worsen during the postpartum period and melatonin secretion is reported to be altered most dramatically by pregnancy and delivery. Since melatonin secretion is cyclical, undergoing diurnal, weekly, seasonal, and annual variations, it is proposed that the pineal gland may be the "prime mover" underlying the spontaneous exacerbations and remissions in MS. PMID:1342015

  6. Parkinsonism as an unusual presenting symptom of pineal gland teratoma.

    PubMed

    Dolendo, Mae Concepcion J; Lin, Tan Poh; Tat, Ong Hian; Chong, Quah Thuan; Timothy, Lee Kam Yiu

    2003-04-01

    We report a case of a 14-year-old Chinese boy with immature teratoma of the pineal gland who manifested with parkinsonism. Diagnostic evaluation revealed hydrocephalus and an immature teratoma of the pineal gland extending to the thalamus. An urgent ventriculoperitoneal shunt was inserted, and chemotherapy was given to reduce the tumor size. The tumor was completely excised 2 months after diagnosis with improvement of clinical signs and symptoms. His symptoms recurred 3 months later with sudden onset of obtundation, tremors, cogwheel rigidity, and marked bradykinesia. Magnetic resonance imaging (MRI) revealed a small enhancing lesion in the pineal region and progressive hydrocephalus on serial studies. He was treated with carbidopa/levodopa and amantadine, but marked improvement was only observed after reprogramming his VP shunt. Features consistent with the growing teratoma syndrome were noted during this period. These were progressive pineal gland tumor enlargement documented on MRI without increase in previously elevated alpha-fetoprotein levels. The tumor continued to enlarge despite gamma knife radiosurgery. Secondary parkinsonism is a rare presentation of pineal gland tumors and has not been reported in association with the growing teratoma syndrome.

  7. The role of pineal gland and exogenous melatonin on the irradiation stress response of suprarenal gland.

    PubMed

    Alicelebić, Selma; Mornjaković, Zakira; Susko, Irfan; Cosović, Esad; Beganović-Petrović, Amira

    2006-11-01

    Pineal gland has and antistressogenic role. Its main hormone, melatonin, has radio protective effect on endocrine and other dynamic tissues. In our previous study, we have shown that pinealectomy changes the behavior of suprarenal gland in totally irradiated rats. The aim of this study is to evaluate the effect of exogenous melatonin on suprarenal gland of rats with or without pineal gland. Four months after pinealectomy (experimental group) or shampinealectomy (control group), adult Wistar male rats were daily treated with 0,2 mg of melatonin intraperitoneally, during two weeks. Thereafter, all animals were totally irradiated with 8 Gy of Gamma rays produced from Cobalt 60. Animals who survived were sacrificed on the 17(th) post irradiation day. Qualitative and quantitative characteristics of the suprarenal gland were studied using histological methods. The results show that exogenous melatonin had protective role on suprarenal gland in totally irradiated rats and that those effects were more pronounced in the presence of pineal gland.

  8. [Influence of peptides from pineal gland on thymus function at aging].

    PubMed

    Lin'kova, N S; Poliakova, V O; Trofimov, A V; Sevost'ianova, N N; Kvetnoĭ, I M

    2010-01-01

    The interference between thymus and pineal gland during their involution is considered in this review. The research data about influence of thymus peptides on pineal gland and pineal peptides on thymus is summarized. Analysis of these data showed that pineal peptides (epithalamin, epitalon) had more effective geroprotective effect on thymus involution in comparison with geroprotective effect of thymic peptides (thymalin, thymogen) on involution of pineal gland. The key mechanisms of pineal peptides effect on thymus dystrophy is immunoendocrine cooperation, which is realized as transcription's activation of various proteins.

  9. The midline pineal "eye": MR and CT characteristics of the pineal gland with and without benign cyst formation.

    PubMed

    Jinkins, J R; Xiong, L; Reiter, R J

    1995-09-01

    The purpose of this study was to evaluate the magnetic resonance imaging characteristics of pineal cysts and pineal calcifications and to determine the incidence of benign pineal cysts. Two-hundred-fifty magnetic resonance examinations were retrospectively examined for the incidence of pineal cysts. In addition, 60 collected cases of pineal cysts were evaluated with regard to cross sectional diameter and magnetic resonance signal characteristics. Finally, the magnetic resonance signal characteristics of pineal tissue in 50 patients were compared to companion computed tomographic scans that were scrutinized for the presence or absence of calcification. The incidence of pineal cysts as revealed by magnetic resonance imaging in this study was 10.8%. The minimal and maximal measurements ranged from a low of 2 x 2 x 2 mm to a high of 10 x 12 x 10 mm. The magnetic resonance signal intensities of pineal cyst as compared to cerebrospinal fluid were iso- or hyperintense on all magnetic resonance sequences in the majority of cases. Calcifications of the pineal gland as revealed by computed tomography tended to be isointense to gray matter if the calcifications were small and hypointense to gray matter if large on all magnetic resonance acquisitions. A careful analysis of the magnetic resonance signal characteristics enables the recognition of moderate- to large-sized pineal calcifications and their differentiation from large pineal cysts. However, small cysts of the pineal gland can be difficult or impossible to distinguish on magnetic resonance imaging from calcifications without comparison with computed tomography. PMID:8609598

  10. The Cartesian clock metaphor for pineal gland operation pervades the origin of modern chronobiology.

    PubMed

    Barrera-Mera, B; Barrera-Calva, E

    1998-01-01

    In theoretical descriptions formulated during the 1600s, R. Descartes attributed a clock-like role to the pineal gland. He established the belief that pineal function underlies the laws of the universe that determine the cyclic sleep-awake states in man. Recent reports about pineal circadian pacemakers now validate the brilliant accuracy of Cartesian thought, in relation to the relevant role of the pineal gland.

  11. Calcium, calcification, and melatonin biosynthesis in the human pineal gland: a postmortem study into age-related factors.

    PubMed

    Schmid, H A; Requintina, P J; Oxenkrug, G F; Sturner, W

    1994-05-01

    It is believed that pineal calcification may be age-associated and that the well-demonstrated age-related decline in melatonin biosynthesis may be an expression of an alteration in calcium homeostasis in the pinealocyte. Prior correlations of melatonin to calcium deposition and age were made on the basis of radiological or semiquantitative analysis. In this postmortem study of 33 subjects (age range 3 months to 65 years) calcium deposits measured by atomic absorption spectrometry correlated positively with age in day and night samples (day: r = 0.56, P < 0.05; night: r = 0.818, P < 0.001). Nighttime (2200 h to 0800 h) pineal melatonin content (HPLC fluorometry) was higher than daytime melatonin levels (nighttime 3.80 +/- 0.3 vs. daytime 0.85 +/- 0.4 ng/mg protein). Nighttime calcium levels in the supernatant correlated negatively with melatonin content (r = -0.59, P < 0.05). PMID:7807371

  12. Comparison of three methods for the estimation of pineal gland volume using magnetic resonance imaging.

    PubMed

    Acer, Niyazi; Ilıca, Ahmet Turan; Turgut, Ahmet Tuncay; Ozçelik, Ozlem; Yıldırım, Birdal; Turgut, Mehmet

    2012-01-01

    Pineal gland is a very important neuroendocrine organ with many physiological functions such as regulating circadian rhythm. Radiologically, the pineal gland volume is clinically important because it is usually difficult to distinguish small pineal tumors via magnetic resonance imaging (MRI). Although many studies have estimated the pineal gland volume using different techniques, to the best of our knowledge, there has so far been no stereological work done on this subject. The objective of the current paper was to determine the pineal gland volume using stereological methods and by the region of interest (ROI) on MRI. In this paper, the pineal gland volumes were calculated in a total of 62 subjects (36 females, 26 males) who were free of any pineal lesions or tumors. The mean ± SD pineal gland volumes of the point-counting, planimetry, and ROI groups were 99.55 ± 51.34, 102.69 ± 40.39, and 104.33 ± 40.45 mm(3), respectively. No significant difference was found among the methods of calculating pineal gland volume (P > 0.05). From these results, it can be concluded that each technique is an unbiased, efficient, and reliable method, ideally suitable for in vivo examination of MRI data for pineal gland volume estimation.

  13. The function of very long chain polyunsaturated fatty acids in the pineal gland.

    PubMed

    Catalá, Angel

    2010-02-01

    The mammalian pineal gland is a prominent secretory organ with a high metabolic activity. Melatonin (N-acetyl-5-methoxytryptamine), the main secretory product of the pineal gland, efficiently scavenges both the hydroxyl and peroxyl radicals counteracting lipid peroxidation in biological membranes. Approximately 25% of the total fatty acids present in the rat pineal lipids are represented by arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3). These very long chain polyunsaturated fatty acids play important roles in the pineal gland. In addition to the production of melatonin, the mammalian pineal gland is able of convert these polyunsaturated fatty acids into bioactive lipid mediators. Lipoxygenation is the principal lipoxygenase (LOX) activity observed in the rat pineal gland. Lipoxygenation in the pineal gland is exceptional because no other brain regions express significant LOX activities under normal physiological conditions. The rat pineal gland expresses both 12- and 15-lipoxygenase (LOX) activities, producing 12- and 15-hydroperoxyeicosatetraenoic acid (12- and 15-HpETE) from arachidonic acid and 14- and 17-hydroxydocosahexaenoic acid (14- and 17-HdoHE) from docosahexaenoic acid, respectively. The rat pineal also produces hepoxilins via LOX pathways. The hepoxilins are bioactive epoxy-hydroxy products of the arachidonic acid metabolism via the 12S-lipoxygenase (12S-LOX) pathway. The two key pineal biochemical functions, lipoxygenation and melatonin synthesis, may be synergistically regulated by the status of n-3 essential fatty acids.

  14. The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus.

    PubMed

    Yamazaki, Fumiyoshi; Møller, Morten; Fu, Cong; Clokie, Samuel J; Zykovich, Artem; Coon, Steven L; Klein, David C; Rath, Martin F

    2015-01-01

    Lhx9 is a member of the LIM homeobox gene family. It is expressed during mammalian embryogenesis in the brain including the pineal gland. Deletion of Lhx9 results in sterility due to failure of gonadal development. The current study was initiated to investigate Lhx9 biology in the pineal gland. Lhx9 is highly expressed in the developing pineal gland of the rat with transcript abundance peaking early in development; transcript levels decrease postnatally to nearly undetectable levels in the adult, a temporal pattern that is generally similar to that reported for Lhx9 expression in other brain regions. Studies with C57BL/6J Lhx9(-/-) mutant mice revealed marked alterations in brain and pineal development. Specifically, the superficial pineal gland is hypoplastic, being reduced to a small cluster of pinealocytes surrounded by meningeal and vascular tissue. The deep pineal gland and the pineal stalk are also reduced in size. Although the brains of neonatal Lhx9(-/-) mutant mice appear normal, severe hydrocephalus develops in about 70% of the Lhx9(-/-) mice at 5-8 weeks of age; these observations are the first to document that deletion of Lhx9 results in hydrocephalus and as such indicate that Lhx9 contributes to the maintenance of normal brain structure. Whereas hydrocephalus is absent in neonatal Lhx9(-/-)mutant mice, the neonatal pineal gland in these animals is hypoplastic. Accordingly, it appears that Lhx9 is essential for early development of the mammalian pineal gland and that this effect is not secondary to hydrocephalus.

  15. The pineal gland and the mode of onset of schizophrenia.

    PubMed

    Sandyk, R

    1992-01-01

    Recent studies suggest that abnormal melatonin functions may be implicated in the pathophysiology of schizophrenia. Since there is evidence that the presence of pineal calcification (PC) may relate, among other factors, to disturbances in melatonin secretion, I investigated in 23 chronic institutionalized schizophrenic patients the relationship of PC size on CT scan to the mode of onset of schizophrenia which carries both developmental and prognostic significance. Patients with gradual onset schizophrenia had PC size that was significantly larger than those with sudden onset (8.94 +/- 3.96 mm vs. 4.80 +/- 1.75 mm p < .025). These findings suggest that the nature of onset of schizophrenia may be influenced by the activity of the pineal gland, which may exert a role in the development and prognosis of the illness. PMID:1305641

  16. TLR4 and CD14 receptors expressed in rat pineal gland trigger NFKB pathway.

    PubMed

    da Silveira Cruz-Machado, Sanseray; Carvalho-Sousa, Claudia Emanuele; Tamura, Eduardo Koji; Pinato, Luciana; Cecon, Erika; Fernandes, Pedro Augusto Carlos Magno; de Avellar, Maria Christina Werneck; Ferreira, Zulma Silva; Markus, Regina Pekelmann

    2010-09-01

    Nuclear factor-kappa B (NFKB), a pivotal player in inflammatory responses, is constitutively expressed in the pineal gland. Corticosterone inhibits pineal NFKB leading to an enhancement of melatonin production, while tumor necrosis factor (TNF) leads to inhibition of Aa-nat transcription and the production of N-acetylserotonin in cultured glands. The reduction in nocturnal melatonin surge favors the mounting of the inflammatory response. Despite these data, there is no clear evidence of the ability of the pineal gland to recognize molecules that signal infection. This study investigated whether the rat pineal gland expresses receptors for lipopolysaccharide (LPS), the endotoxin from the membranes of Gram-negative bacteria, and to establish the mechanism of action of LPS. Here, we show that pineal glands possess both CD14 and toll-like receptor 4 (TLR4), membrane proteins that bind LPS and trigger the NFKB pathway. LPS induced the nuclear translocation of p50/p50 and p50/RELA dimers and the synthesis of TNF. The maximal expression of TNF in cultured glands coincides with an increase in the expression of TNF receptor 1 (TNFR1) in isolated pinealocytes. In addition, LPS inhibited the synthesis of N-acetylserotonin and melatonin. Therefore, the pineal gland transduces Gram-negative endotoxin stimulation by producing TNF and inhibiting melatonin synthesis. Here, we provide evidence to reinforce the idea of an immune-pineal axis, showing that the pineal gland is a constitutive player in the innate immune response.

  17. Post-natal growth in the rat pineal gland: a stereological study.

    PubMed

    Erbagci, H; Kizilkan, N; Ozbag, D; Erkilic, S; Kervancioglu, P; Canan, S; Gumusburun, E

    2012-10-01

    The purpose was to observe the changes in a rat pineal gland using stereological techniques during lactation and post-weaning periods. Thirty Wistar albino rats were studied during different post-natal periods using light microscopy. Pineal gland volume was estimated using the Cavalieri Method. Additionally, the total number of pinealocytes was estimated using the optical fractionator technique. Pineal gland volume displayed statistically significant changes between lactation and after weaning periods. A significant increase in pineal gland volume was observed from post-natal day 10 to post-natal day 90. The numerical density of pinealocytes became stabilized during lactation and decreased rapidly after weaning. However, the total number of pinealocytes continuously increased during post-natal life of all rats in the study. However, this increment was not statistically significant when comparing the lactation and after weaning periods. The increase in post-natal pineal gland volume may depend on increment of immunoreactive fibres, capsule thickness or new synaptic bodies.

  18. Postnatal neurogenesis in the cow pineal gland: an immunohistochemical study.

    PubMed

    Gómez Esteban, M B; Muñoz Mosqueira, M I; Arroyo, A A; Muñoz Barragán, L

    2013-03-01

    In the pineal gland of cows and rats structures designated rosettes have been described both during embryonic development and in adult animals. In order to investigate the possible nature of the cells comprising such structures, in the present work we studied the pineal glands from 10 cows of one- or four-years-old using conventional immunocytochemical and confocal microscopy techniques. As markers of glial cells, we used anti-vimentin (Vim) and glial fibrillary acidic protein (GFAP) and anti-S-100 sera, and the pinealocytes were labelled with β-III tubulin. As a marker of stem cells, we used an antinestin serum, while an anti-PCNA serum was employed to label proliferating cells. To explore the neuronal nature of some cells of the rosettes, we used an anti-SRIF serum. The rosettes were seen to be present throughout the glandular parenchyma and displayed a central cavity surrounded by cells, most of which expressed all or just some of the above glial labels and nestin, although there were also some rosettes with cells that expressed β-III tubulin and other cells that expressed SRIF. Likewise, in the cells of the rosettes the cell nucleus showed strong expression of PCNA. Confocal microscopy revealed that the walls of the rosettes contained cells that coexpressed Vim/S-100, Vim/GFAP and Vim/nestin. The number of rosettes was significantly greater in the animals of one year of age with respect to the four-year-old cows. The present findings allow us to suggest that rosettes are evolving structures and that most of the cells present in their walls should be considered stem cells, and hence responsible for the postnatal neurogenesis occurring in the pineal gland of cows.

  19. Leptin modulates norepinephrine-mediated melatonin synthesis in cultured rat pineal gland.

    PubMed

    Peliciari-Garcia, Rodrigo Antonio; Andrade-Silva, Jéssica; Cipolla-Neto, José; Carvalho, Carla Roberta de Oliveira

    2013-01-01

    Pineal melatonin synthesis can be modulated by many peptides, including insulin. Because melatonin appears to alter leptin synthesis, in this work we aimed to investigate whether leptin would have a role on norepinephrine- (NE-)mediated melatonin synthesis in cultured rat pineal glands. According to our data, cultured rat pineal glands express leptin receptor isoform b (Ob-Rb). Pineal expression of Ob-Rb mRNA was also observed in vivo. Administration of leptin (1 nM) associated with NE ( 1 µM) reduced melatonin content as well as arylalkylamine-N-acetyl transferase (AANAT) activity and expression in cultured pineal glands. Leptin treatment per se induced the expression of STAT3 in cultured pineal glands, but STAT3 does not participate in the leptin modulation of NE-mediated pineal melatonin synthesis. In addition, the expression of inducible cAMP early repressor (ICER) was further induced by leptin challenge when associated with NE. In conclusion, leptin inhibition of pineal melatonin synthesis appears to be mediated by a reduction in AANAT activity and expression as well as by increased expression of Icer mRNA. Peptidergic signaling within the pineal gland appears to be one of the most important signals which modulates melatonin synthesis; leptin, as a member of this system, is not an exception.

  20. Modulation of Aanat gene transcription in the rat pineal gland.

    PubMed

    Ho, Anthony K; Chik, Constance L

    2010-01-01

    The main function of the rat pineal gland is to transform the circadian rhythm generated in the suprachiasmatic nucleus into a rhythmic signal of circulating melatonin characterized by a large nocturnal increase that closely reflects the duration of night period. This is achieved through the tight coupling between environmental lighting and the expression of arylalkylamine-N-acetyltransferase, the rhythm-controlling enzyme in melatonin synthesis. The initiation of Aanat transcription at night is controlled largely by the norepinephrine-stimulated phosphorylation of cAMP response element-binding protein by protein kinase A. However, to accurately reflect the duration of darkness, additional signaling mechanisms also participate to fine-tune the temporal profile of adrenergic-induced Aanat transcription. Here, we reviewed some of these signaling mechanisms, with emphasis on the more recent findings. These signaling mechanisms can be divided into two groups: those involving modification of constitutively expressed proteins and those requiring synthesis of new proteins. This review highlights the pineal gland as an excellent model system for studying neurotransmitter-regulated rhythmic gene expression.

  1. An autopsy case of sudden unexpected death due to a glial cyst of the pineal gland.

    PubMed

    Na, Joo-Young; Lee, Kyung-Hwa; Kim, Hyung-Seok; Park, Jong-Tae

    2014-09-01

    Pineal cysts are usually asymptomatic; however, they may rarely cause symptoms such as chronic headache, paroxysmal headache with gaze paresis, postural syncope, loss of consciousness, and sudden death. A 30-year-old woman with no specific medical history except chronic headache was found collapsed in a public toilet per se. Postmortem examination revealed no external injuries or internal diseases except a cystic lesion of the pineal gland. Histologic examination showed an internal cyst surrounded by glial tissues and pineal parenchyma that was diagnosed as a glial cyst of the pineal gland. Although the pineal cyst cannot be confirmed as the cause of death, it was considered, as no other cause was evident. Herein, we report a pineal cyst considered as an assumed cause of death.

  2. Homeobox genes in the rodent pineal gland: roles in development and phenotype maintenance.

    PubMed

    Rath, Martin F; Rohde, Kristian; Klein, David C; Møller, Morten

    2013-06-01

    The pineal gland is a neuroendocrine gland responsible for nocturnal synthesis of melatonin. During early development of the rodent pineal gland from the roof of the diencephalon, homeobox genes of the orthodenticle homeobox (Otx)- and paired box (Pax)-families are expressed and are essential for normal pineal development consistent with the well-established role that homeobox genes play in developmental processes. However, the pineal gland appears to be unusual because strong homeobox gene expression persists in the pineal gland of the adult brain. Accordingly, in addition to developmental functions, homeobox genes appear to be key regulators in postnatal phenotype maintenance in this tissue. In this paper, we review ontogenetic and phylogenetic aspects of pineal development and recent progress in understanding the involvement of homebox genes in rodent pineal development and adult function. A working model is proposed for understanding the sequential action of homeobox genes in controlling development and mature circadian function of the mammalian pinealocyte based on knowledge from detailed developmental and daily gene expression analyses in rats, the pineal phenotypes of homebox gene-deficient mice and studies on development of the retinal photoreceptor; the pinealocyte and retinal photoreceptor share features not seen in other tissues and are likely to have evolved from the same ancestral photodetector cell.

  3. [Expression of AIF and CGRP markers in pineal gland and thymus during aging].

    PubMed

    Lin'kova, N S; Katanugina, A S; Khavinson, V Kh

    2011-01-01

    We investigated the expression of AIF (apoptotic inducing factor) and CGRP (calcitonin gene related peptide) at autopsy material of pineal gland and thymus of people after 60 years old. The expression of AIF and CGRP was identified in both organs, but it did not change with age, which demonstrates the probable safety of functional activity of neuroimmunoendocrine system at aging. We found correlation between expression AIF and CGRP at pineal gland, but the correlation at thymus wasn't found. It is possible that pineal gland can express unidentified signal molecule controlling the expression of AIF and CGRP.

  4. Molecular, enzymatic and functional properties of rhodopsin kinase from rat pineal gland.

    PubMed

    Palczewski, K; Carruth, M E; Adamus, G; McDowell, J H; Hargrave, P A

    1990-01-01

    Rhodopsin kinase activity from rat pineal gland and from rat retina are indistinguishable, based upon determination of a variety of enzymatic and molecular properties. Both activities are independent of calcium, cyclic nucleotides, and calmodulin. Both are activated by spermine and inhibited by adenosine and some rhodopsin kinase specific adenosine derivatives such as sangivamycin. The Km's for rhodopsin, ATP, and GTP are indistinguishable for the protein kinase in extracts from the retina and from the pineal gland. The apparent molecular weight of the kinase from both sources, as determined by gel filtration and autoradiography of the 32P-labeled autophosphorylated kinase, is about 70 kDa. Rhodopsin kinase activity from pineal binds in a light-dependent manner to rhodopsin in rod outer segments as does the enzyme from retina. Monoclonal antibodies against bovine rhodopsin were used in an immunochemical study that identified a rhodopsin-immunoreactive protein in rat pineal gland and retina. Using an ELISA we demonstrated the presence of a rhodopsin-immunoreactive protein in rat pineal gland equivalent to 0.075 pmol rhodopsin per gland. Frog pineal organ (Rana catesbiana) contains 33 times more of this rhodopsin-like protein than does rat pineal gland. PMID:2402884

  5. Pineal gland function is required for colon antipreneoplastic effects of physical exercise in rats.

    PubMed

    Frajacomo, F T T; de Paula Garcia, W; Fernandes, C R; Garcia, S B; Kannen, V

    2015-10-01

    Light-at-night exposure enhances the risk of cancer. Colon cancer is among the most dangerous tumors affecting humankind. Physical exercise has shown positive effects against colon cancer. Here, we investigated whether pineal gland modulates antipreneoplastic effects of physical exercise in the colon. Surgical and non-surgical pineal impairments were performed to clarify the relationship between the pineal gland activity and manifestation of colonic preneoplastic lesions. Next, a progressive swimming training was applied in rats exposed or not to either non-surgical pineal impairment or carcinogen treatment for 10 weeks. Both surgical and non-surgical pineal impairments increased the development of colon preneoplasia. It was further found that impairing the pineal gland function, higher rates of DNA damage were induced in colonic epithelial and enteric glial cells. Physical exercise acted positively against preneoplasia, whereas impairing the pineal function with constant light exposure disrupts its positive effects on the development of preneoplastic lesions in the colon. This was yet related to increased DNA damage in glial cells and enteric neuronal activation aside from serum melatonin levels. Our findings suggest that protective effects of physical exercise against colon cancer are dependent on the pineal gland activity.

  6. Restricted feeding restores rhythmicity in the pineal gland of arrhythmic suprachiasmatic-lesioned rats.

    PubMed

    Feillet, Céline A; Mendoza, Jorge; Pévet, Paul; Challet, Etienne

    2008-12-01

    In mammals, the rhythmic synthesis of melatonin by the pineal gland is tightly controlled by the master clock located in the suprachiasmatic nuclei (SCN). In behaviourally arrhythmic SCN-lesioned rats, we investigated the effects of daily restricted feeding (RF) on pineal melatonin synthesis. RF restored not only a rhythmic transcription of the rate-limiting enzyme for melatonin biosynthesis [arylalkylamine-N-acetyltransferase (AANAT)] and a rhythmic expression of c-FOS but also a rhythmic synthesis of melatonin in the pineal gland. In control rats without functional SCN and fed ad libitum, a daily immobilization stress did not restore any rhythmicity in the pineal gland. Interestingly, a combination of RF and daily stress prior to the time of food access did not markedly impair AaNat mRNA and c-FOS rhythmicity but did abolish the restoration of rhythmic pineal melatonin. These data indicate that the synchronizing effects of RF on the pineal rhythmicity are not due to, and cannot be mimicked by, high levels of circulating glucocorticoids. In keeping with the multi-oscillatory nature of the circadian system, the rhythmicity of pineal melatonin in mammals, until now an exclusive output of the SCN, can also be controlled by daily feeding cues when the SCN clock is lacking. Thus, the present study demonstrates that daily RF in SCN-lesioned rats provides, probably via sympathetic fibres, synchronizing stimuli strong enough to drive rhythmicity in the pineal gland.

  7. Abnormal EEG and calcification of the pineal gland in schizophrenia.

    PubMed

    Sandyk, R; Kay, S R

    1992-01-01

    Computed tomographic (CT) studies of the brain in schizophrenic patients have demonstrated a variety of structural abnormalities. We reported recently an association between pineal calcification (PC) and cortical and prefrontal cortical atrophy, and third ventricular size on CT scan in chronic schizophrenic patients. These findings indicate that in schizophrenia PC is associated with the morphological brain abnormalities associated with the disease. If PC is, indeed, related to organic cerebral pathology, then one would expect a higher prevalence of pineal gland pathology among patients with electroencephalographic (EEG) abnormalities by comparison to those with a normal EEG. To investigate this hypothesis, we studied the prevalence of PC on CT scan in a sample of 52 neuroleptic-treated schizophrenic patients (29 men, 23 women, mean age: 51.3 years SD = 9.1), of whom 10 (19.2%) had an abnormal EEG. The prevalence of PC in patients with EEG abnormalities was significantly greater by comparison to those with a normal EEG (90.0% vs. 54.8%, X2 = 4.24, p < .05). Since both groups did not differ on any of the historical and demographic data, and since PC was unrelated to neuroleptic exposure, these findings suggest that in schizophrenia PC may be related to the disease process and that it may be a marker of subcortical pathology. PMID:1342008

  8. Historical and cultural aspects of the pineal gland: comparison between the theories provided by Spiritism in the 1940s and the current scientific evidence.

    PubMed

    Lucchetti, Giancarlo; Daher, Jorge C; Iandoli, Decio; Gonçalves, Juliane P B; Lucchetti, Alessandra L G

    2013-01-01

    Significance has been attached to the pineal gland in numerous different cultures and beliefs. One religion that has advanced the role of the pineal gland is Spiritism. The objective of the present study was to compile information on the pineal gland drawing on the books of Francisco Cândido Xavier written through psychography and to carry out a critical analysis of their scientific bases by comparing against evidence in the current scientific literature. A systematic search using the terms "pineal gland" and "epiphysis" was conducted of 12 works allegedly dictated by the spirit "André Luiz". All information on the pineal having potential correlation with the field of medicine and current studies was included. Specialists in the area were recruited to compile the information and draw parallels with the scientific literature. The themes related to the pineal gland were: mental health, reproductive function, endocrinology, relationship with physical activity, spiritual connection, criticism of the theory that the organ exerts no function, and description of a hormone secreted by the gland (reference alluding to melatonin, isolated 13 years later). The historical background for each theme was outlined, together with the theories present in the Spiritist books and in the relevant scientific literature. The present article provides an analysis of the knowledge the scientific community can acquire from the history of humanity and from science itself. The process of formulating hypotheses and scientific theories can benefit by drawing on the cultural aspects of civilization, taking into account so-called non-traditional reports and theories.

  9. Daily variation of constitutively activated nuclear factor kappa B (NFKB) in rat pineal gland.

    PubMed

    Cecon, Erika; Fernandes, Pedro A; Pinato, Luciana; Ferreira, Zulma S; Markus, Regina P

    2010-01-01

    In mammals, the production of melatonin by the pineal gland is mainly controlled by the suprachiasmatic nuclei (SCN), the master clock of the circadian system. We have previously shown that agents involved in inflammatory responses, such as cytokines and corticosterone, modulate pineal melatonin synthesis. The nuclear transcription factor NFKB, detected by our group in the rat pineal gland, modulates this effect. Here, we evaluated a putative constitutive role for the pineal gland NFKB pathway. Male rats were kept under 12 h:12 h light-dark (LD) cycle or under constant darkness (DD) condition. Nuclear NFKB was quantified by electrophoretic mobility shift assay on pineal glands obtained from animals killed throughout the day at different times. Nuclear content of NFKB presented a daily rhythm only in LD-entrained animals. During the light phase, the amount of NFKB increased continuously, and a sharp drop occurred when lights were turned off. Animals maintained in a constant light environment until ZT 18 showed diurnal levels of nuclear NFKB at ZT15 and ZT18. Propranolol (20 mg/kg, i.p., ZT 11) treatment, which inhibits nocturnal sympathetic input, impaired nocturnal decrease of NFKB only at ZT18. A similar effect was observed in free-running animals, which secreted less nocturnal melatonin. Because melatonin reduces constitutive NFKB activation in cultured pineal glands, we propose that this indolamine regulates this transcription factor pathway in the rat pineal gland, but not at the LD transition. The controversial results regarding the inhibition of pineal function by constant light or blocking sympathetic neurotransmission are discussed according to the hypothesis that the prompt effect of lights-off is not mediated by noradrenaline, which otherwise contributes to maintaining low levels of nuclear NFKB at night. In summary, we report here a novel transcription factor in the pineal gland, which exhibits a constitutive rhythm dependent on environmental photic

  10. The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus

    PubMed Central

    Yamazaki, Fumiyoshi; Møller, Morten; Fu, Cong; Clokie, Samuel J.; Zykovich, Artem; Coon, Steven L.; Klein, David C.; Rath, Martin F.

    2014-01-01

    Lhx9 is a member of the LIM homeobox gene family. It is expressed during mammalian embryogenesis in the brain including the pineal gland. Deletion of Lhx9 results in sterility due to failure of gonadal development. The current study was initiated to investigate Lhx9 biology in the pineal gland. Lhx9 is highly expressed in the developing pineal gland of the rat with transcript abundance peaking early in development; transcript levels decrease postnatally to nearly undetectable levels in the adult, a temporal pattern that is generally similar to that reported for Lhx9 expression in other brain regions. Studies with C57BL/6J Lhx9−/− mutant mice revealed marked alterations in brain and pineal development. Specifically, the superficial pineal gland is hypoplastic, being reduced to a small cluster of pinealocytes surrounded by meningeal and vascular tissue. The deep pineal gland and the pineal stalk are also reduced in size. Although the brains of neonatal Lhx9−/− mutant mice appear normal, severe hydrocephalus develops in about 70 % of the Lhx9−/− mice at 5–8 weeks of age; these observations are the first to document that deletion of Lhx9 results in hydrocephalus and as such indicate that Lhx9 contributes to the maintenance of normal brain structure. Whereas hydrocephalus is absent in neonatal Lhx9−/−mutant mice, the neonatal pineal gland in these animals is hypoplastic. Accordingly, it appears that Lhx9 is essential for early development of the mammalian pineal gland and that this effect is not secondary to hydrocephalus. PMID:24647753

  11. Vesicular Glutamate Transporter 2 Expression in the Rat Pineal Gland: Detailed Analysis of Expression Pattern and Regulatory Mechanism

    NASA Astrophysics Data System (ADS)

    Yoshida, Sachine; Hisano, Setsuji

    Melatonin, a hormone secreted by the pineal gland, is closely related physiologically to circadian rhythm, sleep and reproduction, and also psychiatrically to mood disorders in humans. Under circadian control, melatonin secretion is modulated via nocturnal autonomic (adrenergic) stimulation to the gland, which expresses vesicular glutamate transporter (VGLUT) 1, VGLUT2 and a VGLUT1 splice variant (VGLUT1v), glutamatergic markers. Expression of VGLUT2 gene and protein in the intact gland has been reported to exhibit a rhythmic change during a day. To study VGLUT2 expression is under adrenergic control, we here performed an in vitro experiment using dispersed pineal cells of rats. Stimulation of either β-adrenergic receptor or cAMP production to the pineal cells was shown to increase mRNA level of VGLUT2, but not VGLUT1 and VGLUT1v. Because an ability of glutamate to inhibit melatonin production was previously reported in the cultured gland, it is likely that pineal VGLUT2 transports glutamate engaged in the inhibition of melatonin production.

  12. Rhodopsin Kinase Activity in the Mammalian Pineal Gland and Other Tissues

    NASA Astrophysics Data System (ADS)

    Somers, Robert L.; Klein, David C.

    1984-10-01

    Rhodopsin kinase, an enzyme involved in photochemical transduction in the retina, has been found in the mammalian pineal gland in amounts equal to those in the retina; other tissues had 7 percent of this amount, or less. This finding suggests that, in mammals, rhodopsin kinase functions in the pineal gland and other tissues to phosphorylate rhodopsin-like integral membrane receptors and is thereby involved in signal transduction.

  13. Functional unity of the thymus and pineal gland and study of the mechanisms of aging.

    PubMed

    Polyakova, V O; Linkova, N S; Kvetnoy, I M; Khavinson, V Kh

    2011-09-01

    The data on the morphology and functions of the thymus and pineal gland in individuals of different age are analyzed and common mechanisms of involution of these organs during aging and the consequencies of this process are discussed. Based on the data on the molecular changes in the thymus and pineal gland during aging, the authors hypothesize the functional unity of these organs and their mutual complementarity in the maintenance of normal immune and endocrine status during aging.

  14. The photoreceptive cells of the pineal gland in adult zebrafish (Danio rerio).

    PubMed

    Laurà, Rosaria; Magnoli, Domenico; Zichichi, Rosalia; Guerrera, Maria Cristina; De Carlos, Felix; Suárez, Alberto Álvarez; Abbate, Francesco; Ciriaco, Emilia; Vega, Jose Antonio; Germanà, Antonino

    2012-03-01

    The zebrafish pineal gland plays a fundamental role in the regulation of the circadian rhythm through the melatonin secretion. The pinealocytes, also called photoreceptive cells, are considered the morphofunctional unit of pineal gland. In literature, the anatomical features, the cellular characteristics, and the pinealocytes morphology of zebrafish pineal gland have not been previously described in detail. Therefore, this study was undertaken to analyze the structure and ultrastructure, as well as the immunohistochemical profile of the zebrafish pineal gland with particular reference to the pinealocytes. Here, we demonstrated, using RT-PCR, immunohistochemistry and transmission electron microscopy, the expression of the mRNA for rhodopsin in the pineal gland of zebrafish, as well as its cellular localization exclusively in the pinealocytes of adult zebrafish. Moreover, the ultrastructural observations demonstrated that the pinealocytes were constituted by an outer segment with numerous lamellar membranes, an inner segment with many mitochondria, and a basal pole with the synapses. Our results taken together demonstrated a central role of zebrafish pinealocytes in the control of pineal gland functions.

  15. Low-grade oligodendroglioma of the pineal gland: a case report and review of the literature

    PubMed Central

    2010-01-01

    Background Gliomas are a very rare subtype of pineal region tumours, whereas oligodendrogliomas of the pineal region are exceedingly rare, since there have been only 3 cases of anaplastic oligodedrogliomas reported this far. Methods-Results We present a case of a low-grade oligodendroglioma arising in the pineal gland of a 37 year-old woman. The patient presented with diplopia associated with a cystic pineal region mass demonstrated on MRI. Total resection was performed and histological examination showed that the cystic wall consisted of tumour cells with a central nucleus a perinuclear halo and minimal pleomorphism. Immnunohistochemical analysis showed that these cells were diffusely positive for CD57, and negative for GFAP, CD10, CD99, cytokeratins, neurofilaments and synaptophysin. FISH analysis was performed in a small number of neoplastic cells, which were not exhausted after immunohistochemistry and did not reveal deletion of 1p and 19q chromosome arms. However, the diagnosis of a low grade oligodendroglioma of the pineal gland was assigned. Conclusion Although the spectrum of tumours arising in the pineal gland is broad, the reports of oligodendrogliomas confined to this location are exceedingly rare, and to the best of our knowledge there is no report of a low-grade oligodendroglioma. However, they should be added in the long list of tumours arising in the pineal gland. PMID:20849631

  16. Evidence of Pineal Gland Calcification on CBCT is Not Insignificant: What Else You Might Discover about Your Patient.

    PubMed

    Fore, Stacy

    2016-01-01

    The use of CBCT technology in the dental office is increasing rapidly. These scans provide information on anatomy not previously evaluated with traditional 2D films. One structure often mentioned in a CBCT radiology report is the pineal gland. The pineal gland will show evidence of calcification, but this calcification is often dismissed as a normal aging process. This review of the function and influence of the pineal gland may influence the doctor to complete further evaluation of the patient.

  17. Evidence of Pineal Gland Calcification on CBCT is Not Insignificant: What Else You Might Discover about Your Patient.

    PubMed

    Fore, Stacy

    2016-01-01

    The use of CBCT technology in the dental office is increasing rapidly. These scans provide information on anatomy not previously evaluated with traditional 2D films. One structure often mentioned in a CBCT radiology report is the pineal gland. The pineal gland will show evidence of calcification, but this calcification is often dismissed as a normal aging process. This review of the function and influence of the pineal gland may influence the doctor to complete further evaluation of the patient. PMID:27319034

  18. Distribution of calcified concretions and calcium ions in the pig pineal gland.

    PubMed

    Lewczuk, B; Przybylska, B; Wyrzykowski, Z

    1994-01-01

    Serial sections of pig pineal glands were stained with von Kossa's and Alizarin red S methods to determine the occurrence and localization of calcified concretions. In the pineal glands of pigs aged eight months, concretions were not found. A small number of concretions was observed in all investigated pineal glands of three years old pigs. The concretions were distributed in the connective tissue of the pineal capsule and septa. The potassium pyroantimonate method was used for ultracytochemical localization of calcium ions. In pinealocytes, precipitates were observed in nuclei, mitochondria, Golgi apparatus, endoplasmic reticulum and cytoplasmic matrix. Single precipitates were found on the outer membranes of dense bodies, multivesicular bodies and lysosomes. There were no differences in the amount or the localization of precipitates between dark and light pinealocytes and between pinealocytes of animals aged both eight months and three years. The results suggest that: (1) the calcified concretions in the pig pineal gland are formed by the leptomeningeal tissue without participation of the pinealocytes, (2) cytoplasmic dense bodies, specific components of the pig pineal gland, are only slightly involved in calcium turnover in the pinealocytes. PMID:7758619

  19. Biochemical and hormonal evaluation of pineal glands exposed in vitro to magnetic fields. Final report

    SciTech Connect

    Anderson, L.E.; Leung, F.C.; Miller, D.L.

    1998-11-01

    It has been reported that exposure to extremely low frequency (ELF) magnetic fields can significantly alter pineal melatonin metabolism in vivo. However, whether such changes are due to direct or indirect effects of field exposure has not been clearly demonstrated. The objective of this research project was to examine the effects of magnetic fields on melatonin metabolism in pineal glands in vitro. Chicken pineal glands were cultured in a modified incubator encircled by a magnetic field exposure system. The incubator, that was remote from but attached to a standard laboratory incubator, contained a regulated light source for modulation of the light/dark cycle (12:12 L/D). Pineal glands from 4--6 week old chickens were maintained under 95% O{sub 2}, 5% CO{sub 2} in a static culture system. Because of problems due to contamination and loss of viability of such a system, a perfusion system was developed for EMF studies. Both single and multiple chicken pineal glands were used in the perfusion studies and were kept viable in the perfusion chamber by a continuous flow of medium at 39 C for up to 8 days. Perfusate samples were collected into a fraction collector and were subsequently kept frozen at {minus} 20 C until assays were performed. Melatonin secreted by the cultured pineal glands and released into the medium was measured by a melatonin double antibody radioimmunoassay (RIA) using {sup 125}I-melatonin as the label.

  20. Rax : developmental and daily expression patterns in the rat pineal gland and retina.

    PubMed

    Rohde, Kristian; Klein, David C; Møller, Morten; Rath, Martin F

    2011-09-01

    Retina and anterior neural fold homeobox (Rax) gene encodes a transcription factor essential for vertebrate eye development. Recent microarray studies indicate that Rax is expressed in the adult rat pineal gland and retina. The present study reveals that Rax expression levels in the rat change significantly during retinal development with a peak occurring at embryonic day 18, whereas Rax expression in the pineal is relatively delayed and not detectable until embryonic day 20. In both tissues, Rax is expressed throughout postnatal development into adulthood. In the mature rat pineal gland, the abundance of Rax transcripts increases 2-fold during the light period with a peak occurring at dusk. These findings are consistent with the evidence that Rax is of functional importance in eye development and suggest a role of Rax in the developing pineal gland. In addition, it would appear possible that Rax contributes to phenotype maintenance in the mature retina and pineal gland and may facilitate 24-h changes in the pineal transcriptome.

  1. Circadian changes in long noncoding RNAs in the pineal gland

    PubMed Central

    Coon, Steven L.; Munson, Peter J.; Cherukuri, Praveen F.; Sugden, David; Rath, Martin F.; Møller, Morten; Clokie, Samuel J. H.; Fu, Cong; Olanich, Mary E.; Rangel, Zoila; Werner, Thomas; Mullikin, James C.; Klein, David C.; Benjamin, Betty; Blakesley, Robert; Bouffard, Gerry; Brooks, Shelise; Chu, Grace; Coleman, Holly; Dekhtyar, Mila; Gregory, Michael; Guan, Xiaobin; Gupta, Jyoti; Han, Joel; Hargrove, April; Ho, Shi-ling; Johnson, Taccara; Legaspi, Richelle; Lovett, Sean; Maduro, Quino; Masiello, Cathy; Maskeri, Baishali; McDowell, Jenny; Montemayor, Casandra; Novotny, Betsy; Park, Morgan; Riebow, Nancy; Schandler, Karen; Schmidt, Brian; Sison, Christina; Stantripop, Mal; Thomas, James; Vemulapalli, Meg; Young, Alice

    2012-01-01

    Long noncoding RNAs (lncRNAs) play a broad range of biological roles, including regulation of expression of genes and chromosomes. Here, we present evidence that lncRNAs are involved in vertebrate circadian biology. Differential night/day expression of 112 lncRNAs (0.3 to >50 kb) occurs in the rat pineal gland, which is the source of melatonin, the hormone of the night. Approximately one-half of these changes reflect nocturnal increases. Studies of eight lncRNAs with 2- to >100-fold daily rhythms indicate that, in most cases, the change results from neural stimulation from the central circadian oscillator in the suprachiasmatic nucleus (doubling time = 0.5–1.3 h). Light exposure at night rapidly reverses (halving time = 9–32 min) levels of some of these lncRNAs. Organ culture studies indicate that expression of these lncRNAs is regulated by norepinephrine acting through cAMP. These findings point to a dynamic role of lncRNAs in the circadian system. PMID:22864914

  2. Homeobox genes and melatonin synthesis: regulatory roles of the cone-rod homeobox transcription factor in the rodent pineal gland.

    PubMed

    Rohde, Kristian; Møller, Morten; Rath, Martin Fredensborg

    2014-01-01

    Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT) enzyme activity. In the rodent, Aanat gene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a cAMP-based induction of Aanat transcription. However, additional transcriptional control mechanisms exist. Homeobox genes, which are generally known to encode transcription factors controlling developmental processes, are also expressed in the mature rodent pineal gland. Among these, the cone-rod homeobox (CRX) transcription factor is believed to control pineal-specific Aanat expression. Based on recent advances in our understanding of Crx in the rodent pineal gland, we here suggest that homeobox genes play a role in adult pineal physiology both by ensuring pineal-specific Aanat expression and by facilitating cAMP response element-based circadian melatonin production.

  3. Homeobox Genes and Melatonin Synthesis: Regulatory Roles of the Cone-Rod Homeobox Transcription Factor in the Rodent Pineal Gland

    PubMed Central

    Rath, Martin Fredensborg

    2014-01-01

    Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT) enzyme activity. In the rodent, Aanat gene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a cAMP-based induction of Aanat transcription. However, additional transcriptional control mechanisms exist. Homeobox genes, which are generally known to encode transcription factors controlling developmental processes, are also expressed in the mature rodent pineal gland. Among these, the cone-rod homeobox (CRX) transcription factor is believed to control pineal-specific Aanat expression. Based on recent advances in our understanding of Crx in the rodent pineal gland, we here suggest that homeobox genes play a role in adult pineal physiology both by ensuring pineal-specific Aanat expression and by facilitating cAMP response element-based circadian melatonin production. PMID:24877149

  4. Atypical pleomorphic neoplasms of the pineal gland: Case report and review of the literature

    PubMed Central

    Praver, M.; D’Amico, R.; Arraez, C.; Zacharia, B. E.; Varma, H.; Goldman, J. E.; Bruce, J. N.; Canoll, P.

    2015-01-01

    Background: Pineal region tumors are rare and diverse. Among them exist reports of pleomorphic xanthroastrocytoma (PXA) and pleomorphic granular cell astrocytoma (PGCA) of the pineal gland. These related tumors are remarkably similar sharing pleomorphic histologic features with only minor immunohistochemical and ultrastructural differences. Case Description: We present a case of a 42-year old right-handed woman presented with a longstanding history of migraine headaches which had worsened over the two months leading up to her hospitalization. MRI revealed a 1.7 × 1.3 × 1.6 cm intensely enhancing lesion originating in the pineal gland. The tumor closely resembled PGCA but did not strictly fit the diagnostic requirements of either PGCA or PXA. Conclusion: The present case highlights the exotic nature of pineal region tumors with pleomorphic cell histology. Given the diverse range of tumors encountered in the pineal region, pathological confirmation is mandatory. Favorable clinical outcomes demonstrate that surgical resection alone can yield excellent long-term results for tumors falling within the spectrum of pleomorphic lesions of the pineal gland. PMID:26257987

  5. Photoperiodic inhibition of testicular development is mediated by the pineal gland in white-footed mice

    SciTech Connect

    Johnston, P.G.; Boshes, M.; Zucker, I.

    1982-05-01

    White-footed mice were maintained in short or long photoperiods from birth to 60 days of age (10 h vs. 14 h of light per day). Testes weights and spermatogenesis were substantially reduced in short daylengths. Pinealectomy at 5-7 days of age eliminated the suppressive effect of photoperiod on the reproductive system. However, testicular development was not retarded in intact males kept from 25 to 60 days of age in short daylengths. Exposure to short daylengths prior to 25 days of age contributes to photoperiodic inhibition of testicular development. Removal of the pineal gland did not consistently affect gonadal maturation in long photoperiods. The pineal gland transduces the effects of short daylengths on reproductive development. Some effects of long daylengths on the neuroendocrine axis of white-footed mice may also be mediated by the pineal gland.

  6. 68Ga-DOTATATE uptake in pineal gland, a rare physiological variant: case series.

    PubMed

    Riaz, Saima; Syed, Rizwan; Skoura, Evangelia; Alshammari, Alshaima; Gaze, Mark; Sajjan, Rakesh; Halsey, Richard; Bomanji, Jamshed

    2015-11-01

    (68)Ga-DOTATATE PET-CT is widely used for the evaluation of neuroendocrine tumours. Knowledge of the physiological distribution of the radiotracer is of critical importance in characterizing focal areas of uptake. In this case series, we report three paediatric cases (average age 4.7 years ± 0.6 SD) with diagnosed advanced stage IV Neuroblastoma. Two had (68)Ga-DOTATATE PET-CT scans and one underwent (68)Ga-DOTATATE PET-MRI scan to assess for suitability of molecular therapy. Focal increased tracer uptake in the pineal gland was noted in all cases with no morphological abnormality on the corresponding CT and MRI scans. The uptake within the gland was thought to be a physiological variant rather than metastases owing to the heterogeneity of somatostatin receptors expression. The pineal gland has been reported to express somatostatin receptors. The physiological distribution of (68)Ga-DOTATATE uptake in the pineal gland is not routinely seen. Furthermore, the possibility of pineal meningioma is very unlikely as pineal meningiomas are very rare and there was no convincing morphological evidence of meningiomas on CT/MRI scan.

  7. [Substrates and possible mechanisms of pineal gland moon-sensory function in context of redusome hypothesis of aging and control of biological time in ontogenesis].

    PubMed

    Ivanov, S V

    2008-01-01

    As a result of comparison of the normative factors on human pineal gland volume (8 age groups, n=411) with similar factors obtained in the days of the moon phase extremes (n=49) the following phenomena have been determined. As a rule all the moon phase extremes, in particular the new moon, are accompanied by an appreciable reduce of pineal gland volume, a sort of systole. These changes depend on the age factor. The results of the research advance indirect arguments for the redusome hypothesis of aging.

  8. Nucleolus-like bodies in the pineal gland of the adult yak (Bos grunniens).

    PubMed

    Xie, Zhaohui H; Gan, Ping

    2013-05-28

    The pineal glands of adult yak were studied electron microscopically. Nucleolus-like bodies (NLBs) were found mostly in the pinealocytes and the interstitial cells of the pineal glands of the yak. The NLBs were electron-dense, round or ovoid bodies with a diameter of 50 nm - 500 nm. Two types of granules were identified as melanin. These may correspond to different stages of a progressive storage of melanin. Rough endoplasmic reticula with abundant ribosomes were observed. There was no correlation between the number of NLBs and the sex of the animals.

  9. Preliminary report on the correlations among pineal concretions, prostatic calculi and age in human adult males.

    PubMed

    Mori, Ryoichi; Kodaka, Tetsuo; Sano, Tsuneyoshi

    2003-09-01

    By using quantitative image analysis of soft X-ray photographs on the bulk of extracted pineal glands and prostates, we made a preliminary investigation into the correlations among pineal concretions (% by mass), prostatic calculi (% by mass) and age (years) in 40 human adult males, ranging in age from 31 to 95 years (mean (+/-SD) 69.9 +/- 15.2 years), who died and underwent the routine dissection course. The mass concentrations of pineal concretions and prostatic calculi were 17.68 +/- 13.56% (range 0-51.34%) and 0.93 +/- 1.31% (range 0-5.82%), respectively. There was no correlation between the mass concentration of pineal concretions and aging (r = 0.03; P < 1.0). There was no correlation between mass concentration of prostatic calculi and aging (r = 0.28; P < 0.5). No pineal concretions and no prostatic calculi were observed in seven and 10 cases, respectively; in addition, in one case, neither-concretions nor calculi were seen. From such data and from the previously reported suggestion on the counteracting functions between the pineal gland and prostate, a negative correlation between the mass concentrations of pineal concretions and prostatic calculi was expected. This was certainly obtained, but the correlation was low (r = -0.39; P < 0.05). Such a low correlation and no correlations between the concentrations of pineal concretions and aging or between prostatic calculi and aging may have been caused by the examination of relatively older humans. Therefore, further investigations using a number of pair samples collected from males including younger age generations will be necessary. PMID:14527133

  10. Preliminary report on the correlations among pineal concretions, prostatic calculi and age in human adult males.

    PubMed

    Mori, Ryoichi; Kodaka, Tetsuo; Sano, Tsuneyoshi

    2003-09-01

    By using quantitative image analysis of soft X-ray photographs on the bulk of extracted pineal glands and prostates, we made a preliminary investigation into the correlations among pineal concretions (% by mass), prostatic calculi (% by mass) and age (years) in 40 human adult males, ranging in age from 31 to 95 years (mean (+/-SD) 69.9 +/- 15.2 years), who died and underwent the routine dissection course. The mass concentrations of pineal concretions and prostatic calculi were 17.68 +/- 13.56% (range 0-51.34%) and 0.93 +/- 1.31% (range 0-5.82%), respectively. There was no correlation between the mass concentration of pineal concretions and aging (r = 0.03; P < 1.0). There was no correlation between mass concentration of prostatic calculi and aging (r = 0.28; P < 0.5). No pineal concretions and no prostatic calculi were observed in seven and 10 cases, respectively; in addition, in one case, neither-concretions nor calculi were seen. From such data and from the previously reported suggestion on the counteracting functions between the pineal gland and prostate, a negative correlation between the mass concentrations of pineal concretions and prostatic calculi was expected. This was certainly obtained, but the correlation was low (r = -0.39; P < 0.05). Such a low correlation and no correlations between the concentrations of pineal concretions and aging or between prostatic calculi and aging may have been caused by the examination of relatively older humans. Therefore, further investigations using a number of pair samples collected from males including younger age generations will be necessary.

  11. In silico genome wide mining of conserved and novel miRNAs in the brain and pineal gland of Danio rerio using small RNA sequencing data.

    PubMed

    Agarwal, Suyash; Nagpure, Naresh Sahebrao; Srivastava, Prachi; Kushwaha, Basdeo; Kumar, Ravindra; Pandey, Manmohan; Srivastava, Shreya

    2016-03-01

    MicroRNAs (miRNAs) are small, non-coding RNA molecules that bind to the mRNA of the target genes and regulate the expression of the gene at the post-transcriptional level. Zebrafish is an economically important freshwater fish species globally considered as a good predictive model for studying human diseases and development. The present study focused on uncovering known as well as novel miRNAs, target prediction of the novel miRNAs and the differential expression of the known miRNA using the small RNA sequencing data of the brain and pineal gland (dark and light treatments) obtained from NCBI SRA. A total of 165, 151 and 145 known zebrafish miRNAs were found in the brain, pineal gland (dark treatment) and pineal gland (light treatment), respectively. Chromosomes 4 and 5 of zebrafish reference assembly GRCz10 were found to contain maximum number of miR genes. The miR-181a and miR-182 were found to be highly expressed in terms of number of reads in the brain and pineal gland, respectively. Other ncRNAs, such as tRNA, rRNA and snoRNA, were curated against Rfam. Using GRCz10 as reference, the subsequent bioinformatic analyses identified 25, 19 and 9 novel miRNAs from the brain, pineal gland (dark treatment) and pineal gland (light treatment), respectively. Targets of the novel miRNAs were identified, based on sequence complementarity between miRNAs and mRNA, by searching for antisense hits in the 3'-UTR of reference RNA sequences of the zebrafish. The discovery of novel miRNAs and their targets in the zebrafish genome can be a valuable scientific resource for further functional studies not only in zebrafish but also in other economically important fishes.

  12. In silico genome wide mining of conserved and novel miRNAs in the brain and pineal gland of Danio rerio using small RNA sequencing data

    PubMed Central

    Agarwal, Suyash; Nagpure, Naresh Sahebrao; Srivastava, Prachi; Kushwaha, Basdeo; Kumar, Ravindra; Pandey, Manmohan; Srivastava, Shreya

    2015-01-01

    MicroRNAs (miRNAs) are small, non-coding RNA molecules that bind to the mRNA of the target genes and regulate the expression of the gene at the post-transcriptional level. Zebrafish is an economically important freshwater fish species globally considered as a good predictive model for studying human diseases and development. The present study focused on uncovering known as well as novel miRNAs, target prediction of the novel miRNAs and the differential expression of the known miRNA using the small RNA sequencing data of the brain and pineal gland (dark and light treatments) obtained from NCBI SRA. A total of 165, 151 and 145 known zebrafish miRNAs were found in the brain, pineal gland (dark treatment) and pineal gland (light treatment), respectively. Chromosomes 4 and 5 of zebrafish reference assembly GRCz10 were found to contain maximum number of miR genes. The miR-181a and miR-182 were found to be highly expressed in terms of number of reads in the brain and pineal gland, respectively. Other ncRNAs, such as tRNA, rRNA and snoRNA, were curated against Rfam. Using GRCz10 as reference, the subsequent bioinformatic analyses identified 25, 19 and 9 novel miRNAs from the brain, pineal gland (dark treatment) and pineal gland (light treatment), respectively. Targets of the novel miRNAs were identified, based on sequence complementarity between miRNAs and mRNA, by searching for antisense hits in the 3′-UTR of reference RNA sequences of the zebrafish. The discovery of novel miRNAs and their targets in the zebrafish genome can be a valuable scientific resource for further functional studies not only in zebrafish but also in other economically important fishes. PMID:26981358

  13. Developmental and diurnal expression of the synaptosomal-associated protein 25 (Snap25) in the rat pineal gland.

    PubMed

    Karlsen, Anna S; Rath, Martin F; Rohde, Kristian; Toft, Trine; Møller, Morten

    2013-06-01

    Snap25 (synaptosomal-associated protein) is a 25 kDa protein, belonging to the SNARE-family (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) of proteins, essential for synaptic and secretory vesicle exocytosis. Snap25 has by immunohistochemistry been demonstrated in the rat pineal gland but the biological importance of this is unknown. In this study, we demonstrate a high expression of mRNA encoding Snap25 in all parts of the rat pineal complex, the superficial-, and deep-pineal gland, as well as in the pineal stalk. Snap25 showed a low pineal expression during embryonic stages with a strong increase in expression levels just after birth. The expression showed no day/night variations. Neither removal of the sympathetic input to the pineal gland by superior cervical ganglionectomy nor bilateral decentralization of the superior cervical ganglia significantly affected the expression of Snap25 in the gland. The pineal expression levels of Snap25 were not changed following intraperitoneal injection of isoproterenol. The strong expression of Snap25 in the pineal gland suggests the presence of secretory granules and microvesicles in the rat pinealocyte supporting the concept of a vesicular release. At the transcriptional level, this Snap25-based release mechanism does not exhibit any diurnal rhythmicity and is regulated independently of the sympathetic nervous input to the gland.

  14. Melatonin and pineal gland peptides are able to correct the impairment of reproductive cycles in rats.

    PubMed

    Arutjunyan, Alexander; Kozina, Ljudmila; Milyutina, Yulia; Korenevsky, Andrew; Stepanov, Michael; Arutyunov, Vladimir

    2012-12-01

    Catecholamines play an important role in the hypothalamic regulation of the synthesis and secretion of gonadotropin- releasing hormone, or gonadoliberin. We have shown that melatonin and the pineal gland peptides (epithalamine and epitalon) exert a correcting influence on the diurnal dynamics of norepinephrine (NE) in the medial preoptic area (MPA) and of dopamine (DA) in the median eminence with arcuate nuclei (ME-Arc) disturbed by single administration of the neurotoxic xenobiotic 1,2-dimethylhydrazine (DMH) in female rats. It has been found that experiments with DMH administration can be used as an animal model of female reproductive system premature aging. The investigation of epithalamine (a polypeptide preparation from the bovine pineal gland) effect on circadian rhythms disturbed by the neurotoxic compound DMH has shown a recovery of the diurnal dynamics of NE in MPA. In addition, NE was found to decrease from 9:30 till 11 o'clock, Circadian Time (CT), which was typical of control animals. Epitalon (Ala-Glu-Asp-Gly) proved to be more effective in ME-Arc. This peptide prevents the xenobiotic caused disturbance of DA diurnal rhythm, keeping this metabolite low at 5 o'clock (CT) with it having increased by 11 o'clock (CT). The data obtained suggest that the pineal gland is important for the circadian signal normalization needed for gonadoliberin surge on the day of proestrus. Melatonin and peptides of the pineal gland can be considered as effective protectors of female reproductive system from xenobiotics and premature aging.

  15. Insulin modulates norepinephrine-mediated melatonin synthesis in cultured rat pineal gland

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mammalian pineal gland synthesizes melatonin in a circadian manner, peaking during the dark phase. This synthesis is primarily regulated by sympathetic innervations via noradrenergic fibers, but is also modulated by many peptidergic and hormonal systems. A growing number of studies reveal a comp...

  16. Rhodopsin expression in the zebrafish pineal gland from larval to adult stage.

    PubMed

    Magnoli, Domenico; Zichichi, Rosalia; Laurà, Rosaria; Guerrera, Maria Cristina; Campo, Salvatore; de Carlos, Felix; Suárez, Alberto Álvarez; Abbate, Francesco; Ciriaco, Emilia; Vega, Jose Antonio; Germanà, Antonino

    2012-03-01

    The zebrafish pineal gland plays an important role in different physiological functions including the regulation of the circadian clock. In the fish pineal gland the pinealocytes are made up of different segments: outer segment, inner segment and basal pole. Particularly, in the outer segment the rhodopsin participates in the external environment light reception that represents the first biochemical step in the melatonin production. It is well known that the rhodopsin in the adult zebrafish is well expressed in the pineal gland but both the expression and the cellular localization of this protein during development remain still unclear. In this study using qRT-PCR, sequencing and immunohistochemistry the expression as well as the protein localization of the rhodopsin in the zebrafish from larval (10 dpf) to adult stage (90 dpf) were demonstrated. The rhodopsin mRNA expression presents a peak of expression at 10 dpf, a further reduction to 50 dpf before increasing again in the adult stage. Moreover, the cellular localization of the rhodopsin-like protein was always localized in the pinealocyte at all ages examined. Our results demonstrated the involvement of the rhodopsin in the zebrafish pineal gland physiology particularly in the light capture during the zebrafish lifespan.

  17. Insulin modulates norepinephrine-mediated melatonin synthesis in cultured rat pineal gland.

    PubMed

    Garcia, Rodrigo Antonio Peliciari; Afeche, Solange Castro; Scialfa, Julieta Helena; do Amaral, Fernanda Gaspar; dos Santos, Sabrina Heloísa José; Lima, Fabio Bessa; Young, Martin Elliot; Cipolla-Neto, José

    2008-01-01

    The mammalian pineal gland synthesizes melatonin in a circadian manner, peaking during the dark phase. This synthesis is primarily regulated by sympathetic innervations via noradrenergic fibers, but is also modulated by many peptidergic and hormonal systems. A growing number of studies reveal a complex role for melatonin in influencing various physiological processes, including modulation of insulin secretion and action. In contrast, a role for insulin as a modulator of melatonin synthesis has not been investigated previously. The aim of the current study was to determine whether insulin modulates norepinephrine (NE)-mediated melatonin synthesis. The results demonstrate that insulin (10(- 8)M) potentiated norepinephrine-mediated melatonin synthesis and tryptophan hydroxylase (TPOH) activity in ex vivo incubated pineal glands. When ex vivo incubated pineal glands were synchronized (12h NE-stimulation, followed by 12h incubation in the absence of NE), insulin potentiated NE-mediated melatonin synthesis and arylalkylamine-N-acetyltransferase (AANAT) activity. Insulin did not affect the activity of hydroxyindole-O-methyltranferase (HIOMT), nor the gene expression of tpoh, aanat, or hiomt, under any of the conditions investigated. We conclude that insulin potentiates NE-mediated melatonin synthesis in cultured rat pineal gland, potentially through post-transcriptional events.

  18. Effects of 60-Hz electric fields on serotonin metabolism in the rat pineal gland

    SciTech Connect

    Anderson, L.E.; Hilton, D.I.; Phillips, R.D.; Wilson, B.W.; Chess, E.K.

    1982-06-01

    Serotonin and two of its metabolites, melatonin and 5-methoxytryptophol, exhibit circadian rhythmicity in the pineal gland. We recently reported a marked reduction in the normal night-time increase in melatonin concentration in the pineal glands of rats exposed to 60-Hz electric fields. Concomitant with the apparent abolition of melatonin rhythmicity, serotonin-N-acetyl transferase (SNAT) activity was suppressed. We have now conducted studies to determine if abolition of the rhythm in melatonin production in electric-field-exposed rats arises solely from interference in SNAT activity, or if the availability of pineal serotonin is a factor that is affected by exposure. Pineal serotonin concentrations were compared in rats that were either exposed or sham exposed to 65 kV/m for 30 days. Sham-exposed animals exhibited normal diurnal rhythmicity for pineal concentrations of both melatonin and serotonin; melatonin levels increased markedly during the dark phase with a concurrent decrease in serotonin levels. In the exposed animals, however, normal serotonin rhythmicity was abolished; serotonin levels in these animals did not increase during the light period. The conclusion that electric field exposure results in a biochemical alteration in SNAT enzyme activity can be inferred from the loss of both serotonin and melatonin rhythmicity, as well as by direct measurement of SNAT activity itself. 35 references, 3 figures, 1 table.

  19. Posttranslational regulation of TPH1 is responsible for the nightly surge of 5-HT output in the rat pineal gland.

    PubMed

    Huang, Zheping; Liu, Tiecheng; Chattoraj, Asamanja; Ahmed, Samreen; Wang, Michael M; Deng, Jie; Sun, Xing; Borjigin, Jimo

    2008-11-01

    Serotonin (5-hydroxytryptamine, 5-HT), a precursor for melatonin production, is produced abundantly in the pineal gland of all vertebrate animals. The synthesis of 5-HT in the pineal gland is rate limited by tryptophan hydroxylase 1 (TPH1) whose activity displays a twofold increase at night. Earlier studies from our laboratory demonstrate that pineal 5-HT secretion exhibits dynamic circadian rhythms with elevated levels during the early night, and that the increase is controlled by adrenergic signaling at night. In this study, we report that (a) 5-HT total output from the pineal gland and TPH1 protein levels both display diurnal rhythms with a twofold increase at night; (b) stimulation of cAMP signaling elevates 5-HT output in vivo; (c) 5-HT total output and TPH1 protein content in rat pineal gland are both acutely inhibited by light exposure at night. Consistent with these findings, molecular analysis of TPH1 protein revealed that (a) TPH1 is phosphorylated at the serine 58 in vitro and in the night pineal gland; and (b) phosphorylation of TPH1 at this residue is required for cAMP-enhanced TPH1 protein stability. These data support the model that increased nocturnal 5-HT synthesis in the pineal gland is mediated by the phosphorylation of TPH1 at the serine 58, which elevates the TPH1 protein content and activity at night.

  20. Endocrine rhythms in the brown bear (Ursus arctos): Evidence supporting selection for decreased pineal gland size

    PubMed Central

    Ware, Jasmine V; Nelson, O Lynne; Robbins, Charles T; Carter, Patrick A; Sarver, Brice A J; Jansen, Heiko T

    2013-01-01

    Many temperate zone animals adapt to seasonal changes by altering their physiology. This is mediated in large part by endocrine signals that encode day length and regulate energy balance and metabolism. The objectives of this study were to determine if the daily patterns of two important hormones, melatonin and cortisol, varied with day length in captive brown bears (Ursus arctos) under anesthetized and nonanesthetized conditions during the active (March–October) and hibernation periods. Melatonin concentrations varied with time of day and season in nonanesthetized female bears despite exceedingly low nocturnal concentrations (1–4 pg/mL) in the active season. In contrast, melatonin concentrations during hibernation were 7.5-fold greater than those during the summer in anesthetized male bears. Functional assessment of the pineal gland revealed a slight but significant reduction in melatonin following nocturnal light application during hibernation, but no response to beta-adrenergic stimulation was detected in either season. Examination of pineal size in two bear species bears combined with a phylogenetically corrected analysis of pineal glands in 47 other species revealed a strong relationship to brain size. However, pineal gland size of both bear species deviated significantly from the expected pattern. Robust daily plasma cortisol rhythms were observed during the active season but not during hibernation. Cortisol was potently suppressed following injection with a synthetic glucocorticoid. The results suggest that melatonin and cortisol both retain their ability to reflect seasonal changes in day length in brown bears. The exceptionally small pineal gland in bears may be the result of direct or indirect selection. PMID:24303132

  1. Interleukin-1 β Modulates Melatonin Secretion in Ovine Pineal Gland: Ex Vivo Study.

    PubMed

    Herman, A P; Bochenek, J; Skipor, J; Król, K; Krawczyńska, A; Antushevich, H; Pawlina, B; Marciniak, E; Tomaszewska-Zaremba, D

    2015-01-01

    The study was designed to determine the effect of proinflammatory cytokine, interleukin- (IL-) 1β, on melatonin release and expression enzymes essential for this hormone synthesis: arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT) in ovine pineal gland, taking into account the immune status of animals before sacrificing. Ewes were injected by lipopolysaccharide (LPS; 400 ng/kg) or saline, two hours after sunset during short day period (December). Animals were euthanized three hours after the injection. Next, the pineal glands were collected and divided into four explants. The explants were incubated with (1) medium 199 (control explants), (2) norepinephrine (NE; 10 µM), (3) IL-1β (75 pg/mL), or (4) NE + IL-1β. It was found that IL-1β abolished (P < 0.05) NE-induced increase in melatonin release. Treatment with IL-1β also reduced (P < 0.05) expression of AA-NAT enzyme compared to NE-treated explants. There was no effect of NE or IL-1β treatment on gene expression of HIOMT; however, the pineal fragments isolated from LPS-treated animals were characterized by elevated (P < 0.05) expression of HIOMT mRNA and protein compared to the explants from saline-treated ewes. Our study proves that IL-1β suppresses melatonin secretion and its action seems to be targeted on the reduction of pineal AA-NAT protein expression.

  2. Interleukin-1β Modulates Melatonin Secretion in Ovine Pineal Gland: Ex Vivo Study

    PubMed Central

    Herman, A. P.; Bochenek, J.; Skipor, J.; Król, K.; Krawczyńska, A.; Antushevich, H.; Pawlina, B.; Marciniak, E.; Tomaszewska-Zaremba, D.

    2015-01-01

    The study was designed to determine the effect of proinflammatory cytokine, interleukin- (IL-) 1β, on melatonin release and expression enzymes essential for this hormone synthesis: arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT) in ovine pineal gland, taking into account the immune status of animals before sacrificing. Ewes were injected by lipopolysaccharide (LPS; 400 ng/kg) or saline, two hours after sunset during short day period (December). Animals were euthanized three hours after the injection. Next, the pineal glands were collected and divided into four explants. The explants were incubated with (1) medium 199 (control explants), (2) norepinephrine (NE; 10 µM), (3) IL-1β (75 pg/mL), or (4) NE + IL-1β. It was found that IL-1β abolished (P < 0.05) NE-induced increase in melatonin release. Treatment with IL-1β also reduced (P < 0.05) expression of AA-NAT enzyme compared to NE-treated explants. There was no effect of NE or IL-1β treatment on gene expression of HIOMT; however, the pineal fragments isolated from LPS-treated animals were characterized by elevated (P < 0.05) expression of HIOMT mRNA and protein compared to the explants from saline-treated ewes. Our study proves that IL-1β suppresses melatonin secretion and its action seems to be targeted on the reduction of pineal AA-NAT protein expression. PMID:26339621

  3. Significant anti-tumor effect of bevacizumab in treatment of pineal gland glioblastoma multiforme.

    PubMed

    Mansour, Joshua; Fields, Braxton; Macomson, Samuel; Rixe, Olivier

    2014-12-01

    Glioblastoma multiforme (GBM) is the most aggressive subtype of malignant gliomas. Current standard treatment for GBM involves a combination of cytoreduction through surgical resection, followed by radiation with concomitant and adjuvant chemotherapy (temozolomide). The role of bevacizumab in the treatment of GBM continues to be a topic of ongoing research and debate. Despite aggressive treatment, these tumors remain undoubtedly fatal, especially in the elderly. Furthermore, tumors present in the pineal gland are extremely rare, accounting for only 0.1-0.4 % of all adult brain tumors, with this location adding to the complexity of treatment. We present a case of GBM, at the rare location of pineal gland, in an elderly patient who was refractory to initial standard of care treatment with radiation and concomitant and adjuvant temozolomide, but who developed a significant response to anti-angiogenic therapy using bevacizumab.

  4. Functional development of the circadian clock in the zebrafish pineal gland.

    PubMed

    Ben-Moshe, Zohar; Foulkes, Nicholas S; Gothilf, Yoav

    2014-01-01

    The zebrafish constitutes a powerful model organism with unique advantages for investigating the vertebrate circadian timing system and its regulation by light. In particular, the remarkably early and rapid development of the zebrafish circadian system has facilitated exploring the factors that control the onset of circadian clock function during embryogenesis. Here, we review our understanding of the molecular basis underlying functional development of the central clock in the zebrafish pineal gland. Furthermore, we examine how the directly light-entrainable clocks in zebrafish cell lines have facilitated unravelling the general mechanisms underlying light-induced clock gene expression. Finally, we summarize how analysis of the light-induced transcriptome and miRNome of the zebrafish pineal gland has provided insight into the regulation of the circadian system by light, including the involvement of microRNAs in shaping the kinetics of light- and clock-regulated mRNA expression. The relative contributions of the pineal gland central clock and the distributed peripheral oscillators to the synchronization of circadian rhythms at the whole animal level are a crucial question that still remains to be elucidated in the zebrafish model.

  5. Nocturnal headache associated with melatonin deficiency due to a pineal gland cyst.

    PubMed

    Karadaş, Omer; Ipekdal, Ilker H; Ulaş, Umit H; Odabaşi, Zeki

    2012-02-01

    The cyclic nature of some of headache disorders is closely related to melatonin, which is secreted by the pineal gland. We report a 29-year-old male patient with a 2.5-year history of headaches that woke him in the middle of the night. These headaches were pulsatile and continued until sunrise. During these attacks he also suffered from allodynia over the scalp, bilateral conjunctival hyperemia, and nervousness. His brain MRI showed a 5mm by 4mm neuroepithelial cyst in the pineal gland. The peak plasma melatonin level that was measured at 2 am was 28 pg/mL. The patient underwent oral melatonin treatment (6 mg/day). After 1 month he experienced a 70% reduction in his symptoms. When the melatonin dosage was increased to 10mg/day he became headache-free, and 5 months after the treatment began, had no complaints. His 5-month follow-up plasma melatonin level at 2 am was 61 pg/mL. To our knowledge this is the first report of a patient with nocturnal headache associated with a low level of melatonin due to a neuroepithelial cyst in the pineal gland.

  6. Ultrastructural interrelationship between the pineal gland and the testis in the male rat.

    PubMed

    Kuş, I; Sarsilmaz, M; Ogetürk, M; Yilmaz, B; Keleştimur, H; Oner, H

    2000-01-01

    The ultrastructural interrelationship between the pineal gland and testis was evaluated in the rat. Wistar rats were divided into 6 groups. Groups I and II were sham-orchidectomized and orchidectomized rats, respectively. Rats in group III were orchidectomized and daily injected with testosterone propionate (TP) for 1 month. Groups IV and V were sham-pinealectomized and pinealectomized, respectively. Group VI was pinealectomized and daily injected with melatonin for 2 months. All animals were anesthetized with ketamine for fixation by vascular perfusion. Pineal glands of groups I, II, and III and the testes of groups IV, V, and VI were removed and weighed. All specimens were examined by electron microscopy. Orchidectomy caused an increase of lipid droplets, cytoplasmic dense bodies, and lysosomes. Rough endoplasmic reticulum, Golgi apparatus, and mitochondria were extensive in the cytoplasm. TP administration to orchidectomized rats resulted in formation of less extensive lipid droplets and mitochondria. In pinealectomized rats, golgi complex, mitochondria, and enlarged smooth endoplasmic reticulum were extensive in the cytoplasm of Leydig cells. Formation of cytoplasmic secretory granules and osmiophilic bodies was observed. Testicular weight increased compared to group IV. Melatonin decreased testicular weight in comparison to group V and prevented ultrastructural changes. Pinealectomy and orchidectomy caused hyperactivity in Leydig cells and pinealocytes, respectively, which suggests a mutual relationship between the pineal gland and testis in the rat.

  7. Functional Development of the Circadian Clock in the Zebrafish Pineal Gland

    PubMed Central

    Ben-Moshe, Zohar; Foulkes, Nicholas S.

    2014-01-01

    The zebrafish constitutes a powerful model organism with unique advantages for investigating the vertebrate circadian timing system and its regulation by light. In particular, the remarkably early and rapid development of the zebrafish circadian system has facilitated exploring the factors that control the onset of circadian clock function during embryogenesis. Here, we review our understanding of the molecular basis underlying functional development of the central clock in the zebrafish pineal gland. Furthermore, we examine how the directly light-entrainable clocks in zebrafish cell lines have facilitated unravelling the general mechanisms underlying light-induced clock gene expression. Finally, we summarize how analysis of the light-induced transcriptome and miRNome of the zebrafish pineal gland has provided insight into the regulation of the circadian system by light, including the involvement of microRNAs in shaping the kinetics of light- and clock-regulated mRNA expression. The relative contributions of the pineal gland central clock and the distributed peripheral oscillators to the synchronization of circadian rhythms at the whole animal level are a crucial question that still remains to be elucidated in the zebrafish model. PMID:24839600

  8. Seasonal postembryonic maturation of the diurnal rhythm of serotonin in the chicken pineal gland.

    PubMed

    Piesiewicz, Aneta; Kedzierska, Urszula; Turkowska, Elzbieta; Adamska, Iwona; Majewski, Pawel M

    2015-02-01

    Previously, we have demonstrated the postembryonic development of chicken (Gallus gallus domesticus L.) pineal gland functions expressed as changes in melatonin (MEL) biosynthesis. Pineal concentrations of MEL and its precursor serotonin (5-HT) were shown to increase between the 2nd and 16th day of life. We also found that levels of the mRNAs encoding the enzymes participating in the final two steps of MEL biosynthesis from 5-HT: arylalkylamine-N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase (HIOMT), as well as their enzymatic activities, were raised during postembryonic development. Moreover, the manner of these changes was season-of-hatch dependent, even in animals kept under constant laboratory conditions (L:D 12:12). The most pronounced changes were seen in the concentrations of 5-HT and MEL, as well as in Aanat mRNA level and its enzymatic activity. The high daily variability in 5-HT content suggested that season- and age-dependent changes in the activity of the chicken pineal gland might rely on the availability of 5-HT, i.e. it may be limited by changes in pineal tryptophan (TRP) and/or 5-hydroxytryptophan (5-HTP) levels as well as by the activity of tryptophan hydroxylase (TPH) and aromatic l-amino acid decarboxylase (AADC): two enzymes participating in the conversion of TRP to 5-HT. The present study was undertaken with the following objectives: (1) to examine whether the pineal concentration of the 5-HT precursors TRP and 5-HTP exhibit age- and season-related changes; (2) to look for season-related differences in the transcription of the Tph1 and Ddc genes encoding enzymes TPH and AADC; (3) to identify the step(s) in postembryonic development in which these season-related variations in pineal gland function are most pronounced. Male Hy-line chickens hatched in the summer or winter, from eggs laid by hens held in L:D 16:8 conditions were kept from the day of hatch in L:D 12:12 conditions. At the age of 2 or 9 days, animals were sacrificed

  9. Expression and regulation of Icer mRNA in the Syrian hamster pineal gland.

    PubMed

    Diaz, Elena; Garidou, Marie-Laure; Dardente, Hugues; Salingre, Anthony; Pévet, Paul; Simonneaux, Valérie

    2003-04-10

    Inducible-cAMP early repressor (ICER) is a potent inhibitor of CRE (cAMP-related element)-driven gene transcription. In the rat pineal gland, it has been proposed to be part of the mechanisms involved in the shutting down of the transcription of the gene coding for arylalkylamine N-acetyltransferase (AA-NAT, the melatonin rhythm-generating enzyme). In this study, we report that ICER is expressed in the pineal gland of the photoperiodic rodent Syrian hamster although with some difference compared to the rat. In the Syrian hamster pineal, Icer mRNA levels, low at daytime, displayed a 20-fold increase during the night. Nighttime administration of a beta-adrenergic antagonist, propranolol, significantly reduced Icer mRNA levels although daytime administration of a beta-adrenergic agonist, isoproterenol, was unable to raise the low amount of Icer mRNA. These observations indicate that Icer mRNA expression is induced by the clock-driven norepinephrine release and further suggest that this stimulation is restricted to nighttime, as already observed for Aa-nat gene transcription. Furthermore, we found that the daily profile of Icer mRNA displayed photoperiodic variation with a lengthening of the nocturnal peak in short versus long photoperiod. These data indicate that ICER may be involved in both daily and seasonal regulation of melatonin synthesis in the Syrian hamster.

  10. Pineal gland of a nocturnal bird, Indian spotted owlet, Athene brama: morphological and endocrine observations.

    PubMed

    Haldar, C; Guchhait, P

    2000-07-01

    It has been reported that owls (Strigiformes) do not have a pineal gland. However, our light microscopy study revealed an intermediate form of tubulofollicular and solid-type large pineal gland in a tropical owlet, Athene brama. The epithelial cells forming follicles (6-8) in the distal region and the solid cluster of parenchymal cells of different diameters in the proximal region anteriorly tapered with a long cylindrical stalk and continued into commissural organs and choroid plexus. The intrapineal localization of perivascular nerve fibers and blood vessels clearly explained the sympathetic innervation as well as vascularization of this neuroendocrine gland. Further, electron microscopy revealed a developed intracellular structure of the pinealocytes with a large number of mitochondria, Golgi bodies, and granular as well as clear vesicles in the process terminals. The evidence of intrapinealocyte lipid droplets and dense bodies and a moderate amount of melatonin in plasma (ranging from 100-365 pg/mL) during different reproductive phases finally proved a defined secretory activity of the gland in this tropical, nocturnal bird.

  11. The in vitro maintenance of clock genes expression within the rat pineal gland under standard and norepinephrine-synchronized stimulation.

    PubMed

    Andrade-Silva, Jéssica; Cipolla-Neto, José; Peliciari-Garcia, Rodrigo A

    2014-01-01

    Although the norepinephrine (NE) synchronization protocol was proved to be an important procedure for further modulating in vitro pineal melatonin synthesis, the maintenance of clock genes under the same conditions remained to be investigated. The aim of this study was to investigate the maintenance of the clock genes expression in pineal gland cultures under standard and NE-synchronized stimulation. The glands were separated into three experimental groups: Control, Standard (acute NE-stimulation), and NE-synchronized. The expression of Bmal1, Per2, Cry2, Rev-erbα, the clock controlled gene Dbp and Arylalkylamine-N-acetyltransferase were investigated, as well as melatonin content. No oscillations were observed in the expression of the investigated genes from the control group. Under Standard NE stimulation, the clock genes did not exhibit a rhythmic pattern of expression. However, in the NE-synchronized condition, a rhythmic expression pattern was observed in all cases. An enhancement in pineal gland responsiveness to NE stimulation, reflected in an advanced synthesis of melatonin was also observed. Our results reinforce our previous hypothesis that NE synchronization of pineal gland culture mimics the natural rhythmic release of NE in the gland, increasing melatonin synthesis and keeping the pineal circadian clock synchronized, ensuring the fine adjustments that are relied in the clockwork machinery.

  12. The contribution of the pineal gland on daily rhythms and masking in diurnal grass rats, Arvicanthis niloticus.

    PubMed

    Shuboni, Dorela D; Agha, Amna A; Groves, Thomas K H; Gall, Andrew J

    2016-07-01

    Melatonin is a hormone rhythmically secreted at night by the pineal gland in vertebrates. In diurnal mammals, melatonin is present during the inactive phase of the rest/activity cycle, and in primates it directly facilitates sleep and decreases body temperature. However, the role of the pineal gland for the promotion of sleep at night has not yet been studied in non-primate diurnal mammalian species. Here, the authors directly examined the hypothesis that the pineal gland contributes to diurnality in Nile grass rats by decreasing activity and increasing sleep at night, and that this could occur via effects on circadian mechanisms or masking, or both. Removing the pineal gland had no effect on the hourly distribution of activity across a 12:12 light-dark (LD) cycle or on the patterns of sleep-like behavior at night. Masking effects of light at night on activity were also not significantly different in pinealectomized and control grass rats, as 1h pulses of light stimulated increases in activity of sham and pinealectomized animals to a similar extent. In addition, the circadian regulation of activity was unaffected by the surgical condition of the animals. Our results suggest that the pineal gland does not contribute to diurnality in the grass rat, thus highlighting the complexity of temporal niche transitions. The current data raise interesting questions about how and why genetic and neural mechanisms linking melatonin to sleep regulatory systems might vary among mammals that reached a diurnal niche via parallel and independent pathways.

  13. Adenosine triphosphate inhibits melatonin synthesis in the rat pineal gland.

    PubMed

    Souza-Teodoro, Luis Henrique; Dargenio-Garcia, Letícia; Petrilli-Lapa, Camila Lopes; Souza, Ewerton da Silva; Fernandes, Pedro A C M; Markus, Regina P; Ferreira, Zulma S

    2016-03-01

    Adenosine triphosphate (ATP) is released onto the pinealocyte, along with noradrenaline, from sympathetic neurons and triggers P2Y1 receptors that enhance β-adrenergic-induced N-acetylserotonin (NAS) synthesis. Nevertheless, the biotransformation of NAS into melatonin, which occurs due to the subsequent methylation by acetylserotonin O-methyltransferase (ASMT; EC 2.1.1.4), has not yet been evaluated in the presence of purinergic stimulation. We therefore evaluated the effects of purinergic signaling on melatonin synthesis induced by β-adrenergic stimulation. ATP increased NAS levels, but, surprisingly, inhibited melatonin synthesis in an inverse, concentration-dependent manner. Our results demonstrate that enhanced NAS levels, which depend on phospholipase C (PLC) activity (but not the induction of gene transcription), are a post-translational effect. By contrast, melatonin reduction is related to an ASMT inhibition of expression at both the gene transcription and protein levels. These results were independent of nuclear factor-kappa B (NF-kB) translocation. Neither the P2Y1 receptor activation nor the PLC-mediated pathway was involved in the decrease in melatonin, indicating that ATP regulates pineal metabolism through different mechanisms. Taken together, our data demonstrate that purinergic signaling differentially modulates NAS and melatonin synthesis and point to a regulatory role for ATP as a cotransmitter in the control of ASMT, the rate-limiting enzyme in melatonin synthesis. The endogenous production of melatonin regulates defense responses; therefore, understanding the mechanisms involving ASMT regulation might provide novel insights into the development and progression of neurological disorders since melatonin presents anti-inflammatory, neuroprotective, and neurogenic effects.

  14. Alpha-2 adrenergic activity of bromocriptine and quinpirole in chicken pineal gland. Effects on melatonin synthesis and ( sup 3 H)rauwolscine binding

    SciTech Connect

    Zawilska, J.; Iuvone, P.M. )

    1990-12-01

    In the pineal gland and retina of chickens, serotonin N-acetyl-transferase (NAT) activity and melatonin content are modulated by different receptors, alpha-2 adrenergic receptors in pineal gland and D2-dopamine receptors in retina. The effect of two D2-dopamine receptor agonists, bromocriptine and quinpirole (LY 171555), on melatonin synthesis in these tissues was investigated. Systemic administrations of bromocriptine and quinpirole decreased nocturnal NAT activity and melatonin content of both pineal gland and retina. Bromocriptine was equipotent in the two tissues, whereas quinpirole was approximately 100-fold more potent in retina than in pineal gland. In pineal gland, the suppressive effects of bromocriptine and quinpirole on NAT activity were blocked by yohimbine, a selective alpha-2 adrenergic receptor antagonist, but not by spiperone, a D2-dopamine receptor antagonist. In contrast, bromocriptine- and quinpirole-induced decreases of the enzyme activity in retina were antagonized by spiperone, and not affected by yohimbine. The nocturnal increase of NAT activity of pineal glands in vitro was inhibited with an order of potency clonidine greater than bromocriptine greater than quinpirole. Additionally, bromocriptine and quinpirole displaced the specific binding of (3H)rauwolscine, an alpha-2 adrenergic receptor antagonist, to membranes from chicken pineal gland, with potencies comparable to those observed for inhibition of NAT activity in vitro. It is suggested that bromocriptine and quinpirole, in addition to their D2-dopaminergic activity, can stimulate alpha-2 adrenergic receptors in pineal gland of chicken.

  15. Gliosarcomas arising from the pineal gland region: uncommon localization and rare tumors.

    PubMed

    Sugita, Yasuo; Terasaki, Mizuhiko; Tanigawa, Ken; Ohshima, Koichi; Morioka, Motohiro; Higaki, Koichi; Nakagawa, Setsuko; Shimokawa, Shoko; Nakashima, Susumu

    2016-02-01

    Gliosarcomas are a variant of glioblastomas and present a biphasic pattern, with coexisting glial and mesenchymal components. In this study, two unusual cases are presented. Case 1 is a 52-year-old woman with a headache and memory disturbance for a month. Case 2 is an 18-year-old man with a headache lasting two weeks. In both cases, an MRI revealed enhancing T1-low to iso, T2-iso to high intensity lesions in the pineal gland region. Histologically, in case 1, the tumor showed spindle cell proliferation with disorganized fascicles and cellular pleomorphism. Tumor cells variously exhibited oncocytic transformation. Immunohistochemically, most of the spindle tumor cells were positive for myoglobin and desmin. Some of the tumor cells were positive for GFAP and S-100 protein. On the other hand, all tumor cells were positive for CD133, Musashi1, and SOX-2 which are the markers of neural stem cells. In case 2, the tumor showed monotonous proliferation of short spindle cells with disorganized fascicles and cellular atypism. The morphological distinction between glial and mesenchymal components was not apparent. Immunohistochemically, most of the spindle tumor cells were positive for desmin. Glial tumor cells that were dispersed within the sarcoma as single cells were positive for GFAP. In addition, all tumor cells were positive for CD133, Musashi1 and SOX-2. Based on these microscopic appearances, and immunohistochemical findings, these cases were diagnosed as gliosarcomas arising from the pineal gland region. These results also indicated that pluripotential cancer stem cells differentiated into glial and muscle cell lines at the time of tumor growth. In a survey of previous publications on gliosarcoma arising from the pineal gland, these cases are the second and third reports found in English scientific writings.

  16. Structural organization of the human S-antigen gene. cDNA, amino acid, intron, exon, promoter, in vitro transcription, retina, and pineal gland.

    PubMed

    Yamaki, K; Tsuda, M; Kikuchi, T; Chen, K H; Huang, K P; Shinohara, T

    1990-12-01

    S-Antigen (S-Ag) is a major soluble photoreceptor protein involved in the visual transduction cascade. Several S-Ag cDNAs and a gene coding for human S-Ag were isolated from cDNA and gene libraries. The gene sequences of the coding, noncoding, and 5'-flanking regions of the gene were determined. The S-Ag gene was approximately 50 kbp (kilobase pairs) in length and contained 16 exons and 15 introns. The length of most exons was less than 100 base pairs (bp) and the smallest one was only 10 bp. In contrast, the length of most introns was larger than 2 kbp, and the gene comprised 97% intron and 3% exon. The splice sites for donor and acceptor were in good agreement with the GT/AG rule. The S-Ag protein of 403 amino acid residues was translated from a mRNA of 1.9 kbp, and the mRNA was transcribed from a gene of 50 kbp. The 5'-flanking region of the gene, approximately 1.1 kbp long, had no known regulatory elements for transcription such as TATA, GC, and CCAAT boxes. Interestingly, the 5'-flanking region had promoter activity in an in vitro transcription assay using a nuclear extract of rat brain. A major transcription start site was found at 387 bp upstream from the translation start site ATG. Our results indicate that the sequence of S-Ag promoter differs from other known promoters and may, perhaps, be specific for photoreceptor rod cells and pinealocytes.

  17. Rosette-forming glioneuronal tumor in the pineal gland and the third ventricle: a case with radiological and clinical implications

    PubMed Central

    Xu, Junqing; Yang, Yong; Liu, Ying; Wei, Mengqi; Ren, Jing; Chang, Yingjuan; Huan, Yi; Yin, Hong

    2012-01-01

    A 39-year-old man presented with more than 20 years history of episodic headache and one year history of dizziness, impaired vision and memory disorders. Computed tomography and Magnetic resonance imaging revealed a cystic mass involving the pineal gland, tectum and the third ventricle and obstruction of the aqueduct. Interestingly, the fourth ventricle was not involved in this case. The pathological diagnosis was rosette forming glioneuronal tumor (RGNT). These lesions are considered low-grade tumors (WHO grade I). We describe here the fifth reported patient with a pineal gland RGNT and the eighth reported patient with a RGNT outside the fourth ventricle. PMID:23256084

  18. Pineal Gland Calcification in Kurdistan: A Cross-Sectional Study of 480 Roentgenograms

    PubMed Central

    Mohammed, Kahee A.; Ismail, Honer A.; Geneus, Christian J.; Tobo, Betelihem B.; Buchanan, Paula M.; Zelicoff, Alan P.

    2016-01-01

    Objective The goal of this study was to compare the incidence of Pineal Gland Calcification (PGC) by age group and gender among the populations living in the Kurdistan Region-Iraq. Methods This prospective study examined skull X-rays of 480 patients between the ages of 3 and 89 years who sought care at a large teaching public hospital in Duhok, Iraq from June 2014 to November 2014. Descriptive statistics and a binary logistic regression were used for analysis. Results The overall incidence rate of PGC among the study population was 26.9% with the 51–60 age group and males having the highest incidence. PGC incidence increased after the first decade and remained steady until the age of 60. Thereafter the incidence began to decrease. Logistic regression analysis revealed that both age and gender significantly affected the risk of PGC. After adjusting for age, males were 1.94 (95% CI, 1.26–2.99) times more likely to have PGC compared to females. In addition, a one year increase in age increases the odds of developing PGC by 1.02 (95% CI, 1.01–1.03) units after controlling for the effects of gender. Conclusion Our analysis demonstrated a close relationship between PGC and age and gender, supporting a link between the development of PGC and these factors. This study provides a basis for future researchers to further investigate the nature and mechanisms underlying pineal gland calcification. PMID:27415622

  19. Circadian dynamics of the cone-rod homeobox (CRX) transcription factor in the rat pineal gland and its role in regulation of arylalkylamine N-acetyltransferase (AANAT).

    PubMed

    Rohde, Kristian; Rovsing, Louise; Ho, Anthony K; Møller, Morten; Rath, Martin F

    2014-08-01

    The cone-rod homeobox (Crx) gene encodes a transcription factor in the retina and pineal gland. Crx deficiency influences the pineal transcriptome, including a reduced expression of arylalkylamine N-acetyltransferase (Aanat), a key enzyme in nocturnal pineal melatonin production. However, previous functional studies on pineal Crx have been performed in melatonin-deficient mice. In this study, we have investigated the role of Crx in the melatonin-proficient rat pineal gland. The current study shows that pineal Crx transcript levels exhibit a circadian rhythm with a peak in the middle of the night, which is transferred into daily changes in CRX protein. The study further shows that the sympathetic innervation of the pineal gland controls the Crx rhythm. By use of adenovirus-mediated short hairpin RNA gene knockdown targeting Crx mRNA in primary rat pinealocyte cell culture, we here show that intact levels of Crx mRNA are required to obtain high levels of Aanat expression, whereas overexpression of Crx induces Aanat transcription in vitro. This regulatory function of Crx is further supported by circadian analysis of Aanat in the pineal gland of the Crx-knockout mouse. Our data indicate that the rhythmic nature of pineal CRX protein may directly modulate the daily profile of Aanat expression by inducing nighttime expression of this enzyme, thus facilitating nocturnal melatonin synthesis in addition to its role in ensuring a correct tissue distribution of Aanat expression.

  20. Neuropeptide Y as a presynaptic modulator of norepinephrine release from the sympathetic nerve fibers in the pig pineal gland.

    PubMed

    Ziółkowska, N; Lewczuk, B; Przybylska-Gornowicz, B

    2015-01-01

    Norepinephrine (NE) released from the sympathetic nerve endings is the main neurotransmitter controlling melatonin synthesis in the mammalian pineal gland. Although neuropeptide Y (NPY) co-exists with NE in the pineal sympathetic nerve fibers it also occurs in a population of non-adrenergic nerve fibers located in this gland. The role of NPY in pineal physiology is still enigmatic. The present study characterizes the effect of NPY on the depolarization-evoked 3H-NE release from the pig pineal explants. The explants of the pig pineal gland were loaded with 3H-NE in the presence of pargyline and superfused with Tyrode medium. They were exposed twice to the modified Tyrode medium containing 60 mM of K+ to evoke the 3H-NE release via depolarization. NPY, specific agonists of Y1- and Y2- receptors and pharmacologically active ligands of α2-adrenoceptors were added to the medium before and during the second depolarization. The radioactivity was measured in medium fractions collected every 2 minutes during the superfusion. NPY (0.1-10 μM) significantly decreased the depolarization-induced 3H-NE release. Similar effect was observed after the treatment with Y2-agonist: NPY13-36, but not with Y1-agonist: [Leu31,Pro34]-NPY. The tritium overflow was lower in the explants exposed to the 5 μM NPY and 1 μM rauwolscine than to rauwolscine only. The effects of 5 μM NPY and 0.05 μM UK 14,304 on the depolarization-evoked 3H-NE release were additive. The results show that NPY is involved in the regulation of NE release from the sympathetic terminals in the pig pineal gland, inhibiting this process via Y2-receptors.

  1. This pineal gland does not mediate phase shifts in the disc shedding rhythm of the rat retina

    SciTech Connect

    Goldman, A.I.

    1982-01-01

    Albino rats were subjected to pinealectomy, superior cervical ganglionectomy, or the appropriate sham preparation and were placed in lighting conditions so that light onset was advanced by 10 hr. After 6 days of this regimen, all animals exhibited a complete shift in their outer segment disc shedding rhythm, indicating that the pineal gland is not a factor in mediating such a shift.

  2. Cartesian theories on the passions, the pineal gland and the pathogenesis of affective disorders: an early forerunner.

    PubMed

    López-Muñoz, F; Alamo, C

    2011-03-01

    The relationship between physical and functional alterations in the pineal gland, the 'passions' (emotions or feelings) and psychopathology has been a constant throughout the history of medicine. One of the most influential authors on this subject was René Descartes, who discussed it in his work The Treatise on the Passions of the Soul (1649). Descartes believed that 'passions' were sensitive movements that the soul, located in the pineal gland, experienced due to its union with the body, by circulating animal spirits. Descartes described sadness as one of the six primitive passions of the soul, which leads to melancholy if not remedied. Cartesian theories had a great deal of influence on the way that mental pathologies were considered throughout the entire 17th century and during much of the 18th century, but the link between the pineal gland and psychiatric disorders it was definitively highlighted in the 20th century, with the discovery of melatonin in 1958. The recent development of a new pharmacological agent acting through melatonergic receptors (agomelatine) has confirmed the close link between the pineal gland and affective disorders.

  3. Characterization of binding sites for [3H]-DTG, a selective sigma receptor ligand, in the sheep pineal gland.

    PubMed

    Abreu, P; Sugden, D

    1990-09-14

    Specific binding sites for [3H]-1,3 di-ortho-tolylguanidine ([3H]-DTG), a selective radiolabeled sigma receptor ligand, were detected and characterized in sheep pineal gland membranes. The binding of [3H]-DTG to sheep pineal membranes was rapid and reversible with a rate constant for association (K+1) at 25 degrees C of 0.0052 nM-1.min-1 and rate constant for dissociation (K-1) 0.0515 min-1, giving a Kd (K-1/K+1) of 9.9 nM. Saturation studies demonstrated that [3H]-DTG binds to a single class of sites with an affinity constant (Kd) of 27 +/- 3.4 nM, and a total binding capacity (Bmax) of 1.39 +/- 0.03 pmol/mg protein. Competition experiments showed that the relative order of potency of compounds for inhibition of [3H]-DTG binding to sheep pineal membranes was as follows: trifluoperazine = DTG greater than haloperidol greater than pentazocine greater than (+)-3-PPP greater than (+/-)SKF 10,047. Some steroids (testosterone, progesterone, deoxycorticosterone) previously reported to bind to the sigma site in brain membranes were very weak inhibitors of [3H]-DTG binding in the present study. The results indicate that [3H]-DTG binding sites having the characteristics of sigma receptors are present in sheep pineal gland. The physiological importance of these sites in regulating the synthesis of the pineal hormone melatonin awaits further study. PMID:2169739

  4. MicroRNAs in the pineal gland: miR-483 regulates melatonin synthesis by targeting arylalkylamine N-acetyltransferase.

    PubMed

    Clokie, Samuel J H; Lau, Pierre; Kim, Hyun Hee; Coon, Steven L; Klein, David C

    2012-07-20

    MicroRNAs (miRNAs) play a broad range of roles in biological regulation. In this study, rat pineal miRNAs were profiled for the first time, and their importance was evaluated by focusing on the main function of the pineal gland, melatonin synthesis. Massively parallel sequencing and related methods revealed the miRNA population is dominated by a small group of miRNAs as follows: ~75% is accounted for by 15 miRNAs; miR-182 represents 28%. In addition to miR-182, miR-183 and miR-96 are also highly enriched in the pineal gland, a distinctive pattern also found in the retina. This effort also identified previously unrecognized miRNAs and other small noncoding RNAs. Pineal miRNAs do not exhibit a marked night/day difference in abundance with few exceptions (e.g. 2-fold night/day differences in the abundance of miR-96 and miR-182); this contrasts sharply with the dynamic 24-h pattern that characterizes the pineal transcriptome. During development, the abundance of most pineal gland-enriched miRNAs increases; however, there is a marked decrease in at least one, miR-483. miR-483 is a likely regulator of melatonin synthesis, based on the following. It inhibits melatonin synthesis by pinealocytes in culture; it acts via predicted binding sites in the 3"-UTR of arylalkylamine N-acetyltransferase (Aanat) mRNA, the penultimate enzyme in melatonin synthesis, and it exhibits a developmental profile opposite to that of Aanat transcripts. Additionally, a miR-483 targeted antagonist increased melatonin synthesis in neonatal pinealocytes. These observations support the hypothesis that miR-483 suppresses Aanat mRNA levels during development and that the developmental decrease in miR-483 abundance promotes melatonin synthesis.

  5. Is the pineal gland involved in the pathogenesis of endometrial carcinoma.

    PubMed

    Sandyk, R; Anastasiadis, P G; Anninos, P A; Tsagas, N

    1992-01-01

    The pathogenesis of endometrial carcinoma, which is the most common malignant neoplasm of the female genital tract, is unknown. It is believed that a prolonged period of increased estrogenic exposure unopposed by progesterone may underlie the malignant transformation of the endometrial cells. In the following communication, we propose that deficient melatonin functions may be an additional endocrine factor implicated in the pathogenesis of endometrial carcinoma. This hypothesis is based on the observations that: (a) melatonin has antiestrogenic properties; (b) melatonin stimulates progesterone production which opposes the action of estrogens; (c) an increased rate of endometrial hyperplasia, a premalignant condition, has been noted during the winter, a time of year associated with diminished melatonin secretion; (d) an increased incidence of anovulatory cycles, which is a risk factor for endometrial carcinoma, occurs in the winter; (e) melatonin secretion decreases sharply during the menopause, a period associated with an increased risk of endometrial carcinoma; (f) obesity, which is a major risk factor for endometrial carcinoma, is associated with impaired circadian melatonin secretion; (g) diabetes mellitus, which is an additional risk factor for endometrial carcinoma, is associated with decreased melatonin secretion and an increased rate of pineal calcification; and (h) the prevalence of endometrial carcinoma is lower in the black population compared to the white population. Similarly, the incidence of pineal calcification, which reflects the secretory activity of the gland, is significantly lower in the African and American black populations as compared to the white population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1342018

  6. Is the pineal gland involved in the pathogenesis of endometrial carcinoma.

    PubMed

    Sandyk, R; Anastasiadis, P G; Anninos, P A; Tsagas, N

    1992-01-01

    The pathogenesis of endometrial carcinoma, which is the most common malignant neoplasm of the female genital tract, is unknown. It is believed that a prolonged period of increased estrogenic exposure unopposed by progesterone may underlie the malignant transformation of the endometrial cells. In the following communication, we propose that deficient melatonin functions may be an additional endocrine factor implicated in the pathogenesis of endometrial carcinoma. This hypothesis is based on the observations that: (a) melatonin has antiestrogenic properties; (b) melatonin stimulates progesterone production which opposes the action of estrogens; (c) an increased rate of endometrial hyperplasia, a premalignant condition, has been noted during the winter, a time of year associated with diminished melatonin secretion; (d) an increased incidence of anovulatory cycles, which is a risk factor for endometrial carcinoma, occurs in the winter; (e) melatonin secretion decreases sharply during the menopause, a period associated with an increased risk of endometrial carcinoma; (f) obesity, which is a major risk factor for endometrial carcinoma, is associated with impaired circadian melatonin secretion; (g) diabetes mellitus, which is an additional risk factor for endometrial carcinoma, is associated with decreased melatonin secretion and an increased rate of pineal calcification; and (h) the prevalence of endometrial carcinoma is lower in the black population compared to the white population. Similarly, the incidence of pineal calcification, which reflects the secretory activity of the gland, is significantly lower in the African and American black populations as compared to the white population.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Glutamate Transporter-Mediated Glutamate Secretion in the Mammalian Pineal Gland

    PubMed Central

    Kim, Mean-Hwan; Uehara, Shunsuke; Muroyama, Akiko; Hille, Bertil; Moriyama, Yoshinori; Koh, Duk-Su

    2008-01-01

    Glutamate transporters are expressed throughout the central nervous system where their major role is to clear released glutamate from presynaptic terminals. Here we report a novel function of the transporter in rat pinealocytes. This electrogenic transporter conducted inward current in response to L-glutamate and L- or D-aspartate and depolarized the membrane in patch clamp experiments. Ca2+ imaging demonstrated that the transporter-mediated depolarization induced a significant Ca2+ influx through voltage-gated Ca2+ channels. The Ca2+ rise finally evoked glutamate exocytosis as detected by carbon-fiber amperometry and by high-performance liquid chromatography. In pineal slices with densely packed pinealocytes, glutamate released from the cells effectively activated glutamate transporters in neighboring cells. The Ca2+ signal generated by KCl depolarization or acetylcholine propagated through several cell layers by virtue of the regenerative ‘glutamate-induced glutamate release’. Therefore we suggest that glutamate transporters mediate synchronized elevation of L-glutamate and thereby efficiently down-regulate melatonin secretion via previously identified inhibitory metabotropic glutamate receptors in the pineal gland. PMID:18945893

  8. History of the pineal region tumor.

    PubMed

    Mottolese, C; Szathmari, A

    2015-01-01

    The pineal gland has interested humans from millenniums. In this paper we review back in the history and the evolution of the pineal gland surgery. Originally, this surgery used to carry a high rate of morbidity and mortality. Nowadays the development of the anesthetic, radiological, surgical and intensive care techniques have been responsible of an improvement of the surgical results and better quality of life. It is always interesting to know from where we come.

  9. Pineal gland as an endocrine gravitational lunasensor: manifestation of moon-phase dependent morphological changes in mice.

    PubMed

    Gerasimov, A V; Kostyuchenko, V P; Solovieva, A S; Olovnikov, A M

    2014-10-01

    We found that some morphological properties of the pineal gland and submandibular salivary gland of mice are significantly distinct at the new and full moon. We suppose that the differences are initiated by the displacements of the electron-dense concretions in the secretory vesicles of pinealocytes. This presumably occurs under the influence of the gravitational field, which periodically changes during different phases of the moon. It seems that the pinealocyte is both an endocrine and gravisensory cell. A periodic secretion of the pineal gland probably stimulates, in a lunaphasic mode, the neuroendocrine system that, in turn, periodically exerts influence on different organs of the body. The observed effect probably serves, within the lifelong clock of a brain, to control development and aging in time.

  10. Pineal gland as an endocrine gravitational lunasensor: manifestation of moon-phase dependent morphological changes in mice.

    PubMed

    Gerasimov, A V; Kostyuchenko, V P; Solovieva, A S; Olovnikov, A M

    2014-10-01

    We found that some morphological properties of the pineal gland and submandibular salivary gland of mice are significantly distinct at the new and full moon. We suppose that the differences are initiated by the displacements of the electron-dense concretions in the secretory vesicles of pinealocytes. This presumably occurs under the influence of the gravitational field, which periodically changes during different phases of the moon. It seems that the pinealocyte is both an endocrine and gravisensory cell. A periodic secretion of the pineal gland probably stimulates, in a lunaphasic mode, the neuroendocrine system that, in turn, periodically exerts influence on different organs of the body. The observed effect probably serves, within the lifelong clock of a brain, to control development and aging in time. PMID:25519065

  11. Stimulation of 3H-norepinephrine release by trifluoperazine from rat pineal glands.

    PubMed

    Yurko, K A; Quenzer, L F

    1986-04-14

    Trifluoperazine (5-200 microM) stimulated the release of 3H-NE from isolated whole pineal glands in a dose dependent manner. Trifluoperazine-induced release was not dependent on extracellular Ca++, whereas 60 mM K+-evoked release was attenuated in the presence of EGTA and zero Ca++ Krebs. 60 mM K+ and 50 microM trifluoperazine produced an additive effect on 3H-NE release. Clonidine (5 microM) significantly reduced trifluoperazine-induced release by approximately 50% in the presence of Ca++, and in its absence, clonidine significantly attenuated the trifluoperazine response by 42%. Thus trifluoperazine may be acting upon the alpha 2 receptor or intracellular stores of Ca++. These intracellular interactions remain for further study.

  12. Melatonin Synthesis: Acetylserotonin O-Methyltransferase (ASMT) Is Strongly Expressed in a Subpopulation of Pinealocytes in the Male Rat Pineal Gland.

    PubMed

    Rath, Martin F; Coon, Steven L; Amaral, Fernanda G; Weller, Joan L; Møller, Morten; Klein, David C

    2016-05-01

    The rat pineal gland has been extensively used in studies of melatonin synthesis. However, the cellular localization of melatonin synthesis in this species has not been investigated. Here we focus on the localization of melatonin synthesis using immunohistochemical methods to detect the last enzyme in melatonin synthesis, acetylserotonin O-methyltransferase (ASMT), and in situ hybridization techniques to study transcripts encoding ASMT and two other enzymes in melatonin synthesis, tryptophan hydroxylase (TPH)-1 and aralkylamine N-acetyltransferase. In sections of the rat pineal gland, marked cell-to-cell differences were found in ASMT immunostaining intensity and in the abundance of Tph1, Aanat, and Asmt transcripts. ASMT immunoreactivity was localized to the cytoplasm in pinealocytes in the parenchyma of the superficial pineal gland, and immunopositive pinealocytes were also detected in the pineal stalk and in the deep pineal gland. ASMT was found to inconsistently colocalize with S-antigen, a widely used pinealocyte marker; this colocalization was seen in cells throughout the pineal complex and also in displaced pinealocyte-like cells of the medial habenular nucleus. Inconsistent colocalization between ASMT and TPH protein was also detected in the pineal gland. ASMT protein was not detected in extraepithalamic parts of the central nervous system or in peripheral tissues. The findings in this report are of special interest because they provide reason to suspect that melatonin synthesis varies significantly among individual pinealocytes.

  13. Diurnal expression of clock genes in pineal gland and brain and plasma levels of melatonin and cortisol in Atlantic salmon parr and smolts.

    PubMed

    Huang, Tien-sheng; Ruoff, Peter; Fjelldal, Per G

    2010-10-01

    In Atlantic salmon, the preadaptation to a marine life, i.e., parr-smolt transformation, and melatonin production in the pineal gland are regulated by the photoperiod. However, the clock genes have never been studied in the pineal gland of this species. The aim of the present study was to describe the diurnal expression of clock genes (Per1-like, Cry2, and Clock) in the pineal gland and brain of Atlantic salmon parr and smolts in freshwater, as well as plasma levels of melatonin and cortisol. By employing an out-of-season smolt production model, the parr-smolt transformation was induced by subjecting triplicate groups of parr to 6 wks (wks 0 to 6) under a 12 h:12 h light-dark (LD) regime followed by 6 wks (wks 6 to 12) of continuous light (LL). The measured clock genes in both pineal gland and brain and the plasma levels of melatonin and cortisol showed significant daily variations in parr under LD in wk 6, whereas these rhythms were abolished in smolts under LL in wk 12. In parr, the pineal Per1-like and Cry2 expression peaked in the dark phase, whereas the pineal Clock expression was elevated during the light phase. Although this study presents novel findings on the clock gene system in the teleost pineal gland, the role of this system in the regulation of smoltification needs to be studied in more detail.

  14. Season-dependent postembryonic maturation of the diurnal rhythm of melatonin biosynthesis in the chicken pineal gland.

    PubMed

    Piesiewicz, A; Kedzierska, U; Podobas, E; Adamska, I; Zuzewicz, K; Majewski, P M

    2012-11-01

    Previously, we have demonstrated that the timing of the nocturnal peak of activity of the pineal arylalkylamine-N-acetyltransferase - a key enzyme in the melatonin biosynthesis pathway - in 3-wk-old chickens kept from the day of hatch under controlled laboratory conditions (L:D 12:12) varies depending on the season of hatch (summer vs. winter). The present study was undertaken to answer the following questions: (1) are season-related differences seen in the level of transcription of genes encoding enzymes of the melatonin biosynthesis pathway? (2) Does the pineal content of the main precursor (serotonin) and the final product (melatonin) exhibit age- and season-related changes? (3) At which step in postembryonic development are these season-related variations in pineal gland function most pronounced? Male Hy-line chickens hatched in the summer or winter, from eggs laid by hens held on L:D 16:8, were kept from the day of hatch under L:D 12:12 conditions. At the age of 2, 9, or 16 d, chickens were sacrificed every 2 h over a 24-h period and their pineal glands, isolated under dim red light, were processed for the measurement of (i) the level of Aanat and Asmt (acetylserotonin O-methyltransferase) mRNAs encoding the two last enzymes involved in melatonin biosynthesis, (ii) the activity of these enzymes, and (iii) the pineal content of serotonin and melatonin. Circadian rhythmicity of all the measured parameters was evaluated by the cosinor method. The levels of Aanat mRNA, AANAT enzymatic activity, and the pineal melatonin content changed during postembryonic development in a manner that was dependent on the season of hatch. Furthermore, the diurnal profile of Asmt mRNA was elevated during the light phase. In "winter" birds, the pattern and amplitude of the diurnal rhythm of accumulation of this transcript did not change with age, while in "summer" birds it increased in an age-related way. In contrast, the enzymatic activity of hydroxyindole-O-methyltransferase (HIOMT

  15. Characterization of transgenic zebrafish lines that express GFP in the retina, pineal gland, olfactory bulb, hatching gland, and optic tectum.

    PubMed

    Fang, Wei; Bonaffini, Sarah; Zou, Jian; Wang, Xiaolei; Zhang, Cen; Tsujimura, Taro; Kawamura, Shoji; Wei, Xiangyun

    2013-01-01

    Transgenic animals are powerful tools to study gene function invivo. Here we characterize several transgenic zebrafish lines that express green fluorescent protein (GFP) under the control of the LCR(RH2)-RH2-1 or LCR(RH2)-RH2-2 green opsin regulatory elements. Using confocal immunomicroscopy, stereo-fluorescence microscopy, and Western blotting, we show that the Tg(LCR(RH2)-RH2-1:GFP)(pt112) and Tg(LCR(RH2)-RH2-2:GFP)(pt115) transgenic zebrafish lines express GFP in the pineal gland and certain types of photoreceptors. In addition, some of these lines also express GFP in the hatching gland, optic tectum, or olfactory bulb. Some of the expression patterns differ significantly from previously published similar transgenic fish lines, making them useful tools for studying the development of the corresponding tissues and organs. In addition, the variations of GFP expression among different lines corroborate the notion that transgenic expression is often subjected to position effect, thus emphasizing the need for careful verification of expression patterns when transgenic animal models are utilized for research.

  16. A direct influence of moonlight intensity on changes in melatonin production by cultured pineal glands of the golden rabbitfish, Siganus guttatus.

    PubMed

    Takemura, Akihiro; Ueda, Satomi; Hiyakawa, Nanae; Nikaido, Yoshiaki

    2006-04-01

    Rabbitfish are a restricted lunar-synchronized spawner that spawns around a species-specific lunar phase. It is not known how the fish perceive changes in cues from the moon. One possible explanation is that rabbitfish utilize changes in moonlight intensity to establish synchrony. The purpose of the present study was to examine whether or not the pineal gland of the golden rabbitfish can directly perceive changes in moonlight intensity. Isolated pineal glands were statically cultured under natural or artificial light conditions and melatonin secreted into the culture medium was measured using a time-resolved fluoroimmunoassay. Under an artificial light/dark cycle, melatonin secretion significantly increased during the dark phase. Under continuous light conditions, melatonin secretion was suppressed, while culture under continuous dark conditions seemed to duplicate melatonin secretion corresponding to the light/dark cycle in which the fish were acclimated. When cultured pineal glands were kept under natural light conditions on the dates of the full and the new moon, small amounts of melatonin were secreted at night. Moreover, exposure of cultured pineal glands to artificial and natural light conditions resulted in a significant decrease of melatonin secretion within 2 hr. These results suggest that the isolated pineal gland of golden rabbitfish responds to environmental light cycles and that 'brightness' of the night moon has an influence on melatonin secretion from the isolated pineal gland.

  17. Decreased melatonin biosynthesis, calcium flux, pineal gland calcification and aging: a hypothetical framework.

    PubMed

    Schmid, H A

    1993-01-01

    Increased pineal calcifications and decreased pineal melatonin biosynthesis, both age related, support the notion of a pineal bio-organic timing mechanism. Decreased calcium ion availability is the single common denominator of diminished beta-postreceptor- and alpha-receptor-stimulating functions in beta-receptor potentiation, which is necessary for nocturnal peak melatonin production. A comprehensive framework for the interaction of aging pineal cell mechanisms, calcium flux and melatonin biosynthesis is presented. PMID:8244046

  18. Benign symptomatic glial cysts of the pineal gland: a report of seven cases and review of the literature.

    PubMed Central

    Klein, P; Rubinstein, L J

    1989-01-01

    Seven cases of clinically symptomatic benign glial cyst of the pineal gland are reported. The cysts' size ranged from 1.0-4.5 cm in diameter. They were characterised by a golden or, less frequently, brown-reddish proteinaceous or haemorrhagic fluid content. The cyst wall, up to 2 mm thick, consisted of clusters of normal pineal parenchymal cells, often compressed and distorted, surrounded by reactive gliotic tissue which sometimes contained Rosenthal fibres. The presenting clinical features included headache (6/7), signs of raised intracranial pressure, partial or complete Parinaud's syndrome (5/7), cerebellar deficits (2/7), corticospinal and corticopontine fibre (2/7) or sensory (1/7) deficits, and emotional disturbances (2/7). CT and MRI (in 2/7 cases) scans showed a hypodense or nonhomogeneous lesion in the region of the pineal gland, with or without contrast enhancement. Surgical excision resulted in complete clearance of the symptoms in 5/7 patients. The previous literature is reviewed and the clinicopathological correlations and the possible pathogenetic mechanisms are discussed. The need to distinguish this benign lesion from other mass lesions of the pineal region, in particular from pinealocytoma, is stressed. Images PMID:2677249

  19. The morphology of the pineal gland of the yellow-toothed cavy (Galea Spixii Wagler, 1831) and red-rumped agouti (Dasyprocta leporina linnaeus, 1758).

    PubMed

    Câmara, Felipe Venceslau; Lopes, Igor Renno Guimarães; de Oliveira, Gleidson Benevides; Bezerra, Ferdinando Vinicius Fernandes; de Oliveira, Radan Elvis Matias; Oliveira Júnior, Carlos Magno; Silva, Alexandre Rodrigues; de Oliveira, Moacir Franco

    2015-08-01

    The pineal gland is an endocrine gland found in all mammals. This article describes the morphology of this important gland in two species of Caviideae, namely the yellow-toothed cavy and the red-rumped agouti. Ten adult animals of the two species used in current analysis were retrieved from the Center for the Multiplication of Wild Animals (CEMAS/UFERSA) and euthanized. The glands were removed and photographed in situ and ex situ. They were fixed in a paraformaldehyde solution 4% or glutaraldehyde 2.5% solution and submitted to routine histological techniques respectively for light and scanning electron microscopy. Macroscopically, the pineal gland with its elongated structure may be found between the cerebral hemispheres facing the rostral colliculi. Microscopically, pinealocytes and some glia cells were predominant. Contrastingly, to the cavy's pineal gland, a capsule covered the organ in the agouti, with the emission of incomplete septa to the interior, which divided it into two lobules. Light and scanning electron microscopes failed to show calcareous concretions in the pineal gland. Based on the topography of the cavy's and agouti's pineal gland, it may be classified as supra-callosum and ABC type.

  20. Sympathetic neural control of indoleamine metabolism in the rat pineal gland

    NASA Technical Reports Server (NTRS)

    Lynch, H. J.; Hsuan, M.; Wurtman, R. J.

    1975-01-01

    The mechanisms responsible for the acceleration in rat pineal biosynthetic activity in response to prolonged exposure to darkness or to immobilization were investigated in animals whose pineals were surgically denervated. Some animals were adrenalectomized to remove one potential source of circulating catecholamines, and some were subjected to a partial chemical sympathectomy accomplished by a series of intravenous injections of 6-hydroxydopamine. Results suggest that N-acetyltransferase (NAT) activity can be enhanced either by release of norepinephrine from sympathetic terminals within the pineal or from sympathetic nerve terminals elsewhere. The stress of immobilization stimulates the pineal by increasing circulating catecholamines. Photic control of pineal function requires intact pineal sympathetic innervation, since the onset of darkness apparently does not cause a sufficient rise in circulating catecholamines to stimulate the pineal. The present studies suggest that nonspecific stress triggers increased biosynthesis and secretion of melatonin; it is possible that this hormone may participate in mechanisms of adaptation.

  1. Immunohistochemical localization of irisin in skin, eye, and thyroid and pineal glands of the crested porcupine (Hystrix cristata).

    PubMed

    Gençer Tarakçı, B; Girgin, A; Timurkaan, S; Yalçın, M H; Gür, F M; Karan, M

    2016-08-01

    Irisin was first identified in muscle cells. We detected irisin immunoreactivity in various organs of the crested porcupine (Hystrix cristata). In the epidermis, irisin immunoreactivity was localized mainly in stratum basale, stratum spinosum and stratum granulosum layers; immunoreactivity was not observed in the stratum corneum. In the dermis, irisin was found in the external and internal root sheath, cortex and medulla of hair follicles, and in sebaceous glands. Irisin immunoreactivity was found in the neural retina and skeletal muscle fibers associated with the eye. The pineal and thyroid glands also exhibited irisin immunoreactivity. PMID:27192184

  2. Immunohistochemical localization of irisin in skin, eye, and thyroid and pineal glands of the crested porcupine (Hystrix cristata).

    PubMed

    Gençer Tarakçı, B; Girgin, A; Timurkaan, S; Yalçın, M H; Gür, F M; Karan, M

    2016-08-01

    Irisin was first identified in muscle cells. We detected irisin immunoreactivity in various organs of the crested porcupine (Hystrix cristata). In the epidermis, irisin immunoreactivity was localized mainly in stratum basale, stratum spinosum and stratum granulosum layers; immunoreactivity was not observed in the stratum corneum. In the dermis, irisin was found in the external and internal root sheath, cortex and medulla of hair follicles, and in sebaceous glands. Irisin immunoreactivity was found in the neural retina and skeletal muscle fibers associated with the eye. The pineal and thyroid glands also exhibited irisin immunoreactivity.

  3. Calcification of the pineal gland: relationship to laterality of the epileptic foci in patients with complex partial seizures.

    PubMed

    Sandyk, R

    1992-01-01

    The right and left temporal lobes differ from each other with respect to the rate of intrauterine growth, the timing of maturation, rate of aging, anatomical organization, neurochemistry, metabolic rate, electroencephalographic measures, and function. These functional differences between the temporal lobes underlies the different patterns of psychopathology and endocrine reproductive disturbances noted in patients with temporolimbic epilepsy. The right hemisphere has greater limbic and reticular connections than the left. Since the pineal gland receives direct innervation from the limbic system and the secretion of melatonin is influenced by an input from the reticular system, I propose that lesions in the right temporal lobe have a greater impact on pineal melatonin functions as opposed to those in the left dominant temporal lobe. Consequently, since calcification of the pineal gland is thought to reflect past secretory activity of the gland, I predicted a higher prevalence of pineal calcification (PC) in epileptic patients with right temporal lobe as opposed to those with left temporal lobe foci. To investigate this hypothesis, the prevalence of PC on CT scan was studied in a sample of 70 patients (43 men, 27 women, mean age: 29.2 years, range 9-58; SD = 10.1) with complex partial seizures, of whom 49 (70.0%) had a right temporal lobe focus. PC was present in 51 patients (72.8%) and was unrelated to any of the historical and demographic data surveyed. In the patients with a focus in the right temporal lobe, PC was present in 46 cases (93.8%) as compared to 5 of 21 patients (23.8%) with left temporal lobe foci.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1341678

  4. Hydroxyindole-O-methyltransferase activity in the pineal gland of the muskox (Ovibos moschatus).

    PubMed

    Tedesco, S C; Morton, D J; Reiter, R J

    1994-04-01

    Characteristics of hydroxyindole-O-methyltransferase (HIOMT) activity were examined in pineal gland tissue from 10 muskoxen shot by native hunters in November, 1990. The enzyme preferentially methylated N-acetylserotonin, with other hydroxyindole compounds showing relatively low affinities; activity peaked sharply at pH 8.2. HIOMT was noncompetitively inhibited by its substrate, N-acetylserotonin, and competitively inhibited by its product S-adenosylhomocysteine. The catalytic mechanism appeared to be ordered as described in previous studies: S-adenosylmethionine was the obligatory first substrate, followed by N-acetylserotonin; methyl transfer then occurred and the products, melatonin and S-adenosylhomocysteine, were released sequentially. Interestingly, the inhibition constant (Ki) for N-acetylserotonin was relatively close to the Michaelis-Menten constant (Km), which might allow physiological concentrations of N-acetylserotonin to inhibit HIOMT activity in vivo. This effect could be relevant to the ecology of free-living muskoxen during the dramatic seasonal fluctuations in dietary protein and daily photoperiod associated with their arctic habitat.

  5. Hydroxyindole-O-methyltransferase activity in the pineal gland of the muskox (Ovibos moschatus).

    PubMed

    Tedesco, S C; Morton, D J; Reiter, R J

    1994-04-01

    Characteristics of hydroxyindole-O-methyltransferase (HIOMT) activity were examined in pineal gland tissue from 10 muskoxen shot by native hunters in November, 1990. The enzyme preferentially methylated N-acetylserotonin, with other hydroxyindole compounds showing relatively low affinities; activity peaked sharply at pH 8.2. HIOMT was noncompetitively inhibited by its substrate, N-acetylserotonin, and competitively inhibited by its product S-adenosylhomocysteine. The catalytic mechanism appeared to be ordered as described in previous studies: S-adenosylmethionine was the obligatory first substrate, followed by N-acetylserotonin; methyl transfer then occurred and the products, melatonin and S-adenosylhomocysteine, were released sequentially. Interestingly, the inhibition constant (Ki) for N-acetylserotonin was relatively close to the Michaelis-Menten constant (Km), which might allow physiological concentrations of N-acetylserotonin to inhibit HIOMT activity in vivo. This effect could be relevant to the ecology of free-living muskoxen during the dramatic seasonal fluctuations in dietary protein and daily photoperiod associated with their arctic habitat. PMID:7932034

  6. Amyloid β peptide directly impairs pineal gland melatonin synthesis and melatonin receptor signaling through the ERK pathway.

    PubMed

    Cecon, Erika; Chen, Min; Marçola, Marina; Fernandes, Pedro A C; Jockers, Ralf; Markus, Regina P

    2015-06-01

    Melatonin is the hormone produced by the pineal gland known to regulate physiologic rhythms and to display immunomodulatory and neuroprotective properties. It has been reported that Alzheimer disease patients show impaired melatonin production and altered expression of the 2 G protein-coupled melatonin receptors (MTRs), MT₁ and MT₂, but the underlying mechanisms are not known. Here we evaluated whether this dysfunction of the melatonergic system is directly caused by amyloid β peptides (Aβ(1-40) and Aβ(1-42)). Aβ treatment of rat pineal glands elicited an inflammatory response within the gland, evidenced by the up-regulation of 52 inflammatory genes, and decreased the production of melatonin up to 75% compared to vehicle-treated glands. Blocking NF-κB activity prevented this effect. Exposure of HEK293 cells stably expressing recombinant MT₁ or MT₂ receptors to Aβ lead to a 40% reduction in [(125)I]iodomelatonin binding to MT₁. ERK1/2 activation triggered by MTRs, but not by the β₂-adrenergic receptor, was markedly impaired by Aβ in HEK293 transfected cells, as well as in primary rat endothelial cells expressing endogenous MTRs. Our data reveal the melatonergic system as a new target of Aβ, opening new perspectives to Alzheimer disease diagnosis and therapeutic intervention.

  7. Developmental and diurnal dynamics of Pax4 expression in the mammalian pineal gland: nocturnal down-regulation is mediated by adrenergic-cyclic adenosine 3',5'-monophosphate signaling.

    PubMed

    Rath, Martin F; Bailey, Michael J; Kim, Jong-So; Ho, Anthony K; Gaildrat, Pascaline; Coon, Steven L; Møller, Morten; Klein, David C

    2009-02-01

    Pax4 is a homeobox gene that is known to be involved in embryonic development of the endocrine pancreas. In this tissue, Pax4 counters the effects of the related protein, Pax6. Pax6 is essential for development of the pineal gland. In this study we report that Pax4 is strongly expressed in the pineal gland and retina of the rat. Pineal Pax4 transcripts are low in the fetus and increase postnatally; Pax6 exhibits an inverse pattern of expression, being more strongly expressed in the fetus. In the adult the abundance of Pax4 mRNA exhibits a diurnal rhythm in the pineal gland with maximal levels occurring late during the light period. Sympathetic denervation of the pineal gland by superior cervical ganglionectomy prevents the nocturnal decrease in pineal Pax4 mRNA. At night the pineal gland is adrenergically stimulated by release of norepinephrine from the sympathetic innervation; here, we found that treatment with adrenergic agonists suppresses pineal Pax4 expression in vivo and in vitro. This suppression appears to be mediated by cAMP, a second messenger of norepinephrine in the pineal gland, based on the observation that treatment with a cAMP mimic reduces pineal Pax4 mRNA levels. These findings suggest that the nocturnal decrease in pineal Pax4 mRNA is controlled by the sympathetic neural pathway that controls pineal function acting via an adrenergic-cAMP mechanism. The daily changes in Pax4 expression may influence gene expression in the pineal gland.

  8. Phosphodiesterase 10A in the rat pineal gland: localization, daily and seasonal regulation of expression and influence on signal transduction.

    PubMed

    Spiwoks-Becker, Isabella; Wolloscheck, Tanja; Rickes, Oliver; Kelleher, Debra K; Rohleder, Nils; Weyer, Veronika; Spessert, Rainer

    2011-01-01

    The cyclic nucleotide phosphodiesterase 10A (PDE10A) is highly expressed in striatal spiny projection neurons and represents a therapeutic target for the treatment of psychotic symptoms. As reported previously [J Biol Chem 2009; 284:7606-7622], in this study PDE10A was seen to be additionally expressed in the pineal gland where the levels of PDE10A transcript display daily changes. As with the transcript, the amount of PDE10A protein was found to be under daily and seasonal regulation. The observed cyclicity in the amount of PDE10A mRNA persists under constant darkness, is blocked by constant light and is modulated by the lighting regime. It therefore appears to be driven by the master clock in the suprachiasmatic nucleus (SCN). Since adrenergic agonists and dibutyryl-cAMP induce PDE10A mRNA, the in vitro clock-dependent control of Pde10a appears to be mediated via a norepinephrine → β-adrenoceptor → cAMP/protein kinase A signaling pathway. With regard to the physiological role of PDE10A in the pineal gland, the specific PDE10A inhibitor papaverine was seen to enhance the adrenergic stimulation of the second messenger cAMP and cGMP. This indicates that PDE10A downregulates adrenergic cAMP and cGMP signaling by decreasing the half-life of both nucleotides. Consistent with its effect on cAMP, PDE10A inhibition also amplifies adrenergic induction of the cAMP-inducible gene arylalkylamine N-acetyltransferase (Aanat) which codes the rate-limiting enzyme in pineal melatonin formation. The findings of this study suggest that Pde10a expression is under circadian and seasonal regulation and plays a modulatory role in pineal signal transduction and gene expression.

  9. Effect of L-NAME-induced hypertension on melatonin receptors and melatonin levels in the pineal gland and the peripheral organs of rats.

    PubMed

    Benova, Miroslava; Herichova, Iveta; Stebelova, Katarina; Paulis, Ludovit; Krajcirovicova, Kristina; Simko, Fedor; Zeman, Michal

    2009-04-01

    Melatonin plays a role in blood pressure (BP) control. The aim of this study was to determine whether melatonin concentrations and melatonin receptor levels are altered in L-NAME-treated, NO-deficient hypertensive rats. Two groups of male adult Wistar rats were investigated: rats (n=36) treated with NO-synthase inhibitor L-NAME (40 mg kg(-1)) and age-matched controls (n=36). BP was measured weekly by tail-cuff plethysmography. After 4 weeks, L-NAME administration increased BP (178+/-1 vs. control 118+/-1 mm Hg). At the end of treatment, rats were killed in regular 4 h intervals over a 24-h period. Melatonin concentrations in the plasma, pineal gland, heart and kidney and melatonin receptor (MT(1)) density in the aorta were determined. A significant daily rhythm of melatonin concentrations was found in the blood, pineal gland, kidney and heart of both control and hypertensive rats. Peak nighttime pineal melatonin concentrations were higher in L-NAME-treated rats than in controls (3.38+/-0.48 vs. 1.75+/-0.33 ng per pineal gland). No differences between both groups were found in melatonin concentrations in blood, kidney and heart or in the MT(1) receptor density in the aorta. Our results suggest that L-NAME treatment enhances melatonin production in the pineal gland, potentially by decreasing an inhibitory effect of NO on melatonin production in the pineal gland. However, the enhanced pineal melatonin formation was insufficient to increase melatonin concentrations in circulation, heart and kidney of L-NAME-treated rats, indicating an increased use of melatonin in hypertensive animals.

  10. Pineal gland calcification, lumbar intervertebral disc degeneration and abdominal aorta calcifying atherosclerosis correlate in low back pain subjects: A cross-sectional observational CT study.

    PubMed

    Turgut, Ahmet Tuncay; Sönmez, Iclal; Cakıt, Burcu Duyur; Koşar, Pınar; Koşar, Uğur

    2008-06-01

    The goal of this cross-sectional observational study was to assess the possible impact of pineal gland calcification upon the intervertebral disc degeneration and abdominal aorta atherosclerosis in subjects with low back pain, and to investigate the course of these processes with aging. The study was carried out on 81 (66 women and 15 men) subjects: younger than 45 years (group X, n=22), 45-65 years of age (group Y, n=45), and older than 65 years (group Z, n=14). In addition to clinical data, computed tomography (CT) scan of the brain as well as X-ray and CT examination of the lumbar spine were recorded in this study. The degree of disc degeneration and calcification rates of aortic wall and pineal gland were independently determined by two radiologists. Both ratio of calcified pineal gland and density of pineal calcification increased progressively with aging. Also, both the degree of aortic wall calcification and disc degeneration score increased with advancing age. On CT scan, a positive correlation between degree of aortic wall calcification and disc degeneration score was found (r=0.306, p<0.01). Importantly, there was a positive association between calcification of the pineal gland and degenerative disc disease in X-ray or CT study (r=0.378 and r=0.295, p<0.005 and p<0.01, respectively), as well as between abdominal aorta atherosclerosis and pineal calcification (r=0.634, p<0.001). Our findings suggest that there is a significant interaction between pineal gland calcification and lumbar intervertebral disc degeneration and also abdominal aorta atherosclerosis. However, further studies with a larger subject cohorts are needed. PMID:18215511

  11. Fluoride concentrations in the pineal gland, brain and bone of goosander (Mergus merganser) and its prey in Odra River estuary in Poland.

    PubMed

    Kalisinska, Elzbieta; Bosiacka-Baranowska, Irena; Lanocha, Natalia; Kosik-Bogacka, Danuta; Krolaczyk, Katarzyna; Wilk, Aleksandra; Kavetska, Katarzyna; Budis, Halina; Gutowska, Izabela; Chlubek, Dariusz

    2014-12-01

    The aim of the study was to investigate fluoride concentrations in bone, brain and pineal gland of goosander Mergus merganser wintering in the Odra estuary (Poland) as well as in fish originating from its digestive tract. The fluoride concentrations were determined with potentiometric method. Medians of concentrations in goosander had the highest and the lowest values in pineal gland and brain (>760 and <190 mg/kg, respectively). Fluoride concentration in the pineal gland was significantly greater than in the bone and the brain of the duck. In fish, the fluoride concentration ranged from 37 to 640 mg/kg and significant correlation was revealed between the fluoride concentration and fish weight and length. Based on own results and data of other authors, a daily fluoride intake by the goosander in the Odra estuary was estimated at 15 mg. So high fluoride concentrations like in the duck have not been found in mammal brains.

  12. [The sexual peculiarities of aging changes in circannual rhythms of pineal gland, hypophysis, adrenal cortex and thymus functions in healthy subjects].

    PubMed

    Labunets, I F

    2013-01-01

    The interrelations of circannual rhythms of the functional state of pineal gland, hypophysis, adrenal cortex, thymus in healthy women and men from 20 to 79 years were studied. Fluctuations of melatonin, ACTH, cortisol and thymic serum factor, which were exchanged in aging (the season peaks of hormones and its acrophase) were found in blood of healthy 20-29 years old people. The changes of rhythmicity of indices were in male earlier (pineal gland and hypophysis over 30 years, thymus and adrenal cortex over 40 years) and more impressive than in women. The aging changes of pineal gland function's rhythm in healthy subjects have important role for changes of interrelations of circannual rhythms hypophysis, adrenal cortex and thymus.

  13. Unusual ultrastructural features in the superficial pineal gland of the yellow-bellied country rat (Rattus losea Swinhoe).

    PubMed

    Huang, H T; Lin, H S; Sun, J H; Wang, P Y

    1989-01-01

    The ultrastructure of the superficial pineal gland of the yellow-bellied country rat (Rattus losea Swinhoe), living under natural climatic conditions at the margin of the tropical region, was studied with special reference to the seasonal changes. In the rainy season with average monthly rainfall of 400 mm (light phase of 13.5 h, and temperature of 28 degrees C) the gland was characterized by the presence of frequent large vacuoles containing flocculent material (LVFs), large condensed inclusions (LCIs) in the pinealocytes, and extensive accumulations of presumptive secretion in the extracellular compartment, suggesting an enhanced secretory activity. In the dry season with average monthly rainfall of 13 mm (light phase of 11 h, and temperature of 19 degrees C), however, the pinealocytes were characterized by the presence of numerous clear spindles, which exhibited acid phosphatase activity; at this time there were few LVFs and LCIs and rare extracellular accumulations, suggesting a declined glandular activity. We conclude that the cellular activity of the pineal gland in R. losea, living under tropical climatic conditions, is synchronized with the annual changes of rainfall, which is apparently more important than the annual changes of photoperiod and temperature.

  14. CSF generation by pineal gland results in a robust melatonin circadian rhythm in the third ventricle as an unique light/dark signal.

    PubMed

    Tan, Dun-Xian; Manchester, Lucien C; Reiter, Russel J

    2016-01-01

    Pineal gland is an important organ for the regulation of the bio-clock in all vertebrate species. Its major secretory product is melatonin which is considered as the chemical expression of darkness due to its circadian peak exclusively at night. Pineal melatonin can be either released into the blood stream or directly enter into the CSF of the third ventricle via the pineal recess. We have hypothesized that rather than the peripheral circulatory melatonin circadian rhythm serving as the light/dark signal, it is the melatonin rhythm in CSF of the third ventricle that serves this purpose. This is due to the fact that melatonin circadian rhythm in the CSF is more robust in terms of its extremely high concentration and its precise on/off peaks. Thus, extrapineal-generated melatonin or diet-derived melatonin which enters blood would not interfere with the bio-clock function of vertebrates. In addition, based on the relationship of the pineal gland to the CSF and the vascular structure of this gland, we also hypothesize that pineal gland is an essential player for CSF production. We feel it participates in both the formation and reabsorption of CSF. The mechanisms associated with these processes are reviewed and discussed in this brief review.

  15. A reproductive phase-dependent effect of dietary L-tryptophan on pineal gland and gonad of a nocturnal bird, Indian spotted owlet Athene brama.

    PubMed

    Guchhait, P; Haldar, C

    2001-01-01

    Unlike other temperate owls, Indian spotted owlet Athene brama possesses a well-developed pineal gland that secrets moderate amount of hydroxy- (serotonin) and methoxy- (melatonin) indoles in circulation. However, in this study, we have reported the response of this endocrine gland to exogenous L-Tryptophan (precursor of the above indoles), and also its effect on gonads of this nocturnal bird. During breeding phase or pineal inactive phase (March), oral treatment of L-Trp (0.5 mg/100 g Bwt/day) significantly increased the pineal gland wt and plasma melatonin (MEL) level, while decreased the gonadal wt and plasma sex steroids levels (estradiol and progesterone in female and testosterone in male). Interestingly, during reproductively quiescent phase or pineal active phase (August), similar amount of L-Trp significantly decreased the plasma MEL level, while increased the above sex steroid levels in plasma. Finally, the results show a clear reproductive phase-dependent inverse effect of L-Trp on pineal gland and gonads for both sexes of the spotted owlets, and suggest that the therapeutic use of this amino acid would be a great advantage for controlling the reproduction of these economically important birds.

  16. Moonlight affects nocturnal Period2 transcript levels in the pineal gland of the reef fish Siganus guttatus.

    PubMed

    Sugama, Nozomi; Park, Ji-Gweon; Park, Yong-Ju; Takeuchi, Yuki; Kim, Se-Jae; Takemura, Akihiro

    2008-09-01

    The golden rabbitfish Siganus guttatus is a reef fish with a restricted lunar-synchronized spawning cycle. It is not known how the fish recognizes cues from the moon and exerts moon-related activities. In order to evaluate the perception and utilization of moonlight by the fish, the present study aimed to clone and characterize Period2 (Per2), a light-inducible clock gene in lower vertebrates, and to examine daily variations in rabbitfish Per2 (rfPer2) expression as well as the effect of light and moonlight on its expression in the pineal gland. The partially-cloned rfPer2 cDNA (2933 bp) was highly homologous (72%) to zebrafish Per2. The rfPer2 levels increased at ZT6 and decreased at ZT18 in the whole brain and several peripheral organs. The rfPer2 expression in the pineal gland exhibited a daily variation with an increase during daytime. Exposing the fish to light during nighttime resulted in a rapid increase of its expression in the pineal gland, while the level was decreased by intercepting light during daytime. Two hours after exposing the fish to moonlight at the full moon period, the rfPer2 expression was upregulated. These results suggest that rfPer2 is a light-inducible clock gene and that its expression is affected not only by daylight but also by moonlight. Since the rfPer2 expression level during the full moon period was higher than that during the new moon period, the monthly variation in the rfPer2 expression is likely to occur with the change in amplitude between the full and new moon periods.

  17. A possible role of collagen fibrils in the process of calcification observed in the capsule of the pineal gland in aging rats.

    PubMed

    Humbert, W; Cuisinier, F; Voegel, J C; Pévet, P

    1997-06-01

    The relationship between collagen fibrils and calcified concretions exclusively appearing in the pineal gland of adult/aging rats has been investigated. Deposits of lanthanum, which replace calcium ions are distributed along collagen fibrils with a repeating period of about 70 nm. Calcium has been detected histochemically between collagen bundles surrounding extracellular concretions by means of the pyroantimonate method and by X-ray microanalysis. It is associated with phosphorus. The data presented here suggest that collagen fibrils are involved in the genesis and growth of extracellular concretions located in the connective tissue surrounding the pineal gland of aging rats. PMID:9134857

  18. Redox capacity of the pineal gland in rats. Effect of castration.

    PubMed

    Ianăs, O; Olinescu, R; Bădescu, I

    1993-01-01

    The day/night cycle-induced effects, and the effect of castration on pineal oxidative potential in rats, were studied herein. Experiments were made in adult and castrated Wistar rats kept under normal light conditions during winter (on December and January). Castration was performed 72 hrs before sacrification. Groups of 6 intact or castrated animals were sacrificed at 4 hr-intervals during 24 hrs (the day/night cycle). Blood and pineal were then taken. Peroxides and total pineal antioxidants in plasma and pineal homogenate were assessed by chemiluminescence. The results obtained prove that photoperiod is involved in the organism oxidative potential, and that pineal is involved in the diurnal rhythm of this potential. Pineal peroxide and antioxidative concentrations show circadian variations with minimum and maximal values during the day or the night, which are also reflected at the plasma level. In the first half of the morning are registered increased peroxide and decreased antioxidative levels while at night the diagrams are reversed. As compared to the intact group, in the castrated one antioxidants and peroxides maintain their biorhythms but their concentrations are significantly changed. The diagram of pineal peroxides in the castrated group is situated above that of the intact one, with statistically significant differences only at midday (12:00). Taking into account the antioxidative characteristics of melatonin, one can suppose that maximum pineal antioxidative levels during the night might be due to maximum concentrations of nocturnal melatonin. The significant increase in peroxide concentration and the decrease in antioxidants after castration would partly explain the physiologic status of the elderly with decreased melatonin production and increased oxidative processes. PMID:7697061

  19. Redox capacity of the pineal gland in rats. Effect of castration.

    PubMed

    Ianăs, O; Olinescu, R; Bădescu, I

    1993-01-01

    The day/night cycle-induced effects, and the effect of castration on pineal oxidative potential in rats, were studied herein. Experiments were made in adult and castrated Wistar rats kept under normal light conditions during winter (on December and January). Castration was performed 72 hrs before sacrification. Groups of 6 intact or castrated animals were sacrificed at 4 hr-intervals during 24 hrs (the day/night cycle). Blood and pineal were then taken. Peroxides and total pineal antioxidants in plasma and pineal homogenate were assessed by chemiluminescence. The results obtained prove that photoperiod is involved in the organism oxidative potential, and that pineal is involved in the diurnal rhythm of this potential. Pineal peroxide and antioxidative concentrations show circadian variations with minimum and maximal values during the day or the night, which are also reflected at the plasma level. In the first half of the morning are registered increased peroxide and decreased antioxidative levels while at night the diagrams are reversed. As compared to the intact group, in the castrated one antioxidants and peroxides maintain their biorhythms but their concentrations are significantly changed. The diagram of pineal peroxides in the castrated group is situated above that of the intact one, with statistically significant differences only at midday (12:00). Taking into account the antioxidative characteristics of melatonin, one can suppose that maximum pineal antioxidative levels during the night might be due to maximum concentrations of nocturnal melatonin. The significant increase in peroxide concentration and the decrease in antioxidants after castration would partly explain the physiologic status of the elderly with decreased melatonin production and increased oxidative processes.

  20. Ultradian oscillation in expression of four melatonin receptor subtype genes in the pineal gland of the grass puffer, a semilunar-synchronized spawner, under constant darkness.

    PubMed

    Ikegami, Taro; Maruyama, Yusuke; Doi, Hiroyuki; Hattori, Atsuhiko; Ando, Hironori

    2015-01-01

    Melatonin receptor gene expression as well as melatonin synthesis and secretion activities were examined in the pineal gland of the grass puffer, which exhibits unique lunar/tidal cycle-synchronized mass spawing: spawning occurs before high tide on the day of spring tide during spawing season. Melatonin synthesizing activity was assessed by the abundance of arylalkylamine N-acetyltransferase 2 (AANAT2) mRNA. The amount of aanat2 mRNA was low during light phase and initiated to increase after the light was turned off. The secretion of melatonin from primary pineal organ culture was stimulated after the light was turned off and ceased immediately after the light was turned on. The expression levels of four melatonin receptor subtype genes (mel 1a 1.4, mel 1a 1.7, mel1b, and mel1c) showed synchronous variations, and the levels tended to be high during the dark phase under light/dark conditions. These results suggest that the action of melatonin on the pineal gland is highly dependent on light and photoperiod, possibly with stronger action during night time. Under constant darkness, the expression of four melatonin receptor subtype genes showed unique ultradian oscillations with the period of 14.0-15.4 h, suggesting the presence of a circatidal oscillator in the pineal gland. The present results indicate that melatonin may serve local chronobiological functions in the pineal gland. These cyclic expressions of melatonin receptor genes in the pineal gland may be important in the control of the lunar/tidal cycle-synchronized mass spawning in the grass puffer.

  1. Ultradian oscillation in expression of four melatonin receptor subtype genes in the pineal gland of the grass puffer, a semilunar-synchronized spawner, under constant darkness

    PubMed Central

    Ikegami, Taro; Maruyama, Yusuke; Doi, Hiroyuki; Hattori, Atsuhiko; Ando, Hironori

    2015-01-01

    Melatonin receptor gene expression as well as melatonin synthesis and secretion activities were examined in the pineal gland of the grass puffer, which exhibits unique lunar/tidal cycle-synchronized mass spawing: spawning occurs before high tide on the day of spring tide during spawing season. Melatonin synthesizing activity was assessed by the abundance of arylalkylamine N-acetyltransferase 2 (AANAT2) mRNA. The amount of aanat2 mRNA was low during light phase and initiated to increase after the light was turned off. The secretion of melatonin from primary pineal organ culture was stimulated after the light was turned off and ceased immediately after the light was turned on. The expression levels of four melatonin receptor subtype genes (mel1a1.4, mel1a1.7, mel1b, and mel1c) showed synchronous variations, and the levels tended to be high during the dark phase under light/dark conditions. These results suggest that the action of melatonin on the pineal gland is highly dependent on light and photoperiod, possibly with stronger action during night time. Under constant darkness, the expression of four melatonin receptor subtype genes showed unique ultradian oscillations with the period of 14.0–15.4 h, suggesting the presence of a circatidal oscillator in the pineal gland. The present results indicate that melatonin may serve local chronobiological functions in the pineal gland. These cyclic expressions of melatonin receptor genes in the pineal gland may be important in the control of the lunar/tidal cycle-synchronized mass spawning in the grass puffer. PMID:25688184

  2. Comparative histology of pineal calcification.

    PubMed

    Vígh, B; Szél, A; Debreceni, K; Fejér, Z; Manzano e Silva, M J; Vígh-Teichmann, I

    1998-07-01

    The pineal organ (pineal gland, epiphysis cerebri) contains several calcified concretions called "brain sand" or acervuli (corpora arenacea). These concretions are conspicuous with imaging techniques and provide a useful landmark for orientation in the diagnosis of intracranial diseases. Predominantly composed of calcium and magnesium salts, corpora arenacea are numerous in old patients. In smaller number they can be present in children as well. The degree of calcification was associated to various diseases. However, the presence of calcified concretions seems not to reflect a specific pathological state. Corpora arenacea occur not only in the actual pineal tissue but also in the leptomeninges, in the habenular commissure and in the choroid plexus. Studies with the potassium pyroantimonate (PPA) method on the ultrastructural localization of free calcium ions in the human pineal, revealed the presence of calcium alongside the cell membranes, a finding that underlines the importance of membrane functions in the production of calcium deposits. Intrapineal corpora arenacea are characterized by a surface with globular structures. Meningeal acervuli that are present in the arachnoid cover of the organ, differ in structure from intrapineal ones and show a prominent concentric lamination of alternating dark and light lines. The electron-lucent lines contain more calcium than the dark ones. There is a correlation between the age of the subject and the number of layers in the largest acervuli. This suggests that the formation of these layers is connected to circannual changes in the calcium level of the organ. The histological organization of the human pineal is basically the same as that of mammalian experimental animals. Pineal concretions present in mammalian animal species are mainly of the meningeal type. Meningeal cells around acervuli contain active cytoplasmic organelles and exhibit alkaline phosphatase reaction in the rat and mink, an indication of a presumable

  3. Expression and cellular localization of the transcription factor NeuroD1 in the developing and adult rat pineal gland.

    PubMed

    Castro, Analía E; Benitez, Sergio G; Farias Altamirano, Luz E; Savastano, Luis E; Patterson, Sean I; Muñoz, Estela M

    2015-05-01

    Circadian rhythms govern many aspects of mammalian physiology. The daily pattern of melatonin synthesis and secretion is one of the classic examples of circadian oscillations. It is mediated by a class of neuroendocrine cells known as pinealocytes which are not yet fully defined. An established method to evaluate functional and cytological characters is through the expression of lineage-specific transcriptional regulators. NeuroD1 is a basic helix-loop-helix transcription factor involved in the specification and maintenance of both endocrine and neuronal phenotypes. We have previously described developmental and adult regulation of NeuroD1 mRNA in the rodent pineal gland. However, the transcript levels were not influenced by the elimination of sympathetic input, suggesting that any rhythmicity of NeuroD1 might be found downstream of transcription. Here, we describe NeuroD1 protein expression and cellular localization in the rat pineal gland during development and the daily cycle. In embryonic and perinatal stages, protein expression follows the mRNA pattern and is predominantly nuclear. Thereafter, NeuroD1 is mostly found in pinealocyte nuclei in the early part of the night and in cytoplasm during the day, a rhythm maintained into adulthood. Additionally, nocturnal nuclear NeuroD1 levels are reduced after sympathetic disruption, an effect mimicked by the in vivo administration of α- and β-adrenoceptor blockers. NeuroD1 phosphorylation at two sites, Ser(274) and Ser(336) , associates with nuclear localization in pinealocytes. These data suggest that NeuroD1 influences pineal phenotype both during development and adulthood, in an autonomic and phosphorylation-dependent manner.

  4. The light-induced transcriptome of the zebrafish pineal gland reveals complex regulation of the circadian clockwork by light.

    PubMed

    Ben-Moshe, Zohar; Alon, Shahar; Mracek, Philipp; Faigenbloom, Lior; Tovin, Adi; Vatine, Gad D; Eisenberg, Eli; Foulkes, Nicholas S; Gothilf, Yoav

    2014-04-01

    Light constitutes a primary signal whereby endogenous circadian clocks are synchronized ('entrained') with the day/night cycle. The molecular mechanisms underlying this vital process are known to require gene activation, yet are incompletely understood. Here, the light-induced transcriptome in the zebrafish central clock organ, the pineal gland, was characterized by messenger RNA (mRNA) sequencing (mRNA-seq) and microarray analyses, resulting in the identification of multiple light-induced mRNAs. Interestingly, a considerable portion of the molecular clock (14 genes) is light-induced in the pineal gland. Four of these genes, encoding the transcription factors dec1, reverbb1, e4bp4-5 and e4bp4-6, differentially affected clock- and light-regulated promoter activation, suggesting that light-input is conveyed to the core clock machinery via diverse mechanisms. Moreover, we show that dec1, as well as the core clock gene per2, is essential for light-entrainment of rhythmic locomotor activity in zebrafish larvae. Additionally, we used microRNA (miRNA) sequencing (miR-seq) and identified pineal-enhanced and light-induced miRNAs. One such miRNA, miR-183, is shown to downregulate e4bp4-6 mRNA through a 3'UTR target site, and importantly, to regulate the rhythmic mRNA levels of aanat2, the key enzyme in melatonin synthesis. Together, this genome-wide approach and functional characterization of light-induced factors indicate a multi-level regulation of the circadian clockwork by light. PMID:24423866

  5. LC/MS/MS analysis of the endogenous dimethyltryptamine hallucinogens, their precursors, and major metabolites in rat pineal gland microdialysate.

    PubMed

    Barker, Steven A; Borjigin, Jimo; Lomnicka, Izabela; Strassman, Rick

    2013-12-01

    We report a qualitative liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for the simultaneous analysis of the three known N,N-dimethyltryptamine endogenous hallucinogens, their precursors and metabolites, as well as melatonin and its metabolic precursors. The method was characterized using artificial cerebrospinal fluid (aCSF) as the matrix and was subsequently applied to the analysis of rat brain pineal gland-aCSF microdialysate. The method describes the simultaneous analysis of 23 chemically diverse compounds plus a deuterated internal standard by direct injection, requiring no dilution or extraction of the samples. The results demonstrate that this is a simple, sensitive, specific and direct approach to the qualitative analysis of these compounds in this matrix. The protocol also employs stringent MS confirmatory criteria for the detection and confirmation of the compounds examined, including exact mass measurements. The excellent limits of detection and broad scope make it a valuable research tool for examining the endogenous hallucinogen pathways in the central nervous system. We report here, for the first time, the presence of N,N-dimethyltryptamine in pineal gland microdialysate obtained from the rat.

  6. Endocrine glands

    MedlinePlus

    Endocrine glands release (secrete) hormones into the bloodstream. The endocrine glands include: Adrenal Hypothalamus Islets of Langerhans in the pancreas Ovaries Parathyroid Pineal Pituitary Testes Thyroid

  7. Multiple sclerosis: the role of the pineal gland in its timing of onset and risk of psychiatric illness.

    PubMed

    Sandyk, R; Awerbuch, G I

    1993-09-01

    The incidence of multiple sclerosis (MS) is age-dependent being rare prior to age 10, unusual prior to age 15, with a peak in the mid 20s. It has been suggested, therefore, that the clinical manifestation of MS is dependent upon having passed the pubertal period. Since pineal melatonin secretion declines from childhood to puberty and as melatonin is an immunomodulator, we have proposed that the dramatic decline in melatonin secretion just prior to the onset of the physical manifestations of puberty may disrupt immune responses resulting in either reactivation of the infective agent or in an increased susceptibility to post-pubertal infection. The fall in melatonin secretion during pre-puberty may also increase the susceptibility of these patients to affective disorder which is associated with lower melatonin secretion and the presence of a phase-advance of their biological rhythms. We predicted, therefore, a higher incidence of affective disorder in patients with pubertal or post-pubertal onset of MS compared to those in whom the disease manifested later. To test this hypothesis, we studied the incidence of affective disorder in relation to age of onset of first neurological symptoms in 31 MS patients, 6 of whom manifested symptoms of MS prior to age 18 (mean = 16.8 years). All patients with pubertal onset MS and only 48% of the control group had an affective disorder. The pubertal onset patients also had a significantly lower nocturnal melatonin levels and a lower incidence of pineal calcification on CT scan. These findings thus support the hypothesis implicating the pineal gland in the timing of onset of MS and in the risk for the development of affective disorder. PMID:8225803

  8. Melatonin rhythm onset in the adult siberian hamster: influence of photoperiod but not 60-Hz magnetic field exposure on melatonin content in the pineal gland and in circulation.

    PubMed

    Yellon, S M; Truong, H N

    1998-02-01

    To determine the relationship between pineal melatonin production and its appearance in circulation, the rising phase of the pineal and serum melatonin rhythm was studied in the adult Siberian hamster. Melatonin concentrations increased in the pineal gland and in serum at 1.50 and 1.75 h, respectively, relative to lights off in long days (16 h of light/day) and at 2.00 and 2.75 h, respectively, in short days (10 h of light/day). Thus, a photoperiod-dependent melatonin rise in circulation lagged production by the pineal gland by 0.50 h--a delay of 0.75 h in short-day hamsters versus 0.25 h in long-day hamsters. Following initiation of this rise, concentrations that were typical of the nighttime peak were achieved within 2 h of melatonin rhythm onset, regardless of photoperiod. To determine whether clock control of the rising phase of the melatonin rhythm, in the absence of photoperiod cues, may be disrupted by perturbations in the ambient magnetic field, hamsters in constant darkness were acutely exposed to a 1-Gauss, 60-Hz magnetic field for 15 min or were daily exposed to this treatment for 14 or 21 days. Neither the melatonin rise in pineal content or circulation during subjective night was affected by acute or chronic magnetic field exposures; testes regression similarly occurred in sham and daily magnetic field-exposed hamsters in constant darkness. These findings indicate that magnetic field exposures are unlikely to serve as a zeitgeber for the circadian mechanism that controls onset of the melatonin rhythm; rather, photoperiod is a predominant cue that may differentially regulate the rising phase of melatonin production in the pineal gland and concentration in circulation.

  9. The relationship of thought disorder to third ventricle width and calcification of the pineal gland in chronic schizophrenia.

    PubMed

    Sandyk, R

    1993-01-01

    Since the early writings of Bleuler in 1908, it has been recognized that schizophrenia is a heterogenous disorder with diversity in symptomatology, course, prognosis, and probably etiology. Over the past 50 years, considerable research has been devoted to the prognosis of schizophrenia and despite variability among findings, certain historical and clinical predictors have been established. A recent study undertaken in 58 DSM-III diagnosed schizophrenic inpatients found that of the various clinical clusters assessed prospectively, thought disorder stood out as the single most salient predictor of poor outcome (Kay & Murrill, 1990). In the present study I have investigated the relationship of thought disorder to CT scan measures of third ventricle width (TVW), prefrontal cortical atrophy, and cortical atrophy in 14 chronic schizophrenic patients. In addition, I have studied the relationship of thought disorder to pineal calcification (PC) and choroid plexus (CP) sizes in 20 chronic schizophrenic patients. TVW and PC size were the only neuroradiological measures found to be associated with the degree of thought disorder. These findings suggest that both diencephalic damage and calcification of the pineal gland may be related to disorganized thinking in schizophrenia and, by inference, to an unfavorable prognosis. PMID:8063514

  10. The role of the pineal gland in the photoperiodic control of bird song frequency and repertoire in the house sparrow, Passer domesticus.

    PubMed

    Wang, Gang; Harpole, Clifford E; Paulose, Jiffin; Cassone, Vincent M

    2014-04-01

    Temperate zone birds are highly seasonal in many aspects of their physiology. In mammals, but not in birds, the pineal gland is an important component regulating seasonal patterns of primary gonadal functions. Pineal melatonin in birds instead affects seasonal changes in brain song control structures, suggesting the pineal gland regulates seasonal song behavior. The present study tests the hypothesis that the pineal gland transduces photoperiodic information to the control of seasonal song behavior to synchronize this important behavior to the appropriate phenology. House sparrows, Passer domesticus, expressed a rich array of vocalizations ranging from calls to multisyllabic songs and motifs of songs that varied under a regimen of different photoperiodic conditions that were simulated at different times of year. Control (SHAM) birds exhibited increases in song behavior when they were experimentally transferred from short days, simulating winter, to equinoctial and long days, simulating summer, and decreased vocalization when they were transferred back to short days. When maintained in long days for longer periods, the birds became reproductively photorefractory as measured by the yellowing of the birds' bills; however, song behavior persisted in the SHAM birds, suggesting a dissociation of reproduction from the song functions. Pinealectomized (PINX) birds expressed larger, more rapid increases in daily vocal rate and song repertoire size than did the SHAM birds during the long summer days. These increases gradually declined upon the extension of the long days and did not respond to the transfer to short days as was observed in the SHAM birds, suggesting that the pineal gland conveys photoperiodic information to the vocal control system, which in turn regulates song behavior.

  11. Age-related changes in the incidence of pineal gland calcification in Turkey: A prospective multicenter CT study.

    PubMed

    Turgut, Ahmet Tuncay; Karakaş, Hakkı Muammer; Ozsunar, Yelda; Altın, Levent; Ceken, Kağan; Alıcıoğlu, Banu; Sönmez, Iclal; Alparslan, Ahmet; Yürümez, Belde; Celik, Tayfun; Kazak, Eda; Geyik, Pınar Özdemir; Koşar, Uğur

    2008-06-01

    The goal of this cross-sectional observational study was to determine the incidence of pineal gland calcification (PGC), to investigate the interaction of PGC and aging, and to compare the incidence of PGC among the populations living in Turkey. In a prospective study the rate of PGC on CT scans of 1376 individuals in six referral centers from different regions of Turkey was investigated, with emphasis on effects of climatological parameters and aging on PGC. It was found that the incidence of PGC increased rapidly after first decade and the increase remains gradual thereafter, higher in males than in females for all age groups. There was a significant difference for incidence and degree of PGC between different clinics and between both sexes (p<0.001). In addition, there was a significant difference for the degree of PGC between the clinics in low altitude group and those in high altitude group (p<0.001 for each). Logistic regression analysis revealed that age, sex, altitude and intensity of sunlight exposure significantly affected the risk of PGC (odds ratios (OR) 1.335, 95% confidence intervals (CI) 1.261-1.414, p<0.001; OR 1.900, 95% CI 1.486-2.428, p<0.001; OR 0.715, 95% CI 0.517-0.990, p<0.05; OR 0.997, 95% CI 0.994-0.999, p<0.01, respectively). Furthermore, by multiple linear regression analysis, high altitude and increased intensity of sunlight exposure were found to affect the degree of PGC (beta=0.003, p<0.001). It is concluded that there is a close relationship between PGC and the aforementioned parameters, supporting a link between the development of PGC and these. This study provides some reference data for new clinical studies on the putative role of pineal gland in future. PMID:18420391

  12. Adrenergic signals direct rhythmic expression of transcriptional repressor CREM in the pineal gland.

    PubMed

    Stehle, J H; Foulkes, N S; Molina, C A; Simonneaux, V; Pévet, P; Sassone-Corsi, P

    1993-09-23

    Transcription factor CREM appears to play a key physiological and developmental role within the hypothalamic-pituitary-gonadal axis. This axis is modulated by the pineal hormone melatonin, whose production is in turn driven by the endogenous clock. There is striking circadian fluctuation of a novel CREM isoform, ICER, which is expressed at high levels during the night. ICER is generated from an alternative, intronic promoter and functions as a powerful repressor of cyclic AMP-induced transcription. Rhythmic adrenergic signals originated by the clock direct ICER expression by stimulation of the cAMP signal transduction pathway.

  13. Radiometric assay for phenylethanolamine N-methyltransferase and catechol O-methyltransferase in a single tissue sample: application to rat hypothalamic nuclei, pineal gland, and heart

    SciTech Connect

    Culman, J.; Torda, T.; Weise, V.K.

    1987-08-01

    A simple and highly sensitive method for simultaneous assay of phenylethanolamine N-methyltransferase (PNMT) and catechol O-methyltransferase (COMT) is described. These enzymes are determined in a single tissue homogenate using S-(methyl-/sup 3/H) adenosyl-L-methionine as methyl donor and sequentially incubating with the substrates phenylethanolamine and epinephrine. The radioactive products of the enzymatic reactions, N-methylphenylethanolamine and metanephrine, are extracted and then separated by thin-layer chromatography. The identity of the reaction products has been established chromatographically and the conditions for both enzymatic reactions in the assay procedure have been defined. Measurement of PNMT activity in the rat pineal gland or in minute fragments of other tissues (e.g., brain nuclei) has not been possible using previously described methods. Activities of PNMT and COMT in the rat pineal gland, various hypothalamic nuclei, and the auricular and ventricular myocardia are herein reported.

  14. PLURIVESICULAR SECRETORY PROCESSES AND NERVE ENDINGS IN THE PINEAL GLAND OF THE RAT

    PubMed Central

    De Robertis, Eduardo; de Iraldi, Amanda Pellegrino

    1961-01-01

    The pineal body of white normal rats, 1.5 to 3 months old, was studied under the electron microscope. A single type of parenchymal cell—the pinealocyte—is recognized as the main component of the tissue, and some of the structural characteristics of the nucleus and cytoplasm are described. The main morphological characteristic of the pinealocytes is represented by club-shaped perivascular expansions connected to the cell by thin pedicles. They are found lying in a large, clear space surrounding the blood capillaries. The name plurivesicular secretory processes is proposed, to emphasize the main structural feature and the probable function of these cellular expansions. A tubulofibrillar component is mainly found in the pedicle, and within the expansion there are numerous small mitochondria and densily packed vesicles of about 425 A. Two types of vesicles, one with a homogeneous content and another with a very dense osmium deposit, are described. Between the two types there are intermediary forms. In these processes, mitochondria show profound changes which may lead to complete vacuolization. The significance of this plurivesicular secretory component is discussed in the light of recent work on the biogenic amines of the pineal body and preliminary experiments showing the release of the vesicles containing dense granules after treatment with reserpine. These vesicles are interpreted as the site of storage of some of the biogenic amines. Bundles of unmyelinated nerve fibers and endings on large blood vessels which also contain a plurivesicular content are described and tentatively interpreted as adrenergic nerve terminals. PMID:13720811

  15. The effect of chronic morphine or methadone exposure and withdrawal on clock gene expression in the rat suprachiasmatic nucleus and AA-NAT activity in the pineal gland.

    PubMed

    Pačesová, D; Novotný, J; Bendová, Z

    2016-07-18

    The circadian rhythms of many behavioral and physiological functions are regulated by the major circadian pacemaker in the suprachiasmatic nucleus. Long-term opiate addiction and drug withdrawal may affect circadian rhythmicity of various hormones or the sleep/activity pattern of many experimental subjects; however, limited research has been done on the long-term effects of sustained opiate administration on the intrinsic rhythmicity in the suprachiasmatic nucleus and pineal gland. Here we compared the effects of repeated daily treatment of rats with morphine or methadone and subsequent naloxone-precipitated withdrawal on the expression of the Per1, Per2, and Avp mRNAs in the suprachiasmatic nucleus and on arylalkylamine N-acetyltransferase activity in the pineal gland. We revealed that 10-day administration and withdrawal of both these drugs failed to affect clock genes and Avp expression in the SCN. Our results indicate that opioid-induced changes in behavioral and physiological rhythms originate in brain structures downstream of the suprachiasmatic nucleus regulatory output pathway. Furthermore, we observed that acute withdrawal from methadone markedly extended the period of high night AA-NAT activity in the pineal gland. This suggests that withdrawal from methadone, a widely used drug for the treatment of opioid dependence, may have stronger impact on melatonin synthesis than withdrawal from morphine. PMID:27070740

  16. Effects of Melatonin on Morphological and Functional Parameters of the Pineal Gland and Organs of Immune System in Rats During Natural Light Cycle and Constant Illumination.

    PubMed

    Litvinenko, G I; Shurlygina, A V; Gritsyk, O B; Mel'nikova, E V; Tenditnik, M V; Avrorov, P A; Trufakin, V A

    2015-10-01

    We studied the response of the pineal gland and organs of the immune system to melatonin treatment in Wistar rats kept under conditions of abnormal illumination regimen. The animals were kept under natural light regimen or continuous illumination for 14 days and then received daily injections of melatonin (once a day in the evening) for 7 days. Administration of melatonin to rats kept at natural light cycle was followed by a decrease in percent ratio of CD4+8+ splenocytes and CD4-8+ thymocytes. In 24-h light with the following melatonin injections were accompanied by an increase in percent rate and absolute amount of CD4+8+ cells in the spleen, and a decrease in percent rate of CD11b/c and CD4-8+ splenocytes. In the thymus amount of CD4-8+ cells increased, and absolute number of CD4+25+ cells reduced. Melatonin significantly decreased lipofuscin concentration in the pineal gland during continuous light. Direction and intensity of effects of melatonin on parameters of cell immunity and state of the pineal gland were different under normal and continuous light conditions. It should be taken into account during using of this hormone for correction of immune and endocrine impairments developing during change in light/dark rhythm.

  17. Multiple sclerosis: the role of puberty and the pineal gland in its pathogenesis.

    PubMed

    Sandyk, R

    1993-02-01

    Epidemiological studies demonstrate that the incidence of multiple sclerosis (MS) is age-dependent being rare prior to age 10, unusual prior to age 15, with a peak in the mid 20s. It has been suggested that the manifestation of MS is dependent upon having passed through the pubertal period. In the present communication, I propose that critical changes in pineal melatonin secretion, which occur in temporal relationship to the onset of puberty, are intimately related to the timing of onset of the clinical manifestations of MS. Specifically, it is suggested that the fall in melatonin secretion during the prepubertal period, which may disrupt pineal-mediated immunomodulation, may stimulate either the reactivation of the infective agent or increase the susceptibility to infection during the pubertal period. Similarly, the rapid fall in melatonin secretion just prior to delivery may account for the frequent occurrence of relapse in MS patients during the postpartum period. In contrast, pregnancy, which is associated with high melatonin concentrations, is often accompanied by remission of symptoms. Thus, the presence of high melatonin levels may provide a protective effect, while a decline in melatonin secretion may increase the risk for the development and exacerbation of the disease. The melatonin hypothesis of MS may explain other epidemiological and clinical phenomena associated with the disease such as the low incidence of MS in the black African and American populations, the inverse correlation with sun light and geomagnetic field exposure, the occurrence of relapses in relation to seasonal changes and fluctuations in mood, and the association of MS with affective illness and malignant disease. Therapeutically, this hypothesis implies that application of bright light therapy or the use of other major synchronizers of circadian rhythms such as sleep deprivation or application of external weak magnetic fields may be beneficial in the treatment and/or prophylaxis of

  18. Calcium concrements in the pineal gland of the Arctic fox (Vulpes lagopus) and their relationship to pinealocytes, glial cells and type I and III collagen fibers.

    PubMed

    Bulc, M; Lewczuk, B; Prusik, M; Gugołek, A; Przybylska-Gornowicz, B

    2010-01-01

    The aim of the present study was to analyze the presence and morphology of the pineal concretions in the Arctic fox and their relationship to pinealocytes, glial cells and collagen fibers. Pineals collected from 7-8 month-old and 3-4 year-old foxes (6 in each age-group) were investigated. Sections of the glands were stained with HE, Mallory's method and alizarin red S as well as subjected to a combined procedure involving immunofluorescent staining with antibodies against antigen S, glial fibril acid protein (GFAP), type I and III collagen and histochemical staining with alizarin red S. The pineal concretions were found in 2 of 6 investigated Arctic foxes aged 3 years and they were not observed in animals aged 7-8 months. The acervuli were present in the parenchyma and the connective tissue septa. They were more numerous in the distal part than in the proximal part of the gland. The acervuli stained with alizarin red S revealed an intensive red fluorescence, what enabled the use of this compound in a combined histochemical-immunofluorescent procedure. A majority of cells in the fox pineal showed positive staining with antibodies against antigen S, a marker of pinealocytes. GFAP-positive cells were especially numerous in the proximal part of the gland. Both antigen S- and GFAP-positive cells were frequently observed close to the concrements. Collagen fibers of type I and III were found in the capsule, connective tissue septa and vessels. Immunoreactive fibers did not form any capsules or basket-like structures surrounding the concrements. PMID:20731181

  19. Early development of circadian rhythmicity in the suprachiamatic nuclei and pineal gland of teleost, flounder (Paralichthys olivaeus), embryos.

    PubMed

    Mogi, Makoto; Uji, Susumu; Yokoi, Hayato; Suzuki, Tohru

    2015-08-01

    Circadian rhythms enable organisms to coordinate multiple physiological processes and behaviors with the earth's rotation. In mammals, the suprachiasmatic nuclei (SCN), the sole master circadian pacemaker, has entrainment mechanisms that set the circadian rhythm to a 24-h cycle with photic signals from retina. In contrast, the zebrafish SCN is not a circadian pacemaker, instead the pineal gland (PG) houses the major circadian oscillator. The SCN of flounder larvae, unlike that of zebrafish, however, expresses per2 with a rhythmicity of daytime/ON and nighttime/OFF. Here, we examined whether the rhythm of per2 expression in the flounder SCN represents the molecular clock. We also examined early development of the circadian rhythmicity in the SCN and PG. Our three major findings were as follows. First, rhythmic per2 expression in the SCN was maintained under 24 h dark (DD) conditions, indicating that a molecular clock exists in the flounder SCN. Second, onset of circadian rhythmicity in the SCN preceded that in the PG. Third, both 24 h light (LL) and DD conditions deeply affected the development of circadian rhythmicity in the SCN and PG. This is the first report dealing with the early development of circadian rhythmicity in the SCN in fish.

  20. EXTIRPATION OF THE PINEAL BODY

    PubMed Central

    Dandy, Walter E.

    1915-01-01

    1. Following the removal of the pineal I have observed no sexual precocity or indolence, no adiposity or emaciation, no somatic or mental precocity or retardation. 2. Our experiments seem to have yielded nothing to sustain the view that the pineal gland has an active endocrine function of importance either in the very young or adult dogs. 3. The pineal is apparently not essential to life and seems to have no influence upon the animal's well being. PMID:19867913

  1. Survey of spontaneous dystrophic mineralisation of pineal gland in ageing rats.

    PubMed

    Majeed, S K

    1997-11-01

    The survey included 151 rats from several carcinogenicity studies up to 104 weeks and 260 rats from short-term studies up to 52 weeks. All studies were performed during the period 1990-1996. Young rats up to 52 weeks of age showed normal structural appearance, in 134 male rats the incidence of mineralisation was 6.3% and in 126 females the incidence was only slightly less at 5.6%. In ageing rats, 70-104 weeks, 88 males and 63 females showed far higher incidence of mineralisation, 83% and 57% respectively, showing that the incidence of mineralisation in ageing rats was higher in males than females. The focal mineralisation occurred mainly at the margin of the gland in the subcapsular region mostly adjacent to small blood vessels. On occasions these involved the parenchymal cells in the middle part of the gland. The focal mineralisation stained positive with von Kossa indicating presence of calcium and also with PAS (Pariodic Acid-Schiff method), indicating presence of neutral mucopolysaccharide. There was no evidence of positivity with Perl's stain (for ferric salts), Toluidine blue (for protein) or Alcian blue (for acid mucopolysaccharides). With Oil Red O there was evidence of presence of fat or lipid in pinealocytes. PMID:9428987

  2. Light-Emitting Diodes and Cool White Fluorescent Light Similarly Suppress Pineal Gland Melatonin and Maintain Retinal Function and Morphology in the Rat. Part 1

    NASA Technical Reports Server (NTRS)

    Holley, Daniel C.; Heeke, D.; Mele, G.

    1999-01-01

    Currently, the light sources most commonly used in animal habitat lighting are cool white fluorescent or incandescent lamps. We evaluated a novel light-emitting diode (LED) light source for use in animal habitat lighting by comparing its effectiveness to cool white fluorescent light (CWF) in suppressing pineal gland melatonin and maintaining normal retinal physiology and morphology in the rat. Results of pineal melatonin suppression experiments showed equal suppression of pineal melatonin concentrations for LED light and CWF light at five different light illuminances (100, 40, 10, 1 and 0.1 lux). There were no significant differences in melatonin suppression between LED and CWF light when compared to unexposed controls. Retinal physiology was evaluated using electroretinography. Results show no differences in a-wave implicit times and amplitudes or b-wave implicit times and amplitudes between 100-lux LED-exposed rats and 100-lux CWF-exposed rats. Results of retinal histology assessment show no differences in retinal thickness rod outer segment length and number of rod nuclei between rats exposed to 100-lux LED and 100-lux CWF for days. Furthermore, the retinal pigmented epithelium and rod outer segments of all eyes observed were in good condition and of normal thickness. This study indicates that LED light does not cause retinal damage and can suppress pineal melatonin at similar intensities as a conventional CWF light source. These data suggest that LED light sources may be suitable replacements for conventional light sources used in the lighting of rodent vivariums while providing many mechanical and economical advantages.

  3. Expression and cellular localizaion of melatonin-synthesizing enzymes in rat and human salivary glands.

    PubMed

    Shimozuma, Masashi; Tokuyama, Reiko; Tatehara, Seiko; Umeki, Hirochika; Ide, Shinji; Mishima, Kenji; Saito, Ichiro; Satomura, Kazuhito

    2011-04-01

    Melatonin, discovered in 1958, is secreted by the pineal gland primarily during the night. Its secretion is controlled by the light/dark cycle of the environment. Melatonin is also produced in and secreted by various extrapineal organs, tissues and cells and its synthesizing enzyme arylalkylamine N-acetyltransferase (AANAT) is expressed in various extrapineal organs, tissues and cells. Recently, it was reported that melatonin is present in saliva, but it is not certain where melatonin was synthesized and whether it was secreted into saliva and what function it may have in saliva. The present study was performed to investigate where melatonin was synthesized and whether it was secreted by salivary glands into saliva. We performed immunohistochemical analysis of the expression of AANAT in rat parotid, submandibular and sublingual glands and the expression of both AANAT and hydroxyindole-O-methyltransferase (HIOMT) in human submandibular glands. We evaluated the expression of AANAT and HIOMT mRNA in rat submandibular glands by quantitative reverse transcription-polymerase chain reaction. As a result, we observed expression of AANAT in epithelial cells of striated ducts in rat salivary glands and expression of AANAT, HIOMT and melatonin in epithelial cells of striated ducts in human submandibular glands. In addition, we also confirmed the expression of the most potent melatonin receptor, melatonin 1a receptor, in rat buccal mucosa. Our findings suggest that melatonin might be produced and secreted by salivary glands directly into saliva and that it might play some physiological role in the oral cavity.

  4. Humanization of the mouse mammary gland.

    PubMed

    Wronski, A; Arendt, L M; Kuperwasser, Charlotte

    2015-01-01

    Although mouse models have provided invaluable information on the mechanisms of mammary gland development, anatomical and developmental differences between human and mice limit full understanding of this fundamental process. Humanization of the mouse mammary gland by injecting immortalized human breast stromal cells into the cleared murine mammary fat pad enables the growth and development of human mammary epithelial cells or tissue. This facilitates the characterization of human mammary gland development or tumorigenesis by utilizing the mouse mammary fat pad. Here we describe the process of isolating human mammary stromal and epithelial cells as well as their introduction into the mammary fat pads of immunocompromised mice.

  5. The foetal pig pineal gland is richly innervated by nerve fibres containing catecholamine-synthesizing enzymes, neuropeptide Y (NPY) and C-terminal flanking peptide of NPY, but it does not secrete melatonin.

    PubMed

    Bulc, Michał; Lewczuk, Bogdan; Prusik, Magdalena; Całka, Jarosław

    2013-05-01

    Innervation of the mammalian pineal gland during prenatal development is poorly recognized. Therefore, immunofluorescence studies of the pineals of 70- and 90-day-old foetuses of the domestic pig were performed using antibodies against tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DβH), neuropeptide Y (NPY) and C-terminal flanking peptide of NPY (CPON). The investigated glands were supplied by numerous nerve fibres containing TH and DβH. The density of these fibres was higher in the distal and middle parts of the gland than in the proximal one. NPY and CPON were identified in the majority of DβH-positive fibres as well as in a small population of DβH-negative fibres localized mainly in the proximal part of the pineal. The immunoreactive fibres were more numerous in 90-day-old foetuses than in 70-day-old ones. The effect of norepinephrine on melatonin secretion by the foetal pineals in the short-term organ culture was studied to determine the role of DβH-positive fibres during prenatal life. For the same purpose melatonin was measured in the blood in the umbilical cords and in the jugular vein of the mother. The pineals of both groups of foetuses did not secrete melatonin in the organ culture, independently of the presence or absence of norepinephrine in the medium. Melatonin concentrations in the blood in the umbilical cords of foetuses from the same litter and in the jugular vein of their mother were similar. The presence of adrenergic nerve fibres in the pig pineal during gestation does not seem to be associated with the control of melatonin secretion.

  6. The Pineal Gland

    ERIC Educational Resources Information Center

    Kimbrough, T. Daniel; Llewellyn, Gerald C.

    1973-01-01

    Describes a surgical technique for performing pinealectomics, applicable to classroom and laboratory studies, by using a head-holding device for small animals and a flat dissecting tray outfitted with holding straps for larger animals. (CC)

  7. Pineal cyst: a review of clinical and radiological features.

    PubMed

    Choy, Winward; Kim, Won; Spasic, Marko; Voth, Brittany; Yew, Andrew; Yang, Isaac

    2011-07-01

    Pineal cysts (PCs) are benign and often asymptomatic lesions of the pineal region that are typically small and do not change in size over time. PCs appear as small, well circumscribed, unilocular masses that either reside within or completely replace the pineal gland. This article reviews and discusses the characteristic features of PCs-clinical, histological, and identifiable by various imaging modalities-which assist clinicians in narrowing the differential diagnosis for pineal lesions. PMID:21801982

  8. Pineal Calcification Among Black Patients

    PubMed Central

    Fan, Kuang-Jaw

    1983-01-01

    A postmortem histopathological study was done in 233 pineal glands of black patients. Among them, 70 percent showed microscopic evidence of calcification in the pineal parenchyma. The frequency of calcification increased with age. However, the severity of calcification reached the peak in the 60 to 69 year old age group and then gradually declined. As compared to males, females had slightly higher frequency and reached the peak of severity in younger age groups. When pineal calcification was compared among patients with various malignancies, a higher frequency and more severe calcification were observed in patients with carcinoma of the prostate and the pancreas. A lower frequency and less severe calcification were observed in patients with carcinoma of the breast and the cervix. The results of this study emphasize the important role of sex hormone in genesis of pineal calcification. PMID:6631985

  9. Pineal calcification among black patients.

    PubMed

    Fan, K J

    1983-08-01

    A postmortem histopathological study was done in 233 pineal glands of black patients. Among them, 70 percent showed microscopic evidence of calcification in the pineal parenchyma. The frequency of calcification increased with age. However, the severity of calcification reached the peak in the 60 to 69 year old age group and then gradually declined. As compared to males, females had slightly higher frequency and reached the peak of severity in younger age groups. When pineal calcification was compared among patients with various malignancies, a higher frequency and more severe calcification were observed in patients with carcinoma of the prostate and the pancreas. A lower frequency and less severe calcification were observed in patients with carcinoma of the breast and the cervix. The results of this study emphasize the important role of sex hormone in genesis of pineal calcification.

  10. [THE CHANGES OF THE INTERRELATIONS OF THE PINEAL GLAND AND THE ORGANS OF THE IMMUNE SYSTEM IN RATS IN RESPONSE TO MELATONIN ADMINISTRATION IN LIGHT REGIME DISTURBANCES].

    PubMed

    Litvinenko, G I; Gritzyk, O B; Mel'nikova, Ye V; Avrorov, P A; Tenditnik, M V; Shurlygina, A V; Trufakin, V A

    2015-01-01

    In this work the correlation analysis was applied to detect the integrated response of the pineal gland (PG) and immunocompetent organs of male Wistar rats in response to administration of melatonin (MT) in light regime disturbances. Animals were kept for 14 days under natural or continuous light (CL). Then for 7 days they received the injections of either 0.9% solution of sodium chloride or MT, after which the rats were decapitated and the mass of their body, PG, thymus and spleen was determined. The lymphocyte subpopulations of the thymus and spleen were studied by flow cytometry. The amount of lipofuscin in PG was assessed by the intensity of autofluorescence in organ frozen sections in 560-600 nm wavelength range. It was found that under the influence of MT, the number of intraorgan correlations in the immune system increased, regardless of the light regime. In animals on CL treated with MT, the number of interorgan connections was reduced, while negative correlations appeared between PG lipofuscin content and cellular composition of the spleen. The synchronizing and adaptogenic effects of MT were most pronounced under conditions of CL.

  11. Primary pineal malignant melanoma

    PubMed Central

    Cedeño Diaz, Oderay Mabel; Leal, Roberto García; La Cruz Pelea, Cesar

    2011-01-01

    Primary pineal malignant melanoma is a rare entity, with only thirteen cases reported in the world literature to date. We report a case of a 70-year-old man, who consulted with gait disturbance of six months duration, associated in the last month with dizziness, visual abnormalities and diplopia. No other additional melanocytic lesions were found elsewhere. The magnetic resonance showed a 25 mm expansive mass in the pineal gland that was associated with hydrocephaly, ventricular and transependimary oedema. The lesion was partially excised by a supracerebellar infratentorial approach. The histological examination revealed a melanoma. The patient received radiation therapy, but died of disease 16 weeks later. We herein review the literature on this rare tumour and comment on its clinical, radiological and histopathological features and differential diagnosis. PMID:24765293

  12. Pineal anlage tumour - a rare entity with divergent histology.

    PubMed

    Ahuja, Arvind; Sharma, Mehar Chand; Suri, Vaishali; Sarkar, Chitra; Sharma, B S; Garg, Ajay

    2011-06-01

    Pineal anlage tumour is a rare tumour of the pineal gland that is not listed in the 2007 World Health Organization classification of tumours of the central nervous system. Pineal anlage has been defined as a primary pineal tumour with both neuroepithelial and ectomesenchymal differentiation but without endodermal differentiation. We report a pineal anlage tumour in a 4-month-old boy, the youngest patient reported with this rare tumour, with a brief review of the literature. Clinicians and neuropathologists should be aware of this entity as it is likely to be misdiagnosed as a teratoma or a melanocytic tumour of the central nervous system.

  13. Scanning electron microscopy and electron probe microanalysis studies of human pineal concretions.

    PubMed

    Kodaka, T; Mori, R; Debari, K; Yamada, M

    1994-10-01

    The calcareous concretions of human pineal bodies were investigated with scanning electron microscopy and electron probe microanalysis. The initial concretions measuring 5-7 microns in diameter may have started at the calcified pinealocytes. They grew appositionally forming concentric laminations, and then the simple calcospherulites over 20 microns occasionally aggregated with each other. Some of them became numerous spherulite-aggregated concretions. Others individually grew with scallop-shaped concentric laminations at intervals of 0.05-1 microns and became lobated calcospherulites up to 0.5 mm. The concretions over 0.5 mm were formed by their attachments. The major elements were Ca and P, while traces of S, Mg, and Na were detected. In the calcification and crystallization values, the center of the concretions over 50 microns was significantly higher than the periphery, while there were no differences among the centers and also among the peripheries. The Ca and P amounts in the center were 30.8% and 14.2% by weight and the Ca/P molar ratio was 1.68; thereby the sand-grain-shaped crystals may be nearly hydroxyapatite, as reported previously. PMID:7699308

  14. Critical time delay of the pineal melatonin rhythm in humans due to weak electromagnetic exposure.

    PubMed

    Halgamuge, Malka N

    2013-08-01

    Electromagnetic fields (EMFs) can increase free radicals, activate the stress response and alter enzyme reactions. Intracellular signalling is mediated by free radicals and enzyme kinetics is affected by radical pair recombination rates. The magnetic field component of an external EMF can delay the "recombination rate" of free radical pairs. Magnetic fields thus increase radical life-times in biological systems. Although measured in nanoseconds, this extra time increases the potential to do more damage. Melatonin regulates the body's sleep-wake cycle or circadian rhythm. The World Health Organization (WHO) has confirmed that prolonged alterations in sleep patterns suppress the body's ability to make melatonin. Considerable cancer rates have been attributed to the reduction of melatonin production as a result of jet lag and night shift work. In this study, changes in circadian rhythm and melatonin concentration are observed due to the external perturbation of chemical reaction rates. We further analyze the pineal melatonin rhythm and investigate the critical time delay or maturation time of radical pair recombination rates, exploring the impact of the mRNA degradation rate on the critical time delay. The results show that significant melatonin interruption and changes to the circadian rhythm occur due to the perturbation of chemical reaction rates, as also reported in previous studies. The results also show the influence of the mRNA degradation rate on the circadian rhythm's critical time delay or maturation time. The results support the hypothesis that exposure to weak EMFs via melatonin disruption can adversely affect human health.

  15. Alternative Isoform Analysis of Ttc8 Expression in the Rat Pineal Gland Using a Multi-Platform Sequencing Approach Reveals Neural Regulation

    PubMed Central

    Mullikin, James C.; Klein, David C.; Park, Morgan; Coon, Steven L.

    2016-01-01

    Alternative isoform regulation (AIR) vastly increases transcriptome diversity and plays an important role in numerous biological processes and pathologies. However, the detection and analysis of isoform-level differential regulation is difficult, particularly in the face of complex and incompletely-annotated transcriptomes. Here we have used Illumina short-read/high-throughput RNA-Seq to identify 55 genes that exhibit neurally-regulated AIR in the pineal gland, and then used two other complementary experimental platforms to further study and characterize the Ttc8 gene, which is involved in Bardet-Biedl syndrome and non-syndromic retinitis pigmentosa. Use of the JunctionSeq analysis tool led to the detection of several novel exons and splice junctions in this gene, including two novel alternative transcription start sites which were found to display disproportionately strong neurally-regulated differential expression in several independent experiments. These high-throughput sequencing results were validated and augmented via targeted qPCR and long-read Pacific Biosciences SMRT sequencing. We confirmed the existence of numerous novel splice junctions and the selective upregulation of the two novel start sites. In addition, we identified more than 20 novel isoforms of the Ttc8 gene that are co-expressed in this tissue. By using information from multiple independent platforms we not only greatly reduce the risk of errors, biases, and artifacts influencing our results, we also are able to characterize the regulation and splicing of the Ttc8 gene more deeply and more precisely than would be possible via any single platform. The hybrid method outlined here represents a powerful strategy in the study of the transcriptome. PMID:27684375

  16. Adaptation of the disector method to rare small organelles in TEM sections exemplified by counting synaptic bodies in the rat pineal gland

    PubMed Central

    JASTROW, HOLGER; VON MACH, MARC-A.; VOLLRATH, LUTZ

    1997-01-01

    The disector is the only objective method for quantifying particles of variable size in a given volume. With this method, cell organelles are identified on adjacent sections, but only those present in one section are counted. When counting extremely rare structures in transmission electron microscope sections (physical disector), the usual procedure of counting on electron micrographs is limited for economic reasons (e.g. micrographs highly outnumbering the investigated structures). Hence, to apply this unbiased stereological method, a modification of the physical disector concerning 3 aspects has been developed. (1) The prerequisite of screening large corresponding tissue areas (here ∼65000 μm2) was fulfilled by examining tissue areas along the edges of ultrathin sections. (2) The size of the counting frame was determined by measuring the lengths of the section margins (minus a guard area) by means of a Morphomat. This value was multiplied by the width of the investigated tissue zone, corresponding to the diameter of the electron microscope viewing screen. (3) Disector counting was carried out simultaneously on both sections (bidirectional disector) to improve efficiency. In the present study tiny synaptic bodies (SBs) were quantitated by disector in a rat pineal gland, yielding ∼30 SBs/1000 μm3. By contrast, single section profile counts of SBs amounted to 90 SBs/20000 μm2. Since the presently described adaptation of the disector is time-consuming, it is proposed to determine a proportion factor allowing to estimate number of structures per volume based on single section profile counts. This would decrease the evaluation time by more than 50%. PMID:9418996

  17. Diagnosis and treatment of pineal region tumors

    SciTech Connect

    Neuwelt, E.A.

    1984-01-01

    The aim of this volume is to review the pertinent literature dealing with pineal tumors and thus aid in the handling of these rather uncommon lesions. After the first, introductory, chapter, three chapters treat the pathology and diagnosis of pineal tumors. There is also one chapter on intracranial germ cell tumors (natural history and pathogenesis) and one on the normal function of the pineal gland. With the exception of the chapter on diagnostic radiology of pineal tumors, which seems somewhat superficial, these five chapters summarize current knowledge about the nature of these complex lesions and their symptomatology very well. The next nine chapters deal with biopsy and surgery of these tumors and how to manage the patient. The first of these gives a historical review of the development of surgical techniques - from the first attempt by Horsley in 1905 to the microsurgical techniques of today. It is followed by a very important and detailed description of the microsurgical anatomy of the pineal region.

  18. Pineal Function: Impact of Microarray Analysis

    PubMed Central

    Klein, David C.; Bailey, Michael J.; Carter, David A.; Kim, Jong-so; Shi, Qiong; Ho, Anthony; Chik, Constance; Gaildrat, Pascaline; Morin, Fabrice; Ganguly, Surajit; Rath, Martin F.; Møller, Morten; Sugden, David; Rangel, Zoila G.; Munson, Peter J.; Weller, Joan L.; Coon, Steven L.

    2009-01-01

    Microarray analysis has provided a new understanding of pineal function by identifying genes that are highly expressed in this tissue relative to other tissues and also by identifying over 600 genes that are expressed on a 24-hour schedule. This effort has highlighted surprising similarity to the retina and has provided reason to explore new avenues of study including intracellular signaling, signal transduction, transcriptional cascades, thyroid/retinoic acid hormone signaling, metal biology, RNA splicing, and the role the pineal gland plays in the immune/inflammation response. The new foundation that microarray analysis has provided will broadly support future research on pineal function. PMID:19622385

  19. Meibomian gland dysfunction. I. Keratin protein expression in normal human and rabbit meibomian glands.

    PubMed

    Jester, J V; Nicolaides, N; Smith, R E

    1989-05-01

    The expression of keratin proteins from meibomian glands and their correlation with skin epidermal keratins were determined. Keratin proteins were localized in both human and rabbit meibomian glands by indirect immunofluorescence using mouse monoclonal antibodies AE1, AE2 and AE3, which are known to react with human epidermal keratins as well as with keratins from other sources. Keratin proteins from rabbit meibomian glands were further isolated and characterized by SDS-PAGE and immunoblot using mouse monoclonal antibodies AE1 and AE3. Meibomian glands from human and rabbit showed similar immunofluorescent staining with each monoclonal antibody. AE1 antibody, which stains human basal epithelial cells of skin, stains all duct epithelial cells in the human but only the superficial duct epithelial cells in the rabbit meibomian gland. AE2 antibody, which stains human suprabasal epithelial cells of skin and is a marker for fully keratinized epithelia, stains the suprabasal epithelial cells of the central duct and ductules in both the human and rabbit meibomian gland. AE3 antibody, which stains all human epithelial cells of skin, stains all epithelial cells of the duct and ductules, as well as the basal epithelial cells of the acinus in both the human and rabbit meibomian gland. Keratins isolated from whole rabbit meibomian glands contained a 65-67 kD and 58 kD AE3-positive, and a 56.5 kD and 50 kD AE1-positive keratin protein. Expression of 65-67 kD/56.5 kD keratin proteins, and the immunofluorescent staining of the duct epithelium by the AE2 antibody, indicate that the meibomian gland duct epithelium is committed to the process of keratinization.

  20. The pineal volume: a three-dimensional volumetric study in healthy young adults using 3.0 T MR data.

    PubMed

    Sun, Bo; Wang, Dan; Tang, Yuchun; Fan, Lingzhong; Lin, Xiangtao; Yu, Taifei; Qi, Hengtao; Li, Zhenping; Liu, Shuwei

    2009-11-01

    It is usually difficult to distinguish small pineal tumors via routine or enhanced magnetic resonance (MR) scan. The knowledge of normal pineal size is helpful to detect small pineal lesions, while very few true volumetric data of pineal glands have been reported. Therefore, we obtained the accurate reference range of normal pineal volumes in 112 individuals aged 20-30 years recruited randomly from a healthy community sample. Transverse and sagittal 3.0T magnetic resonance data were obtained using three-dimensional (3D) T1-weighted FSPGR and T2-weighted SE sequences. True pineal volumes were measured from T1-weighted images, while estimated volumes were calculated using pineal length, width and height. All the glands were divided into three types according to the maximum inner diameter of pineal cysts. The prevalence of asymptomatic pineal cyst is 25.00%, with a slight female predominance. In the whole sample, we found no gender differences of pineal volume, but a significant gender difference of pineal volume index. A significant correlation between pineal volume and asymptomatic cyst was found. After excluding cases with big pineal cysts, there were significant correlations between pineal volume and head circumference, body height and body weight, respectively. This study suggests that asymptomatic pineal cysts may exert an important influence on pineal volume.

  1. Morphological Features of the Porcine Lacrimal Gland and Its Compatibility for Human Lacrimal Gland Xenografting

    PubMed Central

    Gaffling, Simone; Asano, Nagayoshi; Hampel, Ulrike; Garreis, Fabian; Hornegger, Joachim; Paulsen, Friedrich

    2013-01-01

    In this study, we present first data concerning the anatomical structure, blood supply and location of the lacrimal gland of the pig. Our data indicate that the porcine lacrimal gland may serve as a potential xenograft candidate in humans or as an animal model for engineering of a bioartificial lacrimal gland tissue construct for clinical application. For this purpose, we used different macroscopic preparation techniques and digital reconstruction of the histological gland morphology to gain new insights and important information concerning the feasibility of a lacrimal gland transplantation from pig to humans in general. Our results show that the lacrimal gland of the pig reveals a lot of morphological similarities to the analogous human lacrimal gland and thus might be regarded as a xenograft in the future. This is true for a similar anatomical location within the orbit as well as for the feeding artery supply to the organ. Functional differences concerning the composition of the tear fluid, due to a different secretory unit distribution within the gland tissue will, however, be a challenge in future investigations. PMID:24069265

  2. Age-related incidence of pineal calcification detected by computed tomography

    SciTech Connect

    Zimmerman, R.A.; Bilaniuk, L.T.

    1982-03-01

    The age-related incidence of detectable pineal calcification in 725 patients (age range, newborn-20 yrs) suggests that there is a relationship between calcification and the hormonal role played by the pineal gland in the regulation of sexual development. Pineal calcification (demonstrated by computed tomography (CT) on 8-mm-thick sections) in patients less than 6 years old should be looked upon with suspicion, and follow-up CT should be considered to exclude the possible development of a pineal neoplasm.

  3. [The role of the pineal body in the endocrine control of puberty].

    PubMed

    Aleandri, V; Spina, V; Ciardo, A

    1997-01-01

    The pineal gland plays an important role in reproductive endocrinology. The epiphysis regulates seasonal variations in reproductive function of seasonally breeding animals. In humans, even if they are not seasonal breeders, the role of the pineal in reproductive endocrinology seems to be important as well. It appears to be of particular importance the endocrine control of the gland on pubertal sexual maturation. Even if not all researchers agree, several data suggest that elevated melatonin levels-characteristic of prepubertal age-keep the hypothalamic-pituitary-gonadal axis in quiescence: thus, an inhibitory effect on pubertal development is exerted. Subsequently, the decreasing serum melatonin with advancing age would result in activation of the hypothalamic pulsatile secretion of GnRH- and therefore of the reproductive axis-with consequent onset of pubertal phenomena. The production rate of melatonin does not change with age and no growth in pineal size from 1 to 15 years of age has been demonstrated by nuclear magnetic resonance (NMR) studies. Therefore the decrease of serum melatonin concentrations has been proposed to be due to the increase in body mass or, according to another hypothesis, to be also temporally linked to sexual maturation. Furthermore, recently, it has been suggested in rats that the pineal influences not only the pubertal sexual maturation, but even the gonadal and genital development and function of offspring, already during intrauterine life. Investigations are needed to evaluate this hypothesis in humans.

  4. Pineal region tumors: computed tomographic-pathologic spectrum

    SciTech Connect

    Futrell, N.N.; Osborn, A.G.; Cheson. B.D.

    1981-11-01

    While several computed tomographic (CT) studies of posterior third ventricular neoplasms have included descriptions of pineal tumors, few reports have concentrated on these uncommon lesions. Some authors have asserted that the CT appearance of many pineal tumors is virtually pathognomonic. A series of nine biopsy-proved pineal gland and eight other presumed tumors is presented that illustrates their remarkable heterogeneity in both histopathologic and CT appearance. These tumors included germinomas, teratocarcinomas, hamartomas, and other varieties. They had variable margination, attentuation, calcification, and suprasellar extension. Germinomas have the best response to radiation therapy. Biopsy of pineal region tumors is now feasible and is recommended for treatment planning.

  5. Computed tomographic evaluation of pineal calcification.

    PubMed

    Kohli, N; Rastogi, H; Bhadury, S; Tandon, V K

    1992-04-01

    A prospective study to ascertain the incidence of normally calcified pineal gland, was carried out in 1000 consecutive patients from different parts of Uttar Pradesh (India), undergoing cranial computed tomography for reasons other than a pineal or parapineal pathology. A total of 167 (16.70%) patients were found to have calcified pineals. Of these 128 were males and 39 females. The incidence rose from 1.16 per cent in the first decade to 31.88 per cent above the age of 50 yr. The percentage incidence of normal pineal calcification was lower than that seen in the Western population. No significant difference was found between men and women in any age group. Although calcification appeared as early as the first decade, this percentage was significantly lower than in the higher age groups. Significantly higher incidence rates were seen in the second decade, third decade and sixth decade onwards. PMID:1428055

  6. Nonvisual photoreceptors of the deep brain, pineal organs and retina.

    PubMed

    Vigh, B; Manzano, M J; Zádori, A; Frank, C L; Lukáts, A; Röhlich, P; Szél, A; Dávid, C

    2002-04-01

    The role of the nonvisual photoreception is to synchronise periodic functions of living organisms to the environmental light periods in order to help survival of various species in different biotopes. In vertebrates, the so-called deep brain (septal and hypothalamic) photoreceptors, the pineal organs (pineal- and parapineal organs, frontal- and parietal eye) and the retina (of the "lateral" eye) are involved in the light-based entrain of endogenous circadian clocks present in various organs. In humans, photoperiodicity was studied in connection with sleep disturbances in shift work, seasonal depression, and in jet-lag of transmeridional travellers. In the present review, experimental and molecular aspects are discussed, focusing on the histological and histochemical basis of the function of nonvisual photoreceptors. We also offer a view about functional changes of these photoreceptors during pre- and postnatal development as well as about its possible evolution. Our scope in some points is different from the generally accepted views on the nonvisual photoreceptive systems. The deep brain photoreceptors are hypothalamic and septal nuclei of the periventricular cerebrospinal fluid (CSF)-contacting neuronal system. Already present in the lancelet and representing the most ancient type of vertebrate nerve cells ("protoneurons"), CSF-contacting neurons are sensory-type cells sitting in the wall of the brain ventricles that send a ciliated dendritic process into the CSF. Various opsins and other members of the phototransduction cascade have been demonstrated in telencephalic and hypothalamic groups of these neurons. In all species examined so far, deep brain photoreceptors play a role in the circadian and circannual regulation of periodic functions. Mainly called pineal "glands" in the last decades, the pineal organs actually represent a differentiated form of encephalic photoreceptors. Supposed to be intra- and extracranially outgrown groups of deep brain photoreceptors

  7. Dynamic OCT of sweat glands of human finger tip

    NASA Astrophysics Data System (ADS)

    Haruna, Masamitsu; Ueda, Yoshihiro; Ohmi, Masato; Fuji, Toshie

    2006-02-01

    Dynamic optical coherence tomography (OCT) is demonstrated for dynamic study of sweat glands of human finger tip using the all-optical-fiber imaging system. Stress-induced and physical activation of sweat glands can be observed clearly in time-sequential OCT images. The method for image data acquisition is presented as well as the experimental results.

  8. Serum-Induced Differentiation of Human Meibomian Gland Epithelial Cells

    PubMed Central

    Sullivan, David A.; Liu, Yang; Kam, Wendy R.; Ding, Juan; Green, Karin M.; Shaffer, Scott A.; Hatton, Mark P.; Liu, Shaohui

    2014-01-01

    Purpose. We hypothesize that culturing immortalized human meibomian gland epithelial cells in serum-containing medium will induce their differentiation. The purpose of this investigation was to begin to test our hypothesis, and explore the impact of serum on gene expression and lipid accumulation in human meibomian gland epithelial cells. Methods. Immortalized and primary human meibomian gland epithelial cells were cultured in the presence or absence of serum. Cells were evaluated for lysosome and lipid accumulation, polar and neutral lipid profiles, and gene expression. Results. Our results support our hypothesis that serum stimulates the differentiation of human meibomian gland epithelial cells. This serum-induced effect is associated with a significant increase in the expression of genes linked to cell differentiation, epithelium development, the endoplasmic reticulum, Golgi apparatus, vesicles, and lysosomes, and a significant decrease in gene activity related to the cell cycle, mitochondria, ribosomes, and translation. These cellular responses are accompanied by an accumulation of lipids within lysosomes, as well as alterations in the fatty acid content of polar and nonpolar lipids. Of particular importance, our results show that the molecular and biochemical changes of immortalized human meibomian gland epithelial cells during differentiation are analogous to those of primary cells. Conclusions. Overall, our findings indicate that immortalized human meibomian gland epithelial cells may serve as an ideal preclinical model to identify factors that control cellular differentiation in the meibomian gland. PMID:24867579

  9. Two components of the pineal organ in the mink (Mustela vison): their structural similarity to submammalian pineal complexes and calcification.

    PubMed

    Vigh, B; Vigh-Teichmann, I

    1992-12-01

    The pineal complex in the mink (Mustela vison) consists of a larger ventral and a smaller dorsal pineal. Both organs contain pinealocytes, neurons, glial cells, nerve fibers and synapses in an organization characteristic of nervous tissue. The cellular elements are arranged circularly around strait lumina. These lumina correspond to the photoreceptor spaces of submammalian pineals. A 9 + 0-type cilium marks the receptory pole of the pinealocytes which may form an inner-segment-like dendrite terminal in the pineal lumina. The cilia correspond to outer segments which form photoreceptor membrane multiplications in the pineal of submammalians and in certain insectivorous and mustelid mammals (bat, hedgehog, ferret). Axonal processes of the pinealocytes contain synaptic ribbons and terminate on intrapineal neurons of both organs. This pattern represents a neural efferentation of the pineal nervous tissue. The axonal processes of pinealocytes also form neurohormonal endings which pierce the perivascular limiting glial membrane in the ventral as well as in the dorsal pineal. The upper pineal ("epipineal") of the mink may correspond to the parapineal, frontal, or parietal organs of submammalian pineal complexes. Both pineals are encapsulated by the meningeal tissue of the brain stem. Afferent vasomotor axons of the meninges innervate smooth muscle cells of pineal arterioles. There are corpora arenacea in the pineal arachnoid and in the pineal nervous tissue, primarily in the ventral pineal. The localization of calcium ions detected around the membrane of pineal cells by pyroantimonate cytochemistry suggests membrane activity as the source of the calcium ions. The accumulation of calcium by the pinealocytes may be due to their neurosensory character. The mink is the first animal described to have both intrapineal and meningeal concrements like the human pineal. PMID:1295547

  10. Human kallikrein 8 expression in salivary gland tumors.

    PubMed

    Darling, Mark R; Tsai, Sam; Jackson-Boeters, Linda; Daley, Thomas D; Diamandis, Eleftherios P

    2008-09-01

    The human kallikrein 8 protein (KLK8) is expressed in many normal tissues including esophagus, skin, testis, tonsil, kidney, breast, and salivary gland, and is found in biological fluids including breast milk, amniotic fluid, seminal fluid and serum. It has also been shown to be a biomarker and prognostic factor for breast cancer. The aim of this study was to determine whether KLK8 is expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), in order to compare normal with tumor tissues. Pleomorphic adenomas, adenoid cystic carcinomas, polymorphous low grade adenocarcinomas, acinic cell carcinomas, mucoepidermoid carcinomas, and adenocarcinomas NOS of both minor and major salivary glands were examined. The results of this study indicate that most salivary gland tumors show high levels of expression of KLK8.

  11. Human kallikrein 13 expression in salivary gland tumors.

    PubMed

    Darling, M R; Jackson-Boeters, L; Daley, T D; Diamandis, E P

    2006-01-01

    The human kallikrein 13 protein (hK13) is expressed in many normal tissues. Petraki et al have previously described presence of hK13 in salivary gland tissue, localized to duct epithelia and some acinar cells. The aim of this study was to determine whether hK13 is expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), in order to compare normal with tumor tissues. Pleomorphic adenomas (PA), adenoid cystic carcinomas (ACC), polymorphous low grade adenocarcinomas (PLGA), acinic cell carcinomas (ACI), mucoepidermoid carcinomas (MEC) and adenocarcinomas not otherwise specified (ANOS) of both minor and major salivary glands were examined. The results of this study indicate that most salivary gland tumors show high levels of expression of hK13. Overall, staining in PA was significantly less than that seen in normal salivary gland tissue. PLGA, ACC and ANOS each stained significantly more than normal salivary gland tissue while MEC and ACI did not. Ductal cells and cells lining duct-like structures showed a higher intensity of staining than non-ductal cells in most tumors. Tumors which exhibited only non-ductal cells also exhibited cytoplasmic staining. In conclusion, we demonstrate the high expression of hK13 in several common salivary gland tumors.

  12. Frequency of varicella zoster virus DNA in human adrenal glands.

    PubMed

    Badani, Hussain; White, Teresa; Schulick, Nicole; Raeburn, Christopher D; Topkaya, Ibrahim; Gilden, Don; Nagel, Maria A

    2016-06-01

    Varicella zoster virus (VZV) becomes latent in ganglionic neurons derived from neural crest cells. Because the adrenal gland also contains medullary chromaffin cells of neural crest origin, we examined human adrenal glands and medullary chromaffin cell tumors (pheochromocytomas) for VZV and herpes simplex virus type 1 (HSV-1). We found VZV, but not HSV-1, DNA in 4/63 (6 %) normal adrenal glands. No VZV transcripts or antigens were detected in the 4 VZV DNA-positive samples. No VZV or HSV-1 DNA was found in 21 pheochromocytomas.

  13. Cancer as the main aging factor for humans: the fundamental role of 5-methoxy-tryptamine in reversal of cancer-induced aging processes in metabolic and immune reactions by non-melatonin pineal hormones.

    PubMed

    Lissoni, Paolo; Messina, Giuseppina; Rovelli, Franco

    2012-12-01

    Aging and advanced cancer are characterized by similar neuroendocrine and immune deficiencies; the most important of them consist of diminished nocturnal production of the pineal hormone melatonin (MLT) and decreased production of IL-2. At present, however, it is known that the pineal gland may produce indole hormones other than MLT. The most investigated of them is represented by 5-methoxy-tryptamine (5-MTT), which may exert antitumor, anticachectic, and immunomodulating effects under experimental conditions, in addition to those effects produced by MLT itself. In an attempt to obtain some preliminary data in human subjects about the potential therapeutic properties of 5-MTT, three different studies of 5-MTT have been carried out in advanced solid tumor patients. The first study of MLT plus 5-MTT included 14 thrombocytopenic cancer patients who did not respond to MLT alone. In the second study we have compared the clinical efficacy of MLT plus 5-MTT in a group of 25 untreatable metastatic cancer patients to the results obtained in a control group of 25 cancer patients receiving MLT alone. Finally, the third study of MLT plus 5-MTT included 14 untreatable metastatic cancer patients who did not respond to MLT alone. In all of these studies, MLT and 5-MTT were given orally at the level of 20 mg/day in the evening and at 5 mg/day during the period of maximum light. A normalization of platelet number was achieved by MLT plus 5-MTT in 5 of 14 (36%) thrombocytopenic cancer patients who did not respond to MLT alone. The percentage of disease control obtained by MLT plus 5-MTT in untreatable metastatic cancer patients was significantly higher than that achieved by MLT alone (15/25 [60%] vs. 8/25 [32%], P < 0.05). Finally, the association of 5-MTT with MLT induced disease stabilization in 4 of 14 (29%) untreatable metastatic cancer patients who did not respond to MLT alone.

  14. Pineal parenchymal tumor of intermediate differentiation.

    PubMed

    Patil, Meena; Karandikar, Manjiri

    2015-01-01

    The 2007 World Health Organization classification of tumors of the central nervous system identified "pineal parenchymal tumor of intermediate differentiation" (PPTID) as a new pineal parenchymal neoplasm, located between pineocytoma and pineoblastoma as grade II or III. Because of the small number of reported cases, the classification of PPT is still a matter of controversy. We report a case of PPTID. A 25-year-old female patient was admitted to hospital with complaints of a headache, nausea, vomiting since 1-year. Computed tomography/magnetic resonance imaging of the brain showed well-defined, mildly enhancing lesion in the region of the pineal gland with areas of calcification. The tumor was excised. After 3 years, she presented with metastasis in thoracic and lumbosacral spinal region. This is a rare event. PMID:26549088

  15. Anatomy and histology of rodent and human major salivary glands: -overview of the Japan salivary gland society-sponsored workshop-.

    PubMed

    Amano, Osamu; Mizobe, Kenichi; Bando, Yasuhiko; Sakiyama, Koji

    2012-10-31

    MAJOR SALIVARY GLANDS OF BOTH HUMANS AND RODENTS CONSIST OF THREE PAIRS OF MACROSCOPIC GLANDS: parotid, submandibular, and sublingual. These glands secrete serous, mucous or mixed saliva via the proper main excretory ducts connecting the glandular bodies with the oral cavity. A series of discoveries about the salivary ducts in the 17th century by Niels Stensen (1638-1686), Thomas Wharton (1614-1673), and Caspar Bartholin (1655-1738) established the concept of exocrine secretion as well as salivary glands. Recent investigations have revealed the endocrine functions of parotin and a variety of cell growth factors produced by salivary glands.The present review aims to describe macroscopic findings on the major salivary glands of rodents and the microscopic differences between those of humans and rodents, which review should be of interest to those researchers studying salivary glands.

  16. Effect of testosterone on the hypothalamic-pituitary-gonadal axis of pinealectomized and pineal-intact male rats.

    PubMed

    Wallen, E P; Turek, F W

    1979-05-15

    Previous studies indicate that steroid hormones alter pineal biochemistry, and it has been suggested that at least part of the negative feedback effect of steroid hormones on pituitary gonadotropin release may be mediated by the pineal gland. In this study, pinealectomy did not alter the inhibitory effect of testosterone on neuroendocine-gonadal activity in the male rat, suggesting that the pineal gland does not mediate the response of the rat hypothalamic-pituitary axis to testosterone.

  17. Immunopathological study of neuropeptide expression in human salivary gland neoplasms.

    PubMed

    Hayashi, Y; Deguchi, H; Nakahata, A; Kurashima, C; Hirokawa, K

    1990-01-01

    The immunoreactivity of anti-neuron-specific enolase (NSE) and anti-Leu-7 on formalin-fixed sections of human salivary gland neoplasms was determined by the avidin-biotin-peroxidase complex method. In addition, neuropeptides, such as vasoactive intestinal polypeptide, somatostatin, and substance P, in human salivary gland neoplasms were expressed, whereas other polypeptides, including glucagon, cholecystokinin, leu-enkephalin and calcitonin, were absent. When 182 paraffin-embedded examples of human salivary gland tumors, including 112 benign and 70 malignant neoplasms, were examined immunohistochemically, positive immunoreactivity was observed in: 51 cases with NSE (59%) and 46 cases with Leu-7 (54%) of 86 pleomorphic adenomas; 11 cases with Leu-7 (61%) of 18 Warthin's tumors; 7 cases with Leu-7 (58%) of 12 acinic cell carcinomas; 5 cases with NSE (31%) of 16 adenoid cystic carcinomas; 5 cases with NSE (42%) and 4 cases with Leu-7 (33%) of 12 adenocarcinomas; 4 cases with NSE (25%) and 6 cases with Leu-7 (38%) of 16 undifferentiated carcinomas. The other tumors, such as oxyphilic adenomas, basal cell adenomas, epidermoid carcinomas, and mucoepidermoid carcinomas, were nonreactive. Neuropeptides were observed in the neoplastic epithelial cells of certain tumors such as Warthin's tumors, acinic cell carcinomas, adenocarcinomas and undifferentiated carcinomas. These findings suggest the possibility that cells of neuroendocrine origin, present in certain neoplastic salivary gland epithelia may play a significant role in the histogenesis of human salivary gland neoplasms.

  18. Human kallikrein 6 expression in salivary gland tumors.

    PubMed

    Darling, M R; Jackson-Boeters, L; Daley, T D; Diamandis, E P

    2006-03-01

    Human kallikrein 6 (hK6), also known as zyme/protease M/neurosin), is expressed in many normal glandular tissues. The aim of this study was to determine whether hK6 is expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), using an immunohistochemical method. Pleomorphic adenomas (PA), adenoid cystic carcinomas, polymorphous low-grade adenocarcinomas, acinic cell carcinomas, mucoepidermoid carcinomas, and adenocarcinomas not otherwise specified of both minor and major salivary glands were examined. Cells lining duct-like structures and non-duct-like cells were scored. Only in PA of minor salivary gland origin was overall staining higher in duct-like than in non-duct-like cells. In all other tumors exhibiting both types of cells, hK6 staining was similar in both duct-like and non-duct-like cells. Tumors that exhibited non-duct-like cells only also exhibited cytoplasmic staining. Results of this study show that salivary gland tumors express hK6, apparently downregulated in comparison with normal salivary gland tissue, and that this expression is not specific for any of the tumors studied.

  19. Changes in Gene Expression in Human Meibomian Gland Dysfunction

    PubMed Central

    Liu, Shaohui; Richards, Stephen M.; Lo, Kristine; Hatton, Mark; Fay, Aaron

    2011-01-01

    Purpose. Meibomian gland dysfunction (MGD) may be the leading cause of dry eye syndrome throughout the world. However, the precise mechanism(s) underlying the pathogenesis of this disease is unclear. This study was conducted to identify meibomian gland genes that may promote the development and/or progression of human MGD. Methods. Lid tissues were obtained from male and female MGD patients and age-matched controls after eyelid surgeries (e.g., to correct entropion or ectropion). Meibomian glands were isolated and processed for RNA extraction and the analysis of gene expression. Results. The results show that MGD is associated with significant alterations in the expression of almost 400 genes in the human meibomian gland. The levels of 197 transcripts, including those encoding various small proline-rich proteins and S100 calcium-binding proteins, are significantly increased, whereas the expression of 194 genes, such as claudin 3 and cell adhesion molecule 1, is significantly decreased. These changes, which cannot be accounted for by sex differences, are accompanied by alterations in many gene ontologies (e.g., keratinization, cell cycle, and DNA repair). The findings also show that the human meibomian gland contains several highly expressed genes that are distinct from those in an adjacent tissue (i.e., conjunctival epithelium). Conclusions. The results demonstrate that MGD is accompanied by multiple changes in gene expression in the meibomian gland. The nature of these alterations, including the upregulation of genes encoding small proline-rich proteins and S100 calcium-binding proteins, suggest that keratinization plays an important role in the pathogenesis of MGD. PMID:21372006

  20. Precursors of hexoneogenesis within the human mammary gland

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The human mammary gland is capable of de novo synthesis of glucose and galactose (hexoneogenesis); however, the carbon source is incompletely understood. In this study, we investigated the role of acetate, glutamine, lactate and glycerol as potential carbon sources for hexoneogenesis. Healthy breast...

  1. Morphology of human suprarenal glands: a parameter for comparison.

    PubMed

    Anand, M K; Anand, C; Choudhry, R; Sabharwal, A

    1998-01-01

    Forty suprarenal glands were studied, 20 being dissected from aborted fetuses of 9 to 36 weeks' gestation and 20 obtained from human cadavers of ages 1 day to 60 years. All the specimens were from a Northern India population. The side and shape of each suprarenal gland was noted and documented. The length, breadth, thickness and volume of each gland were measured and tabulated in terms of age. The mean length, breadth and thickness in fetuses of 9-36 weeks were found to be 1.4 cm, 1 cm and 0.45 cm respectively. In the postnatal age group the measurements were 4.5 cm, 2.08 cm and 0.66 cm respectively. The commonest shape of the suprarenal glands on left side was semilunar but on the right side it was highly variable: triangular, tetrahedral, inverted Y or V shaped. On comparison of the gross measurements with available ultrasound and CT scan data it was found that both the length and thickness in the population studied were greater than reported in the literature. A knowledge of these variations is very important in diagnosis of abnormalities of the suprarenal gland, of which tumoral enlargement is rather common.

  2. Human salivary gland stem cells ameliorate hyposalivation of radiation-damaged rat salivary glands.

    PubMed

    Jeong, Jaemin; Baek, Hyunjung; Kim, Yoon-Ju; Choi, Youngwook; Lee, Heekyung; Lee, Eunju; Kim, Eun Sook; Hah, Jeong Hun; Kwon, Tack-Kyun; Choi, Ik Joon; Kwon, Heechung

    2013-11-15

    Salivary function in mammals may be defective for various reasons, such as aging, Sjogren's syndrome or radiation therapy in head and neck cancer patients. Recently, tissue-specific stem cell therapy has attracted public attention as a next-generation therapeutic reagent. In the present study, we isolated tissue-specific stem cells from the human submandibular salivary gland (hSGSCs). To efficiently isolate and amplify hSGSCs in large amounts, we developed a culture system (lasting 4-5 weeks) without any selection. After five passages, we obtained adherent cells that expressed mesenchymal stem cell surface antigen markers, such as CD44, CD49f, CD90 and CD105, but not the hematopoietic stem cell markers, CD34 and CD45, and that were able to undergo adipogenic, osteogenic and chondrogenic differentiation. In addition, hSGSCs were differentiated into amylase-expressing cells by using a two-step differentiation method. Transplantation of hSGSCs to radiation-damaged rat salivary glands rescued hyposalivation and body weight loss, restored acinar and duct cell structure, and decreased the amount of apoptotic cells. These data suggest that the isolated hSGSCs, which may have characteristics of mesenchymal-like stem cells, could be used as a cell therapy agent for the damaged salivary gland.

  3. Anatomy of the human mammary gland: Current status of knowledge.

    PubMed

    Hassiotou, Foteini; Geddes, Donna

    2013-01-01

    Mammary glands are unique to mammals, with the specific function of synthesizing, secreting, and delivering milk to the newborn. Given this function, it is only during a pregnancy/lactation cycle that the gland reaches a mature developmental state via hormonal influences at the cellular level that effect drastic modifications in the micro- and macro-anatomy of the gland, resulting in remodeling of the gland into a milk-secretory organ. Pubertal and post-pubertal development of the breast in females aids in preparing it to assume a functional state during pregnancy and lactation. Remarkably, this organ has the capacity to regress to a resting state upon cessation of lactation, and then undergo the same cycle of expansion and regression again in subsequent pregnancies during reproductive life. This plasticity suggests tight hormonal regulation, which is paramount for the normal function of the gland. This review presents the current status of knowledge of the normal macro- and micro-anatomy of the human mammary gland and the distinct changes it undergoes during the key developmental stages that characterize it, from embryonic life through to post-menopausal age. In addition, it discusses recent advances in our understanding of the normal function of the breast during lactation, with special reference to breastmilk, its composition, and how it can be utilized as a tool to advance knowledge on normal and aberrant breast development and function. Finally, anatomical and molecular traits associated with aberrant expansion of the breast are discussed to set the basis for future comparisons that may illuminate the origin of breast cancer.

  4. Nocturnal feeding in the mouse--opiate and pineal influences.

    PubMed

    Kavaliers, M; Hirst, M; Teskey, G C

    1985-03-11

    Mice displayed daily rhythms in their basal and morphine-induced food intake, consuming significantly greater amounts of food at night. Non-invasive inhibition of the activity of the pineal gland by either exposure to a bright pulse of light or treatment with the L-amino-acid decarboxylase inhibitor, benserazide, reduced the elevated night-time food intakes. These effects on feeding were most evident on the first night the activity of the pineal was reduced. On subsequent nights light pulses had a diminished effect on basal and morphine-induced food intake. These results suggest that although the enhanced nocturnal food intake of mice may be modulated by pineal and opioid sensitive mechanisms, pineal activity is not essential for the expression of opioid-mediated feeding.

  5. Papillary tumor of pineal region: A rare entity

    PubMed Central

    Patil, Meena; Karandikar, Manjiri

    2016-01-01

    Pineal tumors comprise 0.4 – 1.0% of intracranial space-occupying lesions in adults. Papillary tumor of pineal region (PTPR) is a very rare entity. It has been newly described in WHO 2007 classification of brain tumors. Only a few case reports are available in the literature. We report a case of a 60 year-old female presenting with headache, giddiness and reduced vision. Imaging studies showed a pineal mass with areas of hemorrhage. All ventricles were normal. There was a past history of a pineal gland tumor excised 2 years ago. This case is being reported for its rarity and aggressiveness in the form of recurrence. Limited/available immunohistochemistry workup has been done. PMID:27695568

  6. Papillary tumor of pineal region: A rare entity

    PubMed Central

    Patil, Meena; Karandikar, Manjiri

    2016-01-01

    Pineal tumors comprise 0.4 – 1.0% of intracranial space-occupying lesions in adults. Papillary tumor of pineal region (PTPR) is a very rare entity. It has been newly described in WHO 2007 classification of brain tumors. Only a few case reports are available in the literature. We report a case of a 60 year-old female presenting with headache, giddiness and reduced vision. Imaging studies showed a pineal mass with areas of hemorrhage. All ventricles were normal. There was a past history of a pineal gland tumor excised 2 years ago. This case is being reported for its rarity and aggressiveness in the form of recurrence. Limited/available immunohistochemistry workup has been done.

  7. Expression of steroidogenic enzymes in human sebaceous glands.

    PubMed

    Inoue, Takayoshi; Miki, Yasuhiro; Kakuo, Shingo; Hachiya, Akira; Kitahara, Takashi; Aiba, Setsuya; Zouboulis, Christos C; Sasano, Hironobu

    2014-09-01

    Androgens are well known to influence sebum synthesis and secretion. Various factors related to androgen biosynthesis are expressed in human sebaceous glands. In this study, immunohistochemical analysis of human skin specimens from 43 subjects indicated that various androgen-producing and -metabolizing enzymes were functionally localized to sebocytes accumulating lipid droplets and that the exclusive expression of 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2 (HSD17B2)) in sebaceous glands was negatively correlated with that of peroxisome proliferator-activated receptor gamma (PPARγ (PPARG)), which also significantly changed in an age-dependent manner. We also demonstrated that the changes of 17β-HSD2 expression in human immortalized sebocytes (SZ95) influenced the expressions of sebogenesis-related factors. In addition, the overexpression of 17β-HSD2 in SZ95 significantly increased the androstenedione production and markedly decreased the amounts of testosterone and dihydrotestosterone when DHEA was added externally. On the other hand, the phosphorylation of mammalian target of rapamycin, which is well known to induce sebum secretion and the onset and/or aggravation of acne, was increased by the addition of testosterone in the presence of IGF1 in hamster sebocytes. These results all indicated that local androgen biosynthesis and metabolism in human sebaceous glands could play a pivotal role in sebum synthesis and secretion. PMID:24938708

  8. Distinct effects of the serotonin-noradrenaline reuptake inhibitors milnacipran and venlafaxine on rat pineal monoamines.

    PubMed

    Muneoka, Katsumasa; Kuwagata, Makiko; Ogawa, Tetsuo; Shioda, Seiji

    2015-06-17

    Monoamine systems are involved in the pathology and therapeutic mechanism of depression. The pineal gland contains large amounts of serotonin as a precursor for melatonin, and its activity is controlled by noradrenergic sympathetic nerves. Pineal diurnal activity and its release of melatonin are relevant to aberrant states observed in depression. We investigated the effects on pineal monoamines of serotonin-noradrenaline reuptake inhibitors, which are widely used antidepressants. Four days of milnacipran treatment led to an increase in noradrenaline and serotonin levels, whereas 4 days of venlafaxine treatment reduced 5-hydroxyindoleacetic acid levels; both agents induced an increase in dopamine levels. Our data suggest that milnacipran increases levels of the precursor for melatonin synthesis by facilitating the noradrenergic regulation of pineal activity and that venlafaxine inhibits serotonin reuptake into noradrenergic terminals on the pineal gland. PMID:26016648

  9. Nicotine induces DNA damage in human salivary glands.

    PubMed

    Ginzkey, Christian; Kampfinger, Katja; Friehs, Gudrun; Köhler, Christian; Hagen, Rudolf; Richter, Elmar; Kleinsasser, Norbert H

    2009-01-10

    The tobacco alkaloid nicotine is responsible for addiction to tobacco and supposed to contribute to tobacco carcinogensis, too. Recently, genotoxic effects of nicotine have been reported in human cells from blood and upper aerodigestive tract. Because of nicotine accumulation in saliva, the study of possible in vitro genotoxic effects of nicotine have been extended to human salivary gland cells. Specimens of parotid glands of 10 tumor patients were obtained from tumor-free tissue. Single cells were prepared by enzymatic digestion immediately after surgery and exposed for 1h to 0.125-4.0mM of nicotine. Possible genotoxic effects were determined by the Comet assay using the % DNA in tail (DT) as a reliable indicator of DNA damage. Nicotine induced a significant dose-dependent increase of DNA migration in parotid gland single-cells. The mean DT was 1.12-fold (0.125mM) to 2.24-fold (4.0mM) higher compared to control. The lowest concentration eliciting significant DNA damage within 1h, 0.25mM nicotine, is only 10-fold higher than maximal concentrations of nicotine reported in saliva after unrestricted smoking. Although conclusive evidence for a carcinogenic potential of nicotine is still lacking, the safety of long-term nicotine replacement therapy should be carefully monitored. PMID:18852035

  10. Thirty years of human pineal research: do we know its clinical relevance?

    PubMed

    García-Patterson, A; Puig-Domingo, M; Webb, S M

    1996-01-01

    A role for melatonin in humans is becoming evident in an increasing number of clinical situations. Marked variations in the magnitude of the nocturnal melatonin peak are observed throughout the human lifespan. The highest levels occur in children and then fall during puberty and further during adulthood. A negative correlation between circulating melatonin and sex steroids has been observed in a number of instances, and appears to be independent of concomitant gonadotrophins. No clear melatonin pattern has been observed in pituitary tumors, but in large lesions that involve the hypothalamus, a reduced nocturnal rise has been reported. Reported effects of exogenously administered melatonin are variable, probably reflecting differences in dose and timing; a slight stimulation of prolactin, as well as a partial inhibition of gonadotrophins, has been reported, which explains its utility as an oral contraceptive, associated with a progestogen. A potential clinical use of melatonin as an oncostatic drug still awaits confirmation, although experimental data firmly support this possibility. The indole has also been used to hasten entrainment of subjects travelling across various time zones, and has been found to be specially useful in eastward travel. Finally, changes in the normal melatonin circadian pattern have been reported in psychiatric diseases and in sudden infant death syndrome. PMID:8648556

  11. Pineal calcification in relation to menopause in schizophrenia.

    PubMed

    Sandyk, R

    1992-01-01

    I have suggested that critical changes in melatonin secretion, as mediated by the pineal gland, may exert a crucial role in the onset and pathogenesis of schizophrenia. Since pineal calcification (PC) is thought to reflect the metabolic and secretory activity of the gland, I investigated in 29 randomly selected chronic institutionalized female schizophrenic patients the association of PC on CT scan with premenopausal (prior to age 40) versus menopausal (ages 40-55) onset of illness. The premenopausal patients were found to show a significantly higher prevalence of PC than the menopausal patients (55.5% vs. 18.1%; X2 = 3.93, df = 1, p < .05). Since PC was unrelated to historical, demographic, and treatment variables, these findings highlight the importance of the pineal gland for the timing of the onset of schizophrenia, particularly in relation to the female reproductive state. The results carry theoretical implications on the pathogenesis of schizophrenia and suggest that the pineal gland may exert a protective effect against its onset. PMID:1305625

  12. Pineal toxoplasmosis mimicking pineal tumor in an AIDS patient.

    PubMed

    Poon, T P; Behbahani, M; Matoso, I; Kim, B

    1994-07-01

    A pineal mass in a patient with acquired immunodeficiency syndrome (AIDS) is reported. Computed tomography (CT) scan revealed a nodular mass in the pineal region with foci of calcification and obstruction of the aqueduct mimicking a pineal tumor. At autopsy, the brain revealed a well-circumscribed lesion with central necrosis in the pineal region suggestive of toxoplasma and involving the periaqueductal area. Susceptibility of a patient with AIDS to opportunistic infections should be considered. PMID:8064908

  13. Effects of Age and Dysfunction on Human Meibomian Glands

    PubMed Central

    Nien, Chyong Jy; Massei, Salina; Lin, Gloria; Nabavi, Cameron; Tao, Jeremiah; Brown, Donald J.; Paugh, Jerry R.; Jester, James V.

    2015-01-01

    Objective To identify age-related changes in human meibomian glands that may be associated with meibomian gland dysfunction (MGD). Methods Excess eyelid tissue from 36 patients (age range, 18–95 years, 19 female, 17 male) who underwent canthoplasty procedures were used. Dermatologic history, age, and presence of MGD were recorded. Samples were frozen, sectioned, and stained with specific antibodies against peroxisome proliferator–activated receptor γ(PPARγ) to identify meibocyte differentiation, Ki67 nuclear antigen to identify cycling cells, and CD45 to identify inflammatory cell infiltration. Results Staining for PPARγ showed cytoplasmic and nuclear localization in the 2 youngest subjects (ages, 18 and 44 years). Older individuals (>60 years) showed predominantly nuclear staining, with cytoplasmic staining limited to the basal acinar cells in 17 of 31 subjects. The number of Ki67 positively stained basal cells were significantly elevated in the younger compared with older subjects based on linear regression analysis (r2= 0.35; P <.001). There was also a significant correlation between MG expression grade and CD45 cell infiltration (r =0.414; P =.05). Conclusions These results indicate that aging human meibomian glands show decreased meibocyte differentiation and cell cycling that is associated with the development of MGD. Findings also suggest that altered PPARγ signaling may lead to acinar atrophy and development of an age-related hyposecretory MGD. Clinical Relevance Meibomian gland dysfunction and evaporative dry eye are common age-related eyelid disorders. Understanding the underlying mechanism of MGD may lead to the development of novel therapeutic strategies to treat this disease. PMID:21482872

  14. Chronic exposure to 60-Hz electric fields: effects on pineal function in the rat

    SciTech Connect

    Wilson, B.W.; Anderson, L.E.; Hilton, D.I.; Philips, R.D.

    1980-01-01

    As a component of studies to search for effects of 60-Hz electric field exposure on mammalian endocrine function, concentrations of melatonin, 5-methoxytryptophol, and serotonin-N-acetyl transferase activity were measured in the pineal glands of rats exposed or sham-exposed at 65 kV/m for 30 days.In two replicate experiments there were statistically significant differences between exposed and control rats in that the normal nocturnal increase in pineal melatonin content was depressed in the exposed animals. Concentrations of 5-methoxytryptophol were increased in the pineal glands of the exposed groups when compared to sham-exposed controls. An alteration was also observed in serotonin-N-acetyl transferase activity, with lower levels measured in pineal glands from exposed animals.

  15. Pineal melatonin synthesis in Syrian hamsters: A summary

    NASA Astrophysics Data System (ADS)

    Rollag, M. D.

    1982-12-01

    During the past decade there has been ample documentation of the proposition that the pineal gland mediates photoperiodic influences upon reproductive behavior of hamsters. It is commonly hypothesized that the pineal gland expresses its activity by transformation of photoperiodic information into an hormonal output, that hormone being melatonin. If this hypothesis is correct, there must be some essential diffrence in melatonin's output when hamsters are exposed to different photoperiodic environments. The experiments summarized in this communication analyze pineal melatonin contents in Syrian hamsters maintained in a variety of photoperiodic conditions during different physiological states. The results demonstrate that adult hamsters have a daily surge in pineal melatonin content throughout their lifetime when exposed to simulated annual photoperiodic cycles. There is some fluctuation in the amount of pineal melatonin produced during different physiological states and photoperiodic environments, but these fluctuations seem small when compared to those normally found for other regulatory hormones. When hamsters are exposed to different photoperiodic regimens, the daily melatonin surge maintains a relatively constant phase relationship with respect to the onset of daily activity. There is a concomitant change in its phase relationship with respect to light-dark transitions.

  16. Human kallikrein 3 (prostate specific antigen) and human kallikrein 5 expression in salivary gland tumors.

    PubMed

    Darling, M R; Tsai, S; Jackson-Boeters, L; Daley, T D; Diamandis, E P

    2006-01-01

    The human kallikrein 5 protein (hK5) is expressed in many normal tissues, most notably in skin, breast, salivary gland and esophagus. It has also been shown to be a potential biomarker for breast, ovarian and testicular cancer. Human kallikrein 3 (hK3; prostate-specific antigen) is the most useful marker for adenocarcinoma of the prostate gland. The aim of this study was to determine whether hK3 and hK5 are expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), in order to compare normal with tumor tissues. Pleomorphic adenomas, adenoid cystic carcinomas, polymorphous low-grade adenocarcinomas, acinic cell carcinomas, mucoepidermoid carcinomas and adenocarcinomas not otherwise specified of both minor and major salivary glands were examined. The results of this study indicate that most salivary gland tumors do not show high levels of expression of hK5. Staining was most prominent in keratinizing epithelia in pleomorphic adenomas. hK3 is not expressed in salivary gland tumors.

  17. Human Salivary Gland Stem Cells Functionally Restore Radiation Damaged Salivary Glands.

    PubMed

    Pringle, Sarah; Maimets, Martti; van der Zwaag, Marianne; Stokman, Monique A; van Gosliga, Djoke; Zwart, Erik; Witjes, Max J H; de Haan, Gerald; van Os, Ronald; Coppes, Rob P

    2016-03-01

    Adult stem cells are often touted as therapeutic agents in the regenerative medicine field, however data detailing both the engraftment and functional capabilities of solid tissue derived human adult epithelial stem cells is scarce. Here we show the isolation of adult human salivary gland (SG) stem/progenitor cells and demonstrate at the single cell level in vitro self-renewal and differentiation into multilineage organoids. We also show in vivo functionality, long-term engraftment, and functional restoration in a xenotransplantation model. Indeed, transplanted human salisphere-derived cells restored saliva production and greatly improved the regenerative potential of irradiated SGs. Further selection for c-Kit expression enriched for cells with enhanced regenerative potencies. Interestingly, interaction of transplanted cells with the recipient SG may also be involved in functional recovery. Thus, we show for the first time that salispheres cultured from human SGs contain stem/progenitor cells capable of self-renewal and differentiation and rescue of saliva production. Our study underpins the therapeutic promise of salisphere cell therapy for the treatment of xerostomia. PMID:26887347

  18. WISP-2 expression in human salivary gland tumors.

    PubMed

    Kouzu, Yukinao; Uzawa, Katsuhiro; Kato, Masaki; Higo, Morihiro; Nimura, Yoshinori; Harada, Koji; Numata, Tsutomu; Seki, Naohiko; Sato, Mitsunobu; Tanzawa, Hideki

    2006-04-01

    This study was designed to disclose detailed genetic mechanisms in salivary gland tumors (SGTs) for development of novel independent marker. We constructed an in-house cDNA microarray carrying 2,201 cDNA clones derived from SGT and oral squamous cell carcinoma cDNA libraries. Four cell lines that originated from the SGT-derived cell lines were analyzed using this microarray system. The genes identified by our microarray system were further analyzed at the mRNA or protein expression level in other types of human cancer cell lines and clinical samples (ten normal salivary glands [NSGs], eleven pleomorphic adenomas, ten adenoid cystic carcinomas and three adenocarcinomas). Two up-regulated genes and six down-regulated genes were identified in common when compared with the control RNA. Of the up-regulated genes, WISP-2, which plays an important role in breast carcinogenesis, was selected for further analyses. We found a higher expression of the WISP-2 gene in the SGT-derived cell lines compared with other types of human cancer cell lines. Furthermore, WISP-2 mRNA and protein expression levels in NSGs were significantly higher than those in SGTs. These results suggest that WISP-2 could be a reliable independent marker and that down-regulation or loss of the WISP-2 gene may be associated with the development of SGTs.

  19. [Primary teratocarcinoma of the pineal region].

    PubMed

    Masini, T; Tarocchi, A; Cappricci, E; Gullotta, F

    1989-01-01

    Primary Teratocarcinoma of Pineal Region. A case of a 12 year old boy admitted for intracranial hypertension of sudden onset has been reported. CT scanning and MR showed a triventricular hydrocephalus due to a space-occupying lesion of the pineal region. Tonic-clonic fits of the upper limbs and Parinaud syndrome were followed by loss of consciousness. Intervention I: ventriculo-peritoneal shunt with sampling of CSF and assay for beta-HCG, alpha FP and CEA, which proved negative. Cytology for neoplastic cells in cerebrospinal fluid was negative. Intervention II: grossly total removal of the tumor. This was followed by partial remission of Parinaud syndrome, total remission of the hypertensive symptoms and discharge on day 12. The 3 cm. whitish-pink tumor of rubbery consistency proved on histological examination to be a teratocarcinoma. The patient was further submitted to chemioterapy and irradiation but died 7 months after the second intervention. This is a rare tumor, much more than teratoma of the pineal gland, which is relatively frequent. It is interesting histologically because of the presence not only of chondroid and mesenchymal portions but also of adamantinomatous rudiments and of epithelial zones resembling embryonal carcinoma of the testis.

  20. Matrigel improves functional properties of primary human salivary gland cells.

    PubMed

    Maria, Ola M; Zeitouni, Anthony; Gologan, Olga; Tran, Simon D

    2011-05-01

    Currently, there is no effective treatment available to patients with irreversible loss of functional salivary acini caused by Sjogren's syndrome or after radiotherapy for head and neck cancer. A tissue-engineered artificial salivary gland would help these patients. The graft cells for this device must establish tight junctions in addition to being of fluid-secretory nature. This study analyzed a graft source from human salivary glands (huSG) cultured on Matrigel. Cells were obtained from parotid and submandibular glands, expanded in vitro, and then plated on either Matrigel-coated (2 mg/mL) or uncoated culture dish. Immunohistochemistry, transmission electron microscopy, quantitative real-time-polymerase chain reaction, Western blot, and transepithelial electrical resistance were employed. On Matrigel, huSG cells adopted an acinar phenotype by forming three-dimensional acinar-like units (within 24 h of plating) as well as a monolayer of cells. On uncoated surfaces (plastic), huSG cells only formed monolayers of ductal cells. Both types of culture conditions allowed huSG cells to express tight junction proteins (claudin-1, -2, -3, -4; occludin; JAM-A; and ZO-1) and adequate transepithelial electrical resistance. Importantly, 99% of huSG cells on Matrigel expressed α-amylase and the water channel protein Aquaporin-5, as compared to <5% of huSG cells on plastic. Transmission electron microscopy confirmed an acinar phenotype with many secretory granules. Matrigel increased the secretion of α-amylase two to five folds into the media, downregulated certain salivary genes, and regulated the translation of acinar proteins. This three-dimensional in vitro serum-free cell culture method allows the organization and differentiation of huSG cells into salivary cells with an acinar phenotype.

  1. Age-related differences in the structure of human pineal calcium deposits: results of transmission electron microscopy and mineralographic microanalysis.

    PubMed

    Schmid, H A; Raykhtsaum, G

    1995-01-01

    Pineal tissue calcifications (male, ages 14, 47, 62, 82), which were metallographically embedded and polished at controlled levels and studied by transmission electron microscopy and microanalytic spectroscopy, showed age-related differences. Results show that concentrically arranged crescent-shaped lamellae increase in number and decrease in width with age. Calcium (Ca) and phosphorus (P) per point measurements in dark and light lamellae at various distances from the core show Ca/P molar ratios between 1.49-1.62 in the 82-year-old specimen as compared to 1.26 to 1.41 in the younger specimens. The 62-year-old specimens show a decrease in P and an increase in Ca from periphery to center. These data and other descriptive details suggest that the sum of these changes represent remodelling of the mineralogical structure within the same calcification throughout the life span. PMID:7776174

  2. Dynamic OCT of mentally stress-induced sweating in sweat glands of the human finger tip

    NASA Astrophysics Data System (ADS)

    Ohmi, Masato; Ueda, Yoshihiro; Haruna, Masamitsu

    2007-02-01

    We demonstrate in-vivo imaging of sweat glands of human finger tip using the dynamic optical coherence tomography (OCT). Mentally-stress-induced sweating in sweat glands of human finger tip can be observed clearly in time-sequential OCT images. In the experiment, a sweat pore opened clearly on the skin surface according to a stimulus of sound.

  3. Weight gain increases human aromatase expression in mammary gland.

    PubMed

    Chen, Dong; Zhao, Hong; Coon, John S; Ono, Masanori; Pearson, Elizabeth K; Bulun, Serdar E

    2012-05-15

    Adulthood weight gain predicts estrogen receptor-positive breast cancer. Because local estrogen excess in the breast likely contributes to cancer development, and aromatase is the key enzyme in estrogen biosynthesis, we investigated the role of local aromatase expression in weight gain-associated breast cancer risk in a humanized aromatase (Arom(hum)) mouse model containing the coding region and the 5'-regulatory region of the human aromatase gene. Compared with littermates on normal chow, female Arom(hum) mice on a high fat diet gained more weight, and had a larger mammary gland mass with elevated total human aromatase mRNA levels via promoters I.4 and II associated with increased levels of their regulators TNFα and C/EBPβ. There was no difference in total human aromatase mRNA levels in gonadal white adipose tissue. Our data suggest that diet-induced weight gain preferentially stimulates local aromatase expression in the breast, which may lead to local estrogen excess and breast cancer risk.

  4. Salivary gland lymph nodes. The site of lymphadenopathies and lymphomas associated with human immunodeficiency virus infection.

    PubMed

    Ioachim, H L; Ryan, J R; Blaugrund, S M

    1988-12-01

    Normally, lymph nodes are intimately associated with the salivary glands, particularly the parotid gland. Several lymph nodes are embedded in the parotid gland, other lymph nodes are adjacent to the submaxillary gland, and ectopic salivary gland acini and ducts are commonly present in cervical lymph nodes. These salivary gland lymph nodes may become the primary site of the benign lymphadenopathy and the malignant lymphomas characteristically associated with human immunodeficiency virus (HIV) infection. This report of a series of HIV-associated lymphatic lesions originating in salivary gland lymph nodes comprises nine cases of salivary gland masses that were surgically excised, it includes six cases of lymphadenitides and three cases of lymphoma--all originating in salivary gland lymph nodes and showing the histologic lesions known to occur in association with the acquired immunodeficiency syndrome. The HIV-related infections and neoplasias located in the salivary gland lymph nodes raise interesting questions about the possible etiologic role of an oral portal of entry and of the virus-infected saliva. The recognition of their clinical and pathologic features is indispensable to enable correct diagnosis and treatment.

  5. Expression of the gene encoding growth hormone in the human mammary gland

    SciTech Connect

    Mol, J.A.; Misdorp, W.; Rijnberk, A.

    1995-10-01

    Progestins cause a syndrome of growth hormone (GH) excess and enhanced mammary tumorigenesis in the dog. This has been regarded as being specific for the dog. Recently we reported that progestin-induced GH excess originates from foci of hyperplastic ductular epithelium of the mammary gland in the dog. In the present report we demonstrate by reverse-transcriptase PCR and immunohistochemistry that a main factor involved in tissue growth, i.e. GH, is also expressed in normal and neoplastic human mammary glands. The gene expressed in the human mammary gland proved to be identical to the gene encoding GH in the pituitary gland. The role of progesterone in the GH expression of the human mammary gland needs, however, to be proven. It is hypothesized that this locally produced hGH may play a pathogenetic role in breast cancer. 21 refs., 2 figs., 1 tab.

  6. Lrig1 Expression in Human Sebaceous Gland Tumors

    PubMed Central

    Pünchera, Jöri; Barnes, Laurent; Kaya, Gürkan

    2016-01-01

    Background Sebaceous glands contribute significantly to the barrier functions of the skin. However, little is known about their homeostasis and tumorigenesis. Recently, increased expression of stem cell marker Lrig1 has been reported in sebaceous carcinoma-like tumors of K14ΔNLef1 transgenic mice. In this study, we analyzed the Lrig1 expression in human sebaceous tumors. Methods Twenty-eight formalin-fixed paraffin-embedded sebaceous tumor specimens (7 sebaceous hyperplasias, 7 sebaceous adenomas, 10 sebaceomas and 4 sebaceous carcinomas) were stained with anti-Lrig1, anti-CD44v3 and anti-Ki67 antibody. Results Four (100%) sebaceous carcinomas, 8 (80%) sebaceomas, 3 (43%) sebaceous adenomas and no sebaceous hyperplasia showed Lrig1 overexpression. Discussion and Conclusion Lrig1 is a known tumor suppressor gene and is usually considered to be an indicator of poorly aggressive tumors. In human sebaceous tumors, the stronger Lrig1 staining in sebaceous carcinoma compared to other sebaceous tumors might be a feature of an advanced stage in tumorigenesis and a bad prognosis. In our study, 100% of sebaceous carcinomas revealed Lrig1 overexpression. We propose that Lrig1 may be used as a possible new marker of poorly differentiated sebaceous carcinoma. PMID:27504445

  7. Pineal arylalkylamine N-acetyltransferase (Aanat) gene expression as a target of inflammatory mediators in the chicken.

    PubMed

    Piesiewicz, Aneta; Kedzierska, Urszula; Adamska, Iwona; Usarek, Michal; Zeman, Michal; Skwarlo-Sonta, Krystyna; Majewski, Pawel Marek

    2012-11-01

    Previously, we demonstrated that experimental peritonitis in chickens was attenuated by treatment with exogenous melatonin, while the developing inflammation decreased pineal AANAT activity. This suggested the existence of a bidirectional relationship between the activated immune system and pineal gland function. The aim of the present study was to identify the step(s) in the chicken pineal melatonin biosynthetic pathway that are affected by inflammation. Peritonitis was evoked by i.p. injection of thioglycollate solution, either 2h after the start, or 2h before the end of the light period, and the animals were sacrificed 4h later. The effect of inflammation on the expression of genes encoding enzymes participating in melatonin biosynthesis in the pineal gland, i.e. tryptophan hydroxylase 1 (Tph1), dopa decarboxylase (Ddc), arylalkylamine N-acetyltransferase (Aanat) and acetylserotonin O-methyltransferase (Asmt), was evaluated by qPCR. The pineal and serum melatonin concentration as well as the content of its precursors in the pineal gland were measured, along with the activity of the relevant biosynthetic enzymes. Developing peritonitis caused an increase in the pineal levels of the Tph1 mRNA during the night and the Asmt mRNA during the day, while nocturnal Aanat transcription was reduced. Both the pineal and serum melatonin level and the pineal content of N-acetylserotonin (NAS) were decreased during the night in birds with peritonitis. The amount and activity of pineal AANAT were significantly reduced, while the activity of HIOMT was increased under these experimental conditions. These results indicate that the observed decrease in MEL biosynthesis in chickens with developing inflammation is a result of transcriptional downregulation of the Aanat gene, followed by reduced synthesis and activity of the encoded enzyme.

  8. Precursors of hexoneogenesis within the human mammary gland.

    PubMed

    Mohammad, Mahmoud A; Maningat, Patricia; Sunehag, Agneta L; Haymond, Morey W

    2015-04-15

    The human mammary gland is capable of de novo synthesis of glucose and galactose (hexoneogenesis); however, the carbon source is incompletely understood. In this study, we investigated the role of acetate, glutamine, lactate and glycerol as potential carbon sources for hexoneogenesis. Healthy breastfeeding women were studied following a 24-h fast on two occasions separated by 1-3 wk. Five women were infused with [U-¹³C]lactate or [1,2-¹³C₂]glutamine and five women with [U-¹³C]glycerol or [1,2-¹³C₂]acetate. Enrichments of ¹³C in plasma and milk substrates were analyzed using GC-MS. Infusion of labeled lactate, glycerol, glutamine, and acetate resulted in plasma glucose being 22.0±3.7, 11.2±1.0, 2.5±0.5, and 1.3±0.2% labeled, respectively. Lactate, glutamine, or acetate did not contribute to milk glucose or galactose (0-2%). In milk, ¹³C-free glycerol enrichment was one-fourth that in plasma but free glycerol concentration in milk was fourfold higher than in plasma. Using [U-¹³C]glycerol and by accounting for tracer dilution, glycerol alone contributed to 10±2 and 69±11% of the hexoneogenesis of milk glucose and galactose, respectively. During [U-¹³C]glycerol infusion, the ratio of M₃ enrichment on 4-6 carbons/M₃ on 1-3 carbons of galactose was higher (P<0.05, 1.22±0.05) than those of glucose in plasma (1.05±0.03) and milk (1.07±0.02). Reanalysis of samples from a previous study involving [U-¹³C]glucose infusion alone suggested labeling a portion of galactose consistent with pentose phosphate pathway (PPP) activity. We conclude that, although lactate contributed significantly to gluconeogenesis, glycerol alone provides the vast majority of substrate for hexoneogenesis. The relative contribution of the PPP vs. the reversal Embden-Meyerhof pathway to hexoneogenesis within the human mammary gland remains to be determined.

  9. Pineal and habenula calcification in schizophrenia.

    PubMed

    Sandyk, R

    1992-01-01

    Animal data indicate that melatonin secretion is stimulated by the paraventricular nucleus (PVN) of the hypothalamus and that lesions of the PVN mimic the endocrine effects of pinealectomy. Since the PVN lies adjacent to the third ventricle, I propose that periventricular damage, which is found in schizophrenia and may account for the third ventricular dilatation seen on computed tomographic (CT), may disrupt PVN-pineal interactions and ultimately enhance the process of pineal calcification (PC). To investigate this hypothesis, I conducted CT study on the relationship of PC size to third ventricular width (TVW) in 12 chronic schizophrenic patients (mean age: 33.7 years; SD = 7.3). For comparison, I also studied the relationship of PC size to the ventricular brain ratio and prefrontal cortical atrophy. As predicted, there was a significant correlation between PC size and TVW (r pbi = .61, p < .05), whereas PC was unrelated to the control neuroradiological measures. The findings support the hypothesis that periventricular damage may be involved in the process of PC in schizophrenia and may indirectly implicate damage to the PVN in the mechanisms underlying dysfunction of the pineal gland in schizophrenia. In a second study, I investigated the prevalence of habenular calcification (HAC) on CT in a cohort of 23 chronic schizophrenic-patients (mean age: 31.2 years; SD = 5.95). In this sample HAC was present in 20 patients (87%). Since the prevalence of HAC in a control population of similar age is only 15% these data reveal an almost 6-fold higher prevalence of HAC (X2 = 84.01, p < .0001) in chronic schizophrenia as compared to normal controls. The implications of HAC for the pathophysiology of schizophrenia are discussed in light of the central role of the habenula in the regulation of limbic functions.

  10. Pineal and habenula calcification in schizophrenia.

    PubMed

    Sandyk, R

    1992-01-01

    Animal data indicate that melatonin secretion is stimulated by the paraventricular nucleus (PVN) of the hypothalamus and that lesions of the PVN mimic the endocrine effects of pinealectomy. Since the PVN lies adjacent to the third ventricle, I propose that periventricular damage, which is found in schizophrenia and may account for the third ventricular dilatation seen on computed tomographic (CT), may disrupt PVN-pineal interactions and ultimately enhance the process of pineal calcification (PC). To investigate this hypothesis, I conducted CT study on the relationship of PC size to third ventricular width (TVW) in 12 chronic schizophrenic patients (mean age: 33.7 years; SD = 7.3). For comparison, I also studied the relationship of PC size to the ventricular brain ratio and prefrontal cortical atrophy. As predicted, there was a significant correlation between PC size and TVW (r pbi = .61, p < .05), whereas PC was unrelated to the control neuroradiological measures. The findings support the hypothesis that periventricular damage may be involved in the process of PC in schizophrenia and may indirectly implicate damage to the PVN in the mechanisms underlying dysfunction of the pineal gland in schizophrenia. In a second study, I investigated the prevalence of habenular calcification (HAC) on CT in a cohort of 23 chronic schizophrenic-patients (mean age: 31.2 years; SD = 5.95). In this sample HAC was present in 20 patients (87%). Since the prevalence of HAC in a control population of similar age is only 15% these data reveal an almost 6-fold higher prevalence of HAC (X2 = 84.01, p < .0001) in chronic schizophrenia as compared to normal controls. The implications of HAC for the pathophysiology of schizophrenia are discussed in light of the central role of the habenula in the regulation of limbic functions. PMID:1305634

  11. Shadow response in the blind cavefish Astyanax reveals conservation of a functional pineal eye

    PubMed Central

    Yoshizawa, Masato; Jeffery, William R.

    2013-01-01

    SUMMARY The blind cavefish Astyanax mexicanus undergoes bilateral eye degeneration during embryonic development. Despite the absence of light in the cave environment, cavefish have retained a structurally intact pineal eye. We show here that contrary to visual degeneration in the bilateral eyes, the cavefish pineal eye has conserved the ability to detect light. Larvae of two different Astyanax cavefish populations and the con-specific sighted surface-dwelling form (surface fish) respond similarly to light dimming by shading the pineal eye. As a response to shading, cavefish larvae swim upward vertically. This behavior resembles that of amphibian tadpoles rather than other teleost larvae, which react to shadows by swimming downward. The shadow response is highest at 1.5-days post-fertilization (d.p.f.), gradually diminishes, and is virtually undetectable by 7.5 d.p.f. The shadow response was substantially reduced after surgical removal of the pineal gland from surface fish or cavefish larvae, indicating that it is based on pineal function. In contrast, removal of one or both bilateral eye primordia did not affect the shadow response. Consistent with its light detecting capacity, immunocytochemical studies indicate that surface fish and cavefish pineal eyes express a rhodopsin-like antigen, which is undetectable in the degenerating bilateral eyes of cavefish larvae. We conclude that light detection by the pineal eye has been conserved in cavefish despite a million or more years of evolution in complete darkness. PMID:18203983

  12. Pineal and photoperiodic influences on fat deposition, pelage, and testicular activity in male meadow voles.

    PubMed

    Smale, L; Dark, J; Zucker, I

    1988-01-01

    Pinealectomy completely prevented gonadal regression as well as reduction in body weight and white adipose tissue content of the gonadal and retroperitoneal fat deposits in male meadow voles transferred from long to short day lengths. Pineal influences on pelage characteristics depended on which parameter was assessed. For instance, the increase in guard hair length observed in short-day control voles was blocked by pinealectomy; however, a similar increase in underhair length was unaffected by removal of the pineal gland. Photoperiod-dependent changes in fat deposition, testicular activity, and guard hair length presumably rely on altered pineal secretory activity to transduce the effects of day length on the neuroendocrine axis; however, mechanisms independent of pineal activity may be capable of mediating photoperiodic control of underhair growth. PMID:2979644

  13. The relationship of pineal calcification to cerebral atrophy on CT scan in multiple sclerosis.

    PubMed

    Sandyk, R; Awerbuch, G I

    1994-05-01

    Calcification is a known morphological feature of the pineal gland. The mechanisms underlying the development of pineal calcification (PC) are elusive although there is experimental evidence that calcification may be a marker of the past secretory activity of the gland and/or of degeneration. The increased incidence of PC with aging suggests that it may reflect cerebral degenerative changes as well. In a recent Editorial in this Journal it was proposed that the pineal gland is implicated in the pathogenesis of multiple sclerosis (MS). Cerebral atrophy, which can be demonstrated on CT scan, is a common feature of MS resulting from demyelination and gliosis. If PC is a marker of a cerebral degenerative process, then one would expect a higher incidence of calcification of the gland in patients with cerebral atrophy compared to those without cerebral atrophy. To test this hypothesis, we studied the incidence of PC on CT scan in a cohort of 48 MS patients, 21 of whom had cerebral atrophy. For the purpose of comparison, we also assessed the incidence of choroid plexus calcification (CPC) in relation to cerebral atrophy. PC was found in 42 patients (87.5%) and its incidence in patients with cerebral atrophy was significantly higher compared to the incidence in patients without cerebral atrophy (100% vs. 77.7%; p < .025). In contrast, CPC was unrelated to cerebral atrophy or to PC thus supporting the notion of a specific association between the pineal gland and the pathogenesis of MS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7960471

  14. Cytochemical investigation on lipids in human major salivary glands. A light and electron microscope study.

    PubMed

    Sirigu, P; Diaz, G; Lantini, M S; Del Fiacco, M

    1976-01-01

    The localization of lipids in the secretion of human parotid and submandibular glands has been here investigated. Ultrastructural observations following lipid extraction and histochemical data showed that lipid components are not present in the secretory granules. In fact, while histochemical reactions are completely negative, secretory granules from lipid-depleted glands retain all their morphological characters. These results led us to emphasize that, at least in human seromucous cells, lipids are not directly involved in the salivary secretion. This conclusion, which is supported by the biochemical data concerning the lipid content in human saliva, disagrees with the findings obtained in rat and guinea pig salivary glands. However, this discrepancy may be ascribed to the specific biochemical and ultrastructural differences found in the salivary glands of the various mammalian species. PMID:1023331

  15. Enzyme histochemistry in the developing suprarenal gland of human embryos.

    PubMed

    Lichnovský, V; Lojda, Z

    1989-01-01

    The localization of the activities of some selected phosphatases, peptidases and dehydrogenases were studied in cryostat sections of the developing anlage of the suprarenal gland of human embryos from 8 to 20 weeks of the intra-uterine life. In the youngest fetuses under our notice (weeks 8-12), the activity of alkaline phosphatase (AP) on the cellular membranes of the fetal cortex was very low. In contrast, the activity of acid phosphatase (AcP) was comparatively high. Peak activity was found in the cells of the central zone of the fetal cortex. Compared to the activity of the latter, the activity of non-specific esterase (ANE) was somewhat lower. Both its localization and the gradient were identical with those of acid phosphatase. Of the peptidases studied, only dipeptidyl peptidase IV (DPP IV) exhibited slight activity in deeper layers of the primitive fetal cortex after week 8. The other peptidases exhibited only traces of activity. As early as in the first stages followed, the activity of glycero-3-phosphate-dehydrogenase (alpha-GPDH) was very high in all cells of the differentiating fetal cortex. The intensity of the activity of succinate dehydrogenase (SDH) was markedly lower. In older fetuses (weeks 13-20) there was a gradual increase in the activities of most enzymes, seen, after week 15 of the intrauterine life, also in the cells of the so-called definitive cortex. Most pronounced were the increases in the activities of acid phosphatase and non-specific esterase. The relatively low activities of the enzymes under study point to a relatively low degree of cell differentiation of both the primitive and, after week 15, the definitive cortex. Pronounced morphological and functional changes occur after the 20th week of the intrauterine life.

  16. Computed tomography study of pineal calcification in schizophrenia.

    PubMed

    Bersani, G; Garavini, A; Taddei, I; Tanfani, G; Nordio, M; Pancheri, P

    1999-06-01

    Computed tomography studies concerning pineal calcification (PC) in schizophrenia have been conducted mainly by one author who correlated this calcification with several aspects of the illness. On the basis of these findings the aim of the present study was to analyze size and incidence of pineal gland calcification by CT in schizophrenics and healthy controls, and to verify the relationship between pineal calcification and age, and the possible correlation with psychopathologic variables. Pineal calcification was measured on CT scans of 87 schizophrenics and 46 controls divided into seven age subgroups of five years each. No significant differences in PC incidence and mean size between patients and controls were observed as far as the entire group was considered. PC size correlated with age both in schizophrenics and controls. We found a higher incidence of PC in schizophrenics in the age subgroup of 21-25 years, and a negative correlation with positive symptoms of schizophrenia in the overall group. These findings could suggest a premature calcific process in schizophrenics and a probable association with 'non-paranoid' aspects of the illness. Nevertheless the potential role of this process possibly related to some aspects of the altered neurodevelopment in schizophrenia is still unclear. PMID:10572342

  17. Linoleic acid content of human meibum is associated with telangiectasia and plugging of gland orifices in meibomian gland dysfunction.

    PubMed

    Arita, Reiko; Mori, Naoto; Shirakawa, Rika; Asai, Kei; Imanaka, Takahiro; Fukano, Yasufumi; Nakamura, Masatsugu

    2016-04-01

    To examine the relation between changes in the free fatty acid (FFA) composition of human meibum and both objective signs and subjective symptoms of meibomian gland dysfunction (MGD), we analyzed the FFA content of meibum collected from both MGD patients and control subjects. Thirty-eight patients with MGD (13 men and 25 women; mean age ± SD, 66.9 ± 15.0 years) were evaluated. Various objective signs and subjective symptoms of MGD were assessed. Meibum was analyzed by liquid chromatography-Fourier transform mass spectrometry, and the relation between the FFA composition of meibum and each objective sign and subjective symptom was examined by principal component analysis (PCA). No relation was apparent between the FFA composition of meibum and individual subjective symptoms or objective signs of MGD. However, a PCA score plot for meibum samples grouped on the basis of the severity of both telangiectasia and plugging of meibomian gland orifices revealed clear separation of mild and severe groups. This separation of the two groups was largely due to a significantly increased linoleic acid content in meibum of the severe group (3.56%, versus 0.70% of total FFAs in the mild group). The relative amount of linoleic acid in meibum was thus associated with the severity of telangiectasia and plugging of gland orifices in MGD, suggesting that this FFA might contribute to the pathogenesis of these signs.

  18. Linoleic acid content of human meibum is associated with telangiectasia and plugging of gland orifices in meibomian gland dysfunction.

    PubMed

    Arita, Reiko; Mori, Naoto; Shirakawa, Rika; Asai, Kei; Imanaka, Takahiro; Fukano, Yasufumi; Nakamura, Masatsugu

    2016-04-01

    To examine the relation between changes in the free fatty acid (FFA) composition of human meibum and both objective signs and subjective symptoms of meibomian gland dysfunction (MGD), we analyzed the FFA content of meibum collected from both MGD patients and control subjects. Thirty-eight patients with MGD (13 men and 25 women; mean age ± SD, 66.9 ± 15.0 years) were evaluated. Various objective signs and subjective symptoms of MGD were assessed. Meibum was analyzed by liquid chromatography-Fourier transform mass spectrometry, and the relation between the FFA composition of meibum and each objective sign and subjective symptom was examined by principal component analysis (PCA). No relation was apparent between the FFA composition of meibum and individual subjective symptoms or objective signs of MGD. However, a PCA score plot for meibum samples grouped on the basis of the severity of both telangiectasia and plugging of meibomian gland orifices revealed clear separation of mild and severe groups. This separation of the two groups was largely due to a significantly increased linoleic acid content in meibum of the severe group (3.56%, versus 0.70% of total FFAs in the mild group). The relative amount of linoleic acid in meibum was thus associated with the severity of telangiectasia and plugging of gland orifices in MGD, suggesting that this FFA might contribute to the pathogenesis of these signs. PMID:26919787

  19. Similarity of GATA-3 Expression between Rat and Human Mammary Glands.

    PubMed

    Kinoshita, Yuichi; Yoshizawa, Katsuhiko; Emoto, Yuko; Yuki, Michiko; Yuri, Takashi; Shikata, Nobuaki; Tsubura, Airo

    2014-07-01

    The GATA family members are zinc finger transcription factors involved in cell differentiation and proliferation. In particular, GATA-3 is necessary for mammary gland maturation and is a useful marker in the characterization of mammary carcinoma in humans. The expression of GATA-3 protein in normal mammary glands, fibroadenomas and carcinomas was immunohistochemically compared in female rats and humans. In normal mammary glands of rats and humans, scattered luminal cells in the acini and whole ductal epithelial cells were positive for GATA-3 in the nuclei. No positive cells were detected in rat or human fibroadenomas. In rat and human mammary carcinomas, the nuclei of proliferating luminal-derived cancer cells expressed GATA-3. Therefore, GATA-3 protein is a candidate marker for mammary carcinoma in rats as well as humans.

  20. Anion exchanger immunoreactivity in human salivary glands in health and Sjögren's syndrome.

    PubMed Central

    Vázquez, J. J.; Vázquez, M.; Idoate, M. A.; Montuenga, L.; Martínez-Ansó, E.; Castillo, J. E.; García, N.; Medina, J. F.; Prieto, J.

    1995-01-01

    Salivary gland ducts play a relevant role in saliva secretion through transport processes. Na(+)-independent chloride-bicarbonate anion exchangers (AE) may be involved in these processes by generating ion fluxes into the salivary secretion. In Sjögren's syndrome, a disorder with gland dysfunction, there might be an impaired expression of AE proteins. Here we study AE immunoreactivities in human salivary glands, both in health and in Sjögren's syndrome. Immunohistochemistry was carried out on salivary glands from normal subjects and patients with Sjögren's syndrome, using two monoclonal antibodies against AE1 and AE2. Normal salivary glands showed AE2 immunoreactivity, which was restricted to the epithelium of the ducts, with no staining at the acini. A strong positivity was seen in the basolateral portion of the striated ducts, while interlobular duct cells showed a discrete positivity at their apical pole. In salivary glands from most of the patients with Sjögren's syndrome, AE2 immunoreactivity was absent in the ducts as well as in the acini. In both normal and diseased salivary glands, AE1 immunoreactivity was only located at the erythrocyte membrane. The recently reported AE0 was discarded because no AE0 message was found in salivary glands by reverse transcription polymerase chain reaction. In conclusion, AE2 immunoreactivity is observed in the ducts of normal salivary glands, particularly in the striated ducts. AE2 immunoreactivity is virtually absent in salivary glands from patients with Sjögren's syndrome, which may reflect either a loss of AE2 after inflammatory atrophy, or a primary defect occurring in the disease. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:7778681

  1. Parotid gland is the main source of human salivary epidermal growth factor

    SciTech Connect

    Thesleff, I.; Viinikka, L.; Saxen, L.; Lehtonen, E.; Perheentupa, J.

    1988-01-01

    To clarify the production of human epidermal growth factor (EGF) by different salivary glands, the authors measured its concentration by radioimmunoassay separately in whole saliva, in parotid gland (PG) saliva and in mixed submandibular (SMG) and sublingual gland (SLG) saliva. Also, they studied the presence of EGF in PG and SMG by immunohistochemistry. The mean concentrations of EDG in PG saliva was higher than in whole saliva, which in turn was higher than in mixed SMG + SLG saliva. No sex difference existed in any salivary gland EGF. Immunohistochemistry revealed EGF in the acinar cells of both PG and SMG, buy only in PG there were prominent EDG deposits in luminal spaces. Their data suggest that EDG is produced by both PG and SMG, but that more of it is secreted from the PG. This result is new and challenges the general view that human salivary EDG is mainly from SMG.

  2. Evidence for feedback control of pineal melatonin secretion.

    PubMed

    Bedrosian, Tracy A; Herring, Kamillya L; Walton, James C; Fonken, Laura K; Weil, Zachary M; Nelson, Randy J

    2013-05-10

    Melatonin is the principle hormonal product of the pineal gland. It is secreted with a robust daily rhythm, peaking near the middle of the night. During the daytime, concentrations remain very low, as exposure to light robustly suppresses its secretion. The regulation of melatonin by light is well-characterized, but an interesting feature of the daily melatonin rhythm is that its peak occurs near the middle of the night and then levels begin to drop hours before morning light exposure. The mechanism underlying the light-independent drop in melatonin during late night remains unspecified. Feedback control is one mechanism of hormone regulation, but no studies thus far have explored the possibility of such regulation in the pineal of white-footed mice (Peromyscus leucopus). The pineal gland and SCN express melatonin receptors, and melatonin regulates its own receptor density in the brain. We investigated the possibility of feedback control of melatonin by administering melatonin receptor antagonists to female white-footed mice and then measuring plasma melatonin concentrations. In the first experiment, we observed that luzindole, a dual MT1/MT2 receptor antagonist administered 1h after lights off, caused an increase in plasma melatonin both 1 and 2h later. In a second experiment, we did not observe a change in melatonin concentrations following injection of an antagonist specific for the MT2 subtype. These results suggest the possibility of feedback control of melatonin release, occurring preferentially through the MT1 receptor subtype. PMID:23528860

  3. Expression of ghrelin in human fetal adrenal glands and paraadrenal nerve ganglions.

    PubMed

    Obara-Moszyńska, Monika; Kedzia, Andrzej; Chmielnicka-Kopaczyk, Maria

    2009-01-01

    The aim of this paper was assessment of location, expression and role of ghrelin in the development and maturation of human fetal adrenal glands and paraadrenal nerve ganglions. Immunohistochemistry was used. The strongest expression of ghrelin was detected in the fetal zone of the adrenal glands, in the neuroepithelial cells of the medullar portion of the adrenals and in few nerve ganglion cells. Ghrelin takes part in molecular processes of proliferation and maturation, and does not influence on steroidogenesis.

  4. Effect of Growth Factors on the Proliferation and Gene Expression of Human Meibomian Gland Epithelial Cells

    PubMed Central

    Liu, Shaohui; Kam, Wendy R.; Ding, Juan; Hatton, Mark P.; Sullivan, David A.

    2013-01-01

    Purpose. We hypothesize that growth factors, including epidermal growth factor (EGF) and bovine pituitary extract (BPE), induce proliferation, but not differentiation (e.g., lipid accumulation), of human meibomian gland epithelial cells. We also hypothesize that these actions involve a significant upregulation of genes linked to cell cycle processes, and a significant downregulation of genes associated with differentiation. Our objective was to test these hypotheses. Methods. Immortalized human meibomian gland and conjunctival epithelial cells were cultured for varying time periods in the presence or absence of EGF, BPE, EGF + BPE, or serum, followed by cell counting, neutral lipid staining, or RNA isolation for molecular biological procedures. Results. Our studies show that growth factors stimulate a significant, time-dependent proliferation of human meibomian gland epithelial cells. These effects are associated with a significant upregulation of genes linked to cell cycle, DNA replication, ribosomes, and translation, and a significant decrease in those related to cell differentiation, tissue development, lipid metabolic processes, and peroxisome proliferator-activated receptor signaling. Serum-induced differentiation, but not growth factor-related proliferation, elicits a pronounced lipid accumulation in human meibomian gland epithelial cells. This lipogenic response is unique, and is not duplicated by human conjunctival epithelial cells. Conclusions. Our results demonstrate that EGF and BPE stimulate human meibomian gland epithelial cells to proliferate. Further, our findings show that action is associated with an upregulation of cell cycle and translation ontologies, and a downregulation of genetic pathways linked to differentiation and lipid biosynthesis. PMID:23493293

  5. Development of a nude mouse model to study human sebaceous gland physiology and pathophysiology.

    PubMed

    Petersen, M J; Zone, J J; Krueger, G G

    1984-10-01

    Study of human sebaceous gland physiology and pathophysiology is limited by lack of an adequate animal model. This study was designed to develop an animal model using human face skin grafted onto the nude mouse to study human sebaceous glands. Full-thickness human face skin was grafted onto 60 adult male nude mice. 4 wk after grafting, androgens, which are known to stimulate sebaceous glands, were administered to test the system. Androgens were administered to 21 animals by implanted catheters that were filled with testosterone (T) or dihydrotestosterone (DHT). Empty catheters were implanted in 15 control animals. Graft biopsies and blood for androgen levels were obtained at time 1 (pre-catheter) and time 2 (26 d after catheter implantation). Three assessments were made on each biopsy: sebaceous gland volume, using an image analyzing computer; sebaceous cell size; and sebaceous gland labeling index. 29 mice completed the study through time 2. In the androgen-treated group, T levels (nanogram per milliliter) five times increased to 4.92 +/- 0.35, and DHT levels (nanogram per milliliter) increased 50 times to 16.70. In the androgen-treated group, sebaceous gland volume (micron 3 X 10(-3) increased from 896 +/- 194 to 3,233 +/- 754 (P less than 0.001), sebaceous cell area (micron 2) increased from 167 +/- 12 to 243 +/- 19 (P less than 0.001), and labeling index (percentage) increased from 2.7 +/- 0.7 to 6.4 +/- 0.9 (P less than 0.01). In the control group, sebaceous gland volume fell from 1,070 +/- 393 to 417 +/- 99 (NS), sebaceous cell size remained the same, and the labeling index fell from 5.1 +/- 1.9 to 3.2 +/- 1.1. After androgen administration, Halowax N-34, a known comedogen, or its vehicle, was applied to 15 grafts for 2-6 wk. Twice as many microcomedones were seen in the Halowax-treated grafts, compared with vehicle-treated grafts at the end of this time period. No visible comedones were produced. This study demonstrated that: (a) human sebaceous glands can

  6. Experiment K-6-19. Pineal physiology in microgravity: Relation to rat gonadal function

    NASA Technical Reports Server (NTRS)

    Holley, D.; Soliman, M. R. I.; Kaddis, F.; Markley, C.; Krasnov, I.

    1990-01-01

    One of the most interesting concomitants to spaceflight and exposure to microgravity has been the disturbing alteration in calcium metabolism and resulting skeletal effects. It was recognized as early as 1685 (cited in Kitay and Altschule, 1954) that the pineal of humans calcified with age. However, little can be found in the literature relating calcification and pineal function. Given the link between exposure to microgravity and perturbation of calcium metabolism and the fact that the pineal is apparently one of the only soft tissues to calcify, researchers examined pineal calcium content following the spaceflight. Researchers concluded that the spaceflight resulted in a stress response as indicated by adrenal hypertrophy, that gonadal function was compromised, and that the pineal may be linked as part of the mechanism of the responses noted.

  7. Electron microprobe analysis of human labial gland secretory granules in cystic fibrosis

    SciTech Connect

    Izutsu, K.; Johnson, D.; Schubert, M.; Wang, E.; Ramsey, B.; Tamarin, A.; Truelove, E.; Ensign, W.; Young, M.

    1985-06-01

    X-ray microanalysis of freeze-dried labial gland cryosections revealed that Na concentration was doubled and the Ca/S concentration ratio was decreased in secretory granules of labial glands from patients with cystic fibrosis (CF) when compared with glands from normal subjects. Other results suggested that the decrease in the Ca/S concentration ratio resulted from an increase in S concentration. These findings imply that mucous granules in labial saliva showed a CF-related increase in Na and S content, and such changes would be expected to affect the rheology of the mucus after exocytosis. In contrast with a previous study in human parotid glands, no evidence was found for CF-related changes in cytoplasmic or nuclear Na, K, and Ca concentrations. Significant elemental differences were found between secretory granules and nuclei and cytoplasm of control cells.

  8. Pineal concretions in turkey (Meleagris gallopavo) as a result of collagen-mediated calcification.

    PubMed

    Przybylska-Gornowicz, B; Lewczuk, B; Prusik, M; Bulc, M

    2009-04-01

    The intra-pineal calcification is a well-known phenomenon in mammals, however it is almost completely unknown in birds. The aim of the present work was to analyze morphology and genesis of the pineal concretions in the turkey. The studies were performed on the pineals collected from one-year-old turkeys (Meleagris gallopavo). In addition to standard morphological methods, the alizarin red S and potassium pyroantimonate methods were employed for localization of calcium at the light and electron microscopy level. In light microscopy, calcified concretions with diameters from 300 microm to 2 mm and quantities from 3 to 6 per gland were observed in all the examined pineals. They were stained red with alizarin S and showed the presence of collagen in Mallory's staining. Two types of cells were noted inside the concretion: polygonal and elongated ones. Using electron microscopy, three parts were distinguished within the calcification area. The peripheral part contained densely packed collagen fibrils, some elongated cells and numerous pyroantimonate precipitates demonstrating the presence of calcium ions. In the intermediate part, the fibrils were covered by almost continuous sheets of pyroantimonate precipitates and fused side by side. The central part showed an appearance of calcified hard tissue and contained some polygonal (osteocyte-like) cells. The obtained data demonstrated that the formation of the pineal concretions in the turkey is associated with the mineralization of collagen. This process is completely different from the mechanisms responsible for the formation of the concretions in the mammalian pineal. PMID:19224443

  9. Pineal concretions in turkey (Meleagris gallopavo) as a result of collagen-mediated calcification.

    PubMed

    Przybylska-Gornowicz, B; Lewczuk, B; Prusik, M; Bulc, M

    2009-04-01

    The intra-pineal calcification is a well-known phenomenon in mammals, however it is almost completely unknown in birds. The aim of the present work was to analyze morphology and genesis of the pineal concretions in the turkey. The studies were performed on the pineals collected from one-year-old turkeys (Meleagris gallopavo). In addition to standard morphological methods, the alizarin red S and potassium pyroantimonate methods were employed for localization of calcium at the light and electron microscopy level. In light microscopy, calcified concretions with diameters from 300 microm to 2 mm and quantities from 3 to 6 per gland were observed in all the examined pineals. They were stained red with alizarin S and showed the presence of collagen in Mallory's staining. Two types of cells were noted inside the concretion: polygonal and elongated ones. Using electron microscopy, three parts were distinguished within the calcification area. The peripheral part contained densely packed collagen fibrils, some elongated cells and numerous pyroantimonate precipitates demonstrating the presence of calcium ions. In the intermediate part, the fibrils were covered by almost continuous sheets of pyroantimonate precipitates and fused side by side. The central part showed an appearance of calcified hard tissue and contained some polygonal (osteocyte-like) cells. The obtained data demonstrated that the formation of the pineal concretions in the turkey is associated with the mineralization of collagen. This process is completely different from the mechanisms responsible for the formation of the concretions in the mammalian pineal.

  10. Responses of young Xenopus laevis tadpoles to light dimming: possible roles for the pineal eye.

    PubMed

    Jamieson, D; Roberts, A

    2000-06-01

    When the light is dimmed, the pineal eye of hatchling Xenopus laevis tadpoles excites the central pattern generator for swimming, but the behavioural significance of pineal excitation is unclear. We show that tadpoles spend 99 % of their time hanging from the surface meniscus or solid objects using mucus secreted by a cement gland on the head. Attachment inhibits swimming, but unattached tadpoles swim spontaneously. Provided that their pineal eye is intact, they attach closer to the water surface in the dark than in the light and attach preferentially to the underside of floating objects that cast shadows. Dimming causes tadpoles swimming horizontally to turn upwards and is very effective in initiating upward swimming in unattached tadpoles. Similar pineal-dependent responses during swimming are present up to stage 44. Pinealectomy blocks responses to dimming at all stages. Recordings from immobilised tadpoles reveal that light dimming induces faster fictive swimming and that pineal activity is increased for up to 20 min during sustained light dimming. We suggest that the increase in pineal discharge during dimming increases the probability of upward swimming and, in this way, increases the probability of tadpoles attaching to objects higher in the water column that cast shadows.

  11. A new concept for melatonin deficit: on pineal calcification and melatonin excretion.

    PubMed

    Kunz, D; Schmitz, S; Mahlberg, R; Mohr, A; Stöter, C; Wolf, K J; Herrmann, W M

    1999-12-01

    Even though exogenous melatonin has proven to influence sleep and circadian parameters, low endogenous melatonin is not related to sleep disturbances, nor does it predict response to melatonin replacement therapy. In this manuscript, we present a new concept towards a definition of a melatonin deficit. The purpose of the study was to introduce a marker for an intra-individual decrease in melatonin production. Therefore, we developed a method to quantify the degree of pineal calcification (DOC) using cranial computed tomography. Combining pineal DOC with the organs's size, we estimated the uncalcified pineal gland volume. This estimation was positively and significantly associated with 6-sulfatoxymelatonin (aMT6s), collected over 24 hours in urine, in 26 subjects. Data yielded evidence that the decline in aMT6s excretion with age can be sufficiently explained by an increased pineal calcification. These results suggest that DOC might be useful as an indicator of an intra-individual, decreased capability of the pineal gland to produce melatonin. DOC might prove to be a response-marker for melatonin replacement therapy and a vulnerability marker of the circadian timing system. PMID:10633482

  12. The Influence of 13-cis Retinoic Acid on Human Meibomian Gland Epithelial Cells

    PubMed Central

    Ding, Juan; Kam, Wendy R.; Dieckow, Julia; Sullivan, David A.

    2013-01-01

    Purpose. Meibomian gland dysfunction (MGD) is a primary cause of dry eye disease. One of the risk factors for MGD is exposure to 13-cis retinoic acid (13-cis RA), a metabolite of vitamin A. However, the mechanism is not well understood. We hypothesize that 13-cis RA inhibits cell proliferation, promotes cell death, alters gene and protein expressions, and attenuates cell survival pathways in human meibomian gland epithelial cells. Methods. To test our hypotheses, immortalized human meibomian gland epithelial cells were cultured with or without 13-cis RA for varying doses and time. Cell proliferation, cell death, gene expression, and proteins involved in proliferation/survival and inflammation were evaluated. Results. We found that 13-cis RA inhibited cell proliferation, induced cell death, and significantly altered the expression of 6726 genes, including those involved in cell proliferation, cell death, differentiation, keratinization, and inflammation, in human meibomian gland epithelial cells. Further, 13-cis RA also reduced the phosphorylation of Akt and increased the generation of interleukin-1β and matrix metallopeptidase 9. Conclusions. Exposure to 13-cis RA inhibits cell proliferation, increases cell death, alters gene expression, changes signaling pathways, and promotes inflammatory mediator and protease expression in meibomian gland epithelial cells. These effects may be responsible, at least in part, for the 13-cis RA–related induction of MGD. PMID:23722388

  13. Tumors of the pineal region.

    PubMed

    Piovan, E; Beltramello, A

    1996-01-01

    The role played by neuroradiologic examinations in the diagnosis of neoformations of the pineal region is considered. Results of reports of literature are compared with the personal experience (40 patients) to draw possible significant conclusions for the diagnosis of the oncological type. First, intrinsic pineal lesions should be separated from those of adjacent structures. Reliable discriminating parameters useful in the differential diagnosis are represented by sex and age. Diagnosis based on biochemistry with markers was shown not to be univocal. A further separation can be based on CT and MRI findings. In particular, teratomas appear as solid tumors with calcification and fat. The latter is depicted on MRI even if minimal. To the contrary, germinomas do not contain fat and are markedly enhancing. Microcysts seem to be more common in tumors originating from parenchymal pineal cells. A reliable differential diagnosis is however possible only for small-sized lesions where identification of the anatomical structure of origin is easier. PMID:8677341

  14. Morphology and morphometry of the human sublingual glands in mouth floor enlargements of edentulous patients

    PubMed Central

    de SÁ, Josiane Costa Rodrigues; TOLENTINO, Elen de Souza; AZEVEDO-ALANIS, Luciana Reis; IWAKI FILHO, Liogi; LARA, Vanessa Soares; DAMANTE, José Humberto

    2013-01-01

    Asymptomatic mouth floor enlargements may be observed in edentulous patients. These masses, which protrude from the mouth floor, may complicate the fitting of dentures and require surgery. Whether this "entity" may be considered an anatomical variation of the mouth floor or represent specific alterations in the sublingual gland is not known. Objective The aim of this work is to investigate the morphological and morphometric aspects of the sublingual glands of edentulous patients with mouth floor enlargements and compare the glands of these patients with the sublingual glands of human cadavers. Material and Methods Microscopic evaluation was performed on human sublingual glands from edentulous patients with mouth floor enlargements (n=20) and edentulous cadavers (n=20). The patients and cadavers were of similar ages. The data were compared using Mann-Whitney U, Fisher's exact and Student's t tests (p<0.05). Results Acinar atrophy, duct-like structures, mononuclear infiltrates, replacement of parenchyma with fibrous/adipose tissue, mucous extravasation and oncocytosis were similar between the groups (p>0.05). Only the variables "autolysis" and "congested blood vessels" presented statistical difference between groups (p=0.014; p=0.043). The morphometric study revealed that the volume densities of acini, ducts, stroma and adipose tissue were similar between the groups (p>0.05). Conclusion The microscopic characteristics of the sublingual glands in mouth floor enlargements in edentulous patients correspond to characteristics associated with the normal aging process. The glands are not pathological and represent an age-related alteration that occurs with or without the presence of the mouth floor enlargements. PMID:24473720

  15. Establishment of functional acinar-like cultures from human salivary glands.

    PubMed

    Jang, S I; Ong, H L; Gallo, A; Liu, X; Illei, G; Alevizos, I

    2015-02-01

    Disorders of human salivary glands resulting from therapeutic radiation treatment for head and neck cancers or from the autoimmune disease Sjögren syndrome (SS) frequently result in the reduction or complete loss of saliva secretion. Such irreversible dysfunction of the salivary glands is due to the impairment of acinar cells, the major glandular cells of protein, salt secretion, and fluid movement. Availability of primary epithelial cells from human salivary gland tissue is critical for studying the underlying mechanisms of these irreversible disorders. We applied 2 culture system techniques on human minor salivary gland epithelial cells (phmSG) and optimized the growth conditions to achieve the maintenance of phmSG in an acinar-like phenotype. These phmSG cells exhibited progenitor cell markers (keratin 5 and nanog) as well as acinar-specific markers-namely, α-amylase, cystatin C, TMEM16A, and NKCC1. Importantly, with an increase of the calcium concentration in the growth medium, these phmSG cells were further promoted to acinar-like cells in vitro, as indicated by an increase in AQP5 expression. In addition, these phmSG cells also demonstrated functional calcium mobilization, formation of epithelial monolayer with high transepithelial electrical resistance (TER), and polarized secretion of α-amylase secretion after β-adrenergic receptor stimulation. Taken together, suitable growth conditions have been established to isolate and support culture of acinar-like cells from the human salivary gland. These primary epithelial cells can be useful for study of molecular mechanisms involved in regulating the function of acinar cells and in the loss of salivary gland function in patients.

  16. 60-Hz electric-field effects on pineal melatonin rhythms: time course for onset and recovery

    SciTech Connect

    Wilson, B.W.; Chess, E.K.; Anderson, L.E.

    1986-01-01

    Rats exposed for 3 weeks to uniform 60-Hz electric fields of 39 kV/m (effective field strength) failed to show normal pineal gland circadian rhythms in serotonin N-acetyl transferase activity and melatonin concentrations. The time required for recovery of the melatonin rhythm after cessation of field exposure was determined to be less than 3 days. The rapid recovery suggests that the overall metabolic competence of the pineal is not permanently compromised by electric-field exposure, and that the circadian rhythm effect may be neuronally mediated.

  17. "Sebocytes' makeup": novel mechanisms and concepts in the physiology of the human sebaceous glands.

    PubMed

    Tóth, Balázs I; Oláh, Attila; Szöllosi, Attila G; Czifra, Gabriella; Bíró, Tamás

    2011-06-01

    The pilosebaceous unit of the human skin consists of the hair follicle and the sebaceous gland. Within this "mini-organ", the sebaceous gland has been neglected by the researchers of the field for several decades. Actually, it was labeled as a reminiscence of human development ("a living fossil with a past but no future"), and was thought to solely act as a producer of sebum, a lipid-enriched oily substance which protects our skin (and hence the body) against various insults. However, due to emerging research activities of the past two decades, it has now become evident that the sebaceous gland is not only a "passive" cutaneous "relic" to establish the physico-chemical barrier function of the skin against constant environmental challenges, but it rather functions as an "active" neuro-immuno-endocrine cutaneous organ. This review summarizes recent findings of sebaceous gland research by mainly focusing on newly discovered physiological functions, novel regulatory mechanisms, key events in the pathology of the gland, and future directions in both experimental and clinical dermatology.

  18. [Changes in human meibum with meibomian gland dysfunction].

    PubMed

    Hu, Xiaodan; Lyu, Huibin; Jiang, Xiaodan; Li, Xuemin

    2015-03-01

    Meibomian gland dysfunction (MGD) is a common ocular surface disease, characterized by terminal duct obstruction and (or) qualitative and quantitative changes in the glandular secretion. Meibomian lipids are a mixture consisting of various lipids, and they form the lipid layer of tear film and play important roles in preventing the evaporation and maintaining the stability of tear film. Patients with MGD may have different compositions of meibomian lipids, which could be an important indicator for diagnosis of MGD. The methods to analyze the composition of meibomian lipids mainly include chromatography and spectrum analysis. Because the pathogenic factors of MGD are still unclear, the main treatment is to relieve the symptoms. It can contribute to diagnose and treat MGD if we can find some convenient and effective methods to analyze the quality and quantity of meibomian lipids.

  19. [Changes in human meibum with meibomian gland dysfunction].

    PubMed

    Hu, Xiaodan; Lyu, Huibin; Jiang, Xiaodan; Li, Xuemin

    2015-03-01

    Meibomian gland dysfunction (MGD) is a common ocular surface disease, characterized by terminal duct obstruction and (or) qualitative and quantitative changes in the glandular secretion. Meibomian lipids are a mixture consisting of various lipids, and they form the lipid layer of tear film and play important roles in preventing the evaporation and maintaining the stability of tear film. Patients with MGD may have different compositions of meibomian lipids, which could be an important indicator for diagnosis of MGD. The methods to analyze the composition of meibomian lipids mainly include chromatography and spectrum analysis. Because the pathogenic factors of MGD are still unclear, the main treatment is to relieve the symptoms. It can contribute to diagnose and treat MGD if we can find some convenient and effective methods to analyze the quality and quantity of meibomian lipids. PMID:26268646

  20. Regulation of period 1 expression in cultured rat pineal

    NASA Technical Reports Server (NTRS)

    Fukuhara, Chiaki; Dirden, James C.; Tosini, Gianluca

    2002-01-01

    The aim of the present study was to investigate the in vitro expression of Period 1 (Per1), Period 2 (Per2) and arylalkylamine N-acetyltransferase (AA-NAT) genes in the rat pineal gland to understand the mechanism(s) regulating the expression of these genes in this organ. Pineals, when maintained in vitro for 5 days, did not show circadian rhythmicity in the expression of any of the three genes monitored. Norepinephrine (NE) induced AA-NAT and Per1, whereas its effect on Per2 was negligible. Contrary to what was observed in other systems, NE stimulation did not induce circadian expression of Per1. The effect of NE on Per1 level was dose- and receptor subtype-dependent, and both cAMP and cGMP induced Per1. Per1 was not induced by repeated NE - or forskolin - stimulation. Protein synthesis was not necessary for NE-induced Per1, but it was for reduction of Per1 following NE stimulation. Per1 transcription in pinealocytes was activated by BMAL1/CLOCK. Our results indicate that important differences are present in the regulation of these genes in the mammalian pineal. Copyright 2002 S. Karger AG, Basel.

  1. Histamine H1 receptor induces cytosolic calcium increase and aquaporin translocation in human salivary gland cells.

    PubMed

    Kim, Ji-Hyun; Park, Seong-Hae; Moon, Young Wha; Hwang, Sungmin; Kim, Donghoon; Jo, Su-Hyun; Oh, Seog Bae; Kim, Joong Soo; Jahng, Jeong Won; Lee, Jong-Ho; Lee, Sung Joong; Choi, Se-Young; Park, Kyungpyo

    2009-08-01

    One of the common side effects of antihistamine medicines is xerostomia (dry mouth). The current consensus is that antihistamine-induced xerostomia comes from an antimuscarinic effect. Although the effect of antihistamines on salivary secretion is both obvious and significant, the cellular mechanism whereby this happens is still unclear because of the lack of knowledge of histamine signaling in human salivary glands. Here, we have studied histamine receptors and the effect of antihistamines on human submandibular acinar cells. In primary cultured human submandibular gland and a HSG cell line, histamine increased the intracellular Ca(2+) concentration. The histamine-induced cytosolic free Ca(2+) concentration ([Ca(2+)](i)) increase was inhibited by histamine H1 receptor-specific antagonists, and the expression of the functional histamine H1 receptor was confirmed by reverse transcription-polymerase chain reaction. Interestingly, histamine pretreatment did not inhibit a subsequent carbachol-induced [Ca(2+)](i) rise without "heterologous desensitization." Chlorpheniramine inhibited a carbachol-induced [Ca(2+)](i) increase at a 100-fold greater concentration than histamine receptor antagonism, whereas astemizole and cetrizine showed more than 1000-fold difference, which in part explains the xerostomia-inducing potency among the antihistamines. Notably, histamine resulted in translocation of aquaporin-5 to the plasma membrane in human submandibular gland cells and green fluorescent protein-tagged aquaporin-5 expressing HSG cells. We found that histidine decarboxylase and the histamine H1 receptor are broadly distributed in submandibular gland cells, whereas choline acetyltransferase is localized only at the parasympathetic terminals. Our results suggest that human salivary gland cells express histamine H1 receptors and histamine-synthesizing enzymes, revealing the cellular mechanism of antihistamine-induced xerostomia. PMID:19443731

  2. Changes in human meibum lipid with meibomian gland dysfunction using principal component analysis.

    PubMed

    Borchman, Douglas; Yappert, Marta C; Foulks, Gary N

    2010-08-01

    Changes in the phase transition temperatures and conformation of human meibum lipid with age and meibomian gland dysfunction have been quantified but with analysis of less than 1% of the infrared spectral range. The remaining 99% of the spectral range was analyzed with principal component analysis (PCA) and confirms our previous studies and reveal further insights into changes that occur in meibum with age and disease. Infrared spectra of meibum from 41 patients diagnosed with meibomian gland dysfunction (Md) and 32 normal donors (Mn) were measured. Principal component analysis (PCA) was used to quantify the variance among the spectra and meibum protein was quantified using the infrared carbonyl and amide I and II bands. A training set of spectra was used to discriminate between Mn and Md with an accuracy of 93%. This shows that certain spectral regions (eigenvectors) contain compositional and structural information about the changes that occur with the principal component (variable), meibomian gland dysfunction. The spectral features of the major eigenvector indicate that Md contains more protein and relatively less CH(3) and cis = CH band intensity compared to Mn. The amount of protein was confirmed from relative infrared band intensities. Our study supports the idea that compositional differences result in meibum that is less fluid and more viscous with meibomian gland dysfunction so that less lipid flows out of the meibomian gland orifice as observed clinically. This study also demonstrates the power of the combination of infrared spectroscopy and PCA as a diagnostic tool that discriminates between Mn and Md.

  3. In vitro transformation of cell lines from human salivary gland tumors.

    PubMed

    Queimado, L; Lopes, C; Du, F; Martins, C; Fonseca, I; Bowcock, A M; Soares, J; Lovett, M

    1999-05-31

    Explanted cells from salivary gland tumors are particularly difficult to propagate in vitro and not efficiently immortalized by agents such as simian virus 40. Human papillomavirus 16 (HPV16) has been widely used to transform cells of epithelial origin, but its use for salivary gland cell transformation has not been described. In this study, we employed viral constructs containing the E6/E7 genes of HPV16 to infect and stably transform 9 salivary gland tumor cell cultures. Four of the tumor cell cultures were derived from benign tumors and 5 from malignant tumors. All of the original cell cultures were diploid; however, 6 contained subpopulations of cells with structural abnormalities. All 9 cell cultures were successfully transformed, and 8 were immortalized. The resulting cell lines have decreased serum requirements, exhibit a high proliferation rate, are E6/E7-positive and form colonies in soft agar. Immuno-histochemical and molecular studies confirmed that the transformed cells were indeed epithelial/myoepithelial in origin. All of the transformed cell lines had a diploid or near-diploid karyotype, and 2 contained the original translocated chromosomes in all cells. Our report represents a new application of the E6/E7 system in immortalizing salivary gland cell cultures, resulting in retention of the cellular features found in the native tissue without a general destabilization of the karyotype. These types of tissue culture resources should prove useful for positional cloning and functional studies of genes involved in salivary gland oncogenesis.

  4. Correlation of human Bub1 expression with tumor-proliferating activity in salivary gland tumors.

    PubMed

    Shigeishi, Hideo; Yoneda, Shingo; Taki, Masayuki; Nobumori, Takeshi; Ohta, Kouji; Higashikawa, Koichiro; Yasui, Wataru; Kamata, Nobuyuki

    2006-04-01

    Human Bub1 plays an important role at the spindle assembly check-point to prevent cell cycle progression following spindle damage. We examined the expression of Bub1 mRNA and protein in 21 human salivary gland tumors (7 pleomorphic adenomas, 2 warthin tumors, 5 mucoepidermoid carcinomas, 3 adenoid cystic carcinomas and 4 acinic cell carcinomas) and 3 normal submandibular glands using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) or western blotting. The mean expression levels of Bub1 mRNA and protein were higher in malignant tumors (0.12+/-0.028/1.75+/-0.53) than normal submandibular glands (0.042+/-0.014/0.19+/-0.044) and benign tumors (0.058+/-0.01/0.97+/-0.44). We found a significant association between the level of Bub1 mRNA/protein expression and clinical stage in malignant tumors (Mann-Whitney U test, p=0.019/p=0.016). We analyzed its relation with the proliferative activity monitored by the Ki-67 labeling index by immunohistochemistry as well as the expression of proliferating cell nuclear antigen (PCNA) by Western blotting. A significant correlation was found between Bub1 mRNA/protein expression and the Ki-67 labeling index in salivary gland tumors (Spearman's correlation coefficient by rank test, p=0.026/p=0.002). These results indicate that increased expression of the human Bub1 gene is closely linked to abnormal cell proliferation in malignant conditions.

  5. Regulation of melatonin secretion in the pineal organ of the domestic duck--an in vitro study.

    PubMed

    Prusik, M; Lewczuk, B; Ziółkowska, N; Przybylska-Gornowicz, B

    2015-01-01

    The aim of study was to determine the mechanisms regulating melatonin secretion in the pineal organs of 1-day-old and 9-month-old domestic ducks. The pineals were cultured in a superfusion system under different light conditions. Additionally, some explants were treated with norepinephrine. The pineal glands of 1-day-old ducks released melatonin in a well-entrained, regular rhythm during incubation under a 12 hrs light:12 hrs dark cycle and adjusted their secretory activity to a reversed 12 hrs dark:12 hrs light cycle within 2 days. In contrast, the diurnal changes in melatonin secretion from the pineals of 9-month-old ducks were largely irregular and the adaptation to a reversed cycle lasted 3 days. The pineal organs of nestling and adult ducks incubated in a continuous light or darkness secreted melatonin in a circadian rhythm. The treatment with norepinephrine during photophases of a light-dark cycle resulted in: 1) a precise adjustment of melatonin secretion rhythm to the presence of this catecholamine in the culture medium, 2) a very high amplitude of the rhythm, 3) a rapid adaptation of the pineal secretory activity to a reversed light-dark cycle. The effects of norepinephrine were similar in the pineal organs of nestlings and adults. In conclusion, melatonin secretion in the duck pineal organ is controlled by three main mechanisms: the direct photoreception, the endogenous generator and the noradrenergic transmission. The efficiency of intra-pineal, photosensitivity-based regulatory mechanism is markedly lower in adult than in nestling individuals.

  6. CRX Is a Diagnostic Marker of Retinal and Pineal Lineage Tumors

    PubMed Central

    Santagata, Sandro; Maire, Cecile L.; Idbaih, Ahmed; Geffers, Lars; Correll, Mick; Holton, Kristina; Quackenbush, John; Ligon, Keith L.

    2009-01-01

    Background CRX is a homeobox transcription factor whose expression and function is critical to maintain retinal and pineal lineage cells and their progenitors. To determine the biologic and diagnostic potential of CRX in human tumors of the retina and pineal, we examined its expression in multiple settings. Methodology/Principal Findings Using situ hybridization and immunohistochemistry we show that Crx RNA and protein expression are exquisitely lineage restricted to retinal and pineal cells during normal mouse and human development. Gene expression profiling analysis of a wide range of human cancers and cancer cell lines also supports that CRX RNA is highly lineage restricted in cancer. Immunohistochemical analysis of 22 retinoblastomas and 13 pineal parenchymal tumors demonstrated strong expression of CRX in over 95% of these tumors. Importantly, CRX was not detected in the majority of tumors considered in the differential diagnosis of pineal region tumors (n = 78). The notable exception was medulloblastoma, 40% of which exhibited CRX expression in a heterogeneous pattern readily distinguished from that seen in retino-pineal tumors. Conclusions/Significance These findings describe new potential roles for CRX in human cancers and highlight the general utility of lineage restricted transcription factors in cancer biology. They also identify CRX as a sensitive and specific clinical marker and a potential lineage dependent therapeutic target in retinoblastoma and pineoblastoma. PMID:19936203

  7. Cysteamine effects on somatostatin, catecholamines, pineal NAT and melatonin in rats

    SciTech Connect

    Webb, S.M.; Champney, T.H.; Steger, R.W.; Vaughan, M.K.; Reiter, R.J.

    1986-03-01

    The thiol reagent cysteamine was administered to adult male rats with the aim of investigating its effect on different neural and pineal components. As expected, immunoreactive somatostatin decreased in the median eminence (ME) (p less than 0.05) and gastric antrum (p less than 0.05) after cysteamine; however, no significant change was observed in the pineal IRS content after drug treatment. A decrease in norepinephrine was observed in the ME (p less than 0.001), hypothalamus (p less than 0.001) and pineal gland (p less than 0.05), together with a rise in ME (p less than 0.005) and hypothalamic dopamine (p less than 0.005) content; these results are consistent with a dopamine-beta-hydroxylase inhibiting effect of cysteamine. No effect was observed on hypothalamic serotonin and 5-hydroxyindole-acetic acid content. Pineal N-acetyltransferase (NAT) activity was significantly higher (p less than 0.05) after cysteamine than after saline, but no statistically significant effect was observed on pineal melatonin content. The mechanism involved in the NAT rise is presumably not related to the known stimulatory effect of norepinephrine, which fell after cysteamine. It is suggested that cysteamine may act at an intracellular level, inhibiting NAT degradation, an effect demonstrated in vitro and thought to be related to a thiol:disulfide exchange mechanism.

  8. Nonneoplastic pineal cysts: a clinicopathologic study of twenty-one cases.

    PubMed

    Mena, H; Armonda, R A; Ribas, J L; Ondra, S L; Rushing, E J

    1997-10-01

    Twenty-one cases of nonneoplastic pineal cyst are presented. The patients were 13 women and 8 men, with a median age of 33 years. Sixteen patients were symptomatic. Symptomatic cysts had an average size of 16.5 mm. In most cases, symptoms and signs were related to increased intracranial pressure, cerebrospinal fluid obstruction, neuroophthalmologic dysfunction, brainstem and cerebellar compression, and mental status changes. Uncommon clinical presentations in three cases were related to increased cyst size caused by hemorrhage, sudden death, and postural syncope and loss of consciousness. Imaging studies showed a uniform hypodense or hypointense, nonenhancing pineal mass with occasional peripheral calcification and associated with hydrocephalus, aqueductal compression, tectal deformity, and hemorrhage within the cavity, in decreasing order of frequency. Fourteen patients underwent open cyst resection. Histologically, the intact lesions show a unilocular or multilocular cavity, surrounded by a wall comprised of variable amounts of glial tissue, remnants of pineal gland, and an external fibrous capsule. Follow-up information showed 12 patients alive and well without recurrence between 26 and 144 postoperative months. One patient who underwent stereotactic drainage had a recurrence. One symptomatic patient who did not have surgery died suddenly of causes related to the cyst. The present study supports the role of surgical excision for the treatment of symptomatic pineal cysts to obtain adequate tissue for diagnosis and relief of symptoms. The use of histochemical and immunohistochemical studies may prove useful in the distinction of these lesions with astrocytomas and cystic pineal parenchymal tumors. PMID:9869821

  9. Photoperiod: Its importance as an impeller of pineal and seasonal reproductive rhythms

    NASA Astrophysics Data System (ADS)

    Reiter, R. J.

    1980-03-01

    A number of long day breeding rodents depend on seasonal changes in photoperiodic length to synchronize their breeding seasons with the appropriate time of the year. These relationships are particularly conspicuous in the Syrian hamster where day length is vitally important in determining periods of sexual activity and inactivity. The organ in the body whose activity is most closely attuned to the photoperiodic environment is the pineal gland. During periods of darkness the biochemical and secretory activity of the pineal is enhanced with the resultant production of antigonadotrophic principles which are strongly suppressive to reproductive physiology. In this manner, decreasing day lengths of the fall are involved with suppressing sexual capability in male and female hamsters. Throughout the winter months darkness (because of the shorter day lengths and the fact that hamsters remain underground in lightless burrows) holds the gonads in an atrophic condition and thereby prevents hamsters from breeding. As spring approaches the neuroendocrine reproductive axis becomes refractory to the inhibitory effects of darkness and the pineal gland and, as a consequence, the gonads recrudesce allowing the animals to successfully reproduce. The long days of the spring and summer serve to interrupt the refractory period so that when winter approaches shortening day lengths will again, by way of the pineal gland, induce gonadalinvolution. In this scheme both light and darkness are critically important in synchronizing the phases of the annual reproductive cycle of the hamster with the appropriate season of the year. Melatonin may be the pineal hormone which mediates the effects of darkness on reproductive physiology.

  10. Evidence for pineal involvement in timing implantation in the western spotted skunk.

    PubMed

    May, R; Mead, R A

    1986-01-01

    Experiments were designed to test the hypothesis that the pineal gland mediates the effects of changing day length and thereby synchronizes implantation within the population of spotted skunks. Intact, sham-superior cervical ganglionectomized (SCGx), SCGx, and SCGx/bilateral orbitally enucleated (B1) pregnant skunks were subjected to a natural photoperiod, and the duration of the preimplantation period was monitored. In a second set of experiments, melatonin was administered to pregnant skunks via two methods to determine whether or not this pineal hormone would mimic the effects of short day photoperiods or B1 on duration of the preimplantation period. Bilateral SCGx, which presumably denervated the pineal, had no effect on the average duration of the preimplantation period (232 +/- 57 vs. 199 +/- 6 days). However, SCGx reversed the inhibitory effect of B1 on implantation as SCGx/B1 animals had an average duration of the preimplantation period that was not significantly different from intact controls (262 +/- 46 vs. 214 +/- 11 days) but was significantly shortened in comparison to enucleated animals (262 +/- 46 vs. 316 +/- 45 days). Melatonin significantly lengthened the duration of the preimplantation period in animals receiving either daily afternoon injections of melatonin or those receiving melatonin Silastic capsule implants. These results are consistent with the hypothesis that the pineal gland synchronizes photoperiod-induced blastocyst implantation in the western spotted skunk.

  11. Stem cells in the development and differentiation of the human adrenal glands.

    PubMed

    Terada, Tadashi

    2015-01-01

    There are no studies on stem cells (SCs) and development and differentiation (DD) of the human adrenal glands. The SCs in DD of the adrenal glands were herein investigated histochemically and immunohistochemically in 18 human embryonic adrenal glands at gestational week (GW) 7-40. At 7 GW, the adrenal glands were present, and at 7 GW, numerous embryonic SCs (ESCs) are seen to create the adrenal cortex. The ESCs were composed exclusively of small cells with hyperchromatic nuclei without nucleoli. The ESCs were positive for neural cell adhesion molecule, KIT, neuron-specific enolase, platelet-derived growth factor receptor-α, synaptophysin, and MET. They were negative for other SC antigens, including chromogranin, ErbB2, and bcl-2. They were also negative for lineage antigens, including cytokeratin (CK)7, CK8, CK18, and CK19, carcinoembryonic antigen, carbohydrate antigen 19-9, epithelial membrane antigen, HepPar1, mucin core apoprotein (MUC)1, MUC2, MUC5AC, and MUC6, and cluster differentiation (CD)3, CD45, CD20, CD34, and CD31. The Ki-67 labeling index (LI) was high (Ki-67 LI = around 20%). α-Fetoprotein was positive in the ESCs and adrenal cells. The ESC was first seen in the periphery of the adrenal cortex at 7-10 GW. The ESC migrates into the inner part of the adrenal cortex. Huge islands of ESC were present near the adrenal, and they appeared to provide the ESC of the adrenal. At 16 GW, adrenal medulla appeared, and the adrenal ESCs were present in the periphery or the cortex, in the cortical parenchyma, corticomedullary junctions, and in the medulla. The adrenal essential architecture was established around 20 GW; however, there were still ESCs. At term, there are a few ESCs. These data suggest that the adrenal glands were created by ESCs.

  12. Presence of kisspeptin-like immunoreactivity in human adrenal glands and adrenal tumors.

    PubMed

    Takahashi, Kazuhiro; Shoji, Itaru; Shibasaki, Akiko; Kato, Ichiro; Hiraishi, Keisuke; Yamamoto, Hajime; Kaneko, Kiriko; Murakami, Osamu; Morimoto, Ryo; Satoh, Fumitoshi; Ito, Sadayoshi; Totsune, Kazuhito

    2010-05-01

    Kisspeptins are neuropeptides which activate the hypothalamo-pituitary gonadal axis and are considered to play important physiological roles in the reproduction. Kisspeptins have also been reported to stimulate the aldosterone secretion from the adrenal cortex. However, the expression of kisspeptins in human adrenal glands and adrenal tumors has not been clarified yet. We, therefore, studied the presence of kisspeptin-like immunoreactivity (LI) in human adrenal glands and adrenal tumors (adrenocortical adenomas, adrenocortical carcinomas, and pheochromocytomas) by radioimmunoassay and immunocytochemistry. Kisspeptin-LI was detected in all the tissues examined; normal portions of adrenal glands (3.0 +/- 2.3 pmol/g wet weight, n = 21, mean +/- SD), aldosterone-producing adenomas (4.6 +/- 3.3 pmol/g wet weight, n = 10), cortisol-producing adenomas (2.7 +/- 1.4 pmol/g wet weight, n = 14), adrenocortical carcinomas (1.7 +/- 0.2 pmol/g wet weight, n = 4), and pheochromocytomas (1.8 +/- 0.8 pmol/g wet weight, n = 6). There was no significant difference in kisspeptin-LI levels among them. Immunocytochemistry showed positive kisspeptin-immunostaining in normal adrenal glands, with stronger immunostaining found in the medulla. Furthermore, positive kisspeptin-immunostaining was found in all types of adrenal tumors examined; adrenocortical adenomas, adrenocortical carcinomas, and pheochromocytomas. The intensity of kisspeptin-immunostaining in these adrenal tumors was, however, not so strong as that in normal adrenal medulla. The present study has shown for the first time the presence of kisspeptin-LI in adrenal glands and adrenal tumors.

  13. Proteomic Analysis of Pure Human Airway Gland Mucus Reveals a Large Component of Protective Proteins

    PubMed Central

    Joo, Nam Soo; Evans, Idil Apak T.; Cho, Hyung-Ju; Park, Il-Ho; Engelhardt, John F.; Wine, Jeffrey J.

    2015-01-01

    Airway submucosal glands contribute to innate immunity and protect the lungs by secreting mucus, which is required for mucociliary clearance and which also contains antimicrobial, anti-inflammatory, anti-proteolytic and anti-oxidant proteins. We stimulated glands in tracheal trimmings from three lung donors and collected droplets of uncontaminated mucus as they formed at the gland orifices under an oil layer. We analyzed the mucus using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Analysis identified 5486 peptides and 441 proteins from across the 3 samples (269–319 proteins per subject). We focused on 269 proteins common to at least 2 0f 3 subjects, of which 102 (38%) had protective or innate immunity functions. While many of these have long been known to play such roles, for many others their cellular protective functions have only recently been appreciated in addition to their well-studied biologic functions (e.g. annexins, apolipoproteins, gelsolin, hemoglobin, histones, keratins, and lumican). A minority of the identified proteins are known to be secreted via conventional exocytosis, suggesting that glandular secretion occurs via multiple mechanisms. Two of the observed protective proteins, major vault protein and prohibitin, have not been observed in fluid from human epithelial cultures or in fluid from nasal or bronchoalveolar lavage. Further proteomic analysis of pure gland mucus may help clarify how healthy airways maintain a sterile environment. PMID:25706550

  14. Mammary gland-specific expression of biologically active human osteoprotegerin in transgenic mice.

    PubMed

    Sung, Yoon-Young; Lee, Chul-Sang

    2013-03-01

    Osteoprotegerin (OPG) is a secreted glycoprotein that regulates bone resorption by inhibiting differentiation and activation of osteoclast, thereby potentially useful for the treatment of many bone diseases associated with increased bone loss. In this study, we designed a novel cDNA expression cassette by modifying the potent and mammary gland-specific goat β-casein/hGH hybrid gene construct and examined human OPG (hOPG) cDNA expression in transgenic mice. Six transgenic mice all successfully expressed hOPG in their milk at the level of 0.06-2,000 µg/ml. An estimated molecular weight of the milk hOPG was 55 kDa in SDS-PAGE, which is the same as a naturally glycosylated monomer. This hOPG expression was highly specific to the mammary glands of transgenic mice. hOPG mRNA was not detected in any organs analyzed except mammary gland. Functional integrity of milk hOPG was evaluated by TRAP (tartrate-resistant acid phosphatase) activity assay in bone marrow cell cultures. OPG ligand (OPG-L) treatment increased TRAP activity by two fold but it was completely abolished by co-treatment with transgenic milk containing hOPG. Taken together, our novel cDNA expression cassette could direct an efficient expression of biologically active hOPG, a potential candidate pharmaceutical for bone diseases, only in the mammary gland of transgenic mice.

  15. Effectiveness of skin absorption of tincture of I in blocking radioiodine from the human thyroid gland

    SciTech Connect

    Miller, K.L.; Coen, P.E.; White, W.J.; Hurst, W.J.; Achey, B.E.; Lang, C.M.

    1989-06-01

    Topical application of tincture of iodine (I) was found to be effective in blocking the thyroid uptake of orally administered /sup 131/I in humans. Abdominal skin application of tincture of I resulted in an approximately 82% reduction in the uptake of /sup 131/I by the thyroid gland. The effectiveness varied among individuals and may have depended on the quantity applied and on the application site. In each study group, elevated levels of serum I were observed.

  16. Associations of pineal volume, chronotype and symptom severity in adults with attention deficit hyperactivity disorder and healthy controls.

    PubMed

    Bumb, Jan Malte; Mier, Daniela; Noelte, Ingo; Schredl, Michael; Kirsch, Peter; Hennig, Oliver; Liebrich, Luisa; Fenske, Sabrina; Alm, Barbara; Sauer, Carina; Leweke, Franz Markus; Sobanski, Esther

    2016-07-01

    The pineal gland, as part of the human epithalamus, is the main production site of peripheral melatonin, which promotes the modulation of sleep patterns, circadian rhythms and circadian preferences (morningness vs. eveningness). The present study analyses the pineal gland volume (PGV) and its association with circadian preferences and symptom severity in adult ADHD patients compared to healthy controls. PGV was determined manually using high-resolution 3T MRI (T1-magnetization prepared rapid gradient echo) in medication free adult ADHD patients (N=74) compared to healthy controls (N=86). Moreover, the Morningness-Eveningness Questionnaire (MEQ), the ADHD Diagnostic Checklist and the Wender-Utah Rating Scale were conducted. PGV differed between both groups (patients: 59.9±33.8mm(3); healthy controls: 71.4±27.2mm(3), P=0.04). In ADHD patients, more eveningness types were revealed (patients: 29%; healthy controls: 17%; P=0.05) and sum scores of the MEQ were lower (patients: 45.8±11.5; healthy controls 67.2±10.1; P<0.001). Multiple regression analyses indicated a positive correlation of PGV and MEQ scores in ADHD (β=0.856, P=0.003) but not in healthy controls (β=0.054, P=0.688). Patients' MEQ scores (β=-0.473, P=0.003) were negatively correlated to ADHD symptoms. The present results suggest a linkage between the PGV and circadian preference in adults with ADHD and an association of the circadian preference to symptom severity. This may facilitate the development of new chronobiological treatment approaches for the add-on treatment in ADHD. PMID:27150337

  17. Pineal Diffuse Large B-Cell Lymphoma Concomitant With Pituitary Prolactinoma: Possible Correlation Between 2 Distinguished Pathologies: A Case Report.

    PubMed

    Kim, Yeong-Jin; Kim, Hee Kyung; Yang, Deok-Hwan; Jung, Shin; Noh, Myung-Giun; Lee, Jae-Hyuk; Lee, Kyung-Hwa; Moon, Kyung-Sub

    2016-02-01

    This is the first reported case of pineal lymphoma with concomitant prolactin-producing pituitary adenoma.A 51-year-old male experienced worsening headaches accompanied by nausea, diplopia, and memory loss for 1 month. Cranial nerve examination revealed bilateral upward gaze limitation with convergence impairment, which is known as Parinaud syndrome. Magnetic resonance images revealed a mass in the pineal gland with a coexisting mass within the enlarged sella fossa. Hormone analysis revealed hyperprolactinemia. The pineal mass was removed without injuring the hypothalamus, brain stem, or any neighboring vessels. Pathology examination confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) involving the pineal gland. After further studies, the pineal lymphoma was determined to be a secondary tumor from a gastric primary tumor. The patient died 6 months after diagnosis due to systemic progression of DLBCL.Although the mechanistic link between hyperprolactinemia and lymphoma progression has not been clarified on a clinical basis, high prolactin levels may contribute to the rapid progression and therapeutic resistance of the lymphoma.

  18. Pineal Diffuse Large B-Cell Lymphoma Concomitant With Pituitary Prolactinoma: Possible Correlation Between 2 Distinguished Pathologies

    PubMed Central

    Kim, Yeong-Jin; Kim, Hee Kyung; Yang, Deok-Hwan; Jung, Shin; Noh, Myung-Giun; Lee, Jae-Hyuk; Lee, Kyung-Hwa; Moon, Kyung-Sub

    2016-01-01

    Abstract This is the first reported case of pineal lymphoma with concomitant prolactin-producing pituitary adenoma. A 51-year-old male experienced worsening headaches accompanied by nausea, diplopia, and memory loss for 1 month. Cranial nerve examination revealed bilateral upward gaze limitation with convergence impairment, which is known as Parinaud syndrome. Magnetic resonance images revealed a mass in the pineal gland with a coexisting mass within the enlarged sella fossa. Hormone analysis revealed hyperprolactinemia. The pineal mass was removed without injuring the hypothalamus, brain stem, or any neighboring vessels. Pathology examination confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) involving the pineal gland. After further studies, the pineal lymphoma was determined to be a secondary tumor from a gastric primary tumor. The patient died 6 months after diagnosis due to systemic progression of DLBCL. Although the mechanistic link between hyperprolactinemia and lymphoma progression has not been clarified on a clinical basis, high prolactin levels may contribute to the rapid progression and therapeutic resistance of the lymphoma. PMID:26937937

  19. Human mesenchymal stem cells cultured with salivary gland biopsies adopt an epithelial phenotype.

    PubMed

    Maria, Ola M; Tran, Simon D

    2011-06-01

    Sjogren's syndrome and radiotherapy for head and neck cancer result in severe xerostomia and irreversible salivary gland damage for which no effective treatment is currently available. Cell culture methods of primary human salivary gland epithelial cells (huSGs) are slow and cannot provide a sufficient number of cells. In addition, the majority of cultured huSGs are of a ductal phenotype and thus not fluid/saliva secretory cells. Some reports indicated that mesenchymal stem cells (MSCs) possessed the potential to differentiate into epithelial cells. To test this hypothesis with huSGs, a coculture system containing 2 chambers separated by a polyester membrane was used to study the capacity of human MSCs to adopt an epithelial phenotype when cocultured with human salivary gland biopsies. Results were that 20%-40% of cocultured MSCs expressed tight junction proteins [claudin-1 (CLDN-1), -2, -3, and -4; occludin; junctional adhesion molecule-A; and zonula occludens-1] as well as other epithelial markers [aquaporin-5, α-amylase (α-AMY), and E-cadherin], and generated a higher transepithelial electrical resistance. Electron microscopy demonstrated that these MSCs had comparable cellular structures to huSGs, such as tight junction structures and numerous secretory granules. Quantitative real time (RT)-polymerase chain reaction revealed an upregulation of several salivary genes (aquaporin-5, AMY, and CLDN-2). Moreover, the amounts of α-AMY detected in cocultured MSCs were comparable to those detected in huSGs control cultures. These data suggest that cocultured MSCs can demonstrate a temporary change into a salivary gland acinar phenotype.

  20. [Influence of pineal hormone melatonin on behavioral disturbances and neurological status of animals after hemorrhagic stroke].

    PubMed

    Arushanian, E B; Naumov, S S

    2011-01-01

    Experimental hemorrhagic stroke causes behavior and locomotor activity with memory impairment and neurological disturbances in rats. These shifts are weaker in the evening hours than after morning testing. The repeated administration of the pineal gland hormone melatonin (melaxen) during one week significantly decreases behavior and neurological deficits as well as pathomorphological signs in the lesion focus. The normalizing effect of the hormone is more distinct in the evening.

  1. Acinar autolysis and mucous extravasation in human sublingual glands: a microscopic postmortem study

    PubMed Central

    AZEVEDO-ALANIS, Luciana Reis; TOLENTINO, Elen de Souza; de ASSIS, Gerson Francisco; CESTARI, Tânia Mary; LARA, Vanessa Soares; DAMANTE, José Humberto

    2015-01-01

    Although some morphological investigations on aged human sublingual glands (HSG) found eventual phenomena identified as autolysis and mucous extravasation, the exact meaning of these findings has not been elucidated. Objective The aim of this work is to investigate whether acinar autolysis and mucous extravasation are related to the aging process in human sublingual glands. We also speculate if autolytic changes may assist forensic pathologists in determining time of death. Material and Methods 186 cadavers’ glands were allocated to age groups: I (0–30 years); II (31–60), and III (61–90). Time and mode of death were also recorded. Acinar autolysis and mucous extravasation were classified as present or absent. Ultrastructural analysis was performed using transmission electron microscopy (TEM). Data were compared using Mann-Whitney U, Spearman’s correlation coefficient, Kruskal-Wallis, and Dunn tests (p<0.05). Results There was correlation between age and acinar autolysis (r=0.38; p=0.0001). However, there was no correlation between autolysis and time of death. No differences were observed between genders. TEM showed mucous and serous cells presenting nuclear and membrane alterations and mucous cells were more susceptible to autolysis. Conclusion Acinar autolysis occurred in all age groups and increased with age while mucous extravasation was rarely found. Both findings are independent. Autolysis degrees in HSG could not be used to determine time of death. PMID:26537715

  2. Examination of Duct Physiology in the Human Mammary Gland

    PubMed Central

    Mills, Dixie; Gomberawalla, Ameer; Gordon, Eva J.; Tondre, Julie; Nejad, Mitra; Nguyen, Tinh; Pogoda, Janice M.; Rao, Jianyu; Chatterton, Robert; Henning, Susanne; Love, Susan M.

    2016-01-01

    Background The human breast comprise several ductal systems, or lobes, which contain a small amount of fluid containing cells, hormones, proteins and metabolites. The complex physiology of these ducts is likely a contributing factor to the development of breast cancer, especially given that the vast majority of breast cancers begin in a single lobular unit. Methods We examined the levels of total protein, progesterone, estradiol, estrone sulfate, dehydroepiandrosterone sulfate, and macrophages in ductal fluid samples obtained from 3 ducts each in 78 women, sampled twice over a 6 month period. Samples were processed for both cytological and molecular analysis. Intraclass correlation coefficients and mixed models were utilized to identify significant data. Results We found that the levels of these ductal fluid components were generally uncorrelated among ducts within a single breast and over time, suggesting that each lobe within the breast has a distinct physiology. However, we also found that estradiol was more correlated in women who were nulliparous or produced nipple aspirate fluid. Conclusions Our results provide evidence that the microenvironment of any given lobular unit is unique to that individual unit, findings that may provide clues about the initiation and development of ductal carcinomas. PMID:27073976

  3. An immunohistochemical study of Na+/I- symporter in human thyroid tissues and salivary gland tissues.

    PubMed

    Jhiang, S M; Cho, J Y; Ryu, K Y; DeYoung, B R; Smanik, P A; McGaughy, V R; Fischer, A H; Mazzaferri, E L

    1998-10-01

    The human Na+/I- symporter (hNIS) is the plasma membrane protein that mediates active iodide uptake into several tissues, such as the thyroid and salivary glands. To study the distribution and cellular localization of the hNIS protein, we have generated a polyclonal antibody that could detect the hNIS protein by immunohistochemical staining on tissue sections. In normal thyroids, hNIS expression is heterogeneous, and it is only detected in sporadic thyrocytes of a given follicle. The hNIS protein was not detected in thyroid carcinomas, yet it was detected in the majority of thyrocytes in Graves' thyroids. In salivary glands, hNIS protein was not detected in acinar cells, but it was detected in ductal cells. The hNIS proteins are clustered in the basal and lateral membranes in cells stained positive for hNIS.

  4. Immunohistochemical expression of tenascin in normal human salivary glands and in pleomorphic adenomas.

    PubMed

    Sunardhi-Widyaputra, S; Van Damme, B

    1993-03-01

    The presence of the extracellular matrix glycoprotein tenascin was studied immunohistochemically in normal human salivary glands and in pleomorphic adenomas. Its expression was compared to that of fibronectin, and type IV collagen. In the normal salivary gland, tenascin was found with interruptions in periductal tissues, and continuously in blood vessels, fat cells and around nerve bundles. In pleomorphic adenoma, tenascin was detected surrounding the clusters of epithelioid cells, in areas with a myxoid and a chondroid matrix, and around some myoepithelial cells as a halo. As compared to fibronectin, there is a similar location of tenascin and fibronectin around tumor cell clusters but not in myxoid and chondroid matrices. Fibronectin was found around the cells in chondroid matrix. In conclusion, tenascin is not only found in malignant tumors but also in benign tumors such as pleomorphic adenoma. The presence of tenascin as a halo around myoepithelial cells suggests a role of these cells in development of myxoid and chondroid matrices.

  5. Pineal calcification and its relationship to the fatigue of multiple sclerosis.

    PubMed

    Sandyk, R; Awerbuch, G I

    1994-01-01

    Fatigue is one of the most common clinical features of multiple sclerosis (MS) and is a frequent cause of disability. The pathogenesis of fatigue remains obscure. It may result from impaired propagation of action potentials in areas of demyelination. Other contributors may be mental depression, immobility, and physical disability. The fatigue of MS may be relieved by diverse pharmacological drugs such as amantadine and pemoline, but the mechanisms by which these agents act to ameliorate fatigue are unknown. Attention has been focused recently on the relationship between MS and the pineal gland and evidence has been presented to implicate the pineal gland and melatonin in the pathogenesis of the disease. To investigate this relationship further, we studied in 47 MS patients (mean age: 41.6 +/- 9.9 yrs; mean duration of illness: 13.6 +/- 12.6 yrs) the association between fatigue and incidence of pineal calcification (PC) on CT scan, which is thought to reflect past secretory activity of the gland. For comparison, we also evaluated the incidence of choroid plexus calcification (CPC) in these patients. The sample included 20 patients who experienced ongoing, debilitating fatigue during the course of the disease. 27 patients who did not complain of fatigue served as controls. The two groups were not distinguishable with respect to age, sex, age of onset, chronicity, course (relapsing-remitting vs. chronic progressive), and severity of the disease (ambulatory vs. immobile), as well as the incidence of affective illness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7928120

  6. Development of peptide-containing nerves in the human fetal prostate gland.

    PubMed Central

    Jen, P Y; Dixon, J S

    1995-01-01

    Immunohistochemical methods were used to study the developing peptidergic innervation of the human fetal prostate gland in a series of specimens ranging in gestational age from 13 to 30 wk. The overall innervation of each specimen was visualised using protein gene product 9.5 (PGP), a general nerve marker. The onset and development of specific neuropeptide-containing subpopulations were investigated using antisera to neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), bombesin (BOM), somatostatin (SOM), leu-enkephalin (l-ENK) and met-enkephalin (m-ENK). In addition the occurrence and distribution of presumptive noradrenergic nerves was studied using antisera to dopamine-beta-hydroxylase (D beta H) and tyrosine hydroxylase (TH). At 13 wk numerous branching PGP-immunoreactive (-IR) nerves were observed in the capsule of the developing prostate gland and surrounding the preprostatic urethra but the remainder of the gland was devoid of nerves. The majority of nerves in the capsule contained D beta H and TH and were presumed to be noradrenergic in type while other nerves (in decreasing numbers) contained NPY, l-ENK, SP and CGRP. Nerves associated with the preprostatic urethra did not contain any of the neuropeptides under investigation. At 17 wk the density of nerves in the capsule had increased and occasional m-ENK-, VIP- and BOM-IR nerve fibres were also observed. In addition PGP, D beta H-, TH-, NPY- and l-ENK-IR nerves occurred in association with smooth muscle bundles which at 17 wk were present in the outer part of the gland. Occasional PGP-IR nerves were also present at the base of the epithelium forming some of the prostatic glands. At 23 wk some of the subepithelial nerves showed immunoreactivity for NPY, VIP or l-ENK. At 26 wk smooth muscle bundles occurred throughout the gland and were richly innervated by PGP, D beta H and TH-IR nerves while a less dense plexus was formed by NPY- and l

  7. Bone morphogenetic protein-6 is a marker of serous acinar cell differentiation in normal and neoplastic human salivary gland.

    PubMed

    Heikinheimo, K A; Laine, M A; Ritvos, O V; Voutilainen, R J; Hogan, B L; Leivo, I V; Heikinheimo, A K

    1999-11-15

    Bone morphogenetic protein (BMP-6, also known as vegetal-pale-gene-related and decaplentaplegic-vegetal-related) is a member of the transforming growth factor-beta superfamily of multifunctional signaling molecules. BMP-6 appears to play various biological roles in developing tissues, including regulation of epithelial differentiation. To study the possible involvement of BMP-6 in normal and neoplastic human salivary glands, we compared its mRNA and protein expression in 4 fetal and 15 adult salivary glands and in 22 benign and 32 malignant salivary gland tumors. In situ hybridization and Northern blot analysis indicated that BMP-6 transcripts are expressed at low levels in acinar cells of adult submandibular glands but not in ductal or stromal cells. BMP-6 was immunolocated specifically in serous acini of parotid and submandibular glands. None was found in primitive fetal acini or any other types of cell in adult salivary glands, including mucous acini and epithelial cells of intercalated, striated, and excretory ducts. All 16 cases of acinic cell carcinoma consistently exhibited cytoplasmic BMP-6 staining in the acinar tumor cells. Other cell types in these tumors, including intercalated duct-like cells, clear, vacuolated cells, and nonspecific glandular cells, exhibited no cytoplasmic BMP-6 staining. Other benign and malignant salivary gland tumors lacked BMP-6 immunoreactivity, except in areas of squamous differentiation. The results indicate that in salivary glands, BMP-6 expression is uniquely associated with acinar cell differentiation and suggest that BMP-6 may play a role in salivary gland function. More importantly, our experience of differential diagnostic problems related to salivary gland tumors suggests that the demonstration of consistent and specific BMP-6 immunoreactivity in acinic cell carcinoma is likely to be of clinical value.

  8. Human T-Cell Clones from Autoimmune Thyroid Glands: Specific Recognition of Autologous Thyroid Cells

    NASA Astrophysics Data System (ADS)

    Londei, Marco; Bottazzo, G. Franco; Feldmann, Marc

    1985-04-01

    The thyroid glands of patients with autoimmune diseases such as Graves' disease and certain forms of goiter contain infiltrating activated T lymphocytes and, unlike cells of normal glands, the epithelial follicular cells strongly express histocompatability antigens of the HLA-DR type. In a study of such autoimmune disorders, the infiltrating T cells from the thyroid glands of two patients with Graves' disease were cloned in mitogen-free interleukin-2 (T-cell growth factor). The clones were expanded and their specificity was tested. Three types of clones were found. One group, of T4 phenotype, specifically recognized autologous thyroid cells. Another, also of T4 phenotype, recognized autologous thyroid or blood cells and thus responded positively in the autologous mixed lymphocyte reaction. Other clones derived from cells that were activated in vivo were of no known specificity. These clones provide a model of a human autoimmune disease and their analysis should clarify mechanisms of pathogenesis and provide clues to abrogating these undesirable immune responses.

  9. The use of human sweat gland-derived stem cells for enhancing vascularization during dermal regeneration.

    PubMed

    Danner, Sandra; Kremer, Mathias; Petschnik, Anna Emilia; Nagel, Sabine; Zhang, Ziyang; Hopfner, Ursula; Reckhenrich, Ann K; Weber, Caroline; Schenck, Thilo L; Becker, Tim; Kruse, Charli; Machens, Hans-Günther; Egaña, José T

    2012-06-01

    Vascularization is a key process in tissue engineering and regeneration and represents one of the most important issues in the field of regenerative medicine. Thus, several strategies to improve vascularization are currently under clinical evaluation. In this study, stem cells derived from human sweat glands were isolated, characterized, seeded in collagen scaffolds, and engrafted in a mouse full skin defect model for dermal regeneration. Results showed that these cells exhibit high proliferation rates and express stem cell and differentiation markers. Moreover, cells responded to angiogenic environments by increasing their migration (P<0.001) and proliferation (P<0.05) capacity and forming capillary-like structures. After seeding in the scaffolds, cells distributed homogeneously, interacting directly with the scaffold, and released bioactive molecules involved in angiogenesis, immune response, and tissue remodeling. In vivo, scaffolds containing cells were used to induce dermal regeneration. Here we have found that the presence of the cells significantly improved vascularization (P<0.001). As autologous sweat gland-derived stem cells are easy to obtain, exhibit a good proliferation capacity, and improve vascularization during dermal regeneration, we suggest that the combined use of sweat gland-derived stem cells and scaffolds for dermal regeneration might improve dermal regeneration in future clinical settings.

  10. Endocrine glands

    MedlinePlus

    The endocrine system is primarily composed of glands that produce chemical messengers called hormones. Glands of the endocrine system include the pituitary gland, the thyroid gland, the parathyroid glands, the thymus, ...

  11. Comparative stereological studies on zonation and cellular composition of adrenal glands of normal and anencephalic human fetuses. II. Cellular composition of the gland.

    PubMed

    Bocian-Sobkowska, J; Malendowicz, L K; Woźniak, W

    1997-04-01

    In our previous paper (Bocian-Sobkowska et al., 1997) we demonstrated a striking difference in development of zonation in adrenals of normal and anencephalic human fetuses. The purpose of the present study was to characterize, by means of stereology, the cellular composition of developing adrenals in the same case. Studies were performed on 11 pairs of adrenal glands from normal fetuses and 10 from anencephalic fetuses. In the studied period of development (24 to 39 weeks of intra-uterine life) the average volume of cells in normal glands increased as follows: zona glomerulosa (ZG) from 355 to 870 microns3; zona fasciculata (ZF) from 779 to 1200 microns3; fetal zone (FZ) from 2004 to 2380 microns3: and medulla (M) from 600 to 970 microns3. In anencephalic fetuses, the appropriate values were: ZG-380-680 microns3; ZF-460-680 microns3; FZ-1820-1680 microns3; and M-870-1400 microns3. At the end of the studied period the number of ZG cells in normal fetuses was two fold higher than in anencephalics, ZF cells-6-fold and in FZ-5-fold higher, while in the M the number of cells was nearly equal in both groups. During the whole investigated period of intra-uterine development the total number of adrenocortical cells in normal glands increased ca 2.5-fold, while in anencephalic glands only ca 0.5-fold, reaching at the end ca 40% of normal value. In both normal and anencephalic adrenals the number of ZG and M cells was highly correlated with ZG/M cell ratio, being slightly higher in normal glands. No such relation was demonstrated for cells of the remaining adrenocortical zones. PMID:9151128

  12. Suppression of pineal melatonin in Peromyscus leucopus by different monochromatic wavelengths of visible and near-ultraviolet light (UV-A).

    PubMed

    Benshoff, H M; Brainard, G C; Rollag, M D; Lynch, G R

    1987-09-15

    The purpose of this study was to examine the effects of monochromatic visible and near-ultraviolet radiation (UV-A) on pineal melatonin suppression in the white-footed mouse, Peromyscus leucopus. To this end, mice were entrained to a daily cycle of 8 h of light and 16 h of darkness. During the night when pineal melatonin contents were high, mice were individually exposed for 5 min to specific wavelengths of monochromatic light (10 nm half-peak bandwidths). Control animals received the same handling conditions but no experimental exposure. Pineal glands were collected from animals 18 min after the 5 min experimental exposure and were later assayed for melatonin content. In groups of animals exposed to equal photon densities (2.64 X 10(15) photons/cm2) of either 320, 340, 360, 500, or 560 nm, mean pineal melatonin content was significantly suppressed as compared to the unexposed control animals. The 640 nm wavelength (red) at the same photon density did not suppress pineal melatonin. These experiments are the first to demonstrate light-induced suppression of pineal melatonin in Peromyscus leucopus. In addition, these data reveal a novel finding: the suppression of pineal melatonin content by ultraviolet wavelengths as low as 320 and 340 nm.

  13. Pineal oscillator functioning in the chicken--effect of photoperiod and melatonin.

    PubMed

    Turkowska, Elzbieta; Majewski, Pawel M; Rai, Seema; Skwarlo-Sonta, Krystyna

    2014-02-01

    The avian pineal gland, apart from the hypothalamic master clock (suprachiasmatic nuclei, SCN) and retina, functions as an independent circadian oscillator, receiving external photic cues that it translates into the rhythmical synthesis of melatonin, a biochemical signal of darkness. Functional similarity to the mammalian SCN makes the avian pineal gland a convenient model for studies on biological clock mechanisms in general. Pineal melatonin is produced not only in a light-dependent manner but also remains under the control of the endogenous oscillator, while the possible involvement of melatonin in maintaining cyclic expression of the avian clock genes remains to be elucidated. The aim of the present study was to characterize the diurnal profiles of main clock genes transcription in the pineal glands of chickens exposed to continuous light (LL) and supplemented with exogenous melatonin. We hypothesized that rearing chickens from the day of hatch under LL conditions would evoke a functional pinealectomy, influencing, in turn, pineal clock function. To verify this hypothesis, we examined the diurnal transcriptional profiles of selected clock genes as well as the essential parameters of pineal gland function: transcription of the genes encoding arylalkylamine N-acetyltransferase (Aanat), a key enzyme in melatonin biosynthesis, and the melatonin receptor (Mel1c), along with the blood melatonin level. Chickens hatched in summer or winter were maintained under LD 16:8 and 8:16, corresponding to the respective photoperiods, as the seasonal control groups. Another set of chickens was kept in parallel under LL conditions and some were supplemented with melatonin to check the ability of exogenous hormone to antagonize the effects evoked by continuous light. Twelve-day-old chickens were sacrificed every 3 h over a 24-h period and the mRNAs of selected clock genes, Bmal1, Cry1, Per3, E4bp4, together with those of Aanat and Mel1c, were quantified in the isolated pineal

  14. Melatonin and human puberty: current perspectives.

    PubMed

    Cavallo, A

    1993-10-01

    Many studies of melatonin in human puberty are difficult to interpret in light of methodological considerations such as the use of single blood samples collected either during the day or at night; a small number of observations; the failure to include the temporal characteristics of melatonin secretion; the definition of puberty by the use of broad clinical features without use of hormonal markers of puberty; the lack of control for the actual duration and intensity of light exposure during the days preceding the study; and the cross sectional nature of most studies. The few studies that have examined the plasma melatonin rhythm in humans by multiple blood sampling overnight or over 24 hr suggest that normal pubertal development (as well as normal ovarian function) are not linked to alterations in the plasma melatonin profile. There is, however, some evidence to suggest that disorders of the hypothalamic-pituitary-gonadal axis (delayed puberty, precocious puberty, hypothalamic amenorrhea) may be linked to altered plasma melatonin profile, at least in some cases. These findings, taken together with strong evidence for the role of the pineal gland in the reproductive function of other vertebrate species, render unlikely the inference that the pineal gland has no role in the development and function of the human reproductive axis. Thus, one may speculate that a pineal-puberty relation does exist in humans and that the research techniques applied to date have been inadequate to uncover this relation.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Multielemental analysis of human thyroid glands using particle induced X-ray emission (PIXE)

    NASA Astrophysics Data System (ADS)

    Maeda, K.; Yokode, Y.; Sasa, Y.; Kusuyama, H.; Uda, M.

    1987-03-01

    PIXE spectroscopy has been applied to the analysis of human thyroid glands. Nontumor thyroid tissues taken from different patients showed almost the same composition which fell into the range of the data for normal thyroids given in the literature. On the other hand, a deficiency of iodine and iron was observed in all of the malignant and benign tumor tissues examined here. In some injured tissues considerable deviations of K and Ca from normal concentration levels were also recognized. This work demonstrates an important advantage of PIXE to analyze fugacious elements together with other elements simultaneously.

  16. Atypical Teratomas of the Pineal

    PubMed Central

    Lewis, I.; Baxter, D. W.; Stratford, J. G.

    1963-01-01

    Atypical teratomas of the pineal were studied pathologically and clinically, and five illustrative cases are described. The results of three postmortem examinations are available, while two of the patients are living, one leading a normal life. Pathological verification revealed that two had suprasellar “ectopic” pinealomas. One neoplasm was located in the pineal (collicular) region. The histology of the tumours was identical, consisting of small cells resembling lymphocytes and large cells with prominent nucleoli and mitoses. This feature plus the midline location led to adoption of the term “atypical teratoma”. Patients with collicular pinealomas presented with headache, vomiting, papilledema, Parinaud's syndrome and, rarely, nystagmus retractorius. Diabetes insipidus, visual difficulty and hypopituitarism were characteristic features in those with suprasellar neoplasms. Treatment of collicular pinealoma has consisted of the use of a palliative shunt followed by a course of radiation. Chiasmal decompression and radiation have produced favourable results in patients with suprasellar pinealoma. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12 PMID:20327617

  17. /sup 3/H-retinol derived photopigment in chick pineal membranes

    SciTech Connect

    Wallingford, J.; Zatz, M.

    1986-05-01

    Pineal glands display a day-night rhythm in the synthesis and secretion of melatonin. Dispersed chick pinealocytes retain their ability to respond to light in vitro for at least a week. Pinealocytes incubated overnight with /sup 3/H-retinol in the dark incorporate radioactivity predominantly into retinyl esters. To identify the chick pineal photopigment, SDS-PAGE was performed on radiolabelled preparations of pinealocytes and (intraocularly injected) rat retina. When intact cells or membrane preparations of cultured cells were incubated with NaCNBH/sub 3/, in the dark, a single radioactive peak with an apparent molecular weight of 32,000 daltons was observed. Rat retina preparations revealed a major peak at approximately 40,000 daltons. Protease inhibitors were present in the workup, and radioactivity corresponding to the smaller peak from pineal was not observed in retina. There was no radioactive peak when NaCNBH/sub 3/ was omitted. When samples were boiled in SDS the radioactivity shifted to the origin. These data suggest a protein in pinealocyte membranes which binds retinoid via a Schiff's base. Exposure to light of deoxycholate solubilized pineal membranes reduced the radioactivity associated with the protein. These findings raise the possibility that this protein is the pinealocyte's photopigment. Photopigments smaller than those observed in mammals have been reported in invertebrates.

  18. Precocious puberty associated with a pineal cyst: is it disinhibition of the hypothalamic-pituitary axis?

    PubMed

    Dickerman, Rob D; Stevens, Qualls E; Steide, Jean-Alex; Schneider, Steven J

    2004-06-01

    Accelerated development of secondary sexual characteristics or sexual precocity is a well-known entity. Most authors recognize two groups of patients, those described as having central precocious puberty (CPP) and those with precocious pseudopuberty. CPP results from premature activation of the hypothalamic-pituitary-gonadal axis and pseudopuberty is caused by lesions that secrete gonadotropin-like substances or hormones. The onset of CPP is usually before age 8 in females and age 9 in males; however, there is contention that the age of onset is much earlier and also differs depending on the patients' race. Previously reported causes of CPP include intracranial neoplasm, infection, trauma, hydrocephalus and Angelman's syndrome. Pineal cysts are usually asymptomatic incidental findings, but have been associated with CPP. We present an interesting case of a patient with CPP and an associated pineal cyst. We review the literature on the pathogenesis of CPP and associated pineal cyst, the neuroendocrine relationship between the pineal gland and puberty and the neurosurgical role in these cases.

  19. Pineal physiology in microgravity - Relation to rat gonadal function aboard Cosmos 1887

    NASA Technical Reports Server (NTRS)

    Holley, Daniel C.; Markley, Carol L.; Soliman, Magdi R. I.; Kaddis, Farida; Krasnov, Igor'

    1991-01-01

    Results are reported from an analysis of pineal glands obtained for five male rats flown aboard an orbiting satellite for their melatonin, serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIA), and calcium content. Plasma 5-HT and 5-HIAA were measured. These parameters were compared to indicators of gonadal function: plasma testosterone concentration and spermatogonia development. Plasma melotonin was found to be low at the time of euthanasia and was not different among the experimental groups. Pineal calcium of flight animals was not different from ground controls. Pineal 5-HT and 5-HIAA in the flight group were significantly higher than those in ground controls. These findings suggest a possible increase in pineal 5-HT turnover in flight animals which may result in increased melatonin secretion. It is argued that the alteration of pinal 5-HT turnover and its expected effects on melatonin secretion may partially explain the lower plasma testosterone levels and 4-11 percent fewer spermatogonia cells observed in flight animals.

  20. Tetrodotoxin administration in the suprachiasmatic nucleus prevents NMDA-induced reductions in pineal melatonin without influencing Per1 and Per2 mRNA levels.

    PubMed

    Paul, Ketema N; Gamble, Karen L; Fukuhara, Chiaki; Novak, Colleen M; Tosini, Gianluca; Albers, H Elliott

    2004-05-01

    The suprachiasmatic nucleus (SCN) of the anterior hypothalamus contains a light-entrainable circadian pacemaker. Neurons in the SCN are part of a circuit that conveys light information from retinal efferents to the pineal gland. Light presented during the night acutely increases mRNA levels of the circadian clock genes Per1 and Per2 in the SCN, and acutely suppresses melatonin levels in the pineal gland. The present study investigated whether the ability of light to increase Per1 and Per2 mRNA levels and suppress pineal melatonin levels requires sodium-dependent action potentials in the SCN. Per1 and Per2 mRNA levels in the SCN and pineal melatonin levels were measured in Syrian hamsters injected with tetrodotoxin (TTX) prior to light exposure or injection of N-methyl-D-aspartate (NMDA). TTX inhibited the ability of light to increase Per1 and Per2 mRNA levels and suppress pineal melatonin levels. TTX did not, however, influence the ability of NMDA to increase Per1 and Per2 mRNA levels, though it did inhibit the ability of NMDA to suppress pineal melatonin levels. These results demonstrate that action potentials in the SCN are not necessary for NMDA receptor activation to increase Per1 and Per2 mRNA levels, but are necessary for NMDA receptor activation to decrease pineal melatonin levels. Taken together, these data support the hypothesis that the mechanism through which light information is conveyed to the pacemaker in the SCN is separate from and independent of the mechanism through which light information is conveyed to the SCN cells whose efferents suppress pineal melatonin levels.

  1. Brain and pineal 7α-hydroxypregnenolone stimulating locomotor activity: identification, mode of action and regulation of biosynthesis.

    PubMed

    Tsutsui, Kazuyoshi; Haraguchi, Shogo; Fukada, Yoshitaka; Vaudry, Hubert

    2013-08-01

    Biologically active steroids synthesized in the central and peripheral nervous systems are termed neurosteroids. However, the biosynthetic pathways leading to the formation of neurosteroids are still incompletely elucidated. 7α-Hydroxypregnenolone, a novel bioactive neurosteroid stimulating locomotor activity, has been recently identified in the brain of newts and quail. Subsequently, the mode of action and regulation of biosynthesis of 7α-hydroxypregnenolone have been determined. Moreover, recent studies on birds have demonstrated that the pineal gland, an endocrine organ located close to the brain, is an important site of production of neurosteroids de novo from cholesterol. 7α-Hydroxypregnenolone is a major pineal neurosteroid that stimulates locomotor activity in juvenile chickens, connecting light-induced gene expression with locomotion. This review summarizes the advances in our understanding of the identification, mode of action and regulation of biosynthesis of brain and pineal 7α-hydroxypregnenolone, a potent stimulator of locomotor activity.

  2. Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium.

    PubMed

    Abe, Ayumi; Takano, Kenichi; Kojima, Takashi; Nomura, Kazuaki; Kakuki, Takuya; Kaneko, Yakuto; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo

    2016-06-01

    Tight junctions (TJs) are necessary for salivary gland function and may serve as indicators of salivary gland epithelial dysfunction. IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition which disrupts the TJ associated epithelial barrier. The salivary glands are one of the most frequently involved organs in IgG4-RD, however, changes of the TJ associated epithelial barrier in salivary gland duct epithelium is poorly understood. Here, we investigated the regulation and function of TJs in human submandibular gland ductal epithelial cells (HSDECs) in normal and IgG4-RD. We examined submandibular gland (SMG) tissue from eight control individuals and 22 patients with IgG4-RD and established an HSDEC culture system. Immunohistochemistry, immunocytochemistry, western blotting, and measurement of transepithelial electrical resistance (TER) were performed. Claudin-4, claudin-7, occludin, and JAM-A were expressed at the apical side of the duct epithelium in submandibular gland (SMG) tissue and at the cell borders in HSDECs of normal and IgG4-RD. The expression and distribution of TJs in SMG tissue were not different in control individuals and patients with IgG4-RD in vivo and in vitro. Although interferon-gamma (IFNγ) generally disrupts the integrity and function of TJs, as manifested by decreased epithelial barrier function, IFNγ markedly increased the epithelial barrier function of HSDECs via upregulation of claudin-7 expression in HSDECs from patients with IgG4-RD. This is the first report showing an IFNγ-dependent increase in epithelial barrier function in the salivary gland duct epithelium. Our results provide insights into the functional significance of TJs in salivary gland duct epithelium in physiological and pathological conditions, including IgG4-RD.

  3. Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium.

    PubMed

    Abe, Ayumi; Takano, Kenichi; Kojima, Takashi; Nomura, Kazuaki; Kakuki, Takuya; Kaneko, Yakuto; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo

    2016-06-01

    Tight junctions (TJs) are necessary for salivary gland function and may serve as indicators of salivary gland epithelial dysfunction. IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition which disrupts the TJ associated epithelial barrier. The salivary glands are one of the most frequently involved organs in IgG4-RD, however, changes of the TJ associated epithelial barrier in salivary gland duct epithelium is poorly understood. Here, we investigated the regulation and function of TJs in human submandibular gland ductal epithelial cells (HSDECs) in normal and IgG4-RD. We examined submandibular gland (SMG) tissue from eight control individuals and 22 patients with IgG4-RD and established an HSDEC culture system. Immunohistochemistry, immunocytochemistry, western blotting, and measurement of transepithelial electrical resistance (TER) were performed. Claudin-4, claudin-7, occludin, and JAM-A were expressed at the apical side of the duct epithelium in submandibular gland (SMG) tissue and at the cell borders in HSDECs of normal and IgG4-RD. The expression and distribution of TJs in SMG tissue were not different in control individuals and patients with IgG4-RD in vivo and in vitro. Although interferon-gamma (IFNγ) generally disrupts the integrity and function of TJs, as manifested by decreased epithelial barrier function, IFNγ markedly increased the epithelial barrier function of HSDECs via upregulation of claudin-7 expression in HSDECs from patients with IgG4-RD. This is the first report showing an IFNγ-dependent increase in epithelial barrier function in the salivary gland duct epithelium. Our results provide insights into the functional significance of TJs in salivary gland duct epithelium in physiological and pathological conditions, including IgG4-RD. PMID:26956365

  4. Adrenergic activation of melatonin secretion in ovine pineal explants in short-term superfusion culture occurs via protein synthesis independent and dependent phenomena.

    PubMed

    Lewczuk, Bogdan; Ziółkowska, Natalia; Prusik, Magdalena; Przybylska-Gornowicz, Barbara

    2014-01-01

    The ovine pineal is generally considered as an interesting model for the study on adrenergic regulation of melatonin secretion due to some functional similarities with this gland in the human. The present investigations, performed in the superfusion culture of pineal explants, demonstrated that the norepinephrine-induced elevation of melatonin secretion in ovine pinealocytes comprised of two subsequent periods: a rapid increase phase and a slow increase phase. The first one included the quick rise in release of N-acetylserotonin and melatonin, occurring parallel to elevation of NE concentration in the medium surrounding explants. This rapid increase phase was not affected by inhibition of translation. The second, slow increase phase began after NE level had reached the maximum concentration in the culture medium and lasted about two hours. It was completely abolished by the treatment with translation inhibitors. The obtained results showed for the first time that the regulation of N-acetylserotonin synthesis in pinealocytes of some species like the sheep involves the on/off mechanism, which is completely independent of protein synthesis and works very fast. They provided strong evidence pointing to the need of revision of the current opinion that arylalkylamines N-acetyltransferase activity in pinealocytes is controlled exclusively by changes in enzyme abundance.

  5. Adrenergic Activation of Melatonin Secretion in Ovine Pineal Explants in Short-Term Superfusion Culture Occurs via Protein Synthesis Independent and Dependent Phenomena

    PubMed Central

    2014-01-01

    The ovine pineal is generally considered as an interesting model for the study on adrenergic regulation of melatonin secretion due to some functional similarities with this gland in the human. The present investigations, performed in the superfusion culture of pineal explants, demonstrated that the norepinephrine-induced elevation of melatonin secretion in ovine pinealocytes comprised of two subsequent periods: a rapid increase phase and a slow increase phase. The first one included the quick rise in release of N-acetylserotonin and melatonin, occurring parallel to elevation of NE concentration in the medium surrounding explants. This rapid increase phase was not affected by inhibition of translation. The second, slow increase phase began after NE level had reached the maximum concentration in the culture medium and lasted about two hours. It was completely abolished by the treatment with translation inhibitors. The obtained results showed for the first time that the regulation of N-acetylserotonin synthesis in pinealocytes of some species like the sheep involves the on/off mechanism, which is completely independent of protein synthesis and works very fast. They provided strong evidence pointing to the need of revision of the current opinion that arylalkylamines N-acetyltransferase activity in pinealocytes is controlled exclusively by changes in enzyme abundance. PMID:25133175

  6. Dynamic analysis for mental sweating of a group of eccrin sweat glands on a human fingertip by optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Ohmi, Masato; Tanigawa, Motomu; Wada, Yuki; Haruna, Masamitsu

    2011-05-01

    OCT is highly potential for in vivo observation of human sweating dynamics which affects activity of the sympathetic nerve. In this paper, we demonstrate dynamic OCT analysis of mental sweating of a group of eccrin sweat glands. The sweating dynamics is tracked simultaneously for nineteen sweat glands by time-sequential piled-up en-face OCT images with the frame spacing of 3.3 sec. Strong non-uniformity is observed in mental sweating where the amount of excess sweat is different for each sweat gland although the sweat glands are adjacent to each other. The non-uniformity should be necessary to adjust as precisely the total amount of excess sweat as possible through the sympathetic nerve in response to strength of the stress.

  7. Induction and differentiation of adipose-derived stem cells from human buccal fat pads into salivary gland cells.

    PubMed

    Kawakami, Miyuki; Ishikawa, Hiroshi; Tanaka, Akira; Mataga, Izumi

    2016-07-01

    Atrophy or hypofunction of the salivary gland because of aging or disease leads to hyposalivation that affects patient quality of life by causing dry mouth, deterioration of mastication/deglutition, and poor oral hygiene status. Current therapy for atrophy or hypofunction of the salivary gland in clinical practice focuses on symptom relief using drugs and artificial saliva; therefore, there is still a need to develop new therapies. To investigate potential novel therapeutic targets, we induced the differentiation of salivary gland cells by co-culturing human adipose-derived stem cells isolated from buccal fat pads (hBFP-ASCs) with human salivary-gland-derived fibroblasts (hSG-fibros). We examined their potential for transplantation and tissue neogenesis. Following the culture of hBFP-ASCs and hSG-fibros, differentiated cells were transplanted into the submandibular glands of SCID mice, and their degree of differentiation in tissues was determined. We also examined their potential for functional tissue reconstitution using a three-dimensional (3D) culture system. Co-cultured cells expressed salivary-glandrelated markers and generated new tissues following transplantation in vivo. Moreover, cell reconstituted glandular structures in the 3D culture system. In conclusion, coculture of hSG-fibros with hBFP-ASCs led to successful differentiation into salivary gland cells that could be transplanted to generate new tissues.

  8. Pharmacogenetics of human ABC transporter ABCC11: new insights into apocrine gland growth and metabolite secretion

    PubMed Central

    Ishikawa, Toshihisa; Toyoda, Yu; Yoshiura, Koh-ichiro; Niikawa, Norio

    2013-01-01

    Cell secretion is an important physiological process that ensures smooth metabolic activities and tissue repair as well as growth and immunological functions in the body. Apocrine secretion occurs when the secretory process is accomplished with a partial loss of cell cytoplasm. The secretory materials are contained within secretory vesicles and are released during secretion as cytoplasmic fragments into the glandular lumen or interstitial space. The recent finding that the non-synonymous single nucleotide polymorphisms (SNP) 538G > A (rs17822931; Gly180Arg) in the ABCC11 gene determines the type of earwax in humans has shed light on the novel function of this ABC (ATP-binding cassette) transporter in apocrine glands. The wild-type (Gly180) of ABCC11 is associated with wet-type earwax, axillary osmidrosis, and colostrum secretion from the mammary gland as well as the potential risk of mastopathy. Furthermore, the SNP (538G > A) in the ABCC11 gene is suggested to be a clinical biomarker for the prediction of chemotherapeutic efficacy. The aim of this review article is to provide an overview on the discovery and characterization of genetic polymorphisms in the human ABCC11 gene and to explain the impact of ABCC11 538G > A on the apocrine phenotype as well as the anthropological aspect of this SNP in the ABCC11 gene and patients’ response to nucleoside-based chemotherapy. PMID:23316210

  9. Nicotine and methyl methane sulfonate in mini organ cultures of human parotid gland tissue.

    PubMed

    Ginzkey, Christian; Friehs, Gudrun; Koehler, Christian; Hackenberg, Stephan; Voelker, Hans-Ullrich; Richter, Elmar; Kleinsasser, Norbert H

    2010-08-16

    The aim was to demonstrate the applicability of using mini organ cultures (MOC) of the human parotid gland for indicating DNA damage by nicotine. Macroscopically healthy specimens of human parotid glands (1 mm3) were cultured for 7 d. Morphology was examined after HE and immunohistochemical staining of alpha-amylase. MOC were exposed to 2.0 mM nicotine or 100 microM methyl methane sulfonate (MMS) for 1, 2 and 3 h, followed by a regeneration period of 24 h. DNA damage was assessed by the comet assay. Histological findings demonstrated healthy acinar cells up to 8 days of culture and a strong expression pattern of alpha-amylase. Cells in the centre of mini organs showed a granular cytoplasm starting at day 3. 1-3 h nicotine exposure significantly increased DNA damage as determined by DNA in the tail (DT), with no significant differences with increasing exposure time and only a trend towards decreased values of DT after regeneration. MMS demonstrated a time-dependent increase in DNA damage and distinctly reduced DT values after regeneration. MOC may be used to study DNA damage and repair after repetitive exposure to xenobiotics. They provide additional information for in vitro studies of cells growing in an intact tissue structure. PMID:20466043

  10. Pineal anlage tumor in a 5-month-old boy.

    PubMed

    Olaya, Joffre E; Raghavan, Ravi; Totaro, Laura; Zouros, Alexander

    2010-06-01

    Pineal tumors are rare neoplasms that are categorized into pineoblastomas, pineocytomas, and pineal parenchymal tumors of intermediate differentiation. Pineal anlage tumors are primary pineal tumors with neuroepithelial and ectomesenchymal differentiation and without endodermal differentiation. The authors review the literature and report the case of a 5-month-old boy with a pineal anlage tumor. This is only the sixth case of a pineal anlage tumor reported in the English-language literature adding to the understanding of this tumor's presentation, immunomorphological and molecular characteristics, embryological origin, radiological appearance, treatment outcome, and prognosis.

  11. Cavernous angioma of the pineal region.

    PubMed

    Donati, P; Maiuri, F; Gangemi, M; Gallicchio, B; Sigona, L

    1992-01-01

    The pineal region is one of the most rare localizations of intracranial cavernous angiomas, with only 8 cases reported up today. The Authors report a case of cavernous angioma of such localization and review the pertinent literature. Magnetic resonance allows the correct diagnosis of cavernous malformations on the basis of their typical aspect, even in the absence of histological verification. We suggest that this imaging technique will allow to identify more frequently pineal cavernomas preoperatively, thus avoiding useless irradiation. PMID:1484302

  12. [Melatonin radioimmunoanalysis: evaluation of the pineal function in hyperprolactinemic male rats and controls].

    PubMed

    Villanúa, M A; Esquifino, A I; Tresguerres, J A

    1986-06-01

    A sensitive and specific radioimmunoassay for melatonin quantification in rat pineal and biological fluids is described. The assay utilizes a specific antibody and H3-melatonin as tracer. Bound and free fraction were separated by a saturated sulphate ammonium solution. The sensitivity of the method is 9 pg/ml. The intra and interassay variation coefficient were 10.4 and 13.6% respectively. By means of this RIA the content of melatonin in the pineal gland in male rats made hyperprolactinemic on day 30 of life and their respective sham-operated controls has been evaluated. The results showed that the melatonin content measured at 2 a.m. was reduced in the transplanted animals when compared to control group, not only shortly (48 hours) after the transplant operation, but also in the chronic situation; though suggesting that further investigations are necessary to deepen and understand the interrelationships between prolactin and pineal gland and their effect on the hypothalamic-pituitary-gonadal axis.

  13. Spontaneous lesions in the reproductive tract and mammary gland of female non-human primates.

    PubMed

    Cooper, Timothy K; Gabrielson, Kathleen L

    2007-04-01

    Because of their close phylogenic relationship with humans, the use of non-human primates (NHP) as experimental subjects has a long history in biomedical research. Although research topics have shifted focus and species used have changed, NHP remain vital as models in basic and applied research. While there is a wealth of information available on the spontaneous lesions of NHP, most of this information is fragmented, dated, or narrow in focus, often limited to single case reports. This review attempts to integrate this information to illustrate and enumerate the spectrum of spontaneous pathology of the reproductive tract and mammary gland of NHP. Although not the focus of this review, steroid-related changes are inextricably linked to these tissues, and brief consideration is given to this subject as well. PMID:17342758

  14. Quantitative Analysis of Human Salivary Gland-Derived Intact Proteome Using Top-Down Mass Spectrometry

    SciTech Connect

    Wu, Si; Brown, Joseph N.; Tolic, Nikola; Meng, Da; Liu, Xiaowen; Zhang, Haizhen; Zhao, Rui; Moore, Ronald J.; Pevzner, Pavel A.; Smith, Richard D.; Pasa-Tolic, Ljiljana

    2014-05-31

    There are several notable challenges inherent to fully characterizing the entirety of the human saliva proteome using bottom-up approaches, including polymorphic isoforms, post-translational modifications, unique splice variants, deletions, and truncations. To address these challenges, we have developed a top-down based liquid chromatography-mass spectrometry (LC-MS) approach, which cataloged 20 major human salivary proteins with a total of 83 proteoforms, containing a broad range of post-translational modifications. Among these proteins, several previously reported disease biomarker proteins were identified at the intact protein level, such as beta-2 microglobulin (B2M). In addition, intact glycosylated proteoforms of several saliva proteins were also characterized, including intact N-glycosylated protein prolactin inducible protein (PIP) and O-glycosylated acidic protein rich protein (aPRP). These characterized proteoforms constitute an intact saliva proteoform database, which was used for quantitative comparison of intact salivary proteoforms among six healthy individuals. Human parotid (PS) and submandibular/sublingual gland (SMSL) secretion samples (2 μg of protein each) from six healthy individuals were compared using RPLC coupled with the 12T FTICR mass spectrometer. Significantly different protein and PTM patterns were resolved with high reproducibility between PS and SMSL glands. The results from this study provide further insight into the potential mechanisms of PTM pathways in oral glandular secretion, expanding our knowledge of this complex yet easily accessible fluid. Intact protein LC-MS approach presented herein can potentially be applied for rapid and accurate identification of biomarkers from only a few microliters of human glandular saliva.

  15. Post-Irradiated Human Submandibular Glands Display High Collagen Deposition, Disorganized Cell Junctions, and an Increased Number of Adipocytes.

    PubMed

    Nam, Kihoon; Maruyama, Christina L; Trump, Bryan G; Buchmann, Luke; Hunt, Jason P; Monroe, Marcus M; Baker, Olga J

    2016-06-01

    Salivary glands are vital for maintaining oral health. Head and neck radiation therapy is one of the most common causes of salivary gland hypofunction. Little is known about the structural changes that occur in salivary glands after radiation therapy. The aim of this study is to understand the structural changes that occur in post-irradiated human (submandibular gland [SMG]) as compared with untreated ones. We determined changes in epithelial polarity, presence of collagen deposition, and alteration in adipose tissue. We used formalin-fixed paraffin-embedded human SMG from two female subjects exposed to head and neck irradiation. We utilized hematoxylin and eosin staining and Masson's Trichrome staining. The immunostained tissue sections were examined using confocal microscopy. The number and size of adipocytes per tissue section were calculated using ImageJ, Prism, and SPSS software. Post-irradiated human SMG displayed high collagen deposition, disorganized cell junctions, and an increased number of adipocytes as compared with non-irradiated controls. These findings are important to improve our understanding of the individual risk and variation in radiation-related salivary gland dysfunction.

  16. Utility of fine-needle aspiration in the diagnosis of salivary gland lesions in patients infected with human immunodeficiency virus.

    PubMed

    Chhieng, D C; Argosino, R; McKenna, B J; Cangiarella, J F; Cohen, J M

    1999-10-01

    Fine-needle aspiration (FNA) has been increasingly utilized as a diagnostic tool in evaluating salivary gland masses, primarily to differentiate nonneoplastic from neoplastic lesions. Patients infected with human immunodeficiency virus (HIV) frequently present with salivary gland lesions. In this study, we reviewed the cytology of salivary gland lesions in HIV-infected patients and assessed the value of FNA in the diagnosis of salivary gland lesions in HIV-infected patients. One hundred and three FNAs of salivary gland lesions from 78 HIV-infected patients (63 males and 15 females) were included in our study. The patients' ages ranged from 7-65 yr, with a mean age of 40.9 yr. FNAs were classified into three categories: benign lymphoepithelial lesions (BLL) (77 cases or 74.8%), inflammatory processes (14 cases or 13.6%), including 3 reactive lymphoid hyperplasia, and neoplastic lesions (6 cases or 5.8%). The latter included three malignant lymphomas, a multiple myeloma, a metastatic adenocarcinoma from a lung primary, and a direct extension of basal-cell carcinoma. Six (5.8%) aspirates were nondiagnostic. No false-positive or false-negative cases were noted during follow-up of these patients. In conclusion, FNA is a simple and cost-effective procedure for the diagnosis of HIV-related salivary gland lesions. The majority of these lesions are cystic BLL and can be managed conservatively. Malignant lesions are rarely encountered and are readily recognized by FNA. Diagn. Cytopathol. 1999;21:260-264.

  17. Human immunodeficiency virus type 1 replication within cystic lymphoepithelial lesion of the salivary gland.

    PubMed

    Labouyrie, E; Merlio, J P; Beylot-Barry, M; Delord, B; Vergier, B; Brossard, G; Lacoste, D; Beylot, J; Leng, B; Fleury, H

    1993-07-01

    Cystic lymphoepithelial lesions of salivary glands (CLLSG) are nodular or diffuse salivary gland enlargements that are observed in patients who tested positive for human immunodeficiency virus type 1 (HIV-1). Two cases of CLLSG are reported. Particular emphasis is placed on the presence of HIV-1 major-core protein (P24), HIV-1 RNA sequences, Epstein-Barr virus (EBV) DNA sequences, and lymphocyte receptor gene rearrangement. Lymphoid alterations consisted of explosive hyperplasia with a prominent follicular reticular dendritic cell (DRC) network and numerous intrafollicular CD8+ lymphocytes. Intrafollicular DRC strongly expressed HIV-1 major-core protein and HIV-1 RNA, indicating that most DRCs actively replicated the HIV-1 virus. The presence of active HIV-1 replication within DRC and the absence of clonal EBV infected lymphoid population strongly suggest that CLLSG pathogenesis is primarily induced by HIV-1. The presence of oligoclonal immunoglobulin gene rearrangements in our cases, however, suggest the need of long-term follow-up of such patients to determine whether CLLSG could be a benign prelymphomatous disease.

  18. Pineal-dependent and -independent effects of photoperiod on immune function in Siberian hamsters (Phodopus sungorus)

    PubMed Central

    Wen, Jarvi C.; Dhabhar, Firdaus S.; Prendergast, Brian J.

    2010-01-01

    Siberian hamsters (Phodopus sungorus) exhibit reproductive and immunological responses to photoperiod. Short (<10-h light/day) days induce gonadal atrophy, increase leukocyte concentrations, and attenuate thermoregulatory and behavioral responses to infection. Whereas hamster reproductive responses to photoperiod are dependent on pineal melatonin secretion, the role of the pineal in short-day induced changes in immune function is not fully understood. To examine this, adult hamsters were pinealectomized (PINx) or sham-PINx, and transferred to short days (9-h light/day; SD) or kept in their natal long-day (15-h light/day; LD) photoperiod. Intact and PINx hamsters housed in LD maintained large testes over the next 12 weeks; sham-PINx hamsters exhibited gonadal regression in SD, and PINx abolished this effect. Among pineal-intact hamsters, blood samples revealed increases in leukocyte, lymphocyte, CD62L+ lymphocyte, and T cell counts in SD relative to LD; PINx did not affect leukocyte numbers in LD hamsters, but abolished the SD increase in these measures. Hamsters were then treated with bacterial lipopolysaccharide (LPS), which induced thermoregulatory (fever), behavioral (anorexia, reductions in nest building), and somatic (weight loss) sickness responses in all groups. Among pineal-intact hamsters, febrile and behavioral responses to LPS were attenuated in SD relative to LD. PINx did not affect sickness responses to LPS in LD hamsters, but abolished the ameliorating effects of SD on behavioral responses to LPS. Surprisingly, PINx failed to abolish the effect of SD on fever. In common with the reproductive system, PINx induces the LD phenotype in most aspects of the immune system. The pineal gland is required for photoperiodic regulation of circulating leukocytes and neural-immune interactions that mediate select aspects of sickness behaviors. PMID:17022983

  19. "Their pineal glands aglow": Theosophical physiology in Ulysses.

    PubMed

    Morrisson, Mark S

    2008-01-01

    This article argues that Joyce's engagements with the Theosophy of the Dublin literary world amount to more than simple parody. In Ulysses, Joyce portrays Theosophy's efforts to offer an alternative understanding of physiology to that of the medical establishment as a form of boundary work, an adaptation of the discourse of modern medical research to fashion modern mysticism as a science. Ultimately, Joyce rejects Theosophical physiology and its evolutionary scientism because it provides an unsatisfactory rhetorical body, a failed attempt to renegotiate the boundaries between scientific materialism and spirituality in the awkward modernity of Dublin in 1904. PMID:20836274

  20. "Their pineal glands aglow": Theosophical physiology in Ulysses.

    PubMed

    Morrisson, Mark S

    2008-01-01

    This article argues that Joyce's engagements with the Theosophy of the Dublin literary world amount to more than simple parody. In Ulysses, Joyce portrays Theosophy's efforts to offer an alternative understanding of physiology to that of the medical establishment as a form of boundary work, an adaptation of the discourse of modern medical research to fashion modern mysticism as a science. Ultimately, Joyce rejects Theosophical physiology and its evolutionary scientism because it provides an unsatisfactory rhetorical body, a failed attempt to renegotiate the boundaries between scientific materialism and spirituality in the awkward modernity of Dublin in 1904.

  1. Changes in PACAP immunoreactivity in human milk and presence of PAC1 receptor in mammary gland during lactation.

    PubMed

    Csanaky, Katalin; Banki, Eszter; Szabadfi, Krisztina; Reglodi, Dora; Tarcai, Ibolya; Czegledi, Levente; Helyes, Zsuzsanna; Ertl, Tibor; Gyarmati, Judit; Szanto, Zalan; Zapf, Istvan; Sipos, Erika; Shioda, Seiji; Tamas, Andrea

    2012-11-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with widespread occurrence in the nervous system and peripheral organs, including the mammary gland. Previously, we have shown that PACAP38 is present in the human milk at higher levels than in respective blood samples. However, it is not known how PACAP levels and the expression of PAC1 receptor change during lactation. Therefore, the aim of our study was to investigate PACAP38-like immunoreactivity (PACAP38-LI) in human colostrums and transitional and mature milk during lactation and to compare the expression of PAC1 receptors in lactating and non-lactating mammary glands. We found that PACAP38-LI was significantly higher in human colostrum samples than in the transitional and mature milk. PACAP38-LI did not show any significant changes within the first 10-month period of lactation, but a significant increase was observed thereafter, up to the examined 17th month. Weak expression of PAC1 receptors was detected in non-lactating sheep and human mammary glands, but a significant increase was observed in the lactating sheep samples. In summary, the present study is the first to show changes of PACAP levels in human milk during lactation. The presence of PACAP in the milk suggests a potential role in the development of newborn, while the increased expressions of PAC1 receptors on lactating breast may indicate a PACAP38/PAC1 interaction in the mammary gland during lactation.

  2. [The role of the pineal-thymus system in the regulation of autoimmunity, aging and lifespan].

    PubMed

    Csaba, György

    2016-07-01

    Thymus is an immunoendocrine organ, the hormones of which mainly influence its own lymphatic elements. It has a central role in the immune system, the neonatal removal causes the collapse of immune system and the whole organism. The thymic nurse cells select the bone marrow originated lymphocytes and destroy the autoreactive ones, while thymus originated Treg cells suppress the autoreactive cells in the periphery. The involution of the organ starts after birth, however, this truly happens in the end of puberty only, as before this it is overcompensated by developmental processes. From the end of adolescence the involution allows the life, proliferation and enhanced functioning of some autoreactive cells, which gradually wear down the cells and intercellular materials, causing the aging. The enhanced and mass function of autoreactive cells lead to the autoimmune diseases and natural death. This means that the involution of thymus is not a part of the organismic involution, but an originator of it, which is manifested in the lifespan-pacemaker function. Thus, aging can be conceptualized as a thymus-commanded slow autoimmune process. The neonatal removal of pineal gland leads to the complete destruction of the thymus and the crashing down of the immune system, as well as to wasting disease. The involution of the pineal and thymus runs parallel, because the two organs form a functional unit. It is probable that the pineal gland is responsible for the involution of thymus and also regulates its lifespan determining role. However, the data reviewed here do not prove the exclusive role of the pineal-thymus system in the regulation of aging and lifespan, but only call attention to such possibility. PMID:27346473

  3. Neurotranscriptomics: The Effects of Neonatal Stimulus Deprivation on the Rat Pineal Transcriptome

    PubMed Central

    Hartley, Stephen W.; Coon, Steven L.; Savastano, Luis E.; Mullikin, James C.; Fu, Cong; Klein, David C.

    2015-01-01

    The term neurotranscriptomics is used here to describe genome-wide analysis of neural control of transcriptomes. In this report, next-generation RNA sequencing was using to analyze the effects of neonatal (5-days-of-age) surgical stimulus deprivation on the adult rat pineal transcriptome. In intact animals, more than 3000 coding genes were found to exhibit differential expression (adjusted-p < 0.001) on a night/day basis in the pineal gland (70% of these increased at night, 376 genes changed more than 4-fold in either direction). Of these, more than two thousand genes were not previously known to be differentially expressed on a night/day basis. The night/day changes in expression were almost completely eliminated by neonatal removal (SCGX) or decentralization (DCN) of the superior cervical ganglia (SCG), which innervate the pineal gland. Other than the loss of rhythmic variation, surgical stimulus deprivation had little impact on the abundance of most genes; of particular interest, expression levels of the melatonin-synthesis-related genes Tph1, Gch1, and Asmt displayed little change (less than 35%) following DCN or SCGX. However, strong and consistent changes were observed in the expression of a small number of genes including the gene encoding Serpina1, a secreted protease inhibitor that might influence extracellular architecture. Many of the genes that exhibited night/day differential expression in intact animals also exhibited similar changes following in vitro treatment with norepinephrine, a superior cervical ganglia transmitter, or with an analog of cyclic AMP, a norepinephrine second messenger in this tissue. These findings are of significance in that they establish that the pineal-defining transcriptome is established prior to the neonatal period. Further, this work expands our knowledge of the biological process under neural control in this tissue and underlines the value of RNA sequencing in revealing how neurotransmission influences cell biology. PMID

  4. [The role of the pineal-thymus system in the regulation of autoimmunity, aging and lifespan].

    PubMed

    Csaba, György

    2016-07-01

    Thymus is an immunoendocrine organ, the hormones of which mainly influence its own lymphatic elements. It has a central role in the immune system, the neonatal removal causes the collapse of immune system and the whole organism. The thymic nurse cells select the bone marrow originated lymphocytes and destroy the autoreactive ones, while thymus originated Treg cells suppress the autoreactive cells in the periphery. The involution of the organ starts after birth, however, this truly happens in the end of puberty only, as before this it is overcompensated by developmental processes. From the end of adolescence the involution allows the life, proliferation and enhanced functioning of some autoreactive cells, which gradually wear down the cells and intercellular materials, causing the aging. The enhanced and mass function of autoreactive cells lead to the autoimmune diseases and natural death. This means that the involution of thymus is not a part of the organismic involution, but an originator of it, which is manifested in the lifespan-pacemaker function. Thus, aging can be conceptualized as a thymus-commanded slow autoimmune process. The neonatal removal of pineal gland leads to the complete destruction of the thymus and the crashing down of the immune system, as well as to wasting disease. The involution of the pineal and thymus runs parallel, because the two organs form a functional unit. It is probable that the pineal gland is responsible for the involution of thymus and also regulates its lifespan determining role. However, the data reviewed here do not prove the exclusive role of the pineal-thymus system in the regulation of aging and lifespan, but only call attention to such possibility.

  5. Diffusion characteristics of pediatric pineal tumors

    PubMed Central

    Whitehead, Matthew T; Siddiqui, Adeel; Klimo, Paul; Boop, Frederick A

    2015-01-01

    Background Diffusion weighted imaging (DWI) has been shown to be helpful in characterizing tumor cellularity, and predicting histology. Several works have evaluated this technique for pineal tumors; however studies to date have not focused on pediatric pineal tumors. Objective We evaluated the diffusion characteristics of pediatric pineal tumors to confirm if patterns seen in studies using mixed pediatric and adult populations remain valid. Materials and methods This retrospective study was performed after Institutional Review Board approval. We retrospectively evaluated all patients 18 years of age and younger with pineal tumors from a single institution where preoperative diffusion weighted imaging as well as histologic characterization was available. Results Twenty patients (13 male, 7 female) with pineal tumors were identified: seven with pineoblastoma, four with Primitive Neuroectodermal Tumor (PNET), two with other pineal tumors, and seven with germ cell tumors including two germinomas, three teratomas, and one mixed germinoma-teratoma. The mean apparent diffusion coefficient (ADC) values in pineoblastoma (544 ± 65 × 10–6 mm2/s) and pineoblastoma/PNET (595 ± 144 × 10–6 mm2/s) was lower than that of the germ cell tumors (1284 ± 334 × 10–6 mm2/s; p < 0.0001 vs pineoblastoma). One highly cellular germinoma had an ADC value of 694 × 10–6 mm2/s. Conclusion ADC values can aid in differentiation of pineoblastoma/PNET from germ cell tumors in a population of children with pineal masses. PMID:25963154

  6. Three-dimensional volumetric human meibomian gland investigation using polarization-sensitive optical coherence tomography.

    PubMed

    Ju, Myeong Jin; Shin, Jun Geun; Hoshi, Sujin; Yasuno, Yoshiaki; Lee, Byeong Ha; Tang, Shuo; Eom, Tae Joong

    2014-03-01

    In this study, polarization-sensitive optical coherence tomography (PS-OCT) capable of providing polarization contrasts such as phase retardation and degree of polarization uniformity (DOPU) was used for visualizing human meibomian glands (MGs) and investigating morphological characteristics of them. Especially, with the help of the DOPU contrast, MGs were exclusively extracted from the volumetric OCT image. In vivo PS-OCT measurements were performed on the upper eyelids of different age groups. From these measurements, different age-dependent aspects of the MG structure were also observed. Based on these observations, it can be inferred that the PS-OCT system has the potential for clinical diagnosis and investigation of MG-related dry eye diseases like MG dysfunction (MGD) and acinar atrophy.

  7. Selective secretion of annexin 1, a protein without a signal sequence, by the human prostate gland.

    PubMed

    Christmas, P; Callaway, J; Fallon, J; Jones, J; Haigler, H T

    1991-02-01

    Annexins are primarily intracellular proteins as would be predicted from their lack of hydrophobic signal sequences. However, we now report that the human prostate gland selectively secretes high concentrations of annexin 1 (also called lipocortin 1 and p35) and a proteolytic cleavage product, des1-29-annexin 1, into seminal plasma. Secreted annexin 1 had a blocked amino terminus and was structurally indistinguishable from intracellular annexin 1. Although annexin 1 and the structurally related protein, annexin 4, co-localized to many of the same cells of the ductal epithelium of the prostate, annexin 4 was not secreted. Thus, the secretion of annexin 1 appears to involve a highly selective mechanism that does not involve targeting to the endoplasmic reticulum by a hydrophobic signal sequence.

  8. Differences in Human Meibum Lipid Composition with Meibomian Gland Dysfunction Using NMR and Principal Component Analysis

    PubMed Central

    Foulks, Gary N.; Yappert, Marta C.; Milliner, Sarah E.

    2012-01-01

    Purpose. Nuclear magnetic resonance (NMR) spectroscopy has been used to quantify lipid wax, cholesterol ester terpenoid and glyceride composition, saturation, oxidation, and CH2 and CH3 moiety distribution. This tool was used to measure changes in human meibum composition with meibomian gland dysfunction (MGD). Methods. 1H-NMR spectra of meibum from 39 donors with meibomian gland dysfunction (Md) were compared to meibum from 33 normal donors (Mn). Results. Principal component analysis (PCA) was applied to the CH2/CH3 regions of a set of training NMR spectra of human meibum. PCA discriminated between Mn and Md with an accuracy of 86%. There was a bias toward more accurately predicting normal samples (92%) compared with predicting MGD samples (78%). When the NMR spectra of Md were compared with those of Mn, three statistically significant decreases were observed in the relative amounts of CH3 moieties at 1.26 ppm, the products of lipid oxidation above 7 ppm, and the ═CH moieties at 5.2 ppm associated with terpenoids. Conclusions. Loss of the terpenoids could be deleterious to meibum since they exhibit a plethora of mostly positive biological functions and could account for the lower level of cholesterol esters observed in Md compared with Mn. All three changes could account for the higher degree of lipid order of Md compared with age-matched Mn. In addition to the power of NMR spectroscopy to detect differences in the composition of meibum, it is promising that NMR can be used as a diagnostic tool. PMID:22131391

  9. WISP-1 overexpression upregulates cell proliferation in human salivary gland carcinomas via regulating MMP-2 expression

    PubMed Central

    Li, Fu-Jun; Wang, Xin-Juan; Zhou, Xiao-Li

    2016-01-01

    Background WISP-1 is a member of the CCN family of growth factors and has been reported to play an important role in tumorigenesis by triggering downstream events via integrin signaling. However, little is known about the role of WISP-1 in proliferation of salivary gland carcinoma (SGC) cells. Methods In this study, we investigated the WISP-1 expression in SGC tissues via immunohistochemical staining, Western blotting assay, and real-time quantitative polymerase chain reaction method, and then evaluated the regulatory role of WISP-1 in the growth of SGC A-253 cells. In addition, the role of MMP-2 in the WISP-1-mediated growth regulation was also investigated. Results It was demonstrated that the WISP-1 expression was upregulated at both mRNA and protein levels in 15 of 21 SGC tumor tissues, compared to the non-tumor tissues (five of 21), associated with the lymph node dissection and bone invasion. The in vitro CCK-8 assay and colony-forming assay demonstrated that the exogenous WISP-1 treatment or the WISP-1 overexpression promoted the growth of A-253 cells. In addition, we confirmed that the WISP-1 overexpression upregulated the MMP-2 expression in A-253 cells with the gain-of-function and loss-of-function strategies, and that the MMP-2 knockdown attenuated the WISP-1-mediated growth promotion of A-253 cells. Conclusion We found that WISP-1 was overexpressed in the human SGCs, and the WISP-1 overexpression promoted the salivary gland cell proliferation via upregulating MMP-2 expression. Our study recognized the oncogenic role of WISP-1 in human SGCs, which could serve as a potential target for anticancer therapy. PMID:27799801

  10. Production and processing of milk from transgenic goats expressing human lysozyme in the mammary gland.

    PubMed

    Maga, E A; Shoemaker, C F; Rowe, J D; Bondurant, R H; Anderson, G B; Murray, J D

    2006-02-01

    The potential for applying biotechnology to benefit animal agriculture and food production has long been speculated. The addition of human milk components with intrinsic antimicrobial activity and positive charge to livestock milk by genetic engineering has the potential to benefit animal health, as well as food safety and production. We generated one line of transgenic goats as a model for the dairy cow designed to express human lysozyme in the mammary gland. Here we report the characterization of the milk from 5 transgenic females of this line expressing human lysozyme in their milk at 270 microg/mL or 68% of the level found in human milk. Milk from transgenic animals had a lower somatic cell count, but the overall component composition of the milk and milk production were not different from controls. Milk from transgenic animals had a shorter rennet clotting time and increased curd strength. Milk of such nature may be of benefit to the producer by influencing udder health and milk processing.

  11. Changes in the daily rhythm of serum testosterone levels following superior cervical sympathetic ganglionectomy in the cold-exposed rat: the role of the pineal.

    PubMed

    Peschke, E; Peschke, D; Peil, J; Rúzsás, C; Mess, B

    1988-01-01

    The effect superior cervical sympathetic ganglionectomy (Gx) exerted on the daily rhythm of serum testosterone levels was investigated in cold-exposed rats. Rhythmic changes in pineal and pituitary weights were also measured. 1. Exposure to cold (10 degrees C for 72 h) resulted in a significant decrease of serum testosterone level and in an increase of the pineal weight. 2. In neutral ambient temperature (24 degrees C) Gx, 30 d after operation, led to a moderate, statistically insignificant increase of serum testosterone levels and to decreased pineal weights (statistically significant). 3. The reactions provoked by cold exposure were counteracted by Gx. Testosterone levels, as well as the pineal weight, showed no remarkable change in the Gx, cold-exposed animals. 4. These results confirm our assumption that experimental manipulations of the pineal gland can provoke significant changes in the neuroendocrine system only under special loading circumstances, e.g., cold exposure. Sympathetic denervation of the pineal gland counteracts the cold-induced decrease of testosterone levels by counteracting the pineal antigonadotropic activity. 5. The empirical regression curves of the investigated parameters indicate that Gx or cold exposure provide a shift in the upper and lower limits of the daily rhythm. Partly inverted rhythms were also observed. 6. The presented results are discussed in relation to the parallel changes previously described in serum thyroxin, cholesterol, thyrotropin (TSH), and pituitary TSH levels. Thyroidal-gonadal interactions, as well as cold exposure as a stress-generating factor, have been considered in the possible explanation of the data herein reported. PMID:3367268

  12. Dynamic Observation of Sweat Glands of Human Finger Tip Using All-Optical-Fiber High-Speed Optical Coherence Tomography

    NASA Astrophysics Data System (ADS)

    Ohmi, Masato; Nohara, Kenji; Ueda, Yoshihiro; Fuji, Toshie; Haruna, Masamitsu

    2005-06-01

    High-speed optical coherence tomography (OCT) makes it possible to perform a time-sequential imaging of biological tissue and small organs. In this paper, we demonstrate in vivo observation of dynamics of sweat glands of human finger tip using high-speed OCT with push-pull driven fiber-optic PZT phase modulators. Movement of a sweat droplet through a micro spiral duct can be tracked clearly. An interesting function of sweat glands is found out in time-sequential OCT imaging.

  13. Human postmortem lacrimal and submandibular glands stored in RNAlater are suitable for molecular, biochemical, and cell biological studies

    PubMed Central

    Hawley, Dillon; Aluri, Hema; Armaos, Helene; Kim, Gina; Kublin, Claire

    2016-01-01

    Purpose Gene expression and protein analysis studies require high-quality human tissue which is a challenge and difficult to obtain through live human biopsies. Human postmortem lacrimal gland (LG) and submandibular gland (SMG) tissues have the potential to provide an invaluable source for studying the mechanisms involved in LG and SMG dysfunction. Therefore, we aimed to test the suitability of post-mortem LG and SMG for molecular, biochemical, and cell biological studies. Methods LG and SMG tissue from healthy donors was collected and immediately placed in RNAlater solution and then shipped overnight at 4 °C. After receipt, each gland was divided into three pieces for RNA, protein, and histological analysis, respectively. Total RNA isolated from each LG and SMG was analyzed for RNA integrity using an Agilent Bioanalyzer and reverse transcription–PCR (RT–PCR). For histology, tissues were embedded in paraffin and stained with hematoxylin and eosin. For protein analysis, lysates were prepared and processed for sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE) and western blotting. Results When the LG and SMG samples were preserved in RNAlater, the RNA integrity number (RIN) values from the LG and SMG were >7.0 from all three donors, while the RNAs from tissue not preserved in RNAlater were of poorer quality. The gene and/or protein expression of E-cadherin, aquaporin 5, alpha-smooth muscle actin (α-SMA), β-actin, and GAPDH was preserved in all samples. In addition, histological analyses showed normal tubuloacinar structures of all glands with serous and mucous producing acini within lobules interspersed with adipose fat. Conclusions In this study, we determined that RNA, protein, and histological sections obtained from postmortem human LG and SMG tissue preserved in RNAlater were of high quality. This would provide a viable source of human LG and SMG tissue suitable for studies of diseases that affect these glands, such as Sj

  14. Development and structure of the glandopreputial sulcus of the human clitoris with a special reference to glandopreputial glands.

    PubMed

    van der Putte, Sebastian C J; Sie-Go, Daisy M D S

    2011-01-01

    The structure and development of the sulcus between the glans and prepuce of the human clitoris have hardly been investigated. Interest in its structure was raised when in the female, in contrast to the male, glands were found to develop from the solid lamella-like precursor of the glandopreputial sulcus. It prompted a further histological analysis of the sulcus in female fetuses and newborn and an extension of that study to clitorises of adult women. The investigation showed that in the clitoris, in contrast to the penis, the transformation of the glandopreputial lamella into the open sulcus was mostly incomplete and apparently remained so throughout life. As a most striking and probably exclusively female feature, two to eight eccrine glands developed from the base of the lamella in fetuses older than 14.5 weeks gestation. These glands formed secretory coils near and occasionally inside the adjacent distal corpora cavernosa. Some glands showed atresia, cystic dilatation, and squamous metaplasia. A remarkably similar picture was observed in the adult clitorises, in which the secretory coils were often found between the large blood vessels and nerves to the glans and were connected to the sulcus by long excretory ducts. All glands revealed unmistakably eccrine features. It is suggested that their secretion moistens the female glandopreputial sulcus, which is not lubricated by urethral secretion as in the male. The findings may explain the rare clitoral phimosis, cysts, and some pilonidal sinuses.

  15. In vitro effects of sex hormones in human meibomian gland epithelial cells.

    PubMed

    Schröder, Antje; Abrar, Daniel B; Hampel, Ulrike; Schicht, Martin; Paulsen, Friedrich; Garreis, Fabian

    2016-10-01

    Meibomian gland dysfunction (MGD) is considered the most common cause of dry eye disease (DED). Sex hormones seem to play a role in the pathogenesis of MGD although their involvement is not completely understood. Therefore, in the present study we evaluated the effect of dihydrotestosteron (DHT) and estradiol (β-Est) on an immortalized human meibomian gland epithelial cell line (HMGEC). Protein expression of sex hormone receptors in HMGEC was investigated by western blot. Ultrastructural morphology, Sudan III lipid staining, cell proliferation as well as vitality assays were performed. Furthermore, expression of MGD-associated markers for keratinization (hornerin, involucrin and CK6), proliferation (CK5 and CK14) and lipid synthesis (fatty acid synthase and stearoyl-CoA desaturase) were analyzed by real time RT-PCR. Western blot revealed presence of androgen receptor (AR), estrogen receptors α and -β (ERα, ERβ) and progesterone receptor (PR) in HMGEC. PR, ERα and ERβ expression was significantly induced under cultivation with serum, whereas sex hormones stimulation showed no further effect on protein expression of PR, ERα and ERβ. Our results showed no impact of MGD-associated sex hormones to cellular morphology and lipid accumulation in HMGEC. Cell proliferation was slightly induced through application of sex hormones and supplementation of calcium. However, both sex hormones and calcium altered gene expression of MGD-associated markers. Especially keratinization genes hornerin (HRNR) and cornulin (COR) were induced after application of sex hormones and calcium in serum-free cultivated HMGEC. This may promote keratinization processes that are associated with MGD. Further investigations are necessary to analyze the (hyper)keratinization processes that occur during MGD and using HMGEC as an in vitro model.

  16. Effects of Insulin and High Glucose on Human Meibomian Gland Epithelial Cells

    PubMed Central

    Ding, Juan; Liu, Yang; Sullivan, David A.

    2015-01-01

    Purpose Type 2 diabetes is a risk factor for meibomian gland dysfunction (MGD). We hypothesize that this diabetic impact is due, at least in part, to the effects of insulin resistance/deficiency and hyperglycemia on human meibomian gland epithelial cells (HMGECs). To begin to test this hypothesis, we examined whether insulin and high glucose influence immortalized (I) HMGECs. Methods Immortalized HMGECs were cultured in serum-containing or -free media and treated with insulin, insulin-like growth factor–1 (IGF-1), IGF-1 receptor (R) blocking antibody, and glucose or mannitol for varying time periods. Specific proteins were detected by Western blots, cell proliferation was evaluated by manual cell counting and lipids were assessed with LipidTOX and high performance thin layer chromatography. Results We found that insulin induces a dose-dependent increase in phosphatidylinositide 3-kinase/Akt (AKT) signaling in IHMGECs. This effect involves the IGF-1R, but not the insulin receptor (IR), and is associated with a stimulation of cell proliferation and neutral lipid accumulation. In contrast, high glucose exposure alters cell morphology, causes a progressive cell loss, and significantly reduces the levels of IGF-1R, phospho (p)-AKT, Foxhead box protein O1 (FOXO1), and sterol-regulatory element binding protein (SREBP-1) in IHMGECs. Conclusions Our data show that insulin stimulates, and that high glucose is toxic for, IHMGECs. These results support our hypothesis that insulin resistance/deficiency and hyperglycemia are deleterious for HMGECs and may help explain why type II diabetes is a risk factor for MGD. PMID:26658502

  17. [A rainbow coupling human pathology and endocrinology, with emphasis on the adrenal glands].

    PubMed

    Sasano, N

    1987-03-20

    Recent progress in research methodology particularly of immunocytochemistry has made the viaduct of human pathology through endocrinology a wide bridge. Immunohistochemical demonstration of enzymes working in corticosteroidogenesis is useful for the interpretation of histological findings. Cytochrome P-450C21 was demonstrated in three adrenocortical layers particularly evident in the glomerulosa and reticularis. The reactivity was intensive in hypertrophied cells in focal hyperplasia of autopsy series and adenomas in patients with hyperadrenocorticism. The distribution of extra-adrenal steroid 21-hydroxylase was revealed by immunohistochemistry at the distal and collecting tubules of the kidney, excretory ducts of the pancreas and salivary glands, mammary ducts and ductules and secretory portion of the sweat gland in man. It was postulated that in these target tissues of the mineralocorticoid action considerable amounts of DOC would be produced from plasma progesterone by the extra-adrenal 21-hydroxylase. Histopathological diagnosis of malignancy in adrenal tumors has been extremely difficult. Therefore, follow-up informations of metastasis and/or recurrence and gross findings including the tumor weight have been evaluated as the evidence of malignancy. In adrenocortical tumors plasma steroid patterns and in vitro steroid production which were appreciated in the clinical endocrinology, were corroborated by gross and microscopical findings. Immunohistochemical lectin bindings revealed that only RCA (Ricinus communis agglutinin) might be useful for the marker of adrenocortical malignancies. For establishing histological criteria of malignant pheochromocytomas, 25 adrenal and extra-adrenal tumors associated with metastases were examined. Localized or diffuse proliferation of small-sized cells, fusiform or round in shape, frequently associated with mitotic figures and foci of necrosis was of common feature. Immunoreactive peptide hormones were less compared with benign

  18. CT and MR of pineal region tumors.

    PubMed

    Gouliamos, A D; Kalovidouris, A E; Kotoulas, G K; Athanasopoulou, A K; Kouvaris, J R; Trakadas, S J; Vlahos, L J; Papavasiliou, C G

    1994-01-01

    Magnetic Resonance (MR) imaging features of pineal region tumors were analyzed in 14 oncologic cases. The tumors were classified as germ-cell tumors, glial tumors, pineal parenchymal tumors, meningiomas, and cysts. They demonstrated different MR signal characteristics on precontrast scans and nodular or ring type enhancement with occasional central lucencies, except for benign cysts, which have not shown enhancement. MR images were useful in defining the relationship of the tumor to the posterior third ventricle, sylvian aqueduct, vein of Galen, and tentorium. Although CT can demonstrate in more evident fashion displacement of the original pineal calcification as well as tumor calcifications, MR imaging demonstrates different signal characteristics in germinomas and pineoblastomas which can be a useful adjunct in the evaluation and differential diagnosis of these tumors. PMID:8295504

  19. Posttranscriptional regulation of pineal melatonin synthesis in Octodon degus.

    PubMed

    Lee, Soo Jung; Liu, Tiecheng; Chattoraj, Asamanja; Zhang, Samantha L; Wang, Lijun; Lee, Theresa M; Wang, Michael M; Borjigin, Jimo

    2009-08-01

    Small laboratory animals have provided significant information about melatonin regulation, yet most of these organisms are nocturnal and regulate melatonin synthesis by mechanisms that diverge from those of humans. For example, in all rodents examined, melatonin secretion occurs with a time lag of several hours after the onset of darkness; in addition, arylalkylamine N-acetyltransferase (AANAT), the key enzyme in melatonin synthesis, displays dynamic transcriptional activation specifically at night in all rodents studied to date. In ungulates and primates including humans, on the other hand, melatonin secretion occurs immediately during the early night and is controlled by circadian posttranscriptional regulation of AANAT. We hypothesize that the diurnal Octodon degus (an Hystricognath rodent) could serve as an improved experimental model for studies of human melatonin regulation. To test this, we monitored melatonin production in degus using pineal microdialysis and characterized the regulation of melatonin synthesis by analyzing degu Aanat. Degu pineal melatonin rises with little latency at night, as in ungulates and primates. In addition, degu Aanat mRNA expression displays no detectable diurnal variation, suggesting that, like ungulates and primates, melatonin in this species is regulated by a posttranscriptional mechanism. Compared with AANAT from all rodents examined to date, the predicted amino acid sequence of degu AANAT is phylogenetically more closely related to ungulate and primate AANAT. These data suggest that Octodon degus may provide an ideal model system for laboratory investigation of mechanisms of melatonin synthesis and secretion in diurnal mammals.

  20. A novel TMEM16A splice variant lacking the dimerization domain contributes to calcium-activated chloride secretion in human sweat gland epithelial cells.

    PubMed

    Ertongur-Fauth, Torsten; Hochheimer, Andreas; Buescher, Joerg Martin; Rapprich, Stefan; Krohn, Michael

    2014-11-01

    Sweating is an important physiological process to regulate body temperature in humans, and various disorders are associated with dysregulated sweat formation. Primary sweat secretion in human eccrine sweat glands involves Ca(2+) -activated Cl(-) channels (CaCC). Recently, members of the TMEM16 family were identified as CaCCs in various secretory epithelia; however, their molecular identity in sweat glands remained elusive. Here, we investigated the function of TMEM16A in sweat glands. Gene expression analysis revealed that TMEM16A is expressed in human NCL-SG3 sweat gland cells as well as in isolated human eccrine sweat gland biopsy samples. Sweat gland cells express several previously described TMEM16A splice variants, as well as one novel splice variant, TMEM16A(acΔe3) lacking the TMEM16A-dimerization domain. Chloride flux assays using halide-sensitive YFP revealed that TMEM16A is functionally involved in Ca(2+) -dependent Cl(-) secretion in NCL-SG3 cells. Recombinant expression in NCL-SG3 cells showed that TMEM16A(acΔe3) is forming a functional CaCC, with basal and Ca(2+) -activated Cl(-) permeability distinct from canonical TMEM16A(ac). Our results suggest that various TMEM16A isoforms contribute to sweat gland-specific Cl(-) secretion providing opportunities to develop sweat gland-specific therapeutics for treatment of sweating disorders.

  1. Ultrasonic delivery of silica-gold nanoshells for photothermolysis of sebaceous glands in humans: Nanotechnology from the bench to clinic.

    PubMed

    Paithankar, Dilip; Hwang, Byeong Hee; Munavalli, Girish; Kauvar, Arielle; Lloyd, Jenifer; Blomgren, Richard; Faupel, Linda; Meyer, Todd; Mitragotri, Samir

    2015-05-28

    Recent advances in nanotechnology have provided numerous opportunities to transform medical therapies for the treatment of diseases including cancer, atherosclerosis, and thrombosis. Here, we report, through in vitro studies and in vivo human pilot clinical studies, the use of inert, inorganic silica-gold nanoshells for the treatment of a widely prevalent and researched, yet poorly treated disease of acne. We use ~150nm silica-gold nanoshells, tuned to absorb near-IR light and near-IR laser irradiation to thermally disrupt overactive sebaceous glands in the skin which define the etiology of acne-related problems. Low-frequency ultrasound was used to facilitate deep glandular penetration of the nanoshells. Upon delivery of the nanoshells into the follicles and glands, followed by wiping of superficial nanoshells from skin surface and exposure of skin to near-infrared laser, nanoshells localized in the follicles absorb light, get heated, and induce focal thermolysis of sebaceous glands. Pilot human clinical studies confirmed the efficacy of ultrasonically-delivered silica-gold nanoshells in inducing photothermal disruption of sebaceous glands without damaging collateral skin. PMID:25747145

  2. Dynamic analysis of eccrin sweat glands on human fingertips by optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Haruna, Masamitsu; Ohmi, Masato; Ueda, Yoshihiro; Yamada, Akihiro; Saigusa, Hiroyuki

    2008-02-01

    OCT is highly potential for dynamic analysis of eccrin sweat glands. It is found in our experiment that the spiral lumen of an active sweat gland expands drastically in response to mental stress. Mental-stress-induced sweating is analyzed quantitatively based on time-sequential OCT images.

  3. Human salivary gland acinar cells spontaneously form three-dimensional structures and change the protein expression patterns.

    PubMed

    Chan, Yen-Hui; Huang, Tsung-Wei; Young, Tai-Horng; Lou, Pei-Jen

    2011-11-01

    Applying tissue engineering principles to design an auto-secretory device is a potential solution for patients suffering loss of salivary gland function. However, the largest challenge in implementing this solution is the primary culture of human salivary gland cells, because the cells are highly differentiated and difficult to expand in vitro. This situation leads to the lack of reports on the in vitro cell biology and physiology of human salivary gland cells. This study used a low-calcium culture system to selectively cultivate human parotid gland acinar (PGAC) cells from tissues with high purity in cell composition. This condition enables PGAC cells to continuously proliferate and retain the phenotypes of epithelial acinar cells to express secreting products (α-amylase) and function-related proteins (aquaporin-3, aquaporin-5, and ZO-1). Notably, when the cells reached confluence, three-dimensional (3D) cell aggregates were observed in crowded regions. These self-formed cell spheres were termed post-confluence structures (PCSs). Unexpectedly, despite being cultured in the same media, cells in PCSs exhibited higher expression levels and different expression patterns of function-related proteins compared to the two-dimensional (2D) cells. Translocation of aquoporin-3 from cytosolic to alongside the cell boundaries, and of ZO-1 molecules to the boundary of the PCSs were also observed. These observations suggest that when PGAC cells cultured on the 2D substrate would form PCSs without the help of 3D scaffolds and retain certain differentiation and polarity. This phenomenon implies that it is possible to introduce 2D substrates instead of 3D scaffolds into artificial salivary gland tissue engineering.

  4. Expression of PACAP and PAC1 Receptor in Normal Human Thyroid Gland and in Thyroid Papillary Carcinoma.

    PubMed

    Bardosi, Sebastian; Bardosi, Attila; Nagy, Zsuzsanna; Reglodi, Dora

    2016-10-01

    Pituitary adenylate cyclase activating polypeptide (PACAP) belongs to the vasoactive intestinal peptide-secretin-glucagon peptide family, isolated first from ovine hypothalamus. The diverse physiological effects of PACAP are known mainly from animal experiments, including several actions in endocrine glands. Alteration of PACAP expression has been shown in several tumors, but changes in expression of PACAP and its specific PAC1 receptor in human thyroid gland pathologies have not yet been investigated. Therefore, the aim of the present study was to investigate expression of PACAP and its PAC1 receptor in human thyroid papillary carcinoma, the most common endocrine malignant tumor. PACAP and PAC1 receptor expressions were investigated from thyroid gland samples of patients with papillary carcinomas. The staining intensity of follicular epithelial cells and thyroid colloid of tumor tissue was compared to that of tumor-free tissue in the same thyroid glands in a semi-quantitative way. Our results reveal that both PACAP(-like) and PAC1 receptor(-like) immunoreactivities are altered in papillary carcinoma. Stronger PACAP immunoreactivity was observed in active follicles. Colloidal PACAP immunostaining was either lacking or very weak, and more tumorous cells displayed strong apical immunoreactivity. Regarding PAC1 receptor, cells of the normal thyroid tissue showed strong granular expression, which was lacking in the tumor cells. The cytoplasm of tumor cells displayed weak, minimal staining, while in a few tumor cells we observed strong PAC1 receptor expression. This pattern was similar to that observed in the PACAP expression, but fewer in number. In summary, we showed alteration of PACAP and PAC1 receptor expression in human thyroid papillary carcinoma, indicating that PACAP regulation is disturbed in tumorous tissue of the thyroid gland. The exact role of PACAP in thyroid tumor growth should be further explored.

  5. Expression of PACAP and PAC1 Receptor in Normal Human Thyroid Gland and in Thyroid Papillary Carcinoma.

    PubMed

    Bardosi, Sebastian; Bardosi, Attila; Nagy, Zsuzsanna; Reglodi, Dora

    2016-10-01

    Pituitary adenylate cyclase activating polypeptide (PACAP) belongs to the vasoactive intestinal peptide-secretin-glucagon peptide family, isolated first from ovine hypothalamus. The diverse physiological effects of PACAP are known mainly from animal experiments, including several actions in endocrine glands. Alteration of PACAP expression has been shown in several tumors, but changes in expression of PACAP and its specific PAC1 receptor in human thyroid gland pathologies have not yet been investigated. Therefore, the aim of the present study was to investigate expression of PACAP and its PAC1 receptor in human thyroid papillary carcinoma, the most common endocrine malignant tumor. PACAP and PAC1 receptor expressions were investigated from thyroid gland samples of patients with papillary carcinomas. The staining intensity of follicular epithelial cells and thyroid colloid of tumor tissue was compared to that of tumor-free tissue in the same thyroid glands in a semi-quantitative way. Our results reveal that both PACAP(-like) and PAC1 receptor(-like) immunoreactivities are altered in papillary carcinoma. Stronger PACAP immunoreactivity was observed in active follicles. Colloidal PACAP immunostaining was either lacking or very weak, and more tumorous cells displayed strong apical immunoreactivity. Regarding PAC1 receptor, cells of the normal thyroid tissue showed strong granular expression, which was lacking in the tumor cells. The cytoplasm of tumor cells displayed weak, minimal staining, while in a few tumor cells we observed strong PAC1 receptor expression. This pattern was similar to that observed in the PACAP expression, but fewer in number. In summary, we showed alteration of PACAP and PAC1 receptor expression in human thyroid papillary carcinoma, indicating that PACAP regulation is disturbed in tumorous tissue of the thyroid gland. The exact role of PACAP in thyroid tumor growth should be further explored. PMID:27566169

  6. Down regulation and nuclear localization of human beta-defensin-1 in pleomorphic adenomas of salivary glands.

    PubMed

    Pantelis, Annette; Wenghoefer, Matthias; Haas, Susanne; Merkelbach-Bruse, Sabine; Pantelis, Dimitrios; Jepsen, Søren; Bootz, Friedrich; Winter, Jochen

    2009-06-01

    Although antimicrobial peptides (AMPs) appear to have diverse functional activities in innate immunity, a few reports suggest a potential role of human beta-defensin (hBD)-1 in tumor suppression. The aim of the present study was to compare the expression patterns of hBD-1, -2 and -3 in various features of human salivary gland tissues, such as healthy parenchyma, chronic sialadenitis and intraglandular pleomorphic adenomas, with their adjacent normal tissues. Twenty human salivary gland specimens (five healthy, five chronic sialadenitis, five pleomorphic adenomas and five adenoma adjacent normal tissues (AANTs)) were investigated for mRNA expression levels of hBD-1, -2 and -3 by quantitative real-time RT-PCR. Additionally, immunohistochemistry for the hBD-1, -2 and -3 peptides was performed for analysis of localization. Considerably increased, 80-fold higher hBD-1 and increased hBD-3 mRNA expression levels compared to healthy salivary gland tissues were detected in chronic sialadenitis. In pleomorphic adenomas hBD-2 expression levels were lower, but hBD-1 expression levels were significant decreased (p=0.03) compared to healthy parenchyma. Interestingly, the AANTs showed a 48-fold higher expression of hBD-1 and increased hBD-3 expression compared to the healthy salivary gland. Immunohistochemistry of the tumors showed nuclear hBD-1 localization. For the first time, it was shown that hBD-1 gene expression is significantly decreased in pleomorphic adenomas, while simultaneously the protein is localized in the nucleus. Increased expression levels in glandular inflammation have been described previously albeit not in AANTs. These data support the hypothesis that hBD-1 might be a potential tumor suppressor also in benign salivary gland tumors in addition to other genetic alterations.

  7. Salivary Glands

    MedlinePlus

    ... salivary gland tumors usually show up as painless enlargements of these glands. Tumors rarely involve more than ... otolaryngologist-head and neck surgeon should check these enlargements. Malignant tumors of the major salivary glands can ...

  8. Pituitary gland

    MedlinePlus

    ... glands. Located above the pituitary gland is the hypothalamus. The hypothalamus decides which hormones the pituitary should release by ... messages. In response to hormonal messages from the hypothalamus, the pituitary gland releases the following hormones: GH ( ...

  9. Recent progress in development of transgenic silkworms overexpressing recombinant human proteins with therapeutic potential in silk glands.

    PubMed

    Itoh, Kohji; Kobayashi, Isao; Nishioka, So-Ichiro; Sezutsu, Hideki; Machii, Hiroaki; Tamura, Toshiki

    2016-02-01

    Since 2000, transgenic silkworms have been developed to produce recombinant proteins with therapeutic potential for future clinical use, including antibody preparations. Lysosomal storage diseases (LSDs) are inherited metabolic disorders caused by mutations of lysosomal enzymes associated with excessive accumulation of natural substrates and neurovisceral symptoms. Over the past few years, enzyme replacement therapy (ERT) with human lysosomal enzymes produced by genetically engineered mammalian cell lines has been used clinically to treat several patients with an LSD involving multi-organ symptoms. ERT is based on the incorporation of recombinant glycoenzymes by their binding to glycan receptors on the surface of target cells and their subsequent delivery to lysosomes. However, ERT has several disadvantages, including difficulty mass producing human enzymes, dangers of pathogen contamination, and high costs. Recently, the current authors have succeeded in producing transgenic silkworms overexpressing human lysosomal enzymes in the silk glands and the authors have purified catalytically active enzymes from the middle silk glands. Silk gland-derived human enzymes carrying high-mannose and pauci-mannose N-glycans were endocytosed by monocytes via the mannose receptor pathway and were then delivered to lysosomes. Conjugates with cell-penetrating peptides were also taken up by cultured fibroblasts derived from patients with enzyme deficiencies to restore intracellular catalytic activity and reduce the excessive accumulation of substrates in patient fibroblasts. Transgenic silkworms overexpressing human lysosomal enzymes in the silk glands could serve as future bioresources that provide safe therapeutic enzymes for the treatment of LSDs. Combining recent developments in transglycosylation technology with microbial endoglycosidases will promote the development of therapeutic glycoproteins as bio-medicines. PMID:26971553

  10. Effect of androgen deficiency on the human meibomian gland and ocular surface.

    PubMed

    Krenzer, K L; Dana, M R; Ullman, M D; Cermak, J M; Tolls, D B; Evans, J E; Sullivan, D A

    2000-12-01

    The purpose of this study was to determine whether the chronic use of antiandrogen medications leads to meibomian gland dysfunction, altered lipid profiles in meibomian gland secretions, decreased tear film stability, and evaporative dry eye. Subjects taking antiandrogen therapy for prostatic indications, as well as age-related controls, were asked to complete a questionnaire that assessed dry eye symptoms and then were given a complete anterior segment examination. Moreover, meibomian gland secretions were obtained from each eye and analyzed by high-performance liquid chromatography/mass spectrometry for the relative content of cholesterol, cholesterol esters, wax esters, diglycerides, triglycerides, and specific molecular species in the diglyceride fraction. Our results demonstrate that patients taking antiandrogen treatment, compared with age-related controls, had a: 1) significant increase in the frequency of appearance of tear film debris, an abnormal tear film meniscus, irregular posterior lid margins, conjunctival tarsal injection, and orifice metaplasia of the meibomian glands; 2) significant increase in the degree of ocular surface vital dye staining; 3) significant decrease in the tear film breakup time and quality of meibomian gland secretions; and 4) significant increase in the frequency of light sensitivity, painful eyes, and blurred vision. In addition, the use of antiandrogen pharmaceuticals was associated with significant changes in the relative amounts of lipids in meibomian gland secretions. Our findings indicate that chronic androgen deficiency is associated with meibomian gland dysfunction and dry eye.

  11. Step-by-step protocol to perfuse and dissect the mouse parotid gland and isolation of high-quality RNA from murine and human parotid tissue.

    PubMed

    Watermann, Christoph; Valerius, Klaus Peter; Wagner, Steffen; Wittekindt, Claus; Klussmann, Jens Peter; Baumgart-Vogt, Eveline; Karnati, Srikanth

    2016-04-01

    Macroscopic identification and surgical removal of the mouse parotid gland is demanding because of its anatomic location and size. Moreover, the mouse parotid gland contains high concentrations of RNases, making it difficult to isolate high-quality RNA. So far, appropriate methods for optimal perfusion-fixation and dissection of mouse parotid glands, as well as the isolation of high quality RNA from this tissue, are not available. Here we present a simple, optimized, step-by-step surgical method to perfuse and isolate murine parotid glands. We also compared two common RNA extraction methods (RNeasy Mini Kit versus TRIzol) for their yields of high-quality, intact RNA from human and murine parotid gland tissues that were either snap-frozen or immersed in RNAlater stabilization solution. Mouse parotid tissue that was perfused and immersed in RNAlater and human samples immersed in RNAlater exhibited the best RNA quality, independent of the isolation method. PMID:27071609

  12. Stereology of the Thyroid Gland in Indo-Pacific Bottlenose Dolphin (Tursiops aduncus) in Comparison with Human (Homo sapiens): Quantitative and Functional Implications

    PubMed Central

    Kot, Brian Chin Wing; Lau, Thomas Yue Huen; Cheng, Sammy Chi Him

    2013-01-01

    The mammalian thyroid gland maintains basal metabolism in tissues for optimal function. Determining thyroid volume is important in assessing growth and involution. Volume estimation is also important in stereological studies. Direct measurements of colloid volume and nuclear-to-cytoplasmic ratio of the follicular cells may provide important information about thyroid gland function such as hormone storage and secretion, which helps understand the changes at morphological and functional levels. The present study determined the colloid volume using simple stereological principle and the nuclear-to-cytoplasmic ratio of 4 Indo-Pacific bottlenose dolphins and 2 human thyroid glands. In both dolphin and human thyroid glands, the size of the follicles tended to be quite variable. The distribution of large and small follicles within the thyroid gland was also found to be random in both the dolphin and human thyroid gland; however, the size of follicles appeared to decrease as a function of increasing age in the dolphin thyroid gland. The mean colloid volume of the dolphin thyroid gland and human thyroid gland was 1.22×105 µm3 and 7.02×105 µm3 respectively. The dolphin and human subjects had a significant difference in the mean colloid volume. The mean N/C ratio of the dolphin thyroid follicular epithelia and human follicular epithelia was 0.50 and 0.64 respectively. The dolphin and human subjects had a significant difference in the mean N/C ratio. This information contributes to understanding dolphin thyroid physiology and its structural adaptations to meet the physical demands of the aquatic environment, and aids with ultrasonography and corrective therapy in live subjects. PMID:23690927

  13. Stereology of the thyroid gland in Indo-Pacific bottlenose dolphin (Tursiops aduncus) in comparison with human (Homo sapiens): quantitative and functional implications.

    PubMed

    Kot, Brian Chin Wing; Lau, Thomas Yue Huen; Cheng, Sammy Chi Him

    2013-01-01

    The mammalian thyroid gland maintains basal metabolism in tissues for optimal function. Determining thyroid volume is important in assessing growth and involution. Volume estimation is also important in stereological studies. Direct measurements of colloid volume and nuclear-to-cytoplasmic ratio of the follicular cells may provide important information about thyroid gland function such as hormone storage and secretion, which helps understand the changes at morphological and functional levels. The present study determined the colloid volume using simple stereological principle and the nuclear-to-cytoplasmic ratio of 4 Indo-Pacific bottlenose dolphins and 2 human thyroid glands. In both dolphin and human thyroid glands, the size of the follicles tended to be quite variable. The distribution of large and small follicles within the thyroid gland was also found to be random in both the dolphin and human thyroid gland; however, the size of follicles appeared to decrease as a function of increasing age in the dolphin thyroid gland. The mean colloid volume of the dolphin thyroid gland and human thyroid gland was 1.22×10(5) µm(3) and 7.02×10(5) µm(3) respectively. The dolphin and human subjects had a significant difference in the mean colloid volume. The mean N/C ratio of the dolphin thyroid follicular epithelia and human follicular epithelia was 0.50 and 0.64 respectively. The dolphin and human subjects had a significant difference in the mean N/C ratio. This information contributes to understanding dolphin thyroid physiology and its structural adaptations to meet the physical demands of the aquatic environment, and aids with ultrasonography and corrective therapy in live subjects.

  14. Endodermal cyst in pineal region: Rare location

    PubMed Central

    Lopez-Gonzalez, Miguel Angel; Dolan, Eugen

    2016-01-01

    Background: Pineal tumors are very uncommon intracranial lesions, and endodermal cysts in this location are extremely rare. Case Description: A 49-year-old right-handed female presented with 3 weeks history of progressive dizziness and imbalance. Imaging studies showed 1.8 cm × 1.7 cm × 1.8 cm pineal lesion with small enhancing mural component displacing ventrally the quadrigeminal plate and narrowing of aqueduct of Sylvius without hydrocephalus. In addition, she was found with small interhemispheric lipoma, and small posterior falx possible meningioma. Cerebrospinal fluid markers obtained by lumbar puncture were all negative. She underwent tumor resection, and final pathology reported endodermal cyst. No new deficits were encountered, and her gait imbalance improved significantly by 3 months follow-up. Conclusions: With evidence of enlargement or symptomatic pineal lesions, surgical consideration is necessary. Among pineal lesions, endodermal cysts are extremely uncommon and although benign pathology, long-term follow-up is advised due to unknown chronic behavior. PMID:27217965

  15. Glycomic profile of the human parotid gland between 18th and 26th week of fetal development.

    PubMed

    Rêgo, Moacyr J B M; Silva Filho, Antônio F; Sobral, Ana P V; Beltrão, Eduardo I C

    2016-01-01

    The formation of new and functional structural components of several organs, such as parotid glands, can be influenced by the glycocode. This study analyzed the glycobiology of parotid salivary gland tissue during fetal development using specific biochemical probes (lectins and antibodies). Eleven parotid gland samples from human fetuses were obtained from spontaneous abortions at 14-28 weeks of gestation, and tissue sections were analyzed for lectin histochemistry and immunohistochemistry. From the 18th to 26th week, Canavalia ensiformis agglutinin, wheat germ agglutinin, Ulex europaeus agglutinin-I, peanut agglutinin, Sambucus nigra agglutinin, and Vicia villosa agglutinin lectin staining were predominantly observed in the apical and/or basement membranes of the ducts and tubulo-acinar units. Moreover, the presence of galectin-1 was found in the membrane, cytoplasm, and nucleus of both structures. Conversely, Gal-3 and mucin-1 were restricted to the glandular ducts. The lectin staining pattern changed during the weeks evaluated. Nevertheless, the carbohydrate subcellular localization represented a key factor in the investigation of structural distribution profiles and possible roles of these glycans in initial parotid gland development. These findings are defined by their high biological value and provide an important base for the development of subsequent studies. (J Oral Sci 58, 353-360, 2016). PMID:27665974

  16. Human Epidermal Growth Factor Receptor 2 (HER2/neu) in Salivary Gland Carcinomas: A Review of Literature

    PubMed Central

    Alotaibi, Abdullah Mislat; Alqarni, Mohammed Ali; Alnobi, Abdelrahman

    2015-01-01

    The aim of our study is to assess the relation of human epidermal growth factor receptor 2 or HER2/neu with the development of salivary gland carcinomas and use of Herceptin in the treatment of these cancers. A literature search was conducted using MEDLINE accessed via the National Library of Medicine PubMed interface searching for articles from 1994 up to 2014 relating to the existence of HER-2 protein and gene in salivary gland carcinomas and HER2/neu targeted therapy, written in English language. Almost all the studies in literature reported a frequent over expression and amplification of HER2/nue in salivary duct carcinomas (SDC) compared to other salivary gland cancers. Herceptin given as a monotherapy was not effective. The data on Herceptin combined chemotherapy are potentially promising but inadequate to evaluate drug activity, as patients also received a variety of cytotoxic agents. Therefore, Herceptin contribution to tumour response outcomes could not be precisely determined and the total number of cases is not sufficient. It is recommended that further work involves a large series of HER2/neu positive salivary gland cancers (randomized control trial) treated with chemotherapy with and without Herceptin. This might need multi-institutional cooperation. PMID:25859537

  17. In-vitro depth-dependent hyperthermia of human mammary gland adenocarcinoma.

    PubMed

    Dunn, Andrew W; Zhang, Yu; Mast, David; Pauletti, Giovanni M; Xu, Hong; Zhang, Jiaming; Ewing, Rodney C; Shi, Donglu

    2016-12-01

    Nanoparticle mediated photothermal ablation of cancerous tissue shows promising results and applicability as a highly efficacious treatment method. As a majority of the photothermal work has been conducted with minimal attenuation of the laser before reaching the nanoparticles within surface seeded tumors in-vivo or through buffered media in-vitro, it is important to understand the effects of greater laser attenuation on photothermal efficacy mediated by changes in the scattering and absorption of the laser. Photothermal efficacy using a near infrared (NIR) 785nm laser irradiating polystyrene (PS) stabilized magnetite (Fe3O4) nanoparticles (PS-Fe3O4) is examined on MDA-MB-231 human mammary gland adenocarcinoma in-vitro. Agarose gel columns of various heights were created to simulate soft tissue and subsequently used for NIR laser attenuation. Polystyrene was found to significantly improve magnetite nanoparticle stability in serum containing media and modified Hank's Balanced Salt Solution and was able to induce significant hyperthermic ablation at mass concentrations which also did not elicit significant innate toxicity. Furthermore it was found that the polystyrene coating significantly reduced innate toxicity over 48h compared to uncoated magnetite. Agar gel layers provided similar optical attenuation in the NIR region to skin and prostate. PMID:27612683

  18. MRI-based three-dimensional thermal physiological characterization of thyroid gland of human body.

    PubMed

    Jin, Chao; He, Zhi Zhu; Yang, Yang; Liu, Jing

    2014-01-01

    This article is dedicated to present a MRI (magnetic resonance imaging) based three-dimensional finite element modeling on the thermal manifestations relating to the pathophysiology of thyroid gland. An efficient approach for identifying the metabolic dysfunctions of thyroid has also been demonstrated through tracking the localized non-uniform thermal distribution or enhanced dynamic imaging. The temperature features over the skin surface and thyroid domain have been characterized using the numerical simulation and experimental measurement which will help better interpret the thermal physiological mechanisms of the thyroid under steady-state or water-cooling condition. Further, parametric simulations on the hypermetabolism symptoms of hyperthyroidism and thermal effects within thyroid domain caused by varying breathing airflow in the trachea and blood-flow in artery and vein were performed. It was disclosed that among all the parameters, the airflow volume has the largest effect on the total heat flux of thyroid surface. However, thermal contributions caused by varying the breathing frequency and blood-flow velocity are negligibly small. The present study suggests a generalized way for simulating the close to reality physiological behavior or process of human thyroid, which is of significance for disease diagnosis and treatment planning.

  19. Effect of tympanic neurectomy on human parotid salivary gland. Histopathologic, Histochemical, and Clinical Study.

    PubMed

    Mandour, M A; Helmi, A M; El-Sheikh, M M; El-Garem, F; El-Ghazzawi, E

    1977-06-01

    Five patients with bilateral chronic recurrent parotiditis and ten patients with unilateral persistent paratoid gland fistulas underwent tympanic neurectomies. Two biopsy specimens from the diseased gland were examined. The first biopsy specimen was taken at the time of operation, while the second one was taken six months later. All specimens were subjected to both histopathologic and histochemical investigations. Definite degenerative and atrophic changes occured in all parotid gland specimens taken six months after selective tympanic neurectomy. All patients were completely cured at about that time. This supported the practical indication of the selective tympanic neurectomy for treating certain benign disorders or diseases of the parotid gland that require persistent arrest of the function of its secretory units.

  20. Cytogenetic and molecular observations in human and experimental salivary gland tumors.

    PubMed

    Sandros, J; Stenman, G; Mark, J

    1990-02-01

    The chromosomal banding patterns in 189 benign and malignant salivary gland tumors are reviewed. For comparison, karyotypic data from a recent series of polyoma virus-induced salivary gland tumors in the mouse are discussed. Special interest is focused on the relationships between the highly specific patterns of translocations and deletions in these tumors and different genes involved in neoplasia, in particular oncogenes, and tumor suppressor genes.

  1. A bilateral, superficial location of human sublingual glands: report of a case.

    PubMed

    Moss-Salentijn, L; Hendricks-Klyvert, M

    1987-11-01

    During a routine dissection of a cadaver, the unusual, completely superficial position of both sublingual glandular masses was noticed. Histologically, the glandular masses consisted of a group of minor sublingual glands. It is suggested that the existence of a wide gap between the anterior and posterior parts of the mylohyoid muscle, which was revealed during further dissection, was the primary embryologic anomaly that was responsible for the unusual location of the glands.

  2. Endothelin in human brain and pituitary gland: Presence of immunoreactive endothelin, endothelin messenger ribonucleic acid, and endothelin receptors

    SciTech Connect

    Takahashi, K.; Ghatei, M.A.; Jones, P.M.; Murphy, J.K.; Lam, H.C.; O'Halloran, D.J.; Bloom, S.R. )

    1991-03-01

    The presence of immunoreactive (IR) endothelin, endothelin mRNA, and endothelin receptors in human brain and pituitary gland has been studied by RIA, Northern blot hybridization, and receptor assay. IR endothelin was detected in all five brain regions examined (cerebral cortex, cerebellum, brain stem, basal ganglia, and hypothalamus) (6-10 fmol/g wet wt) and spinal cord (22 +/- 6 fmol/g wet wt, n = 7, mean +/- SEM). Higher concentrations of IR endothelin were found in the pituitary gland (147 +/- 30 fmol/g wet wt). Fast protein liquid chromatographic analysis of the IR endothelin in pituitary gland showed a large IR peak in the position of endothelin-3 and a smaller peak in the position of endothelin-1, whereas IR endothelin in the hypothalamus and brain stem was mainly endothelin-1. Endothelin messenger RNA was detected by Northern blot hybridization in the pituitary but not in hypothalamus. The receptor assay showed that 125I-endothelin-1 binding sites were present in large numbers in all five brain regions but were much less abundant in the pituitary gland. Binding capacity and dissociation constant were 5052 +/- 740 fmol/mg protein and 0.045 +/- 0.007 nM in brain stem and 963 +/- 181 fmol/mg protein and 0.034 +/- 0.009 nM in hypothalamus. In the pituitary gland, there were two classes of binding sites for endothelin with dissociation constants of 0.059 +/- 0.002 nM (binding capacity = 418 +/- 63 fmol/mg protein) and 0.652 +/- 0.103 nM (binding capacity = 1717 +/- 200 fmol/mg protein). Endothelin-1, -2 and -3 were almost equipotent in displacing the binding (IC50 approximately 0.04 nM). These findings are in accord with the possibility that endothelin acts as a neurotransmitter, neuromodulator or neurohormone in man.

  3. The influence of various irradiances of artificial light, twilight, and moonlight on the suppression of pineal melatonin content in the Syrian hamster.

    PubMed

    Brainard, G C; Richardson, B A; Hurlbut, E C; Steinlechner, S; Matthews, S A; Reiter, R J

    1984-01-01

    The purpose of the present studies using artificial light was to determine how the timing and duration of exposure influence the light-induced suppression of pineal melatonin levels in hamsters. An 8-min exposure to 0.186 microW/cm2 of cool white fluorescent light caused a continued depression of pineal melatonin even when animals were returned to darkness. In addition, the pineal gland does not appear to change its sensitivity to light throughout the night. A 20-min exposure to 0.019 microW/cm2 of cool white fluorescent light did not significantly suppress pineal melatonin during any time of the melatonin peak, whereas a 20-min exposure to 0.186 microW/cm2 was capable of always suppressing melatonin. Furthermore, increasing the duration of 0.019-microW/cm2 exposure to 30, 60, 120, or 180 min does not increase the capacity of this irradiance to depress melatonin. Similar to artifical light, natural light has a variable capacity for suppressing nocturnal levels of pineal melatonin. Twilight irradiances of 0.138 microW/cm2 or less did not suppress nocturnal melatonin whereas twilight irradiances of 3.0 microW/cm2 or greater did suppress pineal melatonin. A few animals did have lower melatonin after a 40-min exposure to full moonlight during July (0.045 microW/cm2) or January (0.240 microW/cm2). However, pineal melatonin levels remained high in the majority of animals exposed to full moonlight.

  4. The evolution of sweat glands

    NASA Astrophysics Data System (ADS)

    Folk, G. Edgar; Semken, A.

    1991-09-01

    Mammals have two kinds of sweat glands, apocrine and eccrine, which provide for thermal cooling. In this paper we describe the distribution and characteristics of these glands in selected mammals, especially primates, and reject the suggested development of the eccrine gland from the apocrine gland during the Tertiary geological period. The evidence strongly suggests that the two glands, depending on the presence or absence of fur, have equal and similar functions among mammals; apocrine glands are not primitive. However, there is a unique and remarkable thermal eccrine system in humans; we suggest that this system evolved in concert with bipedalism and a smooth hairless skin.

  5. Dissecting lipid metabolism in meibomian glands of humans and mice: An integrative study reveals a network of metabolic reactions not duplicated in other tissues.

    PubMed

    Butovich, Igor A; McMahon, Anne; Wojtowicz, Jadwiga C; Lin, Feng; Mancini, Ronald; Itani, Kamel

    2016-06-01

    Lipids comprise the bulk of the meibomian gland secretion (meibum) which is produced by meibocytes. Complex arrays of lipogenic reactions in meibomian glands, which we collectively call meibogenesis, have not been explored on a molecular level yet. Our goals were to elucidate the possible biosynthetic pathways that underlie the generation of meibum, reveal similarities in, and differences between, lipid metabolism in meibomian glands and other organs and tissues, and integrate meibomian gland studies into the field of general metabolomics. Specifically, we have conducted detailed analyses of human and mouse specimens using genomic, immunohistochemical, and lipidomic approaches. Among equally highly expressed genes found in meibomian glands of both species were those related to fatty acid elongation, branching, desaturation, esterification, reduction of fatty acids to alcohols, and cholesterol biosynthesis. Importantly, corresponding lipid products were detected in meibum of both species using lipidomic approaches. For the first time, a cohesive, unifying biosynthetic scheme that connects genomic, lipidomic, and immunohistochemical observations is outlined and discussed. PMID:27032494

  6. Direct reprogramming of human fibroblasts into sweat gland-like cells.

    PubMed

    Zhao, Zhiliang; Xu, Mengyao; Wu, Meng; Ma, Kui; Sun, Mengli; Tian, Xiaocheng; Zhang, Cuiping; Fu, Xiaobing

    2015-01-01

    The skin of patients with an extensive deep burn injury is repaired by a process that leaves a hypertrophic scar without sweat glands and therefore loses the function of perspiration. The aim of this study was to identify whether the key factors related to sweat gland development could directly reprogram fibroblasts into sweat gland-like cells. After introducing the NF-κB and Lef-1 genes into fibroblasts, we found that stably transfected fibroblasts expressed specific markers of sweat glands, including CEA, CK7, CK14 and CK19, both at the protein and mRNA levels. The immunofluorescence staining also showed positive expression of CEA, CK7, CK14 and CK19 in induced fibroblasts, but there were no positive cells in the control groups. The expression of Shh and Cyclin D1, downstream genes of NF-κB and Lef-1, were also significantly increased during regeneration. The induced fibroblasts were implanted into an animal model. Twenty days later, iodine-starch perspiration tests showed that 7 out of the 10 cell-treated paws were positive for perspiration, with a distinctive black point-like area appearing in the center of the paw. Contralateral paws tested negative. Histological examination of skin biopsies from experimental and control paws revealed that sweat glands were fully reconstructed in the test paws, with integral, secretory and ductal portions, but were not present in the control paws. This is the first report of successful reprogramming of fibroblasts into sweat gland-like cells, which will provide a new cell source for sweat gland regeneration in patients with extensive deep burns. PMID:26566868

  7. Milk composition studies in transgenic goats expressing recombinant human butyrylcholinesterase in the mammary gland.

    PubMed

    Baldassarre, Hernan; Hockley, Duncan K; Olaniyan, Benjamen; Brochu, Eric; Zhao, Xin; Mustafa, Arif; Bordignon, Vilceu

    2008-10-01

    The use of the mammary gland of transgenic goats as a bioreactor is a well established platform for the efficient production of recombinant proteins, especially for molecules that cannot be adequately produced in traditional systems using genetically engineered microorganisms and cells. However, the extraordinary demand placed on the secretory epithelium by the expression of large amounts of the recombinant protein, may result in a compromised mammary physiology. In this study, milk composition was compared between control and transgenic goats expressing high levels (1-5 g/l) of recombinant human butyrylcholinesterase in the milk. Casein concentration, as evaluated by acid precipitation, was significantly reduced in the transgenic compared with the control goats throughout lactation (P < 0.01). Milk fatty acid composition for transgenic goats, as determined by gas chromatography, was found to have significantly fewer short chain fatty acids (P < 0.01) and more saturated fatty acids (P < 0.05) compared to controls, suggesting an overall metabolic stress and/or decreased expression of key enzymes (e.g. fatty acid synthase, stearoyl-CoA desaturase). The concentration of Na(+), K(+), assessed by atomic absorption spectrophotometry, and serum albumin, determined by bromocresol green dye and scanning densitometry, were similar in transgenic and control goats during the first several weeks of lactation. However, as lactation progressed, a significant increase in Na and serum albumin concentrations and a decrease in K(+) concentration were found in the milk of transgenic goats, while control animals remained unchanged (P < 0.01). These findings suggest that: (a) high expression of recombinant proteins may be associated with a slow-down in other synthetic activities at the mammary epithelium, as evidenced by a reduced casein expression and a decreased de-novo synthesis of fatty acids; (b) the development of permeable tight junctions may be the main mechanism involved in the

  8. Transmission and scanning electron microscopy of the human ceruminous apocrine gland. II. Myoepithelial cells.

    PubMed

    Kawabata, I; Kurosumi, K

    1976-09-01

    The myoepithelial cells of the human ceruminous apocrine gland were observed with transmission and scanning electron microscopes. The myoepithelial cells are long fibrous cells about 100-150 mum in length and 3-5 mum in width. They are arranged in parallel with each other, and their long axes are parallel to that of the secretory tubule itself. The tips of cells are often sharply pointed and their lateral tapering surface may be contiguous with adjacent cells forming a side-by-side contact, while other cells may have a blunt tip which is conjuncted with a similar tip of the next cell forming an end-to-end junction. The myoepithelial cells are joined to each other by desmosomes and there are also desmosomes at their junction with secretory cells. The outer surface of the cell abutting on the basal lamina has some exaggerated densities which are undoubtedly identical to the hemidesmosomes of epidermal cells. There are well developed foldings in the plasma membrane of the secretory cells, but the surface of the myoepithelial cells has very few foldings and projections. The relative shortage of intercellular attachment devices between the secretory and myeopithelial cells makes it easy to peel off the secretory cells to disclose the myoepithelium, a useful feature of scanning electron microscopy. The nucleus-containing part of the cell protrudes slightly upward and invades the secretory epithelium. The cytoplasmic rim surrounding the nucleus contains a small Golgi apparatus and some other organelles. The cytoplasm of the basal half of the cell contains closely packed myofilaments running parallel to the long axis of the cell. There is no definite arrangement of thin and thick myofilaments. Microtubules which often occur in pairs are arranged parallel to the myofilaments.

  9. MUC19 expression in human ocular surface and lacrimal gland and its alteration in Sjögren syndrome patients.

    PubMed

    Yu, D F; Chen, Y; Han, J M; Zhang, H; Chen, X P; Zou, W J; Liang, L Y; Xu, C C; Liu, Z G

    2008-02-01

    This study investigated the expression of MUC19, a newly discovered gel-forming mucin gene, in normal human lacrimal functional unit components and its alteration in Sjögren syndrome patients. Real-time PCR and immunohistochemistry were performed to determine the expression of MUC19 and MUC5AC in human cornea, conjunctiva, and lacrimal gland tissues. Conjunctival impression cytology specimens were collected from normal control subjects and Sjögren syndrome patients for Real-time PCR, PAS staining, and immunohistochemistry assays. In addition, conjunctiva biopsy specimens from both groups were examined for the expression differences of MUC19 and MUC5AC at both mRNA and protein level. The MUC19 mRNA was found to be present in cornea, conjunctiva and lacrimal gland tissues. The immunohistochemical staining of mucins showed that MUC19 was expressed in epithelial cells from corneal, conjunctival, and lacrimal gland tissues. In contrast, MUC5AC mRNA was only present in conjunctiva and lacrimal gland tissues, but not in cornea. Immunostaining demonstrates the co-staining of MUC19 and MUC5AC in conjunctival goblet cells. Consistent with the significant decrease of mucous secretion, both MUC19 and MUC5AC were decreased in conjunctiva of Sjögren syndrome patients compared to normal subjects. Considering the contribution of gel-forming mucins to the homeostasis of the ocular surface, the decreased expression of MUC19 and MUC5AC in Sjögren syndrome patients suggested that these mucins may be involved in the disruption of the ocular surface homeostasis in this disease. PMID:18184611

  10. MUC19 expression in human ocular surface and lacrimal gland and its alteration in Sjögren syndrome patients.

    PubMed

    Yu, D F; Chen, Y; Han, J M; Zhang, H; Chen, X P; Zou, W J; Liang, L Y; Xu, C C; Liu, Z G

    2008-02-01

    This study investigated the expression of MUC19, a newly discovered gel-forming mucin gene, in normal human lacrimal functional unit components and its alteration in Sjögren syndrome patients. Real-time PCR and immunohistochemistry were performed to determine the expression of MUC19 and MUC5AC in human cornea, conjunctiva, and lacrimal gland tissues. Conjunctival impression cytology specimens were collected from normal control subjects and Sjögren syndrome patients for Real-time PCR, PAS staining, and immunohistochemistry assays. In addition, conjunctiva biopsy specimens from both groups were examined for the expression differences of MUC19 and MUC5AC at both mRNA and protein level. The MUC19 mRNA was found to be present in cornea, conjunctiva and lacrimal gland tissues. The immunohistochemical staining of mucins showed that MUC19 was expressed in epithelial cells from corneal, conjunctival, and lacrimal gland tissues. In contrast, MUC5AC mRNA was only present in conjunctiva and lacrimal gland tissues, but not in cornea. Immunostaining demonstrates the co-staining of MUC19 and MUC5AC in conjunctival goblet cells. Consistent with the significant decrease of mucous secretion, both MUC19 and MUC5AC were decreased in conjunctiva of Sjögren syndrome patients compared to normal subjects. Considering the contribution of gel-forming mucins to the homeostasis of the ocular surface, the decreased expression of MUC19 and MUC5AC in Sjögren syndrome patients suggested that these mucins may be involved in the disruption of the ocular surface homeostasis in this disease.

  11. The prevalence of pineal cyst in patients with cerebral palsy

    PubMed Central

    Özmen, Evrim; Derinkuyu, Betül; Samancı, Cesur; Ünlü, Havva Akmaz; Demirkan, Tülin Hakan; Haşıloğlu, Zehra Işık; Kuruoğlu, Sebuh; Adaletli, İbrahim

    2015-01-01

    PURPOSE Pineal cysts are common incidental findings during magnetic resonance imaging (MRI) examinations. The etiology of pineal cyst development is still unclear. We aimed to determine whether there is an association between periventricular leukomalacia and pineal cyst prevalence. METHODS Clinical and MRI data of 201 patients with periventricular leukomalacia (110 female, 91 male; mean age, 6 years; range, 2–18 years) and 687 control patients (355 female, 332 male; mean age, 6 years¸ range, 2–18 years) who did not have any evidence of periventricular leukomalacia were independently evaluated by two radiologists for presence or absence of pineal cyst. RESULTS Pineal cysts were detected in 32.3% of the study group (65/201) and 8.4% of the control group (58/687) (P < 0.001). Patients with periventricular leukomalacia were more likely to have a pineal cyst. In terms of pineal cyst detection on MRI, interobserver reliability was high between the two radiologists. CONCLUSION The prevalence of pineal cysts is higher in patients with periventricular leukomalacia. We suggest that an ischemic process may have a role in the etiopathogenesis of pineal cyst development. PMID:25858521

  12. Effect of human chorionic gonadotropin on mammary gland differentiation and carcinogenesis.

    PubMed

    Russo, I H; Koszalka, M; Russo, J

    1990-10-01

    The observation that mammary carcinogenesis is inhibited in rats which completed a pregnancy prior to exposure to the chemical carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) led us to determine whether the protective effect of pregnancy could be mimicked by treatment with the placental hormone chorionic gonadotropin (hCG). We also studied the effect of this treatment on mammary gland structure and differentiation, and determined whether hCG exerts toxic or collateral effects on body weight and endocrine organs. The systemic effect of hCG on body wt and endocrine organs and mammary gland was studied in outbred virgin Sprague-Dawley rats which at the age of 50 days started receiving 100 IU hCG i.p. daily for 21 days. The animals were subdivided into nine groups of five animals each; one group was killed on the first day of and the others at 5, 10, 15 and 21 days of injection and 5, 10, 15 and 21 days post injection. The effect of the hormonal treatment on the estrous cycle was determined by studying the vaginal smears taken during and after the injection period. The following parameters were determined: body wt, weight and morphology of pituitary gland, adrenals, ovaries and uterine horns. Mammary glands were processed for histology, autoradiography for determination of DNA labeling index (DNA-LI) and whole mount preparation for morphometric studies. The effect of hCG on mammary carcinogenesis was studied in two groups of virgin rats; group I, which at the age of 50 days started receiving a daily i.p. injection of 100 IU hCG for 21 days; 21 days after the last injection they were given 8 mg DMBA/100 g body wt. Group II animals received DMBA only. hCG treated animals gained weight as a function of age at the same rate as controls. Treatment did not modify the weight of adrenal glands. The weight of ovaries, uterus and pituitary gland were transitorily increased by the 15th day of treatment, but had returned to the same values of controls by the time of DMBA

  13. Effect of glucocorticoid on epidermal growth factor receptor in human salivary gland adenocarcinoma cell line HSG.

    PubMed

    Kyakumoto, S; Kurokawa, R; Ota, M

    1990-07-12

    Human salivary gland adenocarcinoma (HSG) cells treated with 10(-6) M triamcinolone acetonide for 48 h exhibited a 1.7- to 2.0-fold increase in [125I]human epidermal growth factor (hEGF) binding capacity as compared with untreated HSG cells. Scatchard analysis of [125I]EGF binding data revealed that the number of binding sites was 83,700 (+/- 29,200) receptors/cell in untreated cells and 160,500 (+/- 35,500) receptors/cell in treated cells. No substantial change in receptor affinity was detected. The dissociation constant of the EGF receptor was 0.78 (+/- 0.26).10(-9) M for untreated cells, whereas it was 0.93 (+/- 0.31).10(-9)M for treated cells. The triamcinolone acetonide-induced increase in [125I]EGF binding capacity was dose-dependent between 10(-9) and 10(-6)M, and maximal binding was observed at 10(-6)M. EGF receptors on HSG cells were affinity-labeled with [125I]EGF by use of the cross-linking reagent disuccinimidyl suberate (DSS). The cross-linked [125I]EGF was 3-4% of the total [125I]EGF bound to HSG cells. The affinity-labeled EGF receptor was detected as a specific 170 kDa band in the autoradiograph after SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Densitometric analysis revealed that triamcinolone acetonide amplified the intensity of this band 2.0-fold over that of the band of untreated cells. EGF receptor synthesis was also measured by immunoprecipitation of [3H]leucine-labeled EGF receptor protein with anti-hEGF receptor monoclonal antibody. Receptor synthesis was increased 1.7- to 1.8-fold when HSG cells were treated with 10(-8)-10(-6)M triamcinolone acetonide for 48 h. When the immunoprecipitated, [35S]methionine-pulse-labeled EGF receptor was analyzed by SDS-PAGE and fluorography, the newly synthesized EGF receptor was detected at the position of 170 kDa; and treatment of HSG cells with triamcinolone acetonide resulted in a 2.0-fold amplification of this 170 kDa band. There was no significant difference in turnover rate of EGF receptor

  14. Primary Malignant Melanoma in the Pineal Region

    PubMed Central

    Hong, Yong-Kil

    2014-01-01

    A 59-year-old male patient had 5-month history of gait disturbance and memory impairment. His initial brain computed tomography scan showed 3.5×2.8 cm sized mass with high density in the pineal region. The tumor was hypointense on T2 weighted magnetic resonance images and hyperintense on T1 weighted magnetic resonance images with heterogenous enhancement of central portion. The tumor was totally removed via the occipital transtentorial approach. Black mass was observed in the operation field, and after surgery, histopathological examination confirmed the diagnosis of malignant melanoma. Whole spine magnetic resonance images and whole body 18-fluoro-deoxyglucose positron emission tomography could not demonstrate the primary site of this melanoma. Scrupulous physical examination of his skin and mucosa was done and dark pigmented lesion on his left leg was found, but additional studies including magnetic resonance images and skin biopsy showed negative finding. As a result, final diagnosis of primary pineal malignant melanoma was made. He underwent treatment with the whole brain radiotherapy and extended local boost irradiation without chemotherapy. His preoperative symptoms were disappeared, and no other specific neurological deficits were founded. His follow-up image studies showed no recurrence or distant metastasis until 26 weeks after surgery. Primary pineal malignant melanomas are extremely rare intracranial tumors, and only 17 cases have been reported since 1899. The most recent case report showed favorable outcome by subtotal tumor resection followed by whole brain and extended local irradiation without chemotherapy. Our case is another result to prove that total tumor resection with radiotherapy can be the current optimal treatment for primary malignant melanoma in the pineal region. PMID:25628812

  15. Neuroendoscopic management of pineal region tumours.

    PubMed

    Ferrer, E; Santamarta, D; Garcia-Fructuoso, G; Caral, L; Rumià, J

    1997-01-01

    The management of pineal tumours remains controversial. During 1994 we treated four consecutive adults (16-44 yrs) harbouring a pineal tumour with a neuroendoscopic procedure. All of them presented with hydrocephalus. Pre-operative workup included cranial computerized tomography (CT), craniospinal magnetic resonance imaging (MRI) and serum levels of biological tumour markers. The endoscopic procedure consisted of a third ventriculostomy followed by biopsy with a flexible, steerable neuroendoscope. Histological diagnosis was achieved in three patients who no longer required a shunt device. Recorded complications were: bleeding during ventriculostomy that prevented us from obtaining a good sample for biopsy, short-term memory loss that cleared over a two-week period, and transient increase of pre-operative hemiparesis. Complications and morbidity are emphasized so as to be avoided with further technical experience. Neuroendoscopy affords a minimally invasive way of reaching three objectives by one-step surgery in the management of pineal region lesions: 1) CSF sample for analysis of tumour markers. 2) Treatment of hydrocephalus by third ventriculostomy. 3) Several biopsy specimens can be obtained identifying tumours which will require further open surgery or adjuvant radiation and/or chemotherapy. PMID:9059706

  16. Comparison of Light Emitting Diodes (LED) and Fluorescent Light on Suppression of Pineal Melatonin in the Rat

    NASA Technical Reports Server (NTRS)

    Winget, Charles M.; Heeke, D. S.; Holley, D. C.; Mele, G.; Brainard, G. C.; Hanifin, J. P.; Rollag, M. D.; Savage, Paul D. (Technical Monitor)

    1997-01-01

    To validate a novel LED array for use in animal habitat lighting by comparing its effectiveness to cool-white fluorescent (CWF) lighting in suppressing pineal gland melatonin. Male Sprague-Dawley rats, 175-200 g, were maintained under control conditions for 2 weeks (food and water ad lib, 12L: 12D CWF, 18 uW/square cm). Dark adapted animals (animals before lights on) were exposed to 5 min of LED or CWF light of similar spectral power distribution. Two groups of rats (LED vs. CWF) were compared at 5 light intensities (100, 40, 1, 1.0, and 0. 1 lux). A control group was placed into the exposure apparatus but not exposed to light. After exposure, pineal glands were rapidly removed and assayed for melatonin by RIA. Results. The dark-exposed control groups matched with the 5 intensity groups (100, 40, 10, 1.0, and 0.1 lux) showed mean + SEM pineal melatonin values of 1167 +/- 136, 1569 +/- 126, 353 +/- 34, 650 +/- 124, and 464 +/- 85, pg/ml respectively. The corresponding CWF exposure data were 393 1 41, 365 +34, 257 +/- 13, 218 +/- 42, and 239 +/- 71 pg/ml, respectively. Corresponding LED exposure data were 439 +/- 25, 462 +/- 50, 231 +/- 6, 164 +/- 12, and 158 +/- 12 pg/ml, respectively. Rats exposed to both experimental light conditions at all illuminances studied showed significant melatonin suppression (p less than 0.01, ANOVA). In no case was the melatonin suppression induced by LED illuminance significantly different from the melatonin suppression elicited by the same intensity of CWF light. The results show that a novel LED light source can suppress pineal melatonin equal to that of a conventional CWF light source.

  17. Characterization of Angiogenesis and Lymphangiogenesis in Human Minor Salivary Glands with Sjögren’s Syndrome

    PubMed Central

    McCall, Andrew D.

    2015-01-01

    Angiogenesis has been proposed to play a role in the inflammation observed in Sjögren’s Syndrome (SS). However, no studies have validated the degree of angiogenesis in salivary glands with SS. Therefore, the goal of this study was to determine the presence and localization of angiogenesis and lymphangiogenesis in salivary glands with SS. We used frozen tissue sections from human minor salivary glands (hMSG) with and without SS in our analyses. To investigate signs of angiogenesis, hMSG tissue lysates were used to detect levels of the pro-angiogenic protein vascular endothelial growth factor (VEGF) by western blot analyses. Additionally, we labeled blood vessels using antibodies specific to platelet endothelial cell adhesion molecule-1 (PECAM-1) and von Willebrand Factor (vWF) to determine blood vessel organization and volume fraction using fluorescence microscopy. Lymphatic vessel organization and volume fraction were determined using antibodies specific to lymphatic vessel endothelial hyaluronan receptor (LYVE-1). Our results suggest that expression levels of VEGF are decreased in hMSG with SS as compared with controls. Interestingly, there were no significant differences in blood or lymphatic vessel organization or volume fraction between hMSG with and without SS, suggesting that angiogenesis and lymphangiogenesis have little impact on the progression of SS. PMID:25636309

  18. Topical spironolactone inhibits dihydrotestosterone receptors in human sebaceous glands: an autoradiographic study in subjects with acne vulgaris.

    PubMed

    Berardesca, E; Gabba, P; Ucci, G; Borroni, G; Rabbiosi, G

    1988-01-01

    The interaction between spironolactone and dihydrotestosterone (DHT) receptors was evaluated with an autoradiographic technique. The inhibition of DHT receptors by spironolactone was found to be related to the decrease of tritiated DHT granules in the sebaceous glands of the treated site. 6 male patients affected by acne vulgaris entered the study. The acute study was performed by applying to 25 cm2 of the back a cream containing 5% spironolactone under occlusive dressing. The dosage of spironolactone applied was 4 mg/cm2 for 48 h. The long-term study was performed by applying the same amount to the entire back, without occlusion, twice daily for 1 month. Skin biopsies were taken at the end of the treatment, incubated with tritiated DHT and processed for autoradiography. Both the acute and the long-term study revealed a decrease of the autoradiographic granules in the treated site. This effect is related to the binding of spironolactone with dihydrotestosterone receptors in the sebaceous glands. Our study demonstrates that 5% topical spironolactone cream acts as an antiandrogen in human sebaceous glands, competing with DHT receptors and producing a decrease of labelled DHT. At the concentrations used the effect has been only local. No side-effects were recorded during both studies. PMID:2972662

  19. Endocrine Glands & Their Hormones

    MedlinePlus

    ... Home » Cancer Registration & Surveillance Modules » Anatomy & Physiology » Endocrine System » Endocrine Glands & Their Hormones Cancer Registration & Surveillance Modules Anatomy & Physiology Intro to the Human Body Body Functions & Life Process Anatomical Terminology Review Quiz ...

  20. Human eccrine sweat gland cells reconstitute polarized spheroids when subcutaneously implanted with Matrigel in nude mice.

    PubMed

    Li, Haihong; Zhang, Mingjun; Chen, Liyun; Li, Xuexue; Zhang, Bingna

    2016-10-01

    Increasing evidence indicates that maintenance of cell polarity plays a pivotal role in the regulation of glandular homeostasis and function. We examine the markers for polarity at different time points to investigate the formation of cell polarity during 3D reconstitution of eccrine sweat glands. Mixtures of eccrine sweat gland cells and Matrigel were injected subcutaneously into the inguinal regions of nude mice. At 2, 3, 4, 5 and 6 weeks post-implantation, Matrigel plugs were removed and immunostained for basal collagen IV, lateral β-catenin, lateroapical ZO-1 and apical F-actin. The results showed that the cell polarity of the spheroids appeared in sequence. Formation of basal polarity was prior to lateral, apical and lateroapical polarity. Collagen IV was detected basally at 2 weeks, β-catenin laterally and ZO-1 lateroapically at 3 weeks, and F-actin apically at 4 weeks post-implantation. At week 5 and week 6, the localization and the positive percentage of collagen IV, β-catenin, ZO-1 or F-actin in spheroids was similar to that in native eccrine sweat glands. We conclude that the reconstituted 3D eccrine sweat glands are functional or potentially functional. PMID:27492422

  1. A case of human intramuscular adrenal gland transplantation as a cure for chronic adrenal insufficiency.

    PubMed

    Grodstein, E; Hardy, M A; Goldstein, M J

    2010-02-01

    Intramuscular endocrine gland transplantation has been well described as it pertains to parathyroid autotransplantation; however, transplantation of the adrenal gland is less well characterized. While adrenal autotransplantation in the setting of Cushing's disease has been described, intramuscular adrenal allotransplantation as a cure for adrenal insufficiency to our knowledge has not been previously carried out. Current treatment for adrenal insufficiency leaves patients without diurnal variation in cortisol release and susceptible to the detrimental effects of chronic hypercortisolism. We describe here the case of a 5-year-old girl with renal failure who had adrenal insufficiency following fulminant meningococcemia that led to requirements for both stress-dose steroid and mineralocorticoid replacement. Ten months after the onset of her disease, she received a simultaneous renal and adrenal gland transplant from her mother. The adrenal gland allograft was morselized into 1 mm(3) segments and implanted into three 2 cm pockets created in her rectus abdominis muscle. Three years after surgery, her allograft remains fully functional, responding well to adrenocorticotropin hormone stimulation and the patient does not require any steroid or mineral-corticoid supplementation. We believe this case represents the first description of successful functional intramuscular adrenal allograft transplantation with long-term follow up as a cure for adrenal insufficiency.

  2. Laser microspectrofluorometry for measuring dynamic changes of intracellular free Ca2+ in human airway gland cells

    NASA Astrophysics Data System (ADS)

    Millot, Jean-Marc; Merten, M.; Sharonov, S.; Figarella, C.; Jacquot, J.; Manfait, Michel

    1996-01-01

    Intracellular Ca2+ is a ubiquitous second messenger that regulates a wide variety of cellular functions including secretion, transepithelial solute and fluid transport. Laser confocal microspectrofluorometry (DILOR, Lille, France) was applied to visualize fluorescence emission spectra of the Indo-1 for measuring the intracellular free Ca2+ levels ([Ca2+]i) in a human tracheal gland immortalized cell line (MM39 cell line). Under a 351 nm laser excitation (0.5 (mu) W), the intracellular spectrum was analyzed as a ratio of the emission intensities at 420 and 500 nm. Previously, the intracellular Ca2+ calibration has been performed to define the relation between the intensity ratio and [Ca2+]i. Dynamic changes of single-cell [Ca2+]i were measured either from one substrate-attached cell or from different adjacent cells in monolayer culture. Measurements of [Ca2+]i are taken successively in different subcellular locations (up to 10 measurement points). Each measurement cycle was repeated 60 times. To do so, an (X,Y) motorized stage coupled with a computer allowed us to store the (X,Y) positions of several chosen points for the laser radiation. Cells were monitored for about 10 min. After agonist stimulation. Upon stimulating with calcium ionophore, 4BrA23187 (1 (mu) M), [Ca2+]i increased immediately up to 10 fold from a resting value of 31 plus or minus 6 nM (n equals 36). Histamine (1 to 100 (mu) M) increased [Ca2+]i in a concentration dependent manner with levels of up to 88 nM and 140 nM for 1 (mu) M and 100 (mu) M concentration, respectively, followed by a smooth decay back to baseline. Removal of extracellular Ca2+ did not abolish the histamine-stimulation [Ca2+]i rise, suggesting that a part of Ca2+ mobilization comes from intracellular Ca2+ stores. These results show that the combined use of the UV microspectrofluorometry and Indo-1 is well adapted and straight forward for the measurement of rapid responses of substrate-attached cells during experiments of long

  3. TNF-α inhibits aquaporin 5 expression in human salivary gland acinar cells via suppression of histone H4 acetylation.

    PubMed

    Yamamura, Yoshiko; Motegi, Katsumi; Kani, Kouichi; Takano, Hideyuki; Momota, Yukihiro; Aota, Keiko; Yamanoi, Tomoko; Azuma, Masayuki

    2012-08-01

    Sjögren's syndrome is a systemic autoimmune disease characterized by reductions in salivary and lacrimal secretions. The mechanisms underlying these reductions remain unclear. We have previously shown that TNF-α plays an important role in the destruction of acinar structures. Here we examined TNF-α's function in the expression of aquaporin (AQP) 5 in human salivary gland acinar cells. Immortalized human salivary gland acinar (NS-SV-AC) cells were treated with TNF-α, and then the expression levels of AQP5 mRNA and protein were analysed. In addition, the mechanisms underlying the reduction of AQP5 expression by TNF-α treatment were investigated. TNF-α-treatment of NS-SV-AC cells significantly suppressed the expression levels of AQP5 mRNA and protein, and reduced the net fluid secretion rate. We examined the expression and activation levels of DNA methyltransferases (Dnmts) in NS-SV-AC cells treated with TNF-α. However, no significant changes were observed in the expression or activation levels of Dnmt1, Dnmt3a or Dnmt3b. Although we also investigated the role of NF-κB activity in the TNF-α-induced suppression of AQP5 expression in NS-SV-AC cells, we detected similar TNF-α suppression of AQP5 expression in non-transfected cells and in a super-repressor form of IκBα cDNA-transfected cell clones. However, interestingly, chromatin immunoprecipitation analysis demonstrated a remarkable decrease in levels of acetylated histone H4 associated with the AQP5 gene promoter after treatment with TNF-α in NS-SV-AC cells. Therefore, our results may indicate that TNF-α inhibition of AQP5 expression in human salivary gland acinar cells is due to the epigenetic mechanism by suppression of acetylation of histone H4.

  4. Retino-hypothalamic-pineal hypothesis in the pathophysiology of primary headaches.

    PubMed

    Deshmukh, Vinod D

    2006-01-01

    Primary headaches include migraine, tension, cluster headaches, paroxysmal hemicrania and miscellaneous headaches unassociated with structural lesions. A putative role of the retino-hypothalamic-pineal (RHP) axis in the pathophysiology of primary headaches is reviewed in terms of (1) retinal dysfunction, (2) hypothalamic dysfunction and human circadian desynchrony, (3) pineal melatonin dysfunction and (4) rostral limbic dysfunction mediating the human stress response. Unified RHP hypothesis is proposed, suggesting that an acute, periodic or chronic, circadian desynchrony and dysfunction of the whole or part of the RHP axis is implicated in the pathophysiology of primary headaches. Supportive evidence for the RHP hypothesis, including recent PET studies showing changes in dorsal pons, hypothalamus and rostral limbic structures, is presented.

  5. Split gland

    DOEpatents

    Petranto, J.J.

    1989-09-05

    A split gland having only three parts is described. The gland has substantially the same stability to the relative motion of the constituent half-gland members during the attachment process to a female fitting as have more complicated designs. Ease of manufacture and use result from the reduction in complexity of the present invention. 15 figs.

  6. Split gland

    DOEpatents

    Petranto, Joseph J.

    1989-01-01

    A split gland having only three parts is described. The gland has substantially the same stability to the relative motion of the constituent half-gland members during the attachment process to a female fitting as have more complicated designs. Ease of manufacture and use result from the reduction in complexity of the present invention.

  7. Review of pineal anlage tumor with divergent histology.

    PubMed

    Berns, Stephen; Pearl, Gary

    2006-08-01

    Pineal anlage tumor is an extremely rare tumor that is not listed in the 2000 World Health Organization Classification of nervous system tumors. It has been defined as a primary pineal tumor with both neuroepithelial and ectomesenchymal differentiation and without endodermal differentiation. We review the literature on this tumor, including the clinical presentation, gross pathology, histopathology, immunohistochemistry, differential diagnosis, and prognosis.

  8. Simian virus 40 sequences and expression of the viral large T antigen oncoprotein in human pleomorphic adenomas of parotid glands.

    PubMed

    Martinelli, Marcella; Martini, Fernanda; Rinaldi, Eliana; Caramanico, Laura; Magri, Eros; Grandi, Enrico; Carinci, Francesco; Pastore, Antonio; Tognon, Mauro

    2002-10-01

    Simian virus 40 (SV40) sequences of the early region coding for the large T antigen (Tag) oncoprotein were investigated in DNA samples from human pleomorphic adenoma (PA) of parotid glands. Specific SV40 sequences were detected, by PCR and filter hybridization with an internal oligoprobe, in 28 of 45 (62%) human PA specimens. None of the DNA samples from 11 normal salivary gland tissues was SV40-positive. DNA sequence analysis, carried out in all PCR amplified products from SV40-positive PA specimens, confirmed the SV40 specificity and indicated that PCR products had a sequence not distinguishable from SV40 DNA wild-type strain 776. SV40 Tag expression was revealed by immunohistochemistry with the specific monoclonal antibody Pab 101 in PA thin sections with a highly sensitive technical approach which retrieved the nuclear viral oncoprotein in 26 out of 28 (93%) samples previously found SV40-positive by PCR. Detection of SV40 sequences and Tag expression in human PA suggests that this oncogenic virus may play a role as a cofactor in the onset and/or progression of this benign neoplasm, or that SV40 DNA could replicate and express the Tag in PA cells.

  9. Low-Grade Oligodendroglioma of the Pineal Region: Case Report.

    PubMed

    Lamis, Fabricio Correa; de Paiva Neto, Manoel Antonio; Stavale, João Norberto; Cavalheiro, Sergio

    2015-07-01

    Background Although germ cell tumors and pineal cell tumors account for most of the histologic tumor subtypes, > 17 different tumors can arise in this location. We report a rare case of a low-grade oligodendroglioma that arose in the pineal region. Clinical Presentation A young woman complaining of a headache underwent magnetic resonance imaging that showed a mass in the pineal region and mild hydrocephalus. A ventriculoperitoneal shunt was performed followed by a near-total tumor removal, due to tumor invasion of the tectal plate and thalamus. The histologic examination confirmed the diagnosis of a low-grade oligodendroglioma. The patient then underwent chemotherapy and radiotherapy as adjuvant therapies. Conclusion Although the pineal region is a common place for a large number of tumoral lesions, low-grade oligodendrogliomas are extremely rare in this location. This case is only the second account of a benign oligodendroglioma of the pineal region reported in the literature.

  10. Phenotype and cell proliferation activity of duct-like structures in human sublingual glands: a histological and immunohistochemical study

    PubMed Central

    TOLENTINO, Elen de Souza; TEIXEIRA, Cleverson Soares; AZEVEDO-ALANIS, Luciana Reis; HONÓRIO, Heitor Marques; DAMANTE, José Humberto

    2015-01-01

    There are several age-related microscopic changes in the salivary glands, including the increase in the number of duct-like structures (DLS). However, the true origin and the phenotype of the DLS are not known. Objective To evaluate the phenotype and the cell proliferation index of the DLS of human sublingual glands. Material and Methods Sixty sublingual glands obtained from human cadavers were divided into two groups - 0-30 and 61-90 years old. The phenotype was estimated by immunostaining for cytokeratin 19 (CK 19) and the S-100 protein as well as by the presence of mucin and glycogen. The cell proliferation index was determined by the Ki-67 antibody. The histochemical techniques used periodic acid-Schiff (PAS) and Alcian Blue. In each captured microscopic field, the DLS were counted to establish a percentage for the staining profile. The statistical analysis was accomplished using Student’s t-test, the Mann-Whitney test and Pearson’s correlation coefficient (p<0.05). Results Comparing both groups, only CK 19 showed a statistically significant difference (p=0.033), with the strongest expression in the elderly group. There was no significant difference between PAS and Alcian Blue (p=0.270). In both groups, the immunostaining for CK 19 was stronger than that for S-100 (p=0.004;p<0.001), but there was no correlation between the two immunomarkers (ρ=-0.163; p=0.315). There was no immunostaining for Ki-67. Conclusions DLS demonstrate a ductal phenotypic profile and do not present cell proliferation activity. DLS may represent a regressive process arising from acini or represent the result of metaplasia. PMID:26221919

  11. BK virus has tropism for human salivary gland cells in vitro: Implications for transmission

    SciTech Connect

    Jeffers, Liesl K.; Madden, Vicki; Webster-Cyriaque, Jennifer

    2009-11-25

    Background: In this study, it was determined that BKV is shed in saliva and an in vitro model system was developed whereby BKV can productively infect both submandibular (HSG) and parotid (HSY) salivary gland cell lines. Results: BKV was detected in oral fluids using quantitative real-time PCR (QRTPCR). BKV infection was determined using quantitative RT-PCR, immunofluorescence and immunoblotting assays. The infectivity of BKV was inhibited by pre-incubation of the virus with gangliosides that saturated the major capsid protein, VP1, halting receptor mediated BKV entry into salivary gland cells. Examination of infected cultures by transmission electron microscopy revealed 45-50 nm BK virions clearly visible within the cells. Subsequent to infection, encapsidated BK virus was detected in the supernatant. Conclusion: We thus demonstrated that BKV was detected in oral fluids and that BK infection and replication occur in vitro in salivary gland cells. These data collectively suggest the potential for BKV oral route of transmission and oral pathogenesis.

  12. Differential scanning calorimetric evaluation of human meibomian gland secretions and model lipid mixtures: transition temperatures and cooperativity of melting

    PubMed Central

    Lu, Hua; Wojtowicz, Jadwiga C.; Butovich, Igor A.

    2013-01-01

    Meibomian gland secretions (or meibum) are produced by holocrine meibomian glands and are secreted in melted form onto the ocular surface of humans and animals to form a protective tear film lipid layer (TFLL). Its protective effect strongly depends on the composition and, hence, thermotropic behavior of meibum. The goal of our study was to quantitatively evaluate the melting characteristics of human meibum and model lipid mixtures using differential scanning microcalorimetry. Standard calorimetric parameters, e.g. changes in calorimetric enthalpy, transition temperatures T(m), cooperativity of melting etc. were assessed. We found that thermotropic behavior of meibum resembled that of relatively simple mixtures of unsaturated wax esters, but showed a lower change in calorimetric enthalpy, which can be indicative of a looser packing of lipids in meibum compared with pure standards and their simple mixtures. The cooperativity of melting of meibomian lipids was comparable to that of an equimolar mixture of four oleic-acid based wax esters. We demonstrated that the phase transitions in meibum start at about 10 to 15 °C and end at 35-36 °C, with T(m) being about 30 °C. The highly asymmetrical shape of the thermotropic peak of meibum is important for the physiology and biophysics of TFLL. PMID:23578711

  13. A connection between extracellular matrix and hormonal signals during the development of the human fetal adrenal gland.

    PubMed

    Chamoux, E; Otis, M; Gallo-Payet, N

    2005-10-01

    The human adrenal cortex, involved in adaptive responses to stress, body homeostasis and secondary sexual characters, emerges from a tightly regulated development of a zone-specific secretion pattern during fetal life. Its development during fetal life is critical for the well being of pregnancy, the initiation of delivery, and even for an adequate adaptation to extra-uterine life. As early as from the sixth week of pregnancy, the fetal adrenal gland is characterized by a highly proliferative zone at the periphery, a concentric migration accompanied by cell differentiation (cortisol secretion) and apoptosis in the central androgen-secreting fetal zone. After birth, a strong reorganization occurs in the adrenal gland so that it better fulfills the newborn's needs, with aldosterone production in the external zona glomerulosa, cortisol secretion in the zona fasciculata and androgens in the central zona reticularis. In addition to the major hormonal stimuli provided by angiotensin II and adrenocorticotropin, we have tested for some years the hypotheses that such plasticity may be under the control of the extracellular matrix. A growing number of data have been harvested during the last years, in particular about extracellular matrix expression and its putative role in the development of the human adrenal cortex. Laminin, collagen and fibronectin have been shown to play important roles not only in the plasticity of the adrenal cortex, but also in cell responsiveness to hormones, thus clarifying some of the unexplained observations that used to feed controversies. PMID:16172742

  14. Expression of Matrix Metalloproteinase (MMP)-20 and Potential Interaction with Dentin Sialophosphoprotein (DSPP) in Human Major Salivary Glands.

    PubMed

    Koli, Komal; Saxena, Geetu; Ogbureke, Kalu U E

    2015-07-01

    Matrix metalloproteinase-20 (MMP-20) expression is widely regarded as tooth-specific, with expression limited to dental hard tissues. Necessary for sound enamel formation, MMP-20 and MMP-2 proteolytically process dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein during tooth formation. In the mid-2000s, three members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) were reported to bind specifically with high affinity (nM) to, and activate, three MMPs in vitro: bone sialoprotein with MMP-2; osteopontin with MMP-3; and dentin matrix protein1 with MMP-9. The SIBLING-MMP interaction was confirmed in biological systems such as the ducts of salivary glands, where all five members of the SIBLINGs are expressed. Recently, we documented MMP-20 expression and interaction with DSPP (another member of the SIBLING family) in human oral squamous cell carcinoma. Here we report the expression of MMP-20, and confirm its co-expression and potential interaction with DSPP in human major salivary gland tissues and cell line using immunohistochemistry, immunofluorescence, western blot, quantitative RT-PCR, and proximity ligation assay. This report reinforces our earlier suggestion that the SIBLING-MMP complexes may be involved in the turnover of extracellular proteins damaged by oxidation byproducts in metabolically active duct epithelial systems.

  15. Pineal region tumors: analysis of treatment results

    SciTech Connect

    Amendola, B.E.; McClatchey, K.; Amendola, M.A.

    1984-07-01

    This article represents a review of 32 patients with pineal region tumors seen and treated at the University of Michigan Medical Center from January 1950 to December 1980. All patients presented with manifestations of increased intracranial pressure: limitation of the upward gaze (Parinaud's syndrome), hydrocephalus and a mass in the posterior aspect of the third ventricle. The tumor was demonstrated by pneumoencephalography, ventriculography, angiography or CT scans. Ventricular decompression was performed in all patients. Twenty-seven patients received post-operative irradiation. The overall 10 year survival for evaluable patients was 16/24 (67%). Few complications were seen.

  16. Human breast cancer cells are redirected to mammary epithelial cells upon interaction with the regenerating mammary gland microenvironment in-vivo.

    PubMed

    Bussard, Karen M; Smith, Gilbert H

    2012-01-01

    Breast cancer is the second leading cause of cancer deaths in the United States. At present, the etiology of breast cancer is unknown; however the possibility of a distinct cell of origin, i.e. a cancer stem cell, is a heavily investigated area of research. Influencing signals from the tissue niche are known to affect stem cells. Literature has shown that cancer cells lose their tumorigenic potential and display 'normal' behavior when placed into 'normal' ontogenic environments. Therefore, it may be the case that the tissue microenvironment is able to generate signals to redirect cancer cell fate. Previously, we showed that pluripotent human embryonal carcinoma cells could be redirected by the regenerating mammary gland microenvironment to contribute epithelial progeny for 'normal' gland development in-vivo. Here, we show that that human metastatic, non-metastatic, and metastasis-suppressed breast cancer cells proliferate and contribute to normal mammary gland development in-vivo without tumor formation. Immunochemistry for human-specific mitochondria, keratin 8 and 14, as well as human-specific milk proteins (alpha-lactalbumin, impregnated transplant hosts) confirmed the presence of human cell progeny. Features consistent with normal mammary gland development as seen in intact hosts (duct, lumen formation, development of secretory acini) were recapitulated in both primary and secondary outgrowths from chimeric implants. These results suggest the dominance of the tissue microenvironment over cancer cell fate. This work demonstrates that cultured human breast cancer cells (metastatic and non-metastatic) respond developmentally to signals generated by the mouse mammary gland microenvironment during gland regeneration in-vivo.

  17. Pineal melatonin is a circadian time-giver for leptin rhythm in Syrian hamsters

    PubMed Central

    Chakir, Ibtissam; Dumont, Stéphanie; Pévet, Paul; Ouarour, Ali; Challet, Etienne; Vuillez, Patrick

    2015-01-01

    Nocturnal secretion of melatonin from the pineal gland may affect central and peripheral timing, in addition to its well-known involvement in the control of seasonal physiology. The Syrian hamster is a photoperiodic species, which displays gonadal atrophy and increased adiposity when adapted to short (winter-like) photoperiods. Here we investigated whether pineal melatonin secreted at night can impact daily rhythmicity of metabolic hormones and glucose in that seasonal species. For that purpose, daily variations of plasma leptin, cortisol, insulin and glucose were analyzed in pinealectomized hamsters, as compared to sham-operated controls kept under very long (16 h light/08 h dark) or short photoperiods (08 h light/16 h dark). Daily rhythms of leptin under both long and short photoperiods were blunted by pinealectomy. Furthermore, the phase of cortisol rhythm under a short photoperiod was advanced by 5.6 h after pinealectomy. Neither plasma insulin, nor blood glucose displays robust daily rhythmicity, even in sham-operated hamsters. Pinealectomy, however, totally reversed the decreased levels of insulin under short days and the photoperiodic variations in mean levels of blood glucose (i.e., reduction and increase in long and short days, respectively). Together, these findings in Syrian hamsters show that circulating melatonin at night drives the daily rhythmicity of plasma leptin, participates in the phase control of cortisol rhythm and modulates glucose homeostasis according to photoperiod-dependent metabolic state. PMID:26074760

  18. Expression of Human NSAID Activated Gene 1 in Mice Leads to Altered Mammary Gland Differentiation and Impaired Lactation.

    PubMed

    Binder, April K; Kosak, Justin P; Janardhan, Kyathanahalli S; Janhardhan, Kyathanahalli S; Moser, Glenda; Eling, Thomas E; Korach, Kenneth S

    2016-01-01

    Transgenic mice expressing human non-steroidal anti-inflammatory drug activated gene 1 (NAG-1) have less adipose tissue, improved insulin sensitivity, lower insulin levels and are resistant to dietary induced obesity. The hNAG-1 expressing mice are more metabolically active with a higher energy expenditure. This study investigates female reproduction in the hNAG-1 transgenic mice and finds the female mice are fertile but have reduced pup survival after birth. Examination of the mammary glands in these mice suggests that hNAG-1 expressing mice have altered mammary epithelial development during pregnancy, including reduced occupancy of the fat pad and increased apoptosis via TUNEL positive cells on lactation day 2. Pups nursing from hNAG-1 expressing dams have reduced milk spots compared to pups nursing from WT dams. When CD-1 pups were cross-fostered with hNAG-1 or WT dams; reduced milk volume was observed in pups nursing from hNAG-1 dams compared to pups nursing from WT dams in a lactation challenge study. Milk was isolated from WT and hNAG-1 dams, and the milk was found to have secreted NAG-1 protein (approximately 25 ng/mL) from hNAG-1 dams. The WT dams had no detectable hNAG-1 in the milk. A decrease in non-esterified free fatty acids in the milk of hNAG-1 dams was observed. Altered milk composition suggests that the pups were receiving inadequate nutrients during perinatal development. To examine this hypothesis serum was isolated from pups and clinical chemistry points were measured. Male and female pups nursing from hNAG-1 dams had reduced serum triglyceride concentrations. Microarray analysis revealed that genes involved in lipid metabolism are differentially expressed in hNAG-1 mammary glands. Furthermore, the expression of Cidea/CIDEA that has been shown to regulate milk lipid secretion in the mammary gland was reduced in hNAG-1 mammary glands. This study suggests that expression of hNAG-1 in mice leads to impaired lactation and reduces pup survival due to

  19. Expression of Human NSAID Activated Gene 1 in Mice Leads to Altered Mammary Gland Differentiation and Impaired Lactation.

    PubMed

    Binder, April K; Kosak, Justin P; Janardhan, Kyathanahalli S; Janhardhan, Kyathanahalli S; Moser, Glenda; Eling, Thomas E; Korach, Kenneth S

    2016-01-01

    Transgenic mice expressing human non-steroidal anti-inflammatory drug activated gene 1 (NAG-1) have less adipose tissue, improved insulin sensitivity, lower insulin levels and are resistant to dietary induced obesity. The hNAG-1 expressing mice are more metabolically active with a higher energy expenditure. This study investigates female reproduction in the hNAG-1 transgenic mice and finds the female mice are fertile but have reduced pup survival after birth. Examination of the mammary glands in these mice suggests that hNAG-1 expressing mice have altered mammary epithelial development during pregnancy, including reduced occupancy of the fat pad and increased apoptosis via TUNEL positive cells on lactation day 2. Pups nursing from hNAG-1 expressing dams have reduced milk spots compared to pups nursing from WT dams. When CD-1 pups were cross-fostered with hNAG-1 or WT dams; reduced milk volume was observed in pups nursing from hNAG-1 dams compared to pups nursing from WT dams in a lactation challenge study. Milk was isolated from WT and hNAG-1 dams, and the milk was found to have secreted NAG-1 protein (approximately 25 ng/mL) from hNAG-1 dams. The WT dams had no detectable hNAG-1 in the milk. A decrease in non-esterified free fatty acids in the milk of hNAG-1 dams was observed. Altered milk composition suggests that the pups were receiving inadequate nutrients during perinatal development. To examine this hypothesis serum was isolated from pups and clinical chemistry points were measured. Male and female pups nursing from hNAG-1 dams had reduced serum triglyceride concentrations. Microarray analysis revealed that genes involved in lipid metabolism are differentially expressed in hNAG-1 mammary glands. Furthermore, the expression of Cidea/CIDEA that has been shown to regulate milk lipid secretion in the mammary gland was reduced in hNAG-1 mammary glands. This study suggests that expression of hNAG-1 in mice leads to impaired lactation and reduces pup survival due to

  20. Pineal region tumors: Clinical symptoms and syndromes.

    PubMed

    Rousselle, C; des Portes, V; Berlier, P; Mottolese, C

    2015-01-01

    The present paper investigates the clinical picture and the different clinical signs that reveal pineal region tumors or appear during the course of the follow-up. Biological malignancy and tumor extension determine the semiology and its setting up mode. Typical endocrine signs, dominated by abnormal puberty development, are frequently a part of the clinical scene. Bifocal or ectopic localization in the hypothalamic-pituitary region is accompanied by other endocrine signs such as ante- or post-pituitary insufficiencies which occur several months or even years after the first neurological signs appear. Due to a mass syndrome and obstructive hydrocephalus, intracranial hypertension signs are frequent but unspecific. A careful ophthalmologic examination is essential to search upward gaze paralysis and other signs of the Parinaud's tetrad or pentad. Midbrain dysfunction, including extrinsic aqueduct stenosis, are also prevalent. Except for abnormal pubertal signs, hyper-melatoninemia (secretory tumors) or a-hypo-melatoninemia (tumors destructing pineal) generally remains dormant. Some patients present sleep problems such as narcolepsy or sleepiness during the daytime as well as behavioral problems. This suggests a hypothalamic extension rather than a true consequence of melatonin secretion anomalies. Similarly, some patients may present signs of a "pinealectomized" syndrome, including (cluster) headaches, tiredness, eventually responsive to melatonin. PMID:24439798

  1. Formation of post-confluence structure in human parotid gland acinar cells on PLGA through regulation of E-cadherin.

    PubMed

    Chan, Yen-Hui; Huang, Tsung-Wei; Chou, Ya-Shuan; Hsu, Sheng-Hao; Su, Wei-Fang; Lou, Pei-Jen; Young, Tai-Horng

    2012-01-01

    As a potential solution for patients to retrieve their lost salivary gland functions, tissue engineering of an auto-secretory device is profoundly needed. Under serum-free environment, primary human parotid gland acinar (PGAC) cells can be obtained. After reaching confluence, PGAC cells spontaneously form three-dimension (3D) cell aggregations, termed post-confluence structure (PCS), and change their behaviors. Poly (lactic-co-glycolic acid) (PLGA) has been widely used in the field of biomedical applications because of its biodegradable properties for desired functions. Nonetheless, the role of PLGA in facilitating PGAC cells to form PCS has seldom been explored to recover epithelial characteristics. In this study, PGAC cells were found to have a greater tendency to form PCS on PLGA than on tissue culture polystyrene (TCPS). By tracing cell migration paths and modulating E-cadherin activity with specific inhibitor or antibody, we demonstrated that the static force of homophilic interaction on surfaces of individual cells, but not the dynamics of cell migration, played a more important role in PCS formation. Thus, PLGA was successfully confirmed to support PGAC cells to form more PCS through the effects on enhancing E-cadherin expression, which is associated with FAK/ILK/Snail expression in PGAC cells. This result indicates that selective appropriate biomaterials may be potentially useful in generating 3D PCS on two-dimension (2D) substrate without fabricating a complex 3D scaffold.

  2. Bufadienolides from parotoid gland secretions of Cuban toad Peltophryne fustiger (Bufonidae): Inhibition of human kidney Na(+)/K(+)-ATPase activity.

    PubMed

    Perera Córdova, Wilmer H; Leitão, Suzana Guimarães; Cunha-Filho, Geraldino; Bosch, Roberto Alonso; Alonso, Isel Pascual; Pereda-Miranda, Rogelio; Gervou, Rodrigo; Touza, Natália Araújo; Quintas, Luis Eduardo M; Noël, François

    2016-02-01

    Parotoid gland secretions of toad species are a vast reservoir of bioactive molecules with a wide range of biological properties. Herein, for the first time, it is described the isolation by preparative reversed-phase HPLC and the structure elucidation by NMR spectroscopy and/or mass spectrometry of nine major bufadienolides from parotoid gland secretions of the Cuban endemic toad Peltophryne fustiger: ψ-bufarenogin, gamabufotalin, bufarenogin, arenobufagin, 3-(N-suberoylargininyl) marinobufagin, bufotalinin, telocinobufagin, marinobufagin and bufalin. In addition, the secretion was analyzed by UPLC-MS/MS which also allowed the identification of azelayl arginine. The effect of arenobufagin, bufalin and ψ-bufarenogin on Na(+)/K(+)-ATPase activity in a human kidney preparation was evaluated. These bufadienolides fully inhibited the Na(+)/K(+)-ATPase in a concentration-dependent manner, although arenobufagin (IC50 = 28.3 nM) and bufalin (IC50 = 28.7 nM) were 100 times more potent than ψ-bufarenogin (IC50 = 3020 nM). These results provided evidence about the importance of the hydroxylation at position C-14 in the bufadienolide skeleton for the inhibitory activity on the Na(+)/K(+)-ATPase.

  3. Function of human eccrine sweat glands during dynamic exercise and passive heat stress

    NASA Technical Reports Server (NTRS)

    Kondo, N.; Shibasaki, M.; Aoki, K.; Koga, S.; Inoue, Y.; Crandall, C. G.

    2001-01-01

    The purpose of this study was to identify the pattern of change in the density of activated sweat glands (ASG) and sweat output per gland (SGO) during dynamic constant-workload exercise and passive heat stress. Eight male subjects (22.8 +/- 0.9 yr) exercised at a constant workload (117.5 +/- 4.8 W) and were also passively heated by lower-leg immersion into hot water of 42 degrees C under an ambient temperature of 25 degrees C and relative humidity of 50%. Esophageal temperature, mean skin temperature, sweating rate (SR), and heart rate were measured continuously during both trials. The number of ASG was determined every 4 min after the onset of sweating, whereas SGO was calculated by dividing SR by ASG. During both exercise and passive heating, SR increased abruptly during the first 8 min after onset of sweating, followed by a slower increase. Similarly for both protocols, the number of ASG increased rapidly during the first 8 min after the onset of sweating and then ceased to increase further (P > 0.05). Conversely, SGO increased linearly throughout both perturbations. Our results suggest that changes in forearm sweating rate rely on both ASG and SGO during the initial period of exercise and passive heating, whereas further increases in SR are dependent on increases in SGO.

  4. In Vivo Laser Scanning Confocal Microscopy of Human Meibomian Glands in Aging and Ocular Surface Diseases.

    PubMed

    Fasanella, Vincenzo; Agnifili, Luca; Mastropasqua, Rodolfo; Brescia, Lorenza; Di Staso, Federico; Ciancaglini, Marco; Mastropasqua, Leonardo

    2016-01-01

    Meibomian glands (MGs) play a crucial role in the ocular surface homeostasis by providing lipids to the superficial tear film. Their dysfunction destabilizes the tear film leading to a progressive loss of the ocular surface equilibrium and increasing the risk for dry eye. In fact, nowadays, the meibomian gland dysfunction is one of the leading causes of dry eye. Over the past decades, MGs have been mainly studied by using meibography, which, however, cannot image the glandular structure at a cellular level. The diffusion of the in vivo laser scanning confocal microscopy (LSCM) provided a new approach for the structural assessment of MGs permitting a major step in the noninvasive evaluation of these structures. LSCM is capable of showing MGs modifications during aging and in the most diffuse ocular surface diseases such as dry eye, allergy, and autoimmune conditions and in the drug-induced ocular surface disease. On the other hand, LSCM may help clinicians in monitoring the tissue response to therapy. In this review, we summarized the current knowledge about the role of in vivo LSCM in the assessment of MGs during aging and in the most diffuse ocular surface diseases.

  5. In Vivo Laser Scanning Confocal Microscopy of Human Meibomian Glands in Aging and Ocular Surface Diseases.

    PubMed

    Fasanella, Vincenzo; Agnifili, Luca; Mastropasqua, Rodolfo; Brescia, Lorenza; Di Staso, Federico; Ciancaglini, Marco; Mastropasqua, Leonardo

    2016-01-01

    Meibomian glands (MGs) play a crucial role in the ocular surface homeostasis by providing lipids to the superficial tear film. Their dysfunction destabilizes the tear film leading to a progressive loss of the ocular surface equilibrium and increasing the risk for dry eye. In fact, nowadays, the meibomian gland dysfunction is one of the leading causes of dry eye. Over the past decades, MGs have been mainly studied by using meibography, which, however, cannot image the glandular structure at a cellular level. The diffusion of the in vivo laser scanning confocal microscopy (LSCM) provided a new approach for the structural assessment of MGs permitting a major step in the noninvasive evaluation of these structures. LSCM is capable of showing MGs modifications during aging and in the most diffuse ocular surface diseases such as dry eye, allergy, and autoimmune conditions and in the drug-induced ocular surface disease. On the other hand, LSCM may help clinicians in monitoring the tissue response to therapy. In this review, we summarized the current knowledge about the role of in vivo LSCM in the assessment of MGs during aging and in the most diffuse ocular surface diseases. PMID:27047965

  6. In Vivo Laser Scanning Confocal Microscopy of Human Meibomian Glands in Aging and Ocular Surface Diseases

    PubMed Central

    Fasanella, Vincenzo; Mastropasqua, Rodolfo; Brescia, Lorenza; Di Staso, Federico; Ciancaglini, Marco; Mastropasqua, Leonardo

    2016-01-01

    Meibomian glands (MGs) play a crucial role in the ocular surface homeostasis by providing lipids to the superficial tear film. Their dysfunction destabilizes the tear film leading to a progressive loss of the ocular surface equilibrium and increasing the risk for dry eye. In fact, nowadays, the meibomian gland dysfunction is one of the leading causes of dry eye. Over the past decades, MGs have been mainly studied by using meibography, which, however, cannot image the glandular structure at a cellular level. The diffusion of the in vivo laser scanning confocal microscopy (LSCM) provided a new approach for the structural assessment of MGs permitting a major step in the noninvasive evaluation of these structures. LSCM is capable of showing MGs modifications during aging and in the most diffuse ocular surface diseases such as dry eye, allergy, and autoimmune conditions and in the drug-induced ocular surface disease. On the other hand, LSCM may help clinicians in monitoring the tissue response to therapy. In this review, we summarized the current knowledge about the role of in vivo LSCM in the assessment of MGs during aging and in the most diffuse ocular surface diseases. PMID:27047965

  7. Vascular endothelial growth factor is constitutively expressed in normal human salivary glands and is secreted in the saliva of healthy individuals.

    PubMed

    Pammer, J; Weninger, W; Mildner, M; Burian, M; Wojta, J; Tschachler, E

    1998-10-01

    The expression of vascular endothelial growth factor (VEGF), a specific mitogen for endothelial cells, was examined in salivary glands and in normal saliva. In normal salivary glands, VEGF mRNA and protein were strongly present in acinar cells, whereas little or no VEGF was found in ductal cells. In chronically inflamed glands, VEGF protein was in addition present in ductal elements and in infiltrating mononuclear cells. No difference of VEGF expression was observed between benign and malignant salivary gland tumours. By ELISA, whole saliva of 24 healthy individuals contained up to 2.5 ng/ml (mean 1.4 ng/ml; SD 0.77 ng/ml) of VEGF, confirming the constitutive secretion of this cytokine by human salivary glands. Western blot analysis of normal saliva under non-reducing conditions detected anti-VEGF reactive protein moieties of approximately 46 kD, corresponding to VEGF secreted by cells in tissue culture. Additional anti-VEGF reactive proteins of approximately 60 and 90 kD were detected in the saliva of some individuals. The presence of considerable quantities of VEGF in normal human saliva suggests an important role for this cytokine in the maintenance of the homeostasis of mucous membranes, with rapid induction of neoangiogenesis by salivary VEGF helping to accelerate wound healing within the oral cavity. Moreover, salivary VEGF may permeabilize intraglandular capillaries and thus participate in the regulation of saliva production itself.

  8. Alpha-human atrial natriuretic polypeptide (. cap alpha. -hANP) specific binding sites in bovine adrenal gland

    SciTech Connect

    Higuchi, K.; Nawata, H.; Kato, K.I.; Ibayashi, H.; Matsuo, H.

    1986-06-13

    The effects of synthetic ..cap alpha..-human atrial natriuretic polypeptide (..cap alpha..-hANP) on steroidogenesis in bovine adrenocortical cells in primary monolayer culture were investigated. ..cap alpha..-hANP did not inhibit basal aldosterone secretion. ..cap alpha..-hANP induced a significant dose-dependent inhibition of basal levels of cortisol and dehydroepiandrosterone (DHEA) secretion and also of aCTH (10/sup -8/M)-stimulated increases in aldosterone, cortisol and DHEA secretion. Visualization of (/sup 125/I) ..cap alpha..-hANP binding sites in bovine adrenal gland by an in vitro autoradiographic technique demonstrated that these sites were highly localized in the adrenal cortex, especially the zona glomerulosa. These results suggest that the adrenal cortex may be a target organ for direct receptor-mediated actions of ..cap alpha..-hANP.

  9. Physico-chemical characterization of human von Ebner gland protein expressed in Escherichia coli: implications for its physiological role.

    PubMed

    Creuzenet, C; Mangroo, D

    1998-11-01

    The human von Ebner gland protein (VEG) was expressed in Escherichia coli and purified to homogeneity. The sequence and mass of the recombinant protein were confirmed, and far and near UV circular dichroic analyses showed that the protein was properly folded. The secondary structure of recombinant VEG consisted of 75% beta-sheets and 12% alpha-helices, and it was found to be stable under acidic conditions, in the presence of alcohol, and at high temperatures. The denaturation temperature was 79 degreesC at pH 3.5, with a denaturation enthalpy (DeltaHd) of 160,600 J/mol. Fluorescence analysis and measurement of the denaturation temperature by circular dichroism did not detect any interaction between VEG and extremely bitter (denatonium benzoate, caffein) or sweet (aspartame) compounds. These results suggest that VEG may not function as a shuttle for transfer of sapid molecules to taste receptors.

  10. Detection of novel CYP11A1-derived secosteroids in the human epidermis and serum and pig adrenal gland.

    PubMed

    Slominski, Andrzej T; Kim, Tae-Kang; Li, Wei; Postlethwaite, Arnold; Tieu, Elaine W; Tang, Edith K Y; Tuckey, Robert C

    2015-10-08

    To investigate whether novel pathways of vitamin D3 (D3) and 7-dehydrocholesterol (7DHC) metabolism initiated by CYP11A1 and previously characterized in vitro, occur in vivo, we analyzed samples of human serum and epidermis, and pig adrenals for the presence of intermediates and products of these pathways. We extracted human epidermis from 13 individuals and sera from 13 individuals and analyzed them by LC/qTOF-MS alongside the corresponding standards. Pig adrenal glands were also analyzed for these steroids and secosteroids. Epidermal, serum and adrenal samples showed the presence of D3 hydroxy-derivatives corresponding to 20(OH)D3, 22(OH)D3, 25(OH)D3, 1,25(OH)2D3, 20,22(OH)2D3, 20,23(OH)2D3, 20,24(OH)2D3, 20,25(OH)2D3, 20,26(OH)2D3, 1,20,23(OH)3D3 and 17,20,23(OH)3D3, plus 1,20(OH)2D3 which was detectable only in the epidermis. Serum concentrations of 20(OH)D3 and 22(OH)D3 were only 30- and 15-fold lower than 25(OH)D3, respectively, and at levels above those required for biological activity as measured in vitro. We also detected 1,20,24(OH)3D3, 1,20,25(OH)3D3 and 1,20,26(OH)3D3 in the adrenals. Products of CYP11A1 action on 7DHC, namely 22(OH)7DHC, 20,22(OH)27DHC and 7-dehydropregnenolone were also detected in serum, epidermis and the adrenal. Thus, we have detected novel CYP11A1-derived secosteroids in the skin, serum and adrenal gland and based on their concentrations and biological activity suggest that they act as hormones in vivo.

  11. Nicotine derived genotoxic effects in human primary parotid gland cells as assessed in vitro by comet assay, cytokinesis-block micronucleus test and chromosome aberrations test.

    PubMed

    Ginzkey, Christian; Steussloff, Gudrun; Koehler, Christian; Burghartz, Marc; Scherzed, Agmal; Hackenberg, Stephan; Hagen, Rudolf; Kleinsasser, Norbert H

    2014-08-01

    Genotoxic effects of nicotine were described in different human cells including salivary gland cells. Based on the high nicotine concentration in saliva of smokers or patients using therapeutic nicotine patches, the current study was performed to evaluate the genotoxic potential of nicotine in human salivary gland cells. Therefore, primary salivary gland cells from 10 patients undergoing parotid gland surgery were exposed to nicotine concentrations between 1 μM and 1000 μM for 1 h in the absence of exogenous metabolic activation. The acinar phenotype was proven by immunofluorescent staining of alpha-amylase. Genotoxic effects were evaluated using the Comet assay, the micronucleus test and the chromosome aberration test. Cytotoxicity and apoptosis were determined by trypan blue exclusion test and Caspase-3 assay. Nicotine was able to induce genotoxic effects in all three assays. The chromosome aberration test was the most sensitive and increases in numerical and structural (chromatid-type and chromosome-type) aberrations were seen at ≥1 μM, whereas increases in micronuclei frequency were detected at 10 μM and DNA damage as measured in the Comet assay was noted at >100 μM. No cytotoxic damage or influence of apoptosis could be demonstrated. Nicotine as a possible risk factor for tumor initiation in salivary glands is still discussed controversially. Our results demonstrated the potential of nicotine to induce genotoxic effects in salivary gland cells. These results were observed at saliva nicotine levels similar to those found after oral or transdermal exposure to nicotine and suggest the necessity of careful monitoring of the use of nicotine in humans. PMID:24698733

  12. NORMAL MAMMARY GLAND MORPHOLOGY IN PUBERTAL FEMALE MICE FOLLOWING IN UTERO AND LACTATIONAL EXPOSURE TO GENISTEIN AT LEVELS COMPARABLE TO HUMAN DIETARY EXPOSURE. (R827402)

    EPA Science Inventory

    The objective of the study was to determine the effect of in utero and lactational exposure to genistein (0, 0.1, 0.5, 2.5 and 10 mg/kg/day) on mammary gland morphology in female B6D2F1 mice at levels comparable to or greater than human exposures. The effect of diethylstilbest...

  13. Pineal region schwannoma arising from the trochlear nerve.

    PubMed

    Chaudhry, Nauman S; Ahmad, Faiz U; Morcos, Jacques J

    2016-10-01

    Schwannomas arising from the trochlear nerve are very rare and to our knowledge, less than 35 histologically documented cases have been reported in the literature. There are no reports of a schwannoma in the pineal region. We report a 24-year-old woman who underwent a para-occipital trans-tentorial approach and gross total excision of a pineal region schwannoma arising from the trochlear nerve. This is the first such reported case. PMID:27496528

  14. Life stage differences in mammary gland gene expression profile in non-human primates

    PubMed Central

    Sielker, Sonja; Wood, Charles E.; Register, Thomas C.; Lees, Cynthia J.; Dewi, Fitriya N.; Williams, J. Koudy; Wagner, Janice D.; Stefenelli, Ulrich; Cline, J. Mark

    2013-01-01

    Breast cancer (BC) is the most common malignancy of women in the developed world. To better understand its pathogenesis, knowledge of normal breast development is crucial, as BC is the result of disregulation of physiologic processes. The aim of this study was to investigate the impact of reproductive life stages on the transcriptional profile of the mammary gland in a primate model. Comparative transcriptomic analyses were carried out using breast tissues from 28 female cynomolgus macaques (Macaca fascicularis) at the following life stages: prepubertal (n = 5), adolescent (n = 4), adult luteal (n = 5), pregnant (n = 6), lactating (n = 3), and postmenopausal (n = 5). Mammary gland RNA was hybridized to Affymetrix GeneChip® Rhesus Macaque Genome Arrays. Differential gene expression was analyzed using ANOVA and cluster analysis. Hierarchical cluster analysis revealed distinct separation of life stage groups. More than 2,225 differentially expressed mRNAs were identified. Gene families or pathways that changed across life stages included those related to estrogen and androgen (ESR1, PGR, TFF1, GREB1, AR, 17HSDB2, 17HSDB7, STS, HSD11B1, AKR1C4), prolactin (PRLR, ELF5, STAT5, CSN1S1), insulin-like growth factor signaling (IGF1, IGFBP1, IGFBP5), extracellular matrix (POSTN, TGFB1, COL5A2, COL12A1, FOXC1, LAMC1, PDG-FRA, TGFB2), and differentiation (CD24, CD29, CD44, CD61, ALDH1, BRCA1, FOXA1, POSTN, DICER1, LIG4, KLF4, NOTCH2, RIF1, BMPR1A, TGFB2). Pregnancy and lactation displayed distinct patterns of gene expression. ESR1 and IGF1 were significantly higher in the adolescent compared to the adult animals, whereas differentiation pathways were overrepresented in adult animals and pregnancy-associated life stages. Few individual genes were distinctly different in postmenopausal animals. Our data demonstrate characteristic patterns of gene expression during breast development. Several of the pathways activated during pubertal development have been implicated in cancer

  15. Morphometrical analysis of the human suprarenal gland between the 4th and 7th months of gestation.

    PubMed

    Nowak, Dariusz; Góralczyk, Krzysztof; Zurada, Anna; Gielecki, Jerzy

    2007-01-01

    The present study's purpose has been to examine the development of the human suprarenal glands (SGs) during the prenatal period. Special attention was paid to sexual dimorphism and the differences between the parameters of the right and left SGs. Specimens were obtained from 187 human fetuses spontaneously aborted between the 4th and 7th months of gestation. The SGs were dissected from the fetuses after an immersion and preservation period of 3-24 months in 9% formalin solution. The mass and linear dimensions of each isolated SG were obtained, and these data revealed a progressive two-fold increase between the 4th and 7th months of gestation. There was a gradual reduction in the ratio of the SG mass to the overall mass of the fetus with a marked decrease evident between the 4th and 5th months. Statistical analysis of both SGs showed significant differences between sexes in the mass and in the thickness of the left SG during the 5th and 6th months of gestation. Differences in the mass and linear dimensions of the left and right SGs were recorded from the 5th month of gestation to the 7th month. The mass and volume of the left SGs were higher than those on the right side. This allometric analysis provides data from a large sample of human fetuses and will later aid in microscopic and ultrasonographic studies.

  16. The human serotonin N-acetyltransferase (EC 2.3.1.87) gene (AANAT): Structure, chromosomal localization, and tissue expression

    SciTech Connect

    Coon, S.L.; Bernard, M.; Roseboom, P.H.

    1996-05-15

    Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AA-NAT, HGMW-approved symbol AANAT;EC 2.3.1.87) is the penultimate enzyme in melatonin synthesis and controls the night/day rhythm in melatonin production in the vertebrate pineal gland. We have found that the human AA-NAT gene spans {approx}2.5 kb, contains four exons, and is located at chromosome 17q25. The open reading frame encodes a 23.2-kDa protein that is {approx}80% identical to sheep and rat AA-NAT. The AA-NAT transcript ({approx}1 kb) is highly abundant in the pineal gland and is expressed at lower levels in the retina and in the Y79 retinoblastoma cell line. AA-NAT mRNA is also detectable at low levels in several brain regions and the pituitary gland, but not in several peripheral tissues examined. Brain and pituitary AA-NAT could modulate serotonin-dependent aspects of human behavior and pituitary function. 31 refs., 5 figs.

  17. cGMP phosphodiesterase activity evaluation in human carcinoma of salivary glands.

    PubMed

    Spoto, G; Mariani, A; Santoleri, F; Fioroni, M; Vitale, D; Piatelli, A; Di Nicola, M; Rubini, C

    2004-01-01

    The aim of this study was to evaluate differences of cGMP-PDE activity in salivary glands, between a control group and different benign tumour groups and, where present, with malign tumour groups. Endogen cGMP was evaluated too. The enzymatic reaction used the method of Spoto et al., with minor variations. The samples were organized in six groups: A (Adenolymphoma and Warthins tumour); B (Pleomorphic Adenoma); C (Basaloid Adenoma); D (Myoepitelioma). The control group was represented by healthy patients. In A and B groups, we have analyzed malign pathologies (Adenocarcinoma and Parotid Lymphoma) The benign tumours have more activity than controls, especially in Myoepitelioma (D) but with a decrement in the C group, which presents lower values of cGMP than the other three groups, where the concentration is similar. Between A and B groups, the activity values of malign tumours are similar, higher than controls and than the other benign pathologies, but not higher than in myoepitelioma. The cyclic concentration is similar for malign pathologies, with concentrations lower than controls, similar to Basaloid Adenoma (C).

  18. Role of Sodium Bicarbonate Cotransporters in Intracellular pH Regulation and Their Regulatory Mechanisms in Human Submandibular Glands.

    PubMed

    Namkoong, Eun; Shin, Yong-Hwan; Bae, Jun-Seok; Choi, Seulki; Kim, Minkyoung; Kim, Nahyun; Hwang, Sung-Min; Park, Kyungpyo

    2015-01-01

    Sodium bicarbonate cotransporters (NBCs) are involved in the pH regulation of salivary glands. However, the roles and regulatory mechanisms among different NBC isotypes have not been rigorously evaluated. We investigated the roles of two different types of NBCs, electroneutral (NBCn1) and electrogenic NBC (NBCe1), with respect to pH regulation and regulatory mechanisms using human submandibular glands (hSMGs) and HSG cells. Intracellular pH (pHi) was measured and the pHi recovery rate from cell acidification induced by an NH4Cl pulse was recorded. Subcellular localization and protein phosphorylation were determined using immunohistochemistry and co-immunoprecipitation techniques. We determined that NBCn1 is expressed on the basolateral side of acinar cells and the apical side of duct cells, while NBCe1 is exclusively expressed on the apical membrane of duct cells. The pHi recovery rate in hSMG acinar cells, which only express NBCn1, was not affected by pre-incubation with 5 μM PP2, an Src tyrosine kinase inhibitor. However, in HSG cells, which express both NBCe1 and NBCn1, the pHi recovery rate was inhibited by PP2. The apparent difference in regulatory mechanisms for NBCn1 and NBCe1 was evaluated by artificial overexpression of NBCn1 or NBCe1 in HSG cells, which revealed that the pHi recovery rate was only inhibited by PP2 in cells overexpressing NBCe1. Furthermore, only NBCe1 was significantly phosphorylated and translocated by NH4Cl, which was inhibited by PP2. Our results suggest that both NBCn1 and NBCe1 play a role in pHi regulation in hSMG acinar cells, and also that Src kinase does not regulate the activity of NBCn1.

  19. Comparison of human coagulation factor VIII expression directed by cytomegalovirus and mammary gland-specific promoters in HC11 cells and transgenic mice.

    PubMed

    Wang, Qing; Hao, Siguo; Ma, Liyuan; Zhang, Wenhao; Wan, Jiangbo; Deng, Xiaohui

    2015-10-01

    Hemophilia A is an inherited X-linked recessive bleeding disorder caused by coagulant factor VIII (FVIII) deficiency. The conventional treatment involves the administration of recombinant human FVIII (rhFVIII) preparations. In this study, the mammary gland 'bioreactor' is designed to specifically and efficiently express a foreign protein hFVIII in the mammary glands of transgenic mice. We constructed a P1A3-hFVIIIBD vector directed by the mammary gland-specific P1A3 promoter, and transiently transfected HC11 cells and mouse mammary glands with P1A3-hFVIIIBD or CMV-hFVIIIBD vectors directed by a ubiquitous cytomegalovirus (CMV) promoter, respectively. We also generated P1A3-hFVIIIBD and CMV-hFVIIIBD transgenic mice by microinjection, respectively. Our data indicated that both vectors effectively expressed hFVIIIBD in HC11 cells at the transcription level, and hFVIIIBD protein was efficiently expressed in mouse milk after the injection of the hFVIIIBD vectors into mouse mammary glands during lactation. In both CMV-hFVIIIBD and P1A3-hFVIIIBD transgenic mice, hFVIIIBD proteins were efficiently expressed in the mammary glands at the mRNA and protein levels. No significant difference was observed in hFVIIIBD levels between the CMV-hFVIIIBD and P1A3-hFVIIIBD transgenic mice (P > 0.05). However, the activity of hFVIII in CMV-directed transgenic mice was slightly higher than that in P1A3-directed transgenic mice (P < 0.05). While hFVIIIBD was present in multiple organs in CMV-hFVIIIBD mice, P1A3-hFVIIIBD mice showed negligible hFVIIIBD expression in organs other than the mammary glands. This study demonstrated that the mammary gland-specific P1A3-hFVIIIBD vector was more suitable for the generation of hFVIIIBD mammary gland bioreactor.

  20. A milk protein gene promoter directs the expression of human tissue plasminogen activator cDNA to the mammary gland in transgenic mice

    SciTech Connect

    Pittius, C.W.; Hennighausen, L.; Lee, E.; Westphal, H.; Nicols, E.; Vitale, J.; Gordon, K. )

    1988-08-01

    Whey acidic protein (WAP) is a major whey protein in mouse milk. Its gene is expressed in the lactating mammary gland and is inducible by steroid and peptide hormones. A series of transgenic mice containing a hybrid gene in which human tissue plasminogen activator (tPA) cDNA is under the control of the murine WAP gene promoter had previously been generated. In this study, 21 tissues from lactating and virgin transgenic female mice containing the WAP-tPA hybrid gene were screened for the distribution of murine WAP and human tPA transcripts. Like the endogenous WAP RNA, WAP-tPA RNA was expressed predominantly in mammary gland tissue and appeared to be inducible by lactation. Whereas WAP transcripts were not detected in 22 tissues of virgin mice, low levels of WAP-tPA RNA, which were not modulated during lactation, were found in tongue, kidney, and sublingual gland. These studies demonstrate that the WAP gene promoter can target the expression of a transgene to the mammary gland and that this expression is inducible during lactation.

  1. Unsolved Mysteries of the Human Mammary Gland: Defining and Redefining the Critical Questions from the Lactation Consultant's Perspective.

    PubMed

    Marasco, Lisa Ann

    2014-12-01

    Despite advances in knowledge about human lactation, clinicians face many problems when advising mothers who are experiencing breastfeeding difficulties that do not respond to normal management strategies. Primary insufficient milk production is now being acknowledged, but incidence rates have not been well studied. Many women have known histories of infertility, polycystic ovary syndrome, obesity, hypertension, insulin resistance, thyroid dysfunction, hyperandrogenism or other hormonal imbalances, while others have no obvious risk factors. Some present with obviously abnormal breasts that are pubescent, tuberous/tubular or asymmetric in shape, raising the question of insufficient mammary gland tissue. Other women have breasts that appear within normal limits yet do not lactate normally. Endocrine disruptors may underlie some of these cases but their impact on human milk production has not been well explored. Similarly, any problem with prolactin such as a deficiency in serum prolactin or receptor number, receptor resistance, or poor bioavailability or bioactivity could underlie some cases of insufficient lactation, yet these possibilities are rarely investigated. A weak or suppressed milk ejection reflex, often assumed to be psychosomatic, could be related to thyroid dysfunction or caused by downstream post-receptor pathway problems. In the absence of sufficient data regarding these situations, desperate mothers may turn to non-evidence-based remedies, sometimes at considerable cost and unknown risk. Research targeted to these clinical dilemmas is critical in order to develop evidence-based strategies and increase breastfeeding duration and success rates. PMID:26084427

  2. Unsolved Mysteries of the Human Mammary Gland: Defining and Redefining the Critical Questions from the Lactation Consultant's Perspective.

    PubMed

    Marasco, Lisa Ann

    2014-12-01

    Despite advances in knowledge about human lactation, clinicians face many problems when advising mothers who are experiencing breastfeeding difficulties that do not respond to normal management strategies. Primary insufficient milk production is now being acknowledged, but incidence rates have not been well studied. Many women have known histories of infertility, polycystic ovary syndrome, obesity, hypertension, insulin resistance, thyroid dysfunction, hyperandrogenism or other hormonal imbalances, while others have no obvious risk factors. Some present with obviously abnormal breasts that are pubescent, tuberous/tubular or asymmetric in shape, raising the question of insufficient mammary gland tissue. Other women have breasts that appear within normal limits yet do not lactate normally. Endocrine disruptors may underlie some of these cases but their impact on human milk production has not been well explored. Similarly, any problem with prolactin such as a deficiency in serum prolactin or receptor number, receptor resistance, or poor bioavailability or bioactivity could underlie some cases of insufficient lactation, yet these possibilities are rarely investigated. A weak or suppressed milk ejection reflex, often assumed to be psychosomatic, could be related to thyroid dysfunction or caused by downstream post-receptor pathway problems. In the absence of sufficient data regarding these situations, desperate mothers may turn to non-evidence-based remedies, sometimes at considerable cost and unknown risk. Research targeted to these clinical dilemmas is critical in order to develop evidence-based strategies and increase breastfeeding duration and success rates.

  3. P2Y2 nucleotide receptor activation up-regulates vascular cell adhesion molecule-1 [corrected] expression and enhances lymphocyte adherence to a human submandibular gland cell line.

    PubMed

    Baker, Olga J; Camden, Jean M; Rome, Danny E; Seye, Cheikh I; Weisman, Gary A

    2008-01-01

    Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease that causes salivary and lacrimal gland tissue destruction resulting in impaired secretory function. Although lymphocytic infiltration of salivary epithelium is associated with SS, the mechanisms involved have not been adequately elucidated. Our previous studies have shown that the G protein-coupled P2Y2 nucleotide receptor (P2Y2R) is up-regulated in response to damage or stress of salivary gland epithelium, and in salivary glands of the NOD.B10 mouse model of SS-like autoimmune exocrinopathy. Additionally, we have shown that P2Y2R activation up-regulates vascular cell adhesion molecule-1 (VCAM-1) expression in endothelial cells leading to the binding of monocytes. The present study demonstrates that activation of the P2Y2R in dispersed cell aggregates from rat submandibular gland (SMG) and in human submandibular gland ductal cells (HSG) up-regulates the expression of VCAM-1. Furthermore, P2Y2R activation mediated the up-regulation of VCAM-1 expression in HSG cells leading to increased adherence of lymphocytic cells. Inhibitors of EGFR phosphorylation and metalloprotease activity abolished P2Y2R-mediated VCAM-1 expression and decreased lymphocyte binding to HSG cells. Moreover, silencing of EGFR expression abolished UTP-induced VCAM-1 up-regulation in HSG cells. These results suggest that P2Y2R activation in salivary gland cells increases the EGFR-dependent expression of VCAM-1 and the binding of lymphocytes, a pathway relevant to inflammation associated with SS.

  4. P2Y2 Nucleotide Receptor Activation Up-regulates Vascular Cell Adhesion Molecular-1 Expression and Enhances Lymphocyte Adherence to a Human Submandibular Gland Cell Line

    PubMed Central

    Baker, Olga J.; Camden, Jean M.; Rome, Danny E.; Seye, Cheikh I.; Weisman, Gary A.

    2007-01-01

    Sjögren’s syndrome (SS) is a chronic inflammatory autoimmune disease that causes salivary and lacrimal gland tissue destruction resulting in impaired secretory function. Although lymphocytic infiltration of salivary epithelium is associated with SS, the mechanisms involved have not been adequately elucidated. Our previous studies have shown that the G protein-coupled P2Y2 nucleotide receptor (P2Y2R) is up-regulated in response to damage or stress of salivary gland epithelium, and in salivary glands of the NOD.B10 mouse model of SS-like autoimmune exocrinopathy. Additionally, we have shown that P2Y2R activation up-regulates vascular cell adhesion molecule-1 (VCAM-1) expression in endothelial cells leading to the binding of monocytes. The present study demonstrates that activation of the P2Y2R in dispersed cell aggregates from rat submandibular gland (SMG) and in human submandibular gland ductal cells (HSG) up-regulates the expression of VCAM-1. Furthermore, P2Y2R activation mediated the up-regulation of VCAM-1 expression in HSG cells leading to increased adherence of lymphocytic cells. Inhibitors of EGFR phosphorylation and metalloprotease activity abolished P2Y2R-mediated VCAM-1 expression and decreased lymphocyte binding to HSG cells. Moreover, silencing of EGFR expression abolished UTP-induced VCAM-1 up-regulation in HSG cells. These results suggest that P2Y2R activation in salivary gland cells increases the EGFR-dependent expression of VCAM-1 and the binding of lymphocytes, a pathway relevant to inflammation associated with SS. PMID:17599409

  5. The harderian gland: a tercentennial review.

    PubMed Central

    Payne, A P

    1994-01-01

    The harderian gland was first described in 1694 by Johann Jacob Harder (1656-1711). It occurs in most terrestrial vertebrates and is located within the orbit where, in some species, it is the largest structure. It may be compound tubular or compound tubuloalveolar, and its secretory duct is usually morphologically distinct only after leaving the substance of the gland to open on the surface of the nictitating membrane. The tubules of the gland are formed of a single layer of columnar epithelial cells surrounded by myoepithelial cells. The chief product(s) of the gland varies between different groups of vertebrates, and epithelial cells possess granules or vacuoles whose contents may be mucous, serous or lipid. In rodents, the gland synthesises lipids, porphyrins and indoles. In the case of lipid vacuoles, the gland is unusual in releasing these by an exocytotic mechanism. It is unclear whether the gland can act both as an exocrine and endocrine organ. There is control of gland structure and synthesis through a variety of humoral agents, including gonadal, thyroid and pituitary hormones; in addition there is a rich autonomic innervation and many neuropeptides have been identified. The proposed functions of the gland are remarkably diverse and include the gland being (1) a source of 'saliva', (2) a site of immune response, (3) a photoprotective organ, (4) part of a retinal-pineal axis, (5) a source of pheromones, (6) a source of thermoregulatory lipids, (7) a site of osmoregulation, and (8) a source of growth factors. The gland is discussed in terms of its embryology and phylogeny, and in relation to ecological variables. Several goals of future research are identified. Images Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 Fig. 16 Fig. 17 Fig. 18 Fig. 19 Fig. 20 Fig. 21 Fig. 22 Fig. 23 Fig. 24 Fig. 25 Fig. 26 Fig. 27 Fig. 28 Fig. 29 Fig. 30 Fig. 31 Fig. 32 Fig. 36 Fig. 37 Fig. 38 Fig. 40 PMID:7559104

  6. Low-Grade Oligodendroglioma of the Pineal Region: Case Report

    PubMed Central

    Lamis, Fabricio Correa; de Paiva Neto, Manoel Antonio; Stavale, João Norberto; Cavalheiro, Sergio

    2015-01-01

    Background Although germ cell tumors and pineal cell tumors account for most of the histologic tumor subtypes, > 17 different tumors can arise in this location. We report a rare case of a low-grade oligodendroglioma that arose in the pineal region. Clinical Presentation A young woman complaining of a headache underwent magnetic resonance imaging that showed a mass in the pineal region and mild hydrocephalus. A ventriculoperitoneal shunt was performed followed by a near-total tumor removal, due to tumor invasion of the tectal plate and thalamus. The histologic examination confirmed the diagnosis of a low-grade oligodendroglioma. The patient then underwent chemotherapy and radiotherapy as adjuvant therapies. Conclusion Although the pineal region is a common place for a large number of tumoral lesions, low-grade oligodendrogliomas are extremely rare in this location. This case is only the second account of a benign oligodendroglioma of the pineal region reported in the literature. PMID:26251811

  7. Melatonin in human preovulatory follicular fluid

    NASA Technical Reports Server (NTRS)

    Brzezinski, Amnon; Seibel, Machelle M.; Lynch, Harry J.; Deng, Mei-Hua; Wurtman, Richard J.

    1987-01-01

    Melatonin, the major hormone of the pineal gland, has antigonadotrophic activity in many mammals and may also be involved in human reproduction. Melatonin suppresses steroidogenesis by ovarian granulosa and luteal cells in vitro. To determine if melatonin is present in the human ovary, preovulatory follicular fluids (n = 32) from 15 women were assayed for melatonin by RIA after solvent extraction. The fluids were obtained by laparoscopy or sonographically controlled follicular puncture from infertile women undergoing in vitro fertilization and embryo transfer. All patients had received clomiphene citrate, human menopausal gonadotropin, and hCG to stimulate follicle formation. Blood samples were obtained by venipuncture 30 rain or less after follicular aspiration. All of the follicular fluids contained melatonim, in concentrations substantially higher than those in the corresponding serum. A positive correlation was found between follicular fluid and serum melatonin levels in each woman; these observations indicate that preovulatory follicles contain substantial amounts of melatonin that may affect ovarian steroidogenesis.

  8. Salivary gland disorders.

    PubMed

    Wilson, Kevin F; Meier, Jeremy D; Ward, P Daniel

    2014-06-01

    Salivary gland disorders include inflammatory, bacterial, viral, and neoplastic etiologies. The presentation can be acute, recurrent, or chronic. Acute suppurative sialadenitis presents as rapid-onset pain and swelling and is treated with antibiotics, salivary massage, hydration, and sialagogues such as lemon drops or vitamin C lozenges. Viral etiologies include mumps and human immunodeficiency virus, and treatment is directed at the underlying disease. Recurrent or chronic sialadenitis is more likely to be inflammatory than infectious; examples include recurrent parotitis of childhood and sialolithiasis. Inflammation is commonly caused by an obstruction such as a stone or duct stricture. Management is directed at relieving the obstruction. Benign and malignant tumors can occur in the salivary glands and usually present as a painless solitary neck mass. Diagnosis is made by imaging (e.g., ultrasonography, computed tomography, magnetic resonance imaging) and biopsy (initially with fine-needle aspiration). Overall, most salivary gland tumors are benign and can be treated with surgical excision.

  9. Localization of Na(+)-K(+)-ATPase α/β, Na(+)-K(+)-2Cl-cotransporter 1 and aquaporin-5 in human eccrine sweat glands.

    PubMed

    Zhang, Mingjun; Zeng, Shaopeng; Zhang, Lei; Li, Haihong; Chen, Lu; Zhang, Xiang; Li, Xuexue; Lin, Changmin; Shu, Shenyou; Xie, Sitian; He, Yunpu; Mao, Xiaoyan; Peng, Lihong; Shi, Lungang; Yang, Lvjun; Tang, Shijie; Fu, Xiaobing

    2014-10-01

    In order to evaluate the function of the repaired or regenerated eccrine sweat glands, we must first localize the proteins involved in sweat secretion and absorption in normal human eccrine sweat glands. In our studies, the cellular localization of Na(+)-K(+)-ATPase α/β, Na(+)-K(+)-2Cl-cotransporter 1 (NKCC1) and aquaporin-5 (AQP5) in eccrine sweat glands were detected by immunoperoxidase labeling. The results showed that Na(+)-K(+)-ATPase α was immunolocalized in the cell membrane of the basal layer and suprabasal layer cells of the epidermis, the basolateral membrane of the secretory coils, and the cell membrane of the outer cells and the basolateral membrane of the luminal cells of the ducts. The localization of Na(+)-K(+)-ATPase β in the secretory coils was the same as Na(+)-K(+)-ATPase α, but Na(+)-K(+)-ATPase β labeling was absent in the straight ducts and epidermis. NKCC1 labeling was seen only in the basolateral membrane of the secretory coils. AQP5 was strongly localized in the apical membrane and weakly localized in the cytoplasm of secretory epithelial cells. The different distribution of these proteins in eccrine sweat glands was related to their functions in sweat secretion and absorption. PMID:25218052

  10. Generation of TALE nickase-mediated gene-targeted cows expressing human serum albumin in mammary glands.

    PubMed

    Luo, Yan; Wang, Yongsheng; Liu, Jun; Cui, Chenchen; Wu, Yongyan; Lan, Hui; Chen, Qi; Liu, Xu; Quan, Fusheng; Guo, Zekun; Zhang, Yong

    2016-02-08

    Targeting exogenous genes at milk protein loci via gene-targeting technology is an ideal strategy for producing large quantities of pharmaceutical proteins. Transcription-activator-like effector (TALE) nucleases (TALENs) are an efficient genome-editing tool. However, the off-target effects may lead to unintended gene mutations. In this study, we constructed TALENs and TALE nickases directed against exon 2 of the bovine β-lactoglobulin (BLG) locus. The nickases can induce a site-specific DNA single-strand break, without inducing double-strand break and nonhomologous end joining mediated gene mutation, and lower cell apoptosis rate than TALENs. After co-transfecting the bovine fetal fibroblasts with human serum albumin (HSA) gene-targeting vector and TALE nickase expression vectors, approximately 4.8% (40/835) of the cell clones contained HSA at BLG locus. Unexpectedly, one homozygous gene-targeted cell clone (1/835, 0.1%) was obtained by targeting both alleles of BLG in a single round of transfection. The recombinant protein mimicking the endogenous BLG was highly expressed and correctly folded in the mammary glands of the targeted cows, and the expression level of HSA was significantly increased in the homozygous targeted cows. Results suggested that the combination of TALE nickase-mediated gene targeting and somatic cell nuclear transfer is a feasible and safe approach in producing gene-targeted livestock.

  11. Generation of TALE nickase-mediated gene-targeted cows expressing human serum albumin in mammary glands

    PubMed Central

    Luo, Yan; Wang, Yongsheng; Liu, Jun; Cui, Chenchen; Wu, Yongyan; Lan, Hui; Chen, Qi; Liu, Xu; Quan, Fusheng; Guo, Zekun; Zhang, Yong

    2016-01-01

    Targeting exogenous genes at milk protein loci via gene-targeting technology is an ideal strategy for producing large quantities of pharmaceutical proteins. Transcription- activator-like effector (TALE) nucleases (TALENs) are an efficient genome-editing tool. However, the off-target effects may lead to unintended gene mutations. In this study, we constructed TALENs and TALE nickases directed against exon 2 of the bovine β-lactoglobulin (BLG) locus. The nickases can induce a site-specific DNA single-strand break, without inducing double-strand break and nonhomologous end joining mediated gene mutation, and lower cell apoptosis rate than TALENs. After co-transfecting the bovine fetal fibroblasts with human serum albumin (HSA) gene-targeting vector and TALE nickase expression vectors, approximately 4.8% (40/835) of the cell clones contained HSA at BLG locus. Unexpectedly, one homozygous gene-targeted cell clone (1/835, 0.1%) was obtained by targeting both alleles of BLG in a single round of transfection. The recombinant protein mimicking the endogenous BLG was highly expressed and correctly folded in the mammary glands of the targeted cows, and the expression level of HSA was significantly increased in the homozygous targeted cows. Results suggested that the combination of TALE nickase-mediated gene targeting and somatic cell nuclear transfer is a feasible and safe approach in producing gene-targeted livestock. PMID:26853907

  12. Basement membrane heparan sulfate proteoglycan (perlecan) synthesized by ACC3, adenoid cystic carcinoma cells of human salivary gland origin.

    PubMed

    Kimura, S; Cheng, J; Toyoshima, K; Oda, K; Saku, T

    1999-02-01

    The biosynthesis of basement membrane heparan sulfate proteoglycan (HSPG), known as perlecan, in ACC3 cells established from a adenoid cystic carcinoma of the human salivary gland was studied using metabolic labeling and immunoprecipitation with discriminative antibodies specific for HSPG core protein. Treatment of immunoprecipitated HSPG with HNO2, heparitinase, and chondroitinase ABC revealed that ACC3 cells synthesized HSPG molecules composed of 470-kDa core protein and heparan sulfate but not of chondroitin sulfate. The core protein was shown to contain complex type N-linked oligosaccharides by digestion with N-glycanase and endoglycosidase H. Pulse-chase experiments showed that the mature form of HSPG was formed in the cells in 30 min and released into the medium thereafter. Degradation of HSPG was also found in the chase period of 3 h. In time course experiments, HSPG was found to be synthesized maximally at day 4 after plating, deposited in the cell layer maximally at day 6, and secreted maximally at day 8. This was also confirmed by immunofluorescence, Northern blotting, and in-situ hybridization. The results indicate that ACC3 cells synthesize, secrete and degrade basement membrane type HSPG, which is analogous to those produced by other cell types, and that the biosynthesis and secretion of HSPG in ACC3 cells are strictly regulated by the cell growth, that may be reflected in the characteristic histology of adenoid cystic carcinomas. PMID:9990141

  13. Adrenal Gland Disorders

    MedlinePlus

    The adrenal glands are small glands located on top of each kidney. They produce hormones that you can't live ... stress and has many other important functions. With adrenal gland disorders, your glands make too much or not ...

  14. Role for the pineal and melatonin in glucose homeostasis: pinealectomy increases night-time glucose concentrations.

    PubMed

    la Fleur, S E; Kalsbeek, A; Wortel, J; van der Vliet, J; Buijs, R M

    2001-12-01

    The effects of melatonin on glucose metabolism are far from understood. In rats, the biological clock generates a 24-h rhythm in plasma glucose concentrations, with declining concentrations in the dark period. We hypothesized that, in the rat, melatonin enhances the dark signal of the biological clock, decreasing glucose concentrations in the dark period. We measured 24-h rhythms of plasma concentrations of glucose and insulin in pinealectomized rats fed ad libitum and subjected to a scheduled feeding regimen with six meals equally distributed over the light/dark cycle and compared them with previous data of intact rats. Pinealectomy dampened the amplitude of the 24-h rhythm in plasma glucose concentrations in rats fed ad libitum, and abolished it completely in rats subjected to the scheduled feeding regimen, while plasma insulin concentrations did not change under both conditions. Pinealectomy abolished the nocturnal decline in plasma glucose concentrations irrespective of whether rats were fed ad libitum or subjected to the scheduled feeding regimen. Melatonin replacement restored 24-h mean plasma glucose concentrations in pinealectomized rats that were subjected to the scheduled feeding regimen but, interestingly, it did not restore the 24-h rhythm. Melatonin treatment also resulted in higher meal-induced insulin responses, probably mediated via an increased sensitivity of the beta-cells. Taken together, our data demonstrate that the pineal hormone, melatonin, influences both glucose metabolism and insulin secretion from the pancreatic beta-cell. The present study also demonstrates that removal of the pineal gland cannot be compensated by mimicking plasma melatonin concentrations only.

  15. Peribiliary Glands as a Niche of Extrapancreatic Precursors Yielding Insulin-Producing Cells in Experimental and Human Diabetes.

    PubMed

    Carpino, Guido; Puca, Rosa; Cardinale, Vincenzo; Renzi, Anastasia; Scafetta, Gaia; Nevi, Lorenzo; Rossi, Massimo; Berloco, Pasquale B; Ginanni Corradini, Stefano; Reid, Lola M; Maroder, Marella; Gaudio, Eugenio; Alvaro, Domenico

    2016-05-01

    Peribiliary glands (PBGs) are niches in the biliary tree and containing heterogeneous endodermal stem/progenitors cells that can differentiate, in vitro and in vivo, toward pancreatic islets. The aim of this study was to evaluate, in experimental and human diabetes, proliferation of cells in PBGs and differentiation of the biliary tree stem/progenitor cells (BTSCs) toward insulin-producing cells. Diabetes was generated in mice by intraperitoneal injection of a single dose of 200 mg/kg (N = 12) or 120 mg/kg (N = 12) of streptozotocin. Liver, pancreas, and extrahepatic biliary trees were en bloc dissected and examined. Cells in PBGs proliferated in experimental diabetes, and their proliferation was greatest in the PBGs of the hepatopancreatic ampulla, and inversely correlated with the pancreatic islet area. In rodents, the cell proliferation in PBGs was characterized by the expansion of Sox9-positive stem/progenitor cells that gave rise to insulin-producing cells. Insulin-producing cells were located mostly in PBGs in the portion of the biliary tree closest to the duodenum, and their appearance was associated with upregulation of MafA and Gli1 gene expression. In patients with type 2 diabetes, PBGs at the level of the hepatopancreatic ampulla contained cells showing signs of proliferation and pancreatic fate commitment. In vitro, high glucose concentrations induced the differentiation of human BTSCs cultures toward pancreatic beta cell fates. The cells in PBGs respond to diabetes with proliferation and differentiation towards insulin-producing cells indicating that PBG niches may rescue pancreatic islet impairment in diabetes. These findings offer important implications for the pathophysiology and complications of this disease. Stem Cells 2016;34:1332-1342. PMID:26850087

  16. [Extraneural metastasis of pineal germinoma through a ventriculoperitoneal shunt, following histological change].

    PubMed

    Uchino, M; Nemoto, M; Ohtsuka, T; Seiki, Y; Shibata, I

    1999-03-01

    Primary germinoma of the central nervous system carries a good prognosis because of their radiosensitivity. Recurrence is rare and extraneural metastases are even more unusual. We report a unique case of a primary intracranial germinoma exhibiting complete response to radiotherapy, but recurring as an intra-abdominal yolk sac tumor. The presence of a VP shunt is thought to have facilitated metastatic spread of the intracranial neoplasm. An 21-year-old (corrected) male was admitted with headache and consciousness disturbance. Computed tomography (CT) revealed an enhanced tumor of the pineal region and hydrocephalus. A ventriculo-peritoneal shunt was emplaced immediately. No serum tumor markers such as alpha-fetoprotein or human chorionic gonadotropin were detectable. A test dose of radiotherapy (whole brain 20Gy) was given. The tumor size was remarkably decreased. Clinical diagnosis was germinoma. Additional whole brain radiation (total 45Gy) and whole spine radiation (20Gy) were given. The tumor and the hydrocephalus regressed completely and the patient returned to school. Three years later, he experienced a feeling of abdominal fullness. CT and echotomography of the abdomen showed a large peritoneal and intra-hepatic tumor. But MRI revealed no recurrent tumor of the pineal lesion or of the other areas in the central nervous system. Radiological and clinical findings showed no tumors in the testis, the retroperitoneal cavity, or the thymus. Laboratory investigation demonstrated elevated serum AFP (26,550 ng/ml). AFP level regressed after combined chemotherapy. However, the patient died due to pneumonia and multiple organ failure. Only needle necropsy was performed. The microscopic appearance of the peritoneal tumor was confirmed to be an endodermal sinus tumor. It was suspected to be a metastasis of the pineal tumor through the V-P shunt system.

  17. [Simplified procedure for cold preservation of human parathyroid gland tissue for replantation].

    PubMed

    Wagner, P K; Rumpelt, H J; Rothmund, M

    1986-04-01

    A simplified technique for cryopreservation of human parathyroid tissue is described. It allows to achieve the same quality of tissue than using the programmable expensive freezing method which is usually employed up to now. Cryovials are placed in a methanol bath. The temperature is decreased by -1 degree C/min down to -25 degrees C, thereafter by -10 degrees C/min down to -70 degrees C by repeated adding of cryo ice-cubes into the methanol. Thereafter the vials are stored in LN2. The temperature lowering is controlled by a stop watch and a thermometer in a reference vial. This simple and cheap technique may allow a more general application of cryopreservation in surgery of hyperparathyroidism. PMID:3709300

  18. Chromosomal patterns in Warthin's tumor. A second type of human benign salivary gland neoplasm.

    PubMed

    Mark, J; Dahlenfors, R; Stenman, G; Nordquist, A

    1990-05-01

    The cytogenetical observations in eight successfully cultured human adenolymphomas are reported. When the results were considered with those of two previously reported cases, three main stemline groups could be distinguished: (a) one with a normal karyotype and noted as a primary or secondary stemline in all hitherto studied tumors; (b) a second group with only numerical changes, either loss of the Y chromosome or trisomy or monosomy 5; and (c) a third group with only structural changes, as a rule with one or two reciprocal translocations. With regard to the last group, studies of many more cases are necessary to decide whether distinctive subgroups exist. Analyses using molecular methods are also urgently needed to clarify whether the normal stemline cells contain submicroscopic changes.

  19. Role of Keratinocyte Growth Factor in the Differentiation of Sweat Gland-Like Cells From Human Umbilical Cord-Derived Mesenchymal Stem Cells

    PubMed Central

    Xu, Yongan; Hong, Yucai; Xu, Mengyan; Ma, Kui; Fu, Xiaobing

    2016-01-01

    Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have higher proliferation potency and lower immune resistance than human bone marrow MSCs and can differentiate into various functional cells. Many regulatory factors, including keratinocyte growth factor (KGF), are involved in the development of skin and cutaneous appendages. Although KGF is important in wound healing, the role of KGF in hUC-MSC differentiation remains unknown. In our previous work, we found the mixing medium (nine parts of basic sweat-gland [SG] medium plus one part of conditioned heat-shock SG medium) could induce hUC-MSC differentiation to sweat gland-like cells (SGCs). In this study, we further improved the inducing medium and determined the effects of KGF in hUC-MSC differentiation. We found KGF expression in the SGCs and that recombinant human KGF could induce hUC-MSC differentiation into SGCs, suggesting KGF plays a pivotal role in promoting hUC-MSC differentiation to SGCs. Furthermore, the SGCs differentiated from hUC-MSCs were applied to severely burned skin of the paw of an in vivo severe combined immunodeficiency mouse burn model. Burned paws treated with SGCs could regenerate functional sparse SGs 21 days after treatment; the untreated control paws could not. Collectively, these results demonstrated that KGF is a critical growth factor for SGC differentiation from hUC-MSCs and the differentiated SGCs from hUC-MSCs may have a potential therapeutic application for regeneration of destroyed SGs and injured skin. Significance There is growing evidence demonstrating a potential therapeutic application of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in injured skin. In the current study, conditioned media and chemically defined media with recombinant human keratinocyte growth factor (KGF) could induce hUC-MSC differentiation into sweat gland-like cells (SGCs). Moreover, the differentiated SGCs from hUC-MSCs could regenerate functional sparse sweat glands in a

  20. The Proteomes of Human Parotid and Submandibular/Sublingual Gland Salivas Collected as the Ductal Secretions

    PubMed Central

    Denny, Paul; Hagen, Fred K.; Hardt, Markus; Liao, Lujian; Yan, Weihong; Arellanno, Martha; Bassilian, Sara; Bedi, Gurrinder S.; Boontheung, Pinmannee; Cociorva, Daniel; Delahunty, Claire M.; Denny, Trish; Dunsmore, Jason; Faull, Kym F.; Gilligan, Joyce; Gonzalez-Begne, Mireya; Halgand, Frédéric; Hall, Steven C.; Han, Xuemei; Henson, Bradley; Hewel, Johannes; Hu, Shen; Jeffrey, Sherry; Jiang, Jiang; Loo, Joseph A.; Ogorzalek Loo, Rachel R.; Malamud, Daniel; Melvin, James E.; Miroshnychenko, Olga; Navazesh, Mahvash; Niles, Richard; Park, Sung Kyu; Prakobphol, Akraporn; Ramachandran, Prasanna; Richert, Megan; Robinson, Sarah; Sondej, Melissa; Souda, Puneet; Sullivan, Mark A.; Takashima, Jona; Than, Shawn; Wang, Jianghua; Whitelegge, Julian P.; Witkowska, H. Ewa; Wolinsky, Lawrence; Xie, Yongming; Xu, Tao; Yu, Weixia; Ytterberg, Jimmy; Wong, David T.; Yates, John R.; Fisher, Susan J.

    2009-01-01

    Saliva is a body fluid with important functions in oral and general health. A consortium of three research groups catalogued the proteins in human saliva collected as the ductal secretions: 1166 identifications—914 in parotid and 917 in submandibular/sublingual saliva—were made. The results showed that a high proportion of proteins that are found in plasma and/or tears are also present in saliva along with unique components. The proteins identified are involved in numerous molecular processes ranging from structural functions to enzymatic/catalytic activities. As expected, the majority mapped to the extracellular and secretory compartments. An immunoblot approach was used to validate the presence in saliva of a subset of the proteins identified by mass spectrometric approaches. These experiments focused on novel constituents and proteins for which the peptide evidence was relatively weak. Ultimately, information derived from the work reported here and related published studies can be used to translate blood-based clinical laboratory tests into a format that utilizes saliva. Additionally, a catalogue of the salivary proteome of healthy individuals allows future analyses of salivary samples from individuals with oral and systemic diseases, with the goal of identifying biomarkers with diagnostic and/or prognostic value for these conditions; another possibility is the discovery of therapeutic targets. PMID:18361515

  1. The proteomes of human parotid and submandibular/sublingual gland salivas collected as the ductal secretions.

    PubMed

    Denny, Paul; Hagen, Fred K; Hardt, Markus; Liao, Lujian; Yan, Weihong; Arellanno, Martha; Bassilian, Sara; Bedi, Gurrinder S; Boontheung, Pinmannee; Cociorva, Daniel; Delahunty, Claire M; Denny, Trish; Dunsmore, Jason; Faull, Kym F; Gilligan, Joyce; Gonzalez-Begne, Mireya; Halgand, Frédéric; Hall, Steven C; Han, Xuemei; Henson, Bradley; Hewel, Johannes; Hu, Shen; Jeffrey, Sherry; Jiang, Jiang; Loo, Joseph A; Ogorzalek Loo, Rachel R; Malamud, Daniel; Melvin, James E; Miroshnychenko, Olga; Navazesh, Mahvash; Niles, Richard; Park, Sung Kyu; Prakobphol, Akraporn; Ramachandran, Prasanna; Richert, Megan; Robinson, Sarah; Sondej, Melissa; Souda, Puneet; Sullivan, Mark A; Takashima, Jona; Than, Shawn; Wang, Jianghua; Whitelegge, Julian P; Witkowska, H Ewa; Wolinsky, Lawrence; Xie, Yongming; Xu, Tao; Yu, Weixia; Ytterberg, Jimmy; Wong, David T; Yates, John R; Fisher, Susan J

    2008-05-01

    Saliva is a body fluid with important functions in oral and general health. A consortium of three research groups catalogued the proteins in human saliva collected as the ductal secretions: 1166 identifications--914 in parotid and 917 in submandibular/sublingual saliva--were made. The results showed that a high proportion of proteins that are found in plasma and/or tears are also present in saliva along with unique components. The proteins identified are involved in numerous molecular processes ranging from structural functions to enzymatic/catalytic activities. As expected, the majority mapped to the extracellular and secretory compartments. An immunoblot approach was used to validate the presence in saliva of a subset of the proteins identified by mass spectrometric approaches. These experiments focused on novel constituents and proteins for which the peptide evidence was relatively weak. Ultimately, information derived from the work reported here and related published studies can be used to translate blood-based clinical laboratory tests into a format that utilizes saliva. Additionally, a catalogue of the salivary proteome of healthy individuals allows future analyses of salivary samples from individuals with oral and systemic diseases, with the goal of identifying biomarkers with diagnostic and/or prognostic value for these conditions; another possibility is the discovery of therapeutic targets.

  2. Morphometric study of the human suprarenal gland in the first postnatal year.

    PubMed

    Bocian-Sobkowska, J

    2000-01-01

    The aim of present, study was to describe adrenal volume, volumes of adrenocortical zones, and stroma volume in 40 adrenals obtained from children between 1st and 370th day during autopsy. The postnatal decrease in adrenal volume was caused mainly by rapid fall of fetal zone (FZ) volume (from 70 to 3% of total adrenal volume), that can be divided into two phases: rapid phase (from birth to the end of the second week) and a slow phase from the 3rd week on. Involution was accompanied by increase of zona glomerulosa (ZG) (from 10 to 25% of total adrenal volume), zona fasciculata ZF (from 10 to 38%) and zona reticularis (ZR), volume (from 1 to 23%). During the whole investigated period the volume of medulla remained constant. The volume fraction of stroma (connective tissue and blood vessels) was highest at the beginning of the first postnatal week and then decreased rapidly at the end of the 2nd week, with the most pronounced changes in the fetal zone and medulla. Performed present stereological study confirms opinion that hemorrhagic mechanisms are involved in the involution process of the human fetal zone.

  3. Melatonin: a "Higgs boson" in human reproduction.

    PubMed

    Dragojevic Dikic, Svetlana; Jovanovic, Ana Mitrovic; Dikic, Srdjan; Jovanovic, Tomislav; Jurisic, Aleksandar; Dobrosavljevic, Aleksandar

    2015-02-01

    As the Higgs boson could be a key to unlocking mysteries regarding our Universe, melatonin, a somewhat mysterious substance secreted by the pineal gland primarily at night, might be a crucial factor in regulating numerous processes in human reproduction. Melatonin is a powerful antioxidant which has an essential role in controlling several physiological reactions, as well as biological rhythms throughout human reproductive life. Melatonin, which is referred to as a hormone, but also as an autocoid, a chronobiotic, a hypnotic, an immunomodulator and a biological modifier, plays a crucial part in establishing homeostatic, neurohumoral balance and circadian rhythm in the body through synergic actions with other hormones and neuropeptides. This paper aims to analyze the effects of melatonin on the reproductive function, as well as to shed light on immunological and oncostatic properties of one of the most powerful hormones.

  4. Ca2+ is a Regulator of the WNK/OSR1/NKCC Pathway in a Human Salivary Gland Cell Line

    PubMed Central

    Park, Soonhong; Ku, Sang Kyun; Ji, Hye Won

    2015-01-01

    Wnk kinase maintains cell volume, regulating various transporters such as sodium-chloride cotransporter, potassium-chloride cotransporter, and sodium-potassium-chloride cotransporter 1 (NKCC1) through the phosphorylation of oxidative stress responsive kinase 1 (OSR1) and STE20/SPS1-related proline/alanine-rich kinase (SPAK). However, the activating mechanism of Wnk kinase in specific tissues and specific conditions is broadly unclear. In the present study, we used a human salivary gland (HSG) cell line as a model and showed that Ca2+ may have a role in regulating Wnk kinase in the HSG cell line. Through this study, we found that the HSG cell line expressed molecules participating in the WNK-OSR1-NKCC pathway, such as Wnk1, Wnk4, OSR1, SPAK, and NKCC1. The HSG cell line showed an intracellular Ca2+ concentration ([Ca2+]i) increase in response to hypotonic stimulation, and the response was synchronized with the phosphorylation of OSR1. Interestingly, when we inhibited the hypotonically induced [Ca2+]i increase with nonspecific Ca2+ channel blockers such as 2-aminoethoxydiphenyl borate, gadolinium, and lanthanum, the phosphorylated OSR1 level was also diminished. Moreover, a cyclopiazonic acid-induced passive [Ca2+]i elevation was evoked by the phosphorylation of OSR1, and the amount of phosphorylated OSR1 decreased when the cells were treated with BAPTA, a Ca2+ chelator. Finally, through that process, NKCC1 activity also decreased to maintain the cell volume in the HSG cell line. These results indicate that Ca2+ may regulate the WNK-OSR1 pathway and NKCC1 activity in the HSG cell line. This is the first demonstration that indicates upstream Ca2+ regulation of the WNK-OSR1 pathway in intact cells. PMID:25954130

  5. The human mammary gland as a target for isoflavones: how does the relation vary in individuals with different ethnicity?

    PubMed

    Maskarinec, Gertraud

    2013-05-01

    Based on observational studies, it appears that soy food consumption provides protection against breast cancer primarily in Asian but not in Western populations. Given the problems in examining the effects of isoflavones directly in the human mammary gland, this review describes epidemiologic studies that investigated the association with biomarkers reflecting hormonal activity of isoflavones, in particular sex steroid levels, mammographic densities, nipple aspirate fluid, and tissue specimens from biopsies or surgeries. Three possible mechanisms that may be responsible for ethnic-specific health effects from these compounds are discussed: genetic variation in metabolic enzymes, timing of exposure, and intestinal metabolism by microbiota. Only a limited number of comparative studies and even fewer nutritional interventions have examined effects and addressed differences in biomarkers between Asian and Western populations. Investigations that looked at estrogens and mammographic densities as endpoints observed some associations in Asian women that were not seen in Caucasians. On the other hand, the low rate of nipple aspirate fluid production and a lack of breast tissue studies make it impossible to evaluate effects of isoflavones on these biomarkers in Asian women. Based on the current evidence, it appears likely that the timing of exposure is the most important determinant of beneficial health effects from soy foods. This may be the result of gut microbiota, which colonize the intestine during childhood and facilitates the hydrolysis of glycosides and the formation of equol from dadzein, a pathway that may result in beneficial health effects. The current evidence is insufficient to answer the question whether women of diverse ethnic groups experience distinct effects from soy isoflavones in breast tissue, but as knowledge about the role of early life nutrition and the development of gut microbiota increases, the potential for diverse metabolic pathways of

  6. High p21RAS expression levels correlate with chromosome 8 rearrangements in benign human mixed salivary gland tumors.

    PubMed

    Stenman, G; Sandros, J; Mark, J; Nordkvist, A

    1989-09-01

    The expression of RAS oncogenes in benign and malignant salivary gland tumors was studied by immunohistochemistry and by immunoblotting using monoclonal antibodies recognizing the HRAS and KRAS gene products. Twenty-eight out of 29 benign pleomorphic adenomas overexpressed p21RAS, whereas only 12 out of 18 malignant salivary gland tumors expressed the p21 protein. The expression levels were also substantially higher in the adenomas than in the malignant tumors, indicating that RAS gene activation appears to be more frequent and of greater importance for benign than for malignant salivary gland tumors. Comparisons of the p21 expression levels with the karyotypes of the pleomorphic adenomas revealed a novel correlation between high p21 expression and chromosome 8 rearrangements. As a hypothesis, it is suggested that a novel gene located on the proximal long arm of chromosome 8, most likely at band q12, is involved in the regulation of RAS gene expression.

  7. Anatomy, biogenesis and regeneration of salivary glands.

    PubMed

    Holmberg, Kyle V; Hoffman, Matthew P

    2014-01-01

    An overview of the anatomy and biogenesis of salivary glands is important in order to understand the physiology, functions and disorders associated with saliva. A major disorder of salivary glands is salivary hypofunction and resulting xerostomia, or dry mouth, which affects hundreds of thousands of patients each year who suffer from salivary gland diseases or undergo head and neck cancer treatment. There is currently no curative therapy for these patients. To improve these patients' quality of life, new therapies are being developed based on findings in salivary gland cell and developmental biology. Here we discuss the anatomy and biogenesis of the major human salivary glands and the rodent submandibular gland, which has been used extensively as a research model. We also include a review of recent research on the identification and function of stem cells in salivary glands, and the emerging field of research suggesting that nerves play an instructive role during development and may be essential for adult gland repair and regeneration. Understanding the molecular mechanisms involved in gland biogenesis provides a template for regenerating, repairing or reengineering diseased or damaged adult human salivary glands. We provide an overview of 3 general approaches currently being developed to regenerate damaged salivary tissue, including gene therapy, stem cell-based therapy and tissue engineering. In the future, it may be that a combination of all three will be used to repair, regenerate and reengineer functional salivary glands in patients to increase the secretion of their saliva, the focus of this monograph. PMID:24862590

  8. Pertussis toxin-sensitive G-protein mediates the alpha 2-adrenergic receptor inhibition of melatonin release in photoreceptive chick pineal cell cultures

    SciTech Connect

    Pratt, B.L.; Takahashi, J.S.

    1988-07-01

    The avian pineal gland is a photoreceptive organ that has been shown to contain postjunctional alpha 2-adrenoceptors that inhibit melatonin synthesis and/or release upon receptor activation. Physiological response and (32P)ADP ribosylation experiments were performed to investigate whether pertussis toxin-sensitive guanine nucleotide-binding proteins (G-proteins) were involved in the transduction of the alpha 2-adrenergic signal. For physiological response studies, the effects of pertussis toxin on melatonin release in dissociated cell cultures exposed to norepinephrine were assessed. Pertussis toxin blocked alpha 2-adrenergic receptor-mediated inhibition in a dose-dependent manner. Pertussis toxin-induced blockade appeared to be noncompetitive. One and 10 ng/ml doses of pertussis toxin partially blocked and a 100 ng/ml dose completely blocked norepinephrine-induced inhibition. Pertussis toxin-catalyzed (32P)ADP ribosylation of G-proteins in chick pineal cell membranes was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Membranes were prepared from cells that had been pretreated with 0, 1, 10, or 100 ng/ml pertussis toxin. In the absence of pertussis toxin pretreatment, two major proteins of 40K and 41K mol wt (Mr) were labeled by (32P)NAD. Pertussis toxin pretreatment of pineal cells abolished (32P) radiolabeling of the 40K Mr G-protein in a dose-dependent manner. The norepinephrine-induced inhibition of both cAMP efflux and melatonin release, as assessed by RIA of medium samples collected before membrane preparation, was also blocked in a dose-dependent manner by pertussis toxin. Collectively, these results suggest that a pertussis toxin-sensitive 40K Mr G-protein labeled by (32P)NAD may be functionally associated with alpha 2-adrenergic signal transduction in chick pineal cells.

  9. Evolution of photosensory pineal organs in new light: the fate of neuroendocrine photoreceptors.

    PubMed Central

    Ekström, Peter; Meissl, Hilmar

    2003-01-01

    Pineal evolution is envisaged as a gradual transformation of pinealocytes (a gradual regression of pinealocyte sensory capacity within a particular cell line), the so-called sensory cell line of the pineal organ. In most non-mammals the pineal organ is a directly photosensory organ, while the pineal organ of mammals (epiphysis cerebri) is a non-sensory neuroendocrine organ under photoperiod control. The phylogenetic transformation of the pineal organ is reflected in the morphology and physiology of the main parenchymal cell type, the pinealocyte. In anamniotes, pinealocytes with retinal cone photoreceptor-like characteristics predominate, whereas in sauropsids so-called rudimentary photoreceptors predominate. These have well-developed secretory characteristics, and have been interpreted as intermediaries between the anamniote pineal photoreceptors and the mammalian non-sensory pinealocytes. We have re-examined the original studies on which the gradual transformation hypothesis of pineal evolution is based, and found that the evidence for this model of pineal evolution is ambiguous. In the light of recent advances in the understanding of neural development mechanisms, we propose a new hypothesis of pineal evolution, in which the old notion 'gradual regression within the sensory cell line' should be replaced with 'changes in fate restriction within the neural lineage of the pineal field'. PMID:14561326

  10. Up-regulation of Store-operated Ca2+ Entry and Nuclear Factor of Activated T Cells Promote the Acinar Phenotype of the Primary Human Salivary Gland Cells.

    PubMed

    Jang, Shyh-Ing; Ong, Hwei Ling; Liu, Xibao; Alevizos, Ilias; Ambudkar, Indu S

    2016-04-15

    The signaling pathways involved in the generation and maintenance of exocrine gland acinar cells have not yet been established. Primary human salivary gland epithelial cells, derived from salivary gland biopsies, acquired an acinar-like phenotype when the [Ca(2+)] in the serum-free medium (keratinocyte growth medium, KGM) was increased from 0.05 mm (KGM-L) to 1.2 mm (KGM-H). Here we examined the mechanism underlying this Ca(2+)-dependent generation of the acinar cell phenotype. Compared with cells in KGM-L, those in KGM-H display enhancement of Orai1, STIM1, STIM2, and nuclear factor of activated T cells 1 (NFAT1) expression together with an increase in store-operated Ca(2+) entry (SOCE), SOCE-dependent nuclear translocation of pGFP-NFAT1, and NFAT-dependent but not NFκB-dependent gene expression. Importantly, AQP5, an acinar-specific protein critical for function, is up-regulated in KGM-H via SOCE/NFAT-dependent gene expression. We identified critical NFAT binding motifs in the AQP5 promoter that are involved in Ca(2+)-dependent up-regulation of AQP5. These important findings reveal that the Ca(2+)-induced switch of salivary epithelial cells to an acinar-like phenotype involves remodeling of SOCE and NFAT signaling, which together control the expression of proteins critically relevant for acinar cell function. Our data provide a novel strategy for generating and maintaining acinar cells in culture.

  11. c-myc, ras p21 and p53 expression in pleomorphic adenoma and its malignant form of the human salivary glands.

    PubMed

    Deguchi, H; Hamano, H; Hayashi, Y

    1993-01-01

    Using an immunohistochemical study and an immunoblot analysis, the expression of cellular oncogenes of the human salivary glands such as c-myc, ras p21, and p53 tumor-suppressor gene in pleomorphic adenomas and its malignant form, carcinoma in pleomorphic adenomas was examined to evaluate a differential biological significance, in comparison with that in normal salivary gland tissues. Immunohistochemically, the c-myc product was detected in 42% of the pleomorphic adenomas and in 56% of the carcinomas in pleomorphic adenoma. The ras p21 expression was observed in 24% of pleomorphic adenomas, and in 50% of carcinomas in pleomorphic adenoma. The p53 protein was detected in 18% of the pleomorphic adenomas and in 67% of the carcinomas in pleomorphic adenoma. Although there was no significant difference between the benign and malignant forms for the expression of c-myc, a statistical significance in ras p21 and p53 expression was found between the pleomorphic adenoma and its malignant form (P < 0.05) and P < 0.001, respectively). An immunoblotting assay clearly demonstrated the expression of c-myc and p53 gene products in both the benign and malignant forms of the pleomorphic adenoma, and that of ras p21 in the malignant form. These results indicate that activation of c-myc and ras p21 proto-oncogenes and the involvement of p53 mutation may play important roles in the malignant transformation of salivary gland pleomorphic adenoma.

  12. Meibomian gland studies: histologic and ultrastructural investigations.

    PubMed

    Jester, J V; Nicolaides, N; Smith, R E

    1981-04-01

    Heightened interest in meibomian gland dysfunction has prompted us to evaluate the normal morphological and ultrastructural characteristics of the meibomian gland. Histologic analysis of human, primate, steer, and rabbit glands revealed evidence of keratinized epithelium extending throughout the meibomian gland duct. Characteristic ultrastructural features of keratinized epithelium identified in primate and rabbit glands included tonofilaments, keratohyaline granules, lamellar bodies, and keratinized squamous cells. Comparison of the meibomian gland duct to the pilosebaceous canal and the sebaceous duct brought out certain dissimilarities such as (1) the lack of a well-developed stratum granulosum and (2) the absence of lipid inclusions within transitional cells from duct to acini. We postulate that abnormalities of the keratinizing process may be responsible for meibomian gland dysfunction states.

  13. Human prominin-1 (CD133) is detected in both neoplastic and non-neoplastic salivary gland diseases and released into saliva in a ubiquitinated form.

    PubMed

    Karbanová, Jana; Laco, Jan; Marzesco, Anne-Marie; Janich, Peggy; Voborníková, Magda; Mokrý, Jaroslav; Fargeas, Christine A; Huttner, Wieland B; Corbeil, Denis

    2014-01-01

    Prominin-1 (CD133) is physiologically expressed at the apical membranes of secretory (serous and mucous) and duct cells of major salivary glands. We investigated its expression in various human salivary gland lesions using two distinct anti-prominin-1 monoclonal antibodies (80B258 and AC133) applied on paraffin-embedded sections and characterized its occurrence in saliva. The 80B258 epitope was extensively expressed in adenoid cystic carcinoma, in lesser extent in acinic cell carcinoma and pleomorphic adenoma, and rarely in mucoepidermoid carcinoma. The 80B258 immunoreactivity was predominately detected at the apical membrane of tumor cells showing acinar or intercalated duct cell differentiation, which lined duct- or cyst-like structures, and in luminal secretions. It was observed on the whole cell membrane in non-luminal structures present in the vicinity of thin-walled blood vessels and hemorrhagic areas in adenoid cystic carcinoma. Of note, AC133 labeled only a subset of 80B258-positive structures. In peritumoral salivary gland tissues as well as in obstructive sialadenitis, an up-regulation of prominin-1 (both 80B258 and AC133 immunoreactivities) was observed in intercalated duct cells. In most tissues, prominin-1 was partially co-expressed with two cancer markers: carcinoembryonic antigen (CEA) and mucin-1 (MUC1). Differential centrifugation of saliva followed by immunoblotting indicated that all three markers were released in association with small membrane vesicles. Immuno-isolated prominin-1-positive vesicles contained CEA and MUC1, but also exosome-related proteins CD63, flotillin-1, flotillin-2 and the adaptor protein syntenin-1. The latter protein was shown to interact with prominin-1 as demonstrated by its co-immunoisolation. A fraction of saliva-associated prominin-1 appeared to be ubiquitinated. Collectively, our findings bring new insights into the biochemistry and trafficking of prominin-1 as well as its immunohistochemical profile in certain types

  14. Salivary gland biopsy

    MedlinePlus

    Biopsy - salivary gland ... You have several pairs of salivary glands that drain into your mouth: A major pair in front of the ears (parotid glands) Another major pair beneath your jaw (submandibular ...

  15. Thymus Gland Anatomy

    MedlinePlus

    ... historical Searches are case-insensitive Thymus Gland, Adult, Anatomy Add to My Pictures View /Download : Small: 720x576 ... Large: 3000x2400 View Download Title: Thymus Gland, Adult, Anatomy Description: Anatomy of the thymus gland; drawing shows ...

  16. Salivary Gland Disorders

    MedlinePlus

    Your salivary glands make saliva - sometimes called spit - and empty it into your mouth through openings called ducts. Saliva makes your ... antibodies that can kill germs. Problems with salivary glands can cause the glands to become irritated and ...

  17. Electrical stimulation of the hypothalamic nucleus paraventricularis mimics the effects of light on pineal melatonin synthesis

    SciTech Connect

    Olcese, J.; Reuss, S.; Steinlechner, S.

    1987-02-02

    In an attempt to clarify further the role of the hypothalamic paraventricular nuclei (PVN) in the control of pineal function, the effects of 2 min electrical stimulation of these nuclei were investigated in acutely blinded, adult, male Sprague-Dawley rats. Pineal serotonin-N-acetyltransferase (NAT) activity, melatonin content and catecholamine levels were measured by means of radio-enzymatic, radioimmunoassay and high-performance liquid-chromatography methods, respectively. All three pineal parameters underwent significant declines following brief PVN stimulation during the night time. These observations lend credence to the view that the neural pathways transmitting light information to the sympathetic innervation controlling pineal melatonin synthesis. 22 references, 1 figure.

  18. A hemorrhagic pineal cyst with a bacterial meningitis-like manifestation and benign outcome.

    PubMed

    Yamamoto, Kanji; Omodaka, Toshikazu; Watanabe, Rie; Kodaira, Minori

    2013-01-01

    Pineal cysts are a common incidental finding in imaging studies, and the majority of such cysts are asymptomatic. However, hemorrhaging pineal cysts, which are considered to be rare, are often associated with severe symptoms. We herein describe the case of a 58-year-old patient with the novel manifestation of a bleeding pineal cyst, who had a benign outcome without any surgical treatment. Although the clinical manifestations resembled those of bacterial meningitis, magnetic resonance images suggested chemical meningitis caused by an intracystic hemorrhage and rupture of the pineal cyst.

  19. Interstitial Fluid Sphingosine-1-Phosphate in Murine Mammary Gland and Cancer and Human Breast Tissue and Cancer Determined by Novel Methods.

    PubMed

    Nagahashi, Masayuki; Yamada, Akimitsu; Miyazaki, Hiroshi; Allegood, Jeremy C; Tsuchida, Junko; Aoyagi, Tomoyoshi; Huang, Wei-Ching; Terracina, Krista P; Adams, Barbara J; Rashid, Omar M; Milstien, Sheldon; Wakai, Toshifumi; Spiegel, Sarah; Takabe, Kazuaki

    2016-06-01

    The tumor microenvironment is a determining factor for cancer biology and progression. Sphingosine-1-phosphate (S1P), produced by sphingosine kinases (SphKs), is a bioactive lipid mediator that regulates processes important for cancer progression. Despite its critical roles, the levels of S1P in interstitial fluid (IF), an important component of the tumor microenvironment, have never previously been measured due to a lack of efficient methods for collecting and quantifying IF. The purpose of this study is to clarify the levels of S1P in the IF from murine mammary glands and its tumors utilizing our novel methods. We developed an improved centrifugation method to collect IF. Sphingolipids in IF, blood, and tissue samples were measured by mass spectrometry. In mice with a deletion of SphK1, but not SphK2, levels of S1P in IF from the mammary glands were greatly attenuated. Levels of S1P in IF from mammary tumors were reduced when tumor growth was suppressed by oral administration of FTY720/fingolimod. Importantly, sphingosine, dihydro-sphingosine, and S1P levels, but not dihydro-S1P, were significantly higher in human breast tumor tissue IF than in the normal breast tissue IF. To our knowledge, this is the first reported S1P IF measurement in murine normal mammary glands and mammary tumors, as well as in human patients with breast cancer. S1P tumor IF measurement illuminates new aspects of the role of S1P in the tumor microenvironment.

  20. Lipomatous infiltration of the canine salivary gland.

    PubMed

    Brown, P J; Lucke, V M; Sozmen, M; Whitbread, T J; Wyatt, J M

    1997-06-01

    Benign connective tumours of the canine salivary glands are rare. This report describes lipomatous infiltration of parotid or submandibular salivary glands in seven dogs in which the glands were enlarged as a result of infiltration by fat cells; they appeared to have been successfully treated by local excision. The precise cause of the lipomatous infiltration in the dogs is unclear but different causes of similar lesions in humans are discussed.

  1. Pineal and ectopic pineal tumors: the role of radiation therapy. [X ray; /sup 60/Co

    SciTech Connect

    Rao, Y.T.R.; Medini, E.; Haselow, R.E.; Jones, T.K. Jr.; Levitt, S.H.

    1981-08-01

    Seventeen patients with pineal tumors and one ectopic (suprasellar) germinoma were treated with radiation therapy. Surgery was restricted to decompression in 16 patients, and only two patients had resection of the tumor. Thirteen of 18 patients are alive without evidence for disease with a ten-year surrvival rate of 88%. The tumor dose ranged from 4000 rads to 6000 rads. No age or dose dependence in survival was noted, but patients with whole brain irradiation or generous volume to include ventricular system had better survival. No case of spinal metastasis was noted. The possibility of increased incidence of meningeal seeding following surgical intervention is considered. From their data, the authors feel that radiation therapy with or without surgical decompression should be the primary treatment for pinealoma. Surgery can be used for diagnosis and/or treatment of patients who show delayed response to radiation. Recommendation is made for the use of whole brain irradiation to 4000 rads followed by a boost to the tumor area to 5000 rads.

  2. Peroxisome proliferator-activated receptor gamma in the human pituitary gland: expression and splicing pattern in adenomas versus normal pituitary.

    PubMed

    Occhi, G; Albiger, N; Berlucchi, S; Gardiman, M; Scanarini, M; Scienza, R; Fassina, A; Mantero, F; Scaroni, C

    2007-07-01

    Pituitary adenomas are slow-growing tumours arising within the pituitary gland. If secreting, they give rise to well-known syndromes such as Cushing's disease or acromegaly; when hormonally inactive, they come to clinical attention often with local mass effects or pituitary deficiency. Peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear hormone receptor with a key role in fat and glucose metabolism, but also involved in several neoplasia, has recently been detected in pituitary adenomas. In the present study, we evaluated the occurrence and splicing profile of PPARgamma in 43 cases of pituitary adenoma of different subtypes and compared it to 12 normal pituitary glands. By real-time polymerase chain reaction, PPARgamma was expressed as much in adrenocorticotrophic hormone (ACTH)-secreting and ACTH-silent adenomas as in controls, with a moderate underexpression in somatotrophinomas and prolactinomas and overexpression in 54% of nonfunctioning pituitary adenomas (NFPA). There was no apparent qualitative change in the splicing profile of pathological pituitary glands, nor was the presence of specific isoforms with dominant negative effects against PPARgamma detected. Western blotting revealed similar expression levels in the different subgroups of pituitary adenomas and normal glands. Immunohistochemistry confirmed PPARgamma expression in approximately one-half of analysed samples. The intra- and intergroup differences observed in pituitary adenomas may represent new elements in the process of understanding the different clinical responses of Cushing's and Nelson patients to PPARgamma-ligand treatment. Moreover, the higher level of PPARgamma expression detected in the NFPA subgroup may suggest its possible role as a molecular target in these pituitary adenomas, paving the way for investigations on the effectiveness of treatment with thiazolidinediones in such patients. PMID:17561883

  3. Cellular pleomorphism in papillary tumors of the pineal region

    PubMed Central

    Magalhães, Juliana; Rostad, Steven; Foltz, Greg; Pytel, Peter; Rodriguez, Fausto J.

    2015-01-01

    Papillary tumor of the pineal region (PTPR) is a recently recognized entity. We present the pathologic findings of two cases of PTPR as examples, and discuss the presence of cellular pleomorphism in these tumors. Patient 1 is a 48-year-old man with a pineal region mass. The tumor had unique biphasic patterns, papillary/pseudopapillary areas, and increased mitotic activity. Juxtaposed areas had marked pleomorphism, including nuclear enlargement, smudgy chromatin, nuclear pseudoinclusions, and cytoplasmic vacuolation. Mitoses were absent in these areas. Immunohistochemical staining revealed strong S100 expression. CAM 5.2 and CK18 were strongly positive in a patchy fashion. MIB1 labeling indices were high in classic PTPR regions but very low in pleomorphic areas. Patient 2 was a 35-year-old male with a pineal region tumor characterized by papillary architecture and overall cellular monotony, rare mitoses, and pleomorphism as a more isolated finding, with associated nuclear enlargement and crowding. S100 and CAM 5.2 labeling were present, and MIB1 labeling index was very low throughout the tumor. We discuss the pathologic and phenotypic features of PTPR. Variable pleomorphism may be present, reflected in size variation and nuclear hyperchromasia, but was not accompanied by increased proliferative activity in these cases, suggesting a degenerative phenomenon. PMID:22622671

  4. Cellular pleomorphism in papillary tumors of the pineal region.

    PubMed

    Magalhães, Juliana; Rostad, Steven; Foltz, Greg; Pytel, Peter; Rodriguez, Fausto J

    2013-04-01

    Papillary tumor of the pineal region (PTPR) is a recently recognized entity. We present the pathologic findings of two cases of PTPR as examples, and discuss the presence of cellular pleomorphism in these tumors. Patient 1 is a 48-year-old man with a pineal region mass. The tumor had unique biphasic patterns, papillary/pseudopapillary areas, and increased mitotic activity. Juxtaposed areas had marked pleomorphism, including nuclear enlargement, smudgy chromatin, nuclear pseudoinclusions, and cytoplasmic vacuolation. Mitoses were absent in these areas. Immunohistochemical staining revealed strong S100 expression. CAM 5.2 and CK18 were strongly positive in a patchy fashion. MIB1 labeling indices were high in classic PTPR regions but very low in pleomorphic areas. Patient 2 was a 35-year-old male with a pineal region tumor characterized by papillary architecture and overall cellular monotony, rare mitoses, and pleomorphism as a more isolated finding, with associated nuclear enlargement and crowding. S100 and CAM 5.2 labeling were present, and MIB1 labeling index was very low throughout the tumor. We discuss the pathologic and phenotypic features of PTPR. Variable pleomorphism may be present, reflected in size variation and nuclear hyperchromasia, but was not accompanied by increased proliferative activity in these cases, suggesting a degenerative phenomenon.

  5. Meibomian gland dysfunction: hyperkeratinization or atrophy?

    PubMed

    Jester, James V; Parfitt, Geraint J; Brown, Donald J