WorldWideScience

Sample records for human adrenal cells

  1. Biogenesis of corticosteroids in monolayer cultures of human foetal adrenal cells

    International Nuclear Information System (INIS)

    Goodyer, C.G.; Torday, J.S.; St George Hall, C.; Smith, B.T.; Giroud, C.J.P.

    1976-01-01

    Human foetal adrenal cells were grown in monolayer culture and their steroidogenic capacity observed for up to a month. The cells produced a complex array of steroids and some of their ester sulphates from endogenous as well as from [ 14 C] and[ 3 H] precursors. ACTH stimulated corticoidogenesis, particularly cortisol secretion, and markedly enhanced the incorporation of progesterone and pregnenolone into cortisol. Following incubation with the same precursors, large amounts of radioactivity remained water soluble. From the butanol extractable material of this fraction, dehydroepiandrosterone sulphate was characterized as the main metabolite of pregnenolone and corticosterone and 11-deoxycorticosterone sulphates as the main metabolites of progesterone. With time in culture there was a decrease in steroidogenesis as well as a steady decline in responsiveness to ACTH, mainly manifested by cortisol secretion. The medium from homologous foetal pituitary cultures stimulated cortisol production by the human adrenal cell monolayer. (author)

  2. Growth-inhibitory effect of TGF-B on human fetal adrenal cells in primary monolayer culture.

    Science.gov (United States)

    Riopel, L; Branchaud, C L; Goodyer, C G; Adkar, V; Lefebvre, Y

    1989-08-01

    We examined the effects of transforming-growth factor-B (TGF-B) on growth ([3H]-thymidine uptake) and function (dehydroepiandrosterone sulfate [DHAS] and cortisol production) of human fetal zone adrenal cells. Results indicate that TGF-B significantly inhibits, in a dose-related manner, both basal and epidermal growth factor (EGF)-stimulated cell growth: IC50 = 0.1-0.25 ng/ml. EGF is ineffective in overcoming the inhibitory effect of TGF-B, suggesting a noncompetitive antagonism between the two factors. Also, the inhibitory effect of TGF-B is additive to that of adrenocorticotropic hormone (ACTH). On the other hand, TGF-B (1 ng/ml) does not significantly change basal or ACTH-stimulated DHAS or cortisol secretion. We conclude that, unlike its effect on other steroid-producing cells, TGF-B inhibits growth of fetal zone cells and does not appear to have a significant inhibitory effect on steroidogenesis.

  3. Modeling Congenital Adrenal Hyperplasia and Testing Interventions for Adrenal Insufficiency Using Donor-Specific Reprogrammed Cells

    Directory of Open Access Journals (Sweden)

    Gerard Ruiz-Babot

    2018-01-01

    Full Text Available Adrenal insufficiency is managed by hormone replacement therapy, which is far from optimal; the ability to generate functional steroidogenic cells would offer a unique opportunity for a curative approach to restoring the complex feedback regulation of the hypothalamic-pituitary-adrenal axis. Here, we generated human induced steroidogenic cells (hiSCs from fibroblasts, blood-, and urine-derived cells through forced expression of steroidogenic factor-1 and activation of the PKA and LHRH pathways. hiSCs had ultrastructural features resembling steroid-secreting cells, expressed steroidogenic enzymes, and secreted steroid hormones in response to stimuli. hiSCs were viable when transplanted into the mouse kidney capsule and intra-adrenal. Importantly, the hypocortisolism of hiSCs derived from patients with adrenal insufficiency due to congenital adrenal hyperplasia was rescued by expressing the wild-type version of the defective disease-causing enzymes. Our study provides an effective tool with many potential applications for studying adrenal pathobiology in a personalized manner and opens venues for the development of precision therapies.

  4. Modeling Congenital Adrenal Hyperplasia and Testing Interventions for Adrenal Insufficiency Using Donor-Specific Reprogrammed Cells.

    Science.gov (United States)

    Ruiz-Babot, Gerard; Balyura, Mariya; Hadjidemetriou, Irene; Ajodha, Sharon J; Taylor, David R; Ghataore, Lea; Taylor, Norman F; Schubert, Undine; Ziegler, Christian G; Storr, Helen L; Druce, Maralyn R; Gevers, Evelien F; Drake, William M; Srirangalingam, Umasuthan; Conway, Gerard S; King, Peter J; Metherell, Louise A; Bornstein, Stefan R; Guasti, Leonardo

    2018-01-30

    Adrenal insufficiency is managed by hormone replacement therapy, which is far from optimal; the ability to generate functional steroidogenic cells would offer a unique opportunity for a curative approach to restoring the complex feedback regulation of the hypothalamic-pituitary-adrenal axis. Here, we generated human induced steroidogenic cells (hiSCs) from fibroblasts, blood-, and urine-derived cells through forced expression of steroidogenic factor-1 and activation of the PKA and LHRH pathways. hiSCs had ultrastructural features resembling steroid-secreting cells, expressed steroidogenic enzymes, and secreted steroid hormones in response to stimuli. hiSCs were viable when transplanted into the mouse kidney capsule and intra-adrenal. Importantly, the hypocortisolism of hiSCs derived from patients with adrenal insufficiency due to congenital adrenal hyperplasia was rescued by expressing the wild-type version of the defective disease-causing enzymes. Our study provides an effective tool with many potential applications for studying adrenal pathobiology in a personalized manner and opens venues for the development of precision therapies. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  5. A genomic atlas of human adrenal and gonad development

    Science.gov (United States)

    del Valle, Ignacio; Buonocore, Federica; Duncan, Andrew J.; Lin, Lin; Barenco, Martino; Parnaik, Rahul; Shah, Sonia; Hubank, Mike; Gerrelli, Dianne; Achermann, John C.

    2017-01-01

    Background: In humans, the adrenal glands and gonads undergo distinct biological events between 6-10 weeks post conception (wpc), such as testis determination, the onset of steroidogenesis and primordial germ cell development. However, relatively little is currently known about the genetic mechanisms underlying these processes. We therefore aimed to generate a detailed genomic atlas of adrenal and gonad development across these critical stages of human embryonic and fetal development. Methods: RNA was extracted from 53 tissue samples between 6-10 wpc (adrenal, testis, ovary and control). Affymetrix array analysis was performed and differential gene expression was analysed using Bioconductor. A mathematical model was constructed to investigate time-series changes across the dataset. Pathway analysis was performed using ClueGo and cellular localisation of novel factors confirmed using immunohistochemistry. Results: Using this approach, we have identified novel components of adrenal development (e.g. ASB4, NPR3) and confirmed the role of SRY as the main human testis-determining gene. By mathematical modelling time-series data we have found new genes up-regulated with SOX9 in the testis (e.g. CITED1), which may represent components of the testis development pathway. We have shown that testicular steroidogenesis has a distinct onset at around 8 wpc and identified potential novel components in adrenal and testicular steroidogenesis (e.g. MGARP, FOXO4, MAP3K15, GRAMD1B, RMND2), as well as testis biomarkers (e.g. SCUBE1). We have also shown that the developing human ovary expresses distinct subsets of genes (e.g. OR10G9, OR4D5), but enrichment for established biological pathways is limited. Conclusion: This genomic atlas is revealing important novel aspects of human development and new candidate genes for adrenal and reproductive disorders. PMID:28459107

  6. Adrenal hormones in human follicular fluid.

    Science.gov (United States)

    Jimena, P; Castilla, J A; Peran, F; Ramirez, J P; Vergara, F; Molina, R; Vergara, F; Herruzo, A

    1992-11-01

    Considerable evidence indicates that adrenal hormones may affect gonadal function. To assess the role of some adrenal hormones in human follicular fluid and their relationship with the ability of the oocyte to be fertilized and then to cleave in vitro, cortisol and dehydroepiandrosterone sulfate were measured in follicular fluid obtained at the time of oocyte recovery for in vitro fertilization from cycles stimulated by clomiphene citrate, human menopausal gonadotropin and human chorionic gonadotropin. Thirty-six follicular fluid containing mature oocyte-corona-cumulus complexes and free of visible blood contamination were included in this study. There was no significant difference in follicular fluid dehydroepiandrosterone sulfate concentration between follicles with oocytes which did or did not fertilize (5.1 +/- 1.1 vs 5.8 +/- 2.0 mumol/l). However, follicular fluid from follicles whose oocytes were not fertilized had levels of cortisol significantly higher than those in follicular fluid from follicles containing successfully fertilized oocytes (406.0 +/- 75.9 vs 339.2 +/- 37.0 nmol/l; p < 0.005). No significant correlations were found between rates of embryo cleavage and cortisol and dehydroepiandrosterone levels in follicular fluid. We conclude that cortisol levels in follicular fluid may provide an index of fertilization outcome, at least in stimulated cycles by clomiphene citrate, human menopausal gonadotropin and human chorionic gonadotropin.

  7. Biosynthesis and metabolism of steroid hormones by human adrenal carcinomas

    OpenAIRE

    Brown, J.W.; Fishman, L.M.

    2000-01-01

    Over a 15-year period, our university-based laboratory obtained 125 adrenal tumors, of which 15 (12%) were adrenal cortical carcinomas. Of these, 6 (40% of the carcinomas) occurred in patients with clear clinical manifestations of steroid hormone excess. Adrenal cortical carcinoma cells derived from the surgically resected tumors in 4 of these patients were isolated and established in primary culture. Radiotracer steroid interconversion studies were carried out with these cultures and also on...

  8. In vivo production of novel vitamin D2 hydroxy-derivatives by human placentas, epidermal keratinocytes, Caco-2 colon cells and the adrenal gland

    Science.gov (United States)

    Slominski, Andrzej T.; Kim, Tae-Kang; Shehabi, Haleem Z.; Tang, Edith; Benson, Heather A. E.; Semak, Igor; Lin, Zongtao; Yates, Charles R.; Wang, Jin; Li, Wei; Tuckey, Robert C.

    2014-01-01

    We investigated the metabolism of vitamin D2 to hydroxyvitamin D2 metabolites ((OH)D2) by human placentas ex-utero, adrenal glands ex-vivo and cultured human epidermal keratinocytes and colonic Caco-2 cells, and identified 20(OH)D2, 17,20(OH)2D2, 1,20(OH)2D2, 25(OH)D2 and 1,25(OH)2D2 as products. Inhibition of product formation by 22R-hydroxycholesterol indicated involvement of CYP11A1 in 20- and 17-hydroxylation of vitamin D2, while use of ketoconazole indicated involvement of CYP27B1 in 1α-hydroxylation of products. Studies with purified human CYP11A1 confirmed the ability of this enzyme to convert vitamin D2 to 20(OH)D2 and 17,20(OH)2D2. In placentas and Caco-2 cells, production of 20(OH)D2 was higher than 25(OH)D2 while in human keratinocytes the production of 20(OH)D2 and 25(OH)D2 were comparable. HaCaT keratinocytes showed high accumulation of 1,20(OH)2D2 relative to 20(OH)D2 indicating substantial CYP27B1 activity. This is the first in vivo evidence for a novel pathway of vitamin D2 metabolism initiated by CYP11A1 and modified by CYP27B1, with the product profile showing tissue- and cell-type specificity. PMID:24382416

  9. Cell-to-cell communication in bilateral macronodular adrenal hyperplasia causing hypercortisolism

    Directory of Open Access Journals (Sweden)

    Herve eLefebvre

    2015-04-01

    Full Text Available It has been well established that, in the human adrenal gland, cortisol secretion is not only controlled by circulating corticotropin but is also influenced by a wide variety of bioactive signals, including conventional neurotransmitters and neuropeptides, released within the cortex by various cell types such as chromaffin cells, neurons, cells of the immune system, adipocytes and endothelial cells. These different types of cells are present in bilateral macronodular adrenal hyperplasia, a rare etiology of primary adrenal Cushing’s syndrome, where they appear intermingled with adrenocortical cells in the hyperplastic cortex. In addition, the genetic events which cause the disease favor abnormal adrenal differenciation that results in illicit expression of paracrine regulatory factors and their receptors in adrenocortical cells. All these defects constitute the molecular basis for aberrant autocrine/paracrine regulatory mechanisms which are likely to play a role in the pathophysiology of bilateral macronodular adrenal hyperplasia-associated hypercortisolism. The present review summarizes the current knowledge on this topic as well as the therapeutic perspectives offered by this new pathophysiological concept.

  10. A genomic atlas of human adrenal and gonad development [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Ignacio del Valle

    2017-04-01

    Full Text Available Background: In humans, the adrenal glands and gonads undergo distinct biological events between 6-10 weeks post conception (wpc, such as testis determination, the onset of steroidogenesis and primordial germ cell development. However, relatively little is currently known about the genetic mechanisms underlying these processes. We therefore aimed to generate a detailed genomic atlas of adrenal and gonad development across these critical stages of human embryonic and fetal development. Methods: RNA was extracted from 53 tissue samples between 6-10 wpc (adrenal, testis, ovary and control. Affymetrix array analysis was performed and differential gene expression was analysed using Bioconductor. A mathematical model was constructed to investigate time-series changes across the dataset. Pathway analysis was performed using ClueGo and cellular localisation of novel factors confirmed using immunohistochemistry. Results: Using this approach, we have identified novel components of adrenal development (e.g. ASB4, NPR3 and confirmed the role of SRY as the main human testis-determining gene. By mathematical modelling time-series data we have found new genes up-regulated with SOX9 in the testis (e.g. CITED1, which may represent components of the testis development pathway. We have shown that testicular steroidogenesis has a distinct onset at around 8 wpc and identified potential novel components in adrenal and testicular steroidogenesis (e.g. MGARP, FOXO4, MAP3K15, GRAMD1B, RMND2, as well as testis biomarkers (e.g. SCUBE1. We have also shown that the developing human ovary expresses distinct subsets of genes (e.g. OR10G9, OR4D5, but enrichment for established biological pathways is limited. Conclusion: This genomic atlas is revealing important novel aspects of human development and new candidate genes for adrenal and reproductive disorders.

  11. A genomic atlas of human adrenal and gonad development [version 2; referees: 4 approved

    Directory of Open Access Journals (Sweden)

    Ignacio del Valle

    2017-10-01

    Full Text Available Background: In humans, the adrenal glands and gonads undergo distinct biological events between 6-10 weeks post conception (wpc, such as testis determination, the onset of steroidogenesis and primordial germ cell development. However, relatively little is currently known about the genetic mechanisms underlying these processes. We therefore aimed to generate a detailed genomic atlas of adrenal and gonad development across these critical stages of human embryonic and fetal development. Methods: RNA was extracted from 53 tissue samples between 6-10 wpc (adrenal, testis, ovary and control. Affymetrix array analysis was performed and differential gene expression was analysed using Bioconductor. A mathematical model was constructed to investigate time-series changes across the dataset. Pathway analysis was performed using ClueGo and cellular localisation of novel factors confirmed using immunohistochemistry. Results: Using this approach, we have identified novel components of adrenal development (e.g. ASB4, NPR3 and confirmed the role of SRY as the main human testis-determining gene. By mathematical modelling time-series data we have found new genes up-regulated with SOX9 in the testis (e.g. CITED1, which may represent components of the testis development pathway. We have shown that testicular steroidogenesis has a distinct onset at around 8 wpc and identified potential novel components in adrenal and testicular steroidogenesis (e.g. MGARP, FOXO4, MAP3K15, GRAMD1B, RMND2, as well as testis biomarkers (e.g. SCUBE1. We have also shown that the developing human ovary expresses distinct subsets of genes (e.g. OR10G9, OR4D5, but enrichment for established biological pathways is limited. Conclusion: This genomic atlas is revealing important novel aspects of human development and new candidate genes for adrenal and reproductive disorders.

  12. Differential regulation of human 3β-hydroxysteroid dehydrogenase type 2 for steroid hormone biosynthesis by starvation and cyclic AMP stimulation: studies in the human adrenal NCI-H295R cell model.

    Directory of Open Access Journals (Sweden)

    Sameer Udhane

    Full Text Available Human steroid biosynthesis depends on a specifically regulated cascade of enzymes including 3β-hydroxysteroid dehydrogenases (HSD3Bs. Type 2 HSD3B catalyzes the conversion of pregnenolone, 17α-hydroxypregnenolone and dehydroepiandrosterone to progesterone, 17α-hydroxyprogesterone and androstenedione in the human adrenal cortex and the gonads but the exact regulation of this enzyme is unknown. Therefore, specific downregulation of HSD3B2 at adrenarche around age 6-8 years and characteristic upregulation of HSD3B2 in the ovaries of women suffering from the polycystic ovary syndrome remain unexplained prompting us to study the regulation of HSD3B2 in adrenal NCI-H295R cells. Our studies confirm that the HSD3B2 promoter is regulated by transcription factors GATA, Nur77 and SF1/LRH1 in concert and that the NBRE/Nur77 site is crucial for hormonal stimulation with cAMP. In fact, these three transcription factors together were able to transactivate the HSD3B2 promoter in placental JEG3 cells which normally do not express HSD3B2. By contrast, epigenetic mechanisms such as methylation and acetylation seem not involved in controlling HSD3B2 expression. Cyclic AMP was found to exert differential effects on HSD3B2 when comparing short (acute versus long-term (chronic stimulation. Short cAMP stimulation inhibited HSD3B2 activity directly possibly due to regulation at co-factor or substrate level or posttranslational modification of the protein. Long cAMP stimulation attenuated HSD3B2 inhibition and increased HSD3B2 expression through transcriptional regulation. Although PKA and MAPK pathways are obvious candidates for possibly transmitting the cAMP signal to HSD3B2, our studies using PKA and MEK1/2 inhibitors revealed no such downstream signaling of cAMP. However, both signaling pathways were clearly regulating HSD3B2 expression.

  13. Biosynthesis and metabolism of steroid hormones by human adrenal carcinomas

    Directory of Open Access Journals (Sweden)

    Brown J.W.

    2000-01-01

    Full Text Available Over a 15-year period, our university-based laboratory obtained 125 adrenal tumors, of which 15 (12% were adrenal cortical carcinomas. Of these, 6 (40% of the carcinomas occurred in patients with clear clinical manifestations of steroid hormone excess. Adrenal cortical carcinoma cells derived from the surgically resected tumors in 4 of these patients were isolated and established in primary culture. Radiotracer steroid interconversion studies were carried out with these cultures and also on mitochondria isolated from homogenized tissues. Large tumors had the lowest steroidogenic activities per weight, whereas small tumors had more moderately depressed enzyme activities relative to cells from normal glands. In incubations with pregnenolone as substrate, 1 mM metyrapone blocked the synthesis of corticosterone and cortisol and also the formation of aldosterone. Metyrapone inhibition was associated with a concomitant increase in the formation of androgens (androstenedione and testosterone from pregnenolone. Administration of metyrapone in vivo before surgery in one patient resulted in a similar increase in plasma androstenedione, though plasma testosterone levels were not significantly affected. In cultures of two of four tumors examined, dibutyryl cAMP stimulated 11ß-hydroxylase activity modestly; ACTH also had a significant stimulatory effect in one of these tumors. Unlike results obtained with normal or adenomatous adrenal cortical tissues, mitochondria from carcinomatous cells showed a lack of support of either cholesterol side-chain cleavage enzyme complex or steroid 11ß-hydroxylase activity by Krebs cycle intermediates (10 mM isocitrate, succinate or malate. This finding is consistent with the concept that these carcinomas may tend to function predominantly in an anaerobic manner, rather than through the oxidation of Krebs cycle intermediates.

  14. Effect of placental factors on growth and function of the human fetal adrenal in vitro.

    Science.gov (United States)

    Riopel, L; Branchaud, C L; Goodyer, C G; Zweig, M; Lipowski, L; Adkar, V; Lefebvre, Y

    1989-11-01

    Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: 1) maximal response to PM was 2-5 times greater; 2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; 3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland.

  15. Effect of placental factors on growth and function of the human fetal adrenal in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Riopel, L.; Branchaud, C.L.; Goodyer, C.G.; Zweig, M.; Lipowski, L.; Adkar, V.; Lefebvre, Y. (McGill Univ.-Montreal Children' s Hospital Research Institute, Quebec (Canada))

    1989-11-01

    Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: (1) maximal response to PM was 2-5 times greater; (2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; (3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland.

  16. Effect of placental factors on growth and function of the human fetal adrenal in vitro

    International Nuclear Information System (INIS)

    Riopel, L.; Branchaud, C.L.; Goodyer, C.G.; Zweig, M.; Lipowski, L.; Adkar, V.; Lefebvre, Y.

    1989-01-01

    Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: (1) maximal response to PM was 2-5 times greater; (2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; (3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland

  17. Early fetal acquisition of the chromaffin and neuronal immunophenotype by human adrenal medullary cells. An immunohistological study using monoclonal antibodies to chromogranin A, synaptophysin, tyrosine hydroxylase, and neuronal cytoskeletal proteins.

    NARCIS (Netherlands)

    Molenaar, W M; Lee, V M; Trojanowski, J Q

    1990-01-01

    The development of chromaffin and neuronal features in the adrenal medulla was studied in normal human fetuses with gestational ages (GAs) of 6-34 weeks. Monoclonal antibodies specific for chromogranin A, synaptophysin, and tyrosine hydroxylase; for different subunits and phosphoisoforms of

  18. Cholinergic regulation of protein phosphorylation in bovine adrenal chromaffin cells

    International Nuclear Information System (INIS)

    Haycock, J.W.; Browning, M.D.; Greengard, P.

    1988-01-01

    Chromaffin cells were isolated from bovine adrenal medullae and maintained in primary culture. After prelabeling with 32 PO 4 , exposure of the chromaffin cells to acetylcholine increased the phosphorylation of a M/sub r/ ≅ 100,000 protein and a M/sub r/ ≅ 60,000 protein (tyrosine hydroxylase), visualized after separation of total cellular proteins in NaDodSO 4 /polyacrylamide gels. Immunoprecipitation with antibodies to three known phosphoproteins (100-kDa, 87-kDa, and protein III) revealed an acetylcholine-dependent phosphorylation of these proteins. These three proteins were also shown to be present in bovine adrenal chromaffin cells by immunolabeling techniques. 100-kDa is a M/sub r/ ≅ 100,000 protein selectively phosphorylated by calcium/calmodulin-dependent protein kinase III, 87-kDa is a M/sub r/ ≅ 87,000 protein selectively phosphorylated by protein kinase C, and protein III is a phosphoprotein doublet of M/sub r/ ≅ 74,000 (IIIa) and M/sub r/ ≅ 55,000 (IIIb) phosphorylated by cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase I. The data demonstrate that cholinergic activation of chromaffin cells increases the phosphorylation of several proteins and that several protein kinase systems may be involved in these effects

  19. Neglected issues concerning teaching human adrenal steroidogenesis in popular biochemistry textbooks.

    Science.gov (United States)

    Han, Zhiyong; Elliott, Mark S

    2017-11-01

    In the human body, the adrenal steroids collectively regulate a plethora of fundamental functions, including electrolyte and water balance, blood pressure, stress response, intermediary metabolism, inflammation, and immunity. Therefore, adrenal steroidogenesis is an important biochemistry topic for students to learn in order for them to understand health consequences caused by deficiencies of enzymes in the adrenal steroidogenic pathways. However, popular biochemistry textbooks contain insufficient information and may sometimes give students a misimpression about certain aspects of human adrenal steroidogenesis. This article highlights two neglected issues in teaching human adrenal steroidogenesis in popular biochemistry textbooks. The purpose of this article is to draw attention to these issues. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(6):469-474, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

  20. Neglected Issues Concerning Teaching Human Adrenal Steroidogenesis in Popular Biochemistry Textbooks

    Science.gov (United States)

    Han, Zhiyong; Elliott, Mark S.

    2017-01-01

    In the human body, the adrenal steroids collectively regulate a plethora of fundamental functions, including electrolyte and water balance, blood pressure, stress response, intermediary metabolism, inflammation, and immunity. Therefore, adrenal steroidogenesis is an important biochemistry topic for students to learn in order for them to understand…

  1. Leydig Cell Tumor Associated with Testicular Adrenal Rest Tumors in a Patient with Congenital Adrenal Hyperplasia due to 11β-Hydroxylase Deficiency

    OpenAIRE

    Charfi, Nadia; Kamoun, Mahdi; Feki Mnif, Mouna; Mseddi, Neila; Mnif, Fatma; Kallel, Nozha; Ben Naceur, Basma; Rekik, Nabila; Fourati, Hela; Daoud, Emna; Mnif, Zainab; Hadj Sliman, Mourad; Sellami-Boudawara, Tahia; Abid, Mohamed

    2012-01-01

    Congenital adrenal hyperplasia (CAH) describes a group of inherited autosomal recessive disorders characterized by enzyme defects in the steroidogenic pathways that lead to the biosynthesis of cortisol, aldosterone, and androgens. Chronic excessive adrenocorticotropic hormone (ACTH) stimulation may result in hyperplasia of ACTH-sensitive tissues in adrenal glands and other sites such as the testes, causing testicular masses known as testicular adrenal rest tumors (TARTs). Leydig cell tumors (...

  2. Angiotensin effects on calcium and steroidogenesis in adrenal glomerulosa cells

    International Nuclear Information System (INIS)

    Elliott, M.E.; Siegel, F.L.; Hadjokas, N.E.; Goodfriend, T.L.

    1985-01-01

    We investigated the role of cellular calcium pools in angiotensin II-stimulated aldosterone synthesis in bovine adrenal glomerulosa cells. Angiotensin II decreased the size of the exchangeable cell calcium pool by 34%, consistent with previous observations that angiotensin II causes decreased uptake of 45 Ca+2 into cells and increased efflux of 45 Ca+2 from preloaded cells. Atomic absorption spectroscopy showed that angiotension II caused a decrease of 21% in total cellular calcium. Angiotensin II caused efflux of 45 Ca+2 in the presence of EGTA and retarded uptake of 45 Ca+2 when choline was substituted for sodium, suggesting that hormone effects on calcium pools do not involve influx of trigger calcium or sodium. Cells incubated in calcium-free buffer and 0.1 mM or 0.5 mM EGTA synthesized reduced (but still significant) amounts of the steroid in response to hormone. Cells incubated in increasing concentrations of extracellular calcium contained increasing amounts of intracellular calcium and synthesized increasing amounts of aldosterone in response to angiotensin II. These results point to the participation of intracellular calcium pools in angiotensin II-stimulated steroidogenesis and the importance of extracellular calcium in maintaining these pools

  3. Monkey Adrenal Chromaffin Cells Express α6β4* Nicotinic Acetylcholine Receptors

    Science.gov (United States)

    Scadden, Mick´l; Carmona-Hidalgo, Beatriz; McIntosh, J. Michael; Albillos, Almudena

    2014-01-01

    Nicotinic acetylcholine receptors (nAChRs) that contain α6 and β4 subunits have been demonstrated functionally in human adrenal chromaffin cells, rat dorsal root ganglion neurons, and on noradrenergic terminals in the hippocampus of adolescent mice. In human adrenal chromaffin cells, α6β4* nAChRs (the asterisk denotes the possible presence of additional subunits) are the predominant subtype whereas in rodents, the predominant nAChR is the α3β4* subtype. Here we present molecular and pharmacological evidence that chromaffin cells from monkey (Macaca mulatta) also express α6β4* receptors. PCR was used to show the presence of transcripts for α6 and β4 subunits and pharmacological characterization was performed using patch-clamp electrophysiology in combination with α-conotoxins that target the α6β4* subtype. Acetylcholine-evoked currents were sensitive to inhibition by BuIA[T5A,P6O] and MII[H9A,L15A]; α-conotoxins that inhibit α6-containing nAChRs. Two additional agonists were used to probe for the expression of α7 and β2-containing nAChRs. Cells with currents evoked by acetylcholine were relatively unresponsive to the α7-selctive agonist choline but responded to the agonist 5-I-A-85380. These studies provide further insights into the properties of natively expressed α6β4* nAChRs. PMID:24727685

  4. Pituitary and adrenal involvement in diffuse large B-cell lymphoma, with recovery of their function after chemotherapy

    OpenAIRE

    Nakashima, Yasuhiro; Shiratsuchi, Motoaki; Abe, Ichiro; Matsuda, Yayoi; Miyata, Noriyuki; Ohno, Hirofumi; Ikeda, Motohiko; Matsushima, Takamitsu; Nomura, Masatoshi; Takayanagi, Ryoichi

    2013-01-01

    Background Diffuse large B-cell lymphoma sometimes involves the endocrine organs, but involvement of both the pituitary and adrenal glands is extremely rare. Involvement of these structures can lead to hypopituitarism and adrenal insufficiency, and subsequent recovery of their function is rarely seen. The present report describes an extremely rare case of pituitary and adrenal diffuse large B-cell lymphoma presenting with hypopituitarism and adrenal insufficiency with subsequent recovery of p...

  5. Incorporation of (14)C-cholesterol in human adrenal corticocarcinoma H295R cell line and online-radiodetection of produced (14)C-steroid hormone metabolites

    DEFF Research Database (Denmark)

    Abdel-Khalik, Jonas; Björklund, Erland; Nielsen, Frederik Knud

    2017-01-01

    in the steroidogenesis of H295R cells, radioactive cholesterol may potentially only need to be added just before the cells are incubated for 72h in well plates. Based on the obtained HPLC-FSA chromatograms, and confirmation of the observations by studies in the literature, a qualitative time profile for the production......, the concept of radiolabeling the steroidogenesis in H295R cells with (14)C-cholesterol and detecting the radiolabeled steroid hormones online was proved and may assist in further toxicological studies....

  6. Cholesterol delivery to the adrenal glands estimated by adrenal venous sampling: An in vivo model to determine the contribution of circulating lipoproteins to steroidogenesis in humans.

    Science.gov (United States)

    Buitenwerf, Edward; Dullaart, Robin P F; Muller Kobold, Anneke C; Links, Thera P; Sluiter, Wim J; Connelly, Margery A; Kerstens, Michiel N

    Cholesterol, required for adrenal steroid hormone synthesis, is at least in part derived from circulating lipoproteins. The contribution of high-density lipoproteins (HDL) and low-density lipoproteins (LDL) to adrenal steroidogenesis in humans is unclear. The aim of the study was to determine the extent to which HDL and LDL are taken up by the adrenal glands using samples obtained during adrenal venous sampling (AVS). AVS was successfully performed in 23 patients with primary aldosteronism. Samples were drawn from both adrenal veins and inferior vena cava (IVC). HDL cholesterol (HDL-C) and lipoprotein particle profiles were determined by nuclear magnetic resonance spectroscopy. Apolipoprotein (apo) A-I and apoB were assayed by immunoturbidimetry. Plasma HDL-C and HDL and LDL particle concentrations (HDL-P and LDL-P) were not lower in samples obtained from the adrenal veins compared with the IVC (HDL-C, P = .59; HDL-P, P = .06; LDL-P, P = .93). ApoB was lower in adrenal venous plasma than in IVC (P = .026; P lipoproteins and steroidogenesis. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  7. Asthma pregnancy alters postnatal development of chromaffin cells in the rat adrenal medulla.

    Directory of Open Access Journals (Sweden)

    Xiu-Ming Wu

    Full Text Available Adrenal neuroendocrine plays an important role in asthma. The activity of the sympathoadrenal system could be altered by early life events. The effects of maternal asthma during pregnancy on the adrenal medulla of offspring remain unknown.This study aims to explore the influence of maternal asthma during pregnancy on the development and function of adrenal medulla in offspring from postnatal day 3 (P3 to postnatal day 60 (P60. Asthmatic pregnant rats (AP, nerve growth factor (NGF-treated pregnant rats (NP and NGF antibody-treated pregnant rats (ANP were sensitized and challenged with ovalbumin (OVA; NP and ANP were treated with NGF and NGF antibody respectively. Offspring rats from the maternal group were divided into four groups: offspring from control pregnant rats (OCP, offspring from AP (OAP, offspring from NP (ONP, and offspring from ANP (OANP. The expressions of phenylethanolamine N-methyltransferase (PNMT protein in adrenal medulla were analyzed. The concentrations of epinephrine (EPI, corticosterone and NGF in serum were measured. Adrenal medulla chromaffin cells (AMCC were prone to differentiate into sympathetic nerve cells in OAP and ONP. Both EPI and PNMT were decreased in OAP from P3 to P14, and then reached normal level gradually from P30 to P60, which were lower from birth to adulthood in ONP. Corticosterone concentration increased significantly in OAP and ONP.Asthma pregnancy may promote AMCC to differentiate into sympathetic neurons in offspring rats and inhibit the synthesis of EPI, resulting in dysfunction of bronchial relaxation.

  8. Dopamine receptors on adrenal chromaffin cells modulate calcium uptake and catecholamine release

    Energy Technology Data Exchange (ETDEWEB)

    Bigornia, L; Suozzo, M; Ryan, K A; Napp, D; Schneider, A S

    1988-10-01

    The presence of dopamine-containing cells in sympathetic ganglia, i.e., small, intensely fluorescent cells, has been known for some time. However, the role of dopamine as a peripheral neurotransmitter and its mechanism of action are not well understood. Previous studies have demonstrated the presence of D2 dopamine receptors on the surface of bovine adrenal chromaffin cells using radioligand binding methods and dopamine receptor inhibition of catecholamine release from perfused adrenal glands. In the present study, we provide evidence confirming a role of dopamine receptors as inhibitory modulators of adrenal catecholamine release from bovine chromaffin cell cultures and further show that the mechanism of modulation involves inhibition of stimulated calcium uptake. Apomorphine gave a dose-dependent inhibition (IC50 = 1 microM) of 45Ca2+ uptake stimulated by either nicotine (10 microM) or membrane depolarization with an elevated K+ level (60 mM). This inhibition was reversed by a series of specific (including stereospecific) dopamine receptor antagonists: haloperidol, spiperone, sulpiride, and (+)-butaclamol, but not (-)-butaclamol. In addition, the calcium channel agonist Bay K 8644 was used to stimulate uptake of 45Ca2+ into chromaffin cells, and this uptake was also inhibited by the dopamine receptor agonist apomorphine. The combined results suggest that dopamine receptors on adrenal chromaffin cells alter Ca2+ channel conductance, which, in turn, modulates catecholamine release.

  9. Leydig Cell Tumor Associated with Testicular Adrenal Rest Tumors in a Patient with Congenital Adrenal Hyperplasia due to 11β-Hydroxylase Deficiency

    Directory of Open Access Journals (Sweden)

    Nadia Charfi

    2012-01-01

    Full Text Available Congenital adrenal hyperplasia (CAH describes a group of inherited autosomal recessive disorders characterized by enzyme defects in the steroidogenic pathways that lead to the biosynthesis of cortisol, aldosterone, and androgens. Chronic excessive adrenocorticotropic hormone (ACTH stimulation may result in hyperplasia of ACTH-sensitive tissues in adrenal glands and other sites such as the testes, causing testicular masses known as testicular adrenal rest tumors (TARTs. Leydig cell tumors (LCTs are make up a very small number of all testicular tumors and can be difficult to distinguish from TARTs. This distinction is interesting because LCTs and TARTs require different therapeutic approaches. Hereby, we present an unusual case of a 19-year-old patient with CAH due to 11β-hydroxylase deficiency, who presented with TARTs and an epididymal Leydig cell tumor.

  10. Intratumoral conversion of adrenal androgen precursors drives androgen receptor-activated cell growth in prostate cancer more potently than de novo steroidogenesis.

    Science.gov (United States)

    Kumagai, Jinpei; Hofland, Johannes; Erkens-Schulze, Sigrun; Dits, Natasja F J; Steenbergen, Jacobie; Jenster, Guido; Homma, Yukio; de Jong, Frank H; van Weerden, Wytske M

    2013-11-01

    Despite an initial response to hormonal therapy, patients with advanced prostate cancer (PC) almost always progress to castration-resistant disease (CRPC). Although serum testosterone (T) is reduced by androgen deprivation therapy, intratumoral T levels in CRPC are comparable to those in prostate tissue of eugonadal men. These levels could originate from intratumoral conversion of adrenal androgens and/or from de novo steroid synthesis. However, the relative contribution of de novo steroidogenesis to AR-driven cell growth is unknown. The relative contribution of androgen biosynthetic pathways to activate androgen receptor (AR)-regulated cell growth and expression of PSA, FKBP5, and TMPRSS2 was studied at physiologically relevant levels of adrenal androgen precursors and intermediates of de novo androgen biosynthesis in human prostate cancer cell lines, PC346C, VCaP, and LNCaP. In PC346C and VCaP, responses to pregnenolone and progesterone were absent or minimal, while large effects of adrenal androgen precursors were found. VCaP CRPC clones overexpressing CYP17A1 did not acquire an increased ability to use pregnenolone or progesterone to activate AR. In contrast, all precursors stimulated growth and gene expression in LNCaP cells, presumably resulting from the mutated AR in these cells. Our data indicate that at physiological levels of T precursors PC cells can generally convert adrenal androgens, while de novo steroidogenesis is not generally possible in PC cells and is not able to support AR transactivation and PC growth. © 2013 Wiley Periodicals, Inc.

  11. Role of calcium in effects of atrial natriuretic peptide on aldosterone production in adrenal glomerulosa cells

    International Nuclear Information System (INIS)

    Chartier, L.; Schiffrin, E.L.

    1987-01-01

    Atrial natriuretic peptide (ANP) inhibits the stimulation of aldosterone secretion by isolated adrenal glomerulosa cells produced by angiotensin II (ANG II), ACTH, and potassium. The effect of ANP on the dose-response curve of aldosterone stimulated by ANG II, ACTH, and potassium on isolated rat adrenal glomerulosa cells was studied. In the presence of ANP the maximal response of aldosterone output stimulated by ANG II or potassium decreased and the half-maximum (EC 50 ) of the response to ACTH was displaced to the right. Because these effects resemble those of calcium-channel blockers, the authors investigated the effect of different concentrations of nifedipine, a dihydropyridine calcium-channel blocker, on the dose-response curve of aldosterone stimulated by ANG II, ACTH, and potassium. Nifedipine produced effects similar to ANP. The maximal response of aldosterone stimulated by ANG II and potassium was decreased and the dose-response curve to ACTH was displaced to the right. ANP decreased the maximal response of aldosterone to the dihydropyridine derivative BAY K8644, a calcium-channel activator, without change in its EC 50 . In contrast, nifedipine displaced the dose-response curve to BAY K8644 to the right as expected of a competitive inhibitor. The effect of ANP and nifedipine on basal and stimulated 45 Ca influx into isolated rat adrenal glomerulosa cells was studied. ANP may act on the rat adrenal glomerulosa cells at least in part by interference with calcium entry

  12. Persistent expression of BMP-4 in embryonic chick adrenal cortical cells and its role in chromaffin cell development

    Directory of Open Access Journals (Sweden)

    Halbach Oliver

    2008-10-01

    Full Text Available Abstract Background Adrenal chromaffin cells and sympathetic neurons both originate from the neural crest, yet signals that trigger chromaffin development remain elusive. Bone morphogenetic proteins (BMPs emanating from the dorsal aorta are important signals for the induction of a sympathoadrenal catecholaminergic cell fate. Results We report here that BMP-4 is also expressed by adrenal cortical cells throughout chick embryonic development, suggesting a putative role in chromaffin cell development. Moreover, bone morphogenetic protein receptor IA is expressed by both cortical and chromaffin cells. Inhibiting BMP-4 with noggin prevents the increase in the number of tyrosine hydroxylase positive cells in adrenal explants without affecting cell proliferation. Hence, adrenal BMP-4 is likely to induce tyrosine hydroxylase in sympathoadrenal progenitors. To investigate whether persistent BMP-4 exposure is able to induce chromaffin traits in sympathetic ganglia, we locally grafted BMP-4 overexpressing cells next to sympathetic ganglia. Embryonic day 8 chick sympathetic ganglia, in addition to principal neurons, contain about 25% chromaffin-like cells. Ectopic BMP-4 did not increase this proportion, yet numbers and sizes of 'chromaffin' granules were significantly increased. Conclusion BMP-4 may serve to promote specific chromaffin traits, but is not sufficient to convert sympathetic neurons into a chromaffin phenotype.

  13. Biosynthesis of Various Steroids in vitro by Isolated Adrenal Cells in Primary Aldosteronism, Cushing's Syndrome, and Adrenogenital Syndrome due to Adrenocortical Adenoma

    OpenAIRE

    MIZUNO, SHIGERU; FUNAHASHI, HIROOMI

    1981-01-01

    To a further understanding of the role of steroid hormones in adrenal disorders, we have prepared free cell system of adrenal cells, using adrenal tissues that had been removed by operation from (i) cases of Cushing's syndrome due to adrenocortical adenoma or adrenocortical hyperplasia, (ii) a case of primary aldosteronism, and (iii) a patient with virilizing adrenal tumor. Twelve important steroid hormones were measured, such as pregnenolone, cortisol and aldosterone, which were produced by ...

  14. Synthesis of hydroxyeicosatetraenoic acids (HETE's) by adrenal glomerulosa cells and incorporation into cellular lipids

    International Nuclear Information System (INIS)

    Campbell, W.B.; Richards, C.F.; Brady, M.T.; Falck, J.R.

    1986-01-01

    The role of lipoxygenase metabolites of arachidonic acid (AA) in the regulation of aldosterone secretion was studied in isolated rat adrenal glomerulosa cells. Cells were incubated with 14 C-AA in the presence of angiotensin (AII). The media was extracted, metabolites isolated by HPLC, and structures of the metabolites determined by UV absorbance and mass spectrometry. The major products were 12- and 15-HETE with lesser amounts of 11- and 5-HETE. When adrenal cells were incubated with 15-, 12- or 5-HPETE or their respective HETE's (0.03-300nM), there was no significant change in basal or AII-stimulated aldosterone release. Cells were incubated with [ 3 H]-AA, -5-HETE, -15-HETE, -12-HETE or -LTB. The cellular lipids were extracted and analyzed by TLC. AA was incorporated into phospholipids (22%), cholesterol esters (50%) and triglycerides (21%). Neither the HETE's or LTB 4 were incorporated into phospholipids. 5-HETE was taken up into di- and mono-glycerides. The rates of incorporation of AA and 5-HETE were similar (+ 1/2 = 10 min). The incorporation of 5-HETE into glycerol esters did not modify the release of aldosterone by the cells. Thus, while adrenal cells synthesize HETE's, these eicosanoids do not appear to alter the synthesis of aldosterone

  15. Effect of angiotensin II, ATP, and ionophore A23187 on potassium efflux in adrenal glomerulosa cells

    International Nuclear Information System (INIS)

    Lobo, M.V.; Marusic, E.T.

    1986-01-01

    Angiotensin II stimulus on perifused bovine adrenal glomerulosa cells elicited an increase in 86Rb efflux from cells previously equilibrated with the radioisotope. When 45Ca fluxes were measured under similar conditions, it was observed that Ca and Rb effluxes occurred within the first 30 s of the addition of the hormone and were independent of the presence of external Ca. The 86Rb efflux due to angiotensin II was inhibited by quinine and apamin. The hypothesis that the angiotensin II response is a consequence of an increase in the K permeability of the glomerulosa cell membrane triggered by an increase in cytosolic Ca is supported by the finding that the divalent cation ionophore A23187 also initiated 86Rb or K loss (as measured by an external K electrode). This increased K conductance was also seen with 10(-4) M ATP. Quinine and apamin greatly reduced the effect of ATP or A23187 on 86Rb or K release in adrenal glomerulosa cells. The results suggest that Ca-dependent K channels or carriers are present in the membranes of bovine adrenal glomerulosa cells and are sensitive to hormonal stimulus

  16. Characterization of insulin-like growth factor I and insulin receptors on cultured bovine adrenal fasciculata cells. Role of these peptides on adrenal cell function

    International Nuclear Information System (INIS)

    Penhoat, A.; Chatelain, P.G.; Jaillard, C.; Saez, J.M.

    1988-01-01

    We have characterized insulin-like growth factor I (IGF-I) and insulin receptors in cultured bovine adrenal cells by binding and cross-linking affinity experiments. At equilibrium the dissociation constant and the number of binding sites per cell for IGF-I were 1.4 +/- (SE) 0.3 x 10(-9) M and 19,200 +/- 2,100, respectively. Under reduction conditions, disuccinimidyl suberate cross-linked [ 125 I]iodo-IGF-I to one receptor complex with an Mr of 125,000. Adrenal cells also contain specific insulin receptors with an apparent dissociation constant (Kd) of 10(-9) M. Under reduction conditions [ 125 I]iodo-insulin binds to one band with an approximate Mr of 125,000. IGF-I and insulin at micromolar concentrations, but not at nanomolar concentrations, slightly stimulated DNA synthesis, but markedly potentiated the mitogenic action of fibroblast growth factor. Adrenal cells cultured in a serum-free medium containing transferrin, ascorbic acid, and insulin (5 micrograms/ml) maintained fairly constant angiotensin-II (A-II) receptor concentration per cell and increased cAMP release on response to ACTH and their steroidogenic response to both ACTH and A-II. When the cells were cultured in the same medium without insulin, the number of A-II receptors significantly decreased to 65% and the increased responsiveness was blunted. Treatment of such cells for 3 days with increasing concentrations of IGF-I (1-100 ng/ml) produced a 2- to 3-fold increase in A-II receptors and enhanced the cAMP response (3- to 4-fold) to ACTH and the steroidogenic response (4- to 6-fold) to ACTH and A-II. These effects were time and dose dependent (ED50 approximately equal to 10(-9) M). Insulin at micromolar concentrations produced an effect similar to that of IGF-I, but at nanomolar concentrations the effect was far less

  17. Pannexin 1 channels: new actors in the regulation of catecholamine release from adrenal chromaffin cells

    Directory of Open Access Journals (Sweden)

    Fanny eMomboisse

    2014-09-01

    Full Text Available Chromaffin cells of the adrenal gland medulla synthesize and store hormones and peptides, which are released into the blood circulation in response to stress. Among them, adrenaline is critical for the fight-or-flight response. This neurosecretory process is highly regulated and depends on cytosolic [Ca2+]. By forming channels at the plasma membrane, pannexin-1 (Panx1 is a protein involved in many physiological and pathological processes amplifying ATP release and/or Ca2+ signals. Here, we show that Panx1 is expressed in the adrenal gland where it plays a role by regulating the release of catecholamines. In fact, inhibitors of Panx1 channels, such as carbenoxolone (Cbx and probenecid, reduced the secretory activity induced with the nicotinic agonist 1,1-dimethyl-4-phenyl-piperazinium (DMPP, 50 µM in whole adrenal glands. A similar inhibitory effect was observed in single chromaffin cells using Cbx or 10Panx1 peptide, another Panx1 channel inhibitors. Given that the secretory response depends on cytosolic [Ca2+] and Panx1 channels are permeable to Ca2+, we studied the possible implication of Panx1 channels in the Ca2+ signaling occurring during the secretory process. In support of this possibility, Panx1 channel inhibitors significantly reduced the Ca2+ signals evoked by DMPP in single chromaffin cells. However, the Ca2+ signals induced by caffeine in the absence of extracellular Ca2+ was not affected by Panx1 channel inhibitors, suggesting that this mechanism does not involve Ca2+ release from the endoplasmic reticulum. Conversely, Panx1 inhibitors significantly blocked the DMPP-induce dye uptake, supporting the idea that Panx1 forms functional channels at the plasma membrane. These findings indicate that Panx1 channels participate in the control the Ca2+ signal that triggers the secretory response of adrenal chromaffin cells. This mechanism could have physiological implications during the response to stress.

  18. Adrenal Fatigue

    Science.gov (United States)

    ... Search Featured Resource New Mobile App DOWNLOAD Adrenal Fatigue October 2017 Download PDFs English Editors Irina Bancos, MD Additional Resources Mayo Clinic What is adrenal fatigue? The term “adrenal fatigue” has been used to ...

  19. Characterisation of CART-containing neurons and cells in the porcine pancreas, gastro-intestinal tract, adrenal and thyroid glands

    Directory of Open Access Journals (Sweden)

    Gunnarsdóttir Anna

    2007-07-01

    Full Text Available Abstract Background The peptide CART is widely expressed in central and peripheral neurons, as well as in endocrine cells. Known peripheral sites of expression include the gastrointestinal (GI tract, the pancreas, and the adrenal glands. In rodent pancreas CART is expressed both in islet endocrine cells and in nerve fibers, some of which innervate the islets. Recent data show that CART is a regulator of islet hormone secretion, and that CART null mutant mice have islet dysfunction. CART also effects GI motility, mainly via central routes. In addition, CART participates in the regulation of the hypothalamus-pituitary-adrenal-axis. We investigated CART expression in porcine pancreas, GI-tract, adrenal glands, and thyroid gland using immunocytochemistry. Results CART immunoreactive (IR nerve cell bodies and fibers were numerous in pancreatic and enteric ganglia. The majority of these were also VIP IR. The finding of intrinsic CART containing neurons indicates that pancreatic and GI CART IR nerve fibers have an intrinsic origin. No CART IR endocrine cells were detected in the pancreas or in the GI tract. The adrenal medulla harboured numerous CART IR endocrine cells, most of which were adrenaline producing. In addition CART IR fibers were frequently seen in the adrenal cortex and capsule. The capsule also contained CART IR nerve cell bodies. The majority of the adrenal CART IR neuronal elements were also VIP IR. CART IR was also seen in a substantial proportion of the C-cells in the thyroid gland. The majority of these cells were also somatostatin IR, and/or 5-HT IR, and/or VIP IR. Conclusion CART is a major neuropeptide in intrinsic neurons of the porcine GI-tract and pancreas, a major constituent of adrenaline producing adrenomedullary cells, and a novel peptide of the thyroid C-cells. CART is suggested to be a regulatory peptide in the porcine pancreas, GI-tract, adrenal gland and thyroid.

  20. Stereotactic body radiotherapy for primary renal cell carcinoma and adrenal metastases.

    Science.gov (United States)

    Kothari, Gargi; Louie, Alexander V; Pryor, David; Vela, Ian; Lo, Simon S; Teh, Bin S; Siva, Shankar

    2017-09-01

    The incidence of renal cell carcinoma (RCC) and metastatic adrenal lesions continues to rise and present evolving complexities in terms of management. Technical challenges in treatment delivery are compounded by the setting of an ageing patient population with multiple medical co-morbidities. While the standard of care treatment for both primary RCC and oligometastatic adrenal lesions has typically been surgery, a number of patients may be medically or surgically inoperable, and for whom alternative options require consideration. Additionally, in metastatic disease, surgery presents an invasive option, sometimes with unacceptable risks of perioperative morbidity and therefore is considered a less desirable option to some. Stereotactic body radiotherapy (SBRT) is an established radiotherapy technique that is rapidly being incorporated into many radiotherapy departments, particu-larly with the increasing availability and capabilities of modern linear accelerators to deliver precise image guided treatment. There are considerable advantages of SBRT including its ability to provide a non-invasive ablative treatment with very few treatment sessions, with emerging evidence showing promising rates of local control (LC) and low associated mor-bidity. This review details the use of SBRT for primary RCC as well as adrenal metastases, focusing on issues including patient selection, technical considerations, and patient out-comes. Furthermore, this review explores some recent insights into the radiobiology of RCC, the immunomodulatory effects of SBRT, and the use of systemic agents with SBRT.

  1. Adrenal adenomas: relationship between histologic lipid-rich cells and CT attenuation number

    International Nuclear Information System (INIS)

    Yamada, Takayuki; Ishibashi, Tadashi; Saito, Haruo; Matsuhashi, Toshio; Majima, Kazuhiro; Tsuda, Masashi; Takahashi, Shoki; Moriya, Takuya

    2003-01-01

    Objective: To evaluate the relationship between lipid-rich cells of the adrenal adenoma and precontrast computed tomographic (CT) attenuation numbers in three clinical groups. Materials and Methods: Thirty-five surgically resected adrenal adenomas were used. The clinical diagnoses of the patients included 13 cases of primary aldosteronism, 15 cases of Cushing's syndrome, and 7 non-functioning tumors. The number of lipid-rich clear cells was counted using a microscopic eyepiece grid that contained 100 squares. The results were expressed as the percentages of lipid-rich areas. Results: There was a strong inverse linear relationship between the percentage of lipid-rich cells and the precontrast CT attenuation number (R 2 =0.724, P<0.0001). There were significantly more lipid-rich cells in the primary aldosteronism and non-functioning tumor cases compared to cases of Cushing's syndrome (P=0.007 and 0.015, respectively). The CT attenuation numbers of the primary aldosteronism cases were significantly lower than those of Cushing's syndrome (P=0.0052). Furthermore, the CT attenuation numbers of the non-functioning tumor cases were lower than those of Cushing's syndrome cases. Conclusion: We showed that adrenal adenomas in primary aldosteronism and non-functioning tumors contain significantly more lipid-rich cells than those in Cushing's syndrome. They also showed significantly lower attenuation than that in Cushing's syndrome on CT scans. Our results suggest that precontrast CT attenuation numbers may be helpful in the differentiation of adenomas from non-adenomatous lesions, which include malignancies

  2. The adrenal gland and the patient with pulmonary tuberculosis infected with human immunodeficiency virus

    Directory of Open Access Journals (Sweden)

    Ifedayo Adeola Odeniyi

    2017-01-01

    Full Text Available Background: The adrenal gland is not spared from the involvement by tuberculosis. One of the recognized causes of adrenal insufficiency (AI is tuberculosis. AI, mostly at the subclinical level, is common in persons with pulmonary tuberculosis (PTB infection, occurring in about 23% of patients. Coinfection with PTB and human immunodeficiency virus (HIV may compromise adrenocortical function and produce significant adrenocortical insufficiency. Objective: To determine if coinfection with tuberculosis and HIV have a compound effect on adrenocortical function in persons with HIV and PTB coinfection. Materials and Methods: Persons with sputum-positive PTB, treatment naive, who met our inclusion criteria, were selected. All the recruited patients were screened for HIV and those positive for HIV infection had confirmatory test. A baseline blood samples for cortisol, fasting plasma glucose, full blood count, and electrolytes were collected between 8.00 h and 9.00 h immediately before administration of adrenocorticotropic hormone (ACTH. The persons received an intravenous bolus injection of 1 μg ACTH (Alliance Pharmaceuticals Ltd., Chippenham, Wiltshire SN15 2BB and blood sample was drawn for cortisol level at 30 min. Results: Forty-four people with PTB infection and forty people with PTB and HIV coinfection met the inclusion criteria of the study. The adrenal response to 1 μg ACTH stimulation in participants with PTB and PTB and HIV coinfection showed that the mean basal cortisol level in the 2 groups was not statistically significant; however, 30-min post-ACTH stimulation cortisol level was 630.84 ± 372.17 and 980.36 ± 344.82 nmol/L (P < 0.001 and increment was 367.79 ± 334.87 and 740.77 ± 317.97 nmol/L (P < 0.001, respectively. Fourteen persons (31.8% with PTB has subnormal adrenal response to ACTH stimulation while only 2 (5% persons with PTB and HIV coinfection has subnormal response. Conclusion: AI, at subclinical level, was less frequent in

  3. Absorbed dose to the human adrenals from iodomethylnorcholesterol (I-131) NP-59: concise communication

    International Nuclear Information System (INIS)

    Carey, J.E.; Thrall, J.H.; Freitas, J.E.; Beierwaltes, W.H.

    1979-01-01

    During the past 2 yrs, adrenal uptake percentage values were measured in more than 40 patients, using an external counting technique. They suggest that the absorbed dose to the adrenals is significantly less than the 150 rads/mCi previously estimated using concentration values from animal adrenals. The measured combined uptake percentage for both adrenals ranged from 0.15% to 0.52% in 21 patients without evidence of adrenal disease, with a mean of 0.33% +- 0.1%; also from 0.22% to 1.5% in 22 patients with Cushing's disease, with a mean uptake of 0.78% +- 0.35%. The absorbed dose to the adrenals was estimated to be 25 rads/mCi for patients without evidence of adrenal disease, and 57 rads/mCi for patients with Cushing's disease. Both values are calculated for the respective mean uptake percentages by using the MIRD formalism

  4. Radioautographic study of the proliferative activity and cell migration in the fetal and neonatal rat adrenal cortex

    International Nuclear Information System (INIS)

    Bertholet, J.-Y.; Idelman, Simon

    1978-01-01

    On the 20th day of fetal life the cell proliferation is higher in the zona glomerulosa. The fate of marked cells in each cell compartment shows centripetal migration. Their displacement, from the 20th day of pregnancy up to five days post-partum, while at that time the adrenal growth is slowered down, suggests a real migration [fr

  5. On the development of extragonadal and gonadal human germ cells

    Directory of Open Access Journals (Sweden)

    A. Marijne Heeren

    2016-02-01

    Full Text Available Human germ cells originate in an extragonadal location and have to migrate to colonize the gonadal primordia at around seven weeks of gestation (W7, or five weeks post conception. Many germ cells are lost along the way and should enter apoptosis, but some escape and can give rise to extragonadal germ cell tumors. Due to the common somatic origin of gonads and adrenal cortex, we investigated whether ectopic germ cells were present in the human adrenals. Germ cells expressing DDX4 and/or POU5F1 were present in male and female human adrenals in the first and second trimester. However, in contrast to what has been described in mice, where ‘adrenal’ and ‘ovarian’ germ cells seem to enter meiosis in synchrony, we were unable to observe meiotic entry in human ‘adrenal’ germ cells until W22. By contrast, ‘ovarian’ germ cells at W22 showed a pronounced asynchronous meiotic entry. Interestingly, we observed that immature POU5F1+ germ cells in both first and second trimester ovaries still expressed the neural crest marker TUBB3, reminiscent of their migratory phase. Our findings highlight species-specific differences in early gametogenesis between mice and humans. We report the presence of a population of ectopic germ cells in the human adrenals during development.

  6. Muscarinic receptor-mediated inositol tetrakisphosphate response in bovine adrenal chromaffin cells

    International Nuclear Information System (INIS)

    Sanborn, B.B.; Schneider, A.S.

    1990-01-01

    Inositol trisphosphate (IP 3 ), a product of the phosphoinositide cycle, mobilizes intracellular Ca 2+ in many cell types. New evidence suggests that inositol tetrakisphosphate (IP 4 ), an IP 3 derivative, may act as another second messenger to further alter calcium homeostasis. However, the function and mechanism of action of IP 4 are presently unresolved. We now report evidence of muscarinic receptor-mediated accumulation of IP 4 in bovine adrenal chromaffin cells, a classic neurosecretory system in which calcium movements have been well studied. Muscarine stimulated an increase in [ 3 H]IP 4 and [ 3 H]IP 3 accumulation in chromaffin cells and this effect was completely blocked by atropine. [ 3 H]IP 4 accumulation was detectable within 15 sec, increased to a maximum by 30 sec and thereafter declined. 2,3-diphosphoglycerate, an inhibitor of IP 3 and IP 4 hydrolysis, enhanced accumulation of these inositol polyphosphates. The results provide the first evidence of a rapid inositol tetrakisphosphate response in adrenal chromaffin cells, which should facilitate the future resolution of the relationship between IP 4 and calcium homeostasis

  7. Metachronous adrenal metastasis from operated contralateral renal cell carcinoma with adrenalectomy and iatrogenic Addison's disease.

    Science.gov (United States)

    Ozturk, Hakan; Karaaslan, Serap

    2014-09-01

    Metachronous adrenal metastasis from contralateral renal cell carcinoma (RCC) surgery is an extremely rare condition. Iatrogenic Addison's disease occurring after metastasectomy (adrenalectomy) is an even rarer clinical entity. We present a case of a 68-year-old male with hematuria and left flank pain 9 years prior. The patient underwent left transperitoneal radical nephrectomy involving the ipsilateral adrenal glands due to a centrally-located, 75-mm in diameter solid mass lesion in the upper pole of the left kidney. The tumour lesion was confined within the renal capsule, and the histo-pathological examination revealed a Fuhrman nuclear grade II clear cell carcinoma. The patient underwent transperitoneal right adrenalectomy. The histopathological examination revealed metastasis of clear cell carcinoma. The patient was diagnosed with iatrogenic Addison's disease based on the measurement of serum cortisol levels and the adrenocorticotropic hormone (ACTH) stimulation test, after which glucocorticoid and mineralocorticoid replacement was initiated. The patient did not have local recurrence or new metastasis in the first year of the follow-up. The decision to perform ipsilateral adrenalectomy during radical nephrectomy constitutes a challenge, and the operating surgeon must consider all these rare factors.

  8. Effect of betel quid on catecholamine secretion from adrenal chromaffin cells.

    Science.gov (United States)

    Wang, C K; Hwang, L S

    1997-10-01

    Health damage and environmental pollution are serious problems caused by betel quid chewing in Taiwan. Many people acquire the habit of chewing betel quid due to its physiological effects, including increased stamina and a general feeling of well-being. In this study, a sympathetic model system of adrenal chromaffin cells and sensory evaluation were used to examine the physiological effects of betel quid and the interaction of all the ingredients (areca fruit, Piper betle inflorescence and red time paste) in betel quid. Physiological effects of cardioacceleration, a slightly drunk feeling, sweating and salivation occurred during the chewing of betel quid (a mixture of areca fruit, Piper betle inflorescence and red lime paste) and a mixture of areca fruit and red lime paste. Both induced much more basal catecholamine secretion from adrenal chromaffin cells than did other ingredients and combinations of ingredients. It was evident that the responses in the sympathetic model system were closely correlated with the physiological feeling of well-being. The inhibitory effects of all the chewing juices on catecholamine secretion evoked by carbachol and a high concentration of potassium (high K+) showed that they perhaps affected the calcium influx through voltage-sensitive channels or the steps involved in secretion after calcium entry to stimulate basal catecholamine secretion from chromaffin cells.

  9. Nicotine-evoked cytosolic Ca2+ increase and cell depolarization in capillary endothelial cells of the bovine adrenal medulla

    Directory of Open Access Journals (Sweden)

    RAÚL VINET

    2009-01-01

    Full Text Available Endothelial cells are directly involved in many functions of the cardiovascular system by regulating blood flow and blood pressure through Ca2+ dependent exocitosis of vasoactive compounds. Using the Ca2+ indicator Fluo-3 and the patch-clamp technique, we show that bovine adrenal medulla capillary endothelial cells (B AMCECs respond to acetylcholine (ACh with a cytosolic Ca2+ increase and depolarization of the membrane potential (20.3±0.9 mV; n=23. The increase in cytosolic Ca2+ induced by 10µM ACh was mimicked by the same concentration of nicotine but not by muscarine and was blocked by 100 µM of hexamethonium. On the other hand, the increase in cytosolic Ca2+ could be depressed by nifedipine (0.01 -100 µM or withdrawal of extracellular Ca2+. Taken together, these results give evidence for functional nicotinic receptors (nAChRs in capillary endothelial cells of the adrenal medulla. It suggests that nAChRs in B AMCECs may be involved in the regulation of the adrenal gland's microcirculation by depolarizing the membrane potential, leading to the opening of voltage-activated Ca2+ channels, influx of external Ca2+ and liberation of vasoactive compounds.

  10. Cell proliferation, movement and differentiation during maintenance of the adult mouse adrenal cortex.

    Directory of Open Access Journals (Sweden)

    Su-Ping Chang

    Full Text Available Appropriate maintenance and regeneration of adult endocrine organs is important in both normal physiology and disease. We investigated cell proliferation, movement and differentiation in the adult mouse adrenal cortex, using different 5-bromo-2'-deoxyuridine (BrdU labelling regimens and immunostaining for phenotypic steroidogenic cell markers. Pulse-labelling showed that cell division was largely confined to the outer cortex, with most cells moving inwards towards the medulla at around 13-20 µm per day, though a distinct labelled cell population remained in the outer 10% of the cortex. Pulse-chase-labelling coupled with phenotypic immunostaining showed that, unlike cells in the inner cortex, most BrdU-positive outer cortical cells did not express steroidogenic markers, while co-staining for BrdU and Ki67 revealed that some outer cortical BrdU-positive cells were induced to proliferate following acute adrenocorticotropic hormone (ACTH treatment. Extended pulse-chase-labelling identified cells in the outer cortex which retained BrdU label for up to 18-23 weeks. Together, these observations are consistent with the location of both slow-cycling stem/progenitor and transiently amplifying cell populations in the outer cortex. Understanding the relationships between these distinct adrenocortical cell populations will be crucial to clarify mechanisms underpinning adrenocortical maintenance and long-term adaptation to pathophysiological states.

  11. Radioautographic study of the synthesis and migration of glycoproteins in the cells of the rat adrenal medulla

    International Nuclear Information System (INIS)

    Benchimol, Sarita; Cantin, Marc

    1978-01-01

    Rats were injected intravenously with ( 3 H) fucose to study the synthesis and migration of glycoproteins into adrenaline-storing and noradrenaline-storing cells of the adrenal medulla and to evaluate the fate of this radioactive sugar in both serum and adrenal-medulla at various time intervals. Radioactivity was decreased in serum by 50% between 5 and 20 min after the injection and by a hundred fold with 1 h. There was a sharp decrease in the radioactivity of the adrenal-medulla between 5 and 20 min after the injection and a slight, continuous decrease thereafter. The adrenal-medullae were fixed 5 min, 20 min, 1 h and 4 h after intravenous injection of [ 3 H] fucose, and radiautographs were analysed quantitatively after development in Microdol X. Kinetic analysis showed that, in both cell types, glycoprotein synthesis is completed in the Golgi complex and glycoproteins migrate subsequently to the secretory granules and to the cell coat. This analysis also revealed that [ 3 H] fucose moves much more rapidly in the Golgi complex of noradrenaline-storing cells than in that of adrenaline-storing cells and appears much earlier in the secretory granules of the former cell type [fr

  12. Catecholamine secretion by chemical hypoxia in guinea-pig, but not rat, adrenal medullary cells: differences in mitochondria.

    Science.gov (United States)

    Harada, K; Endo, Y; Warashina, A; Inoue, M

    2015-08-20

    The effects of mitochondrial inhibitors (CN(-), a complex IV inhibitor and CCCP, protonophore) on catecholamine (CA) secretion and mitochondrial function were explored functionally and biochemically in rat and guinea-pig adrenal chromaffin cells. Guinea-pig chromaffin cells conspicuously secreted CA in response to CN(-) or CCCP, but rat cells showed a little, if any, secretory response to either of them. The resting metabolic rates in rat adrenal medullae did not differ from those in guinea-pig adrenal medullae. On the other hand, the time course of depolarization of the mitochondrial membrane potential (ΔΨm) in guinea-pig chromaffin cells in response to CN(-) was slower than that in rat chromaffin cells, and this difference was abolished by oligomycin, an F1F0-ATPase inhibitor. The extent of CCCP-induced decrease in cellular ATP in guinea-pig chromaffin cells, which was indirectly measured using a Mg(2+) indicator, was smaller than that in rat chromaffin cells. Relative expression levels of F1F0-ATPase inhibitor factor in guinea-pig adrenal medullae were smaller than in rat adrenal medullae, and the opposite was true for F1F0-ATPase α subunit. The present results indicate that guinea-pig chromaffin cells secrete more CA in response to a mitochondrial inhibitor than rat chromaffin cells and this higher susceptibility in the former is accounted for by a larger extent of reversed operation of F1F0-ATPase with the consequent decrease in ATP under conditions where ΔΨm is depolarized. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Mobilisation of store Ca2+ activates tyrosine hydroxylase in bovine adrenal chromaffin cells

    International Nuclear Information System (INIS)

    McKenzie, S.; Marley, P.D.

    2001-01-01

    Full text: Many receptor agonists are able to activate tyrosine hydroxylase (TOH) in bovine adrenal chromaffin cells. The majority of these are dependent on extracellular Ca 2+ for this action. Entry of extracellular Ca 2+ through voltage-operated Ca 2+ channels is very effective at activating TOH. The contribution of the intracellular Ca 2+ stores to TOH activation however is not known. Previous studies have shown that mobilisation of intracellular Ca 2+ stores is effective at increasing phosphorylation of TOH, but its effect on TOH activity has not been studied. Therefore, in the present study, the effect of mobilisation of store Ca 2+ on TOH activity was investigated using primary cultures of bovine adrenal chromaffin cells. Cells were prepared from abattoir tissue and cultured for 3-6 days. TOH activity was determined over 10 minutes, measuring the 14 CO 2 produced following the hydroxylation and rapid decarboxylation of 14 C-tyrosine offered to intact cells. Caffeine increased TOH activity in a concentration-dependent manner with a maximum response of 100% increase at 20mM. This effect was not due to osmolarity since 20mM sucrose had no effect.Nor was it due to inhibition of phosphodiesterases, since the effect of caffeine was still seen in the presence of 1mM IBMX. However,caffeine-induced TOH activation was substantially reduced in the absence of extracellular Ca 2+ . The results suggest that TOH activity can be increased by mobilising intracellular Ca 2+ stores, but that this effect involves extracellular Ca 2+ influx, possibly through store-operated channels. Copyright (2001) Australian Neuroscience Society

  14. Membrane toxicity of abnormal prion protein in adrenal chromaffin cells of scrapie infected sheep.

    Directory of Open Access Journals (Sweden)

    Gillian McGovern

    Full Text Available Transmissible spongiform encephalopathies (TSEs or prion diseases are associated with accumulations of disease specific PrP (PrP(d in the central nervous system (CNS and often the lymphoreticular system (LRS. Accumulations have additionally been recorded in other tissues including the peripheral nervous system and adrenal gland. Here we investigate the effect of sheep scrapie on the morphology and the accumulation of PrP(d in the adrenal medulla of scrapie affected sheep using light and electron microscopy. Using immunogold electron microscopy, non-fibrillar forms of PrP(d were shown to accumulate mainly in association with chromaffin cells, occasional nerve endings and macrophages. PrP(d accumulation was associated with distinctive membrane changes of chromaffin cells including increased electron density, abnormal linearity and invaginations. Internalisation of PrP(d from the chromaffin cell plasma membrane occurred in association with granule recycling following hormone exocytosis. PrP(d accumulation and internalisation from membranes is similarly associated with perturbations of membrane structure and trafficking in CNS neurons and tingible body macrophages of the LRS. These data suggest that a major toxic effect of PrP(d is at the level of plasma membranes. However, the precise nature of PrP(d-membrane toxicity is tissue and cell specific suggesting that the normal protein may act as a multi-functional scaffolding molecule. We further suggest that the co-localisation of PrP(d with exocytic granules of the hormone trafficking system may provide an additional source of infectivity in blood.

  15. Calcitriol-mediated hypercalcemia in a patient with bilateral adrenal non-Hodgkin's B-cell lymphoma case report

    Directory of Open Access Journals (Sweden)

    Ana Abaroa-Salvatierra

    2016-04-01

    Full Text Available Calcitriol-mediated hypercalcemia is a frequent manifestation of hematological malignancies. However, there are a few reports of cases presenting with increased angiotensin-converting enzyme (ACE level, which suggests a possible mechanism similar to that of granulomatous diseases. We present a patient with hypercalcemia, normal parathyroid hormone, and parathyroid hormone-related protein levels but high calcitriol and ACE levels that, after further investigation, was diagnosed with bilateral adrenal non-Hodgkin's B-cell lymphoma. Primary adrenal lymphoma represents only 1% of all non-Hodgkin's lymphomas and is usually asymptomatic but should be considered by clinicians among the malignancies that cause calcitriol-mediated hypercalcemia.

  16. POD-1/Tcf21 overexpression reduces endogenous SF-1 and StAR expression in rat adrenal cells

    Directory of Open Access Journals (Sweden)

    M. M. França

    2015-12-01

    Full Text Available During gonad and adrenal development, the POD-1/capsulin/TCF21transcription factor negatively regulates SF-1/NR5A1expression, with higher SF-1 levels being associated with increased adrenal cell proliferation and tumorigenesis. In adrenocortical tumor cells, POD-1 binds to the SF-1 E-box promoter region, decreasing SF-1 expression. However, the modulation of SF-1 expression by POD-1 has not previously been described in normal adrenal cells. Here, we analyzed the basal expression of Pod-1 and Sf-1 in primary cultures of glomerulosa (G and fasciculata/reticularis (F/R cells isolated from male Sprague-Dawley rats, and investigated whether POD-1 overexpression modulates the expression of endogenous Sf-1 and its target genes in these cells. POD-1 overexpression, following the transfection of pCMVMycPod-1, significantly decreased the endogenous levels of Sf-1 mRNA and protein in F/R cells, but not in G cells, and also decreased the expression of the SF-1 target StAR in F/R cells. In G cells overexpressing POD-1, no modulation of the expression of SF-1 targets, StAR and CYP11B2, was observed. Our data showing that G and F/R cells respond differently to ectopic POD-1 expression emphasize the functional differences between the outer and inner zones of the adrenal cortex, and support the hypothesis that SF-1 is regulated by POD-1/Tcf21 in normal adrenocortical cells lacking the alterations in cellular physiology found in tumor cells.

  17. Localization of 3H-serotonin in the adrenal medullary cells of newborn rats

    International Nuclear Information System (INIS)

    Sudar, F.; Csaba, G.

    1979-01-01

    Newborn rats received 25 μCi 3 H-5-hydroxytryptophan (5-HTP); 30, 60 min or 5 hours later the adrenal glands were removed. Electronmicroscopic autoradiography was carried out after fixation and embedding. As in the cells 5-HTP is formed into serotonin, the distribution of radioactivity actually represents the distribution of serotonin. Activity was found on the cellular, nuclear and catecholamine granule-membranes, and in the nucleus. The activity increased as a function of time at all the above mentioned sites, and in line with this more and more empty catecholamine-granules appeared. Data indicate the existence of intracellular serotonin-receptors and the role of serotonin in the release of catecholamines. (L.E.)

  18. Nanosecond electric pulses differentially affect inward and outward currents in patch clamped adrenal chromaffin cells.

    Directory of Open Access Journals (Sweden)

    Lisha Yang

    Full Text Available This study examined the effect of 5 ns electric pulses on macroscopic ionic currents in whole-cell voltage-clamped adrenal chromaffin cells. Current-voltage (I-V relationships first established that the early peak inward current was primarily composed of a fast voltage-dependent Na+ current (INa, whereas the late outward current was composed of at least three ionic currents: a voltage-gated Ca2+ current (ICa, a Ca2+-activated K+ current (IK(Ca, and a sustained voltage-dependent delayed rectifier K+ current (IKV. A constant-voltage step protocol was next used to monitor peak inward and late outward currents before and after cell exposure to a 5 ns pulse. A single pulse applied at an electric (E-field amplitude of 5 MV/m resulted in an instantaneous decrease of ~4% in peak INa that then declined exponentially to a level that was ~85% of the initial level after 10 min. Increasing the E-field amplitude to 8 or 10 MV/m caused a twofold greater inhibitory effect on peak INa. The decrease in INa was not due to a change in either the steady-state inactivation or activation of the Na+ channel but instead was associated with a decrease in maximal Na+ conductance. Late outward current was not affected by a pulse applied at 5 MV/m. However, for a pulse applied at the higher E-field amplitudes of 8 and 10 MV/m, late outward current in some cells underwent a progressive ~22% decline over the course of the first 20 s following pulse exposure, with no further decline. The effect was most likely concentrated on ICa and IK(Ca as IKV was not affected. The results of this study indicate that in whole-cell patch clamped adrenal chromaffin cells, a 5 ns pulse differentially inhibits specific voltage-gated ionic currents in a manner that can be manipulated by tuning E-field amplitude.

  19. Incorporation of 14C-cholesterol in human adrenal corticocarcinoma H295R cell line and online-radiodetection of produced 14C-steroid hormone metabolites

    DEFF Research Database (Denmark)

    Abdel-Khalik, Jonas; Björklund, Erland; Nielsen, Frederik Knud

    2017-01-01

    in the steroidogenesis of H295R cells, radioactive cholesterol may potentially only need to be added just before the cells are incubated for 72h in well plates. Based on the obtained HPLC-FSA chromatograms, and confirmation of the observations by studies in the literature, a qualitative time profile for the production......, the concept of radiolabeling the steroidogenesis in H295R cells with (14)C-cholesterol and detecting the radiolabeled steroid hormones online was proved and may assist in further toxicological studies....

  20. Human Adrenocortical Remodeling Leading to Aldosterone-Producing Cell Cluster Generation

    Directory of Open Access Journals (Sweden)

    Koshiro Nishimoto

    2016-01-01

    Full Text Available Background. The immunohistochemical detection of aldosterone synthase (CYP11B2 and steroid 11β-hydroxylase (CYP11B1 has enabled the identification of aldosterone-producing cell clusters (APCCs in the subcapsular portion of the human adult adrenal cortex. We hypothesized that adrenals have layered zonation in early postnatal stages and are remodeled to possess APCCs over time. Purposes. To investigate changes in human adrenocortical zonation with age. Methods. We retrospectively analyzed adrenal tissues prepared from 33 autopsied patients aged between 0 and 50 years. They were immunostained for CYP11B2 and CYP11B1. The percentage of APCC areas over the whole adrenal area (AA/WAA, % and the number of APCCs (NOA, APCCs/mm2 were calculated by four examiners. Average values were used in statistical analyses. Results. Adrenals under 11 years old had layered zona glomerulosa (ZG and zona fasciculata (ZF without apparent APCCs. Some adrenals had an unstained (CYP11B2/CYP11B1-negative layer between ZG and ZF, resembling the rat undifferentiated cell zone. Average AA/WAA and NOA correlated with age, suggesting that APCC development is associated with aging. Possible APCC-to-APA transitional lesions were incidentally identified in two adult adrenals. Conclusions. The adrenal cortex with layered zonation remodels to possess APCCs over time. APCC generation may be associated with hypertension in adults.

  1. Amidated joining peptide in the human pituitary, gut, adrenal gland and bronchial carcinoids. Immunocytochemical and immunochemical evidence

    DEFF Research Database (Denmark)

    Bjartell, A; Fenger, M; Ekman, R

    1990-01-01

    The distribution of the proopiomelanocortin-derivated amidated joining peptide (JP-N) was examined in the human pituitary gland, adrenal gland, gut and in three bronchial carcinoids. Double immunostaining showed coexistence of immunoreactive JP-N and other proopiomelanocortin derivatives, e......-N, respectively, but under reduced conditions most of the immunoreactive material appeared as of low molecular weight in both extracts. In conclusion, immunoreactive JP-N is a major product from the processing of proopiomelanocortin in human extrapituitary tissues. The molecular forms of immunoreactive JP......-N correspond to previous findings in the human pituitary gland....

  2. LIPOPOLYSACCHARIDE INDUCES THE PRODUCTION OF DIAGNOSTIC MONOCLONAL ANTIBODY BY HYBRIDOMA CELLS AGAINST CONGENITAL ADRENAL HYPERPLASIA

    Directory of Open Access Journals (Sweden)

    GEK KEE CHUA

    2017-11-01

    Full Text Available The purpose of this research is to screen and identify the potential inducers in maximizing the production of monoclonal antibody by hybridoma 192 cell line for Congenital Adrenal Hyperplasia diagnostic. There are nine inducers used in this research, namely lysozyme, aldolase, sodium butyrate, sodium phosphate, potassium phosphate, dimethyl sulfoxide, lipopolysaccharide, essential amino acids, and nonessential amino acids. Hybridoma 192 cell was cultured in 5% CO2 incubator at 37°C and ˃80% humidity in the medium with different concentrations of inducer agents. The inducers were added at the beginning of the culture and the samples were taken after 72 h of culture. The performance of these inducer agents was assessed based on the maximum monoclonal antibody titer achieved using Enzyme-linked Immunosorbent Assay. Lipopolysaccharide was found to increase the maximum monoclonal antibody titer when supplemented at 8 to 12 µg/mL. After optimization using one-factor central composite design at this range, the optimum point was determined to be 8 µg/mL. Verification experiments shows that lipopolysaccharide enhanced the average specific monoclonal antibody production rate by 56% relative to control. In conclusion, lipopolysaccharide at 8 µg/mL is able to increase the monoclonal antibody specific production of hybridoma 192 cell line.

  3. Essence of "Shen (Kidney) Controlling Bones": Conceptual Analysis Based on Hypothalamic-Pituitary-Adrenal-Osteo-Related Cells Axis.

    Science.gov (United States)

    Xu, Tao-Tao; Jin, Hong-Ting; Tong, Pei-Jian

    2018-04-12

    As a traditional concept of Chinese medicine (CM), the theory of "Shen (Kidney) controlling bones" has been gradually proven. And in modern allopathic medicine, the multiple mechanisms of bone growth, development and regeneration align with the theory. Shen defifi ciency as a pathological condition has a negative effect on the skeleton of body, specififi cally the disorder of bone homeostasis. Present studies indicate that Shen defifi ciency shares a common disorder characterized by dysfunction of hypothalamic-pituitary-adrenal (HPA) axis. HPA axis may be an important regulator of bone diseases with abnormal homeostasis. Therefore, we posit the existence of hypothalamic-pituitary-adrenal-osteo-related cells axis: cells that comprise bone tissue (osteo-related cells) are targets under the regulation of HPA axis in disorder of bone homeostasis. Chinese herbs for nourishing Shen have potential in the development of treatments for disorder of bone homeostasis.

  4. A rare adrenal incidentaloma: adrenal schwannoma.

    Science.gov (United States)

    Adas, Mine; Ozulker, Filiz; Adas, Gokhan; Koc, Bora; Ozulker, Tamer; Sahin, Ilknur Mansuroglu

    2013-01-01

    Adrenal schwannoma is an extremely uncommon cause of incidentaloma. It originates from neural sheath Schwann cells of the adrenal gland. We report the case of a left adrenal schwannoma incidentally discovered in a 32-year-old woman during examination of bloated feeling and stomach ache. The patient was incidentally found to have a left adrenal mass of 9 cm on abdominal ultrasonography. Computed tomography (CT) of the abdomen and [(18)F] fluorodeoxyglucose positron emission tomography (PET) were also performed. Metabolic evaluation was unremarkable. Due to the large size of the tumor, left adrenalectomy was performed. The postoperative course was uneventful. Histological examination established the diagnosis of schwannoma. This diagnosis was supported by immunohistochemistry of S-100 and vimentin positivity. In conclusion, adrenal schwannoma is an extremely rare entity and can grow considerably in size. The present case report emphasizes that clinicians should be aware of the possibility of retroperitoneal schwannoma. Total excision of benign schwannoma is associated with a favorable outcome. To our knowledge, there are case reports of schwannoma with CT and magnetic resonance imaging findings in the literature, although this is the first schwannoma case with PET-CT imaging.

  5. Adrenal scintigraphy

    International Nuclear Information System (INIS)

    Beierwaltes, W.H.

    1979-01-01

    The following items are discussed:anatomy and physiology of adrenal glands, clinical indications of scintigraphy, radiobiology and radiochemistry, scintigraphic imaging, adrenocortical hyperfunction, aldosteronism and hypertension associated with low renin level, excess of androgen, adrenocortical hyperfunction and future perspectives of adrenal scintigraphy. (M.A.) [pt

  6. Adrenal Insufficiency

    Science.gov (United States)

    ... two kinds of AI: • Primary AI, also called Addison’s disease. In this rare condition, the adrenal glands do ... org (search for adrenal) • Information about AI and Addison’s disease from the National Institutes of Health: www. endocrine. ...

  7. Adrenal incidentaloma

    Directory of Open Access Journals (Sweden)

    Arnaldi G.

    2000-01-01

    Full Text Available Incidentally discovered adrenal masses, or adrenal incidentalomas, have become a common clinical problem owing to wide application of radiologic imaging techniques. This definition encompasses a heterogeneous spectrum of pathologic entities, including primary adrenocortical and medullary tumors, benign or malignant lesions, hormonally active or inactive lesions, metastases, and infections. Once an adrenal mass is detected, the clinician needs to address two crucial questions: is the mass malignant, and is it hormonally active? This article provides an overview of the diagnostic clinical approach and management of the adrenal incidentaloma. Mass size is the most reliable variable to distinguish benign and malignant adrenal masses. Adrenalectomy should be recommended for masses greater than 4.0 cm because of the increased risk of malignancy. Adrenal scintigraphy has proved useful in discriminating between benign and malignant lesions. Finally, fine-needle aspiration biopsy is an important tool in the evaluation of oncological patients and it may be useful in establishing the presence of metastatic disease. The majority of adrenal incidentalomas are non-hypersecretory cortical adenomas but an endocrine evaluation can lead to the identification of a significant number of cases with subclinical Cushing's syndrome (5-15%, pheochromocytoma (1.5-13% and aldosteronoma (0-7%. The first step of hormonal screening should include an overnight low dose dexamethasone suppression test, the measure of urinary catecholamines or metanephrines, serum potassium and, in hypertensive patients, upright plasma aldosterone/plasma renin activity ratio. Dehydroepiandrosterone sulfate measurement may show evidence of adrenal androgen excess.

  8. Receptor stimulated formation of inositol phosphates in cultures of bovine adrenal medullary cells: the effects of bradykinin, bombesin and neurotensin.

    Science.gov (United States)

    Bunn, S J; Marley, P D; Livett, B G

    1990-04-01

    The ability of a number of drugs and neuropeptides to stimulate phosphoinositide metabolism in cultured bovine adrenal medullary cells has been assessed. Low concentrations (10 nM) of angiotensin II, bradykinin, histamine, arginine-vasopressin, and bombesin, and high (10 microM) concentrations of oxytocin, prostaglandins E1, and E2, beta-endorphin, and neurotensin stimulated significant accumulation of [3H]inositol phosphates in adrenal medullary cells preloaded with [3H)]inositol. Bradykinin stimulated a significant response at concentration as low as 10pM, with an EC50 of approximately 0.5 nM. The response was markedly inhibited by the bradykinin B2 antagonist [Thi5,8,D-Phe7] bradykinin but not the B1 antagonist [Des-Arg9,Leu8] bradykinin. Higher concentrations of bombesin and neurotensin were required to elicit a response (10 nM and 10 microM respectively). The bombesin response was sensitive to inhibition by the bombesin antagonist [D-Arg1,D-Pro2,D-Trp7,9Leu11]-substance P. In contrast, the neurotensin response was not reduced by the NT1 antagonist [D-Trp11]-neurotensin. These results indicate there are a number of agents that can stimulate phosphatidylinositide hydrolysis in the adrenal medullary cells by acting on different classes of receptors. Such a range of diverse agonists that stimulate inositol phosphate formation will facilitate further analysis of the phosphatidylinositide breakdown in chromaffin cell function.

  9. Adrenal scintigraphy

    International Nuclear Information System (INIS)

    Veen, E.A. van der.

    1978-01-01

    The visualization of functioning adrenocortical tissue by scintigraphy became possible with the introduction of radioiodinated cholesterol derivatives. According to the literature, there is evidence that one of these iodinated cholesterols, 6-β-iodomethyl-nor-cholesterol, concentrates in the adrenal cortex to a much greater extent than 131 I-19-odocholesterol. Results comparing both radiopharmaceuticals are described. The authors investigated the possibility of increasing the uptake of iodinated cholesterol using simultaneous ACTH and the 'cholesterol side-chain cleavage enzymeblocker': aminoglutethimide. The results of adrenal scintigraphy performed in 37 patients are described. Finally, the literature on adrenal scintigraphy is reviewed, and results reported in various studies are compared. (Auth.)

  10. Adrenal Incidentaloma

    Science.gov (United States)

    ... Peer Support Resources Diseases and Conditions Adrenal Disorders Osteoporosis and Bone Health Children and Teen Health Diabetes Heart Health Men's Health Rare Diseases Pituitary Disorders Thyroid Disorders Transgender Health Obesity and Weight Management Women's Health You and Your ...

  11. Marked cortisol production by intracrine ACTH in GIP-treated cultured adrenal cells in which the GIP receptor was exogenously introduced.

    Directory of Open Access Journals (Sweden)

    Hiroko Fujii

    Full Text Available The ectopic expression of the glucose-dependent insulinotropic polypeptide receptor (GIPR in the human adrenal gland causes significant hypercortisolemia after ingestion of each meal and leads to Cushing's syndrome, implying that human GIPR activation is capable of robustly activating adrenal glucocorticoid secretion. In this study, we transiently transfected the human GIPR expression vector into cultured human adrenocortical carcinoma cells (H295R and treated them with GIP to examine the direct link between GIPR activation and steroidogenesis. Using quantitative RT-PCR assay, we examined gene expression of steroidogenic related proteins, and carried out immunofluorescence analysis to prove that forced GIPR overexpression directly promotes production of steroidogenic enzymes CYP17A1 and CYP21A2 at the single cell level. Immunofluorescence showed that the transfection efficiency of the GIPR gene in H295R cells was approximately 5%, and GIP stimulation enhanced CYP21A2 and CYP17A1 expression in GIPR-introduced H295R cells (H295R-GIPR. Interestingly, these steroidogenic enzymes were also expressed in the GIPR (- cells adjacent to the GIPR (+ cells. The mRNA levels of a cholesterol transport protein required for all steroidogenesis, StAR, and steroidogenic enzymes, HSD3β2, CYP11A1, CYP21A2, and CYP17A1 increased 1.2-2.1-fold in GIP-stimulated H295R-GIPR cells. These changes were reflected in the culture medium in which 1.5-fold increase in the cortisol concentration was confirmed. Furthermore, the levels of adenocorticotropic hormone (ACTH receptor and ACTH precursor proopiomelanocortin (POMC mRNA were upregulated 2- and 1.5-fold, respectively. Immunofluorescence showed that ACTH expression was detected in GIP-stimulated H295R-GIPR cells. An ACTH-receptor antagonist significantly inhibited steroidogenic gene expression and cortisol production. Immunostaining for both CYP17A1 and CYP21A2 was attenuated in cells treated with ACTH receptor antagonists

  12. A case of adrenal tumour in a lion (Panthera leo: tomographic and ultrasonographic findings.

    Directory of Open Access Journals (Sweden)

    Maurizio Longo

    2015-07-01

    Full Text Available Adrenal gland tumors are common in humans and in several animal species. Studies concerning this neoplasia in human medicine indicate that clinical signs have a high variability. Adrenal adenomas can be occasionally observed in asymptomatic patients during tomographic studies while estrogen-secreting tumors, known as "feminizing adrenal tumors" (FATs, have been rarely reported. The aim of this study is to describe for the first time the Imaging findings of a captivity lion affected by a neoplastic secreting adrenal tumour. An 8 year-old male lion with progressive lack of secondary sex characteristics, disorexia and weight loss was referred to our Institution. The patient was chemically immobilized to undergo general clinical evaluation, hematologic, serum biochemical and hormonal profile, FIV and FeLV tests. Three months later a total body computed tomography and abdominal ultrasonography were performed. Liver and left adrenal lesions FNABs were performed. Imaging findings showed the presence of an extended expansive neoplastic lesion on the left adrenal gland (40x39x37 mm with right adrenal gland atrophy. Generalized hepatopathy associated with a suspected intrahepatic cholestasis was confirmed by ultrasonography. Cytological evaluation ruled out the presence of neuroendocrine cells without malignancy evidences compatible with the adenomatous nature of the lesion, associated with moderate degenerative hepatopathy. Blood tests reported an estradiol concentration of 462 ng/dl. To our knowledge, this is the first description of adrenal mass in a lion associated with secondary feminization, inappetence and high values of hematic estradiol, referable to a feminizing adrenal tumor (FAT.

  13. [Adrenal tumours in childhood].

    Science.gov (United States)

    Martos-Moreno, G A; Pozo-Román, J; Argente, J

    2013-09-01

    This special article aims to summarise the current knowledge regarding the two groups of tumours with their origin in the adrenal gland: 1) adrenocortical tumours, derived from the cortex of the adrenal gland and 2) phaeochromocytomas and paragangliomas, neuroendocrine tumours derived from nodes of neural crest derived cells symmetrically distributed at both sides of the entire spine (paragangliomas [PG]). These PGs can be functioning tumors that secrete catecholamines, which confers their typical dark colour after staining with chromium salts (chromaffin tumors). Among these, the term phaeochromocytoma (PC) is restricted to those PGs derived from the chromaffin cells in the adrenal medulla (intra-adrenal PGs), whereas the term PG is used for those sympathetic or parasympathetic ones in an extra-adrenal location. We analyse the state of the art of their pathogenic and genetic bases, as well as their clinical signs and symptoms, the tests currently available for performing their diagnosis (biochemical, hormonal, imaging and molecular studies) and management (surgery, pre- and post-surgical medical treatment), considering the current and developing strategies in chemo- and radiotherapy. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  14. Oxygen sensitivity of potassium- and angiotensin II-stimulated aldosterone release by bovine adrenal cells.

    Science.gov (United States)

    Brickner, R C; Raff, H

    1991-04-01

    Angiotensin II (AII) and extracellular K+, acting through different intracellular mechanisms, stimulate aldosterone release in a synergistic fashion. We have previously shown that decreases in oxygen (O2) within the physiological range inhibit AII, cyclic AMP (cAMP) and ACTH-stimulated aldosterone release. The present experiment evaluated the effect of various concentrations of O2 on K+-stimulated aldosterone release in the presence and absence of AII. Dispersed bovine adrenal glomerulosa cells were incubated with different concentrations of K+ (0.9-5.4 mmol/l) without and with AII (10 nmol/l) under different concentrations of O2 (0, 5 or 50%); 21% O2 (pO2 = 19.9 +/- 0.5 kPa,n = 9) was used as reference control for comparison. In all cases, increases in K+ stimulated aldosterone release, an effect augmented by AII. Under 0% O2 (pO2 = 8.1 +/- 0.3 kPa, n = 3) and 5% O2 (pO2 = 12.8 +/- 0.5 kPa, n = 3), aldosterone release stimulated by K+ or K+/AII was significantly inhibited compared with that under 21% O2. Conversely, under 50% O2 (pO2 = 36.3 +/- 2.5 kPa, n = 3), aldosterone release stimulated by K+ or K+/AII was significantly augmented. Cortisol secretion was not significantly affected by 5% or 50% O2 but was significantly decreased under 0% O2. The effect of O2 on K+/AII stimulation of aldosterone release, as well as previous experiments with cAMP, progesterone and ACTH, suggest a final common post-receptor oxygen-sensitive component of the aldosterone synthetic pathway. It is suggested that one or more enzymes in the aldosterone synthetic pathway is/are exquisitely sensitive to small changes in O2 within the physiological range.

  15. Noninvasive Prenatal Diagnosis of Congenital Adrenal Hyperplasia Using Cell-Free Fetal DNA in Maternal Plasma

    Science.gov (United States)

    Tong, Yu K.; Yuen, Tony; Jiang, Peiyong; Pina, Christian; Chan, K. C. Allen; Khattab, Ahmed; Liao, Gary J. W.; Yau, Mabel; Kim, Se-Min; Chiu, Rossa W. K.; Sun, Li; Zaidi, Mone

    2014-01-01

    Context: Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition that arises from mutations in CYP21A2 gene, which encodes for the steroidogenic enzyme 21-hydroxylase. To prevent genital ambiguity in affected female fetuses, prenatal treatment with dexamethasone must begin on or before gestational week 9. Currently used chorionic villus sampling and amniocentesis provide genetic results at approximately 14 weeks of gestation at the earliest. This means that mothers who want to undergo prenatal dexamethasone treatment will be unnecessarily treating seven of eight fetuses (males and three of four unaffected females), emphasizing the desirability of earlier genetic diagnosis in utero. Objective: The objective of the study was to develop a noninvasive method for early prenatal diagnosis of fetuses at risk for CAH. Patients: Fourteen families, each with a proband affected by phenotypically classical CAH, were recruited. Design: Cell-free fetal DNA was obtained from 3.6 mL of maternal plasma. Using hybridization probes designed to capture a 6-Mb region flanking CYP21A2, targeted massively parallel sequencing (MPS) was performed to analyze genomic DNA samples from parents and proband to determine parental haplotypes. Plasma DNA from pregnant mothers also underwent targeted MPS to deduce fetal inheritance of parental haplotypes. Results: In all 14 families, the fetal CAH status was correctly deduced by targeted MPS of DNA in maternal plasma, as early as 5 weeks 6 days of gestation. Conclusions: MPS on 3.6 mL plasma from pregnant mothers could potentially provide the diagnosis of CAH, noninvasively, before the ninth week of gestation. Only affected female fetuses will thus be treated. Our strategy represents a generic approach for noninvasive prenatal testing for an array of autosomal recessive disorders. PMID:24606108

  16. Adrenal neoplasms

    International Nuclear Information System (INIS)

    Low, G.; Dhliwayo, H.; Lomas, D.J.

    2012-01-01

    Adenoma, myelolipoma, phaeochromocytoma, metastases, adrenocortical carcinoma, neuroblastoma, and lymphoma account for the majority of adrenal neoplasms that are encountered in clinical practice. A variety of imaging methods are available for evaluating adrenal lesions including ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine techniques such as meta-iodobenzylguanidine (MIBG) scintigraphy and positron-emission tomography (PET). Lipid-sensitive imaging techniques such as unenhanced CT and chemical shift MRI enable detection and characterization of lipid-rich adenomas based on an unenhanced CT attenuation of ≤10 HU and signal loss on opposed-phase compared to in-phase T1-weighted images, respectively. In indeterminate cases, an adrenal CT washout study may differentiate adenomas (both lipid-rich and lipid-poor) from other adrenal neoplasms based on an absolute percentage washout of >60% and/or a relative percentage washout of >40%. This is based on the principle that adenomas show rapid contrast washout while most other adrenal neoplasms including malignant tumours show slow contrast washout instead. 18 F-2-fluoro-2-deoxy-D-glucose–PET ( 18 FDG-PET) imaging may differentiate benign from malignant adrenal neoplasms by demonstrating high tracer uptake in malignant neoplasms based on the increased glucose utilization and metabolic activity found in most of these malignancies. In this review, the multi-modality imaging appearances of adrenal neoplasms are discussed and illustrated. Key imaging findings that facilitate lesion characterization and differentiation are emphasized. Awareness of these imaging findings is essential for improving diagnostic confidence and for reducing misinterpretation errors.

  17. Metabolism of progesterone-4-14C in organ cultures of fetal adrenal glands in the human being

    International Nuclear Information System (INIS)

    Weber, S.

    1979-01-01

    1. In 72 hours of incubation in two subsequent cultures, progesterone-4- 14 C was converted into different corticosteroids and androgenes by using explants of the adrenal glands in organ cultures, which were taken from a male fetus with a crown-to-rump length of 8.5 cm. In the most cases the water-dilutable metabolites are steroidsulfates. 2. The following individual progesterone metabolites were found: 17α-hydroxyprogesterone-4- 14 C, 16α-hydroxyprogesterone-4- 14 C, corticosterone-4- 14 C, cortisole-4- 14 C, cortisone-4- 14 C, androstendione-4- 14 C, and 11β-hydroxyandrostendione-4- 14 C. 3. These steroides let appear possible the presence and efficacy of the following enzyme systems: 17α-hydroxylase, 16α-hydroxylase, 21-hydroxylase, 11β-hydroxylase, 11β-hydroxysteroide-dehydrogenase, and Csub(17-20) desmolase. 4. Calculations of our dates by the analogue computer, which are present by now, apparently seem to render possible the kinetic of the corticosteroide biosynthesis in the tissue of fetal adrenal glands by organ cultures, because under the present conditions incubations can be carried out for considerably longer periods than by cell fractions, cell homogenates, and organ sections. (orig.) [de

  18. A case of treatment in a patient with synchronous bilateral renal cell carcinoma and simultaneous metastatic involvement of both adrenal glands: Clinical observation

    Directory of Open Access Journals (Sweden)

    V. R. Latypov

    2014-11-01

    Full Text Available Synchronous bilateral renal cell carcinoma occurs in 1.4 % of cases. The probability of bilateral adrenal metastases from renal cell carcinoma is less than 0.5 %. The clinical observation presents a case of synchronous bilateral renal cell carcinoma and simultaneous metastatic involvement of both adrenal glands. A 55‑year-old male patient was adm tted with the signs of hematuria and anemia to the Unit of Urology, Clinic of General Surgery, Siberian State Medical University. He was found to have synchronous bilateral renal cell carcinoma and simultaneous bilateral adrenal involvement. Sequential surgical treatment – radical nephrectomy (with adrenal gland removal on the right side and, after 3 months, adrenalectomy and kidney resection on the left side were performed. All the organs removed displayed tumors that proved to be renal cell carcinomas (a clear cell variant. There were lymph node metastases in the right-sided renal portal. Postoperatively, the investigators performed hormone replacement therapy for adrenal insufficiency, an immunotherapy cycle, three cycles of targeted therapy withsorafenib and sunitinib (at an interval of 0.5–2 years, and insulin therapy for new-onset diabetes mellitus. The duration of a follow-up was 6.2 years. When describing the case, the patient was alive and showed a generalized tumorous process with extensive tumor involvement of the solitary kidney. Sunitinib therapy was used.

  19. A case of treatment in a patient with synchronous bilateral renal cell carcinoma and simultaneous metastatic involvement of both adrenal glands: Clinical observation

    Directory of Open Access Journals (Sweden)

    V. R. Latypov

    2014-01-01

    Full Text Available Synchronous bilateral renal cell carcinoma occurs in 1.4 % of cases. The probability of bilateral adrenal metastases from renal cell carcinoma is less than 0.5 %. The clinical observation presents a case of synchronous bilateral renal cell carcinoma and simultaneous metastatic involvement of both adrenal glands. A 55‑year-old male patient was adm tted with the signs of hematuria and anemia to the Unit of Urology, Clinic of General Surgery, Siberian State Medical University. He was found to have synchronous bilateral renal cell carcinoma and simultaneous bilateral adrenal involvement. Sequential surgical treatment – radical nephrectomy (with adrenal gland removal on the right side and, after 3 months, adrenalectomy and kidney resection on the left side were performed. All the organs removed displayed tumors that proved to be renal cell carcinomas (a clear cell variant. There were lymph node metastases in the right-sided renal portal. Postoperatively, the investigators performed hormone replacement therapy for adrenal insufficiency, an immunotherapy cycle, three cycles of targeted therapy withsorafenib and sunitinib (at an interval of 0.5–2 years, and insulin therapy for new-onset diabetes mellitus. The duration of a follow-up was 6.2 years. When describing the case, the patient was alive and showed a generalized tumorous process with extensive tumor involvement of the solitary kidney. Sunitinib therapy was used.

  20. Insulin-like growth factor I enhances proenkephalin synthesis and dopamine β-hydroxylase activity in adrenal chromaffin cells

    International Nuclear Information System (INIS)

    Wilson, S.P.

    1991-01-01

    Insulin-like growth factor I (IGF-I) increased both the contents of proenkephalin derived enkephalin-containing peptides and the activity of dopamine β-hydroxylase in bovine adrenal chromaffin cells. These increases in dopamine β-hydroxylase and enkephalin-containing peptides continued for at least 8 days. The half-maximal IGF-I concentration for these effects was ∼ 1 nM, with maximal effects observed at 10-30 nM. In contrast, insulin was 1,000-fold less potent. Pretreatment of chromaffin cells with IGF-I increased the rate of [ 35 S]proenkephalin synthesis 4-fold compared to untreated cells. Total protein synthesis increased only 1.5-fold under these conditions. These results suggest that IGF-I may be a normal regulator of chromaffin cell function

  1. Insulin-like growth factor I enhances proenkephalin synthesis and dopamine. beta. -hydroxylase activity in adrenal chromaffin cells

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, S.P. (Univ. of South Carolina School of Medicine, Columbia (USA))

    1991-01-01

    Insulin-like growth factor I (IGF-I) increased both the contents of proenkephalin derived enkephalin-containing peptides and the activity of dopamine {beta}-hydroxylase in bovine adrenal chromaffin cells. These increases in dopamine {beta}-hydroxylase and enkephalin-containing peptides continued for at least 8 days. The half-maximal IGF-I concentration for these effects was {approximately} 1 nM, with maximal effects observed at 10-30 nM. In contrast, insulin was 1,000-fold less potent. Pretreatment of chromaffin cells with IGF-I increased the rate of ({sup 35}S)proenkephalin synthesis 4-fold compared to untreated cells. Total protein synthesis increased only 1.5-fold under these conditions. These results suggest that IGF-I may be a normal regulator of chromaffin cell function.

  2. Direct visualization of secretion from single bovine adrenal chromaffin cells by laser-induced native fluorescence imaging microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Tong, W.; Yeung, E.S. [Ames Laboratory---USDOE and Department of Chemistry, Iowa State University, Ames, Iowa 50011 (United States)

    1998-03-01

    Direct visualization of the secretion process of individual bovine adrenal chromaffin cells was achieved with laser-induced native fluorescence imaging microscopy. By monitoring the native fluorescence of catecholamines excited by the 275 nm laser line with an intensified charge-coupled-device (CCD) camera, we obtained good temporal and spatial resolution simultaneously without using additional fluorescent probes. Large variations were found among individual cells in terms of the amounts of catecholamines secreted and the rates of secretion. Different regions of a cell also behave differently during the secretion process. However, the degree of this local heterogeneity is smaller than in neurons and neuralgia. The influence of deep-ultraviolet (UV) laser excitation on cells is also discussed. This quantitative imaging technique provides a useful noninvasive approach for the study of dynamic cellular changes and the understanding of the molecular mechanisms of secretory processes. {copyright} {ital 1998} {ital Society for Applied Spectroscopy}

  3. Cortisol-dependent stress effects on cell distribution in healthy individuals and individuals suffering from chronic adrenal insufficiency.

    Science.gov (United States)

    Geiger, Ashley M; Pitts, Kenneth P; Feldkamp, Joachim; Kirschbaum, Clemens; Wolf, Jutta M

    2015-11-01

    Chronic adrenal insufficiency (CAI) is characterized by a lack of glucocorticoid and mineralocorticoid production due to destroyed adrenal cortex cells. However, elevated cortisol secretion is thought to be a central part in a well-orchestrated immune response to stress. This raises the question to what extent lack of cortisol in CAI affects stress-related changes in immune processes. To address this question, 28 CAI patients (20 females) and 18 healthy individuals (11 females) (age: 44.3 ± 8.4 years) were exposed to a psychosocial stress test (Trier Social Stress Test: TSST). Half the patients received a 0.03 mg/kg body weight injection of hydrocortisone (HC) post-TSST to mimic a healthy cortisol stress response. Catecholamines and immune cell composition were assessed in peripheral blood and free cortisol measured in saliva collected before and repeatedly after TSST. CAI patients showed norepinephrine (NE) stress responses similar to healthy participants, however, epinephrine (E) as well as cortisol levels were significantly lower. HC treatment post-TSST resulted in cortisol increases comparable to those observed in healthy participants (interaction effects--NE: F=1.05, p=.41; E: F=2.56, p=.045; cortisol: F=13.28, pcortisol's central involvement in post-stress lymphocyte migration from blood into immune-relevant body compartments. As such, future studies should investigate whether psychosocial stress exposure may put CAI patients at an increased health risk due to attenuated immune responses to pathogens. Copyright © 2015. Published by Elsevier Inc.

  4. GATA transcription factors in testicular adrenal rest tumours

    Directory of Open Access Journals (Sweden)

    Manon Engels

    2017-11-01

    Full Text Available Testicular adrenal rest tumours (TARTs are benign adrenal-like testicular tumours that frequently occur in male patients with congenital adrenal hyperplasia. Recently, GATA transcription factors have been linked to the development of TARTs in mice. The aim of our study was to determine GATA expression in human TARTs and other steroidogenic tissues. We determined GATA expression in TARTs (n = 16, Leydig cell tumours (LCTs; n = 7, adrenal (foetal (n = 6 + adult (n = 10 and testis (foetal (n = 13 + adult (n = 8. We found testis-like GATA4, and adrenal-like GATA3 and GATA6 gene expressions by qPCR in human TARTs, indicating mixed testicular and adrenal characteristics of TARTs. Currently, no marker is available to discriminate TARTs from LCTs, leading to misdiagnosis and incorrect treatment. GATA3 and GATA6 mRNAs exhibited excellent discriminative power (area under the curve of 0.908 and 0.816, respectively, while immunohistochemistry did not. GATA genes contain several CREB-binding sites and incubation with 0.1 mM dibutyryl cAMP for 4 h stimulated GATA3, GATA4 and GATA6 expressions in a human foetal testis cell line (hs181.tes. Incubation of adrenocortical cells (H295RA with ACTH, however, did not induce GATA expression in vitro. Although ACTH did not dysregulate GATA expression in the only human ACTH-sensitive in vitro model available, our results do suggest that aberrant expression of GATA transcription factors in human TARTs might be involved in TART formation.

  5. The Human Cell Atlas.

    Science.gov (United States)

    Regev, Aviv; Teichmann, Sarah A; Lander, Eric S; Amit, Ido; Benoist, Christophe; Birney, Ewan; Bodenmiller, Bernd; Campbell, Peter; Carninci, Piero; Clatworthy, Menna; Clevers, Hans; Deplancke, Bart; Dunham, Ian; Eberwine, James; Eils, Roland; Enard, Wolfgang; Farmer, Andrew; Fugger, Lars; Göttgens, Berthold; Hacohen, Nir; Haniffa, Muzlifah; Hemberg, Martin; Kim, Seung; Klenerman, Paul; Kriegstein, Arnold; Lein, Ed; Linnarsson, Sten; Lundberg, Emma; Lundeberg, Joakim; Majumder, Partha; Marioni, John C; Merad, Miriam; Mhlanga, Musa; Nawijn, Martijn; Netea, Mihai; Nolan, Garry; Pe'er, Dana; Phillipakis, Anthony; Ponting, Chris P; Quake, Stephen; Reik, Wolf; Rozenblatt-Rosen, Orit; Sanes, Joshua; Satija, Rahul; Schumacher, Ton N; Shalek, Alex; Shapiro, Ehud; Sharma, Padmanee; Shin, Jay W; Stegle, Oliver; Stratton, Michael; Stubbington, Michael J T; Theis, Fabian J; Uhlen, Matthias; van Oudenaarden, Alexander; Wagner, Allon; Watt, Fiona; Weissman, Jonathan; Wold, Barbara; Xavier, Ramnik; Yosef, Nir

    2017-12-05

    The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community.

  6. Halothane inhibits the cholinergic-receptor-mediated influx of calcium in primary culture of bovine adrenal medulla cells

    International Nuclear Information System (INIS)

    Yashima, N.; Wada, A.; Izumi, F.

    1986-01-01

    Adrenal medulla cells are cholinoceptive cells. Stimulation of the acetylcholine receptor causes the influx of Ca to the cells, and Ca acts as the coupler of the stimulus-secretion coupling. In this study, the authors investigated the effects of halothane on the receptor-mediated influx of 45 Ca using cultured bovine adrenal medulla cells. Halothane at clinical concentrations (0.5-2%) inhibited the influx of 45 Ca caused by carbachol, with simultaneous inhibition of catecholamine secretion. The influx of 45 Ca and the secretion of catecholamines caused by K depolarization were inhibited by a large concentration of Mg, which competes with Ca at Ca channels, but not inhibited by halothane. Inhibition of the 45 Ca influx by halothane was not overcome by increase in the carbachol concentration. Inhibition of the 45 Ca influx by halothane was examined in comparison with that caused by a large concentration of Mg by the application of Scatchard analysis as the function of the external Ca concentration. Halothane decreased the maximal influx of 45 Ca without altering the apparent kinetic constant of Ca to Ca channels. On the contrary, a large concentration of Mg increased the apparent kinetic constant without altering the maximal influx of 45 Ca. Based on these findings, the authors suggest that inhibition of the 45 Ca influx by halothane was not due to the direct competitive inhibition of Ca channels, nor to the competitive antagonism of agonist-receptor interaction. As a possibility, halothane seems to inhibit the receptor-mediated activation of Ca channels through the interference of coupling between the receptor and Ca channels

  7. High grade primary adrenal intravascular large B-cell lymphoma manifesting as Addison disease Linfoma intravascular de alto grado de células B grandes y origen suprarrenal que se manifiesta en forma de enfermedad de Addison

    OpenAIRE

    J. Venizelos; D. Tamiolakis; M. Lambropoulou; G. Alexiadis; G. Petrakis; N. Papadopoulos

    2007-01-01

    We report a rare case of a 68 aged male who presented with adrenal failure and was diagnosed of high grade large B-cell lymphoma primarily arising in the adrenal glands. The patient was administrated with additional chemotherapy but he passed away 7 months later due to infection in the lungs. Intravascular lymphoma should be suspected in patients with bilateral adrenal masses who present with rapidly progressive adrenal insufficiency.Publicamos el caso poco frecuente de un varón de 68 años de...

  8. Synchronous Microscopic Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma of the Adrenal and Lymphoplasmacytic Lymphoma: De Novo Disease or Transformation?

    Science.gov (United States)

    Moonim, Mufaddal T; Nasir, Alia; Hubbard, Jonathan; Ketley, Nicholas; Fields, Paul

    2017-06-01

    Lymphomas arising in the adrenal are rare, and to our knowledge, 2 cases of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphomas (DLBCL) in an adrenal pseudocyst have been reported. We report an incidental EBV-positive DLBCL arising in an adrenal pseudocyst in a 58-year-old man with a 7-year history of lymphoplasmacytic lymphoma (LPL). The DLBCL was present in the fibrinous exudate, while the LPL resided in the cyst wall. The patient underwent de-roofing of the same cyst 3 years previously; review of histology revealed foci of LPL in the cyst wall, but not of DLBCL. There have been reports of similar microscopic EBV-positive DLBCLs within enclosed cystic spaces. However, all these cases were incidental extranodal primary DLBCLs. Since residual LPL was present alongside DLBCL, with similar light chain restriction, we propose that this may represent transformation, rather than a de novo primary EBV-driven lymphoma.

  9. The human cell atlas

    DEFF Research Database (Denmark)

    Regev, Aviv; Teichmann, Sarah A.; Lander, Eric S.

    2017-01-01

    The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international...... collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells...... in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early...

  10. [Immunoendocrine associations in adrenal glands].

    Science.gov (United States)

    Sterzl, I; Hrdá, P

    2010-12-01

    Immune and endocrine systems are basic regulatory mechanisms of organism and, including the nervous system, maintain the organism's homeostasis. The main immune system representatives are mononuclear cells, T- and B-cells and their products, in the endocrine system the main representatives are cells of the glands with inner secretion and their products. One of the most important glands for maintaining homeostasis are adrenal glands. It has been proven that either cells of the immune system, either endocrine cells can, although in trace amounts, produce mutually mediators of both systems (hormones, cytokines). Disorders in one system can lead to pathological symptoms in the other system. Also here represent adrenals an important model.

  11. Adrenal scintigraphy with Scintadren

    International Nuclear Information System (INIS)

    Dabasi, G.; Irto, I.; Hernady, T.; Balint, I.

    1983-01-01

    68 patients with various adrenal disorders have been examined using Scintadren /TRC Amersham, England/. The parameters of adrenal imaging under Dexamethason suppression and after its discontinuance were established

  12. Ketamine inhibits 45Ca influx and catecholamine secretion by inhibiting 22Na influx in cultured bovine adrenal medullary cells

    International Nuclear Information System (INIS)

    Takara, Hiroshi; Wada, Akihiko; Arita, Masahide; Izumi, Futoshi; Sumikawa, Koji

    1986-01-01

    The effects of ketamine, an intravenous anesthetic, on 22 Na influx, 45 Ca influx and catecholamine secretion were investigated in cultured bovine adrenal medullary cells. Ketamine inhibited carbachol-induced 45 Ca influx and catecholamine secretion in a concentration-dependent manner with a similar potency. Ketamine also reduced veratridine-induced 45 Ca influx and catecholamine secretion. The influx of 22 Na caused by carbachol or by veratridine was suppressed by ketamine with a concentration-inhibition curve similar to that of 45 Ca influx and catecholamine secretion. Inhibition by ketamine of the carbachol-induced influx of 22 Na, 45 Ca and secretion of catecholamines was not reversed by the increased concentrations of carbachol. These observations indicate that ketamine, at clinical concentrations, can inhibit nicotinic receptor-associated ionic channels and that the inhibition of Na influx via the receptor-associated ionic channels is responsible for the inhibition of carbachol-induced Ca influx and catecholamine secretion. (Auth.)

  13. Rare myeloid sarcoma/acute myeloid leukemia with adrenal mass after allogeneic mobilization peripheral blood stem cell transplantation

    International Nuclear Information System (INIS)

    Wang, Ya-Fei; Li, Qian; Xu, Wen-Gui; Xiao, Jian-Yu; Pang, Qing-Song; Yang, Qing; Zhang, Yi-Zuo

    2013-01-01

    Myeloid sarcoma (MS) is a rare hematological neoplasm that develops either de novo or concurrently with acute myeloid leukemia (AML). This neoplasm can also be an initial manifestation of relapse in a previously treated AML that is in remission. A 44-year-old male patient was diagnosed with testis MS in a local hospital in August 2010. After one month, bone marrow biopsy and aspiration confirmed the diagnosis of AML. Allogeneic mobilization peripheral blood stem cell transplantation was performed, with the sister of the patient as donor, after complete remission (CR) was achieved by chemotherapy. Five months after treatment, an adrenal mass was detected by positron emission tomography-computed tomography (PET-CT). Radiotherapy was performed for the localized mass after a multidisciplinary team (MDT) discussion. The patient is still alive as of May 2013, with no evidence of recurrent MS or leukemia

  14. The affection of APA microcapsulation on catecholamine and leucine-enkephalin secretion from the bovine adrenal medullary chromaffin cells

    International Nuclear Information System (INIS)

    Guo Shuilong; Cui Xin; Luo Yun; Xue Yilong

    2002-01-01

    The affection of alginate-polylysine-alginate (APA) microcapsulation on catecholamine (CA) and leucine-enkephalin (L-EK) secretion from bovine adrenal medullary chromaffin cells was analysed. Encapsulating BCCs with the APA microcapsulation, the secretion of CA and L-EK in encapsulated BCCs was detected by high-performance liquid chromatography-electrochemical assay and radioimmunoassay, respectively. There is little difference between the encapsulated BCCs and the non-encapsulated BCCs in the secretion of epinephrine (E) and noradrenaline (NE) but the secretion of dopamine (DA) and L-EK in several points decline. The studies indicated that APA microcapsulation of BCCs didn't affect the secretion of E and NE, but did the secretion DA and L-EK in forepart

  15. Adrenal Gland Disorders: Condition Information

    Science.gov (United States)

    ... About Share Facebook Twitter Pinterest Email Print About Adrenal Gland Disorders The adrenal glands, located on the top of ... as estrogen and testosterone. What are adrenal gland disorders? Adrenal gland disorders occur when the adrenal glands do not ...

  16. Studies on the isolation, structural analysis and tissue localization of fetal antigen 1 and its relation to a human adrenal-specific cDNA, pG2

    DEFF Research Database (Denmark)

    Jensen, Charlotte Harken; Teisner, Børge; Højrup, Peter

    1993-01-01

    Fetal antigen 1 was purified from second trimester human amniotic fluid by immunospecific affinity chromatography followed by reversed-phase chromatography. Fetal antigen 1 is a single chain glycoprotein with a M(r) of 32-38 kDa. The amino acid composition revealed a high content of cysteines......, prolines and amino acids (aa) with acidic side-chains indicating that fetal antigen 1 is a compactly folded, strongly hydrophilic molecule. The N-terminal amino acid sequence (37 aa) revealed no homology to other known protein sequences, implying that fetal antigen 1 is a 'novel' human protein. When the aa...... sequence was back-translated into the appropriate degenerate sequence of nucleic acids, fetal antigen 1 could be partially aligned to a 'human adrenal-specific mRNA, pG2'. The indirect immunoperoxidase technique demonstrated fetal antigen 1 in fetal hepatocytes, glandular cells of fetal pancreas...

  17. Comparison of P2 purinergic receptors of aortic endothelial cells with those of adrenal medulla: evidence for heterogeneity of receptor subtype and of inositol phosphate response.

    Science.gov (United States)

    Allsup, D J; Boarder, M R

    1990-07-01

    Vascular endothelial cells from different parts of the circulation are known to show different functional responses, presumably corresponding to physiological roles. Previous studies have shown that ATP acts on P2 purinergic receptors of endothelial cells of major blood vessels, stimulating the formation of inositol phosphates. Here we have compared the action of ATP and congeners acting on endothelial cells of bovine thoracic aorta with cells derived from the microvasculature of bovine adrenal medulla. With measurement of total inositol phosphates, cells from the aorta showed a rank order of agonist potency of 2-methylthio-ATP greater than adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) greater than ADP greater than ATP greater than beta, gamma-imido-ATP greater than beta, gamma-methylene-ATP, consistent with action at receptors of the P2Y subtype. However, with adrenal cells the rank order of potency was ATP gamma S greater than ATP greater than beta, gamma-imido-ATP greater than ADP greater than beta, gamma-methylene-ATP = 2-methylthio-ATP. This profile is not consistent with either P2X or P2Y receptors. When the nature of this inositol phosphate response was analyzed with anion exchange chromatography, it was found that the aortic cells showed an inositol trisphosphate stimulation that peaked within a few seconds and rapidly declined, whereas the response of the adrenal medulla cells continued to rise through 5 min. Analysis of isomers of inositol phosphates revealed a different pattern of metabolism between the two cell types, which may account for the different time course of response. With adrenal cells, ATP at low micromolar concentrations caused a dose-dependent increase in levels of cyclic AMP and had a greater than additive effect on cyclic AMP levels when combined with submaximal stimulation by prostaglandin E2. These results suggest the presence of a P2Y receptor on aortic endothelial cells, with an 'atypical' purinocepter, i.e., neither P2X nor P2Y

  18. Resveratrol inhibits steroidogenesis in human fetal adrenocortical cells at the end of first trimester

    DEFF Research Database (Denmark)

    Savchuk, Iuliia; Morvan, Marie-Line; Søeborg, Tue

    2017-01-01

    SCOPE: Resveratrol has a diverse array of healthful effects on metabolic parameters in different experimental paradigms but has also potential to inhibit steroidogenesis in rodent adrenals. The aim of the present study was to characterize the effects of resveratrol on human fetal adrenal...... steroidogenesis at gestational weeks (GW) 9-12. METHODS AND RESULTS: Adrenals from aborted fetuses (GW10-12) were used to prepare primary cultures of human fetal adrenocortical cells (HFAC). HFAC were treated in the presence or absence of ACTH (10 ng/ml) with or without resveratrol (10 μM) for 24 hours....... The production of steroids by HFAC was analyzed by gas and liquid chromatography coupled to tandem/mass spectrometry. The expression of steroidogenic enzymes at GW 9-12 was quantified by automated Western blotting. We observed that resveratrol significantly suppressed synthesis of dehydroepiandrosterone (DHEA...

  19. Dynamics of cocaine- and amphetamine-regulated transcript containing cell changes in the adrenal glands of two kidney, one clip rats.

    Science.gov (United States)

    Kasacka, Irena; Piotrowska, Zaneta; Janiuk, Izabela; Zbucki, Robert

    2014-10-01

    Taking into consideration the homeostatic disorders resulting from renal hypertension and the essential role of cocaine- and amphetamine-regulated transcript (CART) in maintaining homeostasis by regulating many functions of the body, the question arises as to what extent the renovascular hypertension affects the morphology and dynamics of changes of CART-containing cells in the adrenal glands. The aim of the present study was to examine the distribution, morphology, and dynamics of changes of CART-containing cells in the adrenal glands of "two kidney, one clip" (2K1C) renovascular hypertension model in rats. The studies were carried out on the adrenal glands of rats after 3, 14, 28, 42, and 91 days from the renal artery clipping procedure. To identify neuroendocrine cells, immunohistochemical reaction was performed with the use of a specific antibody against CART. It was revealed that renovascular hypertension causes changes in the endocrine cells containing CART in the adrenal glands of rats. The changes observed in the endocrine cells depend on the time when the rats with experimentally induced hypertension were examined. In the first period of hypertension, the number and immunoreactivity of CART-containing cells were decreased, while from the 28-day test, it significantly increased, as compared to the control rats. CART is relevant to the regulation of homeostasis in the cardiovascular system and seems to be involved in renovascular hypertension. The results of the present work open the possibility of new therapeutic perspectives for the treatment of arterial hypertension, since CART function is involved in their pathophysiology. © 2014 by the Society for Experimental Biology and Medicine.

  20. Human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Abdallah, Basem; Kassem, Moustapha

    2008-01-01

    Mesenchymal stem cells (MSC) are a group of clonogenic cells present among the bone marrow stroma and capable of multilineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. Due to their ease of isolation and their differentiation potential, MSC are being...... introduced into clinical medicine in variety of applications and through different ways of administration. Here, we discuss approaches for isolation, characterization and directing differentiation of human mesenchymal stem cells (hMSC). An update of the current clinical use of the cells is also provided....

  1. Inclusões intracitoplasmáticas hialinas na medular da adrenal de bovinos

    Directory of Open Access Journals (Sweden)

    L.P Mesquita

    2011-02-01

    Full Text Available Cytoplasmic inclusion bodies in adrenal medullary chromaffin cells have been described in various species including humans. These inclusions are believed to be related to certain infectious, toxic and neurodegenerative diseases. No reports concerning such adrenal inclusions have been described in bovines. Adrenal glands from twenty bovines were evaluated in a retrospective study. Seven of these exhibited inclusions - three cases of rabies, two cases of chronic suppurative bronchopneumonia, one case of chronic suppurative peritonitis, and one case of gangrenous mastitis. The inclusions were present in higher numbers especially in cases of rabies and also in one case of chronic suppurative bronchopneumonia. The inclusions were intracytoplasmic, eosinophilic, rounded, single or multiple, of various sizes, strongly stained by PAS and were present in higher numbers in the external layer of the adrenal medulla. The inclusions were negative when subjected to immunohistochemistry for detection of viral antigens in the cases of rabies. Although inclusion bodies were present in adrenal glands devoid of other histological alterations, they were more abundant in cases in which the adrenal gland had other alterations. The correlation between certain diseases and the development of inclusion bodies is not known, which highlights the importance of further studies on these inclusions in adrenal glands of bovines.

  2. Rooibos Flavonoids Inhibit the Activity of Key Adrenal Steroidogenic Enzymes, Modulating Steroid Hormone Levels in H295R Cells

    Directory of Open Access Journals (Sweden)

    Lindie Schloms

    2014-03-01

    Full Text Available Major rooibos flavonoids—dihydrochalcones, aspalathin and nothofagin, flavones—orientin and vitexin, and a flavonol, rutin, were investigated to determine their influence on the activity of adrenal steroidogenic enzymes, 3β-hydroxysteroid dehydrogenase (3βHSD2 and cytochrome P450 (P450 enzymes, P450 17α-hydroxylase/17,20-lyase (CYP17A1, P450 21-hydroxylase (CYP21A2 and P450 11β-hydroxylase (CYP11B1. All the flavonoids inhibited 3βHSD2 and CYP17A1 significantly, while the inhibition of downstream enzymes, CYP21A2 and CYP11B1, was both substrate and flavonoid specific. The dihydrochalcones inhibited the activity of CYP21A2, but not that of CYP11B1. Although rutin, orientin and vitexin inhibited deoxycortisol conversion by CYP11B1 significantly, inhibition of deoxycorticosterone was <20%. These three flavonoids were unable to inhibit CYP21A2, with negligible inhibition of deoxycortisol biosynthesis only. Rooibos inhibited substrate conversion by CYP17A1 and CYP21A2, while the inhibition of other enzyme activities was <20%. In H295R cells, rutin had the greatest inhibitory effect on steroid production upon forskolin stimulation, reducing total steroid output 2.3-fold, while no effect was detected under basal conditions. Nothofagin and vitexin had a greater inhibitory effect on overall steroid production compared to aspalathin and orientin, respectively. The latter compounds contain two hydroxyl groups on the B ring, while nothofagin and vitexin contain a single hydroxyl group. In addition, all of the flavonoids are glycosylated, albeit at different positions—dihydrochalcones at C3' and flavones at C8 on ring A, while rutin, a larger molecule, has a rutinosyl moiety at C3 on ring C. Structural differences regarding the number and position of hydroxyl and glucose moieties as well as structural flexibility could indicate different mechanisms by which these flavonoids influence the activity of adrenal steroidogenic enzymes.

  3. Effect of forskolin and prostaglandin E1 on stimulus secretion coupling in cultured bovine adrenal chromaffin cells.

    Science.gov (United States)

    Marriott, D; Adams, M; Boarder, M R

    1988-02-01

    Treatment of adrenal chromaffin cells with forskolin (0.1-10 microM) stimulated cyclic AMP levels, reduced the maximal stimulation of release of noradrenaline by nicotine, and increased release in response to elevated external potassium and the calcium ionophore A23187. The presence of the phosphodiesterase inhibitor Ro 20-17-24 with forskolin potentiated both the stimulation of cyclic AMP and the inhibition of nicotine-induced noradrenaline release. Dibutyryl cyclic AMP, and the elevation of cyclic AMP with prostaglandin E1, also attenuated nicotine-stimulated release. However, when the stimulation of intracellular cyclic AMP production by prostaglandin E1 was potentiated by low levels of forskolin, there was not a concomitant potentiation of effect on noradrenaline release. Dideoxyforskolin, an analogue of forskolin which does not stimulate adenylate cyclase, inhibited both potassium- and nicotine-stimulated release, probably by a mechanism unrelated to the action of forskolin in these experiments. Using Fura-2 to estimate free intracellular calcium levels, both forskolin and dideoxyforskolin (at 10 microM) reduced the calcium transient in response to nicotine. These results support a model in which elevation of cyclic AMP inhibits the activation of nicotinic receptors, but augments stimulus secretion coupling downstream of calcium entry. The data, however, do not indicate a simple relationship between total intracellular cyclic AMP levels and the attenuation of nicotinic stimulation of release.

  4. Transbilayer transport of a propyltrimethylammonium derivative of diphenylhexatriene (TMAP-DPH) in bovine blood platelets and adrenal chromaffin cells.

    Science.gov (United States)

    Kitagawa, Shuji; Tachikawa, Eiichi; Kashimoto, Takashi

    2002-12-01

    The membrane fluorescent probe N-((4-(6-phenyl-1,3,5-hexatrienyl)phenyl)propyl)trimethylammonium (TMAP-DPH) has an additional three-carbon spacer between the fluorophore and the trimethylammonium substituent of 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH). As a basic study to clarify the transport mechanism of amphiphilic quaternary ammoniums, we observed the characteristics of the transbilayer transport of TMAP-DPH in bovine blood platelets and bovine adrenal chromaffin cells using the albumin extraction method. We compared these inward transport rates with those of TMA-DPH. TMAP-DPH crossed into the cytoplasmic layers of the membranes more slowly than TMA-DPH after rapid binding to the outer halves of the plasma membranes. The transport rate markedly depended on temperature. Time to reach the half-maximal incorporated amount of TMAP-DPH increased threefold accompanied by an increase in the concentration from 0.2 to 1.5 microM. The transport was stimulated significantly by various types of membrane perturbations such as modification of sulfhydryl-groups by N-ethylmaleimide and benzyl alcohol-induced increase in the fluidity of the lipid bilayer. The saturation phenomenon suggested the presence of the regulatory process in the transbilayer transport of TMAP-DPH.

  5. Prolactin induces adrenal hypertrophy

    Directory of Open Access Journals (Sweden)

    E.J. Silva

    2004-02-01

    Full Text Available Although adrenocorticotropic hormone is generally considered to play a major role in the regulation of adrenal glucocorticoid secretion, several reports have suggested that other pituitary hormones (e.g., prolactin also play a significant role in the regulation of adrenal function. The aim of the present study was to measure the adrenocortical cell area and to determine the effects of the transition from the prepubertal to the postpubertal period on the hyperprolactinemic state induced by domperidone (4.0 mg kg-1 day-1, sc. In hyperprolactinemic adult and young rats, the adrenals were heavier, as determined at necropsy, than in the respective controls: adults (30 days: 0.16 ± 0.008 and 0.11 ± 0.007; 46 days: 0.17 ± 0.006 and 0.12 ± 0.008, and 61 days: 0.17 ± 0.008 and 0.10 ± 0.004 mg for treated and control animals, respectively; P < 0.05, and young rats (30 days: 0.19 ± 0.003 and 0.16 ± 0.007, and 60 days: 0.16 ± 0.006 and 0.13 ± 0.009 mg; P < 0.05. We selected randomly a circular area in which we counted the nuclei of adrenocortical cells. The area of zona fasciculata cells was increased in hyperprolactinemic adult and young rats compared to controls: adults: (61 days: 524.90 ± 47.85 and 244.84 ± 9.03 µm² for treated and control animals, respectively; P < 0.05, and young rats: (15 days: 462.30 ± 16.24 and 414.28 ± 18.19; 60 days: 640.51 ± 12.91 and 480.24 ± 22.79 µm²; P < 0.05. Based on these data we conclude that the increase in adrenal weight observed in the hyperprolactinemic animals may be due to prolactin-induced adrenocortical cell hypertrophy.

  6. Adrenal Gland Cancer

    Science.gov (United States)

    ... either benign or malignant. Benign tumors aren't cancer. Malignant ones are. Most adrenal gland tumors are ... and may not require treatment. Malignant adrenal gland cancers are uncommon. Types of tumors include Adrenocortical carcinoma - ...

  7. Acute adrenal crisis

    Science.gov (United States)

    ... adrenal gland is damaged due to, for example, Addison disease or other adrenal gland disease, and surgery The ... Call your health care provider if you have Addison disease and are unable to take your glucocorticoid medicine ...

  8. Adrenal Gland Tumors: Statistics

    Science.gov (United States)

    ... Gland Tumor: Statistics Request Permissions Adrenal Gland Tumor: Statistics Approved by the Cancer.Net Editorial Board , 03/ ... primary adrenal gland tumor is very uncommon. Exact statistics are not available for this type of tumor ...

  9. Human innate lymphoid cells.

    Science.gov (United States)

    Mjösberg, Jenny; Spits, Hergen

    2016-11-01

    Innate lymphoid cells (ILCs) are increasingly acknowledged as important mediators of immune homeostasis and pathology. ILCs act as early orchestrators of immunity, responding to epithelium-derived signals by expressing an array of cytokines and cell-surface receptors, which shape subsequent immune responses. As such, ILCs make up interesting therapeutic targets for several diseases. In patients with allergy and asthma, group 2 innate lymphoid cells produce high amounts of IL-5 and IL-13, thereby contributing to type 2-mediated inflammation. Group 3 innate lymphoid cells are implicated in intestinal homeostasis and psoriasis pathology through abundant IL-22 production, whereas group 1 innate lymphoid cells are accumulated in chronic inflammation of the gut (inflammatory bowel disease) and lung (chronic obstructive pulmonary disease), where they contribute to IFN-γ-mediated inflammation. Although the ontogeny of mouse ILCs is slowly unraveling, the development of human ILCs is far from understood. In addition, the growing complexity of the human ILC family in terms of previously unrecognized functional heterogeneity and plasticity has generated confusion within the field. Here we provide an updated view on the function and plasticity of human ILCs in tissue homeostasis and disease. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  10. Coexistence of Cushing syndrome from functional adrenal adenoma and Addison disease from immune-mediated adrenalitis.

    Science.gov (United States)

    Colucci, Randall; Jimenez, Rafael E; Farrar, William; Malgor, Ramiro; Kohn, Leonard; Schwartz, Frank L

    2012-06-01

    A 56-year-old woman presented with an incidental adrenal adenoma and physical examination findings that included moderate obesity, a slight cervicothoracic fat pad ("buffalo hump"), increased supraclavicular fat pads, and white abdominal striae. Biochemical workup revealed elevated levels of 24-hour urinary free cortisol but normal serum morning cortisol and suppressed levels of corticotropin, suggestive of adrenal-dependent Cushing syndrome. The resected adrenal gland revealed macronodular cortical hyperplasia with a dominant nodule. Other findings included an absent cortisol response to corticotropin stimulation, presence of serum anti-21-hydroxylase antibodies, and mononuclear cell infiltration--consistent with adrenalitis. The findings represent, to the authors' knowledge, the first known case of a patient with coexistent functional cortisol-secreting macronodular adrenal tumor resulting in Cushing syndrome and immune-mediated adrenalitis resulting in Addison disease.

  11. Cytochrome P450c17 (steroid 17α-hydroxylase/17,20 lyase): cloning of human adrenal and testis cDNAs indicates the same gene is expressed in both tissues

    International Nuclear Information System (INIS)

    Chung, B.; Picado-Leonard, J.; Haniu, M.; Bienkowski, M.; Hall, P.F.; Shively, J.E.; Miller, W.L.

    1987-01-01

    P450c17 is the single enzyme mediating both 17α-hydroxylase (steroid 17α-monooxygenase, EC 1.14.99.9) and 17,20 lyase activities in the synthesis of steroid hormones. It has been suggested that different P450c17 isozymes mediate these activities in the adrenal gland and testis. The authors sequenced 423 of the 509 amino acids (83%) of the porcine adrenal enzyme; based on this partial sequence, a 128-fold degenerate 17-mer was synthesized and used to screen a porcine adrenal cDNA library. This yielded a 380-base cloned cDNA, which in turn was used to isolate several human adrenal cDNAs. The longest of these, λ hac 17-2, is 1754 base pairs long and includes the full-length coding region, the complete 3'-untranslated region, and 41 bases of the 5'-untranslated region. This cDNA encodes a protein of 508 amino acids having a predicted molecular weight of 57,379.82. High-stringency screening of a human testicular cDNA library yielded a partial clone containing 1303 identical bases. RNA gel blots and nuclease S1-protection experiments confirm that the adrenal and testicular P450c17 mRNAs are indistinguishable. These data indicate that the testis possesses a P450c17 identical to that in the adrenal. The human amino acid sequence is 66.7% homologous to the corresponding regions of the porcine sequence, and the human cDNA and amino acid sequences are 80.1 and 70.3% homologous, respectively, to bovine adrenal P450c17 cDNA. Both comparisons indicate that a central region comprising amino acid residues 160-268 is hypervariable among these species of P450c17

  12. Ovarian and Adrenal Androgens and Their Link to High Human Chorionic Gonadotropin Levels: A Prospective Controlled Study

    Directory of Open Access Journals (Sweden)

    René Rodríguez-Gutiérrez

    2014-01-01

    Full Text Available Background. Although the association between human chorionic gonadotropin (hCG and hyperandrogenism was identified more than 40 years ago, relevant questions remain unanswered. Design and Methods. We conducted a prospective, longitudinal, and controlled study in 23 women with a diagnosis of a complete hydatidiform mole (HM. Results. All participants completed the study. Before HM evacuation mean hCG was markedly higher in the cases than in the control group (P≤0.001. Free testosterone (T and dehydroepiandrosterone sulfate (DHEA-S were found to be higher in the cases (2.78 ± 1.24 pg/mL and 231.50 ± 127.20 μ/dL when compared to the control group (1.50 ± 0.75 pg/mL and 133.59 ± 60.69 μ/dL (P=0.0001 and 0.001, respectively. There was a strong correlation between hCG and free T/total T/DHEA-S concentrations (r=0.78; P≤0.001, r=0.74;  P≤0.001, and r=0.71;  P≤0.001, respectively. In the cases group 48 hours after HM evacuation, hCG levels were found to be significantly lower when compared to initial levels (P=0.001 and free T and DHEA-S declined significantly (P=0.0002 and 0.009. Conclusion. Before uterus evacuation, hCG, free T, and DHEA-S levels were significantly higher when compared with controls finding a strong correlation between hCG and free T/DHEA-S levels. Forty-eight hours after HM treatment hCG levels declined and the difference was lost. A novel finding of our study is that in cases, besides free T, DHEA-S was also found to be significantly higher and both the ovaries and adrenal glands appear to be the sites of this androgen overproduction.

  13. Cytoplasmic organelles determine complexity and specificity of calcium signalling in adrenal chromaffin cells

    Czech Academy of Sciences Publication Activity Database

    Garsia-Sancho, J.; Verkhratsky, Alexei

    2008-01-01

    Roč. 192, č. 2 (2008), s. 263-271 ISSN 1748-1708 Institutional research plan: CEZ:AV0Z50390512 Keywords : Ca2+ signalling * calcium microdomains * chromaffin cells Subject RIV: JE - Non-nuclear Energetics, Energy Consumption ; Use Impact factor: 2.455, year: 2008

  14. Modulation of agonist-induced inositol phosphate metabolism by cyclic adenosine 3',5'-monophosphate in adrenal glomerulosa cells

    International Nuclear Information System (INIS)

    Baukal, A.J.; Hunyady, L.; Balla, T.; Ely, J.A.; Catt, K.J.

    1990-01-01

    Activation of the cAMP messenger system was found to cause specific changes in angiotensin-II (All)-induced inositol phosphate production and metabolism in bovine adrenal glomerulosa cells. Pretreatment of [3H]inositol-labeled glomerulosa cells with 8-bromo-cAMP (8Br-cAMP) caused both short and long term changes in the inositol phosphate response to stimulation by All. Exposure to 8Br-cAMP initially caused dose-dependent enhancement (ED50 = 0.7 microM) of the stimulatory action of All (50 nM; 10 min) on the formation of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and its immediate metabolites. This effect of 8Br-cAMP was also observed in permeabilized [3H]inositol-labeled glomerulosa cells in which degradation of Ins(1,4,5)P3 was inhibited, consistent with increased activity of phospholipase-C. Continued exposure to 8Br-cAMP for 5-16 h caused selective enhancement of the All-induced increases in D-myo-inositol 1,3,4,6-tetrakisphosphate [Ins(1,3,4,6)P4] and myo-inositol 1,4,5,6-tetrakisphosphate. The long term effect of 8Br-cAMP on the 6-phosphorylated InsP4 isomers, but not the initial enhancement of Ins(1,4,5)P3 formation, was inhibited by cycloheximide. The characteristic biphasic kinetics of All-induced Ins(1,4,5)P3 formation were also changed by prolonged treatment with 8Br-cAMP to a monophasic response in which Ins(1,4,5)P3 increased rapidly and remained elevated during All stimulation. In permeabilized glomerulosa cells treated with 8Br-cAMP for 16 h, the conversion of D-myo-inositol 1,3,4-trisphosphate [Ins(1,3,4)P3] to Ins(1,3,4,6)P4 was consistently increased, whereas dephosphorylation of Ins(1,4,5)P3 to D-myo-inositol 1,4-bisphosphate and of D-myo-inositol 1,3,4,5-tetrakisphosphate to Ins(1,3,4)P3, was reduced

  15. Angiotensin II potentiates prostaglandin stimulation of cyclic AMP levels in intact bovine adrenal medulla cells but not adenylate cyclase in permeabilized cells.

    Science.gov (United States)

    Boarder, M R; Plevin, R; Marriott, D B

    1988-10-25

    The level of cyclic AMP in primary cultures of bovine adrenal medulla cells is elevated by prostaglandin E1. Angiotensin II is commonly reported to act on receptors linked to phosphoinositide metabolism or to inhibition of adenylate cyclase. We have investigated the effect of angiotensin II on prostaglandin E1-stimulated cyclic AMP levels in these primary cultures. Rather than reducing cyclic AMP levels, we have found that angiotensin II powerfully potentiates prostaglandin E1-stimulated cyclic AMP accumulation in intact cells, both in the presence and absence of phosphodiesterase inhibitors. The 50% maximal response was similar to that for stimulation of phosphoinositide breakdown by angiotensin II in these cultures. The potentiation of stimulated cyclic AMP levels was seen, although to a smaller maximum, with the protein kinase C (Ca2+/phospholipid-dependent enzyme) activating phorbol ester tetradecanoyl phorbolacetate and with the synthetic diacylglycerol 1-oleoyl-2-acetylglycerol; pretreatment (24 h) with active phorbol ester, which would be expected to diminish protein kinase C levels, attenuated the angiotensin II potentiation of cyclic AMP. Using digitonin-permeabilized cells we showed that adenylate cyclase activity was stimulated by prostaglandin E1 with the same dose-response relationship as was cyclic AMP accumulation in intact cells, but the permeabilized cells showed no response to angiotensin II. The results are discussed with respect to the hypothesis that the angiotensin II influence on cyclic AMP levels is mediated, in part, by diacylglycerol stimulation of protein kinase C.

  16. Internal Ca2+ mobilization and secretion in bovine adrenal chromaffin cells

    DEFF Research Database (Denmark)

    Cheek, T R; Thastrup, Ole

    1989-01-01

    and the sesquiterpene lactone thapsigargin (TG), which releases internal Ca2+ without concomitant breakdown of inositol lipids or protein kinase C activation, to examine the events which follow depletion of the releasable Ca2+ store in these cells. Monitoring [Ca2+]i using Fura-2 demonstrated that TG released Ca2+ from......-state that was dependent on the continual entry of extracellular Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)...

  17. Influence of bradykinin on diacylglycerol and phosphatidic acid accumulation in cultured bovine adrenal chromaffin cells.

    Science.gov (United States)

    Owen, P J; Boarder, M R

    1991-09-01

    Earlier studies have shown that bradykinin stimulated release of catecholamines from chromaffin cells by an influx of calcium through dihydropyridine-insensitive channels, and also that bradykinin stimulated (poly)phosphoinositide hydrolysis. To investigate membrane-bound second messengers in chromaffin cells, and to elucidate any role these may play in stimulus-secretion coupling, we have studied the influence of bradykinin on diacylglycerol and phosphatidic acid (PA). Using equilibrium labelling of primary cultures of chromaffin cells with [3H]arachidonic acid or [3H]glycerol, we found no influence of bradykinin (10 nM) on labelled diacylglycerol formation, either in the presence or absence of inhibitors of diacylglycerol lipase or kinase. However, when we used cells prelabelled with 32Pi for 2.5 h, we found that bradykinin produced a substantial stimulation of label found in PA, with an EC50 value of about 1 nM. This bradykinin stimulation of [32P]PA formation was only partially dependent on extracellular calcium, in contrast to the smaller response to nicotine, which was completely dependent on extracellular calcium. Short (10 min) pretreatment with tetradecanoylphorbol acetate (TPA) almost completely eliminated the bradykinin-stimulated formation of inositol phosphates, but failed to affect bradykinin stimulation of label in PA, suggesting that PA production in response to bradykinin is not downstream of phospholipase C activation. TPA alone failed to stimulate [32P]PA substantially, whereas long-term (24 or 48 h) treatment with TPA failed to attenuate the response to bradykinin. Diacylglycerol kinase inhibitors were also without effect on the bradykinin stimulation of [32P]PA. These results suggest that bradykinin stimulates PA production by a mechanism independent of the activation of protein kinase C.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Nonislet Cell Tumor Hypoglycemia in a Patient with Adrenal Cortical Carcinoma

    Directory of Open Access Journals (Sweden)

    Se Won Kim

    2016-01-01

    Full Text Available Nonislet cell tumor hypoglycemia (NICTH is a rare but serious paraneoplastic syndrome in which a tumor secretes incompletely processed precursors of insulin-like growth factor-II (IGF-II, causing hypoglycemia. Here, we report an exceptional case of NICTH caused by nonfunctioning adrenocortical carcinoma in a 39-year-old male with recurrent hypoglycemia. The patient’s serum IGF-II/IGF-I ratio had increased to 27.8. The serum level of the IGF-II/IGF-I ratio was normalized after removal of the tumor, and the hypoglycemic attacks no longer occurred after the operation.

  19. The BAR Domain Protein PICK1 Controls Vesicle Number and Size in Adrenal Chromaffin Cells

    DEFF Research Database (Denmark)

    da Silva Pinheiro, Paulo César; Jansen, Anna M; de Wit, Heidi

    2014-01-01

    , a marker for immature granules. In chromaffin cells isolated from a PICK1 knockout (KO) mouse the amount of exocytosis was reduced, while release kinetics and Ca(2+) sensitivity were unaffected. Vesicle-fusion events had a reduced frequency and released lower amounts of transmitter per vesicle (i...... in vesicle number and size, whereas the fusion competence of generated vesicles was unaffected by the absence of PICK1. Viral rescue experiments demonstrated that long-term re-expression of PICK1 is necessary to restore normal vesicular content and secretion, while short-term overexpression is ineffective...

  20. Human leukaemic cells

    International Nuclear Information System (INIS)

    Andronikashvili, E.L.; Mosulishvili, L.M.; Belokobil'skiy, A.I.; Kharabadze, N.E.; Shonia, N.I.; Desai, L.S.; Foley, G.E.

    1976-01-01

    The results of the determination of trace elements in nucleic acids and histones in human leukaemic cells by activation analysis are reported. The Cr 2+ , Fe 2+ , Zn 2+ , Co 2+ and Sb 2+ content of DNA and RNA of leukaemic cells compared to that of lymphocytes from a patient with infectious mononucleosis or a normal donor are shown tabulated. Similar comparisons are shown for the same trace metal content of histones isolated from the same type of cells. It is felt that the results afford further interesting speculation that trace metals may be involved in the interactions between histones and DNA (especially at the binding sites of histones to DNA), which affect transcription characteristics. (U.K.)

  1. The N-terminal neurotensin fragment, NT1-11, inhibits cortisol secretion by human adrenocortical cells.

    Science.gov (United States)

    Sicard, Flavie; Contesse, Vincent; Lefebvre, Hervé; Ait-Ali, Djida; Gras, Marjorie; Cartier, Dorthe; Decker, Annick; Chartrel, Nicolas; Anouar, Youssef; Vaudry, Hubert; Delarue, Catherine

    2006-08-01

    Neurotensin (NT) modulates corticosteroid secretion from the mammalian adrenal gland. The objective of this study was to investigate the possible involvement of NT in the control of cortisol secretion in the human adrenal gland. In vitro studies were conducted on cultured human adrenocortical cells. This study was conducted in a university research laboratory. Adrenal explants from patients undergoing expanded nephrectomy for kidney cancer were studied. Cortisol secretion from cultured adrenocortical cells was measured. NT1-11, the N-terminal fragment of NT, dose-dependently inhibited basal and ACTH-stimulated cortisol production by human adrenocortical cells in primary culture. In contrast, NT had no influence on cortisol output at concentrations up to 10(-6) m. HPLC and RT-PCR analyses failed to detect any significant amounts of NT and NT mRNA, respectively, in adrenal extracts. Molecular and pharmacological studies were performed to determine the type of NT receptor involved in the corticostatic effect of NT1-11. RT-PCR analysis revealed the expression of NT receptor type (NTR) 3 mRNA but not NTR1 and NTR2 mRNAs in the human adrenal tissue. However, the pharmacological profile of the adrenal NT1-11 receptor was different from that of NTR3, indicating that this receptor type is not involved in the action of NT1-11 on corticosteroidogenesis. Our results indicate that NT1-11 may act as an endocrine factor to inhibit cortisol secretion through activation of a receptor distinct from the classical NTR1, NTR2, and NTR3.

  2. New and superior adrenal imaging agent, 131I-6β-iodomethyl-19-nor-cholesterol (NP-59): evaluation in humans

    International Nuclear Information System (INIS)

    Sarkar, S.D.; Cohen, E.L.; Beierwaltes, W.H.; Ice, R.D.; Cooper, R.; Gold, E.N.

    1977-01-01

    We have reported tissue distribution studies in rats and dogs with a new adrenal imaging agent, 131 I-6β-iodomethyl-19-nor-cholesterol (NP-59). This agent concentrated five times higher in the adrenal cortex than 131 I-19-iodocholesterol without increased concentration in non-adrenal tissues. We now report in 34 patients, the findings on scintigraphy with NP-59 compared with angiograms and/or adrenal vein hormone levels and histopathology, including 13 patients with hypercortisolism, 12 with primary aldosteronism, 2 with low renin hypertension, 5 with catecholamine excess, 1 with a liver metastasis from an aldosterone producing adrenal cortical carcinoma, and 1 with anaplastic adrenal cortical carcinoma. NP-59 adrenal cortical uptake was more rapid and intense and background activity was less prominent, allowing earlier and more definite interpretation of images than was possible with 131 I-19-iodocholesterol

  3. Adrenal medullary hyperplasia. Hyperplasia-pheochromocytoma sequence.

    Science.gov (United States)

    Kurihara, K; Mizuseki, K; Kondo, T; Ohoka, H; Mannami, M; Kawai, K

    1990-09-01

    We present a case of unilateral adrenal medullary hyperplasia in a 63-year-old woman with clinical signs and symptoms of pheochromocytoma unassociated with multiple endocrine neoplasia. The surgically removed adrenal gland revealed diffuse medullary hyperplasia with multiple micronodules measuring up to 2 mm. The micronodules were composed of enlarged chromaffin cells with atypia, histologically similar to those of pheochromocytoma, forming small solid alveolar patterns separated by a fibrovascular stroma. Removal of the hyperplastic adrenal gland resulted in disappearance of paroxysmal nocturnal hypertension and palpitation. These results suggest that diffuse and nodular medullary hyperplasia is the precursor of pheochromocytoma.

  4. A radioimmunoassay for the detection of adrenal autoantibodies

    International Nuclear Information System (INIS)

    Kosowicz, J.; Gryczynska, M.; Bottazzo, G.F.

    1986-01-01

    A solid phase radioimmunoassay for adrenal antibodies is described. In the assay plastic tubes coated with adrenal microsomes (100 μg/ml) were incubated with human sera diluted from 1:50 to 1:5000 and the retained antibodies detected by subsequent incubation with 125 I-labelled protein A. The method was precise over the range of serum dilution of 1:250 to 1:5000. In the group of 30 patients with Addison's disease 19 had positive results in adrenal antibody radioimmunoassay (RIA). Comparative studies of RIA and immunofluorescence (IFL) revealed that there was partial correlation of adrenal antibody results in patients with high titre antibodies whereas RIA usually was more sensitive than IFL in patients with low titre antibodies. Computerized tomography (CT) displayed bilateral adrenal atrophy in most patients who had adrenal antibodies. On the other hand, patients with low RIA results and negative IFL antibodies had predominantly adrenal calcifications on scans. (author)

  5. High grade primary adrenal intravascular large B-cell lymphoma manifesting as Addison disease Linfoma intravascular de alto grado de células B grandes y origen suprarrenal que se manifiesta en forma de enfermedad de Addison

    Directory of Open Access Journals (Sweden)

    J. Venizelos

    2007-08-01

    Full Text Available We report a rare case of a 68 aged male who presented with adrenal failure and was diagnosed of high grade large B-cell lymphoma primarily arising in the adrenal glands. The patient was administrated with additional chemotherapy but he passed away 7 months later due to infection in the lungs. Intravascular lymphoma should be suspected in patients with bilateral adrenal masses who present with rapidly progressive adrenal insufficiency.Publicamos el caso poco frecuente de un varón de 68 años de edad que debutó con insuficiencia adrenal y fue diagnosticado de linfoma de alto grado de células B grandes ubicado principalmente en las glándulas suprarrenales. Al paciente le administraron quimioterapia adicional, pero falleció 7 meses después de infección pulmonar. El linfoma intravascular debe sospecharse en los pacientes con masas suprarrenales bilaterales que presenten insuficiencia adrenal rápidamente progresiva.

  6. Human leukaemic cells

    International Nuclear Information System (INIS)

    Andronikashvili, E.L.; Mosulishvili, L.M.; Belokobil'skiy, A.I.; Kharabadze, N.E.; Shonia, N.I.; Desai, L.S.; Foley, G.E.

    1976-01-01

    Trace metals were measured by neutron-activation analyses in purified nucleic acids and histone(s) of lymphocytes from patients with acute lymphocytic leukaemia or infectious mononucleosis, and from normal donors. DNA isolated from lymphocytes of a patient with infectious mononucleosis and a normal donor showed a high content of Cr 2+ , Sb 2+ , Fe 2+ , Zn 2+ , whereas DNA of lymphoblasts from a patient with acute lymphocytic leukaemia had a lower content of these trace metals, but the Co 2+ content was 20-fold higher than in DNA of normal donor lymphocytic cells. Total histones from leukaemic cells had higher contents of most of the trace metals except for Zn 2+ , which was present in lesser concentration than in histones from normal donor lymphocytic cells. Lysine-rich (F1) histones showed lower contents of Cr 2+ , Sb 2+ and Co 2+ , whereas arginine-rich (F3) histones had significantly higher contents of these trace metals. These observations may be of interest in that F3 histones more effectively inhibit RNA synthesis in human lymphocytic cells than do other species of histones. (author)

  7. Just another abdominal pain? Psoas abscess-like metastasis in large cell lung cancer with adrenal insufficiency.

    Science.gov (United States)

    Bernardino, Vera; Val-Flores, Luis Silva; Dias, João Lopes; Bento, Luís

    2015-06-10

    The authors report the case of a 69-year-old man with chronic obstructive pulmonary disease and previous pulmonary tuberculosis, who presented to the emergency department with abdominal and low back pain, anorexia and weight loss, rapidly evolving into shock. An initial CT scan revealed pulmonary condensation with associated cavitation and an iliopsoas mass suggestive of a psoas abscess. He was admitted in an intensive care unit unit; after a careful examination and laboratory assessment, the aetiology was yet undisclosed. MRI showed multiple retroperitoneal lymphadenopathies, bulky nodular adrenal lesions and bilateral iliac lytic lesions. Hypocortisolism was detected and treated with steroids. A CT-guided biopsy to the psoas mass and lytic lesions identified infiltration of non-small lung carcinoma. The patient died within days. Psoas metastases and adrenal insufficiency as initial manifestations of malignancy are rare and can be misdiagnosed, particularly in the absence of a known primary tumour. 2015 BMJ Publishing Group Ltd.

  8. Giant Adrenal Myelolipoma Masquerading as Heart Failure

    Directory of Open Access Journals (Sweden)

    Parijat S. Joy

    2014-03-01

    Full Text Available Adrenal myelolipomas are rare benign tumors of the adrenal cortex composed of adipose and hematopoietic cells. They have been postulated to arise from repeated stimulation by stress, inflammation and ACTH oversecretion. Myelolipomas are usually detected incidentally on imaging and do not require any active intervention besides regular follow-up by imaging. However, myelolipomas may insidiously grow to large sizes and cause mass effects and hemorrhage. Timely diagnosis and surgical resection are curative and lifesaving.

  9. Evaluation of adrenal function in patients with hypothalamic and pituitary disorders : comparison of serum cortisol, urinary free cortisol and the human-corticotrophin releasing hormone test with the insulin tolerance test

    NARCIS (Netherlands)

    Dullaart, RPF; Pasterkamp, SH; Beentjes, JAM; Sluiter, WJ

    OBJECTIVE This study aimed to evaluate the performance of screening tests (serum cortisol and 24-h urinary free cortisol) and the human-corticotrophin releasing hormone (h-CRH) test in the assessment of adrenal function in patients with hypothalamic-pituitary disorders. DESIGN Summary receiver

  10. Congenital Adrenal Hyperplasia

    Science.gov (United States)

    ... Español NICHD Theme Browse AZTopics Browse A-Z Adrenal Gland Disorders Autism Spectrum Disorder (ASD) Down Syndrome Endometriosis Learning ... Funding Opportunities & Notices Health A to Z List Adrenal Gland Disorders About NICHD Research Information Find a Study More ...

  11. Adrenic acid as an inflammation enhancer in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Horas H Nababan, Saut; Nishiumi, Shin; Kawano, Yuki; Kobayashi, Takashi; Yoshida, Masaru; Azuma, Takeshi

    2017-06-01

    This study was designed to identify novel links between lipid species and disease progression in non-alcoholic fatty liver disease (NAFLD). We analyzed lipid species in the liver and plasma of db/db mice fed a choline-deficient l-amino acid-defined, high-fat diet (CDAHFD) using liquid chromatography/mass spectrometry (LC/MS). An in vitro experiment was performed using HepG2 cells stimulated with recombinant human TNFα or IL1β. The expression of steatosis-, inflammation-, and fibrosis-related genes were analyzed. Plasma samples from NAFLD patients were also analyzed by LC/MS. The CDAHFD-fed db/db mice with hepatic steatosis, inflammation, mild fibrosis, obesity, and hypercholesterolemia displayed significantly higher hepatic and plasma levels of free adrenic acid (p < 0.05). The accumulated adrenic acid in the CDAHFD-fed db/db mice was associated with increased expression of ELOVL2 and 5, and the suppression of the acyl-CoA oxidase 1 gene during peroxisomal β-oxidation. The pretreatment of HepG2 cells with adrenic acid enhanced their cytokine-induced cytokines and chemokines mRNA expression. In NAFLD patients, the group with the highest ALT levels exhibited higher plasma adrenic acid concentrations than the other ALT groups (p-value for trend <0.001). Data obtained demonstrated that adrenic acid accumulation contributes to disease progression in NAFLD. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. High risk of adrenal toxicity of N1-desoxy quinoxaline 1,4-dioxide derivatives and the protection of oligomeric proanthocyanidins (OPC) in the inhibition of the expression of aldosterone synthetase in H295R cells

    International Nuclear Information System (INIS)

    Wang, Xu; Yang, Chunhui; Ihsan, Awais; Luo, Xun; Guo, Pu; Cheng, Guyue; Dai, Menghong; Chen, Dongmei; Liu, Zhenli; Yuan, Zonghui

    2016-01-01

    Highlights: • N1-QCT, N1-MEQ and N1-CYA showed more adrenal toxicity than other metabolites. • N1-desoxy QdNOs reduced expression of CYP11B1, CYP11B2 and transcription factors. • OPC increased expression of transcription factors, including CYP11B1 and CYP11B2. • OPC reduced adrenal toxicity induced by N1-desoxy QdNOs. • The results provided a mechanism of adrenal damage caused by QdNO metabolites. - Abstract: Quinoxaline 1,4-dioxide derivatives (QdNOs) with a wide range of biological activities are used in animal husbandry worldwide. It was found that QdNOs significantly inhibited the gene expression of CYP11B1 and CYP11B2, the key aldosterone synthases, and thus reduced aldosterone levels. However, whether the metabolites of QdNOs have potential adrenal toxicity and the role of oxidative stress in the adrenal toxicity of QdNOs remains unclear. The relatively new QdNOs, cyadox (CYA), mequindox (MEQ), quinocetone (QCT) and their metabolites, were selected for elucidation of their toxic mechanisms in H295R cells. Interestingly, the results showed that the main toxic metabolites of QCT, MEQ, and CYA were their N1-desoxy metabolites, which were more harmful than other metabolites and evoked dose and time-dependent cell damage on adrenal cells and inhibited aldosterone production. Gene and protein expression of CYP11B1 and CYP11B2 and mRNA expression of transcription factors, such as NURR1, NGFIB, CREB, SF-1, and ATF-1, were down regulated by N1-desoxy QdNOs. The natural inhibitors of oxidant stress, oligomeric proanthocyanidins (OPC), could upregulate the expression of diverse transcription factors, including CYP11B1 and CYP11B2, and elevated aldosterone levels to reduce adrenal toxicity. This study demonstrated for the first time that N1-desoxy QdNOs have the potential to be the major toxic metabolites in adrenal toxicity, which may shed new light on the adrenal toxicity of these fascinating compounds and help to provide a basic foundation for the

  13. Chapter 13. Adrenal glands

    International Nuclear Information System (INIS)

    Roux, H.; Paulin, R.

    1975-01-01

    The condition of isotopic methods to the functional and morphological exploration of the adrenal glands is shown, with emphasis on the fact that althought the cortico-adrenal responds to these methods the same does not apply to the medullo-adrenal, which expresses its morphological changes by producing deformations on the cortical image. Funtional tests, mainly directed at the cortico-adrenal, are described first: study of exchangeable sodium and potassium; determination of the plasma concentration and metabolic clearance of some steroid hormones (cortisol, corticosterone, aldosterone); evaluation of the renin activity. These tests are based on competitive analysis and radioimmunological methods. Morphological tests are examined next. Adrenal scintigraphy uses a simple technique (intraveinous administration of 131 I 19-iodocholesterol with no special preliminary preparation) which gives good images and is only limited now by the need to avoid over exposure of the gonads to ionising radiations [fr

  14. Effect of α-bungarotoxin and etorphine on acetylcholine-evoked release of endogenous and radiolabeled catecholamines from primary culture of adrenal chromaffin cells

    International Nuclear Information System (INIS)

    Kageyama, H.; Guidotti, A.

    1984-01-01

    Cell cultures of adrenal medulla have become an important research tool to study basic processes that regulate catecholamine storage, release and synthesis. Release has been studied either by labeling with [ 3 H]norepinephrine and measuring release of radioactivity or by measuring the endogenous catecholamines released with HPLC. Acetylcholine (5X10 -6 -10 -4 M) appears to release preferentially norepinephrine, although the cells store more epinephrine than norepinephrine. Etorphine and α-bungarotoxin antagonize the release of catecholamines elicited by acetylcholine. This inhibitory action appears to be greater when the measurement of endogenous catecholamines rather than radioactive norepinephrine is used to monitor the action of acetylcholine. The data suggest that the measurement of endogenous catecholamines by HPLC is preferable to the [ 3 H]NE loading and release technique, especially when analyzing the effects of low concentrations of drugs that are thought to affect nicotinic receptor function. (Auth.)

  15. Genome engineering in human cells.

    Science.gov (United States)

    Song, Minjung; Kim, Young-Hoon; Kim, Jin-Soo; Kim, Hyongbum

    2014-01-01

    Genome editing in human cells is of great value in research, medicine, and biotechnology. Programmable nucleases including zinc-finger nucleases, transcription activator-like effector nucleases, and RNA-guided engineered nucleases recognize a specific target sequence and make a double-strand break at that site, which can result in gene disruption, gene insertion, gene correction, or chromosomal rearrangements. The target sequence complexities of these programmable nucleases are higher than 3.2 mega base pairs, the size of the haploid human genome. Here, we briefly introduce the structure of the human genome and the characteristics of each programmable nuclease, and review their applications in human cells including pluripotent stem cells. In addition, we discuss various delivery methods for nucleases, programmable nickases, and enrichment of gene-edited human cells, all of which facilitate efficient and precise genome editing in human cells.

  16. Alveolar Soft Part Sarcoma Presenting as Hypervascular Adrenal Metastasis

    OpenAIRE

    Goroshi, Manjunath; Lila, Anurag R.; Bandgar, Tushar; Shah, Nalini S.

    2018-01-01

    Hypervascular adrenal masses include pheochromocytoma, metastases caused by clear renal cell carcinoma/hepatocellular carcinoma. Alveolar soft part sarcoma (ASPS) causing hypervascular metastases is not described in the literature. Here, we describe the first case of ASPS presenting as hypervascular metastasis. Our case was a 23-year-old male incidentally detected right adrenal mass during the evaluation of pain in the abdomen. On computed tomography (CT), adrenal mass showed bright enhanceme...

  17. Schwannoma of the adrenal gland

    Directory of Open Access Journals (Sweden)

    Anunayi Jeshtadi

    2014-07-01

    Full Text Available Visceral schwannomas are extremely rare and are usually discov-ered incidentally on USG/CT-Scan. Primary schwannomas of the adrenal gland are extremely uncommon. It has been theorized that they originate from Schwann cells that insulate the nerve fi-bers innervating the adrenal medulla. Histopathological examina-tion coupled with immunohistochemistry provides the definitive diagnosis. A 55 year old normotensive female presented with pain in the right loin since 5 months. Her renal parameters were normal. Contrast enhanced computed tomography of abdomen showed a well delineated 6.5 x 5cms mass at upper pole of her right kidney. 24-hour urinary metanephrine was slightly elevated (3.07mg/24hrs. A decline in Serum cortisol levels was observed following a dexamethasone suppression test (18.89nmol/l. Histopathological examination revealed a spindle cell tumor. Immunohistochemistry showed strong and diffuse positive staining for S-100 with negative expression for CD-117, desmin, CD-34, HMB-45, synaptophysin, chromogranin, cytokeratin, and SMA. Ki-67 index was 2%.A diagnosis of cellular schwannoma of adrenal gland was confirmed.

  18. Primary adrenal sarcomatoid carcinoma

    Directory of Open Access Journals (Sweden)

    Aftab S. Shaikh

    2014-03-01

    Full Text Available Adrenal sarcomatoid carcinomas are extremely rare tumors presenting with extensive locoregional spread at the time of diagnosis. Patients succumb to metastases within a couple of months. As a result, very few cases are reported in the literature until now. We present a case of a 62-year old female with non-functional sarcomatoid carcinoma of the right adrenal gland. There was no radiological evidence of locoregional metastases. Patient underwent right adrenalectomy. Follow up after 3 months showed para-aortic lymphadenopathy and similar left adrenal mass on computed tomography. Patient refused further treatment and succumbed to the disease. A brief case report with review of literature is presented.

  19. Calcified adrenal cyst

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chung Kyu; Choi, Byung Sook [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1970-10-15

    Calcified hemorrhagic adrenal cysts are rather rare and unusual pathologic entity. Especially, the peripheral curvilinear calcification on roentgenogram is fairly characteristic picture of the cysts. Recently, we have experienced in Severance Hospital one of the classical cases of the benign calcified adrenal cyst in 35 year old white mail patient who has had vague abdominal pain and palpable mass in right abdomen. It has been reviewed several reports for adrenal cysts and hoped that this report may call additional attention of radiological diagnosis on this unusual disease.

  20. Luteinizing hormone (LH)-responsive Cushing's syndrome: the demonstration of LH receptor messenger ribonucleic acid in hyperplastic adrenal cells, which respond to chorionic gonadotropin and serotonin agonists in vitro

    NARCIS (Netherlands)

    R.A. Feelders (Richard); W.W. de Herder (Wouter); S.W.J. Lamberts (Steven); L.J. Hofland (Leo); P.M. van Koetsveld (Peter); M. Verhoef-Post (Miriam); A.P.N. Themmen (Axel); F.H. de Jong (Frank); H.J. Bonjer (Jaap); A.J. Clark (Adrian); A-J. van der Lely (Aart-Jan)

    2003-01-01

    textabstractIn a substantial part of adrenal adenomas and hyperplasias from patients with Cushing's syndrome, cortisol production is controlled by the expression of aberrant hormone receptors on adrenocortical cells. We present in vivo and in vitro data of two patients with a

  1. Expression of Siglec-11 by human and chimpanzee ovarian stromal cells, with uniquely human ligands: implications for human ovarian physiology and pathology

    Science.gov (United States)

    Wang, Xiaoxia; Chow, Renee; Deng, Liwen; Anderson, Dan; Weidner, Noel; Godwin, Andrew K; Bewtra, Chanda; Zlotnik, Albert; Bui, Jack; Varki, Ajit; Varki, Nissi

    2011-01-01

    Siglecs (Sialic acid-binding Immunoglobulin Superfamily Lectins) are cell surface signaling receptors of the I-type lectin group that recognize sialic acid-bearing glycans. CD33-related-Siglecs are a subset with expression primarily in cells of hematopoietic origin and functional relevance to immune reactions. Earlier we reported a human-specific gene conversion event that markedly changed the coding region for the extracellular domain of Siglec-11, associated with human-specific expression in microglia (Hayakawa T, Angata T, Lewis AL, Mikkelsen TS, Varki NM, Varki A. 2005. A human-specific gene in microglia. Science. 309:1693). Analyzing human gene microarrays to define new patterns of expression, we observed high levels of SIGLEC11 transcript in the ovary and adrenal cortex. Thus, we examined human and chimpanzee tissues using a well-characterized anti-Siglec-11 mouse monoclonal antibody. Although adrenal expression was variable and confined to infiltrating macrophages in capillaries, ovarian expression of Siglec-11 in both humans and chimpanzees was on fibroblasts, the first example of Siglec expression on mesenchyme-derived stromal cells. Cytokines from such ovarian stromal fibroblasts play important roles in follicle development and ovulation. Stable transfection of SIGLEC11 into a primary human ovarian stromal fibroblast cell line altered the secretion of growth-regulated oncogene α, interleukin (IL)-10, IL-7, transforming growth factor β1 and tumor necrosis factor-α, cytokines involved in ovarian physiology. Probing for Siglec-11 ligands revealed distinct and strong mast cell expression in human ovaries, contrasting to diffuse stromal ligands in chimpanzee ovaries. Interestingly, there was a trend of increased Siglec-11 expression in post-menopausal ovaries compared with pre-menopausal ones. Siglec-11 expression was also found on human ovarian stromal tumors and in polycystic ovarian syndrome, a human-specific disease. These results indicate potential

  2. Functional paraganglioma extra-adrenal

    International Nuclear Information System (INIS)

    Arroyo-Martinez, Laura; Alvarez-Pertuz, Humberto; Acuna-Calvo, Jorge; Montoya-Calles, Juan Diego

    2006-01-01

    Functioning paragangliomas are rare tumours that produce catecholamines.They originate from extra-adrenal chromaffin cells. They are frequently malignant and are associated with high incidence of persistent or recurrent disease after their primary treatment. They are known as glomus, chemodectomas, chromaffin paragangliomas and glomerulocytomas. The location is diverse and reflects the paragangliomar distribution in the body from the base of the skull to the pelvic floor. The paragangliomas are found where there are nodes of the autonomous system, however, approximately 90% of these tumours appear in the adrenal glands (and they constitute the pheochromocytomas) and the remaining 10% is a location extra adrenal, but it has been said that its impact can be underestimated, ranging from 18% to 22% in adults and children up to 30%. The extra-adrenal are originated more frequently in the abdomen (85%), other in the chest (12%) and more rarely in the head and neck (3%). Imaging studies and measurement of non-physiological production of catecholamines may aid in the diagnosis of this entity. Surgery is the treatment of choice. It is presented the case of a primigravidas patient aged 32 with HTAIE requiring caesarean section, who had a postpartum torpid and despite to multiple antihypertensive treatments their pathology was difficult to deal, with ophthalmic complications. Some time later, the patient is studied by hyperhidrosis, laboratory tests and images are requested and it is documented incidentally, a left retroperitoneal tumour, the studies are expanded and reach the correct diagnosis. The tumour required surgical resection. The patient had a satisfactory postoperative period and she discharged with control in the external consultation. (author) [es

  3. Adrenal Gland Disorders

    Science.gov (United States)

    ... Cushing's syndrome, there's too much cortisol, while with Addison's disease, there is too little. Some people are born unable to make enough cortisol. Causes of adrenal gland disorders include Genetic mutations Tumors ...

  4. Analysis of bidirectional pattern synchrony of concentration-secretion pairs: implementation in the human testicular and adrenal axes.

    Science.gov (United States)

    Liu, Peter Y; Pincus, Steven M; Keenan, Daniel M; Roelfsema, Ferdinand; Veldhuis, Johannes D

    2005-02-01

    The hypothalamo-pituitary-testicular and hypothalamo-pituitary-adrenal axes are prototypical coupled neuroendocrine systems. In the present study, we contrasted in vivo linkages within and between these two axes using methods without linearity assumptions. We examined 11 young (21-31 yr) and 8 older (62-74 yr) men who underwent frequent (every 2.5 min) blood sampling overnight for paired measurement of LH and testosterone and 35 adults (17 women and 18 men; 26-77 yr old) who underwent adrenocorticotropic hormone (ACTH) and cortisol measurements every 10 min for 24 h. To mirror physiological interactions, hormone secretion was first deconvolved from serial concentrations with a waveform-independent biexponential elimination model. Feedforward synchrony, feedback synchrony, and the difference in feedforward-feedback synchrony were quantified by the cross-approximate entropy (X-ApEn) statistic. These were applied in a forward (LH concentration template, examining pattern recurrence in testosterone secretion), reverse (testosterone concentration template, examining pattern recurrence in LH secretion), and differential (forward minus reverse) manner, respectively. Analogous concentration-secretion X-ApEn estimates were calculated from ACTH-cortisol pairs. X-ApEn, a scale- and model-independent measure of pattern reproducibility, disclosed 1) greater testosterone-LH feedback coordination than LH-testosterone feedforward synchrony in healthy men and significant and symmetric erosion of both feedforward and feedback linkages with aging; 2) more synchronous ACTH concentration-dependent feedforward than feedback drive of cortisol secretion, independent of gender and age; and 3) enhanced detection of bidirectional physiological regulation by in vivo pairwise concentration-secretion compared with concentration-concentration analyses. The linking of relevant biological input to output signals and vice versa should be useful in the dissection of the reciprocal control of

  5. Adrenal imaging agents

    International Nuclear Information System (INIS)

    Davis, M.A.; Hanson, R.N.; Holman, B.L.

    1980-01-01

    The goals of this proposal are the development of selenium-containing analogs of the aromatic amino acids as imaging agents for the pancreas and of the adrenal cortex enzyme inhibitors as imaging agents for adrenal pathology. The objects for this year include (a) the synthesis of methylseleno derivatives of phenylalanine and tryptophan, and (b) the preparation and evaluation of radiolabeled iodobenzoyl derivatives of the selenazole and thiazole analogs of metyrapone and SU-9055

  6. Fetal Adrenal Demedullation Lowers Circulating Norepinephrine and Attenuates Growth Restriction but not Reduction of Endocrine Cell Mass in an Ovine Model of Intrauterine Growth Restriction

    Directory of Open Access Journals (Sweden)

    Melissa A. Davis

    2015-01-01

    Full Text Available Placental insufficiency is associated with fetal hypoglycemia, hypoxemia, and elevated plasma norepinephrine (NE that become increasingly pronounced throughout the third trimester and contribute to intrauterine growth restriction (IUGR. This study evaluated the effect of fetal adrenal demedullation (AD on growth and pancreatic endocrine cell mass. Placental insufficiency-induced IUGR was created by exposing pregnant ewes to elevated ambient temperatures during mid-gestation. Treatment groups consisted of control and IUGR fetuses with either surgical sham or AD at 98 days gestational age (dGA; term = 147 dGA, a time-point that precedes IUGR. Samples were collected at 134 dGA. IUGR-sham fetuses were hypoxemic, hypoglycemic, and hypoinsulinemic, and values were similar in IUGR-AD fetuses. Plasma NE concentrations were ~5-fold greater in IUGR-sham compared to control-sham, control-AD, and IUGR-AD fetuses. IUGR-sham and IUGR-AD fetuses weighed less than controls. Compared to IUGR-sham fetuses, IUGR-AD fetuses weighed more and asymmetrical organ growth was absent. Pancreatic β-cell mass and α-cell mass were lower in both IUGR-sham and IUGR-AD fetuses compared to controls, however, pancreatic endocrine cell mass relative to fetal mass was lower in IUGR-AD fetuses. These findings indicate that NE, independently of hypoxemia, hypoglycemia and hypoinsulinemia, influence growth and asymmetry of growth but not pancreatic endocrine cell mass in IUGR fetuses.

  7. Fetal Adrenal Demedullation Lowers Circulating Norepinephrine and Attenuates Growth Restriction but not Reduction of Endocrine Cell Mass in an Ovine Model of Intrauterine Growth Restriction

    Science.gov (United States)

    Davis, Melissa A.; Macko, Antoni R.; Steyn, Leah V.; Anderson, Miranda J.; Limesand, Sean W.

    2015-01-01

    Placental insufficiency is associated with fetal hypoglycemia, hypoxemia, and elevated plasma norepinephrine (NE) that become increasingly pronounced throughout the third trimester and contribute to intrauterine growth restriction (IUGR). This study evaluated the effect of fetal adrenal demedullation (AD) on growth and pancreatic endocrine cell mass. Placental insufficiency-induced IUGR was created by exposing pregnant ewes to elevated ambient temperatures during mid-gestation. Treatment groups consisted of control and IUGR fetuses with either surgical sham or AD at 98 days gestational age (dGA; term = 147 dGA), a time-point that precedes IUGR. Samples were collected at 134 dGA. IUGR-sham fetuses were hypoxemic, hypoglycemic, and hypoinsulinemic, and values were similar in IUGR-AD fetuses. Plasma NE concentrations were ~5-fold greater in IUGR-sham compared to control-sham, control-AD, and IUGR-AD fetuses. IUGR-sham and IUGR-AD fetuses weighed less than controls. Compared to IUGR-sham fetuses, IUGR-AD fetuses weighed more and asymmetrical organ growth was absent. Pancreatic β-cell mass and α-cell mass were lower in both IUGR-sham and IUGR-AD fetuses compared to controls, however, pancreatic endocrine cell mass relative to fetal mass was lower in IUGR-AD fetuses. These findings indicate that NE, independently of hypoxemia, hypoglycemia and hypoinsulinemia, influence growth and asymmetry of growth but not pancreatic endocrine cell mass in IUGR fetuses. PMID:25584967

  8. Human stromal (mesenchymal) stem cells

    DEFF Research Database (Denmark)

    Aldahmash, Abdullah; Zaher, Walid; Al-Nbaheen, May

    2012-01-01

    Human stromal (mesenchymal) stem cells (hMSC) represent a group of non-hematopoietic stem cells present in the bone marrow stroma and the stroma of other organs including subcutaneous adipose tissue, placenta, and muscles. They exhibit the characteristics of somatic stem cells of self......-renewal and multi-lineage differentiation into mesoderm-type of cells, e.g., to osteoblasts, adipocytes, chondrocytes and possibly other cell types including hepatocytes and astrocytes. Due to their ease of culture and multipotentiality, hMSC are increasingly employed as a source for cells suitable for a number...

  9. [Addison's disease : Primary adrenal insufficiency].

    Science.gov (United States)

    Pulzer, A; Burger-Stritt, S; Hahner, S

    2016-05-01

    Adrenal insufficiency, a rare disorder which is characterized by the inadequate production or absence of adrenal hormones, may be classified as primary adrenal insufficiency in case of direct affection of the adrenal glands or secondary adrenal insufficiency, which is mostly due to pituitary or hypothalamic disease. Primary adrenal insufficiency affects 11 of 100,000 individuals. Clinical symptoms are mainly nonspecific and include fatigue, weight loss, and hypotension. The diagnostic test of choice is dynamic testing with synthetic ACTH. Patients suffering from chronic adrenal insufficiency require lifelong hormone supplementation. Education in dose adaption during physical and mental stress or emergency situations is essential to prevent life-threatening adrenal crises. Patients with adrenal insufficiency should carry an emergency card and emergency kit with them.

  10. Human innate lymphoid cells

    NARCIS (Netherlands)

    Hazenberg, Mette D.; Spits, Hergen

    2014-01-01

    Innate lymphoid cells (ILCs) are lymphoid cells that do not express rearranged receptors and have important effector and regulatory functions in innate immunity and tissue remodeling. ILCs are categorized into 3 groups based on their distinct patterns of cytokine production and the requirement of

  11. Human innate lymphoid cells

    NARCIS (Netherlands)

    Mjösberg, Jenny; Spits, Hergen

    2016-01-01

    Innate lymphoid cells (ILCs) are increasingly acknowledged as important mediators of immune homeostasis and pathology. ILCs act as early orchestrators of immunity, responding to epithelium-derived signals by expressing an array of cytokines and cell-surface receptors, which shape subsequent immune

  12. Emission tomography for adrenal imaging

    International Nuclear Information System (INIS)

    Britton, K.E.; Shapiro, B.; Hawkins, L.A.

    1980-01-01

    Single photon emission tomography (SPET) of the adrenals was compared to convential gamma camera images. Depths of 19 adrenals were assessed by both the lateral skin-upper kidney pole method and by SPET. Eleven patients with adrenal disorders were also studied. An advantage of using SPET was that the analogue transverse section image showed improvement over the conventional posterior view because the liver activity was well separated from the adrenal. Furthermore, non-adrenal tissue background was virtually eliminated and adrenal depth determination facilitated. (U.K.)

  13. Genetics Home Reference: primary macronodular adrenal hyperplasia

    Science.gov (United States)

    ... Support and Research Foundation: Genetic Changes Found in Cushing's Disease, Adrenal Tumors, and Adrenal Hyperplasia MalaCards: acth-independent ... macronodular adrenal hyperplasia 2 Merck Manual (Home Edition): Cushing ... Adrenal Diseases Foundation: Cushing's Syndrome Orphanet: Cushing syndrome due to ...

  14. Adrenal Chromaffin Cells Exposed to 5-ns Pulses Require Higher Electric Fields to Porate Intracellular Membranes than the Plasma Membrane: An Experimental and Modeling Study.

    Science.gov (United States)

    Zaklit, Josette; Craviso, Gale L; Leblanc, Normand; Yang, Lisha; Vernier, P Thomas; Chatterjee, Indira

    2017-10-01

    Nanosecond-duration electric pulses (NEPs) can permeabilize the endoplasmic reticulum (ER), causing release of Ca 2+ into the cytoplasm. This study used experimentation coupled with numerical modeling to understand the lack of Ca 2+ mobilization from Ca 2+ -storing organelles in catecholamine-secreting adrenal chromaffin cells exposed to 5-ns pulses. Fluorescence imaging determined a threshold electric (E) field of 8 MV/m for mobilizing intracellular Ca 2+ whereas whole-cell recordings of membrane conductance determined a threshold E-field of 3 MV/m for causing plasma membrane permeabilization. In contrast, a 2D numerical model of a chromaffin cell, which was constructed with internal structures representing a nucleus, mitochondrion, ER, and secretory granule, predicted that exposing the cell to the same 5-ns pulse electroporated the plasma and ER membranes at the same E-field amplitude, 3-4 MV/m. Agreement of the numerical simulations with the experimental results was obtained only when the ER interior conductivity was 30-fold lower than that of the cytoplasm and the ER membrane permittivity was twice that of the plasma membrane. A more realistic intracellular geometry for chromaffin cells in which structures representing multiple secretory granules and an ER showed slight differences in the thresholds necessary to porate the membranes of the secretory granules. We conclude that more sophisticated cell models together with knowledge of accurate dielectric properties are needed to understand the effects of NEPs on intracellular membranes in chromaffin cells, information that will be important for elucidating how NEPs porate organelle membranes in other cell types having a similarly complex cytoplasmic ultrastructure.

  15. Evidence for a dihydropyridine-sensitive and conotoxin-insensitive release of noradrenaline and uptake of calcium in adrenal chromaffin cells.

    Science.gov (United States)

    Owen, P. J.; Marriott, D. B.; Boarder, M. R.

    1989-01-01

    1. It has been suggested that neuronal voltage-sensitive calcium channels (VSCC) may be divided into dihydropyridine (DHP)-sensitive (L) and DHP-insensitive (N and T), and that both the L and the N type channels are attenuated by the peptide blocker omega-conotoxin. Here the effects of omega-conotoxin on release of noradrenaline and uptake of calcium in bovine adrenal chromaffin cells were investigated. 2. Release of noradrenaline in response to 25 mM K+, 65 mM K+, 10 nM bradykinin or 10 microM prostaglandin E1 was not affected by omega-conotoxin in the range 10 nM-1 microM. 3. 45Ca2+ uptake stimulated by high K+ and prostaglandin was attenuated by 1 microM nitrendipine and enhanced by 1 microM Bay K 8644; these calcium fluxes were not modified by 20 nM omega-conotoxin. 4. With superfused rat brain striatal slices in the same medium as the above cell studies, release of dopamine in response to 25 mM K+ was attenuated by 20 nM omega-conotoxin. 5. These results show that in these neurone-like cells, release may be effected by calcium influx through DHP-sensitive but omega-conotoxin-insensitive VSCC, a result inconsistent with the suggestion that omega-conotoxin blocks both L-type and N-type neuronal calcium channels. PMID:2470457

  16. Adrenal Insufficiency and Addison's Disease

    Science.gov (United States)

    ... These conditions can lead to an adrenal crisis. Pregnancy Women with adrenal insufficiency who become pregnant are ... can benefit from following a diet rich in sodium. A health care provider or a dietitian can ...

  17. Radiologic evaluation of adrenal glands

    International Nuclear Information System (INIS)

    Pradel, J.; Bruel, J.M.; Taourel, P.; Garnier, T.; Cyteval, C.; Lamarque, J.L.

    1990-01-01

    When a diagnosis of adrenal disorder is suspected on the basis of clinical manifestations and/or laboratory findings, computed tomography (CT) is generally accepted as the imaging procedure of choice for visualization of adrenal areas and localization of lesions. Sonography keeps an important role in discovering adrenal masses during investigation for other suspected abnormality (incidentaloma). 131 I MIBG scintigraphy provides an efficious mean of pheochromocytoma localization and functional characterization. These non invasive procedures have greatly reduced the need for arteriography and venography; adrenal venous sampling is still an useful method for localizing either a tumor or hyperplasia related to primary aldosteronism. MR imaging and CT are nearly equivalent in the detection of adrenal masses: besides MR imaging has a potential for characterization of adrenal masses which might be useful, especially in distinguishing adrenal adenomas from malignant neoplasms, obviating, in some cases, the need of CT guided adrenal biopsy [fr

  18. Adrenal incidentalomas. Primary hyperaldosteronism

    International Nuclear Information System (INIS)

    Murat, A.; Dupas, B.; Zenatti, M.; Aupetit-Faisant, B.; Tenenbaum, F.; Tabarin, A.; Barrat, J.L.; Gosse, P.; Olivier-Puel, F.; Leprat, F.; Trouette, H.; Laurent, F.; Roger, P.

    1993-01-01

    Adrenal incidentalomas are masses incidentally discovered at X rays, ultrasound or MRI examination of the abdomen. In 100 CT scans, one can expect to find two incidentalomas on average. The article by Murat and Dupas is dealing with the strategy of biological, morphological and scintigraphic examinations to be performed in such patients, to assess whether the tumor is of a benign or a malignant nature. Zenatti et al propose a detailed exploration of the aldosterone pathways, since adrenal carcinoma may be responsible for a specific profile of the serum concentrations of mineralo-steroids, compatible with a blockade of the last step of the aldosterone synthesis. The exploration of primary hyperaldosteronism requires biological and imaging techniques. Tabarin et al summarize the main biological parameters and tests available for the diagnosis of this condition and delineate the indications of imaging techniques, associated to hormonal tests to distinguish between adenoma and bilateral adrenal hyperplasia. (author). 104 refs

  19. Stimulated human fibroblast cell survival

    International Nuclear Information System (INIS)

    Smith, B.P.; Gale, K.L.; Einspenner, M.; Greenstock, C.L.; Gentner, N.E.

    1992-01-01

    Techniques for cloning cultured mammalian cells have supported the most universally-accepted method for measuring the induction of lethality by geno-toxicants such as ionizing radiation: the 'survival of colony-forming ability (CFA)' assay. Since most cultured human cell lines exhibit plating efficiency (i.e. the percentage of cells that are capable of reproductively surviving and dividing to form visible colonies) well below 100%, such assays are in essence 'survival of plating efficiency' assays, since they are referred to the plating (or cloning) efficiency of control (i.e. unirradiated) cells. (author). 8 refs., 2 figs

  20. Nonclassic Congenital Adrenal Hyperplasia

    Directory of Open Access Journals (Sweden)

    Selma Feldman Witchel

    2010-01-01

    Full Text Available Nonclassic congenital adrenal hyperplasia (NCAH due to P450c21 (21-hydroxylase deficiency is a common autosomal recessive disorder. This disorder is due to mutations in the CYP21A2 gene which is located at chromosome 6p21. The clinical features predominantly reflect androgen excess rather than adrenal insufficiency leading to an ascertainment bias favoring diagnosis in females. Treatment goals include normal linear growth velocity and “on-time” puberty in affected children. For adolescent and adult women, treatment goals include regularization of menses, prevention of progression of hirsutism, and fertility. This paper will review key aspects regarding pathophysiology, diagnosis, and treatment of NCAH.

  1. Laparoscopic adrenal cortex

    International Nuclear Information System (INIS)

    Peyrolou, A.; Salom, A.; Harguindeguy; Taroco, L.; Ardao, G.; Broli, F. . E mail: andresssss@adinet.com.uy

    2005-01-01

    The paper presents the case of a female patient who carried an aldosterone-secreting tumor of adrenal cortex.In the analysis of diagnosis and para clinical examinations there is particular reference to the laparoscopic surgery mode of treatment.Diagnosis should be established on the basis of clinical and laboratory tests (hypopotassemia and hyperaldosteronism).Tumor topography was confirmed through CT scan, MRI and Scintiscan in left adrenal cortex.Resection was consequently made through laparoscopic surgery.The patients evolution was excellent from the surgical viewpoint,with I levels of blood pressure, potassium and aldosterone returned to normal

  2. Imaging of adrenal disorders

    International Nuclear Information System (INIS)

    Fukuchi, Soitsu

    1982-01-01

    Adrenal scintillation scanning, CT and ultrasonography are compared with the conventional imaging methods. The accuracy of retroperitoneal pneumography and adrenal venography are not high, and they detected only large tumors such as Cushing's syndrome and pheochromocytoma. Scintillation scanning is highly effective for the diagnoses of primary aldosteronism and Cushing's syndrome. However, this technique does not visualize pheochromocytoma or hypopituitarism. CT is noninvasive and of high diagnostic value. It is impossible to diagnose tumors by ultrasonography unless the size is more than 3 cm. (Chiba, N.)

  3. Phosphatidic acid accumulation and catecholamine release in adrenal chromaffin cells: stimulation by high potassium and by nicotine, and effect of a diacylglycerol kinase inhibitor R 59 022.

    Science.gov (United States)

    Owen, P J; Jones, J A; Boarder, M R

    1991-09-01

    Using primary cultures of bovine adrenal chromaffin cells labelled with 32Pi, we show that stimulation with bradykinin, nicotine, or a depolarising concentration of potassium stimulates the accumulation of [32P]phosphatidic acid. The effects of nicotine and potassium are smaller than the effect of bradykinin, and are dependent entirely on extracellular calcium. The diacylglycerol kinase inhibitor R 59 022 attenuates the formation of phosphatidic acid by nicotine and depolarising concentrations of potassium. This inhibitor also blocks the nicotine and potassium stimulation of noradrenaline release from chromaffin cells. Using 45Ca2+ influx studies, we show that the nicotine-evoked calcium influx is also attenuated by R 59 022. These observations contrast with those in another report in which we showed that bradykinin stimulation of either [32P]phosphatidic acid accumulation or noradrenaline release is not affected by R 59 022. It is likely that the calcium influx produced by nicotine and depolarising potassium is blocked by R 59 022 by a mechanism that is independent of its ability to block diacylglycerol kinase. The nicotine- and potassium-stimulated [32P]phosphatidic acid accumulation is a consequence of this calcium influx and presumably reflects calcium activation of either phospholipase C or phospholipase D.

  4. Human embryonic stem cells handbook

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2013-03-01

    Full Text Available After the Nobel prize in physiology or medicine was awarded jointly to Sir John Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent it became imperative to write down the review for a book entirely devoted to human embryonic stem cells (hES, those cells that are a urgent need for researchers, those cells that rekindle the ethical debates and finally, last but not least, those cells whose study paved the way to obtain induced pluripotent stem cells by the OSKC’s Yamanaka method (the OSKC acronim refers, for those not familiar with the topic, to the four stemness genes used to transfect somatic fibroblasts: Oct4, Sox2, Klf4 and c-Myc....

  5. Histologic and Immunohistochemical classification of 41 bovine adrenal gland neoplasms

    DEFF Research Database (Denmark)

    Grossi, Anette Blak; Leifsson, Páll S.; Jensen, Henrik Elvang

    2013-01-01

    . An immunohistochemistry panel consisting of antibodies against melan A, synaptophysin, and CNPase was considered most useful to classify bovine adrenal tumors. However, the distinction between benign and malignant adrenocortical tumors was based on histologic features as in human medicine....

  6. Surgery for adrenal tumors

    International Nuclear Information System (INIS)

    Salamah, S.M.

    2002-01-01

    Objective: To analyze the presentation, localization, pathology, surgical management and outcome of surgery for adrenal gland tumors. Design: Prospective clinico epidemiological study. Place and Duration of Study: The study was conducted at the Department of General Surgery, University Unit, Riyadh medical Complex Kingdom of Saudi Rabia from June, 1991 to may, 2001. Subjects and Methods: A total of 21 cases with adrenal tumors were studied for demographic data, clinical presentation, diagnostic workup, localization, surgical management, pathology and outcome. The outcome of these patients was followed prospectively. Results: The study included 12 female and 9 male patients. The mean age at surgery was 36.7 years. Hypertension (69.%) was the commonest presentation in hypersecretory functional tumors. The localization accuracy for ultrasonography, computerized tomography, MRI and MIBG scan was 95.2%, 98.3% 87.8% and 83.6% respectively. Pheochromocytoma was the most common adrenal pathology observed in 14 (66.6%) cases. The overall morbidity was 19% with no hospital mortality. Complete follow-up of available 19 patients (90.5 %) revealed no tumor recurrence and persistent hypertension in 14.3% cases. Conclusion: surgery on adrenal glands is safe in experienced hands and is recommended in institutes with all backup facilities. (author)

  7. Adrenal pseudocyst. Radiological finds

    International Nuclear Information System (INIS)

    Ortega, E.; Lopez Rasines, G.; Bustos, A.; Otero, M.; Rodriguez, M.I.; Pagola, M.A.

    1991-01-01

    Adrenal cysts are infrequent, the pseudocysts being those that most often produce clinical symptoms. A case of pseudocyst in right suprarenal gland is presented in a young woman with no clinical history, who was studied by means of ultrasound (US) and computerized tomography (CT). (author)

  8. Adrenal insufficiency in pakistani hiv infected patients

    International Nuclear Information System (INIS)

    Afreen, B.; Khan, K.A.; Riaz, A.

    2017-01-01

    Background: Adrenal insufficiency (AI) is the most common endocrine complication among patients with AIDS/HIV infection and there are number of causes of AI in HIV patients. Human immunodeficiency virus directly as well as indirectly destroys adrenal glands. The estimates of its prevalence and severity vary. AI is the most life threatening but readily correctable endocrine complication that occurs in persons with HIV infection. This study was carried out to determine the frequency of Adrenal Insufficiency in HIV patients and their clinical features as proper diagnosis and timely treatment have been shown to improve quality of life and long-term mortality in AIDS patients. Methods: It was a cross sectional survey conducted at HIV clinic and Jinnah Allama Iqbal Institute of Diabetes and Endocrinology, Jinnah Hospital Lahore. Sixty-four HIV positive patients, both male and female, aged above 15 years were included in the study. HIV patients who had recently taken steroids, ketoconazole or rifampicin, determined on history, were excluded from the study. The data was collected on a structured proforma and analysis was performed in SPSS-21.0. Frequency and percentages for adrenal insufficiency and its characteristics were calculated. Chi-square test was used with p<0.05 as statistically significant. Results: In this study, 9 (14.06%) HIV patients were diagnosed with adrenal insufficiency, male to female ratio was 3.5:1 and AI was found statistically significantly associated with fatigue (p<0.008) and weight loss (p<0.001). Conclusion: Adrenal insufficiency was high among the patients with HIV, it was not gender specific but it was found to be associated with fatigue and weight loss. (author)

  9. Zonal variation in the distribution of an alpha 1-acid glycoprotein glycoform receptor in human adrenal cortex

    DEFF Research Database (Denmark)

    Andersen, U O; Bøg-Hansen, T C; Kirkeby, S

    1999-01-01

    receptor was located in the cytoplasm of glomerulosa and outer fasciculata cells. The intensity of the reaction product decreased in the fasciculata, and no staining was seen in inner fasciculata and reticularis. Inhibition with the simple sugars, mannose and GlcNAc confirmed a lectin-like reaction...... specific receptor. The binding of alpha 1-acid glycoprotein glycoform B and alpha 1-acid glycoprotein glycoform C to the glycoform specific receptor is inhibited by the steroid hormones cortisone, aldosterone, estradiol and progesterone but not by testosterone. The pronounced changes in the distribution...

  10. Effects of ACTH on RNA synthesis and migration in the adrenal cortex cells of the young rat, as shown by radioautography

    Energy Technology Data Exchange (ETDEWEB)

    Magalhaes, M.C.; Vitor, A.B.; Magalhaes, M.M.

    1986-01-01

    The effect of ACTH on the RNA synthesis in adrenal zona fasciculata cells of the young rat were studied by light and electron microscope radioautography. Two units of ACTH were administered sc to animals and immediately followed by an iv injection of (/sup 3/)uridine. ACTH-injected and control rats, which received the isotope alone, were sacrificed at various time intervals. Labelling over extranucleolar areas was higher in the ACTH-treated animals at 20 min, then becoming lower than in the controls at 60 min and 24 h. Nucleolar radioactivity, however, was consistently decreased by ACTH at all experimental times. Apart from these changes in the rate of synthesis, the over-all curves of labelling were similar to those in the control animals with a striking peak at 1 h. The short-term increase in extranucleolar RNA synthesis observed after ACTH injection was considered to be consistent with the hypothesis that an enhanced extranucleolar synthesis of mRNA takes place early in stimulated animals and is associated with the synthesis of steroidogenic proteins. On the other hand, the relatively decreased uridine uptake of the label by the nucleolus in ACTH-treated animals, suggests an inhibition of nucleolar transcription with diminished pre-rRNA formation in treated animals.

  11. Effects of ACTH on RNA synthesis and migration in the adrenal cortex cells of the young rat, as shown by radioautography

    International Nuclear Information System (INIS)

    Magalhaes, M.C.; Vitor, A.B.; Magalhaes, M.M.

    1986-01-01

    The effect of ACTH on the RNA synthesis in adrenal zona fasciculata cells of the young rat were studied by light and electron microscope radioautography. Two units of ACTH were administered sc to animals and immediately followed by an iv injection of [ 3 ]uridine. ACTH-injected and control rats, which received the isotope alone, were sacrificed at various time intervals. Labelling over extranucleolar areas was higher in the ACTH-treated animals at 20 min, then becoming lower than in the controls at 60 min and 24 h. Nucleolar radioactivity, however, was consistently decreased by ACTH at all experimental times. Apart from these changes in the rate of synthesis, the over-all curves of labelling were similar to those in the control animals with a striking peak at 1 h. The short-term increase in extranucleolar RNA synthesis observed after ACTH injection was considered to be consistent with the hypothesis that an enhanced extranucleolar synthesis of mRNA takes place early in stimulated animals and is associated with the synthesis of steroidogenic proteins. On the other hand, the relatively decreased uridine uptake of the label by the nucleolus in ACTH-treated animals, suggests an inhibition of nucleolar transcription with diminished pre-rRNA formation in treated animals. (author)

  12. Primary Adrenal Lymphoma Infiltrating in to Pancreas: A Rare Cause of Adrenomegaly

    Directory of Open Access Journals (Sweden)

    Lovelesh Kumar Nigam

    2017-03-01

    Full Text Available Primary adrenal lymphoma is a rare entity and may be suspected in patients having bilateral adrenal masses, with/without lymphadenopathy, and with/without adrenal insufficiency. We report a rare case of a 45-year-old man who presented with pain in the abdomen, with no signs of adrenal insufficiency and bilateral adrenal masses on imaging. Light microscopy findings with immunohistochemistry and flow cytometry confirmed the diagnosis of diffuse large B-cell lymphoma. The patient was offered cyclophosphamide, adriamycin, vincristine, and prednisolone chemotherapy regimen and doing well till the last follow-up. [J Interdiscip Histopathol 2017; 5(1.000: 25-28

  13. Congenital Adrenal Hyperplasia: Unresolved Issues.

    Science.gov (United States)

    Yau, Mabel; Khattab, Ahmed; Poppas, Dix; Ghizzoni, Lucia; New, Maria

    2016-01-01

    Congenital adrenal hyperplasia (CAH) describes a family of disorders that comes from enzymatic deficiencies in cortisol production, with 21-hydroxylase deficiency causing ∼90% of cases. Distinction is made between the severe classical form and milder nonclassical form of CAH. Molecular genetic analysis is used to confirm the hormonal diagnosis. A high rate of genotype-phenotype disconcordance has been found in 21-hydroxylase deficiency. The goal of treatment is to replace with synthetic glucocorticoids and mineralocorticoids and suppress adrenal androgen production. The treatment of patients affected with nonclassical CAH, particularly males, remains controversial. Variable synthetic glucocorticoids are used and new modes of glucocorticoid delivery are under investigation. To improve height, growth hormone and other adjuvant therapies are employed. Long-term outcomes of genital surgery using modern techniques in females affected with classical CAH continue to be investigated. Prenatal treatment with dexamethasone is available to avoid ambiguous genitalia in these females. Although studies have shown its safety to mother and fetus, prenatal treatment is still regarded as experimental. Currently, prenatal diagnosis of CAH can only be obtained through invasive methods. Recently, the detection of cell-free fetal DNA in maternal plasma has made it possible to make this diagnosis earlier and noninvasively. © 2016 S. Karger AG, Basel.

  14. A pilot study to assess the feasibility of measurement of adrenal gland volume by magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Grant, Lee A.; Dixon, Adrian K. (Dept. of Radiology, Cambridge Univ. Teaching Hospitals NHS Foundation Trust, Cambridge (United Kingdom)), e-mail: leegrant100@gmail.com; Napolitano, Antonella; McHugh, Simon M. (GlaxoSmithKline RandD, Clinical Unit Cambridge, Addenbrooke' s Centre for Clinical Investigation, Addenbrooke' s Hospital, Cambridge (United Kingdom)); Miller, Sam (Analysis Applications Research Group, GSK RandD, Harlow, Essex (United Kingdom)); Stephens, Kimberley (Discovery Statistics, GSK RandD, Harlow, Essex (United Kingdom))

    2010-01-15

    Background: Repeated computed tomography (CT) assessment of the adrenal glands is associated with a significant radiation burden. The increasing capabilities of magnetic resonance (MR) volumetric analysis of the adrenals make this a potentially alternative technique in man. Purpose: To determine whether MR imaging could be used to measure adrenal volume, and to determine the intra- and interobserver variation and repeatability of MR volume imaging of adrenals in healthy human subjects. Material and Methods: This was a single-cohort, sequential design, three-part study involving four MRI examinations per subject following ethical approval and informed consent. Information was collected on four healthy subjects (three male and one female). Two different investigators estimated the area of the adrenal gland for each of the 3-mm contiguous slices (and consequently adrenal volume). In order to estimate inter- and intrareader variability, a repeated-measures mixed model was fitted with adrenal volume as the dependent variable. In order to estimate any bias between readers, Bland-Altman methodology was applied. Results: Intraobserver variation for adrenal gland volume is approximately 5% of a 3-cm3 adrenal gland. Interobserver variation is approximately 9% of a 3-cm3 adrenal gland. Potential variation in measurement for adrenal volume from all sources equates to approximately 14% of a 3-cm3 adrenal gland. Verification of image reading by a second investigator (consensus reading) reduces variability. Conclusion: Analysis of adrenal gland volume using MRI is a potentially reliable technique that could be used to assess a pathological change in adrenal size

  15. Incorporation of radioactive sulfate (Na235SO4) by mouse adrenal medullary cells as shown by radioautography

    International Nuclear Information System (INIS)

    Munhoz, C.O.G.; Merzel, J.

    1977-01-01

    Preliminary radioautographic results, observed in the adreno-medullary cells of mice injected with radiosulfate, suggested that the cells might synthetize sulfur-containing compounds. Only further studies could make-clear if sulfate groups are linked to carbohydrate molecules and/or chromaffin granules [pt

  16. Alveolar Soft Part Sarcoma Presenting as Hypervascular Adrenal Metastasis

    Science.gov (United States)

    Goroshi, Manjunath; Lila, Anurag R.; Bandgar, Tushar; Shah, Nalini S.

    2018-01-01

    Hypervascular adrenal masses include pheochromocytoma, metastases caused by clear renal cell carcinoma/hepatocellular carcinoma. Alveolar soft part sarcoma (ASPS) causing hypervascular metastases is not described in the literature. Here, we describe the first case of ASPS presenting as hypervascular metastasis. Our case was a 23-year-old male incidentally detected right adrenal mass during the evaluation of pain in the abdomen. On computed tomography (CT), adrenal mass showed bright enhancement in early arterial phase (unenhanced Hounsfield unit [HU]-45.3; arterial phase HU-158.2). 18- flurodeoxyglucose positron emission tomography/CT showed multiple lesions and was confirmed histologically to be due to ASPS. PMID:29398970

  17. Tuft (caveolated) cells in two human colon carcinoma cell lines.

    OpenAIRE

    Barkla, D. H.; Whitehead, R. H.; Foster, H.; Tutton, P. J.

    1988-01-01

    The presence of an unusual cell type in two human colon carcinoma cell lines is reported. The cells show the same morphology as "tuft" (caveolated) cells present in normal gastrointestinal epithelium. Tuft cells were seen in cell line LIM 1863 growing in vitro and in human colon carcinoma cell line LIM 2210 growing as subcutaneous solid tumour xenografts in nude mice. Characteristic morphologic features of tuft cells included a wide base, narrow apex and a tuft of long microvilli projecting f...

  18. Hyponatraemia secondary to nivolumab-induced primary adrenal failure

    Directory of Open Access Journals (Sweden)

    Harris Trainer

    2016-11-01

    Full Text Available Checkpoint inhibitors, such as ipilimumab and pembrolizumab, have transformed the prognosis for patients with advanced malignant melanoma and squamous non-small-cell lung cancer, and their use will only expand as experience is gained in a variety of other malignancies, for instance, renal and lymphoma. As the use of checkpoint inhibitors increases, so too will the incidence of their unique side effects, termed immune-related adverse events (irAEs, which can affect dermatological, gastrointestinal, hepatic, endocrine and other systems. Nivolumab is a monoclonal antibody that blocks the human programmed death receptor-1 ligand (PD-L1 found on many cancer cells and is licensed for the treatment of advanced malignant melanoma. We describe the first case of nivolumab-induced adrenalitis resulting in primary adrenal failure presenting with hyponatraemia in a 43-year-old man with malignant melanoma. The case highlights the potentially life-threatening complications of checkpoint inhibitors and the need for patient education and awareness of irAEs among the wider clinical community because such side effects require prompt recognition and treatment.

  19. ACTH-induced caveolin-1 tyrosine phosphorylation is related to podosome assembly in Y1 adrenal cells

    International Nuclear Information System (INIS)

    Colonna, Cecilia; Podesta, Ernesto J.

    2005-01-01

    Y1 adrenocortical cells respond to ACTH with a characteristic rounding-up that facilitates cAMP signaling, critical for transport of cholesterol to the mitochondria and increase in steroid secretion. We here demonstrate that caveolin-1 participates in coupling activation of protein kinase A (PKA) to the control of cell shape. ACTH/8-Br-cAMP induced reorganization of caveolin-1-positive structures in correlation with the cellular rounding-up. Concomitant with this change, there was an increase in the phosphorylation of caveolin-1 (Tyr-14) localized at focal adhesions (FA) with reorganization of FA to rounded, ringlike structures. Colocalization with phalloidin showed that phosphocaveolin is present at the edge of actin filaments and that after ACTH stimulation F-actin dots at the cell periphery become surrounded by phosphocaveolin-1. These observations along with electron microscopy studies revealed these structures as podosomes. Podosome assembly was dependent on both PKA and tyrosine kinase activities because their formation was impaired after treatment with specific inhibitors [myristoylated PKI (mPKI) or PP2, respectively] previous to ACTH/8-Br-cAMP stimulation. These results show for the first time that ACTH induces caveolin-1 phosphorylation and podosome assembly in Y1 cells and support the view that the morphological and functional responses to PKA activation in steroidogenic cells are related to cytoskeleton dynamics

  20. Transforming growth factor-beta, but not ciliary neurotrophic factor, inhibits DNA synthesis of adrenal medullary cells in vitro

    DEFF Research Database (Denmark)

    Wolf, N; Krohn, K; Bieger, S

    1999-01-01

    by the neuroendocrine chromaffin cells, which also express the transforming growth factor-beta receptor type II. In contrast to the developmentally related sympathetic neurons, chromaffin cells continue to proliferate throughout postnatal life. Using 5-bromo-2'-deoxyuridine pulse labeling and tyrosine hydroxylase...... immunocytochemistry as a marker for young postnatal rat chromaffin cells, we show that treatment with fibroblast growth factor-2 (1 nM) and insulin-like growth factor-II (10 nM) increased the fraction of 5-bromo-2'-deoxyuridine-labeled nuclei from 1% to about 40% of the cells in the absence of serum. In the presence...... of fibroblast growth factor-2 and insulin-like growth factor-II, transforming growth factor-beta1 (0.08 nM) reduced 5-bromo-2'-deoxyuridine labeling by about 50%, without interfering with chromaffin cell survival or death. Doses lower and higher than 0.08 nM were less effective. Similar effects were seen...

  1. Isolated adrenal paracoccidioidomycosis: Case report

    International Nuclear Information System (INIS)

    Uribe Castro, Jorge Ricardo; Quintana, Humberto; Puentes, Alix Sofia and others

    2011-01-01

    Even though paracoccidioidomycosis has a relatively high prevalence in Latin America in a systemic form, isolated cases, especially compromising the adrenal glands, are uncommon, with only two reported cases. In this article, we report the case of a 55 year-old male with clinical manifestations of adrenal insufficiency. The only imaging finding was the presence of bilateral adrenal masses. The biopsy showed Paracoccidioides brasiliensis infection.

  2. Human glomerular epithelial cell proteoglycans

    International Nuclear Information System (INIS)

    Thomas, G.J.; Jenner, L.; Mason, R.M.; Davies, M.

    1990-01-01

    Proteoglycans synthesized by cultures of human glomerular epithelial cells have been isolated and characterized. Three types of heparan sulfate were detected. Heparan sulfate proteoglycan I (HSPG-I; Kav 6B 0.04) was found in the cell layer and medium and accounted for 12% of the total proteoglycans synthesized. HSPG-II (Kav 6B 0.25) accounted for 18% of the proteoglycans and was located in the medium and cell layer. A third population (9% of the proteoglycan population), heparan sulfate glycosaminoglycan (HS-GAG; Kav 6B 0.4-0.8), had properties consistent with single glycosaminoglycan chains or their fragments and was found only in the cell layer. HSPG-I and HSPG-II from the cell layer had hydrophobic properties; they were released from the cell layer by mild trypsin treatment. HS-GAG lacked these properties, consisted of low-molecular-mass heparan sulfate oligosaccharides, and were intracellular. HSPG-I and -II released to the medium lacked hydrophobic properties. The cells also produced three distinct types of chondroitin sulfates. The major species, chondroitin sulfate proteoglycan I (CSPG-I) eluted in the excluded volume of a Sepharose CL-6B column, accounted for 30% of the proteoglycans detected, and was found in both the cell layer and medium. Cell layer CSPG-I bound to octyl-Sepharose. It was released from the cell layer by mild trypsin treatment. CSPG-II (Kav 6B 0.1-0.23) accounted for 10% of the total 35S-labeled macromolecules and was found predominantly in the culture medium. A small amount of CS-GAG (Kav 6B 0.25-0.6) is present in the cell extract and like HS-GAG is intracellular. Pulse-chase experiments indicated that HSPG-I and -II and CSPG-I and -II are lost from the cell layer either by direct release into the medium or by internalization where they are metabolized to single glycosaminoglycan chains and subsequently to inorganic sulfate

  3. Unilateral testicular tumour associated to congenital adrenal hyperplasia: Failure of specific tumoral molecular markers to discriminate between adrenal rest and leydigioma.

    Science.gov (United States)

    Fenichel, P; Bstandig, B; Roger, C; Chevallier, D; Michels, J-F; Sadoul, J-L; Hieronimus, S; Brucker-Davis, F

    2008-11-01

    Testicular adrenal rest tumours are frequently associated with congenital adrenal hyperplasia (CAH). These ACTH-dependent tumours cannot be easily distinguished histologically from Leydig-cell tumours. We report the case of a 30-year-old man who was explored for infertility, azoospermia and unilateral testicular tumour. High levels of 17-OH progesterone and ACTH, low cortisol and undetectable gonadotropins levels, associated to bilateral adrenal hyperplasia, led to the diagnosis of CAH by 21-OH deficiency with a composite heterozygoty. The testicular tumour was first considered as adrenal rest. However, histological analysis of this unilateral painful tumour showed a steroid-hormone-secreting cell proliferation with atypical and frequent mitosis. To discriminate between a benign adrenal rest tumour and a possible malignant leydigioma, tumoral expression of specific gene products was analyzed by RT-PCR. No 11-beta-hydroxylase nor ACTH receptor mRNAs could be found in the tumour, which did not behave like usual adrenal rest cells. For this unilateral testicular tumour, the lack of adrenal-specific markers associated with a high rate of mitosis and pleiomorphism supported a leydigian origin with malignant potential. However, lack of tumoral LH-R mRNA expression and a tumour-free 3-year follow-up led us to retain the diagnosis of adrenal rest tumour with loss of adrenal gene expression and progressive autonomous behaviour.

  4. Adrenal imaging with technetium-99m-labelled low density lipoproteins

    International Nuclear Information System (INIS)

    Isaacsohn, J.L.; Lees, A.M.; Lees, R.S.; Strauss, H.W.; Barlai-Kovach, M.; Moore, T.J.

    1986-01-01

    Evaluation of adrenal cortical function by external imaging is currently accomplished by injection of radiolabelled analogs of cholesterol. Although the adrenals do utilized exogenous cholesterol for steroid hormone synthesis, the cholesterol is delivered to the glands not as free cholesterol but through the uptake of low density lipoproteins (LDL), which are subsequently degraded within the adrenal cortical cells to provide cholesterol. Thus, we sought to assess the use of /sup 99m/Tc-labelled LDL injected into rabbits to obtain external images of the adrenal glands. Adrenal images of all nine rabbits tested were obtained within 18 to 21 hours after injection of /sup 99m/Tc-LDL. Seven of the rabbits were subjected to adrenal cortical suppression with dexamethasone and then all nine rabbits were imaged a second time. In the untreated animals, visualization of the adrenal glands was accompanied by normal serum cortisol concentrations and accumulation of radiolabel in the adrenals, whereas in the dexamethasone-treated animals, lack of visualization of the adrenal glands was correlated with low serum cortisols, and greatly decreased accumulation of the radionuclide in the adrenals. These findings demonstrate for the first time that LDL, when labelled with /sup 99m/Tc, can be used to evaluate adrenal cortical function by external imaging

  5. Differential regulation of histamine- and bradykinin-stimulated phospholipase C in adrenal chromaffin cells: evidence for involvement of different protein kinase C isoforms.

    Science.gov (United States)

    Sena, C M; Rosário, L M; Parker, P J; Patel, V; Boarder, M R

    1996-03-01

    In this report we investigate the isoforms of protein kinase C (PKC) present in cultured adrenal chromaffin cells with respect to their modulation by treatment with phorbol ester and their possible differential involvement in the regulation of responses to histamine and bradykinin. The presence of individual isoforms of PKC was investigated by using eight isoform specific antisera, as a result of which PKC-alpha, epsilon, and zeta were identified. To characterize down-regulation of these enzymes, cells were incubated for 6-48 h with 1 microM phorbol myristate acetate (PMA). PKC-epsilon down-regulated more rapidly than PKC-alpha. At 12 h, PMA pretreatment, for example, PKC-epsilon was maximally down-regulated (23 +/- 4% of controls), whereas PKC-alpha was unchanged. PKC-alpha showed partial down-regulation by 24 h of PMA pretreatment. PKC-zeta did not down-regulate at any of the times tested. Translocation from cytosol to membrane in response to PMA was also more rapid for PKC-epsilon than for PKC-alpha. The accumulation of total 3H-inositol (poly) phosphates in response to bradykinin or histamine was essentially abolished by prior treatment with 10-min PMA treatment (1 microM). However, with 12-h exposure to PMA, the bradykinin response was restored to the level seen with no prior PMA exposure. The histamine response showed no recovery by 12 h of PMA, but showed partial recovery by 24 h of PMA pretreatment. These observations showed that the restoration of the response to bradykinin corresponds to the loss of PKC-epsilon, whereas the restoration of the histamine response corresponds to the loss of PKC-alpha. This picture was confirmed with further studies on cytosolic Ca2+. The results show that chromaffin cells exhibit an unusual pattern of down-regulation of PKC isoforms on prolonged exposure to PMA, and that there is a differential effect of exposure to PMA on the histamine and bradykinin responses, suggesting that different PLC-linked receptors in chromafin

  6. Effects of Carbenoxolone on the Canine Pituitary-Adrenal Axis.

    Science.gov (United States)

    Teshima, Takahiro; Matsumoto, Hirotaka; Okusa, Tomoko; Nakamura, Yumi; Koyama, Hidekazu

    2015-01-01

    Cushing's disease caused by pituitary corticotroph adenoma is a common endocrine disease in dogs. A characteristic biochemical feature of corticotroph adenomas is their relative resistance to suppressive negative feedback by glucocorticoids. The abnormal expression of 11beta-hydroxysteroid dehydrogenase (11HSD), which is a cortisol metabolic enzyme, is found in human and murine corticotroph adenomas. Our recent studies demonstrated that canine corticotroph adenomas also have abnormal expression of 11HSD. 11HSD has two isoforms in dogs, 11HSD type1 (HSD11B1), which converts cortisone into active cortisol, and 11HSD type2 (HSD11B2), which converts cortisol into inactive cortisone. It has been suggested that glucocorticoid resistance in corticotroph tumors is related to the overexpression of HSD11B2. Therefore it was our aim to investigate the effects of carbenoxolone (CBX), an 11HSD inhibitor, on the healthy dog's pituitary-adrenal axis. Dogs were administered 50 mg/kg of CBX twice each day for 15 days. During CBX administration, no adverse effects were observed in any dogs. The plasma adrenocorticotropic hormone (ACTH), and serum cortisol and cortisone concentrations were significantly lower at day 7 and 15 following corticotropin releasing hormone stimulation. After completion of CBX administration, the HSD11B1 mRNA expression was higher, and HSD11B2 mRNA expression was significantly lower in the pituitaries. Moreover, proopiomelanocortin mRNA expression was lower, and the ratio of ACTH-positive cells in the anterior pituitary was also significantly lower after CBX treatment. In adrenal glands treated with CBX, HSD11B1 and HSD11B2 mRNA expression were both lower compared to normal canine adrenal glands. The results of this study suggested that CBX inhibits ACTH secretion from pituitary due to altered 11HSD expressions, and is potentially useful for the treatment of canine Cushing's disease.

  7. Differential regulation by agonist and phorbol ester of cloned m1 and m2 muscarinic acetylcholine receptors in mouse Y1 adrenal cells and in Y1 cells deficient in cAMP-dependent protein kinase

    International Nuclear Information System (INIS)

    Scherer, N.M.; Nathanson, N.M.

    1990-01-01

    Cloned muscarinic acetylcholine m1 and m2 receptors were expressed in stably transfected mouse Y1 adrenal cells and in a variant Y1 line, Kin-8, which is deficient in cAMP-dependent protein kinase activity (PKA - ). m1 and m2 receptors were rapidly internalized following exposure of transfected PKA + or PKA - cells to the muscarinic agonist carbachol. Thus, agonist-dependent internalization of m1 and m2 did not require PKA activity. A differential effect of PKA on regulation by agonist of the m2 receptor, but not the m1 receptor, was unmasked in PKA - cells. These data indicate that the basal activity of PKA may modulate the agonist-dependent internalization of the m2 receptor, but not the m1 receptor. The internalization of the m1 and m2 receptors in both PKA + and PKA - cells was accompanied by desensitization of functional responses. Exposure of PKA + cells to 10 -7 M phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, resulted in a 30 ± 9% decrease in the number of m1 receptors on the cell surface. The m2 receptor was not internalized following treatment of either PKA + or PKA - cells with PMA. Thus, the m1 and m2 receptors show differential sensitivity to internalization by PMA. Agonist-dependent internalization of the m1 receptor appeared to be independent of activation of PKC because (1) agonist-dependent internalization of m1 was not attenuated in PKA - cells, (2) the rate and extent of internalization of m1 in cells exposed to PMA were less than those in cells exposed to agonist, and (3) treatment of cells with concanavalin A selectivity blocked internalization of m1 in cells exposed to PMA, but not to agonist. The effects of agonist and PMA on receptor internalization were not additive. Exposure of PKA + or PKA - cells to PMA reduced the magnitude of pilocarpine-stimulated PI hydrolysis by about 25%

  8. DNA repair in human cells

    International Nuclear Information System (INIS)

    Regan, J.D.; Carrier, W.L.; Kusano, I.; Furuno-Fukushi, I.; Dunn, W.C. Jr.; Francis, A.A.; Lee, W.H.

    1982-01-01

    Our primary objective is to elucidate the molecular events in human cells when cellular macromolecules such as DNA are damaged by radiation or chemical agents. We study and characterize (i) the sequence of DNA repair events, (ii) the various modalities of repair, (iii) the genetic inhibition of repair due to mutation, (iv) the physiological inhibition of repair due to mutation, (v) the physiological inhibition of repair due to biochemical inhibitors, and (vi) the genetic basis of repair. Our ultimate goals are to (i) isolate and analyze the repair component of the mutagenic and/or carcinogenic event in human cells, and (ii) elucidate the magnitude and significance of this repair component as it impinges on the practical problems of human irradiation or exposure to actual or potential chemical mutagens and carcinogens. The significance of these studies lies in (i) the ubiquitousness of repair (most organisms, including man, have several complex repair systems), (ii) the belief that mutagenic and carcinogenic events may arise only from residual (nonrepaired) lesions or that error-prone repair systems may be the major induction mechanisms of the mutagenic or carcinogenic event, and (iii) the clear association of repair defects and highly carcinogenic disease states in man [xeroderma pigmentosum (XP)

  9. Cushing's syndrome and fetal features resurgence in adrenal cortex-specific Prkar1a knockout mice.

    Directory of Open Access Journals (Sweden)

    Isabelle Sahut-Barnola

    2010-06-01

    Full Text Available Carney complex (CNC is an inherited neoplasia syndrome with endocrine overactivity. Its most frequent endocrine manifestation is primary pigmented nodular adrenocortical disease (PPNAD, a bilateral adrenocortical hyperplasia causing pituitary-independent Cushing's syndrome. Inactivating mutations in PRKAR1A, a gene encoding the type 1 alpha-regulatory subunit (R1alpha of the cAMP-dependent protein kinase (PKA have been found in 80% of CNC patients with Cushing's syndrome. To demonstrate the implication of R1alpha loss in the initiation and development of PPNAD, we generated mice lacking Prkar1a specifically in the adrenal cortex (AdKO. AdKO mice develop pituitary-independent Cushing's syndrome with increased PKA activity. This leads to autonomous steroidogenic genes expression and deregulated adreno-cortical cells differentiation, increased proliferation and resistance to apoptosis. Unexpectedly, R1alpha loss results in improper maintenance and centrifugal expansion of cortisol-producing fetal adrenocortical cells with concomitant regression of adult cortex. Our data provide the first in vivo evidence that loss of R1alpha is sufficient to induce autonomous adrenal hyper-activity and bilateral hyperplasia, both observed in human PPNAD. Furthermore, this model demonstrates that deregulated PKA activity favors the emergence of a new cell population potentially arising from the fetal adrenal, giving new insight into the mechanisms leading to PPNAD.

  10. The human airway epithelial basal cell transcriptome.

    Directory of Open Access Journals (Sweden)

    Neil R Hackett

    2011-05-01

    Full Text Available The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population.Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the "human airway basal cell signature" as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels.The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of the stem/progenitor cells of the human airway epithelium.

  11. [Adrenal insufficiency of the adult].

    Science.gov (United States)

    Jublanc, C; Bruckert, E

    2016-12-01

    Adrenal insufficiency is a rare but life-threatening disorder. Clinical manifestations include fatigue, weight loss, gastrointestinal manifestations and skin hyperpigmentation, the latter being specific of primary adrenal failure. Because of non-specific clinical features of this rare disorder, diagnosis can be delayed and adrenal failure be revealed by an acute crisis. Adrenal insufficiency can be primary (Addison disease), most frequently autoimmune, or secondary, resulting from long term administration of exogenous glucocorticoids or more rarely from pituitary disorders. Monitoring of substitutive treatment is now well codified. Patient education is very important in this chronic disease that remains associated with a persistent high risk of adrenal crisis. Copyright © 2016 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  12. Human regulatory B cells control the TFH cell response.

    Science.gov (United States)

    Achour, Achouak; Simon, Quentin; Mohr, Audrey; Séité, Jean-François; Youinou, Pierre; Bendaoud, Boutahar; Ghedira, Ibtissem; Pers, Jacques-Olivier; Jamin, Christophe

    2017-07-01

    Follicular helper T (T FH ) cells support terminal B-cell differentiation. Human regulatory B (Breg) cells modulate cellular responses, but their control of T FH cell-dependent humoral immune responses is unknown. We sought to assess the role of Breg cells on T FH cell development and function. Human T cells were polyclonally stimulated in the presence of IL-12 and IL-21 to generate T FH cells. They were cocultured with B cells to induce their terminal differentiation. Breg cells were included in these cultures, and their effects were evaluated by using flow cytometry and ELISA. B-cell lymphoma 6, IL-21, inducible costimulator, CXCR5, and programmed cell death protein 1 (PD-1) expressions increased on stimulated human T cells, characterizing T FH cell maturation. In cocultures they differentiated B cells into CD138 + plasma and IgD - CD27 + memory cells and triggered immunoglobulin secretions. Breg cells obtained by Toll-like receptor 9 and CD40 activation of B cells prevented T FH cell development. Added to T FH cell and B-cell cocultures, they inhibited B-cell differentiation, impeded immunoglobulin secretions, and expanded Foxp3 + CXCR5 + PD-1 + follicular regulatory T cells. Breg cells modulated IL-21 receptor expressions on T FH cells and B cells, and their suppressive activities involved CD40, CD80, CD86, and intercellular adhesion molecule interactions and required production of IL-10 and TGF-β. Human Breg cells control T FH cell maturation, expand follicular regulatory T cells, and inhibit the T FH cell-mediated antibody secretion. These novel observations demonstrate a role for the Breg cell in germinal center reactions and suggest that deficient activities might impair the T FH cell-dependent control of humoral immunity and might lead to the development of aberrant autoimmune responses. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  13. Endocannabinoids and Human Sperm Cells

    Directory of Open Access Journals (Sweden)

    Giovanna Zolese

    2010-10-01

    Full Text Available N-acylethanolamides (NAEs are naturally occurring signaling lipids consisting of amides and esters of long-chain polyunsaturated fatty acids. Usually they are present in a very small amounts in many mammalian tissues and cells, including human reproductive tracts and fluids. Recently, the presence of N-arachidonoylethanolamide (anandamide, AEA, the most characterised member of endocannabinoids, and its congeners palmitoylethanolamide (PEA and oleylethanolamide (OEA in seminal plasma, oviductal fluid, and follicular fluids was demonstrated. AEA has been shown to bind not only type-1 (CB1 and type-2 (CB2 cannabinoid receptors, but also type-1 vanilloid receptor (TRPV1, while PEA and OEA are inactive with respect to classical cannabinoid CB1 and CB2 but activate TRPV1 or peroxisome proliferator activate receptors (PPARs. This review concerns the most recent experimental data on PEA and OEA, endocannabinoid-like molecules which appear to exert their action exclusively on sperm cells with altered features, such as membrane characteristics and kinematic parameters. Their beneficial effects on these cells could suggest a possible pharmacological use of PEA and OEA on patients affected by some forms of idiopathic infertility.

  14. The reaction of the cardio-vascular and sympathico-adrenal systems to intellectual activity with emotional stress. [human operator performance

    Science.gov (United States)

    Tomashevskaya, L. I.

    1975-01-01

    The effect of emotiogenic factors on an operator's intellectual activity were studied for differing working regimes on an experimental control panel that provided for light, sonic, and electrocutaneous stimuli. The latter stimulus was activated automatically if the subject gave an incorrect response. It was shown that the working capacity of the operator under stress depends to a great extent on the effect of the emotiogenic factors on the individual functioning characteristics of the cardiovascular and sympathetic-adrenal systems. Moral, intellectual, willpower, emotional, and other personality traits are decisive factors of operator function.

  15. Stem cells in the human breast

    DEFF Research Database (Denmark)

    Petersen, Ole William; Polyak, Kornelia

    2010-01-01

    The origins of the epithelial cells participating in the development, tissue homeostasis, and cancer of the human breast are poorly understood. However, emerging evidence suggests a role for adult tissue-specific stem cells in these processes. In a hierarchical manner, these generate the two main...... mammary cell lineages, producing an increasing number of cells with distinct properties. Understanding the biological characteristics of human breast stem cells and their progeny is crucial in attempts to compare the features of normal stem cells and cancer precursor cells and distinguish these from...... nonprecursor cells and cells from the bulk of a tumor. A historical overview of research on human breast stem cells in primary tissue and in culture reveals the progress that has been made in this area, whereas a focus on the cell-of-origin and reprogramming that occurs during neoplastic conversion provides...

  16. Satellite cells in human skeletal muscle plasticity.

    Science.gov (United States)

    Snijders, Tim; Nederveen, Joshua P; McKay, Bryon R; Joanisse, Sophie; Verdijk, Lex B; van Loon, Luc J C; Parise, Gianni

    2015-01-01

    Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodeling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodeling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodeling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

  17. Imaging findings of neonatal adrenal disorders

    International Nuclear Information System (INIS)

    Yoon, Hye Kyung; Han, Bo Kyung; Lee, Min Hee

    1999-01-01

    In newborn infants, normal adrenal glands are characterized by a relatively thin echogenic center surrounded by a thick, hypoechoic cortical rim as seen on ultrasound (US). Various disorders involving the neonatal adrenal gland include adrenal hemorrhage, hyperplasia, cyst, Wolman's disease, and congenital neuroblastoma. Adrenal hemorrhage is the most common cause of an adrenal mass in the neonate, though differentiation between adrenal hemorrhage and neuroblastoma is in many cases difficult. We describe characteristic US, CT and MR imaging findings in neonates with various adrenal disorders

  18. Imaging findings of neonatal adrenal disorders

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hye Kyung; Han, Bo Kyung; Lee, Min Hee [Sungkyunkwan Univ. College of Medicine, Seoul (Korea, Republic of)

    1999-01-01

    In newborn infants, normal adrenal glands are characterized by a relatively thin echogenic center surrounded by a thick, hypoechoic cortical rim as seen on ultrasound (US). Various disorders involving the neonatal adrenal gland include adrenal hemorrhage, hyperplasia, cyst, Wolman's disease, and congenital neuroblastoma. Adrenal hemorrhage is the most common cause of an adrenal mass in the neonate, though differentiation between adrenal hemorrhage and neuroblastoma is in many cases difficult. We describe characteristic US, CT and MR imaging findings in neonates with various adrenal disorders.

  19. Diagnosis of adrenal tumors

    Energy Technology Data Exchange (ETDEWEB)

    Richter, E.I.; Loesch, H.

    1987-09-01

    Of 155 patients with adrenal disorders, 120 (77%) were correctly diagnosed as negative. There were no correlations between the results of computer tomography and phlebography or between computer tomography and laboratory tests. In 31 patients (20%) a correct diagnosis was obtained and these patients were sent to surgery. Four cases (3%) were shown to be false positive. In these cases (with one exception), both the computer tomography and phlebography results had been overinterpreted. Computer tomography was shown to be a method of high sensitivity and almost as great specificity. Tumors cannot be distinguished by phlebography; only pheochromocytoma shows a characteristic alteration of vessels in arteriograms. In general, an accurate diagnosis requires positive angiography (arterio- or phlebography) results and clear evidence of elevated hormone levels. Only then is surgery indicated.

  20. Diagnosis of adrenal tumors

    International Nuclear Information System (INIS)

    Richter, E.I.; Loesch, H.

    1987-01-01

    Of 155 patients with adrenal disorders, 120 (77%) were correctly diagnosed as negative. There were no correlations between the results of computer tomography and phlebography or between computer tomography and laboratory tests. In 31 patients (20%) a correct diagnosis was obtained and these patients were sent to surgery. Four cases (3%) were shown to be false positive. In these cases (with one exception), both the computer tomography and phlebography results had been overinterpreted. Computer tomography was shown to be a method of high sensitivity and almost as great specificity. Tumors cannot be distinguished by phlebography; only pheochromocytoma shows a characteristic alteration of vessels in arteriograms. In general, an accurate diagnosis requires positive angiography (arterio- or phlebography) results and clear evidence of elevated hormone levels. Only then is surgery indicated. (orig.) [de

  1. Adrenal vein catheterization. Anatomic considerations

    Energy Technology Data Exchange (ETDEWEB)

    El-Sherief, M.A. (Akademiska Sjukhuset, Uppsala (Sweden))

    1982-01-01

    Twenty post-mortem specimens and 93 phlebographies (56 right side, 37 left side) from 44 patients were investigated with respect to the adrenal venous anatomy. At autopsy, the venous orifices displayed in the area of adrenal drainage were injected bilaterally to identify the adrenal vein(s), the surrounding channels and the presence of interconnections. The findings were correlated with those at clinical phlebography, and the different sources of error were elicited. These were mainly found on the right side. Some guidelines are suggested in the hope that these will contribute to eliminate misconceptions.

  2. c-Myc-Dependent Cell Competition in Human Cancer Cells.

    Science.gov (United States)

    Patel, Manish S; Shah, Heta S; Shrivastava, Neeta

    2017-07-01

    Cell Competition is an interaction between cells for existence in heterogeneous cell populations of multicellular organisms. This phenomenon is involved in initiation and progression of cancer where heterogeneous cell populations compete directly or indirectly for the survival of the fittest based on differential gene expression. In Drosophila, cells having lower dMyc expression are eliminated by cell competition through apoptosis when present in the milieu of cells having higher dMyc expression. Thus, we designed a study to develop c-Myc (human homolog) dependent in vitro cell competition model of human cancer cells. Cells with higher c-Myc were transfected with c-myc shRNA to prepare cells with lower c-Myc and then co-cultured with the same type of cells having a higher c-Myc in equal ratio. Cells with lower c-Myc showed a significant decrease in numbers when compared with higher c-Myc cells, suggesting "loser" and "winner" status of cells, respectively. During microscopy, engulfment of loser cells by winner cells was observed with higher expression of JNK in loser cells. Furthermore, elimination of loser cells was prevented significantly, when co-cultured cells were treated with the JNK (apoptosis) inhibitor. Above results indicate elimination of loser cells in the presence of winner cells by c-Myc-dependent mechanisms of cell competition in human cancer cells. This could be an important mechanism in human tumors where normal cells are eliminated by c-Myc-overexpressed tumor cells. J. Cell. Biochem. 118: 1782-1791, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Signaling hierarchy regulating human endothelial cell development.

    Science.gov (United States)

    Kelly, Melissa A; Hirschi, Karen K

    2009-05-01

    Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these studies. Using human embryonic stem cells as a model system, we were able to reproducibly and robustly generate differentiated endothelial cells via coculture on OP9 marrow stromal cells. We found that, in contrast to studies in the mouse, bFGF and VEGF had no specific effects on the initiation of human vasculogenesis. However, exogenous Ihh promoted endothelial cell differentiation, as evidenced by increased production of cells with cobblestone morphology that coexpress multiple endothelial-specific genes and proteins, form lumens, and exhibit DiI-AcLDL uptake. Inhibition of BMP signaling using Noggin or BMP4, specifically, using neutralizing antibodies suppressed endothelial cell formation; whereas, addition of rhBMP4 to cells treated with the hedgehog inhibitor cyclopamine rescued endothelial cell development. Our studies revealed that Ihh promoted human endothelial cell differentiation from pluripotent hES cells via BMP signaling, providing novel insights applicable to modulating human endothelial cell formation and vascular regeneration for human clinical therapies.

  4. Consumption of sucrose from infancy increases the visceral fat accumulation, concentration of triglycerides, insulin and leptin, and generates abnormalities in the adrenal gland.

    Science.gov (United States)

    Díaz-Aguila, Yadira; Castelán, Francisco; Cuevas, Estela; Zambrano, Elena; Martínez-Gómez, Margarita; Muñoz, Alvaro; Rodríguez-Antolín, Jorge; Nicolás-Toledo, Leticia

    2016-03-01

    Consumption of sugar-sweetened beverages promotes the development of metabolic syndrome (MetS) and type 2 diabetes mellitus in humans. One factor related to the appearance of MetS components is the dysfunction of the adrenal gland. In fact, the experimental generation of hyperglycemia has been associated with morphological and microvascular changes in the adrenal glands of rats. We hypothesized that high sucrose consumption from infancy promotes histological disruption of the adrenal glands associated with the appearance of metabolic syndrome indicators. Male Wistar rats were separated at weaning (21 days old) into two groups: free access to tap water (control group, C) or 30 % sucrose diluted in water (sugar-fed group). After 12 weeks, high sucrose consumption promoted an increase in visceral fat accumulation, adipose cell number, and insulin resistance. Also, a rise in the concentration of triglycerides, very low-density lipoprotein, insulin and leptin was observed. In control rats, a histomorphometric asymmetry between the right and left adrenal glands was found. In the sugar-fed group, sucrose consumption produced a major change in adrenal gland asymmetry. No changes in corticosterone serum level were observed in either group. Our results suggest that a high sucrose liquid-diet from early life alters the morphology of adrenocortical zones, leading to MetS indicators.

  5. A case of adrenal Cushing's syndrome with bilateral adrenal masses.

    Science.gov (United States)

    Guo, Ya-Wun; Hwu, Chii-Min; Won, Justin Ging-Shing; Chu, Chia-Huei; Lin, Liang-Yu

    2016-01-01

    A functional lesion in corticotrophin (ACTH)-independent Cushing's syndrome is difficult to distinguish from lesions of bilateral adrenal masses. Methods for distinguishing these lesions include adrenal venous sampling and (131)I-6β-iodomethyl-19-norcholesterol ((131)I-NP-59) scintigraphy. We present a case of a 29-year-old Han Chinese female patient with a history of hypercholesterolaemia and polycystic ovary syndrome. She presented with a 6month history of an 8kg body weight gain and gradual rounding of the face. Serial examinations revealed loss of circadian rhythm of cortisol, elevated urinary free-cortisol level and undetectable ACTH level (Cushing's syndrome presenting with bilateral adrenal masses. The clinical presentation of Cushing' syndrome includes symptoms and signs of fat redistribution and protein-wasting features.The diagnosis of patients with ACTH-independent Cushing's syndrome with bilateral adrenal masses is challenging for localisation of the lesion.Both adrenal venous sampling and (131)I-NP-59 scintigraphy are good methods to use in these patients with Cushing's syndrome presenting with bilateral adrenal masses.

  6. Symmetry breaking in human neuroblastoma cells

    Science.gov (United States)

    Izumi, Hideki; Kaneko, Yasuhiko

    2014-01-01

    Asymmetric cell division (ACD) is a characteristic of cancer stem cells, which exhibit high malignant potential. However, the cellular mechanisms that regulate symmetric (self-renewal) and asymmetric cell divisions are mostly unknown. Using human neuroblastoma cells, we found that the oncosuppressor protein tripartite motif containing 32 (TRIM32) positively regulates ACD. PMID:27308367

  7. Trophoblast lineage cells derived from human induced pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ying, E-mail: ying.chen@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Wang, Kai; Chandramouli, Gadisetti V.R. [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Knott, Jason G. [Developmental Epigenetics Laboratory, Department of Animal Science, Michigan State University (United States); Leach, Richard, E-mail: Richard.leach@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Department of Obstetrics, Gynecology and Women’s Health, Spectrum Health Medical Group (United States)

    2013-07-12

    Highlights: •Epithelial-like phenotype of trophoblast lineage cells derived from human iPS cells. •Trophoblast lineage cells derived from human iPS cells exhibit trophoblast function. •Trophoblasts from iPS cells provides a proof-of-concept in regenerative medicine. -- Abstract: Background: During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and results: Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion: Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro.

  8. Trophoblast lineage cells derived from human induced pluripotent stem cells

    International Nuclear Information System (INIS)

    Chen, Ying; Wang, Kai; Chandramouli, Gadisetti V.R.; Knott, Jason G.; Leach, Richard

    2013-01-01

    Highlights: •Epithelial-like phenotype of trophoblast lineage cells derived from human iPS cells. •Trophoblast lineage cells derived from human iPS cells exhibit trophoblast function. •Trophoblasts from iPS cells provides a proof-of-concept in regenerative medicine. -- Abstract: Background: During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and results: Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion: Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro

  9. Adrenal Hemangioma: A Case of Retroperitoneal Tumor

    Directory of Open Access Journals (Sweden)

    Genta Iwamoto

    2018-01-01

    Full Text Available Introduction. Adrenal hemangioma is a rare disease, with only some 60 cases reported previously. Due to the difficulty of the preoperative diagnosis of adrenal hemangioma, almost all of the cases were diagnosed by a histopathological analysis of surgical specimens. Case Presentation. A 52-year-old man was referred to our department for further examination of his left retroperitoneal tumor. He had received hemodialysis due to chronic renal failure resulting from membranous nephropathy. Computed tomography revealed a mass around his left hilum. Magnetic resonance imaging (MRI and positron-emission tomography (PET-CT were unable to confirm or deny malignancy, and tumor markers, including CEA and CA19-9, showed slight elevation. His tumor grew from 38 mm to 54 mm in diameter in 7 months of follow-up. We therefore planned retroperitoneal tumor resection with left nephrectomy. Histopathologically, hyperplastic small vessels with hemorrhaging and denaturation were seen. The endothelial cells showed no variants or division of the nucleus. Based on this diagnosis, no further therapy was performed. He has had no recurrence in the eight months since the surgery. Conclusion. We herein report a rare case of adrenal hemangioma.

  10. Diffusion inside living human cells

    DEFF Research Database (Denmark)

    Leijnse, N.; Jeon, J. -H.; Loft, Steffen

    2012-01-01

    of the cell or within the nucleus. Also, granules in cells which are stressed by intense laser illumination or which have attached to a surface for a long period of time move in a more restricted fashion than those within healthy cells. For granules diffusing in healthy cells, in regions away from the cell...... cells. For these cells the exact diffusional pattern of a particular granule depends on the physiological state of the cell and on the localization of the granule within the cytoplasm. Granules located close to the actin rich periphery of the cell move less than those located towards to the center...

  11. MR imaging in adrenal diseases

    International Nuclear Information System (INIS)

    Juliani, G.; Avateneo, T.; Potenzoni, F.

    1988-01-01

    Twenty-five patients affected by adrenal glands pathology underwent CT and MRI: 6 nonfuctioning adenomas, 2 Cushing's adenomas, 2 Conn's adenomas, 6 metastases, 3 cystis, 2 carcinomas (Cushing's syndrome), 1 Lymphoma and 3 pheochromocytomas. Diagnosis was subsequently confirmed either at surgery, or autopsy, or with needle biopsy. In all cases normal adrenal glands and pathological lesions were showed by MRI. T1 signal intensity and mass diameter were compared with T2 signal intensity, represented by the intensity ratio between the adrenal mass vs normal hepatic parenchyma. MRI signal intensity, usually high in case of malignancy and low in adenomas, shows a mean value which is much wider than that referred to mass diameter evaluation (carcinoma is larger than adenoma); for this reason those findings have proved to be insufficiently accurate for adrenal tissue characterization, even for the evaluation of cysts and pheochromocytomas. In the same cases CT showed higher accuracy

  12. CT findings of adrenal schwannoma

    International Nuclear Information System (INIS)

    Zhang, Y.-M.; Lei, P.-F.; Chen, M.-N.; Lv, X.-F.; Ling, Y.-H.; Cai, P.-Q.; Gao, J.-M.

    2016-01-01

    Aim: To analyse the computed tomography (CT) imaging features of patients with adrenal schwannoma. Materials and methods: Eight cases of adrenal schwannoma confirmed by histopathology were included in this study. All eight patients had undergone multiphase CT examinations. The features of the adrenal schwannoma in the CT images were analysed retrospectively in detail, including size, shape, margin, radiodensity, calcification, and enhancement pattern. Results: There were six male and two female patients, with a median age of 44.5 years (range, 25–52 years). Two patients complained of right flank pain, and two with left upper abdominal discomfort, while the remaining patients were diagnosed by routine ultrasound examinations. On unenhanced CT images, all cases of adrenal schwannoma were well circumscribed, rounded or oval, heterogeneous masses with cystic components, with two cases exhibiting calcification, and three cases with septa. On enhanced CT images, all cases displayed mild heterogeneous enhancement of the tumour during the arterial phase, and progressive enhancement during the portal venous phase and equilibrium phase. Conclusion: Adrenal schwannoma commonly presents as a well-defined unilateral mass with cystic degeneration, septa, and a characteristic progressive contrast-enhancement pattern on multiphase enhanced scans. - Highlights: • Adrenal schwannomas were extremely rare, and eight cases' medical data of this disease were collected in this study. • They usually presented a well-defined unilateral mass with cystic degeneration and sepations. • They manifested characteristic progressive contrast enhancement pattern on enhanced CT images.

  13. Bases fisiológicas para una interacción entre las células cromafines y las endoteliales de la glándula adrenal Physiological bases for an interaction between chromaffin and endothelial cells from the adrenal gland

    Directory of Open Access Journals (Sweden)

    MARIO LUXORO

    2001-03-01

    Full Text Available En este trabajo tratamos de investigar las posibles interacciones entre las células endoteliales de la glándula adrenal y aquellas sustancias relacionadas con la secreción de las células cromafines. Para lo anterior, estudiamos el efecto de acetilcolina (ACh, o de catecolaminas (CA tanto en el nivel de Ca2+ citoplasmático ([Ca2+]i, como en el potencial de membrana de las células endoteliales. Nuestros resultados muestran que tanto la ACh como la nicotina, pero no la muscarina, son capaces de inducir un aumento del [Ca2+]i y una despolarización de la membrana plasmática de las células endoteliales. El antagonista nicotínico, hexametonium, bloquea tanto el efecto de la ACh como de la nicotina lo que sugiere la presencia de receptores nicotínicos. Por otra parte, las CA (tanto adrenalina como noradrenalina o agonistas a1-adrenérgicos también producen un aumento del [Ca2+]i en las células endoteliales aunque no despolarización evidente. En este caso, el aumento es bifásico siendo la primera fase de un pico rápido e independiente del Ca2+ extracelular en tanto que la segunda se presenta con oscilaciones y depende tanto de que los canales de Ca2+ no estén bloqueados como de la presencia de ese ión en el medio externo. Dado que se ha demostrado que el aumento del [Ca2+]i en las células endoteliales desencadena la secreción de sustancias vasodilatadoras (prostaciclina y óxido nítrico, proponemos que éste sería un mecanismo compensatorio del sistema para contrarestar el enorme efecto vasoconstrictor de las CA secretadas por las células cromafinesIn this work we investigated the possible interactions between the endothelial cells from the adrenal gland and the substances related with the secretion from the chromaffin cells. In order to do so, we studied the effect of acetyl-choline (ACh or of catecholamines (CA on the level of the membrane potential and the cytoplasmic concentration of free calcium ([Ca2+]i in the endothelial

  14. Molecular regulation of human hematopoietic stem cells

    NARCIS (Netherlands)

    van Galen, P.L.J.

    2014-01-01

    Peter van Galen focuses on understanding the determinants that maintain the stem cell state. Using human hematopoietic stem cells (HSCs) as a model, processes that govern self-renewal and tissue regeneration were investigated. Specifically, a role for microRNAs in balancing the human HSC

  15. Profiling adrenal 11β-hydroxyandrostenedione metabolites in prostate cancer cells, tissue and plasma: UPC2-MS/MS quantification of 11β-hydroxytestosterone, 11keto-testosterone and 11keto-dihydrotestosterone.

    Science.gov (United States)

    du Toit, Therina; Bloem, Liezl M; Quanson, Jonathan L; Ehlers, Riaan; Serafin, Antonio M; Swart, Amanda C

    2017-02-01

    Adrenal C 19 steroids serve as precursors to active androgens in the prostate. Androstenedione (A4), 11β-hydroxyandrostenedione (11OHA4) and 11β-hydroxytestosterone (11OHT) are metabolised to potent androgen receptor (AR) agonists, dihydrotestosterone (DHT), 11-ketotestosterone (11KT) and 11-ketodihydrotestosterone (11KDHT). The identification of 11OHA4 metabolites, 11KT and 11KDHT, as active androgens has placed a new perspective on adrenal C11-oxy C 19 steroids and their contribution to prostate cancer (PCa). We investigated adrenal androgen metabolism in normal epithelial prostate (PNT2) cells and in androgen-dependent prostate cancer (LNCaP) cells. We also analysed steroid profiles in PCa tissue and plasma, determining the presence of the C 19 steroids and their derivatives using ultra-performance liquid chromatography (UHPLC)- and ultra-performance convergence chromatography tandem mass spectrometry (UPC 2 -MS/MS). In PNT2 cells, sixty percent A4 (60%) was primarily metabolised to 5α-androstanedione (5αDIONE) (40%), testosterone (T) (10%), and androsterone (AST) (10%). T (30%) was primarily metabolised to DHT (10%) while low levels of A4, 5αDIONE and 3αADIOL (≈20%) were detected. Conjugated steroids were not detected and downstream products were present at <0.05μM. Only 20% of 11OHA4 and 11OHT were metabolised with the former yielding 11keto-androstenedione (11KA4), 11KDHT and 11β-hydroxy-5α-androstanedione (11OH-5αDIONE) and the latter yielding 11OHA4, 11KT and 11KDHT with downstream products <0.03μM. In LNCaP cells, A4 (90%) was metabolised to AST-glucuronide via the alternative pathway while T was detected as T-glucuronide with negligible conversion to downstream products. 11OHA4 (80%) and 11OHT (60%) were predominantly metabolised to 11KA4 and 11KT and in both assays more than 50% of 11KT was detected in the unconjugated form. In tissue, we detected C11-oxy C 19 metabolites at significantly higher levels than the C 19 steroids, with

  16. Nonreutilizaton of adrenal chromaffin granule membranes following secretion

    International Nuclear Information System (INIS)

    Nobiletti, J.B.

    1985-01-01

    The intracellular postexocytotic fate of the adrenal chromaffin granule membrane (reutilization vs. nonreutilization) was addressed through two experimental approaches. First, ( 3 H) leucine pulse-chase labeling experiments were conducted in two systems - the isolated retrograde perfused cat adrenal gland and cultured bovine adrenal chromaffin cells to compare chromaffin granule soluble dopamine-B-hydroxylase (DBH) turnover (marker for granule soluble content turnover) to that of membrane-bound DBH (marker for granule membrane turnover). Experiments in cat adrenal glands showed that at all chase periods the granule distribution of radiolabeled DBH was in agreement with the DBH activity distribution (73% membrane-bound/27% soluble) - a result consistent with parallel turnover of soluble and membrane-bound DBH. Experiments in cultured bovine cells showed that labeled soluble and membrane-bound DBH had parallel turnover patterns and at all chase period, the distribution of radiolabeled DBH between the soluble contents and membranes was similar to the DBH activity distribution (50% soluble/50% membrane-bound). The above experiments showed that the soluble contents and membranes turnover in parallel and are consistent with nonreutilization of chromaffin granule membranes following exocytosis. Isolated retrograde perfused bovine adrenal glands were subjected to repetitive acetylcholine stimulation to induce exocytosis and then the dense and less-dense chromaffin granule fractions were isolated. Since both approaches gave results consistent with membrane nonreutilization, the authors conclude that once a chromaffin granule is involved in exocytosis, its membrane is not reutilized for the further synthesis, storage, and secretion of catecholamines

  17. Human monoclonal antibodies reactive with human myelomonocytic leukemia cells.

    Science.gov (United States)

    Posner, M R; Santos, D J; Elboim, H S; Tumber, M B; Frackelton, A R

    1989-04-01

    Peripheral blood mononuclear cells from a patient with chronic myelogenous leukemia (CML), in remission, were depleted of CD8-positive T-cells and cultured with Epstein-Barr virus. Four of 20 cultures (20%) secreted human IgG antibodies selectively reactive with the cell surfaces of certain human leukemia cell lines. Three polyclonal, Epstein-Barr virus-transformed, B-cell lines were expanded and fused with the human-mouse myeloma analogue HMMA2.11TG/O. Antibody from secreting clones HL 1.2 (IgG1), HL 2.1 (IgG3), and HL 3.1 (IgG1) have been characterized. All three react with HL-60 (promyelocytic), RWLeu4 (CML promyelocytic), and U937 (monocytic), but not with KG-1 (myeloblastic) or K562 (CML erythroid). There is no reactivity with T-cell lines, Burkitt's cell lines, pre-B-leukemia cell lines, or an undifferentiated CML cell line, BV173. Leukemic cells from two of seven patients with acute myelogenous leukemia and one of five with acute lymphocytic leukemia react with all three antibodies. Normal lymphocytes, monocytes, polymorphonuclear cells, red blood cells, bone marrow cells, and platelets do not react. Samples from patients with other diverse hematopoietic malignancies showed no reactivity. Immunoprecipitations suggest that the reactive antigen(s) is a lactoperoxidase iodinatable series of cell surface proteins with molecular weights of 42,000-54,000 and a noniodinatable protein with a molecular weight of 82,000. Based on these data these human monoclonal antibodies appear to react with myelomonocytic leukemic cells and may detect a leukemia-specific antigen or a highly restricted differentiation antigen.

  18. Bilateral Primary Adrenal Lymphoma in a 59- year-old Female

    Directory of Open Access Journals (Sweden)

    Alireza Ahmadi

    2018-02-01

    Full Text Available Occasionally, lymphoma involves the adrenal glands; however, primary adrenal lymphoma (PAL is rare and only few cases have been reported. We report a case of a 59-year-old female with primary adrenal diffuse large B-cell lymphoma (DLBCL manifested by weakness, fatigue, anorexia, and hyper pigmentation of skin. The patient initially responded to intravenous hydrocortisone in large doses by total remission of the symptoms. An abdominal computed tomography scan showed a hypodense mass in the right subdiaphragmatic space, which was suggestive of an adrenal gland tumor with adjacent liver involvement. Additionally, a smaller lesion with similar characteristics was found in the left adrenal gland. The results obtained from adrenal gland needle biopsy confirmed the diagnosis of DLBCL. Moreover, primary laboratory findings demonstrated hyponatremia, hyperkalemia, fasting blood sugar level of 153 mg/dl, and alkaline phosphatase level of 663 U/L. The mentioned symptoms and laboratory findings were indicative of adrenal insufficiency. After about 2 months, her level of consciousness decreased and urinary and fecal incontinence occurred. Therefore, brain involvement was suspected, and magnetic resonance imaging of the brain showed heterogeneous enhancement (24.8 mm in the posterior aspect of the left temporal lobe together with patchy foci of enhancement in around the ventricular areas of the brain that showed metastatic lesions of PAL. This case should remind clinicians that PAL may be a cause of adrenal incidentaloma, especially when the patient presents with the symptoms of adrenal insufficiency.

  19. Human hematopoietic cell culture, transduction, and analyses

    DEFF Research Database (Denmark)

    Bonde, Jesper; Wirthlin, Louisa; Kohn, Donald B

    2008-01-01

    This unit provides methods for introducing genes into human hematopoietic progenitor cells. The Basic Protocol describes isolation of CD34(+) cells, transduction of these cells with a retroviral vector on fibronectin-coated plates, assaying the efficiency of transduction, and establishing long-te...

  20. The lifetime of hypoxic human tumor cells

    International Nuclear Information System (INIS)

    Durand, Ralph E.; Sham, Edward

    1998-01-01

    Purpose: For hypoxic and anoxic cells in solid tumors to be a therapeutic problem, they must live long enough to be therapeutically relevant, or else be rapidly recruited into the proliferating compartment during therapy. We have, therefore, estimated lifetime and recruitment rate of hypoxic human tumor cells in multicell spheroids in vitro, or in xenografted tumors in SCID mice. Materials and Methods: Cell turnover was followed by flow cytometry techniques, using antibodies directed at incorporated halogenated pyrimidines. The disappearance of labeled cells was quantified, and verified to be cell loss rather than label dilution. Repopulation was studied in SiHa tumor xenografts during twice-daily 2.5-Gy radiation exposures. Results: The longevity of hypoxic human tumor cells in spheroids or xenografts exceeded that of rodent cell lines, and cell turnover was slower in xenografts than under static growth as spheroids. Human tumor cells remained viable in the hypoxic regions of xenografts for 4-10 days, compared to 3-5 days in spheroids, and 1-3 days for most rodent cells in spheroids. Repopulation was observed within the first few radiation treatments for the SiHa xenografts and, with accumulated doses of more than 10 Gy, virtually all recovered cells had progressed through at least one S-phase. Conclusion: Our results suggest an important difference in the ability of human vs. rodent tumor cells to withstand hypoxia, and raise questions concerning the increased longevity seen in vivo relative to the steady-state spheroid system

  1. Melanocortin receptor accessory proteins in adrenal gland physiology and beyond.

    Science.gov (United States)

    Novoselova, T V; Jackson, D; Campbell, D C; Clark, A J L; Chan, L F

    2013-04-01

    The melanocortin receptor (MCR) family consists of five G-protein-coupled receptors (MC1R-MC5R) with diverse physiological roles. MC1R controls pigmentation, MC2R is a critical component of the hypothalamic-pituitary-adrenal axis, MC3R and MC4R have a vital role in energy homeostasis and MC5R is involved in exocrine function. The melanocortin receptor accessory protein (MRAP) and its paralogue MRAP2 are small single-pass transmembrane proteins that have been shown to regulate MCR expression and function. In the adrenal gland, MRAP is an essential accessory factor for the functional expression of the MC2R/ACTH receptor. The importance of MRAP in adrenal gland physiology is demonstrated by the clinical condition familial glucocorticoid deficiency, where inactivating MRAP mutations account for ∼20% of cases. MRAP is highly expressed in both the zona fasciculata and the undifferentiated zone. Expression in the undifferentiated zone suggests that MRAP could also be important in adrenal cell differentiation and/or maintenance. In contrast, the role of adrenal MRAP2, which is highly expressed in the foetal gland, is unclear. The expression of MRAPs outside the adrenal gland is suggestive of a wider physiological purpose, beyond MC2R-mediated adrenal steroidogenesis. In vitro, MRAPs have been shown to reduce surface expression and signalling of all the other MCRs (MC1,3,4,5R). MRAP2 is predominantly expressed in the hypothalamus, a site that also expresses a high level of MC3R and MC4R. This raises the intriguing possibility of a CNS role for the MRAPs.

  2. Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells

    NARCIS (Netherlands)

    Guadix, Juan Antonio; Orlova, Valeria V.; Giacomelli, Elisa; Bellin, Milena; Ribeiro, Marcelo C.; Mummery, Christine L.; Pérez-Pomares, José M.; Passier, Robert

    2017-01-01

    Human pluripotent stem cells (hPSCs) are widely used to study cardiovascular cell differentiation and function. Here, we induced differentiation of hPSCs (both embryonic and induced) to proepicardial/epicardial progenitor cells that cover the heart during development. Addition of retinoic acid (RA)

  3. Radiation effects on cultured human lymphoid cells

    International Nuclear Information System (INIS)

    Johansson, L.; Nilsson, K.; Carlsson, J.; Larsson, B.; Jakobsson, P.

    1981-01-01

    The cloning efficiency of human normal and malignant lymphoid cells is usually low. Radiation effects in vitro on such cells can therefore not be analysed with conventional cloning. However, this problem can be circumscribed by using the growth extrapolation method. A panel of human leukemia-lymphoma cell-lines representing Epstein-Barr virus carrying lymphoblastoid cells of presumed non-neoplastic derivation and neoplastic T- and B-lymphocytes was used to test the efficiency of this method. The sensitivity to radiation could be determined for all these cell types. The growth extrapolation method gave generally the same result as conventional cloning demonstrated by comparison with one exceptional cell-line with capacity for cloning in agar. The sensitivity varied largely between the different cell types. A common feature was that none of the cell lines had a good capacity to accumulate sublethal radiation injury. (Auth.)

  4. Energy Generation in the Human Body by the Human Cells ...

    African Journals Online (AJOL)

    We adapted the thermodynamics equation for energy generation in a diesel engine in modeling energy generation in human body by the human cells by doing a thorough study on both systems and saw that the process of energy generation is the same in them. We equally saw that the stages involved in energy generation ...

  5. [Hemorrhagic adrenal pseudocyst: case report].

    Science.gov (United States)

    Basile, G; Buffone, A; Cicciarella, G; di Mari, P; Cirino, E

    2004-01-01

    Adrenal cysts are usually asymptomatic; they are usually identified occasionally during ultrasound or C.T. scans (incidentaloma). Among adrenal cysts the most common types are epithelial cysts and pseudocysts. Intracystic haemorrhage is one of the possible complications of adrenal pseudocysts. We report a case of a young woman with right superior abdominal pain, fever and acute anemia. A C.T. scan showed a 10 cm. mass between the liver and the right kidney. To be sure of the nature of this mass also M.R., urography and C.T.-guided biopsy were carried out. This latter only let us make the final diagnosis of hemorrhagic adrenal pseudocyst. Thereafter, a laparotomic right adrenalectomy was performed, with full recovery of the patient. Adrenal cysts may cause differential diagnostic problems with masses of contiguous organs like kidney, liver and gallbladder. For this reason, ultrasound and C.T. scans may not be sufficient and must be completed by M.R., urography and/or C.T.-guided biopsy. Intracystic hamorrhage, spontaneous or post-traumatic, may cause to the patient acute anemia which, as soon as the diagnosis is confirmed, indicates surgery. The operation usually is a laparotomic adrenalectomy, since the laparoscopic approach is not sufficient to control large masses with active bleeding inside.

  6. Tuft (caveolated) cells in two human colon carcinoma cell lines.

    Science.gov (United States)

    Barkla, D H; Whitehead, R H; Foster, H; Tutton, P J

    1988-09-01

    The presence of an unusual cell type in two human colon carcinoma cell lines is reported. The cells show the same morphology as "tuft" (caveolated) cells present in normal gastrointestinal epithelium. Tuft cells were seen in cell line LIM 1863 growing in vitro and in human colon carcinoma cell line LIM 2210 growing as subcutaneous solid tumour xenografts in nude mice. Characteristic morphologic features of tuft cells included a wide base, narrow apex and a tuft of long microvilli projecting from the apical surface. The microvilli are attached by a core of long microfilaments passing deep into the apical cytoplasm. Between the microvilli are parallel arrays of vesicles (caveoli) containing flocculent material. Two different but not mutually exclusive explanations for the presence of tuft cells are proposed. The first explanation is that tuft cells came from the resected tumour and have survived by mitotic division during subsequent passages. The second explanation suggests that tuft cells are the progeny of undifferentiated tumour cells. Descriptions of tuft cells in colon carcinomas are uncommon and possible reasons for this are presented. The morphology of tuft cells is consistent with that of a highly differentiated cell specialised for absorption, and these new models provide an opportunity to further investigate the structure and function of tuft cells.

  7. Sensing radiosensitivity of human epidermal stem cells

    International Nuclear Information System (INIS)

    Rachidi, Walid; Harfourche, Ghida; Lemaitre, Gilles; Amiot, Franck; Vaigot, Pierre; Martin, Michele T.

    2007-01-01

    Purpose: Radiosensitivity of stem cells is a matter of debate. For mouse somatic stem cells, both radiosensitive and radioresistant stem cells have been described. By contrast, the response of human stem cells to radiation has been poorly studied. As epidermis is a radiosensitive tissue, we evaluated in the present work the radiosensitivity of cell populations enriched for epithelial stem cells of human epidermis. Methods and materials: The total keratinocyte population was enzymatically isolated from normal human skin. We used flow cytometry and antibodies against cell surface markers to isolate basal cell populations from human foreskin. Cell survival was measured after a dose of 2 Gy with the XTT assay at 72 h after exposure and with a clonogenic assay at 2 weeks. Transcriptome analysis using oligonucleotide microarrays was performed to assess the genomic cell responses to radiation. Results: Cell sorting based on two membrane proteins, α6 integrin and the transferrin receptor CD71, allowed isolation of keratinocyte populations enriched for the two types of cells found in the basal layer of epidermis: stem cells and progenitors. Both the XTT assay and the clonogenic assay showed that the stem cells were radioresistant whereas the progenitors were radiosensitive. We made the hypothesis that upstream DNA damage signalling might be different in the stem cells and used microarray technology to test this hypothesis. The stem cells exhibited a much more reduced gene response to a dose of 2 Gy than the progenitors, as we found that 6% of the spotted genes were regulated in the stem cells and 20% in the progenitors. Using Ingenuity Pathway Analysis software, we found that radiation exposure induced very specific pathways in the stem cells. The most striking responses were the repression of a network of genes involved in apoptosis and the induction of a network of cytokines and growth factors. Conclusion: These results show for the first time that keratinocyte

  8. Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Juan Antonio Guadix

    2017-12-01

    Full Text Available Summary: Human pluripotent stem cells (hPSCs are widely used to study cardiovascular cell differentiation and function. Here, we induced differentiation of hPSCs (both embryonic and induced to proepicardial/epicardial progenitor cells that cover the heart during development. Addition of retinoic acid (RA and bone morphogenetic protein 4 (BMP4 promoted expression of the mesodermal marker PDGFRα, upregulated characteristic (proepicardial progenitor cell genes, and downregulated transcription of myocardial genes. We confirmed the (proepicardial-like properties of these cells using in vitro co-culture assays and in ovo grafting of hPSC-epicardial cells into chick embryos. Our data show that RA + BMP4-treated hPSCs differentiate into (proepicardial-like cells displaying functional properties (adhesion and spreading over the myocardium of their in vivo counterpart. The results extend evidence that hPSCs are an excellent model to study (proepicardial differentiation into cardiovascular cells in human development and evaluate their potential for cardiac regeneration. : The authors have shown that hPSCs can be instructed in vitro to differentiate into a specific cardiac embryonic progenitor cell population called the proepicardium. Proepicardial cells are required for normal formation of the heart during development and might contribute to the development of cell-based therapies for heart repair. Keywords: human pluripotent stem cells, proepicardium, progenitor cells, cardiovascular, differentiation

  9. Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Varga, Nora [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary); Vereb, Zoltan; Rajnavoelgyi, Eva [Department of Immunology, Medical and Health Science Centre, University of Debrecen, Debrecen (Hungary); Nemet, Katalin; Uher, Ferenc; Sarkadi, Balazs [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary); Apati, Agota, E-mail: apati@kkk.org.hu [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary)

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer MSC like cells were derived from hESC by a simple and reproducible method. Black-Right-Pointing-Pointer Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. Black-Right-Pointing-Pointer MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.

  10. Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

    International Nuclear Information System (INIS)

    Varga, Nóra; Veréb, Zoltán; Rajnavölgyi, Éva; Német, Katalin; Uher, Ferenc; Sarkadi, Balázs; Apáti, Ágota

    2011-01-01

    Highlights: ► MSC like cells were derived from hESC by a simple and reproducible method. ► Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. ► MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.

  11. Toxicity of diuron in human cancer cells.

    Science.gov (United States)

    Huovinen, Marjo; Loikkanen, Jarkko; Naarala, Jonne; Vähäkangas, Kirsi

    2015-10-01

    Diuron is a substituted phenylurea used as a herbicide to control broadleaf and grass weeds and as a biocidal antifouling agent. Diuron is carcinogenic in rat urinary bladder and toxic to the reproductive system of oysters, sea urchins and lizards. The few studies carried out in human cells do not include the genotoxicity of diuron. We have investigated the toxicity of diuron in human breast adenocarcinoma (MCF-7) and human placental choriocarcinoma (BeWo) cells. The production of reactive oxygen species (ROS) was statistically significantly increased in both cell lines but only at the highest 200 μM concentration. Diuron clearly reduced the viability of BeWo, but not MCF-7 cells. The relative cell number was decreased in both cell lines indicative of inhibition of cell proliferation. In the Comet assay, diuron increased DNA fragmentation in MCF-7 but not in BeWo cells. The expressions of p53 protein, a marker for cell stress, and p21 protein, a transcriptional target of p53, were increased, but only in MCF-7 cells. In conclusion, our results suggest that diuron is cytotoxic and potentially genotoxic in a tissue-specific manner and that ROS play a role in its toxicity. Thus, exposure to diuron may exert harmful effects on fetal development and damage human health. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Regulatory T Cells in Human Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Dong-Jun Peng

    2012-01-01

    Full Text Available Multiple layers of suppressive components including regulatory T (TReg cells, suppressive antigen-presenting cells, and inhibitory cytokines form suppressive networks in the ovarian cancer microenvironment. It has been demonstrated that as a major suppressive element, TReg cells infiltrate tumor, interact with several types of immune cells, and mediate immune suppression through different molecular and cellular mechanisms. In this paper, we focus on human ovarian cancer and will discuss the nature of TReg cells including their subsets, trafficking, expansion, and function. We will briefly review the development of manipulation of TReg cells in preclinical and clinical settings.

  13. Polycystic ovarian disease: the adrenal connection.

    Science.gov (United States)

    Marouliss, George B; Triantafillidis, Ioannis K

    2006-01-01

    Polycystic ovarian disease (PCOD) is characterized by hyperandrogenemia, ovulatory dysfunction and polycystic ovaries (PCO). The increased androgen production in PCOD comes primarily from the ovaries. However, in about 40% of patients there is excessive adrenal androgen production (DHEA, DHEA-Sulfate, Androstenedione, Testosterone and Dihydrotestosterone). The contribution of the adrenal in the PCOD is suggested by the presence of adrenal androgen excess in PCO, the presence of PCO in women with enzymatic adrenal hyperplasia as well as in women with adrenal tumors. However, the cause of adrenal androgen hypersecretion is not yet fully understood but it may include endogenous hypersecretion of the zona reticularis of unclear cause, hypersecretion of cortical-androgen-stimulating hormone (CASH), stress, hyperprolactinemia, adrenal enzymatic defects etc. This short review covers the aspects of adrenal androgen hypersecretion in PCOD.

  14. Genome Editing in Human Pluripotent Stem Cells.

    Science.gov (United States)

    Carlson-Stevermer, Jared; Saha, Krishanu

    2017-01-01

    Genome editing in human pluripotent stem cells (hPSCs) enables the generation of reporter lines and knockout cell lines. Zinc finger nucleases, transcription activator-like effector nucleases (TALENs), and CRISPR/Cas9 technology have recently increased the efficiency of proper gene editing by creating double strand breaks (DSB) at defined sequences in the human genome. These systems typically use plasmids to transiently transcribe nucleases within the cell. Here, we describe the process for preparing hPSCs for transient expression of nucleases via electroporation and subsequent analysis to create genetically modified stem cell lines.

  15. Modeling human infertility with pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Di Chen

    2017-05-01

    Full Text Available Human fertility is dependent upon the correct establishment and differentiation of the germline. This is because no other cell type in the body is capable of passing a genome and epigenome from parent to child. Terminally differentiated germline cells in the adult testis and ovary are called gametes. However, the initial specification of germline cells occurs in the embryo around the time of gastrulation. Most of our knowledge regarding the cell and molecular events that govern human germline specification involves extrapolating scientific principles from model organisms, most notably the mouse. However, recent work using next generation sequencing, gene editing and differentiation of germline cells from pluripotent stem cells has revealed that the core molecular mechanisms that regulate human germline development are different from rodents. Here, we will discuss the major molecular pathways required for human germline differentiation and how pluripotent stem cells have revolutionized our ability to study the earliest steps in human embryonic lineage specification in order to understand human fertility.

  16. Bone Health in Adrenal Disorders

    Directory of Open Access Journals (Sweden)

    Beom-Jun Kim

    2018-03-01

    Full Text Available Secondary osteoporosis resulting from specific clinical disorders may be potentially reversible, and thus continuous efforts to find and adequately treat the secondary causes of skeletal fragility are critical to ameliorate fracture risk and to avoid unnecessary treatment with anti-osteoporotic drugs. Among the hyperfunctional adrenal masses, Cushing's syndrome, pheochromocytoma, and primary aldosteronism are receiving particularly great attention due to their high morbidity and mortality mainly by increasing cardiovascular risk. Interestingly, there is accumulating experimental and clinical evidence that adrenal hormones may have direct detrimental effects on bone metabolism as well. Thus, the present review discusses the possibility of adrenal disorders, especially focusing on pheochromocytoma and primary aldosteronism, as secondary causes of osteoporosis.

  17. Angiomyolipoma and Malignant PEComa: Discussion of Two Rare Adrenal Tumors

    Directory of Open Access Journals (Sweden)

    Douglas Kwazneski II

    2016-01-01

    Full Text Available Angiomyolipoma and PEComa are rare tumors descending from perivascular epithelial cells (PECs, with distinctive IHC, morphological, and ultrastructural features. The kidney is the most frequent site of origin, but not the only one; however, adrenal gland angiomyolipomas are extremely rare. We describe two cases being found in the adrenal glands. Given the paucity of literature on the subject, more information on this disease is necessary for diagnosis and treatment. Here, we describe two complete case reports, from presentation to treatment and follow-up, along with imaging and microscopic pathology samples, and provide a comprehensive review as to the history and current literature available regarding these extremely rare tumors.

  18. Discovery of a novel acyl-CoA: cholesterol acyltransferase inhibitor: the synthesis, biological evaluation, and reduced adrenal toxicity of (4-phenylcoumarin)acetanilide derivatives with a carboxylic acid moiety.

    Science.gov (United States)

    Ogino, Masaki; Nakada, Yoshihisa; Negoro, Nobuyuki; Itokawa, Shigekazu; Nishimura, Satoshi; Sanada, Tsukasa; Satomi, Tomoko; Kita, Shunbun; Kubo, Kazuki; Marui, Shogo

    2011-01-01

    As a part of our research for novel potent and orally available acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors that can be used as anti-atherosclerotic agents, we recently reported the discovery of the (4-phenylcoumarine)acetanilide derivative 1. However, compound 1 showed adrenal toxicity in animal models. In order to search for safer ACAT inhibitors that do not have adrenal toxicity, we examined the inhibitory activity of ACAT in human macrophage and adrenal cells. The introduction of a carboxylic acid moiety on the pendant phenyl ring and the adjustment of the lipophilicity led to the discovery of (2E)-3-[7-chloro-3-[2-[[4-fluoro-2-(trifluoromethyl)phenyl]amino]-2-oxoethyl]-6-methyl-2-oxo-2H-chromen-4-yl]phenyl]acrylic acid (21e), which showed potent ACAT inhibitory activity in macrophages and a selectivity of around 30-fold over adrenal cells. In addition, compound 21e showed high adrenal safety in guinea pigs.

  19. Plasma membrane proteomics of human embryonic stem cells and human embryonal carcinoma cells.

    NARCIS (Netherlands)

    Dormeyer, W.; van Hoof, D.; Braam, S.R.; Heck, A.J.R.; Mummery, C.L.; Krijgsveld, J.

    2008-01-01

    Human embryonic stem cells (hESCs) are of immense interest in regenerative medicine as they can self-renew indefinitely and can give rise to any adult cell type. Human embryonal carcinoma cells (hECCs) are the malignant counterparts of hESCs found in testis tumors. hESCs that have acquired

  20. Guidelines for human embryonic stem cell research

    National Research Council Canada - National Science Library

    Committee on Guidelines for Human Embryonic Stem Cell Research, National Research Council

    2005-01-01

    Since 1998, the volume of research being conducted using human embryonic stem (hES) cells has expanded primarily using private funds because of restrictions on the use of federal funds for such research...

  1. Satellite cells in human skeletal muscle plasticity

    Directory of Open Access Journals (Sweden)

    Tim eSnijders

    2015-10-01

    Full Text Available Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodelling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodelling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodelling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

  2. Differential diagnosis of adrenal gland masses

    International Nuclear Information System (INIS)

    Szolar, D.H.M.; Unger, B.; Preidler, K.; Ranner, G.; Heinz-Peer, G.

    1999-01-01

    Computed tomography (CT) and magnetic resonance (MR) imaging are first line modalities in the evaluation of patients with adrenal gland masses, and have the potential to be very accurate for the localization of adrenal gland masses in patients with diseases associated with hyperfunctioning conditions of the adrenal gland. Both CT and MR imaging allow a specific diagnosis of acute adrenal hemorrhage, adrenal myelolipoma, and adrenal cysts. CT is also helpful in the assessment of patients with Addision's disease, particularly the subacute from secondary to granulomatous diseases. Quantitative evaluation of adrenal masses on unenhanced CT scans and/or qualitative analysis on chemical-shift MR imaging have been shown to be accurate in distinguishing adrenal adenomas from non-adenomas. Attenuation of 11 HE or less on unenhanced CT scans and/or signal loss on opposed phase MR images indicate adenoma with a high specificity and acceptable sensitivity. More recently, delayed-enhanced CT has yielded higher sensitivity and specificity values in distinguishing between adrenal adenomas and non-adenomas than both unenhanced CT and chemical-shift MR imaging do. On delayed-enhanced CT scans, adrenal adenomas exhibit a greater washout of contrast material than do adrenal non-adenomas. Therefore, adrenal non-adenomas have significantly higher attenuation than adenomas on delayed-enhanced CT scans obtained at several arbitrarily chosen time points (3-60 min) after the initiation of contrast material administration. (orig.) [de

  3. Spontaneous Retroperitoneal Hemorrhage from Adrenal Artery Aneurysm

    International Nuclear Information System (INIS)

    Gonzalez Valverde, F.M.; Balsalobre, M.; Torregrosa, N.; Molto, M.; Gomez Ramos, M.J.; Vazquez Rojas, J.L.

    2007-01-01

    Spontaneous adrenal hemorrhage is a very rare but serious disorder of the adrenal gland that can require emergent treatment. We report on a 42-year-old man who underwent selective angiography for diagnosis and treatment of retroperitoneal hemorrhage from small adrenal artery aneurysm. This case gives further details about the value of transluminal artery embolization in the management of visceral aneurysm rupture

  4. Principles and management of adrenal cancer

    International Nuclear Information System (INIS)

    Javadpour, N.

    1987-01-01

    Principles and Management of Adrenal Cancer is a comprehensive presentation of the medical and surgical management of neoplastic diseases of the adrenal glands. It consists of two parts. The first provides an overview of the embryology, anatomy, physiology, pathology, and advances in methods of diagnosis and imaging techniques. The second deals with specific diseases of the adrenal cortex and medulla. (orig./MG)

  5. Neonatal adrenal hemorrhage presenting as acute scrotum

    African Journals Online (AJOL)

    Introduction. In newborns, adrenal hemorrhage is not an uncommon event. The large size of the adrenal cortex contributes to an increased vulnerability to trauma during a difficult delivery [1]. However, the neonatal adrenal hemorrhage may rarely present as inguinoscrotal swelling [2,3]. This condition can simulate torsion of ...

  6. CT and MR imaging of the kidney and adrenal glands: MR imaging of the kidney and adrenal glands

    International Nuclear Information System (INIS)

    Lee, J.K.T.

    1987-01-01

    The normal anatomy of the kidney is clearly demonstrated with MR imaging. The renal cortex can be differentiated from the renal medulla; renal vessels can also be identified. MR imaging can differentiate cystic from solid lesions. The signal intensity of a renal cell carcinoma varies and overlaps with the signal intensities of renal neoplasms of other etiologies. MR imaging is superior to CT in distinguishing vascular from nonvascular structures. It can distinguish collateral vessels from lymph nodes and can disclose tumoral thrombi. MR imaging can also aid in the differentiation of acute rejection from acute tubular necrosis in renal transplant recipients. Both normal and abnormal adrenal glands can be seen on MR imaging. A normal adrenal gland has a signal intensity higher than or equal to that of muscle but lower than that of fat. T1-weighted images offer excellent antomic resolution; T2-weighted images provide additional information about internal characteristics of adrenal neoplasms. Preliminary data indicate that MR imaging is useful in distinguishing nonfunctioning adenomas from adrenal metastases. The role of MR imaging of the kidney and adrenal gland is discussed

  7. Regulation of Adrenal Aldosterone Production by Serine Protease Prostasin

    Directory of Open Access Journals (Sweden)

    Takehiro Ko

    2010-01-01

    Full Text Available A serine protease prostasin has been demonstrated to have a pivotal role in the activation of the epithelial sodium channel. Systemic administration of adenovirus carrying human prostasin gene in rats resulted in an increase in plasma prostasin and aldosterone levels. However, the mechanism by which the elevation of prostasin levels in the systemic circulation stimulated the plasma aldosterone levels remains unknown. Therefore, we examined if prostasin increases the aldosterone synthesis in a human adrenocortical cell line (H295R cells. Luciferase assay using CYP11B2 promoter revealed that prostasin significantly increased the transcriptional activity of CYP11B2. Prostasin significantly increased both CYP11B2 mRNA expression and aldosterone production in a dose-dependent manner. Surprisingly, treatment with camostat mesilate, a potent prostasin inhibitor, had no effect on the aldosterone synthesis by prostasin and also a protease-dead mutant of prostasin significantly stimulated the aldosterone production. A T-type/L-type calcium channel blocker and a protein kinase C (PKC inhibitor significantly reduced the aldosterone synthesis by prostasin. Our findings suggest a stimulatory effect of prostasin on the aldosterone synthesis by adrenal gland through the nonproteolytic action and indicate a new role of prostasin in the systemic circulation.

  8. Bilateral primary adrenal lymphoma presenting with adrenal insufficiency

    DEFF Research Database (Denmark)

    Holm, Jakob; Breum, Leif; Stenfeldt, Katrine

    2012-01-01

    surgery was performed. A new computerized tomography scan showed rapid progression of disease with further enlargement of the adrenal masses and both pulmonary and hepatic metastasis. Needle biopsy was performed but the patient refused further treatment and died before a diagnosis was obtained...

  9. Human stem cells for craniomaxillofacial reconstruction.

    Science.gov (United States)

    Jalali, Morteza; Kirkpatrick, William Niall Alexander; Cameron, Malcolm Gregor; Pauklin, Siim; Vallier, Ludovic

    2014-07-01

    Human stem cell research represents an exceptional opportunity for regenerative medicine and the surgical reconstruction of the craniomaxillofacial complex. The correct architecture and function of the vastly diverse tissues of this important anatomical region are critical for life supportive processes, the delivery of senses, social interaction, and aesthetics. Craniomaxillofacial tissue loss is commonly associated with inflammatory responses of the surrounding tissue, significant scarring, disfigurement, and psychological sequelae as an inevitable consequence. The in vitro production of fully functional cells for skin, muscle, cartilage, bone, and neurovascular tissue formation from human stem cells, may one day provide novel materials for the reconstructive surgeon operating on patients with both hard and soft tissue deficit due to cancer, congenital disease, or trauma. However, the clinical translation of human stem cell technology, including the application of human pluripotent stem cells (hPSCs) in novel regenerative therapies, faces several hurdles that must be solved to permit safe and effective use in patients. The basic biology of hPSCs remains to be fully elucidated and concerns of tumorigenicity need to be addressed, prior to the development of cell transplantation treatments. Furthermore, functional comparison of in vitro generated tissue to their in vivo counterparts will be necessary for confirmation of maturity and suitability for application in reconstructive surgery. Here, we provide an overview of human stem cells in disease modeling, drug screening, and therapeutics, while also discussing the application of regenerative medicine for craniomaxillofacial tissue deficit and surgical reconstruction.

  10. Incidentally Detected Kaposi Sarcoma of Adrenal Gland with Anaplastic Features in an HIV Negative Patient

    Directory of Open Access Journals (Sweden)

    Zeliha Esin Celik

    2016-01-01

    Full Text Available Kaposi sarcoma (KS, a vascular tumor caused by infection with human herpesvirus 8 (HHV8, is a systemic disease that can present with cutaneous lesions with or without visceral involvement. Very few cases of KS, most of which were associated with AIDS, have been reported in the adrenal gland. Anaplastic transformation of KS is a rare clinical presentation known as an aggressive disease with local recurrence and metastatic potential. We report here a 47-year-old HIV negative male presented with extra-adrenal symptoms and had an incidentally detected anaplastic adrenal KS exhibited aggressive clinical course. To the best of our knowledge, this is the first case of anaplastic primary adrenal KS without mucocutaneous involvement but subsequently developed other side adrenal metastases in an HIV negative patient.

  11. Multimodal Regulation of Circadian Glucocorticoid Rhythm by Central and Adrenal Clocks.

    Science.gov (United States)

    Son, Gi Hoon; Cha, Hyo Kyeong; Chung, Sooyoung; Kim, Kyungjin

    2018-05-01

    Adrenal glucocorticoids (GCs) control a wide range of physiological processes, including metabolism, cardiovascular and pulmonary activities, immune and inflammatory responses, and various brain functions. During stress responses, GCs are secreted through activation of the hypothalamic-pituitary-adrenal axis, whereas circulating GC levels in unstressed states follow a robust circadian oscillation with a peak around the onset of the active period of a day. A recent advance in chronobiological research has revealed that multiple regulatory mechanisms, along with classical neuroendocrine regulation, underlie this GC circadian rhythm. The hierarchically organized circadian system, with a central pacemaker in the suprachiasmatic nucleus of the hypothalamus and local oscillators in peripheral tissues, including the adrenal gland, mediates periodicities in physiological processes in mammals. In this review, we primarily focus on our understanding of the circadian regulation of adrenal GC rhythm, with particular attention to the cooperative actions of the suprachiasmatic nucleus central and adrenal local clocks, and the clinical implications of this rhythm in human diseases.

  12. Human neutrophils facilitate tumor cell transendothelial migration.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    Tumor cell extravasation plays a key role in tumor metastasis. However, the precise mechanisms by which tumor cells migrate through normal vascular endothelium remain unclear. In this study, using an in vitro transendothelial migration model, we show that human polymorphonuclear neutrophils (PMN) assist the human breast tumor cell line MDA-MB-231 to cross the endothelial barrier. We found that tumor-conditioned medium (TCM) downregulated PMN cytocidal function, delayed PMN apoptosis, and concomitantly upregulated PMN adhesion molecule expression. These PMN treated with TCM attached to tumor cells and facilitated tumor cell migration through different endothelial monolayers. In contrast, MDA-MB-231 cells alone did not transmigrate. FACScan analysis revealed that these tumor cells expressed high levels of intercellular adhesion molecule-1 (ICAM-1) but did not express CD11a, CD11b, or CD18. Blockage of CD11b and CD18 on PMN and of ICAM-1 on MDA-MB-231 cells significantly attenuated TCM-treated, PMN-mediated tumor cell migration. These tumor cells still possessed the ability to proliferate after PMN-assisted transmigration. These results indicate that TCM-treated PMN may serve as a carrier to assist tumor cell transendothelial migration and suggest that tumor cells can exploit PMN and alter their function to facilitate their extravasation.

  13. HLA engineering of human pluripotent stem cells.

    Science.gov (United States)

    Riolobos, Laura; Hirata, Roli K; Turtle, Cameron J; Wang, Pei-Rong; Gornalusse, German G; Zavajlevski, Maja; Riddell, Stanley R; Russell, David W

    2013-06-01

    The clinical use of human pluripotent stem cells and their derivatives is limited by the rejection of transplanted cells due to differences in their human leukocyte antigen (HLA) genes. This has led to the proposed use of histocompatible, patient-specific stem cells; however, the preparation of many different stem cell lines for clinical use is a daunting task. Here, we develop two distinct genetic engineering approaches that address this problem. First, we use a combination of gene targeting and mitotic recombination to derive HLA-homozygous embryonic stem cell (ESC) subclones from an HLA-heterozygous parental line. A small bank of HLA-homozygous stem cells with common haplotypes would match a significant proportion of the population. Second, we derive HLA class I-negative cells by targeted disruption of both alleles of the Beta-2 Microglobulin (B2M) gene in ESCs. Mixed leukocyte reactions and peptide-specific HLA-restricted CD8(+) T cell responses were reduced in class I-negative cells that had undergone differentiation in embryoid bodies. These B2M(-/-) ESCs could act as universal donor cells in applications where the transplanted cells do not express HLA class II genes. Both approaches used adeno-associated virus (AAV) vectors for efficient gene targeting in the absence of potentially genotoxic nucleases, and produced pluripotent, transgene-free cell lines.

  14. HLA Engineering of Human Pluripotent Stem Cells

    Science.gov (United States)

    Riolobos, Laura; Hirata, Roli K; Turtle, Cameron J; Wang, Pei-Rong; Gornalusse, German G; Zavajlevski, Maja; Riddell, Stanley R; Russell, David W

    2013-01-01

    The clinical use of human pluripotent stem cells and their derivatives is limited by the rejection of transplanted cells due to differences in their human leukocyte antigen (HLA) genes. This has led to the proposed use of histocompatible, patient-specific stem cells; however, the preparation of many different stem cell lines for clinical use is a daunting task. Here, we develop two distinct genetic engineering approaches that address this problem. First, we use a combination of gene targeting and mitotic recombination to derive HLA-homozygous embryonic stem cell (ESC) subclones from an HLA-heterozygous parental line. A small bank of HLA-homozygous stem cells with common haplotypes would match a significant proportion of the population. Second, we derive HLA class I–negative cells by targeted disruption of both alleles of the Beta-2 Microglobulin (B2M) gene in ESCs. Mixed leukocyte reactions and peptide-specific HLA-restricted CD8+ T cell responses were reduced in class I–negative cells that had undergone differentiation in embryoid bodies. These B2M−/− ESCs could act as universal donor cells in applications where the transplanted cells do not express HLA class II genes. Both approaches used adeno-associated virus (AAV) vectors for efficient gene targeting in the absence of potentially genotoxic nucleases, and produced pluripotent, transgene-free cell lines. PMID:23629003

  15. DNA fork displacement rates in human cells

    International Nuclear Information System (INIS)

    Kapp, L.N.; Painter, R.B.

    1981-01-01

    DNA fork displacement rates were measured in 20 human cell lines by a bromodeoxyuridine-313 nm photolysis technique. Cell lines included representatives of normal diploid, Fanconi's anemia, ataxia telangiectasia, xeroderma pigmentosum, trisomy-21 and several transformed lines. The average value for all the cell lines was 0.53 +- 0.08 μm/min. The average value for individual cell lines, however, displayed a 30% variation. Less than 10% of variation in the fork displacement rate appears to be due to the experimental technique; the remainder is probably due to true variation among the cell types and to culture conditions. (Auth.)

  16. DNA fork displacement rates in human cells

    Energy Technology Data Exchange (ETDEWEB)

    Kapp, L.N.; Painter, R.B. (California Univ., San Francisco (USA). Lab. of Radiobiology)

    1981-11-27

    DNA fork displacement rates were measured in 20 human cell lines by a bromodeoxyuridine-313 nm photolysis technique. Cell lines included representatives of normal diploid, Fanconi's anemia, ataxia telangiectasia, xeroderma pigmentosum, trisomy-21 and several transformed lines. The average value for all the cell lines was 0.53 +- 0.08 ..mu..m/min. The average value for individual cell lines, however, displayed a 30% variation. Less than 10% of variation in the fork displacement rate appears to be due to the experimental technique; the remainder is probably due to true variation among the cell types and to culture conditions.

  17. Signaling hierarchy regulating human endothelial cell development

    Science.gov (United States)

    Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these stud...

  18. The biology of human innate lymphoid cells

    NARCIS (Netherlands)

    Bernink, J.H.J.

    2016-01-01

    In this thesis I performed studies to investigate the contribution of human innate lymphoid cells (ILCs) in maintaining the mucosal homeostasis, initiating and/or propagating inflammatory responses, but also - when not properly regulated - how these cells contribute to immunopathology. First I

  19. Trails on 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Leading to Diagnosis of Testicular Adrenal Rest Tumor.

    Science.gov (United States)

    Kashyap, Raghava

    2018-01-01

    Testicular adrenal rest tumors (TARTs) are secondary to hypertrophy of adrenal rest cells in the rete testis in settings of hypersecretion of androgens. We present a case of congenital adrenal hyperplasia with TART with clues to the diagnosis on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT). To the best of our knowledge, this is the first reported case on the role of 18 F-FDG PET/CT in TART.

  20. Genetics Home Reference: intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and ...

    Science.gov (United States)

    ... difference in gene activation is caused by a phenomenon called genomic imprinting. When genomic imprinting reduces the ... 2 links) Eunice Kennedy Shriver National Institute of Child Health and Human Development: Adrenal Gland Disorders National ...

  1. Haematopoietic stem and progenitor cells from human pluripotent stem cells

    Science.gov (United States)

    Sugimura, Ryohichi; Jha, Deepak Kumar; Han, Areum; Soria-Valles, Clara; da Rocha, Edroaldo Lummertz; Lu, Yi-Fen; Goettel, Jeremy A.; Serrao, Erik; Rowe, R. Grant; Malleshaiah, Mohan; Wong, Irene; Sousa, Patricia; Zhu, Ted N.; Ditadi, Andrea; Keller, Gordon; Engelman, Alan N.; Snapper, Scott B.; Doulatov, Sergei; Daley, George Q.

    2018-01-01

    A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts. We recover seven transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that are sufficient to convert haemogenic endothelium into haematopoietic stem and progenitor cells that engraft myeloid, B and T cells in primary and secondary mouse recipients. Our combined approach of morphogen-driven differentiation and transcription-factor-mediated cell fate conversion produces haematopoietic stem and progenitor cells from pluripotent stem cells and holds promise for modelling haematopoietic disease in humanized mice and for therapeutic strategies in genetic blood disorders. PMID:28514439

  2. Intrinsic radiation resistance in human chondrosarcoma cells

    International Nuclear Information System (INIS)

    Moussavi-Harami, Farid; Mollano, Anthony; Martin, James A.; Ayoob, Andrew; Domann, Frederick E.; Gitelis, Steven; Buckwalter, Joseph A.

    2006-01-01

    Human chondrosarcomas rarely respond to radiation treatment, limiting the options for eradication of these tumors. The basis of radiation resistance in chondrosarcomas remains obscure. In normal cells radiation induces DNA damage that leads to growth arrest or death. However, cells that lack cell cycle control mechanisms needed for these responses show intrinsic radiation resistance. In previous work, we identified immortalized human chondrosarcoma cell lines that lacked p16 ink4a , one of the major tumor suppressor proteins that regulate the cell cycle. We hypothesized that the absence of p16 ink4a contributes to the intrinsic radiation resistance of chondrosarcomas and that restoring p16 ink4a expression would increase their radiation sensitivity. To test this we determined the effects of ectopic p16 ink4a expression on chondrosarcoma cell resistance to low-dose γ-irradiation (1-5 Gy). p16 ink4a expression significantly increased radiation sensitivity in clonogenic assays. Apoptosis did not increase significantly with radiation and was unaffected by p16 ink4a transduction of chondrosarcoma cells, indicating that mitotic catastrophe, rather than programmed cell death, was the predominant radiation effect. These results support the hypothesis that p16 ink4a plays a role in the radiation resistance of chondrosarcoma cell lines and suggests that restoring p16 expression will improve the radiation sensitivity of human chondrosarcomas

  3. Asymptomatic myelolipoma of the adrenal.

    Science.gov (United States)

    Hadjigeorgi, C; Lafoyianni, S; Pontikis, Y; Van Vliet-Constantinidou, C

    1992-01-01

    Myelolipoma of the adrenal gland is a rare benign tumour which seldom produces symptoms unless it attains considerable size or hemorrhages into itself. Histologically the tumor is composed of varying proportions of fat and bone marrow elements. We present a case of a male child, with homozygous beta thalassemia and asymptomatic myelolipoma.

  4. Blood sampling from adrenal gland vein

    International Nuclear Information System (INIS)

    Sun Yong; Ni Caifang

    2009-01-01

    Adrenal gland vein sampling is an interventional method to get the blood samples from the adrenal gland vein. The blood is obtained via a catheter which is selectively inserted in the adrenal gland vein. This technique is mainly used to be diagnostic for primary hyperaldosteronism. A full knowledge of the anatomy and variations of the adrenal gland vein, serious preoperative preparation and skilled catheterization manipulation are necessary for obtaining sufficient blood sample and for reducing the occurrence of complications. Providing the physicians with definite diagnostic evidence and being technically feasible, adrenal gland vein sampling should become one of the routine examinations for clarifying the cause of primary hyperaldosteronism. (authors)

  5. DNA repair in human bronchial epithelial cells

    International Nuclear Information System (INIS)

    Fornace, A.J. Jr.; Lechner, J.F.; Grafstrom, R.C.; Harris, C.C.

    1982-01-01

    The purpose of this investigation was to compare the response of human cell types (bronchial epithelial cells and fibroblasts and skin fibroblasts) to various DNA damaging agents. Repair of DNA single strand breaks (SSB) induced by 5 krads of X-ray was similar for all cell types; approximately 90% of the DNA SSB were rejoined within one hour. During excision repair of DNA damage from u.v.-radiation, the frequencies of DNA SSB as estimated by the alkaline elution technique, were similar in all cell types. Repair replication as measured by BND cellulose chromatography was also similar in epithelial and fibroblastic cells after u.v.-irradiation. Similar levels of SSB were also observed in epithelial and fibroblastic cells after exposure to chemical carcinogens: 7,12-dimethylbenz[a]anthracene; benzo[a]pyrene diol epoxide (BPDE); or N-methyl-N-nitro-N-nitrosoguanidine. Significant repair replication of BPDE-induced DNA damage was detected in both bronchial epithelial and fibroblastic cells, although the level in fibroblasts was approximately 40% of that in epithelial cells. The pulmonary carcinogen asbestos did not damage DNA. DNA-protein crosslinks induced by formaldehyde were rapidly removed in bronchial cells. Further, epithelial and fibroblastic cells, which were incubated with formaldehyde and the polymerase inhibitor combination of cytosine arabinoside and hydroxyurea, accumulated DNA SSB at approximately equal frequencies. These results should provide a useful background for further investigations of the response of human bronchial cells to various DNA damaging agents

  6. Interaction of Staphylococci with Human B cells.

    Directory of Open Access Journals (Sweden)

    Tyler K Nygaard

    Full Text Available Staphylococcus aureus is a leading cause of human infections worldwide. The pathogen produces numerous molecules that can interfere with recognition and binding by host innate immune cells, an initial step required for the ingestion and subsequent destruction of microbes by phagocytes. To better understand the interaction of this pathogen with human immune cells, we compared the association of S. aureus and S. epidermidis with leukocytes in human blood. We found that a significantly greater proportion of B cells associated with S. epidermidis relative to S. aureus. Complement components and complement receptors were important for the binding of B cells with S. epidermidis. Experiments using staphylococci inactivated by ultraviolet radiation and S. aureus isogenic deletion mutants indicated that S. aureus secretes molecules regulated by the SaeR/S two-component system that interfere with the ability of human B cells to bind this bacterium. We hypothesize that the relative inability of B cells to bind S. aureus contributes to the microbe's success as a human pathogen.

  7. Adrenal Gland Microenvironment and Its Involvement in the Regulation of Stress-induced Hormone Secretion during Sepsis.

    Directory of Open Access Journals (Sweden)

    Waldemar Kanczkowski

    2016-12-01

    Full Text Available Survival of all living organisms depends on maintenance of a steady state of homeostasis, which process relies on its ability to react and adapt to various physical and emotional threats. The defense against stress is executed by the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal medullary system. Adrenal gland is a major effector organ of stress system. During stress adrenal gland rapidly respond with increased secretion of glucocorticoids and catecholamines into circulation, which hormones, in turn, affect metabolism, to provide acutely energy, vasculature to increase blood pressure and the immune system to prevent it from extensive activation. Sepsis resulting from microbial infections is a sustained and extreme example of stress situation. In many critical ill patients levels of both corticotropin-releasing hormone and adrenocorticotropin, two major regulators of adrenal hormone production, are suppressed. Levels of glucocorticoids however, remain normal or are elevated in these patients, suggesting a shift from central to local intraadrenal regulation of adrenal stress response. Among many mechanisms potentially involved in this process, reduced glucocorticoid metabolism and local intraadrenal activation of hormone production mediated by adrenocortical and chromaffin cell interactions, the adrenal vascular system and the immune-adrenal crosstalk play a key role. Consequently, any impairment in function of these systems, can ultimately affect adrenal stress response. The purpose of this mini review is to present and discuss recent advances in our understanding of the adrenal gland microenvironment, and its role in regulation of stress-induced hormone secretion.

  8. Adrenal Oncocytic Neoplasm with Paradoxical Loss of Important Mitochondrial Steroidogenic Protein: The 18 kDA Translocator Protein

    Directory of Open Access Journals (Sweden)

    Roberto Ruiz-Cordero

    2017-01-01

    Full Text Available The adrenal glands produce a variety of hormones that play a key role in the regulation of blood pressure, electrolyte homeostasis, metabolism, immune system suppression, and the body’s physiologic response to stress. Adrenal neoplasms can be asymptomatic or can overproduce certain hormones that lead to different clinical manifestations. Oncocytic adrenal neoplasms are infrequent tumors that arise from cells in the adrenal cortex and display a characteristic increase in the number of cytoplasmic mitochondria. Since the rate-limiting step in steroidogenesis includes the transport of cholesterol across the mitochondrial membranes, in part carried out by the 18-kDa translocator protein (TSPO, we assessed the expression of TSPO in a case of adrenal oncocytic neoplasm using residual adrenal gland of the patient as internal control. We observed a significant loss of TSPO immunofluorescence expression in the adrenal oncocytic tumor cells when compared to adjacent normal adrenal tissue. We further confirmed this finding by employing Western blot analysis to semiquantify TSPO expression in tumor and normal adrenal cells. Our findings could suggest a potential role of TSPO in the tumorigenesis of this case of adrenocortical oncocytic neoplasm.

  9. Clinical and laboratory evaluation of adrenal dysfunction

    International Nuclear Information System (INIS)

    Ashkar, F.S.; Fishman, L.M.

    1983-01-01

    Because of their special physical and chemical properties, the adrenal secretory products were among the first hormonal substances to be measured by methods other than bioassay. Over the past several years, the development of sensitive and specific methods of hormone assay dependent on the use of radionuclides has revolutionized investigative and clinical endocrinology. While the capacity of defining most abnormalities of adrenal function antedates hormone measurement and adrenal imaging utilizing radioisotopes, the availability of such methods has greatly facilitated and made more precise the diagnostic approach to patients with suspected adrenal dysfunction. As an example of how clinical and laboratory considerations can be integrated into a rational approach to the diagnosis of adrenal disease, the problem of suspected adrenal hyperfunction is analyzed in light of current understanding of its pathophysiology. Reflection demonstrates that suspected primary aldosteronism and adrenal insufficiency are equally amenable to such an approach

  10. Adrenal failure due to bilateral adrenal metastasis of rectal cancer: A case report.

    Science.gov (United States)

    Imaoka, Yuki; Kuranishi, Fumito; Ogawa, Yoshiteru; Okuda, Hiroshi; Nakahara, Masahiro

    2017-01-01

    It is rare for a patient to present with adrenal insufficiency secondary to bilateral adrenal metastases from a malignant colorectal tumor. An 82-year-old Japanese man presented to our hospital with high fever and malaise. He was receiving oral chemotherapy for the treatment of rectal cancer with multiple metastases. Computed tomography showed new bilateral adrenal gland metastases. A rapid adrenocorticotropic hormone (ACTH) test showed adrenal insufficiency. Treatment with hydrocortisone provided immediate symptom improvement. Adrenal insufficiency secondary to bilateral adrenal metastases from rectal cancer is rare. A rapid ACTH test is useful to diagnose adrenal insufficiency. The incidence of adrenal insufficiency may be underestimated in patients with multiple metastasis. Appropriate therapy with adrenal corticosteroid hormone supplementation may lead to a significant improvement in the patient's symptoms and quality of life. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  11. Isolation of Human Innate Lymphoid Cells.

    Science.gov (United States)

    Krabbendam, Lisette; Nagasawa, Maho; Spits, Hergen; Bal, Suzanne M

    2018-06-29

    Innate lymphoid cells (ILCs) are innate immune cells of lymphoid origin that have important effector and regulatory functions in the first line of defense against pathogens, but also regulate tissue homeostasis, remodeling, and repair. Their function mirrors T helper cells and cytotoxic CD8 + T lymphocytes, but they lack expression of rearranged antigen-specific receptors. Distinct ILC subsets are classified in group 1 ILCs (ILC1s), group 2 ILCs (ILC2s), and group 3 ILCs (ILC3s and lymphoid tissue-inducer cells), based on the expression of transcription factors and the cytokines they produce. As the frequency of ILCs is low, their isolation requires extensive depletion of other cell types. The lack of unique cell surface antigens further complicates the identification of these cells. Here, methods for ILC isolation and characterization from human peripheral blood and different tissues are described. © 2018 by John Wiley & Sons, Inc. © 2018 John Wiley & Sons, Inc.

  12. Aberrant gonadotropin-releasing hormone receptor (GnRHR) expression and its regulation of CYP11B2 expression and aldosterone production in adrenal aldosterone-producing adenoma (APA).

    Science.gov (United States)

    Nakamura, Yasuhiro; Hattangady, Namita G; Ye, Ping; Satoh, Fumitoshi; Morimoto, Ryo; Ito-Saito, Takako; Sugawara, Akira; Ohba, Koji; Takahashi, Kazuhiro; Rainey, William E; Sasano, Hironobu

    2014-03-25

    Aberrant expression of gonadotropin-releasing hormone receptor (GnRHR) has been reported in human adrenal tissues including aldosterone-producing adenoma (APA). However, the details of its expression and functional role in adrenals are still not clear. In this study, quantitative RT-PCR analysis revealed the mean level of GnRHR mRNA was significantly higher in APAs than in human normal adrenal (NA) (P=0.004). GnRHR protein expression was detected in human NA and neoplastic adrenal tissues. In H295R cells transfected with GnRHR, treatment with GnRH resulted in a concentration-dependent increase in CYP11B2 reporter activity. Chronic activation of GnRHR with GnRH (100nM), in a cell line with doxycycline-inducible GnRHR (H295R-TR/GnRHR), increased CYP11B2 expression and aldosterone production. These agonistic effects were inhibited by blockers for the calcium signaling pathway, KN93 and calmidazolium. These results suggest GnRH, through heterotopic expression of its receptor, may be a potential regulator of CYP11B2 expression levels in some cases of APA. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Human CD56bright NK Cells

    DEFF Research Database (Denmark)

    Michel, Tatiana; Poli, Aurélie; Cuapio, Angelica

    2016-01-01

    Human NK cells can be subdivided into various subsets based on the relative expression of CD16 and CD56. In particular, CD56(bright)CD16(-/dim) NK cells are the focus of interest. They are considered efficient cytokine producers endowed with immunoregulatory properties, but they can also become c...... NK cell subsets is not fully defined, nor is their precise hematopoietic origin. In this article, we summarize recent studies about CD56(bright) NK cells in health and disease and briefly discuss the current controversies surrounding them....

  14. Evaluating human cancer cell metastasis in zebrafish

    International Nuclear Information System (INIS)

    Teng, Yong; Xie, Xiayang; Walker, Steven; White, David T; Mumm, Jeff S; Cowell, John K

    2013-01-01

    In vivo metastasis assays have traditionally been performed in mice, but the process is inefficient and costly. However, since zebrafish do not develop an adaptive immune system until 14 days post-fertilization, human cancer cells can survive and metastasize when transplanted into zebrafish larvae. Despite isolated reports, there has been no systematic evaluation of the robustness of this system to date. Individual cell lines were stained with CM-Dil and injected into the perivitelline space of 2-day old zebrafish larvae. After 2-4 days fish were imaged using confocal microscopy and the number of metastatic cells was determined using Fiji software. To determine whether zebrafish can faithfully report metastatic potential in human cancer cells, we injected a series of cells with different metastatic potential into the perivitelline space of 2 day old embryos. Using cells from breast, prostate, colon and pancreas we demonstrated that the degree of cell metastasis in fish is proportional to their invasion potential in vitro. Highly metastatic cells such as MDA231, DU145, SW620 and ASPC-1 are seen in the vasculature and throughout the body of the fish after only 24–48 hours. Importantly, cells that are not invasive in vitro such as T47D, LNCaP and HT29 do not metastasize in fish. Inactivation of JAK1/2 in fibrosarcoma cells leads to loss of invasion in vitro and metastasis in vivo, and in zebrafish these cells show limited spread throughout the zebrafish body compared with the highly metastatic parental cells. Further, knockdown of WASF3 in DU145 cells which leads to loss of invasion in vitro and metastasis in vivo also results in suppression of metastasis in zebrafish. In a cancer progression model involving normal MCF10A breast epithelial cells, the degree of invasion/metastasis in vitro and in mice is mirrored in zebrafish. Using a modified version of Fiji software, it is possible to quantify individual metastatic cells in the transparent larvae to correlate with

  15. Experience with surgical treatment for primary malignant adrenal tumors

    Directory of Open Access Journals (Sweden)

    V. R. Latypov

    2016-01-01

    Full Text Available Background. Adrenal tumors occur in 3–10 % of the population and are mostly benign adrenal cortical tumors. Adrenocortical carcinoma is a very rare tumor and has an annual incidence of 1–2 cases per million people. The U.S. National Cancer Data Base registered 4275 patients with adrenocortical carcinoma in 1985 to 2007. It is extremely difficult to assess Russia’s epidemiological data, as reports on adrenocortical carcinoma are not presented separately.Materials and methods. A total of 133 patients (49 men and 84 women (1:1.7 with adrenal tumors were operated on at the clinics of the Siberian State Medical University in the period December 1998 to March 2015. The patients’ mean age was 51.3 (16–80 years (median age 51.0 years. The right and left adrenal glands were affected in 49 (36.9 % and 77 (57.9 % patients, respectively; both adrenal glands were involved in 7 (5.3 %. A group of 21 (15.8 % people with primary malignant adrenal tumors was identified among all the patients. The clinical manifestations of the disease were evaluated from the presence of hormonal activity, gastrointestinal symptoms, pain syndrome, and hypertension. All the patients were operated on under endotracheal anesthesia. The data were statistically processed using the program package Statistica 6.0. Survival rates were analyzed by the Kaplan–Meier method. The Gehan–Wilcoxon test was used to compare the groups.Results. The investigation analyzed treatment results in 21 (15.8 % patients with primary malignant adrenal lesions (Group 1. The most common morphological form was adrenocortical carcinoma in 15 (11.3 % patients (5 men and 10 women (1:2; their mean age was 48.1 years. The right, left, and both adrenal glands were affected in 4, 9, and 2 cases, respectively. In Group 2, other malignant adrenal involvements were identified from 1 case of rare malignant adrenal tumors: malignant pheochromocytoma, sarcoma, melanoma, squamous cell

  16. A prenatally detected adrenal cyst treated by adrenal-sparing ...

    African Journals Online (AJOL)

    Ahmet Dursun and Munevver Ho ¸sgo¨ r. A neonatal case of left adrenal cyst detected in utero and ... Correspondence to Munevver Ho ¸sgör, MD, PhD, Department II of Pediatric. Surgery, Dr Behcet Uz Children's Hospital, Koruturk Mh. ..... Radiology 1986; 161:631–633. 13 Erbil Y, Salmasliog˘lu A, Barbaros U, Bozbora A, ...

  17. Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins

    OpenAIRE

    Hayato Fukusumi; Tomoko Shofuda; Yohei Bamba; Atsuyo Yamamoto; Daisuke Kanematsu; Yukako Handa; Keisuke Okita; Masaya Nakamura; Shinya Yamanaka; Hideyuki Okano; Yonehiro Kanemura

    2016-01-01

    Human neural progenitor cells (hNPCs) have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC) clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB) formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi). Our results showed that expandable hNPCs could be generated from hiPS...

  18. Human Mammary Luminal Epithelial Cells Contain Progenitors to Myoepithelial Cells

    Energy Technology Data Exchange (ETDEWEB)

    Pechoux, Christine; Gudjonsson, Thorarinn; Ronnov-Jessen, Lone; Bissell, Mina J; Petersen, Ole

    1999-02-01

    The origin of the epithelial and myoepithelial cells in the human breast has not been delineated. In this study we have addressed whether luminal epithelial cells and myoepithelial cells are vertically connected, i.e., whether one is the precursor for the other. We used a primary culture assay allowing preservation of basic phenotypic traits of luminal epithelial and myoepithelial cells in culture. The two cell types were then separated immunomagnetically using antibodies directed against lineage-specific cell surface antigens into at best 100% purity. The cellular identity was ascertained by cytochemistry, immunoblotting, and 2-D gel electrophoresis. Luminal epithelial cells were identified by strong expression of cytokeratins 18 and 19 while myoepithelial cells were recognized by expression of vimentin and {alpha}-smooth muscle actin. We used a previously devised culture medium (CDM4) that allows vigorous expansion of proliferative myoepithelial cells and also devised a medium (CDM6) that allowed sufficient expansion of differentiated luminal epithelial cells based on addition of hepatocyte growth factor/scatter factor. The two different culture media supported each lineage for at least five passages without signs of interconversion. We used parallel cultures where we switched culture media, thus testing the ability of each lineage to convert to the other. Whereas the myoepithelial lineage showed no signs of interconversion, a subset of luminal epithelial cells, gradually, but distinctly, converted to myoepithelial cells. We propose that in the mature human breast, it is the luminal epithelial cell compartment that gives rise to myoepithelial cells rather than the other way around.

  19. 3 CFR - Guidelines for Human Stem Cell Research

    Science.gov (United States)

    2010-01-01

    ... 3 The President 1 2010-01-01 2010-01-01 false Guidelines for Human Stem Cell Research Presidential Documents Other Presidential Documents Memorandum of July 30, 2009 Guidelines for Human Stem Cell Research..., scientifically worthy human stem cell research, including human embryonic stem cell research, to the extent...

  20. 21 CFR 864.2280 - Cultured animal and human cells.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cultured animal and human cells. 864.2280 Section... Cultured animal and human cells. (a) Identification. Cultured animal and human cells are in vitro cultivated cell lines from the tissue of humans or other animals which are used in various diagnostic...

  1. Primary adrenal leiomyosarcoma: A case report with immunohistochemical study and review of literature

    Directory of Open Access Journals (Sweden)

    Sanjay D Deshmukh

    2013-01-01

    Full Text Available Primary adrenal mesenchymal tumors are exceptionally rare. Diagnosis is based entirely on histological and immunohistochemical evaluation which is indispensable not only for determining tumor type but also for predicting biological behavior. We report a rare case of primary leiomyosarcoma of the left adrenal gland, in a 60 year old woman who presented with flank pain. Computed tomography revealed a well defined left adrenal tumor which was surgically resected. Histological examination of the tumor showed malignant spindle cells in interlacing fascicles and whorls. Nuclear pleomorphism, tumor giant cells and abnormal mitotic figures were seen. On immunohistochemistry, the tumor cells showed reactivity for smooth muscle actin, vimentin and desmin; and were negative for cytokeratin, S100 protein, CD117 and HMB-45. A diagnosis of primary adrenal leiomyosarcoma was offered. Postoperative recovery of the patient was uneventful and the patient was symptom free with no evidence of tumor metastasis or recurrence 21 months after surgery.

  2. Cell pattern in adult human corneal endothelium.

    Directory of Open Access Journals (Sweden)

    Carlos H Wörner

    Full Text Available A review of the current data on the cell density of normal adult human endothelial cells was carried out in order to establish some common parameters appearing in the different considered populations. From the analysis of cell growth patterns, it is inferred that the cell aging rate is similar for each of the different considered populations. Also, the morphology, the cell distribution and the tendency to hexagonallity are studied. The results are consistent with the hypothesis that this phenomenon is analogous with cell behavior in other structures such as dry foams and grains in polycrystalline materials. Therefore, its driving force may be controlled by the surface tension and the mobility of the boundaries.

  3. Merkel cell distribution in the human eyelid

    Directory of Open Access Journals (Sweden)

    C.A. May

    2013-10-01

    Full Text Available Although Merkel cell carcinoma of the eye lid is reported frequently in the literature, only limited information exists about the distribution of Merkel cells in this tissue. Therefore, serial sections of 18 human cadaver eye lids (donors ages ranging between 63 and 97 years were stained for cytokeratin 20 in various planes. The overall appearance of Merkel cells in these samples was low and mainly located in the outer root layer of the cilia hair follicles. Merkel cells were more frequent in the middle, and almost not detectable at the nasal and temporal edges. The localization is in accordance with that of Merkel cell carcinoma, but concerning the scarce appearance within this adulthood group, a specific physiological role of these cells in the eye lid is difficult to establish.

  4. Haemopoietic progenitor cells in human peripheral blood

    International Nuclear Information System (INIS)

    Zwaan, F.E.

    1980-01-01

    The purpose of the investigation reported is to purify haemopoietic progenitor cells from human peripheral blood using density gradient centrifugation in order to isolate a progenitor cell fraction without immunocompetent cells. The purification technique of peripheral blood flow colony forming unit culture (CFU-c) by means of density gradient centrifugation and a combined depletion of various rosettes is described. The results of several 'in vitro' characteristics of purified CFU-c suspensions and of the plasma clot diffusion chamber culture technique are presented. Irradiation studies revealed that for both human bone marrow and peripheral blood the CFU-c were less radioresistant than clusters. Elimination of monocytes (and granulocytes) from the test suspensions induced an alteration in radiosensitivity pararmeters. The results obtained with the different techniques are described by analysing peripheral progenitor cell activity in myeloproliferative disorders. (Auth.)

  5. T-cell response in human leishmaniasis

    DEFF Research Database (Denmark)

    Kharazmi, A; Kemp, K; Ismail, A

    1999-01-01

    In the present communication we provide evidence for the existence of a Th1/Th2 dichotomy in the T-cell response to Leishmania antigens in human leishmaniasis. Our data suggest that the pattern of IL-4 and IFN-gamma response is polarised in these patients. Lymphocytes from individuals recovered...... from cutaneous leishmaniasis (CL) responded by IFN-gamma production following stimulation with Leishmania antigens whereas cells from patients recovered from visceral leishmaniasis (VL) showed a mixed pattern of IFN-gamma and IL-4 responses. The cells producing these cytokines were predominantly CD4......+. Furthermore, IL-10 plays an important role in the development of post kala azar dermal leishmaniasis (PKDL) from VL. The balance between the parasitic-specific T-cell response plays an important regulatory role in determining the outcome of Leishmania infections in humans....

  6. Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells

    Directory of Open Access Journals (Sweden)

    Chen Chang-Jie

    2010-10-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC still is a big burden for China. In recent years, the third-generation platinum compounds have been proposed as potential active agents for HCC. However, more experimental and clinical data are warranted to support the proposal. In the present study, the effect of lobaplatin was assessed in five HCC cell lines and the underlying molecular mechanisms in terms of cell cycle kinetics were explored. Methods Cytotoxicity of lobaplatin to human HCC cell lines was examined using MTT cell proliferation assay. Cell cycle distribution was determined by flow cytometry. Expression of cell cycle-regulated genes was examined at both the mRNA (RT-PCR and protein (Western blot levels. The phosphorylation status of cyclin-dependent kinases (CDKs and retinoblastoma (Rb protein was also examined using Western blot analysis. Results Lobaplatin inhibited proliferation of human HCC cells in a dose-dependent manner. For the most sensitive SMMC-7721 cells, lobaplatin arrested cell cycle progression in G1 and G2/M phases time-dependently which might be associated with the down-regulation of cyclin B, CDK1, CDC25C, phosphorylated CDK1 (pCDK1, pCDK4, Rb, E2F, and pRb, and the up-regulation of p53, p21, and p27. Conclusion Cytotoxicity of lobaplatin in human HCC cells might be due to its ability to arrest cell cycle progression which would contribute to the potential use of lobaplatin for the management of HCC.

  7. Human Monoclonal Islet Cell Antibodies From a Patient with Insulin- Dependent Diabetes Mellitus Reveal Glutamate Decarboxylase as the Target Antigen

    Science.gov (United States)

    Richter, Wiltrud; Endl, Josef; Eiermann, Thomas H.; Brandt, Michael; Kientsch-Engel, Rosemarie; Thivolet, Charles; Jungfer, Herbert; Scherbaum, Werner A.

    1992-09-01

    The autoimmune phenomena associated with destruction of the β cell in pancreatic islets and development of type 1 (insulin-dependent) diabetes mellitus (IDDM) include circulating islet cell antibodies. We have immortalized peripheral blood lymphocytes from prediabetic individuals and patients with newly diagnosed IDDM by Epstein-Barr virus transformation. IgG-positive cells were selected by anti-human IgG-coupled magnetic beads and expanded in cell culture. Supernatants were screened for cytoplasmic islet cell antibodies using the conventional indirect immunofluorescence test on cryostat sections of human pancreas. Six islet cell-specific B-cell lines, originating from a patient with newly diagnosed IDDM, could be stabilized on a monoclonal level. All six monoclonal islet cell antibodies (MICA 1-6) were of the IgG class. None of the MICA reacted with human thyroid, adrenal gland, anterior pituitary, liver, lung, stomach, and intestine tissues but all six reacted with pancreatic islets of different mammalian species and, in addition, with neurons of rat cerebellar cortex. MICA 1-6 were shown to recognize four distinct antigenic epitopes in islets. Islet cell antibody-positive diabetic sera but not normal human sera blocked the binding of the monoclonal antibodies to their target epitopes. Immunoprecipitation of 35S-labeled human islet cell extracts revealed that a protein of identical size to the enzyme glutamate decarboxylase (EC 4.1.1.15) was a target of all MICA. Furthermore, antigen immunotrapped by the MICA from brain homogenates showed glutamate decarboxylase enzyme activity. MICA 1-6 therefore reveal glutamate decarboxylase as the predominant target antigen of cytoplasmic islet cell autoantibodies in a patient with newly diagnosed IDDM.

  8. Congenital adrenal hyperplasia: Case report.

    OpenAIRE

    Jaime Avaria E.; María José Vargas F.; Loreto Triviño F.; Andrea Gleisner E.

    2013-01-01

    INTRODUCTION: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease whose main cause is the deficiency of 21-hydroxylase, an enzyme involved in the synthesis of cortisol and aldosterone. There are two forms of CAH, a classical and nonclassical form, being the first objective of analysis in the clinical case. Its clinical manifestations vary in severity, depending on the level of hormone deficiency. Within the classic is described the salt-wasting form, whose consequences are ...

  9. Extra-adrenal malignant paragangliomas presenting as mesenteric and pararectal masses: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sun Hye [Dept. of Radiology, Korea University Anam Hospital, Korea University College of Medicine, Seoul (Korea, Republic of); Lee, Jong Mee; Kim, Baek Hui; Kim, Kyeong Ah; Park, Cheol Min [Korea University Guro Hospital, Korea University College of Medicine, Seoul (Korea, Republic of)

    2017-07-15

    Extra-adrenal paraganglioma is a rare tumor arising from the neural crest cells. Most tumors that develop in the abdomen arise from paraganglia along the paravertebral and para-aortic areas, in particular the organ of Zuckerkandl, which is close to the origin of the inferior mesenteric artery. However, extra-adrenal paraganglioma also occurs in relatively rare places such as the urinary bladder, gallbladder, hepatoduodenal ligament, and gastrointestinal tract. Here, we report imaging findings of extra-adrenal paragangliomas presenting as mesenteric and pararectal masses with lymph node metastasis.

  10. Shape Memory of Human Red Blood Cells

    OpenAIRE

    Fischer, Thomas M.

    2004-01-01

    The human red cell can be deformed by external forces but returns to the biconcave resting shape after removal of the forces. If after such shape excursions the rim is always formed by the same part of the membrane, the cell is said to have a memory of its biconcave shape. If the rim can form anywhere on the membrane, the cell would have no shape memory. The shape memory was probed by an experiment called go-and-stop. Locations on the membrane were marked by spontaneously adhering latex spher...

  11. The Role of gsp Mutations on the Development of Adrenal Cortical Tumors and Adrenal Hyperplasias

    Directory of Open Access Journals (Sweden)

    Maria Candida Barisson Villares Fragoso

    2016-07-01

    Full Text Available Somatic GNAS point mutations, commonly known as gsp mutations, are involved in the pathogenesis of McCune Albright syndrome and have also been described in autonomous hormone-producing tumors, such as somatotropinoma, corticotrophoma, thyroid cancer, ovarian and testicular Leydig cell tumors and primary macronodular adrenocortical hyperplasia (PMAH. [1-3]The involvement of gsp mutations in adrenal tumors was first described by Lyons et al. in 1990. Since then, several studies have detected the presence of gsp mutations in adrenal tumors, but none of them could explain its presence along or the mechanism that leads to tumor formation and hormone hypersecretion. As a result, the molecular pathogenesis of the majority of sporadic adrenocortical tumors remains unclear. [3] PMAH has also been reported with gsp somatic mutations in a few cases. Fragoso et al. in 2003 identified two distinct gsp somatic mutations affecting arginine residues on codon 201 of GNAS in a few patients with PMAH who lacked any features or manifestations of McCune Albright syndrome. Followed by this discovery, other studies have continued looking for gsp mutations based on strong prior evidence demonstrating that increased cAMP signaling is sufficient for cell proliferation and cortisol production. [2, 4] With consideration for the previously reported findings, we conjecture that although somatic activating mutations in GNAS are a rare molecular event, these mutations could probably be sufficient to induce the development of macronodule hyperplasia and variable cortisol secretion.In this manuscript, we revised the presence of gsp mutations associated with adrenal cortical tumors and hyperplasia.

  12. Severe polyuria after the resection of adrenal pheochromocytoma.

    Science.gov (United States)

    Tobe, Musashi; Ito, Keiichi; Umeda, Shun; Sato, Akinori; Adaniya, Noriaki; Tanaka, Yuji; Hayakawa, Masamichi; Asano, Tomohiko

    2010-12-01

    A 73-year-old male patient with hypertension and hyperglycemia was referred to our hospital because of a diagnosis regarding his left adrenal tumor. Because the levels of urinary metanephrine and normetanephrine were elevated, and (131) I-MIBG scintigraphy showed intense uptake in the adrenal tumor, the tumor was diagnosed as a pheochromocytoma. An adrenalectomy was carried out. Severe polyuria, which was accompanied by a rapid decrease in central venous pressure, started 1 hour after the operation. Urine output of more than 8000 mL/day continued until the 16th postoperative day. Plasma antidiuretic hormone (ADH) levels were within the normal range. Plasma human atrial natriuretic peptide (hANP) and brain natriuretic peptide (BNP) were elevated postoperatively, and the elevation of these peptides was one possible cause for the severe polyuria. Because ADH levels in the tumor fluid were not elevated, the tumor was not an ADH-secreting tumor. Urinary β2-microglobulin was significantly elevated after the operation, thus suggesting that renal tubule dysfunction might also have been involved in the polyuria. However, the mechanism of polyuria after the resection of adrenal pheochromocytoma is not fully understood. Polyuria after the resection of adrenal pheochromocytoma is extremely rare, and the present subject is the second case to date. © 2010 The Japanese Urological Association.

  13. Human embryonic stem cell lines model experimental human cytomegalovirus latency.

    Science.gov (United States)

    Penkert, Rhiannon R; Kalejta, Robert F

    2013-05-28

    Herpesviruses are highly successful pathogens that persist for the lifetime of their hosts primarily because of their ability to establish and maintain latent infections from which the virus is capable of productively reactivating. Human cytomegalovirus (HCMV), a betaherpesvirus, establishes latency in CD34(+) hematopoietic progenitor cells during natural infections in the body. Experimental infection of CD34(+) cells ex vivo has demonstrated that expression of the viral gene products that drive productive infection is silenced by an intrinsic immune defense mediated by Daxx and histone deacetylases through heterochromatinization of the viral genome during the establishment of latency. Additional mechanistic details about the establishment, let alone maintenance and reactivation, of HCMV latency remain scarce. This is partly due to the technical challenges of CD34(+) cell culture, most notably, the difficulty in preventing spontaneous differentiation that drives reactivation and renders them permissive for productive infection. Here we demonstrate that HCMV can establish, maintain, and reactivate in vitro from experimental latency in cultures of human embryonic stem cells (ESCs), for which spurious differentiation can be prevented or controlled. Furthermore, we show that known molecular aspects of HCMV latency are faithfully recapitulated in these cells. In total, we present ESCs as a novel, tractable model for studies of HCMV latency.

  14. Adrenal failure due to bilateral adrenal metastasis of rectal cancer: A case report

    Directory of Open Access Journals (Sweden)

    Yuki Imaoka

    2017-01-01

    Conclusion: The incidence of adrenal insufficiency may be underestimated in patients with multiple metastasis. Appropriate therapy with adrenal corticosteroid hormone supplementation may lead to a significant improvement in the patient’s symptoms and quality of life.

  15. Human embryonic stem cells: preclinical perspectives

    Directory of Open Access Journals (Sweden)

    Sarda Kanchan

    2008-01-01

    Full Text Available Abstract Human embryonic stem cells (hESCs have been extensively discussed in public and scientific communities for their potential in treating diseases and injuries. However, not much has been achieved in turning them into safe therapeutic agents. The hurdles in transforming hESCs to therapies start right with the way these cells are derived and maintained in the laboratory, and goes up-to clinical complications related to need for patient specific cell lines, gender specific aspects, age of the cells, and several post transplantation uncertainties. The different types of cells derived through directed differentiation of hESC and used successfully in animal disease and injury models are described briefly. This review gives a brief outlook on the present and the future of hESC based therapies, and talks about the technological advances required for a safe transition from laboratory to clinic.

  16. Neocortical glial cell numbers in human brains

    DEFF Research Database (Denmark)

    Pelvig, D.P.; Pakkenberg, H.; Stark, A.K.

    2008-01-01

    Stereological cell counting was applied to post-mortem neocortices of human brains from 31 normal individuals, age 18-93 years, 18 females (average age 65 years, range 18-93) and 13 males (average age 57 years, range 19-87). The cells were differentiated in astrocytes, oligodendrocytes, microglia...... while the total astrocyte number is constant through life; finally males have a 28% higher number of neocortical glial cells and a 19% higher neocortical neuron number than females. The overall total number of neocortical neurons and glial cells was 49.3 billion in females and 65.2 billion in males...... and neurons and counting were done in each of the four lobes. The study showed that the different subpopulations of glial cells behave differently as a function of age; the number of oligodendrocytes showed a significant 27% decrease over adult life and a strong correlation to the total number of neurons...

  17. Optimal glucocorticoid replacement in adrenal insufficiency.

    Science.gov (United States)

    Øksnes, Marianne; Ross, Richard; Løvås, Kristian

    2015-01-01

    Adrenal insufficiency (glucocorticoid deficiency) comprises a group of rare diseases, including primary adrenal insufficiency, secondary adrenal insufficiency and congenital adrenal hyperplasia. Lifesaving glucocorticoid therapy was introduced over 60 years ago, but since then a number of advances in treatment have taken place. Specifically, little is known about short- and long-term treatment effects, and morbidity and mortality. Over the past decade, systematic cohort and registry studies have described reduced health-related quality of life, an unfavourable metabolic profile and increased mortality in patients with adrenal insufficiency, which may relate to unphysiological glucocorticoid replacement. This has led to the development of new modes of replacement that aim to mimic normal glucocorticoid physiology. Here, evidence for the inadequacy of conventional glucocorticoid therapy and recent developments in treatment are reviewed, with an emphasis on primary adrenal insufficiency. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Primitive neuroectodermal tumor of adrenal: Clinical presentation and outcomes

    Directory of Open Access Journals (Sweden)

    Deep Dutta

    2013-01-01

    Full Text Available Primitive neuroectodermal tumor (PNET of adrenal is an extremely rare tumor of neural crest origin. A nonfunctional left adrenal mass (14.6 × 10.5 × 10.0 cm on computed tomography (CT was detected in a 40-year-old lady with abdominal pain, swelling, and left pleural effusion. She underwent left adrenalectomy and left nephrectomy with retroperitoneal resection. Histopathology revealed sheets and nest of oval tumor cells with hyperchromatic nuclei, prominent nucleoli, scanty cytoplasm, brisk mitotic activity, necrosis, lymphovascular invasion, capsular invasion, and extension to the surrounding muscles; staining positive for Mic-2 (CD-99 antigen, vimentin, synaptophysin, and Melan-A. Thoracocentesis, pleural fluid study, and pleural biopsy did not show metastasis. She responded well to vincristine, adriamycin, and cyclophosphamide followed by ifosfamide and etoposide (IE. This is the first report of adrenal peripheral PNET (pPNET from India. This report intends to highlight that pPNET should be suspected in a patient presenting with huge nonfunctional adrenal mass which may be confused with adrenocortical carcinoma.

  19. Melanopsin expressing human retinal ganglion cells

    DEFF Research Database (Denmark)

    Hannibal, Jens; Christiansen, Anders Tolstrup; Heegaard, Steffen

    2017-01-01

    microscopy and 3D reconstruction of melanopsin immunoreactive (-ir) RGCs, we applied the criteria used in mouse on human melanopsin-ir RGCs. We identified M1, displaced M1, M2, and M4 cells. We found two other subtypes of melanopsin-ir RGCs, which were named "gigantic M1 (GM1)" and "gigantic displaced M1...

  20. Secretion of [Met]enkephalyl-Arg6-Phe7-related peptides and catecholamines from bovine adrenal chromaffin cells: modification by changes in cyclic AMP and by treatment with reserpine.

    Science.gov (United States)

    Adams, M; Boarder, M R

    1987-07-01

    Investigations into the effects of culturing bovine adrenal chromaffin cells in the presence (72 h) of dibutyryl cyclic AMP, forskolin, and reserpine on the level and release of [Met]enkephalyl-Arg6-Phe7 immunoreactivity, noradrenaline, and adrenaline are reported. The assay for [Met]enkephalyl-Arg6-Phe7 immunoreactivity recognises both peptide B, the 31-amino acid carboxy-terminal segment of proenkephalin, and its heptapeptide fragment, [Met]enkephalyl-Arg6-Phe7. Treatments that elevate cyclic AMP increase the amount of peptide immunoreactivity in these cells; this is predominantly peptide B-like immunoreactivity in both control cells and cyclic AMP-elevated cells. Treatment with reserpine gives no change in total immunoreactivity levels, but does not result in increased accumulation of the heptapeptide [Met]enkephalyl-Arg6-Phe7 at the expense of immunoreactivity that elutes with its immediate precursor, peptide B. Cyclic AMP treatment causes either no change or a decrease in levels of accumulated noradrenaline and adrenaline. However, the release of [Met]enkephalin-Arg6-Phe7 immunoreactivity, noradrenaline, and adrenaline is increased by 72-h pretreatment with forskolin or dibutyryl cyclic AMP, whether release is stimulated by nicotine or elevated potassium. In each case the molecular form of [Met]enkephalyl-Arg6-Phe7 immunoreactivity that is released approximately reflects the cell content. Pretreatment with reserpine has no effect on the total [Met]enkephalyl-Arg6-Phe7 immunoreactivity released, but does result in an increased release of the heptapeptide and a decrease in release of peptide B-like immunoreactivity. The studies suggest that the levels of [Met]enkephalyl-Arg6-Phe7 and peptide B available for release are controlled both at the level of proenkephalin synthesis and at the level of double-basic residue proteolysis.

  1. Clinical potentials of human pluripotent stem cells.

    Science.gov (United States)

    Mora, Cristina; Serzanti, Marialaura; Consiglio, Antonella; Memo, Maurizio; Dell'Era, Patrizia

    2017-08-01

    Aging, injuries, and diseases can be considered as the result of malfunctioning or damaged cells. Regenerative medicine aims to restore tissue homeostasis by repairing or replacing cells, tissues, or damaged organs, by linking and combining different disciplines including engineering, technology, biology, and medicine. To pursue these goals, the discipline is taking advantage of pluripotent stem cells (PSCs), a peculiar type of cell possessing the ability to differentiate into every cell type of the body. Human PSCs can be isolated from the blastocysts and maintained in culture indefinitely, giving rise to the so-called embryonic stem cells (ESCs). However, since 2006, it is possible to restore in an adult cell a pluripotent ESC-like condition by forcing the expression of four transcription factors with the rejuvenating reprogramming technology invented by Yamanaka. Then the two types of PSC can be differentiated, using standardized protocols, towards the cell type necessary for the regeneration. Although the use of these derivatives for therapeutic transplantation is still in the preliminary phase of safety and efficacy studies, a lot of efforts are presently taking place to discover the biological mechanisms underlying genetic pathologies, by differentiating induced PSCs derived from patients, and new therapies by challenging PSC-derived cells in drug screening.

  2. Pigment Production Analysis in Human Melanoma Cells.

    Science.gov (United States)

    Hopkin, Amelia Soto; Paterson, Elyse K; Ruiz, Rolando; Ganesan, Anand K

    2016-05-25

    The human epidermal melanocyte is a highly specialized pigmented cell that serves to protect the epidermis from ultraviolet (UV) damage through the production of melanin, or melanogenesis. Misregulation in melanogenesis leading to either hyper- or hypo-pigmentation is found in human diseases such as malasma and vitiligo. Current therapies for these diseases are largely unsuccessful and the need for new therapies is necessary. In order to identify genes and or compounds that can alter melanogenesis, methods are required that can detect changes in pigment production as well as expression of key melanogenesis transcription factors and enzymes. Here we describe methods to detect changes in melanogenesis in a human melanoma cell line, MNT-1, by (1) analyzing pigment production by measuring the absorbance of melanin present by spectrophotometry, (2) analyzing transcript expression of potent regulators of melanogenesis by qunatitative reverse-transcription (RT)PCR and (3) analyzing protein expression of potent regulators of melanogenesis by Western blot (WB).

  3. Severe bilateral adrenal hemorrhages in a newborn complicated by persistent adrenal insufficiency

    OpenAIRE

    Zessis, Nicholas R; Nicholas, Jennifer L; Stone, Stephen I

    2018-01-01

    Summary Bilateral adrenal hemorrhages rarely occur during the neonatal period and are often associated with traumatic vaginal deliveries. However, the adrenal gland has highly regenerative capabilities and adrenal insufficiency typically resolves over time. We evaluated a newborn female after experiencing fetal macrosomia and a traumatic vaginal delivery. She developed acidosis and acute renal injury. Large adrenal hemorrhages were noted bilaterally on ultrasound, and she was diagnosed with a...

  4. Insuficiencia suprarrenal primaria por adrenalitis autoimnume

    OpenAIRE

    Muzzo B,Santiago; Izquierdo C,Gianina; Verbeke P,Sandra

    2002-01-01

    We report a 10 years old boy, admitted with a history of asthenia, anorexia and weight loss of 4 kg. Initial laboratory work up showed metabolic acidosis and hyponatremia. The patient had no circadian rhythm of serum cortisol and an adrenal stimulation test confirmed the presence of adrenal insufficiency. Anti-adrenal antibodies were positive. Treatment with cortisol and fluorocortisone resulted in a complete remission of symptoms (Rev Méd Chile 2002; 130: 901-6).

  5. Radiological diagnosis of the adrenal glands

    International Nuclear Information System (INIS)

    Engelbrecht, V.

    2005-01-01

    The adrenal gland is a common site of disease involving hormonal dysfunction as well as benign and malignant masses. Radiology, especially computed tomography (CT) and magnetic resonance (MR), plays a critical role in detecting and characterizing diseases affecting the adrenal gland. This paper contains a summary of the most important diseases of the adrenal gland and presents criteria for differentiating between benign and malignant masses as well as an algorithm for the diagnostic steps in incidentaloma. (orig.)

  6. Ultrasonographi assessment of congenital adrenal masses

    International Nuclear Information System (INIS)

    Muro Velilla, D.; Sanguesa, C.; Alberto, C.; Lopez, A., Benlloch, C.

    1996-01-01

    The demonstrate the utility of ultrasound (US) in the initial assessment and follow-up of newborns with adrenal masses. A series of 21 newborns presenting adrenal mass studied on the basis of US findings, clinical assessment and biochemical data. Seven patients had congenital neuroblastoma, two had a benign tumor and twelve presented adrenal hemorrhage. Postnatal US study of the course of these patients is essential for the differential diagnosis of their lesions when not diagnosed prenatally. (Author) 20 refs

  7. Computed tomography of adrenal Cushing's adenoma

    International Nuclear Information System (INIS)

    Yamada, Takayuki

    1990-01-01

    CT findings of 22 patients with surgically confirmed adrenal Cushing's adenomas were compared with pathologic findings. The cut surfaces of the adenomas showed mixture of yellow and brown areas in various proportions and were classified into three patterns; speckled brown areas in yellow background, geometrically brown areas in yellow background, totally brown or black surface. The maximum diameters of the cut surfaces were measured. The CT appearances of Cushing's adenomas after intravenous contrast administration have various patterns of enhancement and classified into three patterns; speckled, geometrical, and homoenous. The maximum diameters of the adenomas in CT images were also measured. Correlation between the CT and gross appearances of the specimens showed that while brown areas in adenomas were strongly enhanced, yellow areas were poorly enhanced. Histologically, brown areas in adenomas consist of compact-like cells with rich intercellular space and yellow areas consist of clear-like cells with poor intercellular space. The patterns of contrast enhancement some to depend on the cell types of adenomas. Difference in the intercellular space between compact and clear-like cells may have altered the patterns of contrast enhancement. The study also revealed that predominantly brownish adenomas were smaller in size than predominantly yellowish ones. As compact-like cells which make up the brown areas in Cushing's adenoma are thought to be more active in producing and secreting steroid hormones than clear-like cells, this result suggests that clinical symptoms may appear earlier in predominantly brownish adenomas than in predominantly yellowish ones. (author)

  8. An Unusual Case of Adrenal Incidentaloma

    Directory of Open Access Journals (Sweden)

    Turker Tasliyurt

    2014-09-01

    Full Text Available Adrenal incidentalomas are masses accidentally discovered while conducting radiological examinations for other purposes. A major part of adrenal incidentalomas are non-functional adenomas. Silently developing Cushing's syndrome or pheochromocytoma can be observed in adrenal incidentalomas. However, coexistence of Cushing's syndrome and pheochromocytoma at the same time in the same case is quite rare. In the present study, an atypical adrenal incidentaloma case is presented, whose laboratory examinations were compatible with Subclinical Cushing's syndrome, urinary catecholamine metabolites were normal, but who histopathologically had pheochromocytoma diagnosis. [J Contemp Med 2014; 4(3.000: 160-163

  9. The Lateralizing Asymmetry of Adrenal Adenomas

    Science.gov (United States)

    Hao, Meng; Lopez, Diana; Luque-Fernandez, Miguel Angel; Cote, Kathryn; Newfield, Jessica; Connors, Molly; Vaidya, Anand

    2018-01-01

    Abstract Context It is presumed that the incidence of adrenal adenomas is symmetric between the left and right adrenal gland; however, anecdotal observations suggest a potential lateralizing asymmetry. Objective To investigate the symmetry in detection of adrenal adenomas and relevance to patient care. Design Cross-sectional and longitudinal studies. Population and Setting One thousand three hundred seventy-six patients with abdominal computed tomography or magnetic resonance imaging demonstrating benign-appearing adrenal adenomas. Main Outcome Location and size of adrenal adenomas. Results Left-sided adenomas were discovered in 65% of patients, right-sided in 21%, and bilateral adenomas in 14%. Among unilateral adenomas, 75% were left-sided. Left-sided adenomas were more prevalent than right-sided adenomas in each size category except the largest: Adrenal adenomas are substantially more likely to be identified on the left adrenal than the right. This observation may be due to detection bias attributed to the location of the right adrenal, which may preclude identification of right-sided adenomas until they are substantially larger. These findings suggest the potential for an underrecognition of right-sided adenomas that may also impair the accurate detection of bilateral adrenal diseases. PMID:29644340

  10. A prenatally detected adrenal cyst treated by adrenal-sparing surgery

    African Journals Online (AJOL)

    A neonatal case of left adrenal cyst detected in utero and successfully treated by adrenal-sparing surgery is presented and discussed with review of the literature. Incidentally discovered prenatal adrenal masses present a diagnostic dilemma. Benign and malignant conditions can present as a fetal suprarenal mass. There is ...

  11. Adrenal scan in 17-alpha-hydroxylase deficiency: false indication of adrenal adenoma

    International Nuclear Information System (INIS)

    Shore, R.M.; Lieberman, L.M.; Newman, T.J.; Friedman, A.; Bargman, G.J.

    1981-01-01

    A patient who was thought to have testicular feminization syndrome and primary aldosteronism had an adrenal scan that suggested an adrenal adenoma. After later diagnosis of 17-alpha-hydroxylase deficiency, she was treated with glucocorticoids rather than surgery. Her clinical course and a repeat adrenal scan confirmed she did not have a tumor

  12. Human T Cell Memory: A Dynamic View

    Directory of Open Access Journals (Sweden)

    Derek C. Macallan

    2017-02-01

    Full Text Available Long-term T cell-mediated protection depends upon the formation of a pool of memory cells to protect against future pathogen challenge. In this review we argue that looking at T cell memory from a dynamic viewpoint can help in understanding how memory populations are maintained following pathogen exposure or vaccination. For example, a dynamic view resolves the apparent paradox between the relatively short lifespans of individual memory cells and very long-lived immunological memory by focussing on the persistence of clonal populations, rather than individual cells. Clonal survival is achieved by balancing proliferation, death and differentiation rates within and between identifiable phenotypic pools; such pools correspond broadly to sequential stages in the linear differentiation pathway. Each pool has its own characteristic kinetics, but only when considered as a population; single cells exhibit considerable heterogeneity. In humans, we tend to concentrate on circulating cells, but memory T cells in non-lymphoid tissues and bone marrow are increasingly recognised as critical for immune defence; their kinetics, however, remain largely unexplored. Considering vaccination from this viewpoint shifts the focus from the size of the primary response to the survival of the clone and enables identification of critical system pinch-points and opportunities to improve vaccine efficacy.

  13. Development and function of human innate immune cells in a humanized mouse model.

    Science.gov (United States)

    Rongvaux, Anthony; Willinger, Tim; Martinek, Jan; Strowig, Till; Gearty, Sofia V; Teichmann, Lino L; Saito, Yasuyuki; Marches, Florentina; Halene, Stephanie; Palucka, A Karolina; Manz, Markus G; Flavell, Richard A

    2014-04-01

    Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models cannot support development of human innate immune cells, including myeloid cells and natural killer (NK) cells. Here we describe two mouse strains called MITRG and MISTRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked into their respective mouse loci. The human cytokines support the development and function of monocytes, macrophages and NK cells derived from human fetal liver or adult CD34(+) progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MITRG and MISTRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology.

  14. Isolation of Human Skin Dendritic Cell Subsets.

    Science.gov (United States)

    Gunawan, Merry; Jardine, Laura; Haniffa, Muzlifah

    2016-01-01

    Dendritic cells (DCs) are specialized leukocytes with antigen-processing and antigen-presenting functions. DCs can be divided into distinct subsets by anatomical location, phenotype and function. In human, the two most accessible tissues to study leukocytes are peripheral blood and skin. DCs are rare in human peripheral blood (skin covering an average total surface area of 1.8 m(2) has approximately tenfold more DCs than the average 5 L of total blood volume (Wang et al., J Invest Dermatol 134:965-974, 2014). DCs migrate spontaneously from skin explants cultured ex vivo, which provide an easy method of cell isolation (Larsen et al., J Exp Med 172:1483-1493, 1990; Lenz et al., J Clin Invest 92:2587-2596, 1993; Nestle et al., J Immunol 151:6535-6545, 1993). These factors led to the extensive use of skin DCs as the "prototype" migratory DCs in human studies. In this chapter, we detail the protocols to isolate DCs and resident macrophages from human skin. We also provide a multiparameter flow cytometry gating strategy to identify human skin DCs and to distinguish them from macrophages.

  15. Neocortical glial cell numbers in human brains.

    Science.gov (United States)

    Pelvig, D P; Pakkenberg, H; Stark, A K; Pakkenberg, B

    2008-11-01

    Stereological cell counting was applied to post-mortem neocortices of human brains from 31 normal individuals, age 18-93 years, 18 females (average age 65 years, range 18-93) and 13 males (average age 57 years, range 19-87). The cells were differentiated in astrocytes, oligodendrocytes, microglia and neurons and counting were done in each of the four lobes. The study showed that the different subpopulations of glial cells behave differently as a function of age; the number of oligodendrocytes showed a significant 27% decrease over adult life and a strong correlation to the total number of neurons while the total astrocyte number is constant through life; finally males have a 28% higher number of neocortical glial cells and a 19% higher neocortical neuron number than females. The overall total number of neocortical neurons and glial cells was 49.3 billion in females and 65.2 billion in males, a difference of 24% with a high biological variance. These numbers can serve as reference values in quantitative studies of the human neocortex.

  16. The Human Cell Surfaceome of Breast Tumors

    Science.gov (United States)

    da Cunha, Júlia Pinheiro Chagas; Galante, Pedro Alexandre Favoretto; de Souza, Jorge Estefano Santana; Pieprzyk, Martin; Carraro, Dirce Maria; Old, Lloyd J.; Camargo, Anamaria Aranha; de Souza, Sandro José

    2013-01-01

    Introduction. Cell surface proteins are ideal targets for cancer therapy and diagnosis. We have identified a set of more than 3700 genes that code for transmembrane proteins believed to be at human cell surface. Methods. We used a high-throuput qPCR system for the analysis of 573 cell surface protein-coding genes in 12 primary breast tumors, 8 breast cell lines, and 21 normal human tissues including breast. To better understand the role of these genes in breast tumors, we used a series of bioinformatics strategies to integrates different type, of the datasets, such as KEGG, protein-protein interaction databases, ONCOMINE, and data from, literature. Results. We found that at least 77 genes are overexpressed in breast primary tumors while at least 2 of them have also a restricted expression pattern in normal tissues. We found common signaling pathways that may be regulated in breast tumors through the overexpression of these cell surface protein-coding genes. Furthermore, a comparison was made between the genes found in this report and other genes associated with features clinically relevant for breast tumorigenesis. Conclusions. The expression profiling generated in this study, together with an integrative bioinformatics analysis, allowed us to identify putative targets for breast tumors. PMID:24195083

  17. Shape memory of human red blood cells.

    Science.gov (United States)

    Fischer, Thomas M

    2004-05-01

    The human red cell can be deformed by external forces but returns to the biconcave resting shape after removal of the forces. If after such shape excursions the rim is always formed by the same part of the membrane, the cell is said to have a memory of its biconcave shape. If the rim can form anywhere on the membrane, the cell would have no shape memory. The shape memory was probed by an experiment called go-and-stop. Locations on the membrane were marked by spontaneously adhering latex spheres. Shape excursions were induced by shear flow. In virtually all red cells, a shape memory was found. After stop of flow and during the return of the latex spheres to the original location, the red cell shape was biconcave. The return occurred by a tank-tread motion of the membrane. The memory could not be eliminated by deforming the red cells in shear flow up to 4 h at room temperature as well as at 37 degrees C. It is suggested that 1). the characteristic time of stress relaxation is >80 min and 2). red cells in vivo also have a shape memory.

  18. Human somatic cell nuclear transfer and cloning.

    Science.gov (United States)

    2012-10-01

    This document presents arguments that conclude that it is unethical to use somatic cell nuclear transfer (SCNT) for infertility treatment due to concerns about safety; the unknown impact of SCNT on children, families, and society; and the availability of other ethically acceptable means of assisted reproduction. This document replaces the ASRM Ethics Committee report titled, "Human somatic cell nuclear transfer (cloning)," last published in Fertil Steril 2000;74:873-6. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  19. Human induced pluripotent stem cell-derived models to investigate human cytomegalovirus infection in neural cells.

    Directory of Open Access Journals (Sweden)

    Leonardo D'Aiuto

    Full Text Available Human cytomegalovirus (HCMV infection is one of the leading prenatal causes of congenital mental retardation and deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV, has been limited by difficulties in sustaining primary human neuronal cultures. Human induced pluripotent stem (iPS cells now provide an opportunity for such research. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their susceptibility to infection with HCMV strain Ad169. Analysis of iPS cells, iPS-derived neural stem cells (NSCs, neural progenitor cells (NPCs and neurons suggests that (i iPS cells are not permissive to HCMV infection, i.e., they do not permit a full viral replication cycle; (ii Neural stem cells have impaired differentiation when infected by HCMV; (iii NPCs are fully permissive for HCMV infection; altered expression of genes related to neural metabolism or neuronal differentiation is also observed; (iv most iPS-derived neurons are not permissive to HCMV infection; and (v infected neurons have impaired calcium influx in response to glutamate.

  20. Adrenal Castleman's disease mimicking other adrenal neoplasms: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Seung Baek; Lee, Nam Kyung; Kim, Suk; Han, Ga Jin; Ha, Hong Koo; Ku, Ja Yoon; Ahn, Sang Jeong; Lee, Chang Hun [Pusan National University Hospital, Pusan National University School of Medicine, Busan (Korea, Republic of)

    2017-01-15

    We present a rare case of adrenal Castleman's disease with hyaline vascular type mimicking other adrenal neoplasms in a 65-year-old woman. Although rare, the hyaline vascular type of adrenal Castleman's disease should be included in the differential diagnosis if an adrenal mass shows a well-defined, highly enhancing solid adrenal mass with peripheral rim enhancement, multiple satellite lymph nodes, and peritoneal thickening around the dominant mass on computed tomography as shown in this patient.

  1. Testicular Adrenal Rest Tumors (TARTS With Unusual Histological Features in Congenital Adrenal Hyperplasia (CAH

    Directory of Open Access Journals (Sweden)

    Valeri Marianovsky

    2015-07-01

    Full Text Available Congenital adrenal hyperplasia (CAH patients with testicular adrenal rest tumors (TARTs with testicular enlargement present a serious diagnostic challenge. According to the data TARTs are usually benign. They are rare, resulting in paucity in the medical literature regarding their pathological features. We report a case of bilateral synchronous mass-forming TARTs with marked cytological and nuclear atypia misinterpreted as malignant testicular tumors in a 40-years-old man with CAH and CT and MRI data for pheochromocytoma of the right adrenal gland and paraaortal and paracaval lymphadenomegaly. He was previously diagnosed with adrenal cortical carcinoma of the left adrenal gland.

  2. Dopamine receptor repertoire of human granulosa cells

    Directory of Open Access Journals (Sweden)

    Kunz Lars

    2007-10-01

    Full Text Available Abstract Background High levels of dopamine (DA were described in human ovary and recently evidence for DA receptors in granulosa and luteal cells has been provided, as well. However, neither the full repertoire of ovarian receptors for DA, nor their specific role, is established. Human granulosa cells (GCs derived from women undergoing in vitro fertilization (IVF are an adequate model for endocrine cells of the follicle and the corpus luteum and were therefore employed in an attempt to decipher their DA receptor repertoire and functionality. Methods Cells were obtained from patients undergoing IVF and examined using cDNA-array, RT-PCR, Western blotting and immunocytochemistry. In addition, calcium measurements (with FLUO-4 were employed. Expression of two DA receptors was also examined by in-situ hybridization in rat ovary. Effects of DA on cell viability and cell volume were studied by using an ATP assay and an electronic cell counter system. Results We found members of the two DA receptor families (D1- and D2 -like associated with different signaling pathways in human GCs, namely D1 (as expected and D5 (both are Gs coupled and linked to cAMP increase and D2, D4 (Gi/Gq coupled and linked to IP3/DAG. D3 was not found. The presence of the trophic hormone hCG (10 IU/ml in the culture medium for several days did not alter mRNA (semiquantitative RT-PCR or protein levels (immunocytochemistry/Western blotting of D1,2,4,5 DA receptors. Expression of prototype receptors for the two families, D1 and D2, was furthermore shown in rat granulosa and luteal cells by in situ hybridization. Among the DA receptors found in human GCs, D2 expression was marked both at mRNA and protein levels and it was therefore further studied. Results of additional RT-PCR and Western blots showed two splice variants (D2L, D2S. Irrespective of these variants, D2 proved to be functional, as DA raised intracellular calcium levels. This calcium mobilizing effect of DA was observed

  3. Image characteristics of adrenal ganglioneuroma

    International Nuclear Information System (INIS)

    Ohishi, Yukihiko; Machida, Toyohei; Tashiro, Kazuya

    1994-01-01

    The image characteristics of adrenal ganglioneuroma observed in various types of imaging were examined. The subjects of the study were 6 cases of adrenal ganglioneuroma which had been histologically confirmed: the ages of the subjects ranged from 25 to 54 (mean age 41), and the maximum diameter of the tumors were 4 to 7 cm. The diagnostic methods employed in their detection were ultrasonography (US) and computed tomography (CT) in all 6 cases, magnetic resonance imaging (MRI) in 5 cases, and arteriography in 3 cases. On US and CT images, all 6 tumors had clear and smooth boundaries, and were homogeneous. They were hypoechoic on US images and low density on CT images. Of the 5 cases for which contrast CT images had been obtained, one showed a slightly heterogeneous staining. On MRI, the tumors were of lower intensity in comparison to the liver in 4 of 5 cases on the T 1 -weighted images, and the internal structure was homogeneous in 3 cases and heterogeneous in one case. The remaining one case was of isointensity and homogeneous. On the T 2 -weighted images, all 5 cases were of high intensity and heterogeneous. The blood flow distribution in the 3 tumors which were examined by Gd-DTPA dynamic MRI was low and of isointensity to the liver: 2 were heterogeneous and one was homogeneous. T 1 -enhanced images were obtained in 4 cases: 2 were of high intensity and heterogeneous, one was of isointensity and homogeneous, and one was of heterogeneously isointensity. Arteriography indicated that all 3 cases were hypovascular and no vascularization or ruptures were evident. It appeared that the imaging characteristics of adrenal ganglioneuroma were as follows: (1) homogeneous on US and CT images; (2) hypoechoic on US images, low density on CT images and little enhancement on contrast CT images; (3) of low intensity homogeneous on T 1 -weighted images and of high intensity heterogeneous on T 2 -weighted images and little blood flow distribution on dynamic MRI. (author)

  4. Adenomatoid tumor of the adrenal gland in young woman: from clinical and radiological to pathological study

    Directory of Open Access Journals (Sweden)

    Brankica Krstevska

    2016-12-01

    Full Text Available Adenomatoid tumors are neoplasms of mesothelial origin, usually occurring in the male and female genital tracts. Extragenital localization sites such as adrenal glands are rare but have been reported. When found in the adrenals, they represent great clinical, radiological and pathological diagnostic challenge, with wide range of differential diagnoses to be considered. We present a case of a 30 years old female, with incidental ultrasound finding of unilateral tumor in the right adrenal gland. Multi slices CT scan was of value in localizing this tumor, but not in the precise diagnosis. The tumor ranged from 5.6 cm to 6.4 cm in greatest diameter. Clinical and hormonal examinations excluded Sy. Cushing, M. Conn and pheochromocytoma. The patient underwent laparoscopic right adrenalectomy. A large tumor (d: 8×7×3 cm was removed showing no infiltration of the adrenal cortex or medulla, or extra-adrenal extension into the periadrenal adipose tissue. Histological examination showed numerous cystic spaces lined by flattened cubical epithelial cells. The small cystic spaces were separated by edematous fibrovascular stroma with rare epithelial cells with vacuolated cytoplasm. Immunohistochemical staining was positive with vimentin (+, S100 (+, MCA mesothelial Ag (+, CD 68 (+ and negative with acitin (-, CK7 (-, CD3 (-. Adenomatoid tumor is a rare benign neoplasm that should be added in the differential diagnosis of any adrenal tumor occurring in adrenal gland. The histological and immunohistochemical profiles of this adrenal adenomatoid tumor are very supportive in reaching the diagnosis of this benign tumor of a mesothelial cell origin, helping to avoid invasive treatment.

  5. Some Ethical Concerns About Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Zheng, Yue Liang

    2016-10-01

    Human induced pluripotent stem cells can be obtained from somatic cells, and their derivation does not require destruction of embryos, thus avoiding ethical problems arising from the destruction of human embryos. This type of stem cell may provide an important tool for stem cell therapy, but it also results in some ethical concerns. It is likely that abnormal reprogramming occurs in the induction of human induced pluripotent stem cells, and that the stem cells generate tumors in the process of stem cell therapy. Human induced pluripotent stem cells should not be used to clone human beings, to produce human germ cells, nor to make human embryos. Informed consent should be obtained from patients in stem cell therapy.

  6. Cell cycle regulation in human embryonic stem cells: links to adaptation to cell culture.

    Science.gov (United States)

    Barta, Tomas; Dolezalova, Dasa; Holubcova, Zuzana; Hampl, Ales

    2013-03-01

    Cell cycle represents not only a tightly orchestrated mechanism of cell replication and cell division but it also plays an important role in regulation of cell fate decision. Particularly in the context of pluripotent stem cells or multipotent progenitor cells, regulation of cell fate decision is of paramount importance. It has been shown that human embryonic stem cells (hESCs) show unique cell cycle characteristics, such as short doubling time due to abbreviated G1 phase; these properties change with the onset of differentiation. This review summarizes the current understanding of cell cycle regulation in hESCs. We discuss cell cycle properties as well as regulatory machinery governing cell cycle progression of undifferentiated hESCs. Additionally, we provide evidence that long-term culture of hESCs is accompanied by changes in cell cycle properties as well as configuration of several cell cycle regulatory molecules.

  7. Neuronal localization of pituitary adenylate cyclase-activating polypeptide 38 in the adrenal medulla and growth-inhibitory effect on chromaffin cells

    DEFF Research Database (Denmark)

    Frödin, M; Hannibal, J; Wulff, B S

    1995-01-01

    medulla showed PACAP38 immunoreactivity in a widely distributed network of delicate nerve fibers surrounding the chromaffin cells. In a primary culture system, PACAP38 inhibited growth factor-stimulated DNA synthesis by 90% in neonatal and adult rat chromaffin cells with half-maximal inhibition at 4 and 0.......5 nM, respectively, as demonstrated by bromodeoxyuridine pulse-labeling and immunocytochemical staining of cell nuclei. In comparison, corticosterone inhibited neonatal and adult chromaffin cell proliferation by 70% and 95%, respectively, with half-maximal effect at 100 nM. In neonatal chromaffin...

  8. Cell Culture Assay for Human Noroviruses [response

    Energy Technology Data Exchange (ETDEWEB)

    Straub, Tim M.; Honer Zu Bentrup, Kerstin; Orosz Coghlan, Patricia; Dohnalkova, Alice; Mayer, Brooke K.; Bartholomew, Rachel A.; Valdez, Catherine O.; Bruckner-Lea, Cindy J.; Gerba, Charles P.; Abbaszadegan, Morteza A.; Nickerson, Cheryl A.

    2007-07-01

    We appreciate the comments provided by Leung et al., in response to our recently published article “In Vitro Cell Culture Infectivity Assay for Human Noroviruses” by Straub et al. (1). The specific aim of our project was to develop an in vitro cell culture infectivity assay for human noroviruses (hNoV) to enhance risk assessments when they are detected in water supplies. Reverse transcription (RT) qualitative or quantitative PCR are the primary assays for waterborne NoV monitoring. However, these assays cannot distinguish between infectious vs. non-infectious virions. When hNoV is detected in water supplies, information provided by our infectivity assay will significantly improve risk assessment models and protect human health, regardless of whether we are propagating NoV. Indeed, in vitro cell culture infectivity assays for the waterborne pathogen Cryptosporidium parvum that supplement approved fluorescent microscopy assays, do not result in amplification of the environmentally resistant hard-walled oocysts (2). However, identification of life cycle stages in cell culture provides evidence of infectious oocysts in a water supply. Nonetheless, Leung et al.’s assertion regarding the suitability of our method for the in vitro propagation of high titers of NoV is valid for the medical research community. In this case, well-characterized challenge pools of virus would be useful for developing and testing diagnostics, therapeutics, and vaccines. As further validation of our published findings, we have now optimized RT quantitative PCR to assess the level of viral production in cell culture, where we are indeed finding significant increases in viral titer. The magnitude and time course of these increases is dependent on both virus strain and multiplicity of infection. We are currently preparing a manuscript that will discuss these findings in greater detail, and the implications this may have for creating viral challenge pools

  9. Rare primary retroperitoneal teratoma masquerading as adrenal ...

    African Journals Online (AJOL)

    J.M. Ratkal

    Abstract. Objectives: To present a rare case of Primary mature cystic teratoma of right adrenal gland in adult female with an aim to review the published literature. Materials and Methods: The case details of a lady presenting with vague upper abdominal pain and on investigation was found to have a right adrenal mass were ...

  10. Neonatal adrenal hemorrhage mimicking an acute scrotum.

    Science.gov (United States)

    Adorisio, O; Mattei, R; Ciardini, E; Centonze, N; Noccioli, B

    2007-02-01

    Twenty-two cases of scrotal hematoma caused by neonatal adrenal hemorrhage are reported in the literature and unnecessary surgical exploration was performed in nine (41%), suspecting testicular torsion. In this paper, we present a newborn male with right adrenal gland hemorrhage causing right scrotal swelling and discoloration of groin managed conservatively.

  11. Bilateral spontaneous adrenal haemorrhage complicating acute pancreatitis

    International Nuclear Information System (INIS)

    Pianta, M.; Varma, D. K.

    2007-01-01

    Bilateral adrenal haemorrhage is an event that mandates prompt diagnosis and treatment to prevent primary adrenocortical insufficiency and potential death. Presentation can be non-specific and incidentally diagnosed with imaging alone, primarily CT. We present a case of acute pancreatitis with spontaneous bilateral adrenal haemorrhage and briefly discuss imaging and treatment implications

  12. Hypoadrenia following adrenal venography in Cushing's disease

    International Nuclear Information System (INIS)

    Goth, M.; Szilagy, G.; Irsy, G.; Szabolcs, I.; Berentey, E.; Molnar, F.; Magyar, E.

    1984-01-01

    Three patients with Cushing's disease are reported. In two patients the hyperfunction of the adrenal glands creased following selective adrenal venography, moreover hypoadrenia has developed. In the third case necrosis following venography was proved by surgery and confirmed by histology. Regarding the therapeutic possibilities of Cushing's diesease the use of this diagnostic procedure is taken into consideration but not recommended. (orig.)

  13. Nicotinamide extends replicative lifespan of human cells.

    Science.gov (United States)

    Kang, Hyun Tae; Lee, Hyung Il; Hwang, Eun Seong

    2006-10-01

    We found that an ongoing application of nicotinamide to normal human fibroblasts not only attenuated expression of the aging phenotype but also increased their replicative lifespan, causing a greater than 1.6-fold increase in the number of population doublings. Although nicotinamide by itself does not act as an antioxidant, the cells cultured in the presence of nicotinamide exhibited reduced levels of reactive oxygen species (ROS) and oxidative damage products associated with cellular senescence, and a decelerated telomere shortening rate without a detectable increase in telomerase activity. Furthermore, in the treated cells growing beyond the original Hayflick limit, the levels of p53, p21WAF1, and phospho-Rb proteins were similar to those in actively proliferating cells. The nicotinamide treatment caused a decrease in ATP levels, which was stably maintained until the delayed senescence point. Nicotinamide-treated cells also maintained high mitochondrial membrane potential but a lower respiration rate and superoxide anion level. Taken together, in contrast to its demonstrated pro-aging effect in yeast, nicotinamide extends the lifespan of human fibroblasts, possibly through reduction in mitochondrial activity and ROS production.

  14. Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins

    Directory of Open Access Journals (Sweden)

    Hayato Fukusumi

    2016-01-01

    Full Text Available Human neural progenitor cells (hNPCs have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi. Our results showed that expandable hNPCs could be generated from hiPSC clones with diverse somatic tissue origins. The established hNPCs exhibited a mid/hindbrain-type neural identity and uniform expression of neural progenitor genes.

  15. Meta-iodobenzylguanidine adrenal medulla localization

    International Nuclear Information System (INIS)

    Guilloteau, D.; Baulieu, J.L.; Chambon, C.; Valat, C.; Baulieu, F.; Itti, R.; Pourcelot, L.; Besnard, J.C.; Huguet, F.; Narcisse, G.; Viel, C.

    1984-01-01

    In order to investigate the mechanism of uptake of meta-iodobenzylguanidine (mIBG) by the adrenal glands, autoradiographic and pharmacologic studies were performed in mice and dogs receiving radioiodinated mIBG. In mice, on macroautoradiography of whole body section 48 h after 125 I-mIBG, most of the radioactivity was focused in the adrenal glands. On microautoradiography, silver grains were exclusively located in the adrenal medulla. Time counting after phenoxybenzamine, cocaine, and desipramine treatment resulted in 45%, 35%, and 0% inhibition of mIBG uptake, respectively. Tissue counting and scintigraphic studies demonstrated a more than 50% mIBG release from the adrenal glands. These data indicate the high affinity of mIBG for adrenal medulla and suggest that the mIBG and catecholamine uptake mechanisms are onlt partially the same. (orig.)

  16. [Neonatal adrenal hematoma: various modes of presentation].

    Science.gov (United States)

    Fadil, F-Z; Lehlimi, M; Chemsi, M; Habzi, A; Benomar, S

    2014-09-01

    Neonatal adrenal hematoma is a rare condition, most frequently caused by trauma. We report three cases of adrenal hematoma admitted to the Neonatology and Neonatal Intensive Care Unit in the A. Harouchi Children's Hospital, the Ibn Rushd University Hospital in Casablanca, Morocco, over a 2-year period from January 2011 to December 2012. The average age of these patients was 5 days. The clinical presentations were diverse; the most common manifestations were intense jaundice in one case, acute adrenal insufficiency in one case, and severe anemia in the other case. Abdominal ultrasonography was used to confirm the diagnosis and monitor adrenal hemorrhage in all the patients. Analysis of clinical, laboratory, and ultrasonography data showed a favorable prognosis in all the patients. Based on these observations, we discuss the risk factors, clinical presentations, progression and management of neonatal adrenal hemorrhage. Copyright © 2014. Published by Elsevier SAS.

  17. Immortalization of human myogenic progenitor cell clone retaining multipotentiality

    International Nuclear Information System (INIS)

    Hashimoto, Naohiro; Kiyono, Tohru; Wada, Michiko R.; Shimizu, Shirabe; Yasumoto, Shigeru; Inagawa, Masayo

    2006-01-01

    Human myogenic cells have limited ability to proliferate in culture. Although forced expression of telomerase can immortalize some cell types, telomerase alone delays senescence of human primary cultured myogenic cells, but fails to immortalize them. In contrast, constitutive expression of both telomerase and the E7 gene from human papillomavirus type 16 immortalizes primary human myogenic cells. We have established an immortalized primary human myogenic cell line preserving multipotentiality by ectopic expression of telomerase and E7. The immortalized human myogenic cells exhibit the phenotypic characteristics of their primary parent, including an ability to undergo myogenic, osteogenic, and adipogenic terminal differentiation under appropriate culture conditions. The immortalized cells will be useful for both basic and applied studies aimed at human muscle disorders. Furthermore, immortalization by transduction of telomerase and E7 represents a useful method by which to expand human myogenic cells in vitro without compromising their ability to differentiate

  18. Human prostatic cancer cells, PC3, elaborate mitogenic activity which selectively stimulates human bone cells

    International Nuclear Information System (INIS)

    Perkel, V.S.; Mohan, S.; Herring, S.J.; Baylink, D.J.; Linkhart, T.A.

    1990-01-01

    Prostatic cancer typically produces osteoblastic metastases which are not attended by marrow fibrosis. In the present study we sought to test the hypothesis that prostatic cancer cells produce factor(s) which act selectively on human osteoblasts. Such a paracrine mechanism would explain the observed increase in osteoblasts, unaccompanied by an increase in marrow fibroblasts. To test this hypothesis we investigated the mitogenic activity released by the human prostatic tumor cell line, PC3. PC3 cells have been reported previously to produce mitogenic activity for cells that was relatively specific for rat osteoblasts compared to rat fibroblasts. However, the effects of this activity on human cells has not been examined previously. PC3-conditioned medium (CM) (5-50 micrograms CM protein/ml) stimulated human osteoblast proliferation by 200-950% yet did not stimulate human fibroblast proliferation ([3H]thymidine incorporation). PC3 CM also increased cell numbers in human osteoblast but not fibroblast cell cultures. To determine whether the osteoblast-specific mitogenic activity could be attributed to known bone growth factors, specific assays for these growth factors were performed. PC3 CM contained 10 pg insulin-like growth factor (IGF) I, less than 2 pg IGF II, 54 pg basic fibroblast growth factor, and 16 pg transforming growth factor beta/microgram CM protein. None of these growth factors alone or in combination could account for the observed osteoblast-specific PC3 cell-derived mitogenic activity. Furthermore, when 5 micrograms/ml PC3 CM was tested in combination with maximally effective concentrations of either basic fibroblast growth factor, IGF I, IGF II, or transforming growth factor beta, it produced an additive effect suggesting that PC3 CM stimulates osteoblast proliferation by a mechanism independent of these bone mitogens

  19. Adrenal Mass Causing Secondary Hypertension.

    Science.gov (United States)

    Robinson, Darlene Y

    2015-11-01

    Most hypertensive patients have essential (primary) hypertension; only 5% to 10% have a secondary cause. Two clinical characteristics suggestive of secondary hypertension are early onset (hypertension (>180/110 mm Hg). When faced with these findings, clinicians should consider a secondary cause of hypertension. A 22-year-old woman being evaluated for asthma exacerbation in the emergency department was noted to have severe persistent hypertension. Additional evaluation revealed severe hypokalemia, metabolic alkalosis, and hypernatremia. The patient was admitted to the hospital for blood pressure management, electrolyte replacement, and further evaluation of presumed hyperaldosteronism. Diagnostic imaging revealed a large adrenal mass. Surgical resection was performed, leading to a diagnosis of hyperaldosteronism caused by adrenal carcinoma. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Secondary hypertension is far less common than essential hypertension; however, considering the large volume of patients seen in emergency departments, it is likely that some will have secondary hypertension. Emergency physicians should be aware of the clinical characteristics that suggest secondary hypertension so that the appropriate diagnostic and treatment pathways can be pursued. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Differentiation of blood T cells: Reprogramming human induced pluripotent stem cells into neuronal cells

    Directory of Open Access Journals (Sweden)

    Ping-Hsing Tsai

    2015-06-01

    Conclusion: We have developed a safer method to generate integration-free and nonviral human iPSCs from adult somatic cells. This induction method will be useful for the derivation of human integration-free iPSCs and will also be applicable to the generation of iPSCs-derived neuronal cells for drug screening or therapeutics in the near future.

  1. Markers of T Cell Senescence in Humans

    Directory of Open Access Journals (Sweden)

    Weili Xu

    2017-08-01

    Full Text Available Many countries are facing the aging of their population, and many more will face a similar obstacle in the near future, which could be a burden to many healthcare systems. Increased susceptibility to infections, cardiovascular and neurodegenerative disease, cancer as well as reduced efficacy of vaccination are important matters for researchers in the field of aging. As older adults show higher prevalence for a variety of diseases, this also implies higher risk of complications, including nosocomial infections, slower recovery and sequels that may reduce the autonomy and overall quality of life of older adults. The age-related effects on the immune system termed as “immunosenescence” can be exemplified by the reported hypo-responsiveness to influenza vaccination of the elderly. T cells, which belong to the adaptive arm of the immune system, have been extensively studied and the knowledge gathered enables a better understanding of how the immune system may be affected after acute/chronic infections and how this matters in the long run. In this review, we will focus on T cells and discuss the surface and molecular markers that are associated with T cell senescence. We will also look at the implications that senescent T cells could have on human health and diseases. Finally, we will discuss the benefits of having these markers for investigators and the future work that is needed to advance the field of T cell senescence markers.

  2. Human embryonic stem cells and microenvironment

    Directory of Open Access Journals (Sweden)

    Banu İskender

    2014-09-01

    Full Text Available Human embryonic stem cells (hESCs possess a great potential in the field of regenerative medicine by their virtue of pluripotent potential with indefinite proliferation capabilities. They can self renew themselves and differentiate into three embryonic germ layers. Although they are conventionally grown on mitotically inactivated mouse feeder cells, there are in vitro culture systems utilizing feeder cells of human origin in order to prevent cross-species contamination. Recently established in vitro culture systems suggested that direct interaction with feeder cells is not necessary but rather attachment to a substrate is required to ensure long-term, efficient hESC culture in vitro. This substrate is usually composed of a mixture of extracellular matrix components representing in vivo natural niche. In hESC biology, the mechanism of interaction of hESCs with extracellular matrix molecules remained insufficiently explored area of research due to their transient nature of interaction with the in vivo niche. However, an in vitro culture system established using extracellular matrix molecules may provide a safer alternative to culture systems with feeder cells while paving the way to Good Manufacturing Practice-GMP production of hESCs for therapeutic purposes. Therefore, it is essential to study the interaction of extracellular matrix molecules with hESCs in order to standardize in vitro culture systems for large-scale production of hESCs in a less labor-intensive way. This would not only provide valuable information regarding the mechanisms that control pluripotency but also serve to dissect the molecular signaling pathways of directed differentiation for prospective therapeutic applications in the future. J Clin Exp Invest 2014; 5 (3: 486-495

  3. Release of galanin from isolated perfused porcine adrenal glands

    DEFF Research Database (Denmark)

    Holst, J J; Ehrhart-Bornstein, M; Messell, T

    1991-01-01

    We found a high concentration of galanin in extracts of porcine adrenal glands (114 pmol/g). By immunohistochemistry, galanin was localized to groups of medullary cells previously shown to produce norepinephrine. To study mechanisms for the release of galanin, we developed the following in vitro...... model: isolated perfused porcine adrenals with intact splanchnic nerve supply. When the nerves were electrically stimulated, epinephrine and norepinephrine secretion increased 276- and 291-fold, respectively, and galanin release increased up to 1,300-fold. Acetylcholine at 10(-6) M stimulated galanin...... release, and hexamethonium almost abolished the response to nerve stimulation. Galanin infusions had no effect on epinephrine and norepinephrine secretion in concentrations of 10(-8) and 10(-7) M, but increased both cortisol and aldosterone secretion (P less than 0.05). Splanchnic nerve stimulation...

  4. [3H]nitrendipine binding to adrenal capsular membranes

    International Nuclear Information System (INIS)

    Finkel, M.S.; Aguilera, G.; Catt, K.J.; Keiser, H.R.

    1984-01-01

    The physiologic regulation of aldosterone secretion is dependent on extracellular calcium and appears to be mediated by increases in cytosolic free calcium concentration in the zona glomerulosa cell. A specific role for voltage-dependent calcium channels was suggested by previous studies with the calcium channel antagonist verapamil. The authors therefore studied the [ 3 H]nitrendipine calcium channel binding site in adrenal capsules. These studies revealed a single class of saturable, high affinity sites with K/sub D/ = .26 +/- .04 nM and B/sub max/ = 105 +/- 5.7 fmol/mg protein. Specific binding of [ 3 H]nitrendipine was inhibited by calcium channel antagonists with potencies nitrendipine = nifedipine >> verapamil, while diltiazem had no inhibitory effect. In the rat, binding sites for [ 3 H]nitrendipine were located in the adrenal capsule and medulla and were undetectable in the zona fasciculata. Physiologic studies with collagenase-dispersed adrenal glomerulosa cells demonstrated that nifedipine selectively inhibited angiotensin-II and potassium-stimulated steroidogenesis. These observations suggest both a pharmacologic and physiologic role for the nitrendipine binding site in aldosterone production. 17 references, 2 figures, 1 table

  5. Neonatal adrenal hemorrhage presenting as late onset neonatal jaundice

    OpenAIRE

    Qureshi, Umar Amin; Ahmad, Nisar; Rasool, Akhter; Choh, Suhail

    2009-01-01

    Clinical manifestations of adrenal hemorrhage vary depending on the degree and rate of hemorrhage, as well as the amount of adrenal cortex compromised by hemorrhage. We report here a case of neonatal adrenal hemorrhage that presented with late onset neonatal jaundice. The cause of adrenal hemorrhage was birth asphyxia.

  6. Patient-specific workup of adrenal incidentalomas

    Directory of Open Access Journals (Sweden)

    Romy R. de Haan

    Full Text Available Purpose: : To develop a clinical prediction model to predict a clinically relevant adrenal disorder for patients with adrenal incidentaloma. Materials and methods: : This retrospective study is approved by the institutional review board, with waiver of informed consent. Natural language processing is used for filtering of adrenal incidentaloma cases in all thoracic and abdominal CT reports from 2010 till 2012. A total of 635 patients are identified. Stepwise logistic regression is used to construct the prediction model. The model predicts if a patient is at risk for malignancy or hormonal hyperfunction of the adrenal gland at the moment of initial presentation, thus generates a predicted probability for every individual patient. The prediction model is evaluated on its usefulness in clinical practice using decision curve analysis (DCA based on different threshold probabilities. For patients whose predicted probability is lower than the predetermined threshold probability, further workup could be omitted. Results: : A prediction model is successfully developed, with an area under the curve (AUC of 0.78. Results of the DCA indicate that up to 11% of patients with an adrenal incidentaloma can be avoided from unnecessary workup, with a sensitivity of 100% and specificity of 11%. Conclusion: : A prediction model can accurately predict if an adrenal incidentaloma patient is at risk for malignancy or hormonal hyperfunction of the adrenal gland based on initial imaging features and patient demographics. However, with most adrenal incidentalomas labeled as nonfunctional adrenocortical adenomas requiring no further treatment, it is likely that more patients could be omitting from unnecessary diagnostics. Keywords: Adrenal incidentaloma, Patient-specific workup, Prediction model

  7. The Cultivation of Human Granulosa Cells

    Directory of Open Access Journals (Sweden)

    Lenka Brůčková

    2008-01-01

    Full Text Available The major functions of granulosa cells (GCs include the production of steroids, as well as a myriad of growth factors to interact with the oocyte during its development within the ovarian follicle. Also FSH stimulates GCs to convert androgens (coming from the thecal cells to estradiol by aromatase. However, after ovulation the GCs produce progesterone that may maintain a potential pregnancy. Experiments with human GCs are mainly focused on the purification of GCs from ovarian follicular fluid followed by FACS analysis or short-term cultivation. The aim of our study was to cultivate GCs for a long period, to characterize their morphology and phenotype. Moreover, we have cultivated GCs under gonadotropin stimulation in order to simulate different pathological mechanisms during folliculogenesis (e.g. ovarian hyperstimulation syndrome. GCs were harvested from women undergoing in vitro fertilization. Complex oocyte-cumulus oophorus was dissociated by hyaluronidase. The best condition for transport of GCs was optimized as short transport in follicular fluid at 37 °C. GCs expansion medium consisted of DMEM/F12, 2 % FCS, ascorbic acid, dexamethasone, L-glutamine, gentamycine, penicillin, streptomycin and growth factors (EGF, bFGF. GCs transported in follicular fluid and cultivated in 2 % FCS containing DMEM/F12 medium supplemented with follicular fluid presented increased adhesion, proliferation, viability and decreased doubling time. Cell viability was 92 % and mean cell doubling time was 52 hrs. We have optimized transport and cultivation protocols for long-term cultivation of GCs.

  8. Single Cell Dissection of Human Pancreatic Islet Dysfunction in Diabetes

    Science.gov (United States)

    2017-06-01

    of memory T cells , innate cells and the differentiation potential of naive T cells during ME/CFS; and 3) To determine the T cell and innate cell ...apoptosis and the innate immune response in human pancreatic β- cells . Diabetes 64: 3808–3817. Marselli L, Thorne J, Dahiya S, Sgroi DC, Sharma A, Bonner-Weir...interactive nature of CellView aids in cell doublet identification. In the PBMC data, ‘Subcluster-analysis’ reveals a mixture of lymphoid and myeloid

  9. Mechanisms of blood pressure changes following renal irradiation of intact, adrenalectomized, and adrenal regenerating rats

    International Nuclear Information System (INIS)

    Rosenblum, M.

    1977-01-01

    This study was conducted to determine the differences in changes in systolic arterial blood pressure following renal x irradiation (1100 R) in adrenal-intact, adrenalectomized, and adrenal-regenerating rats and to elucidate the involvement or roles of the kidneys and of the adrenal glands in the blood pressure changes. The parameters studied included the following: systolic blood pressure; body weight; food and fluid consumption; urine output; plasma and urine electrolytes; sodium balance; plasma renin activity; plasma corticosterone; renal vascular volume; renal vascular permeability (using 125 I-polyvinylpyrrolidone extravasation rate as an indicator); renal blood flow (using 42 K extraction); kidney weight; hematocrit; and total vascular, plasma, and red cell volumes. Renal x irradiation of intact rats caused polydipsia, polyuria, and reduced urine concentrations of sodium and potassium without significantly affecting blood pressure during the period of study (80 days); plasma renin activity was significantly lowered and had a positive correlation with blood volume; an abnormal blood volume-plasma renin activity relationship is suggested. Adrenalectomy caused prolonged hypotension in saline-maintained rats even though their sodium balance was more positive than that in adrenal-intact or adrenal-regenerating rats with normal or elevated blood pressure. The blood pressure of renally irrradiated, adrenalectomized rats was greater than non-irradiated adrenalectomized rats, but with only borderline significance; it is concluded that the absence of the adrenal glands does not affect the degree or duration of the effects of renal irradiation on blood pressure

  10. Adrenal Ewing's Sarcoma in an Elderly Man.

    Science.gov (United States)

    Toda, Kazuyoshi; Ishii, Sumiyasu; Yasuoka, Hidetoshi; Nishioka, Masaki; Kobayashi, Takayuki; Horiguchi, Kazuhiko; Tomaru, Takuya; Ozawa, Atsushi; Shibusawa, Nobuyuki; Satoh, Tetsurou; Koshi, Hiromi; Segawa, Atsuki; Shimizu, Shin-Ichi; Oyama, Tetsunari; Yamada, Masanobu

    2018-02-15

    Ewing's sarcoma usually arises in the bones of children and adolescents. We herein report a 74-year-old man with Ewing's sarcoma in the adrenal gland. The diagnosis was confirmed by a genetic test, pathological studies, and several imaging studies. He already had multiple liver metastases when he was transferred to our hospital and died on the 37th day. The diagnosis was further confirmed by autopsy studies. Adrenal Ewing's sarcoma is very rare, and our patient was older than other reported cases. Ewing's sarcoma should be considered even in elderly patients with adrenal tumors.

  11. Severe bilateral adrenal hemorrhages in  a  newborn complicated by persistent adrenal insufficiency

    Directory of Open Access Journals (Sweden)

    Nicholas R Zessis

    2018-02-01

    Full Text Available Bilateral adrenal hemorrhages rarely occur during the neonatal period and are often associated with traumatic vaginal deliveries. However, the adrenal gland has highly regenerative capabilities and adrenal insufficiency typically resolves over time. We evaluated a newborn female after experiencing fetal macrosomia and a traumatic vaginal delivery. She developed acidosis and acute renal injury. Large adrenal hemorrhages were noted bilaterally on ultrasound, and she was diagnosed with adrenal insufficiency based on characteristic electrolyte changes and a low cortisol (4.2 μg/dL. On follow-up testing, this patient was unable to be weaned off of hydrocortisone or fludrocortisone despite resolution of hemorrhages on ultrasound. Providers should consider bilateral adrenal hemorrhage when evaluating critically ill neonates after a traumatic delivery. In extreme cases, this may be a persistent process.

  12. Proteomic Analysis of Human Blastocoel Fluid and Blastocyst Cells

    DEFF Research Database (Denmark)

    Linnert Jensen, Pernille; Beck, Hans Christian; Petersen, Jørgen

    The human blastocyst consists of 100-200 cells that are organized in an outer layer of differentiated trophectoderm (TE) cells lining the blastocyst cavity into which the undifferentiated inner cell mass (ICM) protrudes. The cavity of the blastocyst is filled with blastocoel fluid to which all...... the cells of the blastocyst are exposed. The ICM is the starting point for the development of undifferentiated human embryonic stem cells (hESCs), which posses the potential to develop into any cell type present in the adult human body [1,2]. This ability makes hESCs a potential source of cells...

  13. Sympatho-adrenal activation by chronic intermittent hypoxia

    Science.gov (United States)

    Kumar, Ganesh K.; Peng, Ying-Jie

    2012-01-01

    Recurrent apnea with chronic intermittent hypoxia (CIH) is a major clinical problem in adult humans and infants born preterm. Patients with recurrent apnea exhibit heightened sympathetic activity as well as elevated plasma catecholamine levels, and these phenotypes are effectively recapitulated in rodent models of CIH. This article summarizes findings from studies addressing sympathetic activation in recurrent apnea patients and rodent models of CIH and the underlying cellular and molecular mechanisms. Available evidence suggests that augmented chemoreflex and attenuated baroreflex contribute to sympathetic activation by CIH. Studies on rodents showed that CIH augments the carotid body response to hypoxia and attenuates the carotid baroreceptor response to increased sinus pressures. Processing of afferent information from chemoreceptors at the central nervous system is also facilitated by CIH. Adult and neonatal rats exposed to CIH exhibit augmented catecholamine secretion from the adrenal medulla. Adrenal demedullation prevents the elevation of circulating catecholamines in CIH-exposed rodents. Reactive oxygen species (ROS)-mediated signaling is emerging as the major cellular mechanism triggering sympatho-adrenal activation by CIH. Molecular mechanisms underlying increased ROS generation by CIH seem to involve transcriptional dysregulation of genes encoding pro-and antioxidant enzymes by hypoxia-inducible factor-1 and -2, respectively. PMID:22723632

  14. Sympatho-adrenal activation by chronic intermittent hypoxia.

    Science.gov (United States)

    Prabhakar, Nanduri R; Kumar, Ganesh K; Peng, Ying-Jie

    2012-10-15

    Recurrent apnea with chronic intermittent hypoxia (CIH) is a major clinical problem in adult humans and infants born preterm. Patients with recurrent apnea exhibit heightened sympathetic activity as well as elevated plasma catecholamine levels, and these phenotypes are effectively recapitulated in rodent models of CIH. This article summarizes findings from studies addressing sympathetic activation in recurrent apnea patients and rodent models of CIH and the underlying cellular and molecular mechanisms. Available evidence suggests that augmented chemoreflex and attenuated baroreflex contribute to sympathetic activation by CIH. Studies on rodents showed that CIH augments the carotid body response to hypoxia and attenuates the carotid baroreceptor response to increased sinus pressures. Processing of afferent information from chemoreceptors at the central nervous system is also facilitated by CIH. Adult and neonatal rats exposed to CIH exhibit augmented catecholamine secretion from the adrenal medulla. Adrenal demedullation prevents the elevation of circulating catecholamines in CIH-exposed rodents. Reactive oxygen species (ROS)-mediated signaling is emerging as the major cellular mechanism triggering sympatho-adrenal activation by CIH. Molecular mechanisms underlying increased ROS generation by CIH seem to involve transcriptional dysregulation of genes encoding pro-and antioxidant enzymes by hypoxia-inducible factor-1 and -2, respectively.

  15. Persistent Primary Aldosteronism Despite Iatrogenic Adrenal Hemorrhage After Adrenal Vein Sampling.

    Science.gov (United States)

    Okamura, Keisuke; Okuda, Tetsu; Shirai, Kazuyuki; Abe, Ichiro; Kobayashi, Kunihisa; Ishii, Tatsu; Haraoka, Seiji; Urata, Hidenori

    2018-01-01

    Before surgery for primary aldosteronism (PA), localization is evaluated with adrenal vein sampling (AVS). A 56-year-old Japanese woman had a right adrenal mass, hypokalemia, and a high aldosterone/renin ratio. Stress tests confirmed the diagnosis of PA. Subsequently, preoperative AVS was performed and right adrenal hemorrhage (AH) occurred unexpectedly. Because hypertension persisted, laparoscopic right adrenalectomy was performed. Postoperatively, the blood pressure was normalized. Pathological examination revealed an adrenal cortical adenoma largely unaffected by necrosis and hemorrhage. Previous reports have also indicated that AH may not ameliorate PA. We discussed the clinical progress of AH and the measures to prevent causing AH.

  16. A case of adrenal Cushing’s syndrome with bilateral adrenal masses

    Directory of Open Access Journals (Sweden)

    Ya-Wun Guo

    2016-05-01

    Full Text Available A functional lesion in corticotrophin (ACTH-independent Cushing’s syndrome is difficult to distinguish from lesions of bilateral adrenal masses. Methods for distinguishing these lesions include adrenal venous sampling and 131I-6β-iodomethyl-19-norcholesterol (131I-NP-59 scintigraphy. We present a case of a 29-year-old Han Chinese female patient with a history of hypercholesterolaemia and polycystic ovary syndrome. She presented with a 6month history of an 8kg body weight gain and gradual rounding of the face. Serial examinations revealed loss of circadian rhythm of cortisol, elevated urinary free-cortisol level and undetectable ACTH level (<5pg/mL. No suppression was observed in both the low- and high-dose dexamethasone suppression tests. Adrenal computed tomography revealed bilateral adrenal masses. Adrenal venous sampling was performed, and the right-to-left lateralisation ratio was 14.29. The finding from adrenal scintigraphy with NP-59 was consistent with right adrenal adenoma. The patient underwent laparoscopic right adrenalectomy, and the pathology report showed adrenocortical adenoma. Her postoperative cortisol level was 3.2μg/dL, and her Cushingoid appearance improved. In sum, both adrenal venous sampling and 131I-NP-59 scintigraphy are good diagnostic methods for Cushing’s syndrome presenting with bilateral adrenal masses.

  17. Persistent Primary Aldosteronism Despite Iatrogenic Adrenal Hemorrhage After Adrenal Vein Sampling

    Science.gov (United States)

    Okamura, Keisuke; Okuda, Tetsu; Shirai, Kazuyuki; Abe, Ichiro; Kobayashi, Kunihisa; Ishii, Tatsu; Haraoka, Seiji; Urata, Hidenori

    2018-01-01

    Before surgery for primary aldosteronism (PA), localization is evaluated with adrenal vein sampling (AVS). A 56-year-old Japanese woman had a right adrenal mass, hypokalemia, and a high aldosterone/renin ratio. Stress tests confirmed the diagnosis of PA. Subsequently, preoperative AVS was performed and right adrenal hemorrhage (AH) occurred unexpectedly. Because hypertension persisted, laparoscopic right adrenalectomy was performed. Postoperatively, the blood pressure was normalized. Pathological examination revealed an adrenal cortical adenoma largely unaffected by necrosis and hemorrhage. Previous reports have also indicated that AH may not ameliorate PA. We discussed the clinical progress of AH and the measures to prevent causing AH. PMID:29238437

  18. Testosterone-secreting adrenal adenoma in a peripubertal girl

    International Nuclear Information System (INIS)

    Kamilaris, T.C.; DeBold, C.R.; Manolas, K.J.; Hoursanidis, A.; Panageas, S.; Yiannatos, J.

    1987-01-01

    A 15-year-old girl who presented with primary amenorrhea and virilization had an adrenocortical adenoma that secreted predominantly testosterone. To the authors' knowledge, she is the first peripubertal and second youngest patient with a testosterone-secreting adrenal tumor described. Serum dehydroepiandrosterone sulfate and urinary 17-ketosteroid an 17-hydroxycorticosteroid levels were normal. A tumor was located by a computed tomographic (CT) scan and by uptake of 6-β-[ 75 Se] selenomethylnorcholesterol. Microscopic examination of the tumor showed typical features of an adrenocortical adenoma with no histologic features characteristic of Leydig cells. Postoperatively, her hirsutism regressed, she rapidly went through puberty, and regular monthly menstruation started four months later. Finding the source of testosterone in a virilized patient can be difficult. Eleven of the 14 previously described patients with testosterone-secreting adrenal tumors initially underwent misdirected surgery on the ovaries. Review of these cases revealed that results of hormone stimulation and suppression tests are unreliable and that these tumors are usually large. Therefore, CT scanning of the adrenal glands is recommended in all patients suspected of having a testosterone-secreting tumor

  19. Testosterone-secreting adrenal adenoma in a peripubertal girl

    Energy Technology Data Exchange (ETDEWEB)

    Kamilaris, T.C.; DeBold, C.R.; Manolas, K.J.; Hoursanidis, A.; Panageas, S.; Yiannatos, J.

    1987-11-13

    A 15-year-old girl who presented with primary amenorrhea and virilization had an adrenocortical adenoma that secreted predominantly testosterone. To the authors' knowledge, she is the first peripubertal and second youngest patient with a testosterone-secreting adrenal tumor described. Serum dehydroepiandrosterone sulfate and urinary 17-ketosteroid an 17-hydroxycorticosteroid levels were normal. A tumor was located by a computed tomographic (CT) scan and by uptake of 6-..beta..-(/sup 75/Se) selenomethylnorcholesterol. Microscopic examination of the tumor showed typical features of an adrenocortical adenoma with no histologic features characteristic of Leydig cells. Postoperatively, her hirsutism regressed, she rapidly went through puberty, and regular monthly menstruation started four months later. Finding the source of testosterone in a virilized patient can be difficult. Eleven of the 14 previously described patients with testosterone-secreting adrenal tumors initially underwent misdirected surgery on the ovaries. Review of these cases revealed that results of hormone stimulation and suppression tests are unreliable and that these tumors are usually large. Therefore, CT scanning of the adrenal glands is recommended in all patients suspected of having a testosterone-secreting tumor.

  20. Studies in human skin epithelial cell carcinogenesis

    International Nuclear Information System (INIS)

    Lehman, T.A.

    1987-01-01

    Metabolism and DNA adduct formation of benzo[a]pyrene (BP) by human epidermal keratinocytes pretreated with inhibitors or inducer of cytochrame P450 was studied. To study DNA adduct analysis, cultures were pretreated as described above, and then treated with non-radiolabeled BP. DNA was prepared from these cultures, digested to the nucleotide level, and 32 P-postlabeled for adduct analysis. Cultures pretreated with BHA, 7,8-BF or disulfiralm formed significantly fewer BPDE I-dB adducts than non-pretreated cultures, while cultures pretreated with MeBHA formed more BPDE-I-dG adducts. MeBHA increased BP activation and adduct formation inhuman keratinocyte in cultures by inducing a specific isoenzyme of cytochrome P450 which preferentially increases the oxidative metabolism of BP to 7,8 diol BP and 7,8 diol BP to BPDE I. To approximate an in vivo human system, metabolism of BPDE I by human skin xenografts treated with cell cycles modulators was studied. When treated with BPDE I, specific carcinogen-DNA adducts were formed. Separation and identification of these adducts by the 32 P-postlabeling technique indicated that the 7R- and 7S-BPDE I-dG adducts were the major adducts

  1. Extra-adrenal glucocorticoid synthesis: immune regulation and aspects on local organ homeostasis.

    Science.gov (United States)

    Talabér, Gergely; Jondal, Mikael; Okret, Sam

    2013-11-05

    Systemic glucocorticoids (GCs) mainly originate from de novo synthesis in the adrenal cortex under the control of the hypothalamus-pituitary-adrenal (HPA)-axis. However, research during the last 1-2 decades has revealed that additional organs express the necessary enzymes and have the capacity for de novo synthesis of biologically active GCs. This includes the thymus, intestine, skin and the brain. Recent research has also revealed that locally synthesized GCs most likely act in a paracrine or autocrine manner and have significant physiological roles in local homeostasis, cell development and immune cell activation. In this review, we summarize the nature, regulation and known physiological roles of extra-adrenal GC synthesis. We specifically focus on the thymus in which GC production (by both developing thymocytes and epithelial cells) has a role in the maintenance of proper immunological function. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. Technical Challenges in the Derivation of Human Pluripotent Cells

    Directory of Open Access Journals (Sweden)

    Parinya Noisa

    2011-01-01

    Full Text Available It has long been discovered that human pluripotent cells could be isolated from the blastocyst state of embryos and called human embryonic stem cells (ESCs. These cells can be adapted and propagated indefinitely in culture in an undifferentiated manner as well as differentiated into cell representing the three major germ layers: endoderm, mesoderm, and ectoderm. However, the derivation of human pluripotent cells from donated embryos is limited and restricted by ethical concerns. Therefore, various approaches have been explored and proved their success. Human pluripotent cells can also be derived experimentally by the nuclear reprogramming of somatic cells. These techniques include somatic cell nuclear transfer (SCNT, cell fusion and overexpression of pluripotent genes. In this paper, we discuss the technical challenges of these approaches for nuclear reprogramming, involving their advantages and limitations. We will also highlight the possible applications of these techniques in the study of stem cell biology.

  3. Stereological quantification of mast cells in human synovium

    DEFF Research Database (Denmark)

    Damsgaard, T E; Sørensen, Flemming Brandt; Herlin, T

    1999-01-01

    Mast cells participate in both the acute allergic reaction as well as in chronic inflammatory diseases. Earlier studies have revealed divergent results regarding the quantification of mast cells in the human synovium. The aim of the present study was therefore to quantify these cells in the human...... synovium, using stereological techniques. Different methods of staining and quantification have previously been used for mast cell quantification in human synovium. Stereological techniques provide precise and unbiased information on the number of cell profiles in two-dimensional tissue sections of......, in this case, human synovium. In 10 patients suffering from osteoarthritis a median of 3.6 mast cells/mm2 synovial membrane was found. The total number of cells (synoviocytes, fibroblasts, lymphocytes, leukocytes) present was 395.9 cells/mm2 (median). The mast cells constituted 0.8% of all the cell profiles...

  4. Giant adrenal incidentaloma in young patient

    International Nuclear Information System (INIS)

    Andrade, Cristiano Feijo; Espirito Santo, Paulo Rogerio Quieregatto do; Teixeira, Antonio Roberto Franchi

    2000-01-01

    Incidental adrenal tumors are lesions occasionally observed during abdominal US or CT scans. These tumors have been observed in patients without clinical or laboratorial signs of adrenal disease. The authors report a case of a 18 - years - old young man who was admitted to the Franco da Rocha Hospital, Sao Paulo, with abdominal pain and a palpated mass in the epigastrium which began one month ago. These findings were preceded by a blunt trauma at the epigastrium three months earlier. First clinical hypothesis was of a traumatic pancreatic pseudocyst. However, investigation and laparotomy showed a large left adrenal solid mass, weighting 700 g. The mass was removed and histology was performed. There was no evidence of malignant neoplasm, then the diagnostic of incidental adenoma of adrenal was confirmed. The authors hope to stimulate surgeons for early detection of these lesions in order to prevent the complications and improve the prognosis. (author)

  5. Lateral retroperitoneoscopic adrenalectomy for complicated adrenal ...

    African Journals Online (AJOL)

    sected completely, a self-made bag was used to dress up the adrenal ... were stable, and the patients had regained consciousness ... diet and normal ambulation as regards to the requirement ..... The Malaysian Journal of Medical Scienc-.

  6. The Eosinophil Count Tends to Be Negatively Associated with Levels of Serum Glucose in Patients with Adrenal Cushing Syndrome

    Directory of Open Access Journals (Sweden)

    Younghak Lee

    2017-09-01

    Full Text Available BackgroundCushing syndrome is characterized by glucose intolerance, cardiovascular disease, and an enhanced systemic inflammatory response caused by chronic exposure to excess cortisol. Eosinopenia is frequently observed in patients with adrenal Cushing syndrome, but the relationship between the eosinophil count in peripheral blood and indicators of glucose level in patients with adrenal Cushing syndrome has not been determined.MethodsA retrospective study was undertaken of the clinical and laboratory findings of 40 patients diagnosed with adrenal Cushing syndrome at Chungnam National University Hospital from January 2006 to December 2016. Clinical characteristics, complete blood cell counts with white blood cell differential, measures of their endocrine function, description of imaging studies, and pathologic findings were obtained from their medical records.ResultsEosinophil composition and count were restored by surgical treatment of all of the patients with adrenal Cushing disease. The eosinophil count was inversely correlated with serum and urine cortisol, glycated hemoglobin, and inflammatory markers in the patients with adrenal Cushing syndrome.ConclusionSmaller eosinophil populations in patients with adrenal Cushing syndrome tend to be correlated with higher levels of blood sugar and glycated hemoglobin. This study suggests that peripheral blood eosinophil composition or count may be associated with serum glucose levels in patients with adrenal Cushing syndrome.

  7. The Eosinophil Count Tends to Be Negatively Associated with Levels of Serum Glucose in Patients with Adrenal Cushing Syndrome.

    Science.gov (United States)

    Lee, Younghak; Yi, Hyon Seung; Kim, Hae Ri; Joung, Kyong Hye; Kang, Yea Eun; Lee, Ju Hee; Kim, Koon Soon; Kim, Hyun Jin; Ku, Bon Jeong; Shong, Minho

    2017-09-01

    Cushing syndrome is characterized by glucose intolerance, cardiovascular disease, and an enhanced systemic inflammatory response caused by chronic exposure to excess cortisol. Eosinopenia is frequently observed in patients with adrenal Cushing syndrome, but the relationship between the eosinophil count in peripheral blood and indicators of glucose level in patients with adrenal Cushing syndrome has not been determined. A retrospective study was undertaken of the clinical and laboratory findings of 40 patients diagnosed with adrenal Cushing syndrome at Chungnam National University Hospital from January 2006 to December 2016. Clinical characteristics, complete blood cell counts with white blood cell differential, measures of their endocrine function, description of imaging studies, and pathologic findings were obtained from their medical records. Eosinophil composition and count were restored by surgical treatment of all of the patients with adrenal Cushing disease. The eosinophil count was inversely correlated with serum and urine cortisol, glycated hemoglobin, and inflammatory markers in the patients with adrenal Cushing syndrome. Smaller eosinophil populations in patients with adrenal Cushing syndrome tend to be correlated with higher levels of blood sugar and glycated hemoglobin. This study suggests that peripheral blood eosinophil composition or count may be associated with serum glucose levels in patients with adrenal Cushing syndrome. Copyright © 2017 Korean Endocrine Society

  8. Immunologic, hemodynamic, and adrenal incompetence in cirrhosis

    DEFF Research Database (Denmark)

    Risør, Louise Madeleine; Bendtsen, Flemming; Møller, Søren

    2015-01-01

    dysfunction, but is not responsive to volume expansion. Recent research indicates that development of hepatic nephropathy represents a continuous spectrum of functional and structural dysfunction and may be precipitated by the inherent immunologic, adrenal, and hemodynamic incompetence in cirrhosis. New...... research explores several new markers of renal dysfunction that may replace serum creatinine in the future and give new insight on the hepatic nephropathy. Our understanding of the pathophysiological mechanisms causing the immunologic, adrenal, and hemodynamic incompetence, and the impact on renal...

  9. Ultrasound diagnosis of adrenal hemorrhage in meningococcemia

    International Nuclear Information System (INIS)

    Sarnaik, A.P.; Sanfilippo, D.J.K.; Slovis, T.L.; Children's Hospital of Michigan, Detroit; Wayne State Univ., Detroit, MI

    1988-01-01

    Adrenal hemorrhage (AH) is a well-described complication of the neonatal period, anticoagulant therapy, and overwhelming bacterial infection especially with N. meningitis. Until recently the diagnosis of acute AH was based predominantly on autopsy findings. Ultrasound and computed tomography examinations have been successfully used for antemortem detection of AH in neonates and anticoagulated patients. We report two patients with fulminant meningococcal infection who demonstrated bilateral adrenal hemorrhages on ultrasonography. (orig.)

  10. Chronic Heroin Dependence Leading to Adrenal Insufficiency

    Directory of Open Access Journals (Sweden)

    Gautam Das

    2014-01-01

    Full Text Available Opioids have been the mainstay for pain relief and palliation over a long period of time. They are commonly abused by drug addicts and such dependence usually imparts severe physiologic effects on multiple organ systems. The negative impact of opioids on the endocrine system is poorly understood and often underestimated. We describe a patient who developed severe suppression of the hypothalamic-pituitary adrenal (HPA axis leading to secondary adrenal insufficiency due to long standing abuse of opioids.

  11. A Chemical Probe that Labels Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Nao Hirata

    2014-03-01

    Full Text Available A small-molecule fluorescent probe specific for human pluripotent stem cells would serve as a useful tool for basic cell biology research and stem cell therapy. Screening of fluorescent chemical libraries with human induced pluripotent stem cells (iPSCs and subsequent evaluation of hit molecules identified a fluorescent compound (Kyoto probe 1 [KP-1] that selectively labels human pluripotent stem cells. Our analyses indicated that the selectivity results primarily from a distinct expression pattern of ABC transporters in human pluripotent stem cells and from the transporter selectivity of KP-1. Expression of ABCB1 (MDR1 and ABCG2 (BCRP, both of which cause the efflux of KP-1, is repressed in human pluripotent stem cells. Although KP-1, like other pluripotent markers, is not absolutely specific for pluripotent stem cells, the identified chemical probe may be used in conjunction with other reagents.

  12. Alternative Sources of Adult Stem Cells: Human Amniotic Membrane

    Science.gov (United States)

    Wolbank, Susanne; van Griensven, Martijn; Grillari-Voglauer, Regina; Peterbauer-Scherb, Anja

    Human amniotic membrane is a highly promising cell source for tissue engineering. The cells thereof, human amniotic epithelial cells (hAEC) and human amniotic mesenchymal stromal cells (hAMSC), may be immunoprivileged, they represent an early developmental status, and their application is ethically uncontroversial. Cell banking strategies may use freshly isolated cells or involve in vitro expansion to increase cell numbers. Therefore, we have thoroughly characterized the effect of in vitro cultivation on both phenotype and differentiation potential of hAEC. Moreover, we present different strategies to improve expansion including replacement of animal-derived supplements by human platelet products or the introduction of the catalytic subunit of human telomerase to extend the in vitro lifespan of amniotic cells. Characterization of the resulting cultures includes phenotype, growth characteristics, and differentiation potential, as well as immunogenic and immunomodulatory properties.

  13. In Vitro Cardiomyogenic Potential of Human Amniotic Fluid Stem Cells

    OpenAIRE

    Guan, Xuan; Delo, Dawn M.; Atala, Anthony; Soker, Shay

    2011-01-01

    Stem cell therapy for damaged cardiac tissue is currently limited by a number of factors, including the inability to obtain sufficient cell numbers, the potential tumorigenicity of certain types of stem cells, and the possible link between stem cell therapy and the development of malignant arrhythmias. In this study, we investigated whether human amniotic fluid-derived stem (hAFS) cells could be a potential source of cells for cardiac cell therapy by testing the in vitro differentiation capab...

  14. Polychlorinated biphenyl 126 stimulates basal and inducible aldosterone biosynthesis of human adrenocortical H295R cells

    International Nuclear Information System (INIS)

    Li, L.-A.; Wang, P.-W.; Chang, Louis W.

    2004-01-01

    To understand the effects of polychlorinated biphenyls (PCBs) on adrenal aldosterone biosynthesis, we have performed a systematical study to characterize the corresponding steroidogenic response of human adrenocortical cell line H295R to PCB126 exposure. We found that PCB126 at high concentrations stimulated basal and inducible aldosterone production. The aldosterone induction occurred concomitantly with activation of the CYP11B2 gene. Despite the fact that PCB126 acted in synergy with both potassium and angiotensin II (Ang II) in activation of aldosterone synthesis, PCB126 only modestly increased CYP11B2 mRNA expression in the presence of Ang II contrary to the synergistic transcriptional induction elicited by PCB126 and potassium. This implicated that PCB126 had differential interactions with the potassium and Ang II signaling systems in the regulation of aldosterone biosynthesis. In addition, high concentrations of PCB126 elevated transcriptional expression of the type I Ang II receptor (AT 1 ) and might thus sensitize the cellular Ang II responsiveness in both basal and inducible aldosterone biosynthesis. SF-1 was not involved in the PCB126-induced transcriptional regulation despite its importance in steroidogenic gene activation

  15. Trichloroethylene toxicity in a human hepatoma cell line

    Energy Technology Data Exchange (ETDEWEB)

    Thevenin, E.; McMillian, J. [Medical Univ. of Charleston South Carolina, SC (United States)

    1994-12-31

    The experiments conducted in this study were designed to determine the usefullness of hepatocyte cultures and a human hepatoma cell line as model systems for assessing human susceptibility to hepatocellular carcinoma due to exposure to trichloroethylene. The results from these studies will then be analyzed to determine if human cell lines can be used to conduct future experiments of this nature.

  16. Identification of human tissue cross-presenting dendritic cells

    OpenAIRE

    Haniffa, Muzlifah; Collin, Matthew; Ginhoux, Florent

    2013-01-01

    Dendritic cells (DCs) are a heterogeneous group of functionally specialized antigen-presenting cells. We recently characterized the human tissue cross-presenting DCs and aligned the human and mouse DC subsets. Our findings will facilitate the translation of murine DC studies to the human setting and aid the design of DC-based vaccine strategies for infection and cancer immunotherapy.

  17. High density lipoprotein as a source of cholesterol for adrenal steroidogenesis: a study in individuals with low plasma HDL-C

    NARCIS (Netherlands)

    Bochem, Andrea E.; Holleboom, Adriaan G.; Romijn, Johannes A.; Hoekstra, Menno; Dallinga-Thie, Geesje M.; Motazacker, Mahdi M.; Hovingh, G. Kees; Kuivenhoven, Jan A.; Stroes, Erik S. G.

    2013-01-01

    Few studies have addressed the delivery of lipoprotein-derived cholesterol to the adrenals for steroid production in humans. While there is evidence against a role for low-density lipoprotein (LDL), it is unresolved whether high density lipoprotein (HDL) contributes to adrenal steroidogenesis. To

  18. Enhanced casein kinase II activity in human tumour cell cultures

    DEFF Research Database (Denmark)

    Prowald, K; Fischer, H; Issinger, O G

    1984-01-01

    Casein kinase II (CKII) activity is enhanced as much as 2-3 fold in established and 4-5-fold in transformed human cell lines when compared to that of fibroblasts and primary human tumour cell cultures where CKII activity never exceeded a basic level. The high activity of CKII in transformed cells...

  19. MODERATE CYTOTOXICITY OF PROANTHOCYANIDINS TO HUMAN TUMOR-CELL LINES

    NARCIS (Netherlands)

    KOLODZIEJ, H; HABERLAND, C; WOERDENBAG, HJ; KONINGS, AWT

    In the present study the cytotoxicity of 16 proanthocyanidins was evaluated in GLC(4), a human small cell lung carcinoma cell line, and in COLO 320, a human colorectal cancer cell line, using the microculture tetrazolium (MTT) assay. With IC50 values ranging from 18 to >200 mu m following continuous

  20. Isolation and in vitro expansion of human colonic stem cells

    NARCIS (Netherlands)

    Jung, P.; Sato, T.; Merlos-Suarez, A.; Barriga, F.M.; Iglesias, M.; Rossell, D.; Auer, H.; Gallardo, M.; Blasco, M.A.; Sancho, E.; Clevers, H.; Batlle, E.

    2011-01-01

    Here we describe the isolation of stem cells of the human colonic epithelium. Differential cell surface abundance of ephrin type-B receptor 2 (EPHB2) allows the purification of different cell types from human colon mucosa biopsies. The highest EPHB2 surface levels correspond to epithelial colonic

  1. Classic congenital adrenal hyperplasia and puberty.

    Science.gov (United States)

    Charmandari, Evangelia; Brook, Charles G D; Hindmarsh, Peter C

    2004-11-01

    Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders resulting from deficiency of one of the five enzymes required for synthesis of cortisol in the adrenal cortex. The most common form of the disease is classic 21-hydroxylase deficiency, which is characterized by decreased synthesis of glucocorticoids and often mineralocorticoids, adrenal hyperandrogenism and impaired development and function of the adrenal medulla. The clinical management of classic 21-hydroxylase deficiency is often suboptimal, and patients are at risk of developing in tandem iatrogenic hypercortisolism and/or hyperandogenism. Limitations of current medical therapy include the inability to control hyperandrogenism without employing supraphysiologic doses of glucocorticoid, hyperresponsiveness of the hypertrophied adrenal glands to adrenocorticotropic hormone (ACTH) and difficulty in suppressing ACTH secretion from the anterior pituitary. Puberty imposes increased difficulty in attaining adrenocortical suppression despite optimal substitution therapy and adherence to medical treatment. Alterations in the endocrine milieu at puberty may influence cortisol pharmacokinetics and, consequently, the handling of hydrocortisone used as replacement therapy. Recent studies have demonstrated a significant increase in cortisol clearance at puberty and a shorter half-life of free cortisol in pubertal females compared with males. Furthermore, children with classic CAH have elevated fasting serum insulin concentrations and insulin resistance. The latter may further enhance adrenal and/or ovarian androgen secretion, decrease the therapeutic efficacy of glucocorticoids and contribute to later development of the metabolic syndrome and its complications.

  2. The development of human mast cells. An historical reappraisal

    International Nuclear Information System (INIS)

    Ribatti, Domenico

    2016-01-01

    The understanding of mast cell (MC) differentiation is derived mainly from in vitro studies of different stages of stem and progenitor cells. The hematopoietic lineage development of human MCs is unique compared to other myeloid-derived cells. Human MCs originate from CD34"+/CD117"+/CD13"+multipotent hematopoietic progenitors, which undergo transendothelial recruitment into peripheral tissues, where they complete differentiation. Stem cell factor (SCF) is a major chemotactic factor for MCs and their progenitors. SCF also elicits cell-cell and cell-substratum adhesion, facilitates the proliferation, and sustains the survival, differentiation, and maturation, of MCs. Because MC maturation is influenced by local microenvironmental factors, different MC phenotypes can develop in different tissues and organs. - Highlights: • Human mast cells originate from CD34/CD117/CD13 positive multipotent hematopoietic progenitors. • Stem cell factor is a major chemotactic factor for mast cells and their progenitors. • Different mast cell phenotypes can develop in different tissues and organs.

  3. [Effect of drinking boron on microtructure of adrenal gland in rats].

    Science.gov (United States)

    Li, Shenghe; Wang, Jue; Zhou, Jinxing; Jin, Guangming; Gu, Youfang; Xu, Wanxiang

    2012-09-01

    The effects of drinking boron exposure on the mass, organ indexes and structure of adrenal gland were studied in the paper. Methods 192 Sprague-Dawley rats (28 +/- 2 days) with no bacteria infecting were divided into six groups (n = 32, male = female) randomly. Treated rats drunk the distilled water which supplemented with boron of 0, 40, 80, 160, 320 and 640 mg/L, respectively, for 60 days. At the 30th and the 60th day of experiment, 16 rats (n = 8, male = female) of each group were selected and made into narcosis with 10% Chloral Hydrate. The adrenal glands were obtained, weighted and fixed after dissection, then the samples were made into paraffin sections, stained with HE stain and chromaffin, observed and photographed by Olympus CH-30 microphotograph system. Compared with control group, the average mass of adrenal gland of male rats in each experiment group decreased significantly or most significantly at the 30th day of experiment (P boron at 60th day of experiment increased significantly (P boron were better obviously than control group, and the numbers of chromaffin granules in chromaffin cell increased obviously. The histopathological changes of different degree could be observed in the group of 80 to 640 mg/L boron, and they became remarkable with the boron supplementation. By comparative observation, the damage of cells in adrenal medulla appeared ahead of them in adrenal cortex, and the pathological change of adrenal gland in male rats were obvious than female rats. Drinking supplemented with 40 mg/L boron could prompt the structure of adrenal gland in rats, but could cause different degree damage, or even obvious toxic effect when the concentration of boron supplementation in drinking from 80 to 640 mg/L.

  4. Noninvasive Prenatal Diagnosis of Congenital Adrenal Hyperplasia.

    Science.gov (United States)

    Khattab, Ahmed; Yuen, Tony; Sun, Li; Yau, Mabel; Barhan, Ariella; Zaidi, Mone; Lo, Y M Dennis; New, Maria I

    2016-01-01

    A major hallmark of classical congenital adrenal hyperplasia (CAH) is genital ambiguity noted at birth in affected females, which leads to psychological and psychosexual issues in adult life. Attempts to correct genital ambiguity through surgical intervention have been partially successful. Fetal hyperandrogenemia and genital ambiguity have been shown to be preventable by prenatal administration of low-dose dexamethasone initiated before the 9th week of gestation. In 7 of 8 at-risk pregnancies, the unaffected fetus is unnecessarily exposed to dexamethasone for weeks until the diagnosis of classical CAH is ruled out by invasive procedures. This therapeutic dilemma calls for early prenatal diagnosis so that dexamethasone treatment can be directed to affected female fetuses only. We describe the utilization of cell-free fetal DNA in mothers carrying at-risk fetuses as early as 6 gestational weeks by targeted massively parallel sequencing of the genomic region including and flanking the CYP21A2 gene. Our highly personalized and innovative approach should permit the diagnosis of CAH before genital development begins, therefore restricting the purposeful administration of dexamethasone to mothers carrying affected females. © 2016 S. Karger AG, Basel.

  5. Adrenocorticotrophic hormone (ACTH) stimulation of sheep fetal adrenal cortex can occur without increased expression of ACTH receptor (ACTH-R) mRNA

    DEFF Research Database (Denmark)

    Carter, A M; Petersen, Y M; Towstoless, M

    2002-01-01

    In the present study, it was hypothesized that the adrenocorticotrophin hormone receptor (ACTH-R) would be up-regulated in the adrenal gland of the sheep fetus following infusion of physiological amounts of ACTH, as shown for adrenal cortical cells in culture. In chronically catheterized sheep...

  6. Characterization of endothelin receptors on a human neuroblastoma cell line: evidence for the ETA subtype.

    Science.gov (United States)

    Wilkes, L C; Boarder, M R

    1991-11-01

    1. Specific binding sites for synthetic endothelin (ET) isoforms were studied on intact cells of the SK-N-MC cell line, derived from a human neuroblastoma. 2. [125I]-ET-1 (2.5 x 10(-11) M) specifically bound to a single class of binding sites on these cells (Hill coefficient of 1.06 +/- 0.04, n = 3) with an apparent Kd of 1.4 +/- 0.3 x 10(-9) M and a Bmax of 3.1 +/- 1.0 pmol mg-1 protein. [125I]-ET-3 (2.5 x 10(-11) M), did not specifically bind to SK-N-MC cells. 3. The binding of [125I]-ET-1 was competitively inhibited by other ET isoforms, the order of potency being ET-1 greater than sarafotoxin S6b greater than ET-3. 4. Association of 1 nM [125I]-ET-1 at 37 degrees C reached apparent equilibrium at 60-80 min, with half-maximal binding being achieved at 12 min. 5. Dissociation was measured after both 10 min and 60 min of association with 64% and 30% respectively of specifically bound [125I]-ET-1 dissociating. The actual amounts of [125I]-ET-1 dissociated were similar in both cases. 6. Incubation of [125I]-ET-3 with SK-N-MC cells at 37 degrees C for 60 min did not result in significant degradation of this peptide. However, [125I]-ET-1 was broken down by incubation with SK-N-MC cells, the pattern of degradation of dissociable [125I]-ET-1 (and that found in the supernatant) being different from that of non-dissociable [125I]-ET-1. 7. ET-1 concentration-dependently induced an increase in total inositol phosphate accumulation in subconfluent (but not in confluent) cultures of SK-N-MC cells (EC50 = 6.43 +/- 1.9 x 1010M). ET-3 was without effect. 8. These results show that ET-1 specifically binds to SK-N-MC cells with the characteristics of an ETA receptor. Our earlier finding that adrenal chromaffin cells express an ETB receptor indicates the existence of multiple ET receptor types on neuronal cells.

  7. The commitment of human cells to senescence.

    Science.gov (United States)

    Holliday, Robin

    2014-01-01

    Fifty years ago, it was demonstrated by Leonard Hayflick that human diploid fibroblasts grown in culture have a finite lifespan. Since that time, innumerable experiments have been published to discover the mechanism(s) that are responsible for this 'Hayflick limit' to continuous growth. Much new information has been gained, but there are certain features of this experimental system which have not been fully understood. One is the fact that different populations of the foetal lung strains WI-38 and MRC-5 have a range in division potential of at least a millionfold. The commitment theory of cellular aging, published more than 30 years ago, is able to explain this, but it has been consistently ignored. The theory predicts that bottlenecks, which are transient reductions in population size, can significantly reduce lifespan, or increase variability of lifespans. Computer simulations specify the effects of bottlenecks on longevity, and these were confirmed in two series of experiments. Commitment to senescence may be the loss of telomerase, which leads to the erosion of telomeres and the inability to grow indefinitely. Many experiments have been done with skin fibroblasts from human donors of different age, and it was originally thought that in vitro lifespan was inversely correlated with donor age. In these experiments, a single skin biopsy produces a population of cells that are grown to senescence. However, there is no reason to believe that skin fibroblasts are less variable in their in vitro lifespan than foetal lung strains, in which case the data points with skin cells are so variable that they may completely obscure any inverse correlation between culture lifespans and donor age.

  8. Determination of adrenal volume by MRI in healthy children

    DEFF Research Database (Denmark)

    Mouritsen, Annette; Johansen, Marie Lindhardt; Wohlfahrt-Veje, Christine

    2014-01-01

    , to estimate adrenal size in healthy children and to evaluate determinants of adrenal volume such as age, gender, body size, pubic hair stage and serum levels of adrenal androgens. DESIGN: Two hundred and thirty-five healthy children (116 girls and 119 boys) (age range 10.0-14.8 years) were examined by MRI......% of healthy children aged 10-15 years. Adrenal volume increased with age and Tanner stage of pubic hair. Future studies will unravel whether adrenal MRI is useful when evaluating children with adrenal diseases....... (estimate B = 0.34 ml/year, P = 0.03), age (estimate B = 0.05 ml/year, P = 0.021) and pubic hair stage (estimate B = 0.05 ml/stage, P = 0.075). No associations between adrenal size and serum levels of adrenal androgens were observed. CONCLUSION: It was possible to determine adrenal volume by MRI in only 50...

  9. Human Stem Cell Derived Cardiomyocytes: An Alternative ...

    Science.gov (United States)

    Chemical spills and associated deaths in the US has increased 2.6-fold and 16-fold from 1983 to 2012, respectfully. In addition, the number of chemicals to which humans are exposed to in the environment has increased almost 10-fold from 2001 to 2013 within the US. Internationally, a WHO report on the global composite impact of chemicals on health reported that 16% of the total burden of cardiovascular disease was attributed to environmental chemical exposure with 2.5 million deaths per year. Clearly, the cardiovascular system, at all its various developmental and life stages, represents a critical target organ system that can be adversely affected by existing and emerging chemicals (e.g., engineered nanomaterials) in a variety of environmental media. The ability to assess chemical cardiac risk and safety is critically needed but extremely challenging due to the number and categories of chemicals in commerce, as indicated. This presentation\\session will evaluate the use of adult human stem cell derived cardiomyocytes, and existing platforms, as an alternative model to evaluate environmental chemical cardiac toxicity as well as provide key information for the development of predictive adverse outcomes pathways associated with environmental chemical exposures. (This abstract does not represent EPA policy) Rapid and translatable chemical safety screening models for cardiotoxicity current status for informing regulatory decisions, a workshop sponsored by the Society

  10. Efficient and Fast Differentiation of Human Neural Stem Cells from Human Embryonic Stem Cells for Cell Therapy

    Directory of Open Access Journals (Sweden)

    Xinxin Han

    2017-01-01

    Full Text Available Stem cell-based therapies have been used for repairing damaged brain tissue and helping functional recovery after brain injury. Aberrance neurogenesis is related with brain injury, and multipotential neural stem cells from human embryonic stem (hES cells provide a great promise for cell replacement therapies. Optimized protocols for neural differentiation are necessary to produce functional human neural stem cells (hNSCs for cell therapy. However, the qualified procedure is scarce and detailed features of hNSCs originated from hES cells are still unclear. In this study, we developed a method to obtain hNSCs from hES cells, by which we could harvest abundant hNSCs in a relatively short time. Then, we examined the expression of pluripotent and multipotent marker genes through immunostaining and confirmed differentiation potential of the differentiated hNSCs. Furthermore, we analyzed the mitotic activity of these hNSCs. In this report, we provided comprehensive features of hNSCs and delivered the knowledge about how to obtain more high-quality hNSCs from hES cells which may help to accelerate the NSC-based therapies in brain injury treatment.

  11. Failure to visualize adrenal glands in a patient with bilateral adrenal hyperplasia

    International Nuclear Information System (INIS)

    Gordon, L.; Mayfield, R.K.; Levine, J.H.; Lopes-Virella, M.F.; Sagel, J.; Buse, M.G.

    1980-01-01

    A patient with clinical and biochemical evidence of Cushing's disease and severe hyperlipidemia underwent an adrenal imaging procedure with NP-59 (6β-[ 131 I]iodomethyl-19-norcholesterol), without visualization of either gland. Correction of the hyperlipidemia followed by repeated adrenal imaging resulted in bilateral visualization. A pituitary tumor was removed at surgery, confirming the diagnosis of Cushing's disease

  12. Adrenomegaly and septic adrenal hemorrhage (Waterhouse-Friderichsen syndrome) in the setting of congenital adrenal hyperplasia

    OpenAIRE

    Saad, Amin F.; Ford, Kenneth L.; dePrisco, Gregory; Smerud, Michael J.

    2013-01-01

    Congenital adrenal hyperplasia refers to a spectrum of autosomal recessive inherited disorders of steroidogenesis most commonly identified on newborn screenings. We describe a young woman who presented with abdominal pain and on subsequent imaging was found to have features of congenital adrenal hyperplasia. Imaging findings, treatment, and potential complications are discussed.

  13. Adrenomegaly and septic adrenal hemorrhage (Waterhouse-Friderichsen syndrome) in the setting of congenital adrenal hyperplasia.

    Science.gov (United States)

    Saad, Amin F; Ford, Kenneth L; Deprisco, Gregory; Smerud, Michael J

    2013-07-01

    Congenital adrenal hyperplasia refers to a spectrum of autosomal recessive inherited disorders of steroidogenesis most commonly identified on newborn screenings. We describe a young woman who presented with abdominal pain and on subsequent imaging was found to have features of congenital adrenal hyperplasia. Imaging findings, treatment, and potential complications are discussed.

  14. New frontiers in human cell biology and medicine: can pluripotent stem cells deliver?

    Science.gov (United States)

    Goldstein, Lawrence S B

    2012-11-12

    Human pluripotent stem cells provide enormous opportunities to treat disease using cell therapy. But human stem cells can also drive biomedical and cell biological discoveries in a human model system, which can be directly linked to understanding disease or developing new therapies. Finally, rigorous scientific studies of these cells can and should inform the many science and medical policy issues that confront the translation of these technologies to medicine. In this paper, I discuss these issues using amyotrophic lateral sclerosis as an example.

  15. Effects of Human Umbilical Cord Mesenchymal Stem Cells on Human Trophoblast Cell Functions In Vitro

    Directory of Open Access Journals (Sweden)

    Yajing Huang

    2016-01-01

    Full Text Available Trophoblast cell dysfunction is involved in many disorders during pregnancy such as preeclampsia and intrauterine growth restriction. Few treatments exist, however, that target improving trophoblast cell function. Human umbilical cord mesenchymal stem cells (hUCMSCs are capable of self-renewing, can undergo multilineage differentiation, and have homing abilities; in addition, they have immunomodulatory effects and paracrine properties and thus are a prospective source for cell therapy. To identify whether hUCMSCs can regulate trophoblast cell functions, we treated trophoblast cells with hUCMSC supernatant or cocultured them with hUCMSCs. Both treatments remarkably enhanced the migration and invasion abilities of trophoblast cells and upregulated their proliferation ability. At a certain concentration, hUCMSCs also modulated hCG, PIGF, and sEndoglin levels in the trophoblast culture medium. Thus, hUCMSCs have a positive effect on trophoblast cellular functions, which may provide a new avenue for treatment of placenta-related diseases during pregnancy.

  16. CD56 marks human dendritic cell subsets with cytotoxic potential

    NARCIS (Netherlands)

    Roothans, D.; Smits, E.; Lion, E.; Tel, J.; Anguille, S.

    2013-01-01

    Human plasmacytoid and myeloid dendritic cells (DCs), when appropriately stimulated, can express the archetypal natural killer (NK)-cell surface marker CD56. In addition to classical DC functions, CD56(+) DCs are endowed with an unconventional cytotoxic capacity.

  17. Bacteria, fungi, and viruses outnumber human cells 10:1

    Indian Academy of Sciences (India)

    Karen Nelson

    Fig 2. The distribution of the number of human cells by cell type. Sender R ... Type 2 diabetes ... Development of new predictive biomarkers so that preventive ... Microbiome, irrespective of lifestyle and age, which is distinct from races and.

  18. Study of morphological alterations of the adrenal glands in the neoplastic cachexia
    Estudo das alterações morfológicas da glândula adrenal na caquexia neoplásica

    OpenAIRE

    Tânia Longo Mazzuco; Karina Garcia Cotrim; Alexandre Yukio Saito; Marcelo Abbá Macioszek; Eveline Aparecida Isquierdo Fonseca

    2009-01-01

    Advanced cancer occurs with nutritional and metabolic alterations that characterize neoplastic cachexia. When homeostasis is compromised, the adrenal glands have a fundamental role in the neuroendocrine response. Our purpose in this research was to study morphological alterations of the adrenal glands in the development of cancer associated to cachexia. Cachexia experimental model induced by Walker 256 tumor in Wistar rats, was used. Animals were sacrificed 12 days after tumor cells inoculati...

  19. Microspectroscopy of spectral biomarkers associated with human corneal stem cells

    OpenAIRE

    Nakamura, Takahiro; Kelly, Jemma G.; Trevisan, J?lio; Cooper, Leanne J.; Bentley, Adam J.; Carmichael, Paul L.; Scott, Andrew D.; Cotte, Marine; Susini, Jean; Martin-Hirsch, Pierre L.; Kinoshita, Shigeru; Fullwood, Nigel J.; Martin, Francis L.

    2010-01-01

    Purpose Synchrotron-based radiation (SRS) Fourier-transform infrared (FTIR) microspectroscopy potentially provides novel biomarkers of the cell differentiation process. Because such imaging gives a ?biochemical-cell fingerprint? through a cell-sized aperture, we set out to determine whether distinguishing chemical entities associated with putative stem cells (SCs), transit-amplifying (TA) cells, or terminally-differentiated (TD) cells could be identified in human corneal epithelium. Methods D...

  20. Computed tomography of the adrenal glands in Addision's disease

    International Nuclear Information System (INIS)

    Rzymski, K.; Sobieszczyk, S.; Kosowicz, J.; Akademia Medyczna, Poznan

    1984-01-01

    In 30 cases of chronic adrenal insufficiency (Addison's disease) CT of the adrenal glands was performed using a fourth generation scanner and a 2 mm slice thickness. Adrenal glands were visualized in all the cases. In 26 patients the adrenals were atrophied; the adrenal shape was abnormal in 21 patients. In 15 patients CT disclosed calcifications in one or both glands, which were particularly frequent in patients over the age of 50. Atrophy of adrenal glands was of high occurrence in cases of autoimmune origin. (orig.) [de

  1. Clinicopathological correlates of adrenal Cushing's syndrome.

    Science.gov (United States)

    Duan, Kai; Gomez Hernandez, Karen; Mete, Ozgur

    2015-03-01

    Endogenous Cushing's syndrome is a rare endocrine disorder that incurs significant cardiovascular morbidity and mortality, due to glucocorticoid excess. It comprises adrenal (20%) and non-adrenal (80%) aetiologies. While the majority of cases are attributed to pituitary or ectopic corticotropin (ACTH) overproduction, primary cortisol-producing adrenal cortical lesions are increasingly recognised in the pathophysiology of Cushing's syndrome. Our understanding of this disease has progressed substantially over the past decade. Recently, important mechanisms underlying the pathogenesis of adrenal hypercortisolism have been elucidated with the discovery of mutations in cyclic AMP signalling (PRKACA, PRKAR1A, GNAS, PDE11A, PDE8B), armadillo repeat containing 5 gene (ARMC5) a putative tumour suppressor gene, aberrant G-protein-coupled receptors, and intra-adrenal secretion of ACTH. Accurate subtyping of Cushing's syndrome is crucial for treatment decision-making and requires a complete integration of clinical, biochemical, imaging and pathology findings. Pathological correlates in the adrenal glands include hyperplasia, adenoma and carcinoma. While the most common presentation is diffuse adrenocortical hyperplasia secondary to excess ACTH production, this entity is usually treated with pituitary or ectopic tumour resection. Therefore, when confronted with adrenalectomy specimens in the setting of Cushing's syndrome, surgical pathologists are most commonly exposed to adrenocortical adenomas, carcinomas and primary macronodular or micronodular hyperplasia. This review provides an update on the rapidly evolving knowledge of adrenal Cushing's syndrome and discusses the clinicopathological correlations of this important disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. Assessment of adrenal function in liver diseases

    Directory of Open Access Journals (Sweden)

    Sandeep Kharb

    2013-01-01

    Full Text Available Background: In recent times, there are reports of adrenal dysfunction in whole spectrum of liver disease. Adrenal insufficiency (AI has been shown to correlate with progression of liver disease. Hence this study was conducted to assess adrenal function in subjects with acute liver disease (ALD, chronic liver disease (CLD and post liver transplantation (LT. Material and Methods: This study included 25 healthy controls, 25 patients of ALD, 20 subjects of CLD with Child-Pugh stage A (CLD-1 and 30 with Child-Pugh stage B or C (CLD-2, and 10 subjects with LT. All subjects were assessed clinically, biochemically and for adrenal functions. Results: AI was present in 9 (34.6% patients with ALD, 20 (40% patients with CLD and 4 (40% in subjects with LT. AI was more common in CLD-2 (18 patients - 60% than CLD-1 (2 patients - 10%. All patients with chronic liver disease had significantly lower basal cortisol (8.8±4.8, P=0.01, stimulated cortisol (18.2±6.3, P <0.00001 and incremental cortisol (9.4±4.6, P <0.00001 as compared to controls. There was increase in percentage of subjects with adrenal dysfunction with progression of liver disease as assessed by Child-Pugh staging. AI was predicted by lower levels of serum protein, serum albumin, total cholesterol and HDL cholesterol and higher levels of serum bilirubin and INR. Adrenal functions showed recovery following liver transplantation. Conclusions: AI forms important part of spectrum of acute and chronic liver disease. Deterioration of synthetic functions of liver disease predicts presence of AI, and these patients should be evaluated for adrenal dysfunction periodically.

  3. Intestinal Stem Cell Dynamics: A Story of Mice and Humans.

    Science.gov (United States)

    Hodder, Michael C; Flanagan, Dustin J; Sansom, Owen J

    2018-06-01

    Stem cell dynamics define the probability of accumulating mutations within the intestinal epithelium. In this issue of Cell Stem Cell, Nicholson et al. (2018) report that human intestinal stem cell dynamics differ significantly from those of mice and establish that oncogenic mutations are more likely to expand; therefore, "normal" epithelium may carry multiple mutations. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Comparative mutagenesis of human cells in vivo and in vitro

    International Nuclear Information System (INIS)

    Thilly, W.G.

    1992-05-01

    This report discusses measuring methods of point mutations; high density cell cultures for low dose studies; measurement and sequence determination of mutations in DNA; the mutational spectra of styrene oxide and ethlyene oxide in TK-6 cells; mutational spectrum of Cr in human lymphoblast cells; mutational spectra of radon in TK-6 cells; and the mutational spectra of smokeless tobacco

  5. Characterizing the radioresponse of pluripotent and multipotent human stem cells.

    Directory of Open Access Journals (Sweden)

    Mary L Lan

    Full Text Available The potential capability of stem cells to restore functionality to diseased or aged tissues has prompted a surge of research, but much work remains to elucidate the response of these cells to genotoxic agents. To more fully understand the impact of irradiation on different stem cell types, the present study has analyzed the radioresponse of human pluripotent and multipotent stem cells. Human embryonic stem (ES cells, human induced pluripotent (iPS cells, and iPS-derived human neural stem cells (iPS-hNSCs cells were irradiated and analyzed for cell survival parameters, differentiation, DNA damage and repair and oxidative stress at various times after exposure. While irradiation led to dose-dependent reductions in survival, the fraction of surviving cells exhibited dose-dependent increases in metabolic activity. Irradiation did not preclude germ layer commitment of ES cells, but did promote neuronal differentiation. ES cells subjected to irradiation exhibited early apoptosis and inhibition of cell cycle progression, but otherwise showed normal repair of DNA double-strand breaks. Cells surviving irradiation also showed acute and persistent increases in reactive oxygen and nitrogen species that were significant at nearly all post-irradiation times analyzed. We suggest that stem cells alter their redox homeostasis to adapt to adverse conditions and that radiation-induced oxidative stress plays a role in regulating the function and fate of stem cells within tissues compromised by radiation injury.

  6. Sequential cancer mutations in cultured human intestinal stem cells

    NARCIS (Netherlands)

    Drost, Jarno; van Jaarsveld, Richard H.; Ponsioen, Bas; Zimberlin, Cheryl; van Boxtel, Ruben; Buijs, Arjan; Sachs, Norman; Overmeer, René M.; Offerhaus, G. Johan; Begthel, Harry; Korving, Jeroen; van de Wetering, Marc; Schwank, Gerald; Logtenberg, Meike; Cuppen, Edwin; Snippert, Hugo J.; Medema, Jan Paul; Kops, Geert J. P. L.; Clevers, Hans

    2015-01-01

    Crypt stem cells represent the cells of origin for intestinal neoplasia. Both mouse and human intestinal stem cells can be cultured in medium containing the stem-cell-niche factors WNT, R-spondin, epidermal growth factor (EGF) and noggin over long time periods as epithelial organoids that remain

  7. Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics

    Directory of Open Access Journals (Sweden)

    Nigel G. Kooreman

    2017-08-01

    Full Text Available There is growing interest in using embryonic stem cell (ESC and induced pluripotent stem cell (iPSC derivatives for tissue regeneration. However, an increased understanding of human immune responses to stem cell-derived allografts is necessary for maintaining long-term graft persistence. To model this alloimmunity, humanized mice engrafted with human hematopoietic and immune cells could prove to be useful. In this study, an in-depth analysis of graft-infiltrating human lymphocytes and splenocytes revealed that humanized mice incompletely model human immune responses toward allogeneic stem cells and their derivatives. Furthermore, using an “allogenized” mouse model, we show the feasibility of reconstituting immunodeficient mice with a functional mouse immune system and describe a key role of innate immune cells in the rejection of mouse stem cell allografts.

  8. Influence of internal exposure on the morphofunctional characteristics of hypothalamus, pituitary and adrenal gland

    International Nuclear Information System (INIS)

    Derev'yanko, L.P.; Nosov, A.T.

    2004-01-01

    The phase changes in morphofunctional states of hypothalamus, pituitary, cortex and medulla of adrenal gland of rats, which for a long time (9 month) were fed a 137 Cs diary, were determined. At early stages of experiment (7 - 30 days) the enhancing of morphofunctional and secretory activity of cells of hypothalamus, pituitary, cortex and medulla of adrenal gland cells, were observed (total absorbed doses of 0,3 sGy). After 9 months (total absorbed doses of 3,0 sGy) in cells of hypothalamus, pituitary, cortex and medulla of adrenal gland the progressions of dystrophic-destructive changes of intracellular structures with the sings of decreasing of morphofunctional and secretory activities were determined. It is necessary to underline, that the sings of intracellular reparative regeneration, were observed in a small part of cells against the background of presence of dystrophic-destructive changes. In spite of the processes of intracellular reparative regeneration which were observed 9 months later after exposure, the completely renewing of morphofunctional and secretory activities in cells of hypothalamus, pituitary, cortex and medulla of adrenal gland cells were absent

  9. Nanoscale Mechanical Stimulation of Human Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    H Nikukar

    2014-05-01

    We observed significant responses after 1 and 2-week stimulations in cell number, cell shapes and phenotypical markers. Microarray was performed for all groups. Cell count showed normal cell growth with stimulation. However, cell surface area, cell perimeter, and arboration after 1-week stimulation showed significant increases. Immunofluorescent studies have showed significant increase in osteocalcin production after stimulation. Conclusions: Nanoscale mechanical vibration showed significant changes in human mesenchymal stem cell behaviours. Cell morphology changed to become more polygonal and increased expression of the osteoblast markers were noted. These findings with gene regulation changes suggesting nanoscale mechanostimulation has stimulated osteoblastogenesis.  Keywords:  Mesenchymal, Nanoscale, Stem Cells.

  10. X-linked congenital adrenal hypoplasia associated with hypospadias in an Egyptian baby: a case report

    Directory of Open Access Journals (Sweden)

    Metwalley Kotb

    2012-12-01

    Full Text Available Abstract Introduction X-linked congenital adrenal hypoplasia is a rare developmental disorder of the human adrenal cortex and is caused by deletion or mutation of the dosage-sensitive sex reversal adrenal hypoplasia congenita critical region of the X chromosome, gene 1 (DAX-1 gene. Most affected children present with failure to thrive, salt wasting and hypoglycemic convulsions in the first months of life. Hypospadias affects approximately one in 250 live male births. Mutations in the mastermind-like domain-containing 1 (MAMLD1 gene have been implicated as one of the causes of hypospadias in children. To the best of our knowledge, an association between congenital adrenal hypoplasia due to a DAX-1 mutation and hypospadias due to mutation of the MAMLD1 gene has not previously been reported in the literature. Case presentation A 35-day-old male Egyptian baby was referred to our institution for the evaluation of a two-week history of recurrent vomiting associated with electrolyte imbalance. On examination, our patient was found to have hypotension and dehydration. A genital examination showed distal penile hypospadias with chordee and normal testes. He had hyponatremia, hyperkalemia, hypoglycemia and metabolic acidosis. Endocrinological investigations revealed low levels of cortisol, 17-hydroxyprogesterone and aldosterone, with a high level of adrenocorticotrophic hormone. A provisional diagnosis of congenital adrenal hypoplasia associated with hypospadias was made. A molecular genetics study confirmed the diagnosis of X-linked congenital adrenal hypoplasia due to DAX-1 mutations and hypospadias due to MAMLD1 mutation. He was started on hydrocortisone and fludrocortisone treatment. After three weeks of treatment, his symptoms improved and his blood sugar, sodium, potassium and cortisol levels normalized. Conclusions We report the case of an Egyptian baby with an association of congenital adrenal hypoplasia due to DAX-1 mutation and hypospadias due

  11. Canthin-6-one induces cell death, cell cycle arrest and differentiation in human myeloid leukemia cells.

    Science.gov (United States)

    Vieira Torquato, Heron F; Ribeiro-Filho, Antonio C; Buri, Marcus V; Araújo Júnior, Roberto T; Pimenta, Renata; de Oliveira, José Salvador R; Filho, Valdir C; Macho, Antonio; Paredes-Gamero, Edgar J; de Oliveira Martins, Domingos T

    2017-04-01

    Canthin-6-one is a natural product isolated from various plant genera and from fungi with potential antitumor activity. In the present study, we evaluate the antitumor effects of canthin-6-one in human myeloid leukemia lineages. Kasumi-1 lineage was used as a model for acute myeloid leukemia. Cells were treated with canthin-6-one and cell death, cell cycle and differentiation were evaluated in both total cells (Lin + ) and leukemia stem cell population (CD34 + CD38 - Lin -/low ). Among the human lineages tested, Kasumi-1 was the most sensitive to canthin-6-one. Canthin-6-one induced cell death with apoptotic (caspase activation, decrease of mitochondrial potential) and necrotic (lysosomal permeabilization, double labeling of annexin V/propidium iodide) characteristics. Moreover, canthin-6-one induced cell cycle arrest at G 0 /G 1 (7μM) and G 2 (45μM) evidenced by DNA content, BrdU incorporation and cyclin B1/histone 3 quantification. Canthin-6-one also promoted differentiation of Kasumi-1, evidenced by an increase in the expression of myeloid markers (CD11b and CD15) and the transcription factor PU.1. Furthermore, a reduction of the leukemic stem cell population and clonogenic capability of stem cells were observed. These results show that canthin-6-one can affect Kasumi-1 cells by promoting cell death, cell cycle arrest and cell differentiation depending on concentration used. Canthin-6-one presents an interesting cytotoxic activity against leukemic cells and represents a promising scaffold for the development of molecules for anti-leukemic applications, especially by its anti-leukemic stem cell activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Comparison of the glycosphingolipids of human-induced pluripotent stem cells and human embryonic stem cells.

    Science.gov (United States)

    Säljö, Karin; Barone, Angela; Vizlin-Hodzic, Dzeneta; Johansson, Bengt R; Breimer, Michael E; Funa, Keiko; Teneberg, Susann

    2017-04-01

    High expectations are held for human-induced pluripotent stem cells (hiPSC) since they are established from autologous tissues thus overcoming the risk of allogeneic immune rejection when used in regenerative medicine. However, little is known regarding the cell-surface carbohydrate antigen profile of hiPSC compared with human embryonic stem cells (hESC). Here, glycosphingolipids were isolated from an adipocyte-derived hiPSC line, and hiPSC and hESC glycosphingolipids were compared by concurrent characterization by binding assays with carbohydrate-recognizing ligands and mass spectrometry. A high similarity between the nonacid glycosphingolipids of hiPSC and hESC was found. The nonacid glycosphingolipids P1 pentaosylceramide, x2 pentaosylceramide and H type 1 heptaosylceramide, not previously described in human pluripotent stem cells (hPSC), were characterized in both hiPSC and hESC. The composition of acid glycosphingolipids differed, with increased levels of GM3 ganglioside, and reduced levels of GD1a/GD1b in hiPSC when compared with hESC. In addition, the hESC glycosphingolipids sulf-globopentaosylceramide and sialyl-globotetraosylceramide were lacking in hiPSC. Neural stem cells differentiating from hiPSC had a reduced expression of sialyl-lactotetra, whereas expression of the GD1a ganglioside was significantly increased. Thus, while sialyl-lactotetra is a marker of undifferentiated hPSC, GD1a is a novel marker of neural differentiation. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. A DNA Vaccine Protects Human Immune Cells against Zika Virus Infection in Humanized Mice

    Directory of Open Access Journals (Sweden)

    Guohua Yi

    2017-11-01

    Full Text Available A DNA vaccine encoding prM and E protein has been shown to induce protection against Zika virus (ZIKV infection in mice and monkeys. However, its effectiveness in humans remains undefined. Moreover, identification of which immune cell types are specifically infected in humans is unclear. We show that human myeloid cells and B cells are primary targets of ZIKV in humanized mice. We also show that a DNA vaccine encoding full length prM and E protein protects humanized mice from ZIKV infection. Following administration of the DNA vaccine, humanized DRAG mice developed antibodies targeting ZIKV as measured by ELISA and neutralization assays. Moreover, following ZIKV challenge, vaccinated animals presented virtually no detectable virus in human cells and in serum, whereas unvaccinated animals displayed robust infection, as measured by qRT-PCR. Our results utilizing humanized mice show potential efficacy for a targeted DNA vaccine against ZIKV in humans.

  14. Molecular aging and rejuvenation of human muscle stem cells

    DEFF Research Database (Denmark)

    Carlson, Morgan E; Suetta, Charlotte; Conboy, Michael J

    2009-01-01

    . Our findings establish key evolutionarily conserved mechanisms of human stem cell aging. We find that satellite cells are maintained in aged human skeletal muscle, but fail to activate in response to muscle attrition, due to diminished activation of Notch compounded by elevated transforming growth...... factor beta (TGF-beta)/phospho Smad3 (pSmad3). Furthermore, this work reveals that mitogen-activated protein kinase (MAPK)/phosphate extracellular signal-regulated kinase (pERK) signalling declines in human muscle with age, and is important for activating Notch in human muscle stem cells. This molecular......Very little remains known about the regulation of human organ stem cells (in general, and during the aging process), and most previous data were collected in short-lived rodents. We examined whether stem cell aging in rodents could be extrapolated to genetically and environmentally variable humans...

  15. Generation of Corneal Keratocytes from Human Embryonic Stem Cells.

    Science.gov (United States)

    Hertsenberg, Andrew J; Funderburgh, James L

    2016-01-01

    Human Embryonic Stem Cells (hESC) offer an important resource as a limitless supply of any differentiated cell type of the human body. Keratocytes, cells from the corneal stroma, may have the potential for restoration of vision in cell therapy and biomedical engineering applications, but these specialized cells are not readily expanded in vitro. Here we describe a two-part method to produce keratocytes from the H1 hESC cell line. The hESC cells, maintained and expanded in feeder-free culture medium are first differentiated to neural crest cells using the stromal-derived inducing activity (SDIA) of the PA6 mouse embryonic fibroblast cell line. The resulting neural crest cells are selected by their expression of cell-surface CD271 and subsequently cultured as 3D pellets in a defined differentiation medium to induce a keratocyte phenotype.

  16. Nitrophenols isolated from diesel exhaust particles regulate steroidogenic gene expression and steroid synthesis in the human H295R adrenocortical cell line

    International Nuclear Information System (INIS)

    Furuta, Chie; Noda, Shiho; Li Chunmei; Suzuki, Akira K; Taneda, Shinji; Watanabe, Gen; Taya, Kazuyoshi

    2008-01-01

    Studies of nitrophenols isolated from diesel exhaust particles (DEPs), 3-methyl-4-nitrophenol (PNMC) and 4-nitro-3-phenylphenol (PNMPP) have revealed that these chemicals possess estrogenic and anti-androgenic activity in vitro and in vivo and that PNMC accumulate in adrenal glands in vivo. However, the impacts of exposure to these compounds on adrenal endocrine disruption and steroidogenesis have not been investigated. To elucidate the non-receptor mediated effects of PNMC and PNMPP, we investigated the production of the steroid hormones progesterone, cortisol, testosterone, and estradiol-17β and modulation of nine major enzyme genes involved in the synthesis of steroid hormones (CYP11A, CYP11B1, CYP17, CYP19, 17βHSD1, 17βHSD4, CYP21, 3βHSD2, StAR) in human adrenal H295R cells supplied with cAMP. Exposure to 10 -7 to 10 -5 M PNMC and 1 mM 8-Br-cAMP for 48 h decreased testosterone, cortisol, and estradiol-17β levels and increased progesterone secretion. At 10 -5 M, PNMC with 1 mM 8-Br-cAMP significantly stimulated expression of the 17βHSD4 and significantly suppressed expression of 3βHSD2. In comparison, 10 -7 to 2 x 10 -5 M PNMPP with 1 mM 8-Br-cAMP for 48 h decreased concentrations of estradiol-17β, increased progesterone levels, but did not affect testosterone and cortisol secretion due to the significant suppression of CYP17 and the non-significant but obvious suppression of CYP19. Our results clarified steroidogenic enzymes as candidates responsible for the inhibition or stimulation for the production of steroid hormones in the steroidogenic pathway, thus providing the first experimental evidence for multiple mechanisms of disruption of endocrine pathways by these nitrophenols

  17. In vitro proliferation of adult human beta-cells.

    Directory of Open Access Journals (Sweden)

    Sabine Rutti

    Full Text Available A decrease in functional beta-cell mass is a key feature of type 2 diabetes. Glucagon-like peptide 1 (GLP-1 analogues induce proliferation of rodent beta-cells. However, the proliferative capacity of human beta-cells and its modulation by GLP-1 analogues remain to be fully investigated. We therefore sought to quantify adult human beta-cell proliferation in vitro and whether this is affected by the GLP-1 analogue liraglutide.Human islets from 7 adult cadaveric organ donors were dispersed into single cells. Beta-cells were purified by FACS. Non-sorted cells and the beta-cell enriched ("beta-cells" population were plated on extracellular matrix from rat (804G and human bladder carcinoma cells (HTB9 or bovine corneal endothelial ECM (BCEC. Cells were maintained in culture+/-liraglutide for 4 days in the presence of BrdU.Rare human beta-cell proliferation could be observed either in the purified beta-cell population (0.051±0.020%; 22 beta-cells proliferating out of 84'283 beta-cells counted or in the non-sorted cell population (0.055±0.011%; 104 proliferating beta-cells out of 232'826 beta-cells counted, independently of the matrix or the culture conditions. Liraglutide increased human beta-cell proliferation on BCEC in the non-sorted cell population (0.082±0.034% proliferating beta-cells vs. 0.017±0.008% in control, p<0.05.These results indicate that adult human beta-cell proliferation can occur in vitro but remains an extremely rare event with these donors and particular culture conditions. Liraglutide increases beta-cell proliferation only in the non-sorted cell population and only on BCEC. However, it cannot be excluded that human beta-cells may proliferate to a greater extent in situ in response to natural stimuli.

  18. Hybrid clone cells derived from human breast epithelial cells and human breast cancer cells exhibit properties of cancer stem/initiating cells.

    Science.gov (United States)

    Gauck, Daria; Keil, Silvia; Niggemann, Bernd; Zänker, Kurt S; Dittmar, Thomas

    2017-08-02

    The biological phenomenon of cell fusion has been associated with cancer progression since it was determined that normal cell × tumor cell fusion-derived hybrid cells could exhibit novel properties, such as enhanced metastatogenic capacity or increased drug resistance, and even as a mechanism that could give rise to cancer stem/initiating cells (CS/ICs). CS/ICs have been proposed as cancer cells that exhibit stem cell properties, including the ability to (re)initiate tumor growth. Five M13HS hybrid clone cells, which originated from spontaneous cell fusion events between M13SV1-EGFP-Neo human breast epithelial cells and HS578T-Hyg human breast cancer cells, and their parental cells were analyzed for expression of stemness and EMT-related marker proteins by Western blot analysis and confocal laser scanning microscopy. The frequency of ALDH1-positive cells was determined by flow cytometry using AldeRed fluorescent dye. Concurrently, the cells' colony forming capabilities as well as the cells' abilities to form mammospheres were investigated. The migratory activity of the cells was analyzed using a 3D collagen matrix migration assay. M13HS hybrid clone cells co-expressed SOX9, SLUG, CK8 and CK14, which were differently expressed in parental cells. A variation in the ALDH1-positive putative stem cell population was observed among the five hybrids ranging from 1.44% (M13HS-7) to 13.68% (M13HS-2). In comparison to the parental cells, all five hybrid clone cells possessed increased but also unique colony formation and mammosphere formation capabilities. M13HS-4 hybrid clone cells exhibited the highest colony formation capacity and second highest mammosphere formation capacity of all hybrids, whereby the mean diameter of the mammospheres was comparable to the parental cells. In contrast, the largest mammospheres originated from the M13HS-2 hybrid clone cells, whereas these cells' mammosphere formation capacity was comparable to the parental breast cancer cells. All M13HS

  19. Identification of molecules derived from human fibroblast feeder cells that support the proliferation of human embryonic stem cells

    DEFF Research Database (Denmark)

    Anisimov, Sergey V.; Christophersen, Nicolaj S.; Correia, Ana S.

    2011-01-01

    The majority of human embryonic stem cell lines depend on a feeder cell layer for continuous growth in vitro, so that they can remain in an undifferentiated state. Limited knowledge is available concerning the molecular mechanisms that underlie the capacity of feeder cells to support both...... the proliferation and pluripotency of these cells. Importantly, feeder cells generally lose their capacity to support human embryonic stem cell proliferation in vitro following long-term culture. In this study, we performed large-scale gene expression profiles of human foreskin fibroblasts during early...... foreskin fibroblasts to serve as feeder cells for human embryonic stem cell cultures. Among these, the C-KIT, leptin and pigment epithelium-derived factor (PEDF) genes were the most interesting candidates....

  20. Nucleosome Organization in Human Embryonic Stem Cells.

    Directory of Open Access Journals (Sweden)

    Puya G Yazdi

    Full Text Available The fundamental repeating unit of eukaryotic chromatin is the nucleosome. Besides being involved in packaging DNA, nucleosome organization plays an important role in transcriptional regulation and cellular identity. Currently, there is much debate about the major determinants of the nucleosome architecture of a genome and its significance with little being known about its role in stem cells. To address these questions, we performed ultra-deep sequencing of nucleosomal DNA in two human embryonic stem cell lines and integrated our data with numerous epigenomic maps. Our analyses have revealed that the genome is a determinant of nucleosome organization with transcriptionally inactive regions characterized by a "ground state" of nucleosome profiles driven by underlying DNA sequences. DNA sequence preferences are associated with heterogeneous chromatin organization around transcription start sites. Transcription, histone modifications, and DNA methylation alter this "ground state" by having distinct effects on both nucleosome positioning and occupancy. As the transcriptional rate increases, nucleosomes become better positioned. Exons transcribed and included in the final spliced mRNA have distinct nucleosome profiles in comparison to exons not included at exon-exon junctions. Genes marked by the active modification H3K4m3 are characterized by lower nucleosome occupancy before the transcription start site compared to genes marked by the inactive modification H3K27m3, while bivalent domains, genes associated with both marks, lie exactly in the middle. Combinatorial patterns of epigenetic marks (chromatin states are associated with unique nucleosome profiles. Nucleosome organization varies around transcription factor binding in enhancers versus promoters. DNA methylation is associated with increasing nucleosome occupancy and different types of methylations have distinct location preferences within the nucleosome core particle. Finally, computational

  1. Human interleukin for DA cells or leukemia inhibitory factor is released by Vero cells in human embryo coculture.

    Science.gov (United States)

    Papaxanthos-Roche, A; Taupin, J L; Mayer, G; Daniel, J Y; Moreau, J F

    1994-09-01

    In the light of the newly discovered implications of human interleukin for DA cells and leukemia inhibitory factor in embryology, we searched for the presence of this soluble cytokine in the supernatant of Vero cell coculture systems. Using a bioassay as well as a specific ELISA, we demonstrated that Vero cells are able to release large quantities of human interleukin for DA cells and leukemia inhibitory factor in the embryo-growing medium of such cocultures.

  2. Current applications of human pluripotent stem cells: possibilities and challenges.

    Science.gov (United States)

    Ho, Pai-Jiun; Yen, Men-Luh; Yet, Shaw-Fang; Yen, B Linju

    2012-01-01

    Stem cells are self-renewable cells with the differentiation capacity to develop into somatic cells with biological functions. This ability to sustain a renewable source of multi- and/or pluripotential differentiation has brought new hope to the field of regenerative medicine in terms of cell therapy and tissue engineering. Moreover, stem cells are invaluable tools as in vitro models for studying diverse fields, from basic scientific questions such as developmental processes and lineage commitment, to practical application including drug screening and testing. The stem cells with widest differentiation potential are pluripotent stem cells (PSCs), which are rare cells with the ability to generate somatic cells from all three germ layers. PSCs are considered the most optimal choice for therapeutic potential of stem cells, bringing new impetus to the field of regenerative medicine. In this article, we discuss the therapeutic potential of human PSCs (hPSCs) including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), reviewing the current preclinical and clinical data using these stem cells. We describe the classification of different sources of hPSCs, ongoing research, and currently encountered clinical obstacles of these novel and versatile human stem cells.

  3. Sphere-forming cell subpopulations with cancer stem cell properties in human hepatoma cell lines

    Directory of Open Access Journals (Sweden)

    Chen Lei

    2011-06-01

    Full Text Available Abstract Background Cancer stem cells (CSCs are regarded as the cause of tumor formation and recurrence. The isolation and identification of CSCs could help to develop novel therapeutic strategies specifically targeting CSCs. Methods Human hepatoma cell lines were plated in stem cell conditioned culture system allowed for sphere forming. To evaluate the stemness characteristics of spheres, the self-renewal, proliferation, chemoresistance, tumorigenicity of the PLC/PRF/5 sphere-forming cells, and the expression levels of stem cell related proteins in the PLC/PRF/5 sphere-forming cells were assessed, comparing with the parental cells. The stem cell RT-PCR array was performed to further explore the biological properties of liver CSCs. Results The PLC/PRF/5, MHCC97H and HepG2 cells could form clonal nonadherent 3-D spheres and be serially passaged. The PLC/PRF/5 sphere-forming cells possessed a key criteria that define CSCs: persistent self-renewal, extensive proliferation, drug resistance, overexpression of liver CSCs related proteins (Oct3/4, OV6, EpCAM, CD133 and CD44. Even 500 sphere-forming cells were able to form tumors in NOD/SCID mice, and the tumor initiating capability was not decreased when spheres were passaged. Besides, downstream proteins DTX1 and Ep300 of the CSL (CBF1 in humans, Suppressor of hairless in Drosophila and LAG1 in C. elegans -independent Notch signaling pathway were highly expressed in the spheres, and a gamma-secretase inhibitor MRK003 could significantly inhibit the sphere formation ability. Conclusions Nonadherent tumor spheres from hepatoma cell lines cultured in stem cell conditioned medium possess liver CSC properties, and the CSL-independent Notch signaling pathway may play a role in liver CSCs.

  4. Human dental pulp stem cells: Applications in future regenerative medicine

    Science.gov (United States)

    Potdar, Pravin D; Jethmalani, Yogita D

    2015-01-01

    Stem cells are pluripotent cells, having a property of differentiating into various types of cells of human body. Several studies have developed mesenchymal stem cells (MSCs) from various human tissues, peripheral blood and body fluids. These cells are then characterized by cellular and molecular markers to understand their specific phenotypes. Dental pulp stem cells (DPSCs) are having a MSCs phenotype and they are differentiated into neuron, cardiomyocytes, chondrocytes, osteoblasts, liver cells and β cells of islet of pancreas. Thus, DPSCs have shown great potentiality to use in regenerative medicine for treatment of various human diseases including dental related problems. These cells can also be developed into induced pluripotent stem cells by incorporation of pluripotency markers and use for regenerative therapies of various diseases. The DPSCs are derived from various dental tissues such as human exfoliated deciduous teeth, apical papilla, periodontal ligament and dental follicle tissue. This review will overview the information about isolation, cellular and molecular characterization and differentiation of DPSCs into various types of human cells and thus these cells have important applications in regenerative therapies for various diseases. This review will be most useful for postgraduate dental students as well as scientists working in the field of oral pathology and oral medicine. PMID:26131314

  5. Comprehensive evaluation of leukocyte lineage derived from human hematopoietic cells in humanized mice.

    Science.gov (United States)

    Takahashi, Masayuki; Tsujimura, Noriyuki; Otsuka, Kensuke; Yoshino, Tomoko; Mori, Tetsushi; Matsunaga, Tadashi; Nakasono, Satoshi

    2012-04-01

    Recently, humanized animals whereby a part of the animal is biologically engineered using human genes or cells have been utilized to overcome interspecific differences. Herein, we analyzed the detail of the differentiation states of various human leukocyte subpopulations in humanized mouse and evaluated comprehensively the similarity of the leukocyte lineage between humanized mice and humans. Humanized mice were established by transplanting human CD34(+) cord blood cells into irradiated severely immunodeficient NOD/Shi-scid/IL2Rγ(null) (NOG) mice, and the phenotypes of human cells contained in bone marrow, thymus, spleen and peripheral blood from the mice were analyzed at monthly intervals until 4 months after cell transplantation. The analysis revealed that transplanted human hematopoietic stem cells via the caudal vein homed and engrafted themselves successfully at the mouse bone marrow. Subsequently, the differentiated leukocytes migrated to the various tissues. Almost all of the leukocytes within the thymus were human cells. Furthermore, analysis of the differentiation states of human leukocytes in various tissues and organs indicated that it is highly likely that the human-like leukocyte lineage can be developed in mice. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  6. Wharton's Jelly Derived Mesenchymal Stem Cells: Comparing Human and Horse.

    Science.gov (United States)

    Merlo, Barbara; Teti, Gabriella; Mazzotti, Eleonora; Ingrà, Laura; Salvatore, Viviana; Buzzi, Marina; Cerqueni, Giorgia; Dicarlo, Manuela; Lanci, Aliai; Castagnetti, Carolina; Iacono, Eleonora

    2018-08-01

    Wharton's jelly (WJ) is an important source of mesenchymal stem cells (MSCs) both in human and other animals. The aim of this study was to compare human and equine WJMSCs. Human and equine WJMSCs were isolated and cultured using the same protocols and culture media. Cells were characterized by analysing morphology, growth rate, migration and adhesion capability, immunophenotype, differentiation potential and ultrastructure. Results showed that human and equine WJMSCs have similar ultrastructural details connected with intense synthetic and metabolic activity, but differ in growth, migration, adhesion capability and differentiation potential. In fact, at the scratch assay and transwell migration assay, the migration ability of human WJMSCs was higher (P cells, while the volume of spheroids obtained after 48 h of culture in hanging drop was larger than the volume of equine ones (P cell adhesion ability. This can also revealed in the lower doubling time of equine cells (3.5 ± 2.4 days) as compared to human (6.5 ± 4.3 days) (P cell doubling after 44 days of culture observed for the equine (20.3 ± 1.7) as compared to human cells (8.7 ± 2.4) (P cells showed an higher chondrogenic and osteogenic differentiation ability (P staminal phenotype in human and equine WJMSCs, they showed different properties reflecting the different sources of MSCs.

  7. induced acute cytotoxicity in human cervical epithelial carcinoma cells

    African Journals Online (AJOL)

    Molecular basis of arsenite (As +3 )-induced acute cytotoxicity in human cervical epithelial carcinoma cells. ... Libyan Journal of Medicine ... Methods: After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and ...

  8. Novel human multiple myeloma cell line UHKT-893

    Czech Academy of Sciences Publication Activity Database

    Uherková, L.; Vančurová, I.; Vyhlídalová, I.; Pleschnerová, M.; Špička, I.; Mihalová, R.; Březinová, J.; Hodný, Zdeněk; Čermáková, K.; Polanská, V.; Marinov, I.; Jedelský, P.L.; Kuželová, K.; Stöckbauer, P.

    2013-01-01

    Roč. 37, č. 3 (2013), s. 320-326 ISSN 0145-2126 Institutional support: RVO:68378050 Keywords : human myeloma cell line * human multiple myeloma * plasma cell * IL-6 dependence * immunoglobulin * free light chain Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.692, year: 2013

  9. Factors predicting the duration of adrenal insufficiency in patients successfully treated for Cushing disease and nonmalignant primary adrenal Cushing syndrome.

    Science.gov (United States)

    Prete, Alessandro; Paragliola, Rosa Maria; Bottiglieri, Filomena; Rota, Carlo Antonio; Pontecorvi, Alfredo; Salvatori, Roberto; Corsello, Salvatore Maria

    2017-03-01

    Successful treatment of Cushing syndrome causes transient or permanent adrenal insufficiency deriving from endogenous hypercortisolism-induced hypothalamus-pituitary-adrenal-axis suppression. We analyzed pre-treatment factors potentially affecting the duration of adrenal insufficiency. We conducted a retrospective analysis on patients successfully treated for Cushing disease (15 patients) who underwent transsphenoidal surgery, and nonmalignant primary adrenal Cushing syndrome (31 patients) who underwent unilateral adrenalectomy, divided into patients with overt primary adrenal Cushing syndrome (14 patients) and subclinical primary adrenal Cushing syndrome (17 patients). Epidemiological data, medical history, and hormonal parameters depending on the etiology of hypercortisolism were collected and compared to the duration of adrenal insufficiency. The median duration of follow-up after surgery for Cushing disease and primary adrenal Cushing syndrome was 70 and 48 months, respectively. In the Cushing disease group, the median duration of adrenal insufficiency after transsphenoidal surgery was 15 months: younger age at diagnosis and longer duration of signs and symptoms of hypercortisolism before diagnosis and surgery were associated with longer duration of adrenal insufficiency. The median duration of adrenal insufficiency was 6 months for subclinical primary adrenal Cushing syndrome and 18.5 months for overt primary adrenal Cushing syndrome. The biochemical severity of hypercortisolism, the grade of hypothalamus-pituitary-adrenal-axis suppression, and treatment with ketoconazole before surgery accounted for longer duration of adrenal insufficiency. In patients with Cushing disease, younger age and delayed diagnosis and treatment predict longer need for glucocorticoid replacement therapy after successful transsphenoidal surgery. In patients with primary adrenal Cushing syndrome, the severity of hypercortisolism plays a primary role in influencing the duration of

  10. Adrenal hypoplasia congenita: a rare cause of primary adrenal insufficiency and hypogonadotropic hypogonadism

    Directory of Open Access Journals (Sweden)

    Marta Loureiro

    2015-09-01

    Full Text Available Primary adrenal insufficiency is defined by the impaired synthesis of adrenocortical hormones due to an intrinsic disease of the adrenal cortex. Determining its etiology is crucial to allow adequate long-term management and genetic counseling. We report the case of a male adolescent that presented in the neonatal period with adrenal crisis and received replacement therapy for primary adrenal insufficiency. During follow-up, adrenal hypoplasia congenita (AHC was suspected given his persistently raised adrenocorticotropic hormone levels, with markedly low 17-OH progesterone and androstenedione levels. DNA sequence analysis revealed a mutation in NR0B1 gene (c.1292delG, confirming the diagnosis. Delayed puberty and persistent low levels of gonadotropins led to testosterone replacement therapy. X-linked AHC is a rare cause of primary adrenal insufficiency and hypogonadotropic hypogonadism, related to mutations in NR0B1 gene. Despite its rarity, AHC should be considered in patients who present with primary adrenal failure, low levels of 17-OH progesterone and hypogonadotropic hypogonadism.

  11. What Are Some Types of Adrenal Gland Disorders?

    Science.gov (United States)

    ... until the adrenal glands start functioning normally again. Addison's Disease This rare disorder develops when the adrenal glands ... not make enough cortisol. In most cases of Addison's disease, the body also doesn't make enough of ...

  12. Spontaneous rupture of adrenal metastasis from hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Chae Hun; Kim, Hyun Jin; Park, Soo Youn; Hwang, Seong Su; Choi, Hyun Joo [St. Vincent Hospital, Suwon (Korea, Republic of)

    2007-03-15

    Rupture of adrenal tumor from various primary origins is a rather rare event. We report here on a ruptured adrenal metastasis from hepatocellular carcinoma, and this ruptured metastasis was observed at the time of the initial diagnosis.

  13. REVIEW ARTICLE Adrenal lesions encountered in current medical ...

    African Journals Online (AJOL)

    help to characterise an adrenal mass and guide diagnosis. .... Longitudinal ultrasound image demonstrating a well- defined, solid ... Adrenal metastases in a 56-year-old woman with advanced breast carcinoma. ..... of cancer patients.[3].

  14. Neurologic complications of disorders of the adrenal glands.

    Science.gov (United States)

    Bertorini, Tulio E; Perez, Angel

    2014-01-01

    Disorders of the adrenal glands frequently have secondary neurological manifestations, while some diseases that involve the central nervous system are accompanied by adrenal gland dysfunction. Excessive corticosteroid secretions in primary or secondary Cushing's syndrome causes muscle weakness and behavioral disturbances, such as emotional lability and sometimes depression, while adrenal insufficiency may cause fatigue, weakness, and depression. Adrenoleukodystrophy and adrenoneuromyelopathy are X-linked recessive disorders of the metabolism of very long chain fatty acids that manifest with white matter abnormalities of the brain, myelopathy and/or neuropathy, as well as adrenal insufficiency. Other disorders of the adrenal glands include hyperaldosteroidism, which may cause weakness from hypokalemia. Dysfunction of the adrenal medulla causes excessive or deficient secretion of catecholamines, primarily causing cardiovascular symptoms. This chapter reviews the clinical manifestations and diagnostic aspects and treatment of the various disorders of the adrenal glands. Some of the congenital adrenal diseases are also discussed. © 2014 Elsevier B.V. All rights reserved.

  15. Clinical significance of adrenal computed tomography in Addison's disease

    International Nuclear Information System (INIS)

    Sun, Zhong-Hua; Nomura, Kaoru; Toraya, Shohzoh; Ujihara, Makoto; Horiba, Nobuo; Suda, Toshihiro; Tsushima, Toshio; Demura, Hiroshi; Kono, Atsushi

    1992-01-01

    Adrenal computed tomographic (CT) scanning was conducted in twelve patients with Addison's disease during the clinical course. In tuberculous Addison's disease (n=8), three of four patients examined during the first two years after disease onset had bilaterally enlarged adrenals, while one of four had a unilaterally enlarged one. At least one adrenal gland was enlarged after onset in all six patients examined during the first four years. Thereafter, the adrenal glands was atrophied bilaterally, in contrast to adrenal glands in idiopathic Addison's disease which was atrophied bilaterally from disease onset (n=2). Adrenal calcification was a less sensitive clue in tracing pathogenesis, i.e., adrenal calcification was observed in five of eight patients with tuberculous Addison's disease, but not idiopathic patients. Thus, adrenal CT scanning could show the etiology of Addison's disease (infection or autoimmunity) and the phase of Addison's disease secondary to tuberculosis, which may be clinically important for initiating antituberculous treatment. (author)

  16. Magnetic resonance appearance of adrenal hemorrhage in a neonate

    International Nuclear Information System (INIS)

    Willemse, A.P.P.; Feldberg, M.A.M.; Witkamp, T.D.; Coppes, M.J.; Kramer, P.P.G.

    1989-01-01

    The Magnetic Resonance (MR) appearance of adrenal hemorrhage in a neonate is described and compared with Ultrasound (US). The value of US studies in adrenal neonatal hemorrhage is well known. We present the MR appearance of this common condition. (orig.)

  17. Human induced pluripotent stem cells on autologous feeders.

    Directory of Open Access Journals (Sweden)

    Kazutoshi Takahashi

    Full Text Available BACKGROUND: For therapeutic usage of induced Pluripotent Stem (iPS cells, to accomplish xeno-free culture is critical. Previous reports have shown that human embryonic stem (ES cells can be maintained in feeder-free condition. However, absence of feeder cells can be a hostile environment for pluripotent cells and often results in karyotype abnormalities. Instead of animal feeders, human fibroblasts can be used as feeder cells of human ES cells. However, one still has to be concerned about the existence of unidentified pathogens, such as viruses and prions in these non-autologous feeders. METHODOLOGY/PRINCIPAL FINDINGS: This report demonstrates that human induced Pluripotent Stem (iPS cells can be established and maintained on isogenic parental feeder cells. We tested four independent human skin fibroblasts for the potential to maintain self-renewal of iPS cells. All the fibroblasts tested, as well as their conditioned medium, were capable of maintaining the undifferentiated state and normal karyotypes of iPS cells. Furthermore, human iPS cells can be generated on isogenic parental fibroblasts as feeders. These iPS cells carried on proliferation over 19 passages with undifferentiated morphologies. They expressed undifferentiated pluripotent cell markers, and could differentiate into all three germ layers via embryoid body and teratoma formation. CONCLUSIONS/SIGNIFICANCE: These results suggest that autologous fibroblasts can be not only a source for iPS cells but also be feeder layers. Our results provide a possibility to solve the dilemma by using isogenic fibroblasts as feeder layers of iPS cells. This is an important step toward the establishment of clinical grade iPS cells.

  18. Principles and management of adrenal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Javadpour, N.

    1987-01-01

    This book provides information on adrenal diseases of latest developments and guides the clinicians in the care of their patients. The book is divided into two parts. The first section gives an overview of the embryology, anatomy, physiology, markers, pathology, imaging and the current progress in the field. The second edition covers specific diseases of the adrenal cortex and medulla. The increasingly significant roles played by steroids, catecholamines, blockers, computed tomography and magnetic resonance are elucidated and discussed. The contents include: Overview of progress; current problems, and perspectives - embryology anatomy, physiology, and biologic markers; pathology; advances in diagnosis; imaging techniques; adrenal disorders in childhood; primary aldosteronism; Cushing's syndrome; carcinoma; pheochromocytoma; neuroblastoma; metastatic disease; surgical management; and subject index.

  19. Imaging of the adrenal gland lesions

    Directory of Open Access Journals (Sweden)

    Keith Herr

    2014-08-01

    Full Text Available With the steep increase in the use of cross-sectional imaging in recent years, the incidentally detected adrenal lesion, or "incidentaloma", has become an increasingly common diagnostic problem for the radiologist, and a need for an approach to classifying these lesions as benign, malignant or indeterminate with imaging has spurred an explosion of research. While most incidentalomas represent benign disease, typically an adenoma, the possibility of malignant involvement of the adrenal gland necessitates a reliance on imaging to inform management decisions. In this article, we review the literature on adrenal gland imaging, with particular emphasis on computed tomography, magnetic resonance imaging, and photon-emission tomography, and discuss how these findings relate to clinical practice. Emerging technologies, such as contrast-enhanced ultrasonography, dual-energy computed tomography, and magnetic resonance spectroscopic imaging will also be briefly addressed.

  20. Computed tomography of the adrenal glands

    International Nuclear Information System (INIS)

    Buck, J.; Reiser, U.; Heuck, F.

    1982-01-01

    Whole body CT opens a third dimension - in addition with the advantage of being a non-invasive method with relatively negligible risk. Both, the normal CT findings of the adrenal gland and the normal variants in shape and position are described. With help of morphometry and image processing measurements of the size of the adrenal gland of 20 healthy patients were made and are listed; not only the respective normal variants but also hypo-hyperplasia are pointed out. Some examples are suitable for the illustration of pathologic conditions, such as inflammation and benign and malignant primary and secondary neoplasis. Finally, the value of adrenal gland CT is discussed with reference to the other radiologic methods. (orig.)

  1. Bilateral adrenal hemorrhage in polycythemia vera

    Directory of Open Access Journals (Sweden)

    Shruti Bhandari

    2016-09-01

    Full Text Available Bilateral adrenal hemorrhage (BAH is a rare complication typically seen in critically ill patients, which can lead to acute adrenal insufficiency and death unless it is recognized promptly and treated appropriately. We describe the case of a 64-year-old man with polycythemia vera found to be unresponsive with fever, hypotension, tachycardia, and hypoglycemia. Electrocardiogram showed ST-elevation with elevated troponin, hemoglobin, prothrombin time, and partial thromboplastin time. He required aggressive ventilator and vasopressor support. Despite primary coronary intervention, he remained hypotensive. Random cortisol level was low. He received stress dose hydrocortisone with immediate hemodynamic stability. BAH was highly suspected and was confirmed by non-contrast abdominal computed tomography. Prompt recognition and timely initiated treatment remain crucial to impact the mortality associated with acute adrenal insufficiency.

  2. Imaging of the adrenal gland lesions

    Energy Technology Data Exchange (ETDEWEB)

    Herr, Keith [Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA (United States); Muglia, Valdair F. [Universidade de Sao Paulo (FMRP/USP), Ribeirao Preto, SP (Brazil). Faculdade de Medicina; Koff, Walter Jose [Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil). Faculdade de Medicina. Dept. de Cirurgia; Westphalen, Antonio Carlos, E-mail: antonio.westphalen@ucsf.edu [Departments of Radiology and Biomedical Imaging and Urology, School of Medicine, University of California, San Francisco, CA (United States)

    2014-07-15

    With the steep increase in the use of cross-sectional imaging in recent years, the incidentally detected adrenal lesion, or 'incidentaloma', has become an increasingly common diagnostic problem for the radiologist, and a need for an approach to classifying these lesions as benign, malignant or indeterminate with imaging has spurred an explosion of research. While most incidentalomas represent benign disease, typically an adenoma, the possibility of m alignant involvement of the adrenal gland necessitates a reliance on imaging to inform management decisions. In this article, we review the literature on adrenal gland imaging, with particular emphasis on computed tomography, magnetic resonance imaging, and photon-emission tomography, and discuss how these findings relate to clinical practice. Emerging technologies, such as contrast-enhanced ultrasonography, dual-energy computed tomography, and magnetic resonance spectroscopic imaging will also be briefly addressed. (author)

  3. Principles and management of adrenal cancer

    International Nuclear Information System (INIS)

    Javadpour, N.

    1987-01-01

    This book provides information on adrenal diseases of latest developments and guides the clinicians in the care of their patients. The book is divided into two parts. The first section gives an overview of the embryology, anatomy, physiology, markers, pathology, imaging and the current progress in the field. The second edition covers specific diseases of the adrenal cortex and medulla. The increasingly significant roles played by steroids, catecholamines, blockers, computed tomography and magnetic resonance are elucidated and discussed. The contents include: Overview of progress; current problems, and perspectives - embryology anatomy, physiology, and biologic markers; pathology; advances in diagnosis; imaging techniques; adrenal disorders in childhood; primary aldosteronism; Cushing's syndrome; carcinoma; pheochromocytoma; neuroblastoma; metastatic disease; surgical management; and subject index

  4. The association between human papillomavirus and oropharyngeal squamous cell Carcinoma

    DEFF Research Database (Denmark)

    Walvik, Lena; Svensson, Amanda Björk; Friborg, Jeppe

    2016-01-01

    carcinoma using the Bradford Hill criteria. The strength of the association is supported by, detection of human papillomavirus infection and antibodies prior to oropharyngeal squamous cell carcinoma. This is furthermore reinforced by the absence of human papillomavirus DNA in healthy tonsils...... incidence in human papillomavirus positive oropharyngeal squamous cell carcinoma is associated with sexual behaviour. These associations have been repeatedly observed and are in accordance with our current knowledge. The time relation between cause and effect remains the main challenge, due to the lack...... of well-defined premalignant lesions. However, a causal relationship between human papillomavirus infection and oropharyngeal squamous cell carcinoma seems evident....

  5. Freeze-Dried Human Red Blood Cells

    Science.gov (United States)

    1992-04-15

    period in the liquid state. 2. The levels of glycolytic intermediates (ATP, adenosine 5’triphosphate; 2,3-DPG 2, 3- diphosphoglycerate ) in rehydrated...8217 diphosphate, ADP; adenosine 5 monophosphate, AMP; 2,3- diphosphoglycerate . 2.3-DPG and lactate: (2) measurement of cell indices (mean cell volume (MCV), mean...monophosphate: 2,3-DPG. 2.3- diphosphoglycerate : MCV. Mean Cell Volume: MCH, Mean Cell Hemoglobin: MCHC, Mean Cell Hemoglobin Concentrations. ** Lactate levels

  6. Sleep restriction alters the hypothalamic-pituitary-adrenal response to stress

    NARCIS (Netherlands)

    Meerlo, P; Koehl, M; van der Borght, K; Turek, FW

    2002-01-01

    Chronic sleep restriction is an increasing problem in many countries and may have many, as yet unknown, consequences for health and well being. Studies in both humans and rats suggest that sleep deprivation may activate the hypothalamic-pituitary-adrenal (HPA) axis, one of the main neuroendocrine

  7. CD1 and mycobacterial lipids activate human T cells.

    Science.gov (United States)

    Van Rhijn, Ildiko; Moody, D Branch

    2015-03-01

    For decades, proteins were thought to be the sole or at least the dominant source of antigens for T cells. Studies in the 1990s demonstrated that CD1 proteins and mycobacterial lipids form specific targets of human αβ T cells. The molecular basis by which T-cell receptors (TCRs) recognize CD1-lipid complexes is now well understood. Many types of mycobacterial lipids function as antigens in the CD1 system, and new studies done with CD1 tetramers identify T-cell populations in the blood of tuberculosis patients. In human populations, a fundamental difference between the CD1 and major histocompatibility complex systems is that all humans express nearly identical CD1 proteins. Correspondingly, human CD1 responsive T cells show evidence of conserved TCRs. In addition to natural killer T cells and mucosal-associated invariant T (MAIT cells), conserved TCRs define other subsets of human T cells, including germline-encoded mycolyl-reactive (GEM) T cells. The simple immunogenetics of the CD1 system and new investigative tools to measure T-cell responses in humans now creates a situation in which known lipid antigens can be developed as immunodiagnostic and immunotherapeutic reagents for tuberculosis disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Defective repair of UV-damaged DNA in human tumor and SV40-transformed human cells but not in adenovirus-transformed human cells

    International Nuclear Information System (INIS)

    Rainbow, A.J.

    1989-01-01

    The DNA repair capacities of five human tumor cell lines, one SV40-transformed human cell line and one adenovirus-transformed human cell line were compared with that of normal human fibroblasts using a sensitive host cell reactivation (HCR) technique. Unirradiated and UV-irradiated suspensions of adenovirus type 2 (Ad 2) were assayed for their ability to form viral structural antigens (Vag) in the various cell types using immunofluorescent staining. The survival of Vag formation for UV-irradiated Ad 2 was significantly reduced in all the human tumor cell lines and the SV40-transformed human line compared to the normal human fibroblasts, but was apparently normal in the adenovirus-transformed human cells. D 0 values for the UV survival of Ad 2 Vag synthesis in the tumor and virally transformed lines expressed as a percentage of that obtained on normal fibroblast strains were used as a measure of DNA repair capacity. Percent HCR values ranged from 26 to 53% in the tumor cells. These results indicate a deficiency in the repair of UV-induced DNA damage associated with human tumorigenesis and the transformation of human cells by SV40 but not the transformation of human cells by adenovirus. (author)

  9. Generation of hepatocyte- and endocrine pancreatic-like cells from human induced endodermal progenitor cells

    NARCIS (Netherlands)

    Sambathkumar, Rangarajan; Akkerman, Renate; Dastidar, Sumitava; Roelandt, Philip; Kumar, Manoj; Bajaj, Manmohan; Mestre Rosa, Ana Rita; Helsen, Nicky; Vanslembrouck, Veerle; Kalo, Eric; Khurana, Satish; Laureys, Jos; Gysemans, Conny; Faas, Marijke M; de Vos, Paul; Verfaillie, Catherine M

    2018-01-01

    Multipotent Adult Progenitor Cells (MAPCs) are one potential stem cell source to generate functional hepatocytes or β-cells. However, human MAPCs have less plasticity than pluripotent stem cells (PSCs), as their ability to generate endodermal cells is not robust. Here we studied the role of 14

  10. Bilateral adrenal hemorrhage and primary antiphospholipid antibody syndrome

    International Nuclear Information System (INIS)

    Garcia de Iturrospe, C.; Quilez, I.J.; Echevarria, J.J.

    1996-01-01

    Bilateral adrenal hemorrhage is an uncommon entity that is difficult to diagnose given the ambiquity of the clinical signs. Computerized tomography plays a major role in the diagnosis, disclosing enlarged adrenal glands presenting the hyperdense aspect that characterizes this disorders. We present a case of bilateral adrenal hemoorrhage in a patient diagnosed as having primary antiphospholipid antibody syndrome, which is a less common cause of adrenal hemorrhage than those classically reported, such as anticoagulant therapy, sepsis, shock and abdominal injury. (Author) 8 refs

  11. Two cases of neonatal adrenal hemorrhage presenting with persistent jaundice.

    Science.gov (United States)

    Ruffini, E; De Petris, L; Zorzi, G; Paoletti, P; Mambelli, G; Carlucci, A

    2013-01-01

    The adrenal hemorrhage is a relatively rare event in newborns but must be considered in the presence of a persistent unexplained jaundice, especially in presence of predisposing factors. Serial ultrasonography is the modality of choice for initial diagnosis and follow-up of neonatal adrenal hemorrhage. We report two cases of neonatal adrenal hemorrhage presenting with persistent jaundice. The causes of the neonatal adrenal hemorrhages were a difficult vaginal delivery in macrosomic infant and a neonatal infection.

  12. Adult adrenal haemorrhage: an unrecognised complication of renal vein thrombosis

    Energy Technology Data Exchange (ETDEWEB)

    Loke, T.K.L. E-mail: lokekl@ha.org.hk

    2001-07-01

    There are many predisposing factors for neonatal adrenal haemorrhage but the causative factors are different in adults. Several cases of neonatal adrenal haemorrhage have been reported in association with renal vein thrombosis. This complication has not been documented in the adults. The presence of an adrenal mass in the setting of renal vein thrombosis should raise the possibility of adrenal haemorrhage even though this is extremely uncommon in adults.

  13. Proteomic analysis of human blastocoel fluid and blastocyst cells

    DEFF Research Database (Denmark)

    Jensen, Pernille; Beck, Hans Christian; Petersen, Jørgen

    2013-01-01

    Human embryonic stem cells (hESCs) are derived from the inner cell mass (ICM) of the blastocyst and can differentiate into any cell type in the human body. These cells hold a great potential for regenerative medicine, but to obtain enough cells needed for medical treatment, culture is required......, the blastocoel fluid, which is in contact with all the cells in the blastocyst, including hESCs. Fifty-three surplus human blastocysts were donated after informed consent, and blastocoel fluid was isolated by micromanipulation. Using highly sensitive nano-high-pressure liquid chromatography-tandem mass...... from the ICM of the human blastocyst are exposed to via the blastocoel fluid. These results can be an inspiration for the development of improved culture conditions for hESCs....

  14. Automatic computer aided analysis algorithms and system for adrenal tumors on CT images.

    Science.gov (United States)

    Chai, Hanchao; Guo, Yi; Wang, Yuanyuan; Zhou, Guohui

    2017-12-04

    The adrenal tumor will disturb the secreting function of adrenocortical cells, leading to many diseases. Different kinds of adrenal tumors require different therapeutic schedules. In the practical diagnosis, it highly relies on the doctor's experience to judge the tumor type by reading the hundreds of CT images. This paper proposed an automatic computer aided analysis method for adrenal tumors detection and classification. It consisted of the automatic segmentation algorithms, the feature extraction and the classification algorithms. These algorithms were then integrated into a system and conducted on the graphic interface by using MATLAB Graphic user interface (GUI). The accuracy of the automatic computer aided segmentation and classification reached 90% on 436 CT images. The experiments proved the stability and reliability of this automatic computer aided analytic system.

  15. Abnormal number cell division of human thyroid anaplastic carcinoma cell line, SW 1736

    Directory of Open Access Journals (Sweden)

    Keiichi Ikeda

    2015-12-01

    Full Text Available Cell division, during which a mother cell usually divides into two daughter cells during one cell cycle, is the most important physiological event of cell biology. We observed one-to-four cell division during imaging of live SW1736 human thyroid anaplastic carcinoma cells transfected with a plasmid expressing the hybrid protein of green fluorescent protein and histone 2B (plasmid eGFP-H2B. Analysis of the images revealed a mother cell divided into four daughter cells. And one of the abnormally divided daughter cells subsequently formed a dinucleate cell.

  16. Adrenal Hyperandrogenism and Polycystic Ovary Syndrome.

    Science.gov (United States)

    Luque-Ramírez, Manuel; Escobar-Morreale, Héctor F

    2016-01-01

    The prevalence of adrenal hyperandrogenism (AH), as defined by increased circulating dehydroepiandrosterone-sulfate (DHEAS) levels, ranges from 15 to 45% in women with polycystic ovary syndrome (PCOS). The aim of this review is to update the pathogenesis and consequences of AH in PCOS, from molecular genetics to the clinical setting. Mounting evidence derived from animal models suggests that genetically or enviromentally determined prenatal androgen excess, by influencing the hormonal and metabolic phenotype of susceptible female fetuses later in life, may be the capital event for the development of AH in PCOS. Because human placental aromatase activity is likely to prevent any deleterious effect of maternal hyperandrogenemia on the fetus, inheritance of the maternal steroidogenic defect is the more likely culprit, even though other factors such as changes in placental steroidogenesis itself or its nutritional efflux may also be involved in the building a deregulated enzymatic pathway from utero to adult life. Anyhow, the most important issue is whether or not AH influences the cardiometabolic risk of women with PCOS. On the one hand, AH has shown a controversial relationship with carbohydrate metabolism and adiposity, and is also associated with abnormalities in blood pressure regulation in these patients. On the other hand, DHEAS may exert a beneficial effect on the lipid profile of both lean and obese patients. Lastly, available studies in women with PCOS cast doubt upon a protective role of DHEAS levels on subclinical atherosclerosis, despite opposite data from the general population. AH is frequent in patients with PCOS yet unraveling its consequences for the management of this disorder requires future longitudinal studies.

  17. The use of human cells in biomedical research and testing.

    Science.gov (United States)

    Combes, Robert D

    2004-06-01

    The ability to use human cells in biomedical research and testing has the obvious advantage over the use of laboratory animals that the need for species extrapolation is obviated, due to the presence of more-relevant morphological, physiological and biochemical properties, including receptors. Moreover, human cells exhibit the same advantages as animal cells in culture in that different cell types can be used, from different tissues, with a wide range of techniques, to investigate a wide variety of biological phenomena in tissue culture. Human cells can also be grown as organotypic cultures to facilitate the extrapolation from cells to whole organisms. Human cell lines have been available for many years on an ad hoc basis from individual researchers, and also from recognised sources, such as the European Collection of Animal Cell Cultures (ECACC) and, in the USA, the Human Cell Culture Centre (HCCC). Such cells have usually been derived from tumours and this has restricted the variety of types of cells available. This problem has been addressed by using primary human cells that can be obtained from a variety of sources, such as cadavers, diseased tissue, skin strips, peripheral blood, buccal cavity smears, hair follicles and surgical waste from biopsy material that is unsuitable for transplantation purposes. However, primary human cells need to be obtained, processed, distributed and handled in a safe and ethical manner. They also have to be made available at the correct time to researchers very shortly after they become available. It is only comparatively recently that the safe and controlled acquisition of surgical waste and non-transplantable human tissues has become feasible with the establishment of several human tissue banks. Recently, the formation of a UK and European centralised network for human tissue supply has been initiated. The problems of short longevity and loss of specialisation in culture are being approached by: a) cell immortalisation to

  18. The response of human and rodent cells to hyperthermia

    International Nuclear Information System (INIS)

    Roizin-Towle, L.; Pirro, J.P.

    1991-01-01

    Inherent cellular radiosensitivity in vitro has been shown to be a good predictor of human tumor response in vivo. In contrast, the importance of the intrinsic thermosensitivity of normal and neoplastic human cells as a factor in the responsiveness of human tumors to adjuvant hyperthermia has never been analyzed systematically. A comparison of thermal sensitivity and thermo-radiosensitization in four rodent and eight human-derived cell lines was made in vitro. Arrhenius plots indicated that the rodent cells were more sensitive to heat killing than the human, and the break-point was 0.5 degrees C higher for the human than rodent cells. The relationship between thermal sensitivity and the interaction of heat with X rays at low doses was documented by thermal enhancement ratios (TER's). Cells received either a 1 hr exposure to 43 degrees C or a 20 minute treatment at 45 degrees C before exposure to 300 kVp X rays. Thermal enhancement ratios ranged from 1.0 to 2.7 for human cells heated at 43 degrees C and from 2.1 to 5.3 for heat exposures at 45 degrees C. Thermal enhancement ratios for rodent cells were generally 2 to 3 times higher than for human cells, because of the fact that the greater thermosensitivity of rodent cells results in a greater enhancement of radiation damage. Intrinsic thermosensitivity of human cells has relevance to the concept of thermal dose; intrinsic thermo-radiosensitization of a range of different tumor cells is useful in documenting the interactive effects of radiation combined with heat

  19. Ectopic adrenal tissue of spermatic cord in a 3- year- old boy, an incidental finding during orchidopexy: A case report

    Directory of Open Access Journals (Sweden)

    Biserka Pigac

    2017-11-01

    Full Text Available Ectopic adrenal tissue is usually found in kidney and retroperitoneum, yet other locations are considered uncommon. Spermatic cord remains one of the sites where this entity is mostly incidentally found during surgical procedure in childhood. Macroscopically, it represents as yellowish, lipomatous nodule. We present a case of ectopic adrenal tissue of spermatic cord in a 3- year- old boy, found during orchidopexy of the right testicle. Histopathological analysis of the spermatic cord nodule revealed adrenal cortical tissue composed of zona fasciculata cells. Although usually being benign and asymptomatic, cases of hyperplasia, adenoma and carcinoma arising from ectopic adrenal tissue have been reported. Therefore, removal of this tissue, when detected, is recommended.

  20. Ewing's Sarcoma of the Adrenal Gland.

    Science.gov (United States)

    Pal, Dilip Kumar; Chandra, Vipin; Ranjan, Kumar Rajiv; Chakrabortty, Debasis; Banerjee, Manju

    2016-01-01

    Ewing's sarcoma (ES) or primitive neuro-ectodermal tumor (PNET) typically occurs in long or flat bones, the chest wall, extra-skeletal soft tissue, and rarely in solid organs. Incidence of adrenal Ewing's sarcoma is very rare. Here we report a case of Ewing's sarcoma of the right adrenal gland in an 8-year-old girl who presented with an abdominal mass. The huge tumor was managed by preoperative neo-adjuvant chemotherapy followed by surgical resection. She died due to metastasis after five months of surgery.

  1. [Association between Williams syndrome and adrenal insufficiency].

    Science.gov (United States)

    Rchachi, Meryem; Larwanou, Maazou Mahamane; El Ouahabi, Hanan; Ajdi, Farida

    2017-01-01

    Williams syndrome is a developmental disorder including dysmorphia, cardiovascular malformations and a specific neuropsychological profile together with other associated disorders. We report the case of a 17-year old girl, born of a non-inbred marriage, with Williams syndrome discovered during an assessment of degree of failure to thrive. Its association with primary adrenal insufficiency makes it unique. Diagnosis is confirmed by cytogenetic and molecular analysis. Its management consists of the implementation of treatment for adrenal insufficiency associated with a clinico-biological monitoring.

  2. Prenatal Diagnosis of Congenital Adrenal Hyperplasia.

    Science.gov (United States)

    Yau, Mabel; Khattab, Ahmed; New, Maria I

    2016-06-01

    Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency is a monogenic disorder of adrenal steroidogenesis. To prevent genital ambiguity, in girls, prenatal dexamethasone treatment is administered early in the first trimester. Prenatal genetic diagnosis of CAH and fetal sex determination identify affected female fetuses at risk for genital virilization. Advancements in prenatal diagnosis are owing to improved understanding of the genetic basis of CAH and improved technology. Cloning of the CYP21A2 gene ushered in molecular genetic analysis as the current standard of care. Noninvasive prenatal diagnosis allows for targeted treatment and avoids unnecessary treatment of males and unaffected females. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Histology and ultrastructure of the adrenal gland of the greater cane ...

    African Journals Online (AJOL)

    The results showed variations in the thickness of the zones of the cortex and medulla. Histological detail did not differ significantly from that of other rodents. Ultrastructural features showed typical adrenal gland zonation with capsule, cortical cells and medulla. In the cortex copious lipid droplets and myelin bodies were ...

  4. Generation of Functional Thymic Epithelium from Human Embryonic Stem Cells that Supports Host T Cell Development

    OpenAIRE

    Parent, Audrey V.; Russ, Holger A.; Khan, Imran S.; LaFlam, Taylor N.; Metzger, Todd C.; Anderson, Mark S.; Hebrok, Matthias

    2013-01-01

    Inducing immune tolerance to prevent rejection is a key step toward successful engraftment of stem-cell-derived tissue in a clinical setting. Using human pluripotent stem cells to generate thymic epithelial cells (TECs) capable of supporting T cell development represents a promising approach to reach this goal; however, progress toward generating functional TECs has been limited. Here, we describe a robust in vitro method to direct differentiation of human embryonic stem cells (hESCs) into th...

  5. Plasma metanephrine for assessing the selectivity of adrenal venous sampling

    NARCIS (Netherlands)

    Dekkers, T.; Deinum, J.; Schultze Kool, L.J.; Blondin, D.; Vonend, O.; Hermus, A.R.M.M.; Peitzsch, M.; Rump, L.C.; Antoch, G.; Sweep, F.C.; Bornstein, S.R.; Lenders, J.W.M.; Willenberg, H.S.; Eisenhofer, G.

    2013-01-01

    Adrenal vein sampling is used to establish the origins of excess production of adrenal hormones in primary aldosteronism. Correct catheter positioning is confirmed using adrenal vein measurements of cortisol, but this parameter is not always reliable. Plasma metanephrine represents an alternative

  6. [Adrenal tumors. Principles of diagnostics and operative treatment].

    Science.gov (United States)

    Gonsior, A; Pfeiffer, H; Führer, D; Liatsikos, E; Schwalenberg, T; Stolzenburg, J-U

    2010-05-01

    Adrenal masses are very heterogeneous and comprise benign or malignant tumors, unilateral or bilateral masses and variable endocrine activity. Because of these attributes adrenal gland masses are a clinical challenge. This article gives a summary of diagnostic steps and indications for adrenal surgery including perioperative management.

  7. Radiological findings of congenital lipoid adrenal hyperplasia: a case report

    International Nuclear Information System (INIS)

    Kim, Mi Jeong; Shin, Joo Yong; Lee, Hee Jung; Lee, Jin Hee; Sohn, Cheol Ho; Lee, Sung Moon; Kim, Hong; Woo, Seong Ku; Suh, Soo Ji

    2001-01-01

    Congenital lipoid adrenal hyperplasia (CLAH) is a rare autosomal recessive disorder characterized by the marked accumulation of lipids and cholesterol in the adrenal cortex, and the failure of adrenal steroids to synthesise. We report the ultrasound (US), computed tomographic (CT), and magnetic resonance (MR) imaging findings in a four-day-old female neonate with CLAH

  8. Stepwise development of MAIT cells in mouse and human.

    Directory of Open Access Journals (Sweden)

    Emmanuel Martin

    2009-03-01

    Full Text Available Mucosal-associated invariant T (MAIT cells display two evolutionarily conserved features: an invariant T cell receptor (TCRalpha (iTCRalpha chain and restriction by the nonpolymorphic class Ib major histocompatibility complex (MHC molecule, MHC-related molecule 1 (MR1. MR1 expression on thymus epithelial cells is not necessary for MAIT cell development but their accumulation in the gut requires MR1 expressing B cells and commensal flora. MAIT cell development is poorly known, as these cells have not been found in the thymus so far. Herein, complementary human and mouse experiments using an anti-humanValpha7.2 antibody and MAIT cell-specific iTCRalpha and TCRbeta transgenic mice in different genetic backgrounds show that MAIT cell development is a stepwise process, with an intra-thymic selection followed by peripheral expansion. Mouse MAIT cells are selected in an MR1-dependent manner both in fetal thymic organ culture and in double iTCRalpha and TCRbeta transgenic RAG knockout mice. In the latter mice, MAIT cells do not expand in the periphery unless B cells are added back by adoptive transfer, showing that B cells are not required for the initial thymic selection step but for the peripheral accumulation. In humans, contrary to natural killer T (NKT cells, MAIT cells display a naïve phenotype in the thymus as well as in cord blood where they are in low numbers. After birth, MAIT cells acquire a memory phenotype and expand dramatically, up to 1%-4% of blood T cells. Finally, in contrast with NKT cells, human MAIT cell development is independent of the molecular adaptor SAP. Interestingly, mouse MAIT cells display a naïve phenotype and do not express the ZBTB16 transcription factor, which, in contrast, is expressed by NKT cells and the memory human MAIT cells found in the periphery after birth. In conclusion, MAIT cells are selected by MR1 in the thymus on a non-B non-T hematopoietic cell, and acquire a memory phenotype and expand in the

  9. Human induced pluripotent stem cells: A disruptive innovation.

    Science.gov (United States)

    De Vos, J; Bouckenheimer, J; Sansac, C; Lemaître, J-M; Assou, S

    2016-01-01

    This year (2016) will mark the 10th anniversary of the discovery of induced pluripotent stem cells (iPSCs). The finding that the transient expression of four transcription factors can radically remodel the epigenome, transcriptome and metabolome of differentiated cells and reprogram them into pluripotent stem cells has been a major and groundbreaking technological innovation. In this review, we discuss the major applications of this technology that we have grouped in nine categories: a model to study cell fate control; a model to study pluripotency; a model to study human development; a model to study human tissue and organ physiology; a model to study genetic diseases in a dish; a tool for cell rejuvenation; a source of cells for drug screening; a source of cells for regenerative medicine; a tool for the production of human organs in animals. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Chromosome aberration induction in human diploid fibroblast and epithelial cells

    International Nuclear Information System (INIS)

    Scott, D.

    1986-01-01

    The relative sensitivity of cultured human fibroblasts and epithelial cells to radiation-induced chromosomal aberrations was investigated. Lung fibroblast and kidney epithelial cells from the same fetus were compared, as were skin fibroblasts and epithelial keratinocytes from the same foreskin sample. After exposure of proliferating fetal cells to 1.5 Gy X-rays there was a very similar aberration yield in the fibroblasts and epithelial cells. Observations of either little or no difference in chromosomal sensitivity between human fibroblasts and epithelial cells give added confidence that quantitative cytogenetic data obtained from cultured fibroblasts are relevant to the question of sensitivity of epithelial cells which are the predominant cell type in human cancers. (author)

  11. Genome editing: a robust technology for human stem cells.

    Science.gov (United States)

    Chandrasekaran, Arun Pandian; Song, Minjung; Ramakrishna, Suresh

    2017-09-01

    Human pluripotent stem cells comprise induced pluripotent and embryonic stem cells, which have tremendous potential for biological and therapeutic applications. The development of efficient technologies for the targeted genome alteration of stem cells in disease models is a prerequisite for utilizing stem cells to their full potential. Genome editing of stem cells is possible with the help of synthetic nucleases that facilitate site-specific modification of a gene of interest. Recent advances in genome editing techniques have improved the efficiency and speed of the development of stem cells for human disease models. Zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system are powerful tools for editing DNA at specific loci. Here, we discuss recent technological advances in genome editing with site-specific nucleases in human stem cells.

  12. Applied Developmental Biology: Making Human Pancreatic Beta Cells for Diabetics.

    Science.gov (United States)

    Melton, Douglas A

    2016-01-01

    Understanding the genes and signaling pathways that determine the differentiation and fate of a cell is a central goal of developmental biology. Using that information to gain mastery over the fates of cells presents new approaches to cell transplantation and drug discovery for human diseases including diabetes. © 2016 Elsevier Inc. All rights reserved.

  13. Human papilloma virus prevalence in laryngeal squamous cell carcinoma.

    Science.gov (United States)

    Gungor, A; Cincik, H; Baloglu, H; Cekin, E; Dogru, S; Dursun, E

    2007-08-01

    To determine the prevalence and type of human papilloma virus deoxyribonucleic acid (DNA) in cases of laryngeal squamous cell carcinoma. We analysed the prevalence of human papilloma virus infection in archived paraffin block specimens taken from 99 cases of laryngeal squamous cell carcinoma between 1990 and 2005, using polymerase chain reaction techniques. Biopsy specimens from five proven verrucous skin lesions were used as positive controls, and peripheral blood samples from five healthy volunteers were used as negative controls. Four test samples were found to have inadequate deoxyribonucleic acid purity and were therefore excluded from the study. Human papilloma virus deoxyribonucleic acid was detected in seven of 95 cases of laryngeal squamous cell carcinoma (7.36 per cent). Human papilloma virus genotyping revealed double human papilloma virus infection in three cases and single human papilloma virus infection in the remaining four cases. The human papilloma virus genotypes detected were 6, 11 and 16 (the latter detected in only one case). In our series, a very low human papilloma virus prevalence was found among laryngeal squamous cell carcinoma cases. The human papilloma virus genotypes detected were mostly 6 and/or 11, and 16 in only one case. To the best of our knowledge, this is the first report of human papilloma virus prevalence in laryngeal squamous cell carcinoma, based on polymerase chain reaction genotyping in a Turkish population.

  14. Hexavalent chromium induces chromosome instability in human urothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Wise, Sandra S. [Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, Department of Applied Medical Science, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103 (United States); Holmes, Amie L. [Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, Department of Applied Medical Science, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103 (United States); Department of Radiation Oncology, Dana Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215 (United States); Liou, Louis [Department of Pathology, Boston University School of Medicine, 670 Albany St., Boston, MA 02118 (United States); Adam, Rosalyn M. [Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Wise, John Pierce Sr., E-mail: john.wise@louisville.edu [Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, Department of Applied Medical Science, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103 (United States)

    2016-04-01

    Numerous metals are well-known human bladder carcinogens. Despite the significant occupational and public health concern of metals and bladder cancer, the carcinogenic mechanisms remain largely unknown. Chromium, in particular, is a metal of concern as incidences of bladder cancer have been found elevated in chromate workers, and there is an increasing concern for patients with metal hip implants. However, the impact of hexavalent chromium (Cr(VI)) on bladder cells has not been studied. We compared chromate toxicity in two bladder cell lines; primary human urothelial cells and hTERT-immortalized human urothelial cells. Cr(VI) induced a concentration- and time-dependent increase in chromosome damage in both cell lines, with the hTERT-immortalized cells exhibiting more chromosome damage than the primary cells. Chronic exposure to Cr(VI) also induced a concentration-dependent increase in aneuploid metaphases in both cell lines which was not observed after a 24 h exposure. Aneuploidy induction was higher in the hTERT-immortalized cells. When we correct for uptake, Cr(VI) induces a similar amount of chromosome damage and aneuploidy suggesting that the differences in Cr(VI) sensitivity between the two cells lines were due to differences in uptake. The increase in chromosome instability after chronic chromate treatment suggests this may be a mechanism for chromate-induced bladder cancer, specifically, and may be a mechanism for metal-induced bladder cancer, in general. - Highlights: • Hexavalent chromium is genotoxic to human urothelial cells. • Hexavalent chromium induces aneuploidy in human urothelial cells. • hTERT-immortalized human urothelial cells model the effects seen in primary urothelial cells. • Hexavalent chromium has a strong likelihood of being carcinogenic for bladder tissue.

  15. Male germline stem cells in non-human primates

    Directory of Open Access Journals (Sweden)

    S. Sharma

    2017-09-01

    Full Text Available Over the past few decades, several studies have attempted to decipher the biology of mammalian germline stem cells (GSCs. These studies provide evidence that regulatory mechanisms for germ cell specification and migration are evolutionarily conserved across species. The characteristics and functions of primate GSCs are highly distinct from rodent species; therefore the findings from rodent models cannot be extrapolated to primates. Due to limited availability of human embryonic and testicular samples for research purposes, two non-human primate models (marmoset and macaque monkeys are extensively employed to understand human germline development and differentiation. This review provides a broader introduction to the in vivo and in vitro germline stem cell terminology from primordial to differentiating germ cells. Primordial germ cells (PGCs are the most immature germ cells colonizing the gonad prior to sex differentiation into testes or ovaries. PGC specification and migratory patterns among different primate species are compared in the review. It also reports the distinctions and similarities in expression patterns of pluripotency markers (OCT4A, NANOG, SALL4 and LIN28 during embryonic developmental stages, among marmosets, macaques and humans. This review presents a comparative summary with immunohistochemical and molecular evidence of germ cell marker expression patterns during postnatal developmental stages, among humans and non-human primates. Furthermore, it reports findings from the recent literature investigating the plasticity behavior of germ cells and stem cells in other organs of humans and monkeys. The use of non-human primate models would enable bridging the knowledge gap in primate GSC research and understanding the mechanisms involved in germline development. Reported similarities in regulatory mechanisms and germ cell expression profile in primates demonstrate the preclinical significance of monkey models for development of

  16. Physiological Basis for the Etiology, Diagnosis, and Treatment of Adrenal Disorders: Cushing’s Syndrome, Adrenal Insufficiency, and Congenital Adrenal Hyperplasia

    Science.gov (United States)

    Raff, Hershel; Sharma, Susmeeta T.; Nieman, Lynnette K.

    2014-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis is a classic neuroendocrine system. One of the best ways to understand the HPA axis is to appreciate its dynamics in the variety of diseases and syndromes that affect it. Excess glucocorticoid activity can be due to endogenous cortisol overproduction (spontaneous Cushing’s syndrome) or exogenous glucocorticoid therapy (iatrogenic Cushing’s syndrome). Endogenous Cushing’s syndrome can be subdivided into ACTH-dependent and ACTH-independent, the latter of which is usually due to autonomous adrenal overproduction. The former can be due to a pituitary corticotroph tumor (usually benign) or ectopic ACTH production from tumors outside the pituitary; both of these tumor types overexpress the proopiomelanocortin gene. The converse of Cushing’s syndrome is the lack of normal cortisol secretion and is usually due to adrenal destruction (primary adrenal insufficiency) or hypopituitarism (secondary adrenal insufficiency). Secondary adrenal insufficiency can also result from a rapid discontinuation of long-term, pharmacological glucocorticoid therapy because of HPA axis suppression and adrenal atrophy. Finally, mutations in the steroidogenic enzymes of the adrenal cortex can lead to congenital adrenal hyperplasia and an increase in precursor steroids, particularly androgens. When present in utero, this can lead to masculinization of a female fetus. An understanding of the dynamics of the HPA axis is necessary to master the diagnosis and differential diagnosis of pituitary-adrenal diseases. Furthermore, understanding the pathophysiology of the HPA axis gives great insight into its normal control. PMID:24715566

  17. Cytotoxic human CD4(+) T cells

    NARCIS (Netherlands)

    van de Berg, Pablo J.; van Leeuwen, Ester M.; ten Berge, Ineke J.; van Lier, Rene

    2008-01-01

    The induction of adaptive immune responses critically depends on helper signals provided by CD4(+) T cells. These signals not only license antigen presenting cells (APC) to activate naïve CD8(+) T cells leading to the formation of vast numbers of cytotoxic T lymphocytes but also support the

  18. Human Red Cells With Paroxysmal Nocturnal Haemoglobinuria ...

    African Journals Online (AJOL)

    The purified cells were used as hosts for the culture of P.falciparum in vitro. Results show that GPI-linked molecules on the red cell surface are not required for the efficient entry of the parasites, and that the PNH red cells are competent to sustain the growth of P.falciparum. Nigerian Quarterly Journal of Hospital Medicine Vol ...

  19. Human papillomavirus 16 E5 induces bi-nucleated cell formation by cell-cell fusion

    International Nuclear Information System (INIS)

    Hu Lulin; Plafker, Kendra; Vorozhko, Valeriya; Zuna, Rosemary E.; Hanigan, Marie H.; Gorbsky, Gary J.; Plafker, Scott M.; Angeletti, Peter C.; Ceresa, Brian P.

    2009-01-01

    Human papillomaviruses (HPV) 16 is a DNA virus encoding three oncogenes - E5, E6, and E7. The E6 and E7 proteins have well-established roles as inhibitors of tumor suppression, but the contribution of E5 to malignant transformation is controversial. Using spontaneously immortalized human keratinocytes (HaCaT cells), we demonstrate that expression of HPV16 E5 is necessary and sufficient for the formation of bi-nucleated cells, a common characteristic of precancerous cervical lesions. Expression of E5 from non-carcinogenic HPV6b does not produce bi-nucleate cells. Video microscopy and biochemical analyses reveal that bi-nucleates arise through cell-cell fusion. Although most E5-induced bi-nucleates fail to propagate, co-expression of HPV16 E6/E7 enhances the proliferation of these cells. Expression of HPV16 E6/E7 also increases bi-nucleated cell colony formation. These findings identify a new role for HPV16 E5 and support a model in which complementary roles of the HPV16 oncogenes lead to the induction of carcinogenesis

  20. Propagation of human spermatogonial stem cells in vitro.

    Science.gov (United States)

    Sadri-Ardekani, Hooman; Mizrak, Sefika C; van Daalen, Saskia K M; Korver, Cindy M; Roepers-Gajadien, Hermien L; Koruji, Morteza; Hovingh, Suzanne; de Reijke, Theo M; de la Rosette, Jean J M C H; van der Veen, Fulco; de Rooij, Dirk G; Repping, Sjoerd; van Pelt, Ans M M

    2009-11-18

    Young boys treated with high-dose chemotherapy are often confronted with infertility once they reach adulthood. Cryopreserving testicular tissue before chemotherapy and autotransplantation of spermatogonial stem cells at a later stage could theoretically allow for restoration of fertility. To establish in vitro propagation of human spermatogonial stem cells from small testicular biopsies to obtain an adequate number of cells for successful transplantation. Study performed from April 2007 to July 2009 using testis material donated by 6 adult men who underwent orchidectomy as part of prostate cancer treatment. Testicular cells were isolated and cultured in supplemented StemPro medium; germline stem cell clusters that arose were subcultured on human placental laminin-coated dishes in the same medium. Presence of spermatogonia was determined by reverse transcriptase polymerase chain reaction and immunofluorescence for spermatogonial markers. To test for the presence of functional spermatogonial stem cells in culture, xenotransplantation to testes of immunodeficient mice was performed, and migrated human spermatogonial stem cells after transplantation were detected by COT-1 fluorescence in situ hybridization. The number of colonized spermatogonial stem cells transplanted at early and later points during culture were counted to determine propagation. Propagation of spermatogonial stem cells over time. Testicular cells could be cultured and propagated up to 15 weeks. Germline stem cell clusters arose in the testicular cell cultures from all 6 men and could be subcultured and propagated up to 28 weeks. Expression of spermatogonial markers on both the RNA and protein level was maintained throughout the entire culture period. In 4 of 6 men, xenotransplantation to mice demonstrated the presence of functional spermatogonial stem cells, even after prolonged in vitro culture. Spermatogonial stem cell numbers increased 53-fold within 19 days in the testicular cell culture and

  1. Identification of Human Cutaneous Basal Cell Carcinoma Cancer Stem Cells.

    Science.gov (United States)

    Morgan, Huw; Olivero, Carlotta; Patel, Girish K

    2018-04-20

    The cancer stem cell model states that a subset of tumor cells, called "cancer stem cells," can initiate and propagate tumor growth through self-renewal, high proliferative capacity, and their ability to recreate tumor heterogeneity. In basal cell carcinoma (BCC), we have shown that tumor cells that express the cell surface protein CD200 fulfill the cancer stem cell hypothesis. CD200+ CD45- BCC cells represent 0.05-3.96% of all BCC cells and reside in small clusters at the tumor periphery. Using a novel, reproducible in vivo xenograft growth assay, we determined that tumor-initiating cell (TIC) frequencies are approximately 1 per 1.5 million unsorted BCC cells. The CD200+ CD45- BCC subpopulation recreated BCC tumor growth in vivo with typical histological architecture and expression of sonic hedgehog-regulated genes. Reproducible in vivo BCC growth was achieved with as few as 10,000 CD200+ CD45- cells, representing ~1500-fold enrichment. The methods used to identify and purify CD200+ CD45- BCC cells, as well as characterize gene expression, are described herein.

  2. Interactions between human mesenchymal stem cells and natural killer cells.

    Science.gov (United States)

    Sotiropoulou, Panagiota A; Perez, Sonia A; Gritzapis, Angelos D; Baxevanis, Constantin N; Papamichail, Michael

    2006-01-01

    Mesenchymal stem cells (MSCs) are multipotent progenitor cells representing an attractive therapeutic tool for regenerative medicine. They possess unique immunomodulatory properties, being capable of suppressing T-cell responses and modifying dendritic cell differentiation, maturation, and function, whereas they are not inherently immunogenic, failing to induce alloreactivity to T cells and freshly isolated natural killer (NK) cells. To clarify the generation of host immune responses to implanted MSCs in tissue engineering and their potential use as immunosuppressive elements, the effect of MSCs on NK cells was investigated. We demonstrate that at low NK-to-MSC ratios, MSCs alter the phenotype of NK cells and suppress proliferation, cytokine secretion, and cyto-toxicity against HLA-class I- expressing targets. Some of these effects require cell-to-cell contact, whereas others are mediated by soluble factors, including transforming growth factor-beta1 and prostaglandin E2, suggesting the existence of diverse mechanisms for MSC-mediated NK-cell suppression. On the other hand, MSCs are susceptible to lysis by activated NK cells. Overall, these data improve our knowledge of interactions between MSCs and NK cells and consequently of their effect on innate immune responses and their contribution to the regulation of adaptive immunity, graft rejection, and cancer immunotherapy.

  3. Preferential radiosensitization of human prostatic carcinoma cells by mild hyperthermia

    International Nuclear Information System (INIS)

    Ryu, Samuel; Brown, Stephen L.; Kim, Sang-Hie; Khil, Mark S.; Kim, Jae Ho

    1996-01-01

    Purpose: Recent cell culture studies by us and others suggest that some human carcinoma cells are more sensitive to heat than are rodent cells following mild hyperthermia. In studying the cellular mechanism of enhanced thermosensitivity of human tumor cells to hyperthermia, prostatic carcinoma cells of human origin were found to be more sensitive to mild hyperthermia than other human cancer cells. The present study was designed to determine the magnitude of radiosensitization of human prostatic carcinoma cells by mild hyperthermia and to examine whether the thermal radiosensitization is related to the intrinsic thermosensitivity of cancer cells. Methods and Materials: Two human prostatic carcinoma cell lines (DU-145 and PC-3) and other carcinoma cells of human origin, in particular, colon (HT-29), breast (MCF-7), lung (A-549), and brain (U-251) were exposed to temperatures of 40-41 deg. C. Single acute dose rate radiation and fractionated radiation were combined with mild hyperthermia to determine thermal radiosensitization. The end point of the study was the colony-forming ability of single-plated cells. Results: DU-145 and PC-3 cells were found to be exceedingly thermosensitive to 41 deg. C for 24 h, relative to other cancer cell lines. Ninety percent of the prostatic cancer cells were killed by a 24 h heat exposure. Prostatic carcinoma cells exposed to a short duration of heating at 41 deg. C for 2 h resulted in a substantial enhancement of radiation-induced cytotoxicity. The thermal enhancement ratios (TERs) of single acute dose radiation following heat treatment 41 deg. C for 2 h were 2.0 in DU-145 cells and 1.4 in PC-3 cells. The TERs of fractionated irradiation combined with continuous heating at 40 deg. C were similarly in the range of 2.1 to 1.4 in prostate carcinoma cells. No significant radiosensitization was observed in MCF-7 and HT-29 cells under the same conditions. Conclusion: The present data suggest that a significant radiosensitization of

  4. Cloning the interleukin 1 receptor from human T cells

    International Nuclear Information System (INIS)

    Sims, J.E.; Acres, R.B.; Grubin, C.E.; McMahan, C.J.; Wignall, J.M.; March, C.J.; Dower, S.K.

    1989-01-01

    cDNA clones of the interleukin 1 (IL-1) receptor expressed in a human T-cell clone have been isolated by using a murine IL-1 receptor cDNA as a probe. The human and mouse receptors show a high degree of sequence conservation. Both are integral membrane proteins possessing a single membrane-spanning segment. Similar to the mouse receptor, the human IL-1 receptor contains a large cytoplasmic region and an extracellular, IL-1 binding portion composed of three immunoglobulin-like domains. When transfected into COS cells, the human IL-1 receptor cDNA clone leads to expression of two different affinity classes of receptors, with K a values indistinguishable from those determined for IL-1 receptors in the original T-cell clone. An IL-1 receptor expressed in human dermal fibroblasts has also been cloned and sequenced and found to be identical to the IL-1 receptor expressed in T cells

  5. Ultrasound follow up of testicular adrenal rest tumors with congenital adrenal hyperplasia: Report of three cases

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jeong Yeon; Kim, Dong Won; Yoon, Seong Kuk; Nam, Kyung Jin [Dept. of Radiology, Dong-A University Hospital, Busan (Korea, Republic of)

    2014-12-15

    While testicular adrenal rest tumor is generally a rare intratesticular tumor, it is frequent in patients with congenital adrenal hyperplasia. The tumors are diagnosed and followed up by ultrasound examination because these tumors are non-palpable and symptomless in most cases and always benign. Ultrasound imaging features change depending on how congenital adrenal hyperplasia is controlled. We herein report three cases of testicular adrenal rest tumors with different usual and unusual imaging findings and follow-up imaging. Patient 1 was a 14-year-old boy who presented with poor compliance to medication. Patient 2 and 3 were a 10-year-old and 13-year-old boy who presented with precocious puberty and short stature, respectively. Ultrasound examinations demonstrated oval hypoechoic masses and irregular speculated hyperechoic masses in the testes and different serial imaging findings.

  6. Ultrasound follow up of testicular adrenal rest tumors with congenital adrenal hyperplasia: Report of three cases

    International Nuclear Information System (INIS)

    Cho, Jeong Yeon; Kim, Dong Won; Yoon, Seong Kuk; Nam, Kyung Jin

    2014-01-01

    While testicular adrenal rest tumor is generally a rare intratesticular tumor, it is frequent in patients with congenital adrenal hyperplasia. The tumors are diagnosed and followed up by ultrasound examination because these tumors are non-palpable and symptomless in most cases and always benign. Ultrasound imaging features change depending on how congenital adrenal hyperplasia is controlled. We herein report three cases of testicular adrenal rest tumors with different usual and unusual imaging findings and follow-up imaging. Patient 1 was a 14-year-old boy who presented with poor compliance to medication. Patient 2 and 3 were a 10-year-old and 13-year-old boy who presented with precocious puberty and short stature, respectively. Ultrasound examinations demonstrated oval hypoechoic masses and irregular speculated hyperechoic masses in the testes and different serial imaging findings

  7. Radiation response characteristics of human cell in vitro

    International Nuclear Information System (INIS)

    Hall, E.J.

    1987-01-01

    Improvements in tissue culture techniques and growth media have made it possible to culture a range of cells of human origin, both normal and malignant. The most recent addition to the list are endothelial cells. Interesting results have been obtained, some of which may have implications in Radiation Therapy. (i) Repair of Potentially Lethal Damage (PLDR) has been observed in all cell lines investigated; cells of normal origin repair PLD at least as well as malignant cells, which makes clinical trials of PLDR inhibitors of doubtful usefulness. (ii) PLD in fibroblasts of human origin appears to have a component that is repaired rapidly, in a matter of minutes, as well as a slower component that takes hours to repair. (iii) Sublethal damage repair, manifest by a dose-rate effect, has also been observed in all human cell lines tested. Cells of normal tissue origin, including fibroblasts and endothelial cells, exhibit a dose-rate effect that is intermediate between that for cells from traditionally resistant tumors (melanoma and osteosarcoma) and cells from more sensitive tumors (neuroblastoma and breast). (iv) Fibroblasts from patients with Ataxia Telangectasia (AT) are much more sensitive to x-rays, with a D/sub o/ about half that for normal human fibroblasts. Nevertheless repair of both PLD and SLD can be demonstrated in these cells

  8. Derivation of novel human ground state naive pluripotent stem cells.

    Science.gov (United States)

    Gafni, Ohad; Weinberger, Leehee; Mansour, Abed AlFatah; Manor, Yair S; Chomsky, Elad; Ben-Yosef, Dalit; Kalma, Yael; Viukov, Sergey; Maza, Itay; Zviran, Asaf; Rais, Yoach; Shipony, Zohar; Mukamel, Zohar; Krupalnik, Vladislav; Zerbib, Mirie; Geula, Shay; Caspi, Inbal; Schneir, Dan; Shwartz, Tamar; Gilad, Shlomit; Amann-Zalcenstein, Daniela; Benjamin, Sima; Amit, Ido; Tanay, Amos; Massarwa, Rada; Novershtern, Noa; Hanna, Jacob H

    2013-12-12

    Mouse embryonic stem (ES) cells are isolated from the inner cell mass of blastocysts, and can be preserved in vitro in a naive inner-cell-mass-like configuration by providing exogenous stimulation with leukaemia inhibitory factor (LIF) and small molecule inhibition of ERK1/ERK2 and GSK3β signalling (termed 2i/LIF conditions). Hallmarks of naive pluripotency include driving Oct4 (also known as Pou5f1) transcription by its distal enhancer, retaining a pre-inactivation X chromosome state, and global reduction in DNA methylation and in H3K27me3 repressive chromatin mark deposition on developmental regulatory gene promoters. Upon withdrawal of 2i/LIF, naive mouse ES cells can drift towards a primed pluripotent state resembling that of the post-implantation epiblast. Although human ES cells share several molecular features with naive mouse ES cells, they also share a variety of epigenetic properties with primed murine epiblast stem cells (EpiSCs). These include predominant use of the proximal enhancer element to maintain OCT4 expression, pronounced tendency for X chromosome inactivation in most female human ES cells, increase in DNA methylation and prominent deposition of H3K27me3 and bivalent domain acquisition on lineage regulatory genes. The feasibility of establishing human ground state naive pluripotency in vitro with equivalent molecular and functional features to those characterized in mouse ES cells remains to be defined. Here we establish defined conditions that facilitate the derivation of genetically unmodified human naive pluripotent stem cells from already established primed human ES cells, from somatic cells through induced pluripotent stem (iPS) cell reprogramming or directly from blastocysts. The novel naive pluripotent cells validated herein retain molecular characteristics and functional properties that are highly similar to mouse naive ES cells, and distinct from conventional primed human pluripotent cells. This includes competence in the generation

  9. Concise Review: Kidney Generation with Human Pluripotent Stem Cells.

    Science.gov (United States)

    Morizane, Ryuji; Miyoshi, Tomoya; Bonventre, Joseph V

    2017-11-01

    Chronic kidney disease (CKD) is a worldwide health care problem, resulting in increased cardiovascular mortality and often leading to end-stage kidney disease, where patients require kidney replacement therapies such as hemodialysis or kidney transplantation. Loss of functional nephrons contributes to the progression of CKD, which can be attenuated but not reversed due to inability to generate new nephrons in human adult kidneys. Human pluripotent stem cells (hPSCs), by virtue of their unlimited self-renewal and ability to differentiate into cells of all three embryonic germ layers, are attractive sources for kidney regenerative therapies. Recent advances in stem cell biology have identified key signals necessary to maintain stemness of human nephron progenitor cells (NPCs) in vitro, and led to establishment of protocols to generate NPCs and nephron epithelial cells from human fetal kidneys and hPSCs. Effective production of large amounts of human NPCs and kidney organoids will facilitate elucidation of developmental and pathobiological pathways, kidney disease modeling and drug screening as well as kidney regenerative therapies. We summarize the recent studies to induce NPCs and kidney cells from hPSCs, studies of NPC expansion from mouse and human embryonic kidneys, and discuss possible approaches in vivo to regenerate kidneys with cell therapies and the development of bioengineered kidneys. Stem Cells 2017;35:2209-2217. © 2017 AlphaMed Press.

  10. Chemical Conversion of Human Fibroblasts into Functional Schwann Cells

    Directory of Open Access Journals (Sweden)

    Eva C. Thoma

    2014-10-01

    Full Text Available Direct transdifferentiation of somatic cells is a promising approach to obtain patient-specific cells for numerous applications. However, conversion across germ-layer borders often requires ectopic gene expression with unpredictable side effects. Here, we present a gene-free approach that allows efficient conversion of human fibroblasts via a transient progenitor stage into Schwann cells, the major glial cell type of peripheral nerves. Using a multikinase inhibitor, we transdifferentiated fibroblasts into transient neural precursors that were subsequently further differentiated into Schwann cells. The resulting induced Schwann cells (iSCs expressed numerous Schwann cell-specific proteins and displayed neurosupportive and myelination capacity in vitro. Thus, we established a strategy to obtain mature Schwann cells from human postnatal fibroblasts under chemically defined conditions without the introduction of ectopic genes.

  11. Diagnosis of adrenal adenoma and hyperplasia by CT and adrenal scintigraphy

    International Nuclear Information System (INIS)

    Miura, Kentaro; Itami, Jun; Nawano, Shigeru; Okada, Junichi; Ogino, Takashi; Uno, Koichi; Arimizu, Noboru

    1985-01-01

    The evaluation of X-CT and adrenal scintigraphy in diagnosis of Cushing syndrome and primary aldosteronism was studied in 18 patients. In Cushing syndrome, CT appearance of adenoma is commonly larger than that of primary aldosteronism and cleary deliniated by surrounding fat. So, in Cushing syndrome, diagnosis of adenoma on CT is much easier than that of primary aldosteronism, and absence of adenoma on CT suggests adrenal hyperplasia. In primary aldosteronism both of CT and scintigraphy must be performed. (author)

  12. Rho GTPase expression in human myeloid cells.

    Directory of Open Access Journals (Sweden)

    Suzanne F G van Helden

    Full Text Available Myeloid cells are critical for innate immunity and the initiation of adaptive immunity. Strict regulation of the adhesive and migratory behavior is essential for proper functioning of these cells. Rho GTPases are important regulators of adhesion and migration; however, it is unknown which Rho GTPases are expressed in different myeloid cells. Here, we use a qPCR-based approach to investigate Rho GTPase expression in myeloid cells.We found that the mRNAs encoding Cdc42, RhoQ, Rac1, Rac2, RhoA and RhoC are the most abundant. In addition, RhoG, RhoB, RhoF and RhoV are expressed at low levels or only in specific cell types. More differentiated cells along the monocyte-lineage display lower levels of Cdc42 and RhoV, while RhoC mRNA is more abundant. In addition, the Rho GTPase expression profile changes during dendritic cell maturation with Rac1 being upregulated and Rac2 downregulated. Finally, GM-CSF stimulation, during macrophage and osteoclast differentiation, leads to high expression of Rac2, while M-CSF induces high levels of RhoA, showing that these cytokines induce a distinct pattern. Our data uncover cell type specific modulation of the Rho GTPase expression profile in hematopoietic stem cells and in more differentiated cells of the myeloid lineage.

  13. Implications of infectious diseases and the adrenal hypothesis for the etiology of childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    F. Azevedo-Silva

    2010-03-01

    Full Text Available Acute leukemia is the most frequent cancer in children. Recently, a new hypothesis was proposed for the pathogenesis of childhood acute lymphoblastic leukemia (ALL. The so-called "adrenal hypothesis" emphasized the role of endogenous cortisol in the etiology of B-cell precursor ALL. The incidence peak of ALL in children between 3 to 5 years of age has been well documented and is consistent with this view. The adrenal hypothesis proposes that the risk of childhood B-cell precursor ALL is reduced when early childhood infections induce qualitative and quantitative changes in the hypothalamus-pituitary-adrenal axis. It suggests that the increased plasma cortisol levels would be sufficient to eliminate all clonal leukemic cells originating during fetal life. Because Brazil is a continental and tropical country, the exposure to infections is diversified with endemic viral and regionally non-viral infections, with some characteristics that support the recent adrenal hypothesis. Here we discuss this new hypothesis in terms of data from epidemiological studies and the possible implications of the diversity of infections occurring in Brazilian children.

  14. Immune surveillance properties of human NK cell-derived exosomes.

    Science.gov (United States)

    Lugini, Luana; Cecchetti, Serena; Huber, Veronica; Luciani, Francesca; Macchia, Gianfranco; Spadaro, Francesca; Paris, Luisa; Abalsamo, Laura; Colone, Marisa; Molinari, Agnese; Podo, Franca; Rivoltini, Licia; Ramoni, Carlo; Fais, Stefano

    2012-09-15

    Exosomes are nanovesicles released by normal and tumor cells, which are detectable in cell culture supernatant and human biological fluids, such as plasma. Functions of exosomes released by "normal" cells are not well understood. In fact, several studies have been carried out on exosomes derived from hematopoietic cells, but very little is known about NK cell exosomes, despite the importance of these cells in innate and adaptive immunity. In this paper, we report that resting and activated NK cells, freshly isolated from blood of healthy donors, release exosomes expressing typical protein markers of NK cells and containing killer proteins (i.e., Fas ligand and perforin molecules). These nanovesicles display cytotoxic activity against several tumor cell lines and activated, but not resting, immune cells. We also show that NK-derived exosomes undergo uptake by tumor target cells but not by resting PBMC. Exosomes purified from plasma of healthy donors express NK cell markers, including CD56+ and perforin, and exert cytotoxic activity against different human tumor target cells and activated immune cells as well. The results of this study propose an important role of NK cell-derived exosomes in immune surveillance and homeostasis. Moreover, this study supports the use of exosomes as an almost perfect example of biomimetic nanovesicles possibly useful in future therapeutic approaches against various diseases, including tumors.

  15. A review of human cell radiosensitivity in vitro

    International Nuclear Information System (INIS)

    Deschavanne, Patrick J.; Fertil, Bernard

    1996-01-01

    The survival curves of 694 human cell lines irradiated in exponentially growing phase in vitro were collected from the literature. Among them, 271 were derived from tumors, 423 were nontransformed fibroblasts and other normal cell strains from healthy people or people with some genetic disorders. Seventy-six different cell types are identified, and a specific radiosensitivity could be associated with each, using D-bar and surviving fraction at 2 Gy. Technical factors such as culture medium, feeder cells, and scoring method were found to affect intrinsic radiosensitivity. In particular, the cell type is not a discriminating factor when cells are studied in agar. Results obtained with cells irradiated in agar must be used cautiously, depending on how the cells were prepared for the experiments. The use of feeder cells narrows the range of radiosensitivity of human cells. For cells irradiated as monolayer, it was possible to build a scale of radiosensitivity according to cell type, ranging, in terms of D-bar from 0.6 Gy for the most sensitive cell lines to more than 4 Gy for the most resistant. Considering that, in most cases, we could estimate the variation of radiosensitivity within each cell type, our classification among cell types can be used by researchers to place their results in the context of the literature

  16. Adrenal Steroids: Biphasic Effects on Neurons

    NARCIS (Netherlands)

    Joels, M.; Karst, H.; Squire, L.R.

    2009-01-01

    Corticosteroid hormones are released from the adrenal gland after stress. They enter the brain and bind to high-affinity mineralocorticoid and lower affinity glucocorticoid receptors. Through these nuclear receptors, corticosteroids exert long-lasting effects on essential properties of neurons, such

  17. Total Body Opacification 'Technique Neonatal Adrenal Haemorrhage

    African Journals Online (AJOL)

    1971-12-11

    Dec 11, 1971 ... A case is reported illustrating the possible usefulness of total body opacification in the diagnosis of neonatal adrenal haemorrhage. To derive maximum benefit from this principle, the routine use of an early film coupled with high dosage is urged whenever an intravenous pyelogram is performed for ...

  18. Adrenal metabolism of mitotane and related compounds

    International Nuclear Information System (INIS)

    Djanegara, T.K.S.

    1989-01-01

    Mitotane (o,p'-DDD; 1-[2-chlorophenyl]-1-[4-chlorophenyl]-2,2-dichloroethane) has been used in the treatment of Cushing's syndrome due to adrenal hyperfunction and it the drug of choice for adrenocortical carcinoma. The object of this investigation is to study the biotransformation of o,p'-DDD and p,p'-DDD in dogs and bovine adrenal cortex to explain its selective toxicity and mechanism of action. The in vitro biotransformation of 14 C-labeled o,p'-DDD and p,p'-DDD by dog and bovine adrenal cortex as studied. Of the cortex subcellular fractions, the cytosol fraction was found to be the most active in metabolizing the substrates, followed by the mitochondrial fraction. This metabolism including that in cytosolic fractions, did not take place with boiled enzyme preparations and required an NADPH generating system. This study has been directed towards establishing the metabolic activation mechanism which may account for the adrenocorticolytic effect of mitotane in contrast to detoxication by the liver. HPLC and TLC metabolic profiles have been generated from incubations of bovine and dog adrenal cortex homogenates and their subfractions for 14 C-labeled p,p'-DDD, o,p'-DDD and its monochloroethylene derivative, o,p'-DDMU

  19. Unilateral nodular adrenal hyperplasia: Case series

    African Journals Online (AJOL)

    A.F. Kotb

    2016-07-26

    Jul 26, 2016 ... Abstract. Introduction: Nodular adrenal hyperplasia is one of rare causes of adrenocortical hyperplasia. The disease usually presents bilaterally. Few publications discussed the possibility of unilateral disease, in association with hyperaldosteronism or Cushing syndrome. Case series: We are reporting 3 ...

  20. Imaging features of benign adrenal cysts

    International Nuclear Information System (INIS)

    Sanal, Hatice Tuba; Kocaoglu, Murat; Yildirim, Duzgun; Bulakbasi, Nail; Guvenc, Inanc; Tayfun, Cem; Ucoz, Taner

    2006-01-01

    Benign adrenal gland cysts (BACs) are rare lesions with a variable histological spectrum and may mimic not only each other but also malignant ones. We aimed to review imaging features of BACs which can be helpful in distinguishing each entity and determining the subsequent appropriate management