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Sample records for pigmented nodular adrenocortical

  1. Children with Cushing's syndrome: Primary Pigmented Nodular Adrenocortical Disease should always be suspected.

    PubMed

    da Silva, Renata Marques Gonçalves; Pinto, Emília; Goldman, Suzan M; Andreoni, Cássio; Vieira, Teresa C; Abucham, Julio

    2011-03-01

    Primary Pigmented Nodular Adrenocortical Disease (PPNAD) is a rare form of bilateral adrenocortical hyperplasia that is inherited in an autosomal dominant manner and leads to ACTH-independent Cushing's syndrome (CS). PPNAD may be isolated or associated with Carney Complex (CNC). For the diagnosis of PPNAD and CNC, in addition to the hormonal and imaging tests, searching for PRKAR1A mutations may be recommended. The aims of the present study are to discuss the clinical and molecular findings of two Brazilian patients with ACTH-independent CS due to PPNAD and to show the diagnostic challenge CS represents in childhood. Description of two patients with CS and the many sequential steps for the diagnosis of PPNAD is provided. Sequencing analysis of all coding exons of PRKAR1A in the blood, frozen adrenal nodules (patients 1 and 2) and testicular tumor (patient 1) is performed. After several clinical and laboratory drawbacks that misled the diagnostic investigation in both patients, the diagnosis of PPNAD was finally established and confirmed through pathology and molecular studies. In patient 1, sequencing of PRKAR1A gene revealed a novel heterozygous 10-bp deletion in exon 3, present in his blood, adrenal gland and testicular tumor. The etiologic diagnosis of endogenous CS in children is a challenge that requires expertise and a multidisciplinary collaboration for its prompt and correct management. Although rare, PPNAD should always be considered among the possible etiologies of CS, due to the high prevalence of this disease in this age group. PMID:20924687

  2. An unusual presentation of Carney complex with diffuse primary pigmented nodular adrenocortical disease on one adrenal gland and a nonpigmented adrenocortical adenoma and focal primary pigmented nodular adrenocortical disease on the other.

    PubMed

    Tung, Shih-Chen; Hwang, Daw-Yang; Yang, Joseph W; Chen, Wei-Jen; Lee, Chien-Te

    2012-01-01

    A 24-year-old female patient with cushingoid appearance was admitted in May 2000. The endocrine studies showed ACTH-independent Cushing's syndrome. A 2-day high-dose dexamethasone suppression test (HDDST) revealed paradoxical increase of 24 h urinary free cortisol (UFC). Abdominal computed tomography demonstrated a left adrenal nodule (3 x 2 cm in diameter). An adrenal scintigram with ¹³¹I-6β-iodomethyl-19-norcholesterol showed uptake of the isotope in the left adrenal gland and non-visualization in the right adrenal gland throughout the examination course. A retroperitoneoscopic left total adrenalectomy was performed in July 2000. The cut surface of the left adrenal was yellow-tan grossly. Microscopically, the left adrenal nodule contained a nonpigmented adrenocortical adenoma (NP) and another focal primary pigmented nodular adrenocortical disease (PPNAD, FP) mixed lesion. The immunohistochemical studies of CYP17 demonstrate positive in NP and FP of the left adrenal gland. Very low baseline morning plasma cortisol (0.97 μg/dL) and subnormal ACTH (8.16 pg/mL) levels were measured 1.5 months after left adrenalectomy. Right adrenal gland recovered its function 6 months after left adrenalectomy. Plasma cortisol could be suppressed to 3.47 μg/dL by overnight low-dose dexamethasone suppression test 65 months after left adrenalectomy. Cushingoid features still did not appear 122 months after left adrenalectomy. In May 2011, this patient was readmitted due to cushingoid characteristics. Paradoxical rise of 24-h UFC to 2-day HDDST was demonstrated. Ultrasonography of thyroid showed bilateral thyroid cysts. Subtotal right adrenalectomy about 80% of right adrenal was performed. Diffuse PPNAD of the right adrenal was proved pathologically. Immunohischemical stain for CYP17 is positive in the right adrenal gland but weaker positive than that in the left adrenal gland. The genetic study of the peripheral blood, left adrenocortical nodule, and right PPNAD all showed p.R16X

  3. mTOR pathway is activated by PKA in adrenocortical cells and participates in vivo to apoptosis resistance in primary pigmented nodular adrenocortical disease (PPNAD).

    PubMed

    de Joussineau, Cyrille; Sahut-Barnola, Isabelle; Tissier, Frédérique; Dumontet, Typhanie; Drelon, Coralie; Batisse-Lignier, Marie; Tauveron, Igor; Pointud, Jean-Christophe; Lefrançois-Martinez, Anne-Marie; Stratakis, Constantine A; Bertherat, Jérôme; Val, Pierre; Martinez, Antoine

    2014-10-15

    Primary pigmented nodular adrenocortical disease (PPNAD) is associated with inactivating mutations of the PRKAR1A tumor suppressor gene that encodes the regulatory subunit R1α of the cAMP-dependent protein kinase (PKA). In human and mouse adrenocortical cells, these mutations lead to increased PKA activity, which results in increased resistance to apoptosis that contributes to the tumorigenic process. We used in vitro and in vivo models to investigate the possibility of a crosstalk between PKA and mammalian target of rapamycin (mTOR) pathways in adrenocortical cells and its possible involvement in apoptosis resistance. Impact of PKA signaling on activation of the mTOR pathway and apoptosis was measured in a mouse model of PPNAD (AdKO mice), in human and mouse adrenocortical cell lines in response to pharmacological inhibitors and in PPNAD tissues by immunohistochemistry. AdKO mice showed increased mTOR complex 1 (mTORC1) pathway activity. Inhibition of mTORC1 by rapamycin restored sensitivity of adrenocortical cells to apoptosis in AdKO but not in wild-type mice. In both cell lines and mouse adrenals, rapid phosphorylation of mTORC1 targets including BAD proapoptotic protein was observed in response to PKA activation. Accordingly, BAD hyperphosphorylation, which inhibits its proapoptotic activity, was increased in both AdKO mouse adrenals and human PPNAD tissues. In conclusion, mTORC1 pathway is activated by PKA signaling in human and mouse adrenocortical cells, leading to increased cell survival, which is correlated with BAD hyperphosphorylation. These alterations could be causative of tumor formation. PMID:24865460

  4. Use of 3-Dimensional Volumetric Modeling of Adrenal Gland Size in Patients with Primary Pigmented Nodular Adrenocortical Disease.

    PubMed

    Chrysostomou, P P; Lodish, M B; Turkbey, E B; Papadakis, G Z; Stratakis, C A

    2016-04-01

    Primary pigmented nodular adrenocortical disease (PPNAD) is a rare type of bilateral adrenal hyperplasia leading to hypercortisolemia. Adrenal nodularity is often appreciable with computed tomography (CT); however, accurate radiologic characterization of adrenal size in PPNAD has not been studied well. We used 3-dimensional (3D) volumetric analysis to characterize and compare adrenal size in PPNAD patients, with and without Cushing's syndrome (CS). Patients diagnosed with PPNAD and their family members with known mutations in PRKAR1A were screened. CT scans were used to create 3D models of each adrenal. Criteria for biochemical diagnosis of CS included loss of diurnal variation and/or elevated midnight cortisol levels, and paradoxical increase in urinary free cortisol and/or urinary 17-hydroxysteroids after dexamethasone administration. Forty-five patients with PPNAD (24 females, 27.8±17.6 years) and 8 controls (19±3 years) were evaluated. 3D volumetric modeling of adrenal glands was performed in all. Thirty-eight patients out of 45 (84.4%) had CS. Their mean adrenal volume was 8.1 cc±4.1, 7.2 cc±4.5 (p=0.643) for non-CS, and 8.0cc±1.6 for controls. Mean values were corrected for body surface area; 4.7 cc/kg/m(2)±2.2 for CS, and 3.9 cc/kg/m(2)±1.3 for non-CS (p=0.189). Adrenal volume and midnight cortisol in both groups was positively correlated, r=0.35, p=0.03. We conclude that adrenal volume measured by 3D CT in patients with PPNAD and CS was similar to those without CS, confirming empirical CT imaging-based observations. However, the association between adrenal volume and midnight cortisol levels may be used as a marker of who among patients with PPNAD may develop CS, something that routine CT cannot do. PMID:27065461

  5. Primary pigmented nodular adrenocortical disease: the original 4 cases revisited after 30 years for follow-up, new investigations, and molecular genetic findings.

    PubMed

    Carney, J Aidan; Libé, Rossella; Bertherat, Jérôme; Young, William F

    2014-09-01

    The original 4 patients with Cushing syndrome who underwent bilateral adrenalectomy for primary pigmented nodular adrenocortical disease were followed up for an average of 31 years to determine whether they or any of their primary relatives had developed Carney complex or its components. None had. Three of the patients were alive and well; the fourth had died of an unrelated condition. All the adrenal glands contained multiple small, black or brown cortical nodules, up to 4 mm in diameter. The extracapsular extension of the micronodules was limited to the immediate pericapsular adipose tissue and was not considered evidence of low-grade malignancy. Immunocytochemically, the nodules were positive for synaptophysin, inhibin-A, and melan A and negative for vimentin and CD56. Ki-67 antibody stained the cytoplasm of cells in the micronodules but not that of the atrophic cortical cells. The 4 patients had the PRKAR1A deletion that has been associated with the isolated form of primary pigmented nodular adrenocortical disease. PMID:24805858

  6. A Novel Mutation in the type Iα Regulatory Subunit of Protein Kinase A (PRKAR1A) in a Cushing's Syndrome Patient with Primary Pigmented Nodular Adrenocortical Disease.

    PubMed

    Mineo, Ryohei; Tamba, Sachiko; Yamada, Yuya; Okita, Tomonori; Kawachi, Yusuke; Mori, Reiko; Kyo, Mitsuaki; Saisho, Kenji; Kuroda, Yohei; Yamamoto, Koji; Furuya, Akiko; Mukai, Tokuo; Maekawa, Takashi; Nakamura, Yasuhiro; Sasano, Hironobu; Matsuzawa, Yuji

    2016-01-01

    A 40-year-old man presented with Cushing's syndrome due to bilateral adrenal hyperplasia with multiple nodules. Computed tomography scan results were atypical demonstrating an enlargement of the bilateral adrenal glands harboring multiple small nodules, but the lesion was clinically diagnosed to be primary pigmented nodular adrenocortical disease (PPNAD) based on both endocrinological test results and his family history. We performed bilateral adrenalectomy and confirmed the diagnosis histologically. An analysis of the patient and his mother's genomic DNA identified a novel mutation in the type Iα regulatory subunit of protein kinase A (PRKAR1A) gene; p.E17X (c.49G>T). This confirmed the diagnosis of PPNAD which is associated with Carney Complex. PMID:27580546

  7. Protein kinase A alterations in adrenocortical tumors.

    PubMed

    Espiard, S; Ragazzon, B; Bertherat, J

    2014-11-01

    Stimulation of the cAMP pathway by adrenocorticotropin (ACTH) is essential for adrenal cortex maintenance, glucocorticoid and adrenal androgens synthesis, and secretion. Various molecular and cellular alterations of the cAMP pathway have been observed in endocrine tumors. Protein kinase A (PKA) is a central key component of the cAMP pathway. Molecular alterations of PKA subunits have been observed in adrenocortical tumors. PKA molecular defects can be germline in hereditary disorders or somatic in sporadic tumors. Heterozygous germline inactivating mutations of the PKA regulatory subunit RIα gene (PRKAR1A) can be observed in patients with ACTH-independent Cushing's syndrome (CS) due to primary pigmented nodular adrenocortical disease (PPNAD). PRKAR1A is considered as a tumor suppressor gene. Interestingly, these mutations can also be observed as somatic alterations in sporadic cortisol-secreting adrenocortical adenomas. Germline gene duplication of the catalytic subunits Cα (PRKACA) has been observed in patients with PPNAD. Furthermore, exome sequencing revealed recently activating somatic mutations of PRKACA in about 40% of cortisol-secreting adrenocortical adenomas. In vitro and in vivo functional studies help in the progress to understand the mechanisms of adrenocortical tumors development due to PKA regulatory subunits alterations. All these alterations are observed in benign oversecreting tumors and are mimicking in some way cAMP pathway constitutive activation. On the long term, unraveling these alterations will open new strategies of pharmacological treatment targeting the cAMP pathway in adrenal tumors and cortisol-secretion disorders. PMID:25105543

  8. PRKACA: the catalytic subunit of protein kinase A and adrenocortical tumors.

    PubMed

    Berthon, Annabel S; Szarek, Eva; Stratakis, Constantine A

    2015-01-01

    Cyclic-AMP (cAMP)-dependent protein kinase (PKA) is the main effector of cAMP signaling in all tissues. Inactivating mutations of the PRKAR1A gene, coding for the type 1A regulatory subunit of PKA, are responsible for Carney complex and primary pigmented nodular adrenocortical disease (PPNAD). PRKAR1A inactivation and PKA dysregulation have been implicated in various types of adrenocortical pathologies associated with ACTH-independent Cushing syndrome (AICS) from PPNAD to adrenocortical adenomas and cancer, and other forms of bilateral adrenocortical hyperplasias (BAH). More recently, mutations of PRKACA, the gene coding for the catalytic subunit C alpha (Cα), were also identified in the pathogenesis of adrenocortical tumors. PRKACA copy number gain was found in the germline of several patients with cortisol-producing BAH, whereas the somatic Leu206Arg (c.617A>C) recurrent PRKACA mutation was found in as many as half of all adrenocortical adenomas associated with AICS. In vitro analysis demonstrated that this mutation led to constitutive Cα activity, unregulated by its main partners, the PKA regulatory subunits. In this review, we summarize the current understanding of the involvement of PRKACA in adrenocortical tumorigenesis, and our understanding of PKA's role in adrenocortical lesions. We also discuss potential therapeutic advances that can be made through targeting of PRKACA and the PKA pathway. PMID:26042218

  9. The cAMP pathway and the control of adrenocortical development and growth

    PubMed Central

    de Joussineau, Cyrille; Sahut-Barnola, Isabelle; Levy, Isaac; Saloustros, Emmanouil; Val, Pierre; Stratakis, Constantine A.; Martinez, Antoine

    2013-01-01

    In the last 10 years, extensive studies showed that the cAMP pathway is deregulated in patients suffering from adrenocortical tumours, and particularly in primary pigmented nodular adrenocortical disease (PPNAD). Here we describe how evidence arising from the analysis of patients’ data, mouse models and in vitro experiments, have shed light on the cAMP pathway as a central player in adrenal physiopathology. We also show how novel data generated from mouse models may point to new targets for potential therapies. PMID:22019902

  10. Carney complex presenting with a unilateral adrenocortical nodule: a case report

    PubMed Central

    2014-01-01

    Introduction Carney complex is an autosomal dominant syndrome with multiple neoplasms in different sites, including myxomas, endocrine tumors and lentigines lesions. To the best of our knowledge, this is the first report of Carney complex presenting with a unilateral adrenal adenoma associated with a pituitary incidentaloma. Case presentation A 27-year-old Iranian woman was referred to our endocrinology clinic with amenorrhea and hirsutism, further confirming a diagnosis of adrenocorticotropic hormone-independent Cushing’s syndrome. The cause was believed to be a right adrenocortical adenoma based on a computed tomography scan. Our patient underwent a right laparoscopic adrenalectomy and pathological examination revealed pigmented micronodular adrenal hyperplasia. Pituitary magnetic resonance imaging also documented a microadenoma that was considered to be an incidentaloma based on normal pituitary function tests. Recurrence of hypercortisolism led to a left laparoscopic adrenalectomy, providing further evidence for the diagnosis of primary pigmented nodular adrenocortical disease. Carney complex was established in light of her history of cardiac myxomas. Conclusion We present what we believe to be the first case of Carney complex presenting with a unilateral adrenocortical adenoma in association with a pituitary incidentaloma. Although primary pigmented nodular adrenocortical disease is rare as a component of Carney complex, it should be considered in the differential diagnosis of Cushing's syndrome. Rarely, adrenal and pituitary imaging can be misleading. PMID:24499519

  11. Adrenocortical carcinoma

    MedlinePlus

    ... JavaScript. Adrenocortical carcinoma is a cancer of the adrenal glands . Causes Adrenocortical carcinoma is most common in children ... tumor. Symptoms Symptoms of increased cortisol or other adrenal gland hormones: Fatty, rounded hump high on the back ...

  12. Celecoxib reduces glucocorticoids in vitro and in a mouse model with adrenocortical hyperplasia.

    PubMed

    Liu, Sisi; Saloustros, Emmanouil; Berthon, Annabel; Starost, Matthew F; Sahut-Barnola, Isabelle; Salpea, Paraskevi; Szarek, Eva; Faucz, Fabio R; Martinez, Antoine; Stratakis, Constantine A

    2016-01-01

    Primary pigmented nodular adrenocortical disease (PPNAD), whether in the context of Carney complex (CNC) or isolated, leads to ACTH-independent Cushing's syndrome (CS). CNC and PPNAD are caused typically by inactivating mutations of PRKAR1A, a gene coding for the type 1a regulatory subunit (R1α) of cAMP-dependent protein kinase (PKA). Mice lacking Prkar1a, specifically in the adrenal cortex (AdKO) developed CS caused by bilateral adrenal hyperplasia (BAH), which is formed from the abnormal proliferation of fetal-like adrenocortical cells. Celecoxib is a cyclooxygenase 2 (COX2) inhibitor. In bone, Prkar1a inhibition is associated with COX2 activation and prostaglandin E2 (PGE2) production that, in turn, activates proliferation of bone stromal cells. We hypothesized that COX2 inhibition may have an effect in PPNAD. In vitro treatment of human cell lines, including one from a patient with PPNAD, with celecoxib resulted in decreased cell viability. We then treated AdKO and control mice with 1500 mg/kg celecoxib or vehicle. Celecoxib treatment led to decreased PGE2 and corticosterone levels, reduced proliferation and increased apoptosis of adrenocortical cells, and decreased steroidogenic gene expression. We conclude that, in vitro and in vivo, celecoxib led to decreased steroidogenesis. In a mouse model of PPNAD, celecoxib caused histological changes that, at least in part, reversed BAH and this was associated with a reduction of corticosterone levels. PMID:26438728

  13. Celecoxib reduces glucocorticoids in vitro and in a mouse model with adrenocortical hyperplasia

    PubMed Central

    Liu, Sisi; Saloustros, Emmanouil; Berthon, Annabel; Starost, Matthew F.; Sahut-Barnola, Isabelle; Salpea, Paraskevi; Szarek, Eva; Faucz, Fabio R.; Martinez, Antoine; Stratakis, Constantine A.

    2015-01-01

    Primary pigmented nodular adrenocortical disease (PPNAD), whether in the context of Carney complex (CNC) or isolated, leads to adrenocorticotropin hormone (ACTH) - independent Cushing’s syndrome (CS). CNC and PPNAD are caused typically by inactivating mutations of PRKAR1A, a gene coding for the type 1a regulatory subunit (R1α) of cAMP–dependent protein kinase (PKA). Mice lacking Prkar1a, specifically in the adrenal cortex (AdKO) developed CS caused by bilateral adrenal hyperplasia (BAH), which is formed from the abnormal proliferation of fetal-like adrenocortical cells. Celecoxib is a cyclooxygenase-2 (COX2) inhibitor. In bone, Prkar1a inhibition is associated with COX2 activation and prostaglandin E2 (PGE2) production that, in turn, activates proliferation of bone stromal cells. We hypothesized that COX2 inhibition may have an effect in PPNAD. In vitro treatment of human cell lines, including one from a patient with PPNAD, with Celecoxib resulted in decreased cell viability. We then treated AdKO and control mice with 1,500 mg/kg Celecoxib or vehicle. Celecoxib treatment led to decreased PGE2 and corticosterone levels, reduced proliferation and increased apoptosis of adrenocortical cells, and decreased steroidogenic gene expression. We conclude that, in vitro and in vivo, Celecoxib led to decreased steroidogenesis. In a mouse model of PPNAD, Celecoxib caused histological changes that reversed, at least in part, BAH and this was associated with a reduction of corticosterone levels. PMID:26438728

  14. Adrenocortical Carcinoma

    PubMed Central

    Kim, Alex C.; Sabolch, Aaron; Raymond, Victoria M.; Kandathil, Asha; Caoili, Elaine M.; Jolly, Shruti; Miller, Barbra S.; Giordano, Thomas J.

    2014-01-01

    Adrenocortical carcinoma (ACC) is a rare endocrine malignancy, often with an unfavorable prognosis. Here we summarize the knowledge about diagnosis, epidemiology, pathophysiology, and therapy of ACC. Over recent years, multidisciplinary clinics have formed and the first international treatment trials have been conducted. This review focuses on evidence gained from recent basic science and clinical research and provides perspectives from the experience of a large multidisciplinary clinic dedicated to the care of patients with ACC. PMID:24423978

  15. Classification and surgical treatment for 180 cases of adrenocortical hyperplastic disease

    PubMed Central

    Zhang, Yushi; Li, Hanzhong

    2015-01-01

    Objective: To review and discuss the diagnostic and surgical therapeutic methods of adrenocortical hyperplastic disease. Methods: A retrospective analysis was done to 180 adrenocortical hyperplasia patients (74 males, 109 females, aged 6~76 (average 40.1). Studies were done to the relationship between patients’ clinical characteristics, biochemical, endocrinological and imaging examination results, the therapeutic effects. Results: Among all 180 cases, there are 107 Cushing disease (CD), 19 ectopic adrenocorticotropin adrenal hyperplasia (EAAH), 28 adrenocorticotropin independent macronodular adrenal hyperplasia (AIMAH), 4 primary pigmented nodular adrenocortical hyperplasia (PPNAH), and 28 Idiopathic Hyperaldosteronism (IHA). Twenty-four-hour urinary free cortisol (24 h UFC) excretion of CD, EAAH, AIMAH and PPNAH patients were 95.2~535.7 µg (average 287.6 µg), 24.8~808.2 µg (average 307.9 µg), 102.5~3127.0 µg (average 852.5 µg), and 243.8~1124.6 µg (average 564.3 µg). Both low and high-dose dexamethasone suppression tests (DDST) were not suppressed in AIMAH, PPNAH and EAAH groups, but HDDST was suppressed in CD group. CT thin scanning results of 180 patients all showed enlargements in the affected side adrenal gland. Unilateral adrenalectomies were performed in 102 hypercortisolism cases. Local lesion excisions were done to 21 IHA patients. 57 patients had surgeries in both sides of the adrenal glands (39 bilateral total adrenalectomies, 16 total adrenalectomy in one side andsubtotal adrenalectomy in the other, 2 bilateral subtotal adrenalectomies). 106 (59%) patients were followed up for 4~158 (average 32) months. Conclusion: Unilateral adrenalectomy was the first choice for operable adrenocortical hyperplasia patients. The operation mode for the other adrenal gland should be based on the type of hyperplasia and clinical observation. PMID:26770569

  16. Adrenocortical carcinoma.

    PubMed

    Baudin, Eric

    2015-06-01

    Recent developments in the treatment of adrenocortical carcinoma (ACC) include diagnostic and prognostic risk stratification algorithms, increasing evidence of the impact of historical therapies on overall survival, and emerging targets from integrated epigenomic and genomic analyses. Advances include proper clinical and molecular characterization of all patients with ACC, standardization of proliferative index analyses, referral of these patients to large cancer referral centers at the time of first surgery, and development of new trials in patients with well-characterized ACC. Networking and progress in the molecular characterization of ACC constitute the basis for significant future therapeutic breakthroughs. PMID:26038209

  17. Different expression of protein kinase A (PKA) regulatory subunits in cortisol-secreting adrenocortical tumors: Relationship with cell proliferation

    SciTech Connect

    Mantovani, G.; Lania, A.G.; Bondioni, S.; Peverelli, E.; Pedroni, C.; Ferrero, S.; Pellegrini, C.; Vicentini, L.; Arnaldi, G.; Bosari, S.; Beck-Peccoz, P.; Spada, A.

    2008-01-01

    The four regulatory subunits (R1A, R1B, R2A, R2B) of protein kinase A (PKA) are differentially expressed in several cancer cell lines and exert distinct roles in growth control. Mutations of the R1A gene have been found in patients with Carney complex and in a minority of sporadic primary pigmented nodular adrenocortical disease (PPNAD). The aim of this study was to evaluate the expression of PKA regulatory subunits in non-PPNAD adrenocortical tumors causing ACTH-independent Cushing's syndrome and to test the impact of differential expression of these subunits on cell growth. Immunohistochemistry demonstrated a defective expression of R2B in all cortisol-secreting adenomas (n = 16) compared with the normal counterpart, while both R1A and R2A were expressed at high levels in the same tissues. Conversely, carcinomas (n = 5) showed high levels of all subunits. Sequencing of R1A and R2B genes revealed a wild type sequence in all tissues. The effect of R1/R2 ratio on proliferation was assessed in mouse adrenocortical Y-1 cells. The R2-selective cAMP analogue 8-Cl-cAMP dose-dependently inhibited Y-1 cell proliferation and induced apoptosis, while the R1-selective cAMP analogue 8-HA-cAMP stimulated cell proliferation. Finally, R2B gene silencing induced up-regulation of R1A protein, associated with an increase in cell proliferation. In conclusion, we propose that a high R1/R2 ratio favors the proliferation of well differentiated and hormone producing adrenocortical cells, while unbalanced expression of these subunits is not required for malignant transformation.

  18. Adrenocortical endocrine disruption.

    PubMed

    Harvey, Philip W

    2016-01-01

    The adrenal has been neglected in endocrine disruption regulatory testing strategy. The adrenal is a vital organ, adrenocortical insufficiency is recognised in life threatening "adrenal crises" and Addison's disease, and the consequences of off-target toxicological inhibition of adrenocortical steroidogenesis is well recognised in clinical medicine, where drugs such as aminoglutethimide and etomidate killed patients via unrecognised inhibition of adrenocortical steroidogenic enzymes (e.g. CYP11B1) along the cortisol and aldosterone pathways. The consequences of adrenocortical dysfunction during early development are also recognised in the congenital salt wasting and adrenogenital syndromes presenting neonatally, yet despite a remit to focus on developmental and reproductive toxicity mechanisms of endocrine disruption by many regulatory agencies (USEPA EDSTAC; REACH) the assessment of adrenocortical function has largely been ignored. Further, every step in the adrenocortical steroidogenic pathway (ACTH receptor, StAR, CYP's 11A1, 17, 21, 11B1, 11B2, and 3-hydroxysteroid dehydrogenase Δ4,5 isomerase) is known to be a potential target with multiple examples of chemicals inhibiting these targets. Many of these chemicals have been detected in human and wildlife tissues. This raises the question of whether exposure to low level environmental chemicals may be affecting adrenocortical function. This review examines the omission of adrenocortical testing in the current regulatory frameworks; the characteristics that make the adrenal cortex particularly vulnerable to toxic insult; chemicals and their toxicological targets within the adrenocortical steroidogenic pathways; the typical manifestations of adrenocortical toxicity (e.g. human iatrogenically induced pharmacotoxicological adrenal insufficiency, manifestations in typical mammalian regulatory general toxicology studies, manifestations in wildlife) and models of adrenocortical functional assessment. The utility of the

  19. Epibulbar Nodular Fasciitis

    PubMed Central

    Massop, David John; Frederick, Paul Adam; Li, He J.; Lin, Amy

    2016-01-01

    Purpose To report a case of epibulbar nodular fasciitis in a 32-year-old female and provide context by reviewing the current literature. Results Using excisional biopsy, the patient was successfully diagnosed and treated for epibulbar nodular fasciitis. Upon follow-up, there has been no recurrence, consistent with the typical course for nodular fasciitis. Conclusions Epibulbar nodular fasciitis is a rare process that can be successfully treated by surgical resection. While two cases of trauma-associated epibulbar nodular fasciitis have been present in the literature, our case did not have such a history. The etiology of nodular fasciitis remains unclear. PMID:27462253

  20. Stages of Adrenocortical Carcinoma

    MedlinePlus

    ... of Childhood Treatment for more information.) Having certain genetic conditions increases the risk of adrenocortical carcinoma. Anything ... can be a sign of disease. CT scan (CAT scan) : A procedure that makes a series of ...

  1. Familial micronodular adrenocortical disease, Cushing syndrome, and mutations of the gene encoding phosphodiesterase 11A4 (PDE11A).

    PubMed

    Carney, J Aidan; Gaillard, Rolf C; Bertherat, Jérôme; Stratakis, Constantine A

    2010-04-01

    We present the pathologic findings in the adrenal glands of 4 patients, aged 10 to 38 years, with Cushing syndrome and germline inactivating mutations of the gene PDE11A4 that encodes phosphodiesterase11A4. The gene is expressed in the adrenal cortex and catalyses the hydrolysis of cyclic adenosine monophosphate and cyclic guanosine monophosphate. Two of the patients were mother and daughter; the third had no affected relative; the fourth patient inherited the mutation from her father. Three of the group, including the mother and daughter, had the same pathology, primary pigmented nodular adrenocortical disease, a disorder known to be caused by inactivating mutations of the PRKAR1A gene. In these cases, the adrenal glands were small and the pathologic change was deep in the cortex in which numerous pigmented micronodules developed. In the remaining patient, the glands were slightly enlarged primarily owing to a diffuse hyperplasia of the superficial cortex that extended into the epi-adrenal fat. PMID:20351491

  2. A Case of Cushing's Syndrome with Multiple Adrenocortical Adenomas Composed of Compact Cells and Clear Cells.

    PubMed

    Asakawa, Masahiro; Yoshimoto, Takanobu; Ota, Mitsutane; Numasawa, Mitsuyuki; Sasahara, Yuriko; Takeuchi, Takato; Nakano, Yujiro; Oohara, Norihiko; Murakami, Masanori; Bouchi, Ryotaro; Minami, Isao; Tsuchiya, Kyoichiro; Hashimoto, Koshi; Izumiyama, Hajime; Kawamura, Naoko; Kihara, Kazunori; Negi, Mariko; Akashi, Takumi; Eishi, Yoshinobu; Sasano, Hironobu; Ogawa, Yoshihiro

    2016-06-01

    A 58-year-old woman was referred to our hospital for Cushingoid features and diagnosed as adrenal Cushing's syndrome due to a right adrenocortical mass (60 × 55 mm). The mass was composed of three different tumors; the first one was homogeneously lipid-poor neoplasm measuring 20 × 13 mm located at the most dorsal region, the second one was heterogeneous and lipid-rich tumor containing multiple foci of calcification measuring 50 × 32 mm located at the central region, and the last one was heterogeneous harboring dilated and tortuous vessels and lipid-poor one measuring 35 × 18 mm at the most ventral region of the adrenal gland. A right adrenalectomy was subsequently performed by open surgery. Macroscopic and microscopic analyses revealed that all three tumors were adrenocortical adenomas; the first one represents a pigmented adrenocortical adenoma, the second one adrenocortical adenoma associated with degeneration, and the third one adrenocortical adenoma harboring extensive degeneration. Immunohistochemical analysis of the steroidogenic enzymes also revealed that all of the tumors had the capacity of synthesizing cortisol. This is a very rare case of Cushing's syndrome caused by multiple adrenocortical adenomas including a pigmented adenoma. Immunohistochemical analysis of steroidogenic enzymes contributed to understanding of steroidogenesis in each of these three different adrenocortical adenomas in this case. PMID:26961704

  3. Animal models of adrenocortical tumorigenesis

    PubMed Central

    Beuschlein, Felix; Galac, Sara; Wilson, David B.

    2011-01-01

    Over the past decade, research on human adrenocortical neoplasia has been dominated by gene expression profiling of tumor specimens and by analysis of genetic disorders associated with a predisposition to these tumors. Although these studies have identified key genes and associated signaling pathways that are dysregulated in adrenocortical neoplasms, the molecular events accounting for the frequent occurrence of benign tumors and low rate of malignant transformation remain unknown. Moreover, the prognosis for patients with adrenocortical carcinoma remains poor, so new medical treatments are needed. Naturally occurring and genetically engineered animal models afford a means to investigate adrenocortical tumorigenesis and to develop novel therapeutics. This comparative review highlights adrenocortical tumor models useful for either mechanistic studies or preclinical testing. Three model species – mouse, ferret, and dog – are reviewed, and their relevance to adrenocortical tumors in humans is discussed. PMID:22100615

  4. Treatment Option Overview (Adrenocortical Carcinoma)

    MedlinePlus

    ... of Childhood Treatment for more information.) Having certain genetic conditions increases the risk of adrenocortical carcinoma. Anything ... can be a sign of disease. CT scan (CAT scan) : A procedure that makes a series of ...

  5. Salzmann's Nodular Degeneration.

    PubMed

    Maharana, Prafulla K; Sharma, Namrata; Das, Sujata; Agarwal, Tushar; Sen, Seema; Prakash, Gaurav; Vajpayee, Rasik B

    2016-01-01

    Salzmann's nodular degeneration (SND) is a rare, noninflammatory, slowly progressive degenerative disease of the cornea that is characterized by the appearance of nodular bluish gray opacities that vary in number and size. It is usually bilateral; most commonly occurring in people aged 50-60 years old, with a female preponderance; and often associated with a history of prior corneal inflammation. The clinical features usually depend on the location of the nodules. Generally, the nodules of SND are bluish white to gray in color, 1-2 mm in size, and round, conical or prismatic in shape. The overlying Bowman's layer is usually absent from the nodular areas and is partially replaced by granular Periodic Acid Schiff-positive eosinophilic material resembling the basement membrane. Diagnostic investigations include ultrasonic pachymetry, anterior segment optical coherence tomography, ultrasound biomicroscopy, and confocal microscopy. The majority of patients respond well to conservative management with topical lubricants; severe cases may require surgical intervention. The various surgical modalities described include superficial keratectomy, which may be combined with phototherapeutic keratectomy and keratoplasty. Various modifications of these procedures include the use of alcohol-assisted epithelial delamination, intraoperative mitomycin-C or amniotic membrane transplantation to make the procedure easy, reduce the risk of recurrence and improve postoperative comfort. Recurrences are rarely reported; overall, the visual prognosis following treatment is optimal. PMID:26462409

  6. A case of nodular scleroderma.

    PubMed

    Melani, Lucilla; Caproni, Marzia; Cardinali, Carla; Antiga, Emiliano; Bernacchi, Elisabetta; Schincaglia, Emiliano; Fabbri, Paolo

    2005-12-01

    Nodular scleroderma is a rare complication of systemic sclerosis; the pathogenetic implications are still unknown, although many factors are supposed to play a role in lesion development. We report the case of a young woman suffering from systemic sclerosis, who developed nodular lesions during therapeutic management with D-penicillamine and plasmapheresis. In order to better understand the essence of this disease, we examined all the possible pathogenetic mechanisms that could be implicated in nodular lesion development. PMID:16471471

  7. Nodular purpura in infancy

    PubMed Central

    Nagi, N. A.; Al-Dubooni, H. M.; Al-Shirkat, S. A. R.

    1982-01-01

    Seventeen infants with nodular purpura are reported. All these infants suffered from a coagulation abnormality due to vitamin K deficiency. Contributing factors were breast-feeding, the use of milk substitutes, diarrhoea and antimicrobial therapy. The patients responded rapidly and completely to parenteral vitamin K. In the management of infantile diarrhoea use of antibiotics should be restricted to specific bacteriologically proven cases. Vitamin K administration is suggested in infants with prolonged gastroenteritis and limited milk intake and particularly those receiving antibiotics. ImagesFig. 1 PMID:7111112

  8. Nodular fasciitis causing unilateral proptosis.

    PubMed Central

    Perry, R H; Ramani, P S; McAllister, V; Kalbag, R M; Kanagasundaram, C R

    1975-01-01

    A case report of an unusual case of nodular fasciitis in the orbit presenting with unilateral proptosis is described, and the radiological features are outlined. The histological features are discussed and the benign nature of the lesion stressed. Nodular fasciitis arising in the orbit and presenting as unilateral proptosis has not previously been reported in the literature. Images PMID:1060468

  9. Cystic and nodular lung disease.

    PubMed

    Richards, J Caleb; Lynch, David A; Chung, Jonathan H

    2015-06-01

    Diffuse cystic and nodular lung diseases have characteristic imaging findings. The most common causes of cystic lung disease are lymphangioleiomyomatosis and Langerhans cell histiocytosis. Other less common cystic lung diseases include Birt-Hogg-Dube syndrome, lymphocytic interstitial pneumonitis, and light chain deposition disease. Computed tomography is used to differentiate cystic lung disease from emphysema, honeycombing, cavities, and bronchiectasis, which mimic cystic lung disease. Diffuse nodular lung disease are categorized as centrilobular, perilymphatic, and random types. In diffuse nodular lung disease, a specific diagnosis is achieved through a combination of history, physical examination, and imaging findings. PMID:26024606

  10. Adrenocortical Stem and Progenitor Cells—Implications for Adrenocortical Carcinoma

    PubMed Central

    Simon, Derek P.; Hammer, Gary D.

    2012-01-01

    The continuous centripetal repopulation of the adrenal cortex is consistent with a population of cells endowed with the stem/progenitor cell properties of self-renewal and pluripotency. The adrenocortical capsule and underlying undifferentiated cortical cells are emerging as critical components of the stem/progenitor cell niche. Recent genetic analysis has identified various signaling pathways including Sonic Hedgehog (Shh) and Wnt as crucial mediators of adrenocortical lineage and organ homeostasis. Shh expression is restricted to the peripheral cortical cells that express a paucity of steroidogenic genes but give rise to the underlying differentiated cells of the cortex. Wnt/β-catenin signaling maintains the undifferentiated state and adrenal fate of adrenocortical stem/progenitor cells, in part through induction of its target genes Dax1 and inhibin-α, respectively. The pathogenesis of ACC, a rare yet highly aggressive cancer with an extremely poor prognosis, is slowly emerging from studies of the stem/progenitor cells of the adrenal cortex coupled with the genetics of familial syndromes in which ACC occurs. The frequent observation of constitutive activation of Wnt signaling due to loss-of-function mutations in the tumor suppressor gene APC or gain-of-function mutation in β-catenin in both adenomas and carcinomas, suggests perhaps that the Wnt pathway serves an early or initiating insult in the oncogenic process. Loss of p53 might be predicted to cooperate with additional genetic insults such as IGF2 as both are the most common genetic abnormalities in malignant versus benign adrenocortical neoplasms. It is unclear whether other factors such as Pod1 and Pref1, which are implicated in stem/progenitor cell biology in the adrenal and/or other organs, are also implicated in the etiology of adrenocortical carcinoma. The rarity and heterogeneous presentation of ACC makes it difficult to identify the cellular origin and the molecular progression to cancer. A more

  11. Isolation of rat adrenocortical mitochondria

    SciTech Connect

    Solinas, Paola; Fujioka, Hisashi; Tandler, Bernard; Hoppel, Charles L.

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer A method for isolation of adrenocortical mitochondria from the adrenal gland of rats is described. Black-Right-Pointing-Pointer The purified isolated mitochondria show excellent morphological integrity. Black-Right-Pointing-Pointer The properties of oxidative phosphorylation are excellent. Black-Right-Pointing-Pointer The method increases the opportunity of direct analysis of adrenal mitochondria from small animals. -- Abstract: This report describes a relatively simple and reliable method for isolating adrenocortical mitochondria from rats in good, reasonably pure yield. These organelles, which heretofore have been unobtainable in isolated form from small laboratory animals, are now readily accessible. A high degree of mitochondrial purity is shown by the electron micrographs, as well as the structural integrity of each mitochondrion. That these organelles have retained their functional integrity is shown by their high respiratory control ratios. In general, the biochemical performance of these adrenal cortical mitochondria closely mirrors that of typical hepatic or cardiac mitochondria.

  12. The complex of myxomas, spotty skin pigmentation and endocrine overactivity (Carney complex): imaging findings with clinical and pathological correlation.

    PubMed

    Courcoutsakis, Nikos A; Tatsi, Christina; Patronas, Nicholas J; Lee, Chiy-Chia Richard; Prassopoulos, Panos K; Stratakis, Constantine A

    2013-02-01

    The complex of myxomas, spotty skin pigmentation and endocrine overactivity, or Carney complex (CNC), is a familial multiple endocrine neoplasia and lentiginosis syndrome. CNC is inherited in an autosomal dominant manner and is genetically heterogeneous. Its features overlap those of McCune-Albright syndrome and other multiple endocrine neoplasia (MEN) syndromes. Spotty skin pigmentation is the major clinical manifestation of the syndrome, followed by multicentric heart myxomas, which occur at a young age and are the lethal component of the disease. Myxomas may also occur on the skin (eyelid, external ear canal and nipple) and the breast. Breast myxomas, when present, are multiple and bilateral among female CNC patients, an entity which is also described as "breast-myxomatosis" and is a characteristic feature of the syndrome. Affected CNC patients often have tumours of two or more endocrine glands, including primary pigmented nodular adrenocortical disease (PPNAD), an adrenocorticotropin hormone (ACTH)-independent cause of Cushing's syndrome, growth hormone (GH)-secreting and prolactin (PRL)-secreting pituitary adenomas, thyroid adenomas or carcinomas, testicular neoplasms (large-cell calcifying Sertoli cell tumours [LCCSCT]) and ovarian lesions (cysts and cancinomas). Additional infrequent but characteristic manifestations of CNC are psammomatous melanotic schwannomas (PMS), breast ductal adenomas (DAs) with tubular features, and osteochondromyxomas or "Carney bone tumour". Teaching Points • Almost 60 % of the known CNC kindreds have a germline inactivating mutations in the PRKAR1A gene. • Spotty skin pigmentation is the major clinical manifestation of CNC, followed by heart myxomas. • Indicative imaging signs of PPNAD are contour abnormality and hypodense spots within the gland. • Two breast tumours may present in CNC: myxoid fibroadenomas (breast myxomatosis) and ductal adenomas. • Additional findings of CNC are psammomatous melanotic schwannomas

  13. Nodular panniculitis in the dog.

    PubMed

    Baker, B B; Stannard, A A

    1975-10-15

    Nodular panniculitis, a granulomatous inflammatory disease of the subcutaneous fat, was diagnosed in 11 dogs. Clinically, the disease was characterized by development of subcutaneous nodules and intermittent fever and anorexia. Short-term corticosteroid therapy was effective in 10 of the 11 dogs. PMID:1237484

  14. Pathogenesis of benign adrenocortical tumors.

    PubMed

    Vezzosi, Delphine; Bertherat, Jérôme; Groussin, Lionel

    2010-12-01

    Most adrenocortical tumors (ACT) are benign unilateral adrenocortical adenomas, often discovered incidentally. Exceptionally, ACT are bilateral. However bilateral ACT have been very helpful to progress in the pathophysiology of ACT. Although most ACT are of sporadic origin, they may also be part of syndromic and/or hereditary disorders. The identification of the genetics of familial diseases associated with benign ACT has been helpful to define somatic alterations in sporadic ACT: for example, identification of PRKAR1A mutations in Carney complex or alterations of the Wnt/β-catenin pathway in Familial Adenomatous Polyposis Coli. Components of the cAMP signaling pathway-for example, adrenocorticotropic-hormone receptors and other membrane receptors, Gs protein, phosphodiesterases and protein kinase A-can be altered to various degrees in benign cortisol-secreting ACT. These progress have been important for the understanding of the pathogenesis of benign ACT, but already have profound implications for clinical management, for example in unraveling the genetic origin of disease in some patients with ACT. They also have therapeutic consequences, and should help to develop new therapeutic options. PMID:21115158

  15. Single Nodular Pulmonary Amyloidosis: Case Report

    PubMed Central

    Ko, Young Chun; Jeong, Jong Pil; Park, Chan Woo; Seo, Seok Ho; Kim, Jong Taek; Park, Dae Won; Bak, Cheol Min; Moon, Seung Ki; Jo, Shin Hyoung; Kim, Se Mi; Jung, Ah Lon

    2015-01-01

    Amyloidosis is defined as the presence of extra-cellular deposits of an insoluble fibrillar protein, amyloid. The pulmonary involvement of amyloidosis is usually classified as tracheobronchial, parenchymal nodular, or diffuse alveolar septal. A single nodular lesion can mimic various conditions, including malignancy, pulmonary tuberculosis, and fungal infection. To date, only one case of nodular pulmonary amyloidosis has been reported in Korea, a case involving multiple nodular lesions. Here, we report and discuss the case of a patient having single nodular amyloidosis. PMID:26508930

  16. A Large Family with Carney Complex Caused by the S147G PRKAR1A Mutation Shows a Unique Spectrum of Disease Including Adrenocortical Cancer

    PubMed Central

    Anselmo, João; Medeiros, Sandra; Carneiro, Victor; Greene, Elizabeth; Levy, Isaac; Nesterova, Maria; Lyssikatos, Charalampos; Horvath, Anelia; Carney, J. Aidan

    2012-01-01

    Context: Most tumors in Carney complex (CNC) are benign, including primary pigmented nodular adrenocortical disease (PPNAD), the main endocrine tumor in CNC. Adrenocortical cancer (AC) has never been observed in the syndrome. Herein, we describe a large Azorean family with CNC caused by a point mutation in the PRKAR1A gene coding for type 1-α (RIα) regulatory subunit of the cAMP-dependent protein kinase A, in which the index patient presented with AC. Objective: We studied the genotype-phenotype correlation in CNC. Design and Setting: We reported on case series and in vitro testing of the PRKAR1A mutation in a tertiary care referral center. Patients: Twenty-two members of a family were investigated for Cushing syndrome and other CNC components; their DNA was sequenced for PRKAR1A mutations. Results: Cushing syndrome due to PPNAD occurred in four patients, including the proposita who presented with AC and three who had Cushing syndrome and/or PPNAD. Lentigines were found in six additional patients who did not have PPNAD. A base substitution (c.439A>G/p.S147G) in PRKAR1A was identified in the proposita, in the three others with PPNAD, in the proposita's twin daughters who had lentigines but no evidence of hypercortisolism, and in five other family members, including one without lentigines or evidence of hypercortisolism. Unlike in other RIα defects, loss of heterozygosity was not observed in AC. The S147G mutation was compared to other expressed PRKAR1A mutations; it led to decreased cAMP and catalytic subunit binding by RIα and increased protein kinase A activity in vitro. Conclusions: In a large family with CNC, one amino acid substitution caused a spectrum of adrenal disease that ranged from lack of manifestations to cancer. PPNAD and AC were the only manifestations of CNC in these patients, in addition to lentigines. These data have implications for counseling patients with CNC and are significant in documenting the first case of AC in the context of PPNAD

  17. Treatment Options by Stage (Adrenocortical Carcinoma)

    MedlinePlus

    ... of Childhood Treatment for more information.) Having certain genetic conditions increases the risk of adrenocortical carcinoma. Anything ... can be a sign of disease. CT scan (CAT scan) : A procedure that makes a series of ...

  18. Skin Pigment

    MedlinePlus

    ... Professional Version Pigment Disorders Overview of Skin Pigment Albinism Vitiligo Hyperpigmentation Melasma Melanin is the brown pigment ... dark-skinned people produce the most. People with albinism have little or no melanin and thus their ...

  19. Origin and Molecular Pathology of Adrenocortical Neoplasms

    PubMed Central

    Bielinska, M.; Parviainen, H.; Kiiveri, S.; Heikinheimo, M.; Wilson, D.B.

    2008-01-01

    Neoplastic adrenocortical lesions are common in humans and several species of domestic animals. Although there are unanswered questions about the origin and evolution of adrenocortical neoplasms, analysis of human tumor specimens and animal models indicates that adrenocortical tumorigenesis involves both genetic and epigenetic alterations. Chromosomal changes accumulate during tumor progression, and aberrant telomere function is one of the key mechanisms underlying chromosome instability during this process. Epigenetic changes serve to expand the size of the uncommitted adrenal progenitor population, modulate their phenotypic plasticity (i.e., responsiveness to extracellular signals), and increase the likelihood of subsequent genetic alterations. Analyses of heritable and spontaneous types of human adrenocortical tumors have documented alterations in either cell surface receptors or their downstream effectors that impact neoplastic transformation. Many of the mutations associated with benign human adrenocortical tumors result in dysregulated cyclic AMP signaling, whereas key factors/signaling pathways associated with adrenocortical carcinomas include dysregulated expression of the IGF2 gene cluster, activation of the Wnt/β-catenin pathway, and inactivation of the p53 tumor suppressor. A better understanding of the factors and signaling pathways involved in adrenal tumorigenesis is necessary to develop targeted pharmacologic and genetic therapies. PMID:19261630

  20. Human Adrenocortical Carcinoma Cell Lines

    PubMed Central

    Wang, Tao; Rainey, William E.

    2011-01-01

    Summary The human adrenal cortex secretes mineralocorticoids, glucocorticoids and adrenal androgens. These steroids are produced from unique cell types located within the three distinct zones of the adrenal cortex. Disruption of adrenal steroid production results in a variety of diseases that can lead to hypertension, metabolic syndrome, infertility and androgen excess. The adrenal cortex is also a common site for the development of adenomas, and rarely the site for the development of carcinomas. The adenomas can lead to diseases associated with adrenal steroid excess, while the carcinomas are particularly aggressive and have a poor prognosis. In vitro cell culture models provide an important tool to examine molecular and cellular mechanisms controlling both the normal and pathologic function of the adrenal cortex. Herein we discuss the human adrenocortical cell lines and their use as model systems for adrenal studies. PMID:21924324

  1. [Nodular regenerative hyperplasia following liver tuberculosis].

    PubMed

    Boursier, Jérôme; Foulet, Armelle; Pilette, Christophe

    2005-10-01

    We reported a case of nodular regenerative hyperplasia revealed by hemorrhage from portal hypertention and ascites in a 81 years old patient. This patient presented two years ago hepatic tuberculosis well documented by liver biopsy. If this patient do not have exhaustive etiologic research of nodular regenerative hyperplasia, the relationship between the tuberculosis infection and the developpement of this nodular regenerative hyperplasia appears highly probable and must be researched. PMID:16435515

  2. ENDOCRINE TUMOURS: The genomics of adrenocortical tumors.

    PubMed

    Faillot, Simon; Assie, Guillaume

    2016-06-01

    The last decade witnessed the emergence of genomics, a set of high-throughput molecular measurements in biological samples. These pan-genomic and agnostic approaches have revolutionized the molecular biology and genetics of malignant and benign tumors. These techniques have been applied successfully to adrenocortical tumors. Exome sequencing identified new major drivers in all tumor types, including KCNJ5, ATP1A1, ATP2B3 and CACNA1D mutations in aldosterone-producing adenomas (APA), PRKACA mutations in cortisol-producing adenomas (CPA), ARMC5 mutations in primary bilateral macronodular adrenocortical hyperplasia (PBMAH) and ZNRF3 mutations in adrenocortical carcinomas (ACC). Moreover, the various genomic approaches - including exome sequencing, transcriptome, miRNome, genome and methylome - converge into a single molecular classification of adrenocortical tumors. Especially for ACC, two main molecular groups have emerged, showing major differences in outcomes. These ACC groups differ by their gene expression profiles, but also by recurrent mutations and specific DNA hypermethylation patterns in the subgroup of poor outcome. The clinical impact of these findings is just starting. The main altered signaling pathways now become therapeutic targets. The molecular groups of diseases individualize robust subtypes within diseases such as APA, CPA, PBMAH and ACC. A revised nosology of adrenocortical tumors should impact the clinical research. Obvious consequences also include genetic counseling for the new genetic diseases such as ARMC5 mutations in PBMAH, and a better prognostication of ACC based on targeted measurements of a few discriminant molecular alterations. Identifying the main molecular groups of adrenocortical tumors by extensively gathering the molecular variations is a significant step forward towards precision medicine. PMID:26739091

  3. Bilateral pigmented villonodular synovitis of the knee

    PubMed Central

    Shah, Samir H.; Porrino, Jack A.; Green, John R.; Chew, Felix S.

    2015-01-01

    Pigmented villonodular synovitis is a disorder resulting in a villous, nodular, or villonodular proliferation of the synovium, with pigmentation related to the presence of hemosiderin. These lesions are almost exclusively benign with rare reports of malignancy. Pigmented villonodular synovitis can occur in a variety of joints and at any age but most often occurs within the knee in the young adult. Pigmented villonodular synovitis is a rare disease entity, and bilateral synchronous or metachronous involvement of a joint is even more uncommon, with few reports previously described in the literature. We present a case of pigmented villonodular synovitis involving both the right and left knee in the same patient, with radiographic imaging, magnetic resonance imaging, photograph and video intraoperative imaging, and pathologic correlation. PMID:26649121

  4. Adrenocortical suppression in cats given megestrol acetate.

    PubMed

    Chastain, C B; Graham, C L; Nichols, C E

    1981-12-01

    Megestrol acetate was given orally to 8 cats at a dose of 2.5 mg every other day for 2 weeks and to 8 cats at a dose of 5.0 mg every day for 2 weeks. Four cats were designated nontreated controls. Pre-ACTH-stimulated plasma concentrations of cortisol (hydrocortisone) and ACTH-stimulated cortisol and tolerance to large-dose glucose infusion (IV) were determined on each of the 20 cats given megestrol acetate. Cats were restrained with acepromazine maleate and ketamine hydrochloride during blood sample collection and large-dose glucose infusion. Adrenocortical function and tolerance to large-dose glucose infusion were reevaluated for 4 weeks--after 1st and 2nd weeks of megestrol acetate treatment of the treated groups, and after 1st and 2nd weeks when treatment was stopped (ie, experiment weeks 3 and 4). Each week a cat from the control group and 2 cats from the 2 treated groups were selected to determine the changes occurring during the experiment for that week; after collection of plasma samples, each week's 5 selected cats were euthanatized and necropsied. Significant impairment of adrenocortical function and alteration of adrenocortical morphology occurred with both treated groups. The most severe adrenocortical alterations occurred in the cats 1 week after megestrol acetate was no longer given (ie, experiment week 3). Megestrol acetate-induced adrenocortical suppression contributed to the death of 1 cat. It was concluded that if stress occurs to cats on treatment or soon after treatment with megestrol acetate, glucocorticoids should be supplemented. The effects of megestrol acetate on glucose tolerance were overshadowed by the unforeseen intolerance caused by chemical restraint with acepromazine maleate and ketamine hydrochloride. PMID:6280517

  5. Giant adrenal pseudocyst harbouring adrenocortical cancer

    PubMed Central

    Wilkinson, Michael; Fanning, Deirdre Mary; Moloney, James; Flood, Hugh

    2011-01-01

    The authors report a very rare case of adreno-cortical carcinoma arising in a giant adrenal pseudocyst. A 64-year-old woman presented to the emergency department with a 6 week history of progressively worsening severe left abdominal pain, anorexia, anergia and constipation. On examination, she was cachectic with tenderness over the left abdomen and flank. Medical history was significant for gastritis and anaemia. During her investigation, a well-defined para-renal 12×6 centimetre multi-loculated cyst, of uncertain origin was identified on CT. Ultrasound-guided biopsy was not diagnostic. MRI showed the cyst to be likely adrenal in origin. Serum and urinary catecholamines were unremarkable. At laparotomy an unresectable large, tense, fixed, cystic mass was seen to occupy the left side of the abdomen. The cyst was de-roofed. Pathology showed a high-grade poorly differentiated adreno-cortical carcinoma with a pseudo-capsule. She died 2 months postoperatively. PMID:22679267

  6. Adjuvant and Definitive Radiotherapy for Adrenocortical Carcinoma

    SciTech Connect

    Sabolch, Aaron; Feng, Mary; Griffith, Kent; Hammer, Gary; Doherty, Gerard; Ben-Josef, Edgar

    2011-08-01

    Purpose: To evaluate the impact of both adjuvant and definitive radiotherapy on local control of adrenocortical carcinoma. Methods and Materials: Outcomes were analyzed from 58 patients with 64 instances of treatment for adrenocortical carcinoma at the University of Michigan's Multidisciplinary Adrenal Cancer Clinic. Thirty-seven of these instances were for primary disease, whereas the remaining 27 were for recurrent disease. Thirty-eight of the treatment regimens involved surgery alone, 10 surgery plus adjuvant radiotherapy, and 16 definitive radiotherapy for unresectable disease. The effects of patient, tumor, and treatment factors were modeled simultaneously using multiple variable Cox proportional hazards regression for associations with local recurrence, distant recurrence, and overall survival. Results: Local failure occurred in 16 of the 38 instances that involved surgery alone, in 2 of the 10 that consisted of surgery plus adjuvant radiotherapy, and in 1 instance of definitive radiotherapy. Lack of radiotherapy use was associated with 4.7 times the risk of local failure compared with treatment regimens that involved radiotherapy (95% confidence interval, 1.2-19.0; p = 0.030). Conclusions: Radiotherapy seems to significantly lower the risk of local recurrence/progression in patients with adrenocortical carcinoma. Adjuvant radiotherapy should be strongly considered after surgical resection.

  7. Alterations of Phosphodiesterases in Adrenocortical Tumors.

    PubMed

    Hannah-Shmouni, Fady; Faucz, Fabio R; Stratakis, Constantine A

    2016-01-01

    Alterations in the cyclic (c)AMP-dependent signaling pathway have been implicated in the majority of benign adrenocortical tumors (ACTs) causing Cushing syndrome (CS). Phosphodiesterases (PDEs) are enzymes that regulate cyclic nucleotide levels, including cyclic adenosine monophosphate (cAMP). Inactivating mutations and other functional variants in PDE11A and PDE8B, two cAMP-binding PDEs, predispose to ACTs. The involvement of these two genes in ACTs was initially revealed by a genome-wide association study in patients with micronodular bilateral adrenocortical hyperplasia. Thereafter, PDE11A or PDE8B genetic variants have been found in other ACTs, including macronodular adrenocortical hyperplasias and cortisol-producing adenomas. In addition, downregulation of PDE11A expression and inactivating variants of the gene have been found in hereditary and sporadic testicular germ cell tumors, as well as in prostatic cancer. PDEs confer an increased risk of ACT formation probably through, primarily, their action on cAMP levels, but other actions might be possible. In this report, we review what is known to date about PDE11A and PDE8B and their involvement in the predisposition to ACTs. PMID:27625633

  8. Alterations of Phosphodiesterases in Adrenocortical Tumors

    PubMed Central

    Hannah-Shmouni, Fady; Faucz, Fabio R.; Stratakis, Constantine A.

    2016-01-01

    Alterations in the cyclic (c)AMP-dependent signaling pathway have been implicated in the majority of benign adrenocortical tumors (ACTs) causing Cushing syndrome (CS). Phosphodiesterases (PDEs) are enzymes that regulate cyclic nucleotide levels, including cyclic adenosine monophosphate (cAMP). Inactivating mutations and other functional variants in PDE11A and PDE8B, two cAMP-binding PDEs, predispose to ACTs. The involvement of these two genes in ACTs was initially revealed by a genome-wide association study in patients with micronodular bilateral adrenocortical hyperplasia. Thereafter, PDE11A or PDE8B genetic variants have been found in other ACTs, including macronodular adrenocortical hyperplasias and cortisol-producing adenomas. In addition, downregulation of PDE11A expression and inactivating variants of the gene have been found in hereditary and sporadic testicular germ cell tumors, as well as in prostatic cancer. PDEs confer an increased risk of ACT formation probably through, primarily, their action on cAMP levels, but other actions might be possible. In this report, we review what is known to date about PDE11A and PDE8B and their involvement in the predisposition to ACTs.

  9. Nodular fasciitis with degeneration and regression.

    PubMed

    Yanagisawa, Akihiro; Okada, Hideki

    2008-07-01

    Nodular fasciitis is a benign reactive proliferation that is frequently misdiagnosed as a sarcoma. This article describes a case of nodular fasciitis of 6-month duration located in the cheek, which degenerated and spontaneously regressed after biopsy. The nodule was fixed to the zygoma but was free from the overlying skin. The mass was 3.0 cm in diameter and demonstrated high signal intensity on T2-weighted magnetic resonance imaging. A small part of the lesion was biopsied. Pathological and immunohistochemical examinations identified the nodule as nodular fasciitis with myxoid histology. One month after the biopsy, the mass showed decreased signal intensity on T2-weighted images and measured 2.2 cm in size. The signal on T2-weighted images showed time-dependent decreases, and the mass continued to reduce in size throughout the follow-up period. The lesion presented as hypointense to the surrounding muscles on T2-weighted images and was 0.4 cm in size at 2 years of follow-up. This case demonstrates that nodular fasciitis with myxoid histology can change to that with fibrous appearance gradually with time, thus bringing about spontaneous regression. Degeneration may be involved in the spontaneous regression of nodular fasciitis with myxoid appearance. The mechanism of regression, unclarified at present, should be further studied. PMID:18650753

  10. Pigmented casts.

    PubMed

    Miteva, Mariya; Romanelli, Paolo; Tosti, Antonella

    2014-01-01

    Pigmented casts have been reported with variable frequency in scalp biopsies from alopecia areata, trichotillomania, chemotherapy-induced alopecia and postoperative (pressure induced) alopecia. Their presence and morphology in other scalp disorders has not been described. The authors assessed for the presence and morphology of pigmented casts in 308 transversely bisected scalp biopsies from nonscarring and scarring alopecia, referred to the Department of Dermatology, University of Miami within a year. The pigmented casts were present in 21 of 29 cases of alopecia areata (72%), 7 of 7 cases of trichotillomania (100%), 1 case of friction alopecia, 4 of 28 cases of central centrifugal cicatricial alopecia (14%), and 4 of 4 cases of dissecting cellulitis (100%). They did not show any distinguishing features except for the morphology in trichotillomania, which included twisted, linear (zip), and "button"-like pigment aggregation. The linear arrangement was found also in friction alopecia and dissecting cellulitis. Pigmented casts in the hair canals of miniaturized/vellus hairs was a clue to alopecia areata. Pigmented casts can be observed in biopsies of different hair disorders, but they are not specific for the diagnosis. Horizontal sections allow to better assess their morphology and the follicular level of presence of pigmented casts, which in the context of the other follicular findings may be a clue to the diagnosis. PMID:23823025

  11. Laparoscopic Adrenalectomy for Large Adrenocortical Carcinoma

    PubMed Central

    al Qadhi, Hani; al Wahaibi, Khalifa; Rizvi, Syed G.

    2015-01-01

    Background: Adrenocortical cancer (ACC) is a rare disease that is difficult to treat. Laparoscopic adrenalectomy (LA) is performed, even for large adrenocortical carcinomas. However, the oncological effectiveness of LA remains unclear. This review presents the current knowledge of the feasibility and oncological effectiveness of laparoscopic surgery for ACC, with an analysis of data for outcomes and other parameters. Database: A systematic review of the literature was performed by searching the PubMed and Medline databases for all relevant articles in English, published between January 1992 and August 2014 on LA for adrenocortical carcinoma. Discussion: The search resulted in retrieval of 29 studies, of which 10 addressed the outcome of LA versus open adrenalectomy (OA) and included 844 patients eligible for this review. Among these, 206 patients had undergone LA approaches, and 638 patients had undergone OA. Among the 10 studies that compared the outcomes obtained with LA and OA for ACC, 5 noted no statistically significant difference between the 2 groups in the oncological outcomes of recurrence and disease-free survival, whereas the remaining 5 reported inferior outcomes in the LA group. Using a paired t test for statistical analysis, except for tumor size, we found no significant difference in local recurrence, peritoneal carcinomatosis, positive resection margin, and time to recurrence between the LA and OA groups. The overall mean tumor size in patients undergoing LA and OA was 7.1 and 11.2 cm, respectively (P = .0003), and the mean overall recurrence was 61.5 and 57.9%, respectively. The outcome of LA is believed to depend to a large extent on the size and stage of the lesion (I and II being favorable) and the surgical expertise in the center where the patient undergoes the operation. However, the present review shows no difference in the outcome between the 2 approaches across all stages. A poor outcome is likely to result from inadequate surgery

  12. [Retroperitoneal nodular fasciitis: analysis of a case].

    PubMed

    Fabbro, M A; Costa, L; Cimaglia, M L; Donadio, P; Spata, E; Dante, S

    1995-01-01

    A case of nodular fasciitis occurring in a 14-year-old girl is described and the clinical-pathological profile and the diagnostic problems are analyzed. The Authors believe this report useful to be reported for the relative rarity of the disease, especially in children, the very great dimension and the unusual retroperitoneal localization. PMID:8685002

  13. Nodular tertiary syphilis in an immunocompetent patient*

    PubMed Central

    Bittencourt, Maraya de Jesus Semblano; de Brito, Arival Cardoso; Nascimento, Bianca Angelina Macêdodo; Carvalho, Alessandra Haber; Drago, Marion Guimarães

    2016-01-01

    Acquired syphilis can be divided into primary, secondary, latent, and tertiary stages. About 25% of patients with untreated primary syphilis will develop late signs that generally occur after three to five years, with involvement of several organs. The authors present an immunocompetent female who developed a tertiary stage syphilis presenting with long-standing nodular plaques. PMID:27579755

  14. Nodular tertiary syphilis in an immunocompetent patient.

    PubMed

    Bittencourt, Maraya de Jesus Semblano; Brito, Arival Cardoso de; Nascimento, Bianca Angelina Macêdodo; Carvalho, Alessandra Haber; Drago, Marion Guimarães

    2016-01-01

    Acquired syphilis can be divided into primary, secondary, latent, and tertiary stages. About 25% of patients with untreated primary syphilis will develop late signs that generally occur after three to five years, with involvement of several organs. The authors present an immunocompetent female who developed a tertiary stage syphilis presenting with long-standing nodular plaques. PMID:27579755

  15. Nodular lymphocyte-predominant Hodgkin lymphoma.

    PubMed

    Savage, Kerry J; Mottok, Anja; Fanale, Michelle

    2016-07-01

    Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma with distinct clinicopathologic features. It is typified by the presence of lymphocyte predominant (LP) cells, which are CD20(+) but CD15(-) and CD30(-) and are found scattered amongst small B lymphocytes arranged in a nodular pattern. Despite frequent and often late or multiple relapses, the prognosis of NLPHL is very favorable. There is an inherent risk of secondary aggressive non-Hodgkin lymphoma (NHL) and studies support that risk is highest in those with splenic involvement at presentation. Given disease rarity, the optimal management is unclear and opinions differ as to whether treatment paradigms should be similar to or differ from those for classical Hodgkin lymphoma (CHL). This review provides an overview of the existing literature describing pathological subtypes, outcome and treatment approaches for NLPHL. PMID:27496311

  16. Nodular pulmonary amyloidosis associated with asbestos exposure.

    PubMed

    Hiroshima, K; Ohwada, H; Ishibashi, M; Yamamoto, N; Tamiya, N; Yamaguchi, Y

    1996-01-01

    A 71 year old man was admitted for the purpose of diagnosis of a right solitary pulmonary nodule. The size of the nodule was 18 x 18 mm in diameter 2 years ago, but it has become large, 25 x 25 mm in diameter. The nodule was resected by thoracotomy. Microscopically, eosinophilic amorphous, acellular substances were surrounded by inflammatory infiltrates. It stained with Congo red stain and showed green birefringence with polarizing microscopy. Amyloid fibrils were observed electron microscopically. Asbestos bodies were observed in the lung parenchyma around the nodule. This case shows that a nodule in nodular pulmonary amyloidosis can grow gradually and suggests the possibility of asbestos fibers as one of the etiologic factors in nodular pulmonary amyloidosis. PMID:10846552

  17. Nodular secondary syphilis in a woman.

    PubMed

    Glatz, M; Achermann, Y; Kerl, K; Bosshard, P P; Cozzio, A

    2013-01-01

    We report the case of a 21-year-old woman with symmetrically distributed, ulcerated nodules and plaques on the face, neck and arms. Initial differential diagnoses included pyoderma or sarcoidosis based on the clinical presentation and histopathology with non-caseating granulomas. After inefficient treatment with topical and systemic fusidic acid and steroids, we diagnosed nodular secondary syphilis owing to positive serology and immunohistochemical staining of Treponema pallidum in lesional skin. After treatment with benzathine penicillin, skin lesions improved and antibody titres declined significantly within 3 months. Nodular skin lesions in secondary syphilis are rare with 15 reported cases within the last 20 years. Furthermore, the granulomatous histology is often misleading. Our patient's case suggests that the physicians should be aware of syphilis as a possible differential diagnosis also in patients outside a high-risk population for sexually transmitted diseases and with an unusual clinical presentation. PMID:23661656

  18. Directional Solidification of Nodular Cast Iron

    NASA Technical Reports Server (NTRS)

    Curreri, P. A.; Stefanescu, D. M.; Hendrix, J. C.

    1987-01-01

    Cerium enhances formation of graphite nodules. Preliminary experiments in directional solidification of cast iron shows quantitative correlation of graphite microstructure with growth rate and thermal gradient, with sufficient spheroidizing element to form spheroidal graphite under proper thermal conditions. Experimental approach enables use of directional solidification to study solidification of spheriodal-graphite cast iron in low gravity. Possible to form new structural materials from nodular cast iron.

  19. Unusual late nodular presentation of secondary syphilis.

    PubMed

    Lanjouw, E; van der Meijden, W I; den Hollander, J C; Neumann, H A M

    2009-04-01

    A 20-year-old man presented with a five-week history of an eruption of papules and nodules disseminated over his body and face. We propose that this patient has a late form of secondary syphilis with a nodular, granulomatous inflammation in urgent need of treatment. Otherwise late irreversible sequelae could develop and unwanted possible further sexual transmission could take place. PMID:19304976

  20. Birthmarks - pigmented

    MedlinePlus

    ... its own appearance: Cafe-au-lait spots are light tan, the color of coffee with milk. Moles are small clusters of colored skin cells. Mongolian spots (also called Mongolian blue ... dark or light skin Growth of hair from pigmented skin Skin ...

  1. Adrenocortical Gap Junctions and Their Functions

    PubMed Central

    Bell, Cheryl L.; Murray, Sandra A.

    2016-01-01

    Adrenal cortical steroidogenesis and proliferation are thought to be modulated by gap junction-mediated direct cell–cell communication of regulatory molecules between cells. Such communication is regulated by the number of gap junction channels between contacting cells, the rate at which information flows between these channels, and the rate of channel turnover. Knowledge of the factors regulating gap junction-mediated communication and the turnover process are critical to an understanding of adrenal cortical cell functions, including development, hormonal response to adrenocorticotropin, and neoplastic dedifferentiation. Here, we review what is known about gap junctions in the adrenal gland, with particular attention to their role in adrenocortical cell steroidogenesis and proliferation. Information and insight gained from electrophysiological, molecular biological, and imaging (immunocytochemical, freeze fracture, transmission electron microscopic, and live cell) techniques will be provided. PMID:27445985

  2. Serum and growth factor requirements for proliferation of human adrenocortical cells in culture: comparison with bovine adrenocortical cells.

    PubMed

    Hornsby, P J; Sturek, M; Harris, S E; Simonian, M H

    1983-11-01

    Although bovine adrenocortical cells proliferate readily in cell culture, proliferation of fetal or adult human adrenocortical cells has been observed to be limited and preparation of pure proliferating cultures of human adrenocortical cells has not been reported. The growth requirements of fetal human definitive zone adrenocortical cells in culture were compared to the established requirements of bovine adrenocortical cells. The medium used was 1:1 Ham's F12 and Dulbecco's modified Eagle's medium supplemented with transferrin and insulin. Earlier experiments showed that human cells had a greater proliferative response to horse serum than to fetal bovine serum, whereas the opposite was true for bovine cells. When plated on fibronectin-coated dishes and exposed to varying concentrations of horse serum in the presence of 100 ng/ml fibroblast growth factor (FGF), increasing cell growth was observed up to a serum concentration of 50%. When 50% fetal bovine serum was used instead of horse serum proliferation was less. In contrast, bovine adrenocortical cells showed a maximal proliferative response to either fetal bovine serum or horse serum at 10%. Human adrenocortical cells thus have a very high requirement for serum; 50% is the highest level that may be practically used, but the shape of the dose-response curve suggests that this concentration is still suboptimal. Growth was less in the absence of FGF. Epidermal growth factor can partially substitute for FGF. No response to 100 nM placental lactogen was observed. Less growth was observed when dishes were not coated with fibronectin. The factors present in horse serum that are evidently needed in high amounts by human cells are unknown. Despite this lack of knowledge, use of 50% horse serum enabled long-term growth of human adrenocortical cells that are pure by the criterion of retraction in response to ACTH. Nonadrenocortical cells do not show a retraction response. Such long-term cultures may be useful in studies of

  3. Therapeutic considerations for severe nodular acne.

    PubMed

    Newman, Marissa D; Bowe, Whitney P; Heughebaert, Carol; Shalita, Alan R

    2011-02-01

    Severe nodular acne, defined as grade 4 or 5 acne on the Investigator's Static Global Assessment scale, is a skin condition characterized by intense erythema, inflammation, nodules, cysts, and scarring. Both the well known risk of physical scarring and the more recent recognition that acne can be a chronic, psychologically distressing disease with significant adverse effects on a patient's quality of life, have prompted earlier, more aggressive treatment with more effective medications, in the hope of preventing progression to more severe, nodular forms of the disease. Oral antibacterials, primarily tetracyclines, have long been the first-line therapy for severe nodular acne, which frequently remained refractory to therapy. However, concerns of antibacterial adverse effects, patient adherence, and antimicrobial resistance prompted the search for alternate therapies and combinations thereof in order to target the multifactorial pathogenesis of the disease. Isotretinoin, an oral retinoid introduced in 1982, has since become the gold standard therapy in severe acne and has revolutionized its treatment. Several adjunctive agents exist. Oral antibacterials are indicated as an alternative for patients with severe acne who cannot tolerate oral retinoids, or for whom a contraindication exists. In order to prevent bacterial resistance, antibacterials should always be used in combination with benzoyl peroxide, a nonantibiotic antimicrobial agent with anti-inflammatory activity. Topical retinoids are often added to this regimen. In women, hormonal agents, which include oral contraceptives, spironolactone, and oral corticosteroids, and, in Europe, cyproterone acetate, may be used as monotherapy or concomitantly with isotretinoin. For rapid treatment of inflammatory nodules, intralesional corticosteroids are effective. These treatment modalities have been studied, refined, and combined in novel ways in order to target the multifactorial pathogenesis of the disease, and in this

  4. Nodular amyloidosis derived from keratinocytes: an unusual type of primary localized cutaneous nodular amyloidosis.

    PubMed

    Cornejo, Kristine M; Lagana, Frances J; Deng, April

    2015-11-01

    Primary, localized cutaneous amyloidosis includes macular, lichen, and nodular (tumefactive) types in which the amyloid deposits are limited to the dermis without systemic involvement. The material in lichen and macular amyloidosis is derived from epidermal keratinocytes [keratinocyte-derived amyloid (AK)], whereas that in nodular amyloidosis is derived from immunoglobulin light-chains amyloid (AL). Primary, localized cutaneous nodular amyloidosis (PLCNA) is a form of primary, localized cutaneous amyloidosis that has been associated with a risk of progression to systemic amyloidosis. We report an unusual case of nodular AK-type amyloid deposited in the dermis of the feet. The patient is a 60-year-old woman with asymptomatic verrucoid-like lesions present around the medial and lateral aspects of the bilateral heels for 1-2 years. A biopsy showed massive deposition of eosinophilic amorphous material in the papillary and reticular dermis. The material stained positive for Congo red with apple-green birefringence on polarized light. It was also positive for pan-cytokeratin and negative for kappa and lambda light-chain immunostains. An extensive workup was negative for systemic involvement. Lipid chromatography tandem mass spectrometry confirmed that the deposition was AK-type amyloid. We believe that this is the first case of PLCNA with AK deposition. This entity should be included in the differential diagnosis of PLCNA so that an extensive systemic workup may be avoided. PMID:26485243

  5. Retinal pigment epithelium in incontinentia pigmenti.

    PubMed

    Mensheha-Manhart, O; Rodrigues, M M; Shields, J A; Shannon, G M; Mirabelli, R P

    1975-04-01

    An 18-month-old white girl with incontinentia pigmenti presented clinically with leukokoria of the right eye. B-scan ultrasound demonstrated a retrolental mass consistent with a detached retina. Histologic examination of the skin revealed changes compatible with the intermediate verrucous phase of the disease. Microscopic examination of the right eye showed retinal detachment and nodular proliferation of the retinal pigment epithelium. The nodules contained macrophages laden with melanin and lipofuscin. An unusually large amount of lipofuscin was present for a child of this age. The basic pigmentary abnormality may affect the retinal pigment epithelium, resulting in changes in the overlying neurosensory retina that may lead to the retinal dysplasia or retinal detachemnt often associated with this condition. PMID:1119517

  6. Rare cause of pleural nodularity: Splenosis.

    PubMed Central

    Gezer, Suat; Gülhan, S. S. Erkmen; Altinok, Tamer; Agaçkiran, Yetkin; Tastepe, A. Irfan

    2006-01-01

    Splenosis is a rare condition described as ectopic splenic tissue implantation generally after a splenic rupture. A 35-year-old male patient who had a history of splenectomy operation due to gunshot wound seven years ago was referred to our hospital with complaints, including exhaustion, sweating and shortness of breath. Thoracic computed tomography of the patient showed nodular pleural thickenings at the level of the left lower lobe, which proved to be unrelated with the presenting symptoms. The patient underwent a minithoracotomy for diagnosis and treatment. During the intraoperative observation, dark-colored, soft, multiple nodular lesions with a biggest size of 2 cm inside the visceral pleura over an area of 5 x 10 cm in dimension were observed. Also, a few tiny nodules in the lung parenchyma approximately 1-cm deep to the pleural nodules were palpated. The lesions were excised. The histopathological examination of the specimen showed splenic tissue in the lung parenchyma and pleura, so the lesions were accepted as splenosis. Pleuropulmonary splenosis, which develops generally after simultaneous rupture of the diaphragma and spleen, is a very rare condition. Most of the patients are asymptomatic and the lesions are detected accidentally. If the diagnosis can be made preoperatively, surgical excision is not needed. Images Figure 1 Figure 2 PMID:16916134

  7. Extramitochondrial OPA1 and adrenocortical function.

    PubMed

    Fülöp, László; Rajki, Anikó; Katona, Dávid; Szanda, Gergö; Spät, András

    2013-12-01

    We have previously described that silencing of the mitochondrial protein OPA1 enhances mitochondrial Ca(2+) signaling and aldosterone production in H295R adrenocortical cells. Since extramitochondrial OPA1 (emOPA1) was reported to facilitate cAMP-induced lipolysis, we hypothesized that emOPA1, via the enhanced hydrolysis of cholesterol esters, augments aldosterone production in H295R cells. A few OPA1 immunopositive spots were detected in ∼40% of the cells. In cell fractionation studies OPA1/COX IV (mitochondrial marker) ratio in the post-mitochondrial fractions was an order of magnitude higher than that in the mitochondrial fraction. The ratio of long to short OPA1 isoforms was lower in post-mitochondrial than in mitochondrial fractions. Knockdown of OPA1 failed to reduce db-cAMP-induced phosphorylation of hormone-sensitive lipase (HSL), Ca(2+) signaling and aldosterone secretion. In conclusion, OPA1 could be detected in the post-mitochondrial fractions, nevertheless, OPA1 did not interfere with the cAMP - PKA - HSL mediated activation of aldosterone secretion. PMID:23906536

  8. [Diagnostic benefits of adrenocortical scintigraphy in hepatic adrenal rest tumor].

    PubMed

    Ishida, Kosuke; Horii, Rika; Yamashita, Tatsuya; Arai, Kuniaki; Yamashita, Taro; Kagaya, Takashi; Sakai, Yoshio; Mizukoshi, Eishiro; Honda, Masao; Kaneko, Shuichi

    2014-10-01

    An 81-year-old female was referred to our hospital for the examination of an S7 liver tumor. The tumor was suspected to be a hepatic adrenal rest tumor (HART) based on ultrasonography, dynamic CT, Gd-EOB-DTPA-enhanced MRI, and CT during abdominal angiography. After various hormonal tests, the tumor was confirmed as hormonally non-functional. The diagnosis of HART was confirmed based on (131)I-adosterol accumulation in the tumor by adrenocortical scintigraphy. The resected tumor was histologically compatible with HART, and it may have been able to produce cortisol based on the immunohistochemical findings of various adrenocortical hormone metabolic enzymes. Adrenocortical scintigraphy may thus be useful in diagnosing HART. PMID:25283230

  9. Skin Pigmentation Disorders

    MedlinePlus

    Pigmentation means coloring. Skin pigmentation disorders affect the color of your skin. Your skin gets its color from a pigment called melanin. Special cells in the skin make melanin. When these cells become damaged or ...

  10. Adrenocortical involution in rats during oestrus synchronisation with medroxyprogesterone.

    PubMed

    Fell, B F; Campbell, R M; Dinsdale, D

    1977-05-01

    Daily treatment of female rats with medroxyprogesterone acetate in aqueous suspension resulted in adrenocortical atrophy. The doses given were those used for oestrus synchronisation. Intramuscular injections of 2-0 mg medroxyprogesterone acetate were used to investigate the atrophic process. Adrenocortical involution was associated with extensive single cell deletion (apoptosis). It is suggested that theses changes were due to suppression of pituitary ACTH secretion. The cytological changes support the concept that single cell death plays an important role in organ remodelling. Biochemical determinations of DNA, RNA, protein and dry matter, and histological examination, did not reveal significant changes in the liver. PMID:560035

  11. Pitfalls in the management of acute adrenocortical insufficiency: discussion paper.

    PubMed Central

    Waise, A; Young, R J

    1989-01-01

    In patients with acute adrenocortical insufficiency prompt recognition and treatment may be life-saving. Treatment should be initiated immediately before confirmation of the diagnosis. As shown by these case reports, junior staff on acute medical and surgical services, to whom these patients usually first present, may not appreciate that (a) hyponatraemia and hyperkalaemia, in the absence of renal failure, should immediately suggest the diagnosis of adrenal insufficiency and (b) treatment should precede confirmation of the diagnosis. Attempts to correct hyperkalaemia due to adrenocortical insufficiency with insulin and infusions of dextrose is inappropriate and potentially dangerous but seems to be a not unusual mistake. PMID:2614769

  12. Chronic effects of mercuric chloride ingestion on rat adrenocortical function

    SciTech Connect

    Agrawal, R.; Chansouria, J.P.N. )

    1989-09-01

    Mercurial contamination of environment has increased. Mercury accumulates in various organs and adversely affects their functions. Some of the most prominent toxic effects of inorganic mercury compounds include neurotoxicity, hepatotoxicity and nephrotoxicity. Besides this, mercury has also been reported to affect various endocrine glands like pituitary, thyroid, gonadal and adrenal glands. There have been no reports on the toxic effects of chronic oral administration of varying doses of mercuric chloride on adrenocortical function in albino rats. The present work was undertaken to study the adrenocortical response to chronic oral administration of mercuric chloride of varying dose and duration in albino rats.

  13. Metabolic reprogramming: a new relevant pathway in adult adrenocortical tumors

    PubMed Central

    Longatto-Filho, Adhemar; Faria, André M.; Fragoso, Maria C. B. V.; Lovisolo, Silvana M.; Lerário, Antonio M.; Almeida, Madson Q.

    2015-01-01

    Adrenocortical carcinomas (ACCs) are complex neoplasias that may present unexpected clinical behavior, being imperative to identify new biological markers that can predict patient prognosis and provide new therapeutic options. The main aim of the present study was to evaluate the prognostic value of metabolism-related key proteins in adrenocortical carcinoma. The immunohistochemical expression of MCT1, MCT2, MCT4, CD147, CD44, GLUT1 and CAIX was evaluated in a series of 154 adult patients with adrenocortical neoplasia and associated with patients' clinicopathological parameters. A significant increase in was found for membranous expression of MCT4, GLUT1 and CAIX in carcinomas, when compared to adenomas. Importantly MCT1, GLUT1 and CAIX expressions were significantly associated with poor prognostic variables, including high nuclear grade, high mitotic index, advanced tumor staging, presence of metastasis, as well as shorter overall and disease free survival. In opposition, MCT2 membranous expression was associated with favorable prognostic parameters. Importantly, cytoplasmic expression of CD147 was identified as an independent predictor of longer overall survival and cytoplasmic expression of CAIX as an independent predictor of longer disease-free survival. We provide evidence for a metabolic reprogramming in adrenocortical malignant tumors towards the hyperglycolytic and acid-resistant phenotype, which was associated with poor prognosis. PMID:26587828

  14. Pigmented eccrine poroma: report of an atypical case with the use of dermoscopy*

    PubMed Central

    de Almeida, Fabiana Carvalho; Cavalcanti, Silvana Maria de Morais; Medeiros, Ângela Cristina Rapela; Teixeira, Márcia Almeida Galvão

    2013-01-01

    Poromas are uncommon benign neoplasms originating from the terminal ductal portion of the sweat glands, mainly characterized by skin-colored or pink pa pules or nodules, usually on the extremities. Due to their rarity, the pigmented form clinical hypothesis is hardly ever suggested and psychopathology is fundamental. We report a case of pigmented eccrine poroma in the right palmer area, a location considered atypical. We stress the importance of dermoscopy as a method for diagnosis of poromas, especially in the differential diagnosis with other pigmented nodular-popular lesions. PMID:24173189

  15. DNA Methylation Profiling Identifies Global Methylation Differences and Markers of Adrenocortical Tumors

    PubMed Central

    Rechache, Nesrin S.; Wang, Yonghong; Stevenson, Holly S.; Killian, J. Keith; Edelman, Daniel C.; Merino, Maria; Zhang, Lisa; Nilubol, Naris; Stratakis, Constantine A.; Meltzer, Paul S.

    2012-01-01

    Context: It is not known whether there are any DNA methylation alterations in adrenocortical tumors. Objective: The objective of the study was to determine the methylation profile of normal adrenal cortex and benign and malignant adrenocortical tumors. Methods: Genome-wide methylation status of CpG regions were determined in normal (n = 19), benign (n = 48), primary malignant (n = 8), and metastatic malignant (n = 12) adrenocortical tissue samples. An integrated analysis of genome-wide methylation and mRNA expression in benign vs. malignant adrenocortical tissue samples was also performed. Results: Methylation profiling revealed the following: 1) that methylation patterns were distinctly different and could distinguish normal, benign, primary malignant, and metastatic tissue samples; 2) that malignant samples have global hypomethylation; and 3) that the methylation of CpG regions are different in benign adrenocortical tumors by functional status. Normal compared with benign samples had the least amount of methylation differences, whereas normal compared with primary and metastatic adrenocortical carcinoma samples had the greatest variability in methylation (adjusted P ≤ 0.01). Of 215 down-regulated genes (≥2-fold, adjusted P ≤ 0.05) in malignant primary adrenocortical tumor samples, 52 of these genes were also hypermethylated. Conclusions: Malignant adrenocortical tumors are globally hypomethylated as compared with normal and benign tumors. Methylation profile differences may accurately distinguish between primary benign and malignant adrenocortical tumors. Several differentially methylated sites are associated with genes known to be dysregulated in malignant adrenocortical tumors. PMID:22472567

  16. Nodular Fasciitis of the Chest in a Young Woman

    PubMed Central

    Seo, Hong Joo; Ryu, Sang Wan; Lee, Mi Ja; Kim, Dong Hun; Kim, Hyung Ho

    2016-01-01

    Nodular fasciitis is a benign reactive proliferation that usually involves the deep fascia. Although it is relatively common in the adult population, it is often misdiagnosed as sarcoma due to its rapid growth and pathological features. It rarely presents as a chest wall tumor in young patients. Here, we report a case of nodular fasciitis involving the chest wall of an 18-year-old woman and its surgical management. This case underscores the need to consider nodular fasciitis in the differential diagnosis of chest wall tumors in young patients. PMID:26889452

  17. Retroperitoneal nodular fasciitis: magnetic resonance imaging (MRI) and pathological features.

    PubMed

    Meduri; Zuiani; Del Frate C; Bazzocchi

    1998-07-01

    A case of pelvic nodular fasciitis, with particular reference to its peculiar radiological and pathological features is described. Only a few cases of pelvic nodular fasciitis are reported in the English literature and at the best of our knowledge, this is the first case of retroperitoneal origin. This report discusses the role of MRI in the characterization of soft tissue masses. No specific MRI findings of nodular fasciitis were identified and MRI doesn't add any contribution to the differential diagnosis between benign and malignant lesions. As a consequence, the histopathological examination is necessary for a definitive diagnosis. PMID:10358366

  18. Nodular fasciitis of the oro-facial region.

    PubMed

    Subramaniam, Priya; Balakrishna, Ramdas; Mahendra, P; Gilhotra, K

    2012-04-01

    Nodular fasciitis is a benign proliferative spindle-cell lesion that presents as a rapidly growing mass frequently being mistaken for a sarcoma. A rare presentation and treatment of nodular fasciitis in the cheek of an 8-year-old boy is described here. He came with a chief complaint of swelling in the left cheek since 1 month which rapidly increased to the size of a marble, over a period of 1 month. Surgical excision of the lesion was planned under general anesthesia following which the surgical site was closed with resorbable sutures. Based on the history, clinical picture, and histopathological examination, the lesion was diagnosed as nodular fasciitis. Although infrequent in both children and the oral mucosa, nodular fasciitis should be considered in the differential diagnosis of facial tumors in infants and young children. PMID:22629057

  19. Progressive Nodular Histiocytosis Associated with Eale's Disease

    PubMed Central

    Williams, Abhilasha; Thomas, Abraham G; Kwatra, Kanwardeep Singh; Jain, Kunal

    2015-01-01

    Progressive nodular histiocytosis (PNH) is a rare normolipemic macrophage disorder and belongs to a subgroup of non-Langerhans cell histiocytosis (LCHs) which is characterized by a progressive course with no sign of spontaneous resolution but without systemic involvement. We report a 30-year-old gentleman who presented with skin lesions all over the body associated with gradual bilateral painless loss of vision. On examination, approximately 30 to 40, skin-colored, firm, non-tender papules and nodules were noted over the body especially on the face and trunk. A skin biopsy revealed a cellular tumor in the dermis composed of oval to spindle-shaped cells, positive for CD68 but negative for S-100, CD34, CD21, CD35 and HMB45, supporting a diagnosis of spindle cell histiocytic tumor. Ophthalmic examination revealed a generalized arteriolar attenuation in both eyes. He received Tab Imatinib 400 mg OD for 5 months followed by Tab Pazopanib 800 mg OD for 4 months and both the drugs were stopped due to lack of any response in the skin lesions. We report this case due to its rarity, characteristic clinical presentation, and its association with Eale's disease. Primary treatment remains surgical excision of bothersome lesions and optimal systemic treatment is still unknown. PMID:26288410

  20. FLNA genomic rearrangements cause periventricular nodular heterotopia

    PubMed Central

    Clapham, K.R.; Yu, T.W.; Ganesh, V.S.; Barry, B.; Chan, Y.; Mei, D.; Parrini, E.; Funalot, B.; Dupuis, L.; Nezarati, M.M.; du Souich, C.; van Karnebeek, C.

    2012-01-01

    Objective: To identify copy number variant (CNV) causes of periventricular nodular heterotopia (PNH) in patients for whom FLNA sequencing is negative. Methods: Screening of 35 patients from 33 pedigrees on an Affymetrix 6.0 microarray led to the identification of one individual bearing a CNV that disrupted FLNA. FLNA-disrupting CNVs were also isolated in 2 other individuals by multiplex ligation probe amplification. These 3 cases were further characterized by high-resolution oligo array comparative genomic hybridization (CGH), and the precise junctional breakpoints of the rearrangements were identified by PCR amplification and sequencing. Results: We report 3 cases of PNH caused by nonrecurrent genomic rearrangements that disrupt one copy of FLNA. The first individual carried a 113-kb deletion that removes all but the first exon of FLNA. A second patient harbored a complex rearrangement including a deletion of the 3′ end of FLNA accompanied by a partial duplication event. A third patient bore a 39-kb deletion encompassing all of FLNA and the neighboring gene EMD. High-resolution oligo array CGH of the FLNA locus suggests distinct molecular mechanisms for each of these rearrangements, and implicates nearby low copy repeats in their pathogenesis. Conclusions: These results demonstrate that FLNA is prone to pathogenic rearrangements, and highlight the importance of screening for CNVs in individuals with PNH lacking FLNA point mutations. Neurology® 2012;78:269–278 PMID:22238415

  1. Cortisol-secreting adrenocortical tumours in dogs and their relevance for human medicine.

    PubMed

    Galac, Sara

    2016-02-01

    Spontaneous cortisol-secreting adrenocortical tumours in pet dogs are an attractive animal model for their human counterparts. Adrenal morphology and function are similar in dogs and humans, and adrenocortical tumours have comparable clinical and pathological characteristics. Their relatively high incidence in pet dogs represents a potential source of adrenocortical tumour tissue to facilitate research. The molecular characteristics of canine cortisol-secreting adrenocortical tumours suggest that they will be useful for the study of angiogenesis, the cAMP/protein kinase A pathway, and the role of Steroidogenic Factor-1 in adrenal tumourigenesis. Pet dogs with spontaneous cortisol-secreting adrenocortical tumours may also be useful in clinical testing of new drugs and in investigating the molecular background of adrenocortical tumours. PMID:26123587

  2. RSK1 Activation Promotes Invasion in Nodular Melanoma

    PubMed Central

    Salhi, Amel; Farhadian, Joshua A.; Giles, Keith M.; Vega-Saenz de Miera, Eleazar; Silva, Ines P.; Bourque, Caitlin; Yeh, Karen; Chhangawala, Sagar; Wang, Jinhua; Ye, Fei; Zhang, David Y.; Hernando-Monge, Eva; Houvras, Yariv; Osman, Iman

    2016-01-01

    The two major melanoma histologic subtypes, superficial spreading and nodular melanomas, differ in their speed of dermal invasion but converge biologically once they invade and metastasize. Herein, we tested the hypothesis that distinct molecular alterations arising in primary melanoma cells might persist as these tumors progress to invasion and metastasis. Ribosomal protein S6 kinase, 90 kDa, polypeptide 1 (RSK1; official name RPS6KA1) was significantly hyperactivated in human melanoma lines and metastatic tissues derived from nodular compared with superficial spreading melanoma. RSK1 was constitutively phosphorylated at Ser-380 in nodular but not superficial spreading melanoma and did not directly correlate with BRAF or MEK activation. Nodular melanoma cells were more sensitive to RSK1 inhibition using siRNA and the pharmacological inhibitor BI-D1870 compared with superficial spreading cells. Gene expression microarray analyses revealed that RSK1 orchestrated a program of gene expression that promoted cell motility and invasion. Differential overexpression of the prometastatic matrix metalloproteinase 8 and tissue inhibitor of metalloproteinases 1 in metastatic nodular compared with metastatic superficial spreading melanoma was observed. Finally, using an in vivo zebrafish model, constitutive RSK1 activation increased melanoma invasion. Together, these data reveal a novel role for activated RSK1 in the progression of nodular melanoma and suggest that melanoma originating from different histologic subtypes may be biologically distinct and that these differences are maintained as the tumors invade and metastasize. PMID:25579842

  3. Hepatocellular carcinoma in a patient with focal nodular hyperplasia

    PubMed Central

    Lowell, Jeffrey A; Hassan, Anjum; Howard, Todd K

    2002-01-01

    Background Focal nodular hyperplasia is an uncommon liver tumour that typically requires no therapeutic intervention. Case outline A 43-year-old woman with a 20-year history of oral contraceptive use presented with symptomatic bilateral liver masses. Biopsy revealed hepatocellular carcinoma in the right hemiliver and focal nodular hyperplasia in the left hemiliver.At operation,the patient was noted to have multiple liver nodules bilaterally, and all intraoperative biopsies were consistent with focal nodular hyperplasia including a biopsy taken from the region that demonstrated carcinoma preoperatively. Because of the earlier biopsy results and the patient's preoperative symptoms, a right hemihepatectomy was performed. Final pathology revealed hepatocellular carcinoma directly adjacent to an area of focal nodular hyperplasia, as well as multiple other areas of hyperplastic liver tumour. Discussion Although focal nodular hyperplasia is believed to be benign, few studies have followed patients with this tumour beyond three years. Longer-term follow-up studies are needed to determine the natural history of focal nodular hyperplasia, potentially focussing on a subset of patients with either diffuse tumours or prolonged oral contraceptive use. PMID:18332941

  4. RSK1 activation promotes invasion in nodular melanoma.

    PubMed

    Salhi, Amel; Farhadian, Joshua A; Giles, Keith M; Vega-Saenz de Miera, Eleazar; Silva, Ines P; Bourque, Caitlin; Yeh, Karen; Chhangawala, Sagar; Wang, Jinhua; Ye, Fei; Zhang, David Y; Hernando-Monge, Eva; Houvras, Yariv; Osman, Iman

    2015-03-01

    The two major melanoma histologic subtypes, superficial spreading and nodular melanomas, differ in their speed of dermal invasion but converge biologically once they invade and metastasize. Herein, we tested the hypothesis that distinct molecular alterations arising in primary melanoma cells might persist as these tumors progress to invasion and metastasis. Ribosomal protein S6 kinase, 90 kDa, polypeptide 1 (RSK1; official name RPS6KA1) was significantly hyperactivated in human melanoma lines and metastatic tissues derived from nodular compared with superficial spreading melanoma. RSK1 was constitutively phosphorylated at Ser-380 in nodular but not superficial spreading melanoma and did not directly correlate with BRAF or MEK activation. Nodular melanoma cells were more sensitive to RSK1 inhibition using siRNA and the pharmacological inhibitor BI-D1870 compared with superficial spreading cells. Gene expression microarray analyses revealed that RSK1 orchestrated a program of gene expression that promoted cell motility and invasion. Differential overexpression of the prometastatic matrix metalloproteinase 8 and tissue inhibitor of metalloproteinases 1 in metastatic nodular compared with metastatic superficial spreading melanoma was observed. Finally, using an in vivo zebrafish model, constitutive RSK1 activation increased melanoma invasion. Together, these data reveal a novel role for activated RSK1 in the progression of nodular melanoma and suggest that melanoma originating from different histologic subtypes may be biologically distinct and that these differences are maintained as the tumors invade and metastasize. PMID:25579842

  5. Microstructural Characterization of Nodular Ductile Iron

    SciTech Connect

    Springer, H K

    2012-01-03

    The objective of this study is to quantify the graphite particle phase in nodular ductile iron (NDI). This study provides the basis for initializing microstructure in direct numerical simulations, as part of developing microstructure-fracture response models. The work presented here is a subset of a PhD dissertation on spall fracture in NDI. NDI is an ideal material for studying the influence of microstructure on ductile fracture because it contains a readily identifiable second-phase particle population, embedded in a ductile metallic matrix, which serves as primary void nucleation sites. Nucleated voids grow and coalesce under continued tensile loading, as part of the micromechanisms of ductile fracture, and lead to macroscopic failure. For this study, we used 2D optical microscopy and quantitative metallography relationships to characterize the volume fraction, size distribution, nearest-neighbor distance, and other higher-order metrics of the graphite particle phase. We found that the volume fraction was {Phi} = 0.115, the average particle diameter was d{sub avg} = 25.9 {mu}m, the Weibull shape and scaling parameters were {beta} = 1.8 and {eta} = 29.1 {mu}m, respectively, the (first) nearest neighbor distance was L{sub nn} = 32.4 {mu}m, the exponential coefficients for volume fraction fluctuations was A{sub {Phi}} = 1.89 and B{sub {Phi}} = -0.59, respectively. Based on reaching a coefficient-of-variation (COV) of 0.01, the representative volume element (RVE) size was determined to be 8.9L{sub nn} (288 {mu}m).

  6. Pubertal outcome in a female with virilizing adrenocortical carcinoma

    PubMed Central

    Breidbart, Emily; Cameo, Tamara; Garvin, James H.; Hibshoosh, Hanina

    2016-01-01

    Adrenocortical tumors are neoplasms that rarely occur in pediatric patients. Adrenocortical carcinoma (ACC) is even more uncommon, and is an aggressive malignancy with 5-year survival of 55% in a registry series. There is a lack of information on long-term endocrine outcome in survivors. We describe a 10-year follow-up in a patient who presented at 3 years 5 months with a 1-year history of axillary odor and 6 months’ history of pubic hair development with an increased clitoral size. Androgen levels were increased and a pelvic sonogram revealed a suprarenal mass of the left kidney. The tumor was successfully removed. At 6 years 11 months, androgen levels increased again. Workup for tumor recurrence was negative and the findings likely represented early adrenarche. The patient had menarche at an appropriate time and attained a height appropriate for her family. PMID:26812773

  7. Pubertal outcome in a female with virilizing adrenocortical carcinoma.

    PubMed

    Breidbart, Emily; Cameo, Tamara; Garvin, James H; Hibshoosh, Hanina; Oberfield, Sharon E

    2016-04-01

    Adrenocortical tumors are neoplasms that rarely occur in pediatric patients. Adrenocortical carcinoma (ACC) is even more uncommon, and is an aggressive malignancy with 5-year survival of 55% in a registry series. There is a lack of information on long-term endocrine outcome in survivors. We describe a 10-year follow-up in a patient who presented at 3 years 5 months with a 1-year history of axillary odor and 6 months' history of pubic hair development with an increased clitoral size. Androgen levels were increased and a pelvic sonogram revealed a suprarenal mass of the left kidney. The tumor was successfully removed. At 6 years 11 months, androgen levels increased again. Workup for tumor recurrence was negative and the findings likely represented early adrenarche. The patient had menarche at an appropriate time and attained a height appropriate for her family. PMID:26812773

  8. Adrenocortical Cells with Stem/Progenitor Cell Properties: Recent Advances

    PubMed Central

    Kim, Alex; Hammer, Gary D.

    2007-01-01

    The existence and location of undifferentiated cells with the capability of maintaining the homeostasis of the adrenal cortex have long been sought. These cells are thought to remain mostly quiescent with a potential to commit to self-renewal processes or terminal differentiation to homeostatically repopulate the organ. In addition, in response to physiologic stress, the undifferentiated cells undergo rapid proliferation to accommodate organismic need. Sufficient adrenocortical proliferative capacity lasting the lifespan of the host has been demonstrated through cell transplantation and enucleation experiments. Labeling experiments with tritium, BrdU, or trypan blue, as well as transgenic assays support the clonogenic identity and location of these undefined cells within the gland periphery. We define undifferentiated adrenocortical cells as cells devoid of steroidogenic gene expression, and differentiated cells as cells with steroidogenic capacity. In this review, we discuss historic developmental studies together with recent molecular examinations that aim to characterize such populations of cells. PMID:17240045

  9. Adrenocortical tumors and insulin resistance: What is the first step?

    PubMed

    Altieri, Barbara; Tirabassi, Giacomo; Casa, Silvia Della; Ronchi, Cristina L; Balercia, Giancarlo; Orio, Francesco; Pontecorvi, Alfredo; Colao, Annamaria; Muscogiuri, Giovanna

    2016-06-15

    The pathogenetic mechanisms underlying the onset of adrenocortical tumors (ACTs) are still largely unknown. Recently, more attention has been paid to the role of insulin and insulin-like growth factor (IGF) system on general tumor development and progression. Increased levels of insulin, IGF-1 and IGF-2 are associated with tumor cell growth and increased risk of cancer promotion and progression in patients with type 2 diabetes. Insulin resistance and compensatory hyperinsulinemia may play a role in adrenal tumor growth through the activation of insulin and IGF-1 receptors. Interestingly, apparently non-functioning ACTs are often associated with a high prevalence of insulin resistance and metabolic syndrome. However, it is unclear if ACT develops from a primary insulin resistance and compensatory hyperinsulinemia or if insulin resistance is only secondary to the slight cortisol hypersecretion by ACT. The aim of this review is to summarize the current evidence regarding the relationship between hyperinsulinemia and adrenocortical tumors. PMID:26637955

  10. Skin Pigmentation Disorders

    MedlinePlus

    ... skin gets its color from a pigment called melanin. Special cells in the skin make melanin. When these cells become damaged or unhealthy, it affects melanin production. Some pigmentation disorders affect just patches of ...

  11. Plurihormonal Cosecretion by a Case of Adrenocortical Oncocytic Neoplasm.

    PubMed

    Corrales, J J; Robles-Lázaro, C; Sánchez-Marcos, A I; González-Sánchez, M C; Antúnez-Plaza, P; Miralles, J M

    2016-01-01

    Adrenocortical oncocytic neoplasms (oncocytomas) are extremely rare; only approximately 159 cases have been described so far. The majority are nonfunctional and benign. We describe an unusual case of a functional oncocytoma secreting an excess of glucocorticoids (cortisol) and androgens (androstenedione and DHEAS), a pattern of plurihormonal cosecretion previously not reported in men, presenting with endocrine manifestations of Cushing's syndrome. The neoplasm was considered to be of uncertain malignant potential (borderline) according to the Lin-Weiss-Bisceglia criteria. PMID:27413559

  12. Plurihormonal Cosecretion by a Case of Adrenocortical Oncocytic Neoplasm

    PubMed Central

    Corrales, J. J.; Robles-Lázaro, C.; Sánchez-Marcos, A. I.; González-Sánchez, M. C.; Antúnez-Plaza, P.; Miralles, J. M.

    2016-01-01

    Adrenocortical oncocytic neoplasms (oncocytomas) are extremely rare; only approximately 159 cases have been described so far. The majority are nonfunctional and benign. We describe an unusual case of a functional oncocytoma secreting an excess of glucocorticoids (cortisol) and androgens (androstenedione and DHEAS), a pattern of plurihormonal cosecretion previously not reported in men, presenting with endocrine manifestations of Cushing's syndrome. The neoplasm was considered to be of uncertain malignant potential (borderline) according to the Lin-Weiss-Bisceglia criteria. PMID:27413559

  13. Oral pigmentation: A review

    PubMed Central

    Sreeja, C.; Ramakrishnan, K.; Vijayalakshmi, D.; Devi, M.; Aesha, I.; Vijayabanu, B.

    2015-01-01

    Pigmentations are commonly found in the mouth. They represent in various clinical patterns that can range from just physiologic changes to oral manifestations of systemic diseases and malignancies. Color changes in the oral mucosa can be attributed to the deposition of either endogenous or exogenous pigments as a result of various mucosal diseases. The various pigmentations can be in the form of blue/purple vascular lesions, brown melanotic lesions, brown heme-associated lesions, gray/black pigmentations. PMID:26538887

  14. Mouse Models Recapitulating Human Adrenocortical Tumors: What Is Lacking?

    PubMed Central

    Leccia, Felicia; Batisse-Lignier, Marie; Sahut-Barnola, Isabelle; Val, Pierre; Lefrançois-Martinez, A-Marie; Martinez, Antoine

    2016-01-01

    Adrenal cortex tumors are divided into benign forms, such as primary hyperplasias and adrenocortical adenomas (ACAs), and malignant forms or adrenocortical carcinomas (ACCs). Primary hyperplasias are rare causes of adrenocorticotropin hormone-independent hypercortisolism. ACAs are the most common type of adrenal gland tumors and they are rarely “functional,” i.e., producing steroids. When functional, adenomas result in endocrine disorders, such as Cushing’s syndrome (hypercortisolism) or Conn’s syndrome (hyperaldosteronism). By contrast, ACCs are extremely rare but highly aggressive tumors that may also lead to hypersecreting syndromes. Genetic analyses of patients with sporadic or familial forms of adrenocortical tumors (ACTs) led to the identification of potentially causative genes, most of them being involved in protein kinase A (PKA), Wnt/β-catenin, and P53 signaling pathways. Development of mouse models is a crucial step to firmly establish the functional significance of candidate genes, to dissect mechanisms leading to tumors and endocrine disorders, and in fine to provide in vivo tools for therapeutic screens. In this article, we will provide an overview on the existing mouse models (xenografted and genetically engineered) of ACTs by focusing on the role of PKA and Wnt/β-catenin pathways in this context. We will discuss the advantages and limitations of models that have been developed heretofore and we will point out necessary improvements in the development of next generation mouse models of adrenal diseases. PMID:27471492

  15. Overview of plant pigments

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chlorophylls, carotenoids, flavonoids and betalains are four major classes of biological pigments produced in plants. Chlorophylls are the primary pigments responsible for plant green and photosynthesis. The other three are accessary pigments and secondary metabolites that yield non-green colors and...

  16. Mechanical Characterization of Nodular Ductile Iron

    SciTech Connect

    Springer, H K

    2012-01-03

    The objective of this study is to characterize the strength and fracture response of nodular ductile iron (NDI) and its underlying ferritic matrix phase. Quasistatic and split Hopkinson pressure bar (SHPB) compression tests were performed on NDI and a model material for the NDI matrix phase (Fe-Si alloy). Smooth and notch round bar (NRB) samples were loaded in tension until fracture to determine strain-at-failure with varying stress triaxiality. Multiple tests were performed on each small and large smooth bar samples to obtain fracture statistics with sample size. Fracture statistics are important for initializing simulations of fragmentation events. Johnson-Cook strength models were developed for the NDI and the Fe-Si alloy. NDI strength model parameters are: A = 525 MPa, B = 650 MPa, n = 0.6, and C = 0.0205. The average SHPB experimental strain-rate of 2312/s was used for the reference strain-rate in this model. Fe-Si alloy strength model parameters are: A=560 MPa, B = 625 MPa, n = 0.5, and C = 0.02. The average SHPB experimental strain-rate of 2850/s was used for the reference strain-rate in this model. A Johnson-Cook failure model was developed for NDI with model parameters: D{sub 1} = 0.029, D{sub 2} = 0.44, D{sub 3} = -1.5, and D{sub 4} = D{sub 5} = 0. An exponential relationship was developed for the elongation-at-failure statistics as a function of length-scale with model parameters: S{sub f1} = 0.108, S{sub f2} = -0.00169, and L{sub m} = 32.4 {mu}m. NDI strength and failure models, including failure statistics, will be used in continuum-scale simulations of explosively-driven ring fragmentation. The Fe-Si alloy strength model will be used in mesoscale simulations of spall fracture in NDI, where the NDI matrix phase is captured explicitly.

  17. How does cAMP/protein kinase A signaling lead to tumors in the adrenal cortex and other tissues?

    PubMed

    Almeida, Madson Q; Stratakis, Constantine A

    2011-04-10

    The overwhelming majority of benign lesions of the adrenal cortex leading to Cushing syndrome are linked to one or another abnormality of the cAMP signaling pathway. A small number of both massive macronodular adrenocortical disease and cortisol-producing adenomas harbor somatic GNAS mutations. Micronodular adrenocortical hyperplasias are either pigmented (the classic form being that of primary pigmented nodular adrenocortical disease) or non-pigmented; micronodular adrenocortical hyperplasias can be seen in the context of other conditions or isolated; for example, primary pigmented nodular adrenocortical disease usually occurs in the context of Carney complex, but isolated primary pigmented nodular adrenocortical disease has also been described. Both Carney complex and isolated primary pigmented nodular adrenocortical disease are caused by germline PRKAR1A mutations; somatic mutations of this gene that regulates cAMP-dependent protein kinase are also found in cortisol-producing adenomas, and abnormalities of PKA are present in most cases of massive macronodular adrenocortical disease. Micronodular adrenocortical hyperplasias and some cortisol-producing adenomas are associated with phosphodiesterase 11A and 8B defects, coded, respectively, by the PDE11A and PDE8B genes. Mouse models of Prkar1a deficiency also show that increased cAMP signaling leads to tumors in adrenal cortex and other tissues. In this review, we summarize all recent data from ours and other laboratories, supporting the view that Wnt-signaling acts as an important mediator of tumorigenicity induced by abnormal PRKAR1A function and aberrant cAMP signaling. PMID:21111774

  18. Nodular regenerative hyperplasia of the liver in children.

    PubMed

    Moran, C A; Mullick, F G; Ishak, K G

    1991-05-01

    Sixteen cases of nodular regenerative hyperplasia of the liver in children are presented. The patients, 10 girls and 6 boys, were between the ages of 7 months and 13 years, with a median of 6 years. Clinically, nine children presented with hepatomegaly or splenomegaly, with and without signs of portal hypertension. A history of anticonvulsant drug therapy was obtained in four patients. Associated conditions in the remaining three cases were Donohue's syndrome, disseminated intravascular coagulation, and angiomyolipoma of the kidney. In five patients a clinical diagnosis of primary intra-abdominal tumor was made. Follow-up showed that six patients died of causes unrelated to the nodular hyperplasia. Two patients were asymptomatic when last seen 5 and 18 years after the initial diagnosis of nodular hyperplasia. Both patients underwent shunt surgery. No follow-up was available for eight patients. The importance of recognizing this entity in the pediatric age group, as well as its histopathologic differential diagnosis, is stressed. PMID:2035739

  19. Improved clonal and nonclonal growth of human, rat and bovine adrenocortical cells in culture.

    PubMed

    McAllister, J M; Hornsby, P J

    1987-10-01

    This report describes the development of a culture system for long-term growth and cloning of human fetal adrenocortical cells. Optimal conditions for stimulating clonal growth were determined by testing the efficacy of horse serum (HS), fetal bovine serum (FBS), fibroblast growth factor (FGF), epidermal growth factor (EGF), fibronectin, and a combination of growth factors, UltroSer G, in stimulating growth from low density. Optimal conditions for clonal growth were achieved using fibronectin-coated dishes and DME/F12 medium with 10% FBS, 10% HS, 2% UltroSer G, and 100 ng/ml FGF or 100 pM EGF. Conditions for growth at clonal density were found to be optimal for growth of early passage, nonclonal cultures at higher densities. The improved growth conditions used for cloning were shown to allow continued long-term growth of nonclonal human adrenocortical cells without fibroblast overgrowth. All cells in cultures grown in HS, FBS, and UltroSer G had morphologic characteristics of adrenocortical cells, whereas cells grown in FBS only rapidly became overgrown with fibroblasts. Clonal and nonclonal early passage human adrenocortical cells had similar mitogenic responses to FGF and EGF. Whereas FGF, EGF, and UltroSer G showed similar stimulation of DNA synthesis and clonal growth in human adrenocortical cells and human adrenal gland fibroblasts, the tumor promoter 12-O-tetradecanoylphorbol-13-acetate stimulated growth only in adrenocortical cells and was strongly inhibitory to growth in fibroblasts. In both cell types, forskolin inhibited DNA synthesis. Human adrenocortical cell cultures were functional and synthesized cortisol, dehydroepiandrosterone, and dehydroepiandrosterone sulfate. The improved growth conditions for clonal growth of human adrenocortical cells also provided optimal conditions for long-term growth of cultured rat adrenocortical cells and increased the cloning efficiency of cultured bovine adrenocortical cells. PMID:3667487

  20. Expectant management of focal nodular hyperplasia during pregnancy. A case report.

    PubMed

    Kivnick, S; Greenspoon, J S; Kanter, M H; Gee, C; Fullman, H J

    1992-04-01

    A patient with unresectable focal nodular hyperplasia of the liver completed an uncomplicated pregnancy. Although there is a risk of hepatic rupture during pregnancy, expectant management may be an option for some cases of focal nodular hyperplasia. PMID:1593563

  1. Effects of centrifugation on gonadal and adrenocortical steroids in rats

    NASA Technical Reports Server (NTRS)

    Kakihana, R.; Butte, J. C.

    1980-01-01

    Many endocrine systems are sensitive to external changes in the environment. Both the pituitary adrenal and pituitary gonadal systems are affected by stress including centrifugation stress. The effect of centrifugation on the pituitary gonadal and pituitary adrenocortical systems was examined by measuring the gonadal and adrenal steroids in the plasma and brain following different duration and intensity of centrifugation stress in rats. Two studies were completed and the results are presented. The second study was carried out to describe the developmental changes of brain, plasma and testicular testosterone and dihydrotestosterone in Sprague Dawley rats so that the effect of centrifugation stress on the pituitary gonadal syatem could be better evaluated in future studies.

  2. Focal nodular hyperplasia of the liver: a link with sickle cell disease?

    PubMed Central

    Heaton, N D; Pain, J; Cowan, N C; Salisbury, J; Howard, E R

    1991-01-01

    Focal nodular hyperplasia is a benign liver tumour that is rare in children. We report the second case of a child with sickle cell disease presenting with symptomatic focal nodular hyperplasia. The possible pathogenesis of focal nodular hyperplasia and the association with sickle cell disease are discussed. Images Figure 1 Figure 2 Figure 3 PMID:1929517

  3. Microstructural aspects of zircaloy nodular corrosion in steam

    SciTech Connect

    Taylor, D.F.

    1999-07-01

    Zircaloy-2 becomes susceptible to nodular corrosion in high-temperature, high-pressure steam when the total solute concentration of the {beta}-stabilizing alloying elements Fe, Ni and Cr in the {alpha}-zirconium matrix falls below a critical value C{sub c} that is characteristic of the test conditions. C{sub c} for typical commercial Zircaloy-2 in a 24hr/510 C/10.4MPa steam-test is the precipitate-free a-matrix concentration in equilibrium with solute-saturated {beta} phase at about 840 C, the corresponding critical temperature T{sub c}.Thus, immunity to nodular corrosion is a metastable condition for {alpha}-Zircaloy that requires fast cooling from above T{sub c} to achieve adequate solute concentration throughout the matrix. Annealing Zircaloy at any temperature below T{sub c} for a sufficiently long time makes it susceptible to nodular corrosion. In the ({alpha}+{chi}) phase field, where {chi} collectively designates the Fe-, Cr-, and Ni-containing precipitate phases, lowering the solute concentration to less than C{sub c} by Ostwald ripening can require many hundreds of hours. Above about 825 C, the temperature of the ({alpha}+{chi})/({alpha}+{beta}+{chi}) transus, solute-saturated {beta} phase surrounds each precipitate and a strong inverse activity gradient promotes equilibration with the much lower solute concentration in the {alpha} matrix. Sensitization to nodular corrosion occurs most rapidly at about 835 C between the ({alpha}+{chi})/({alpha}+{beta}+{chi}) transus and T{sub c}. Annealing Zircaloy at temperatures above T{sub c} for a sufficiently long time will raise the solute concentration above C{sub c} and, with rapid cooling, heal any degree of susceptibility. Annealing within the protective coarsening window between T{sub c} and about 850 C, the temperature of the ({alpha}+{beta}+{chi})/({alpha}+{beta}) transus, achieves rapid precipitate growth in a matrix immune to nodular corrosion.

  4. Integrated genome-wide analysis of genomic changes and gene regulation in human adrenocortical tissue samples

    PubMed Central

    Gara, Sudheer Kumar; Wang, Yonghong; Patel, Dhaval; Liu-Chittenden, Yi; Jain, Meenu; Boufraqech, Myriem; Zhang, Lisa; Meltzer, Paul S.; Kebebew, Electron

    2015-01-01

    To gain insight into the pathogenesis of adrenocortical carcinoma (ACC) and whether there is progression from normal-to-adenoma-to-carcinoma, we performed genome-wide gene expression, gene methylation, microRNA expression and comparative genomic hybridization (CGH) analysis in human adrenocortical tissue (normal, adrenocortical adenomas and ACC) samples. A pairwise comparison of normal, adrenocortical adenomas and ACC gene expression profiles with more than four-fold expression differences and an adjusted P-value < 0.05 revealed no major differences in normal versus adrenocortical adenoma whereas there are 808 and 1085, respectively, dysregulated genes between ACC versus adrenocortical adenoma and ACC versus normal. The majority of the dysregulated genes in ACC were downregulated. By integrating the CGH, gene methylation and expression profiles of potential miRNAs with the gene expression of dysregulated genes, we found that there are higher alterations in ACC versus normal compared to ACC versus adrenocortical adenoma. Importantly, we identified several novel molecular pathways that are associated with dysregulated genes and further experimentally validated that oncostatin m signaling induces caspase 3 dependent apoptosis and suppresses cell proliferation. Finally, we propose that there is higher number of genomic changes from normal-to-adenoma-to-carcinoma and identified oncostatin m signaling as a plausible druggable pathway for therapeutics. PMID:26446994

  5. Global gene expression response to telomerase in bovine adrenocortical cells

    SciTech Connect

    Perrault, Steven D.; Hornsby, Peter J.; Betts, Dean H. . E-mail: bettsd@uoguelph.ca

    2005-09-30

    The infinite proliferative capability of most immortalized cells is dependent upon the presence of the enzyme telomerase and its ability to maintain telomere length and structure. However, telomerase may be involved in a greater system than telomere length regulation, as recent evidence has shown it capable of increasing wound healing in vivo, and improving cellular proliferation rate and survival from apoptosis in vitro. Here, we describe the global gene expression response to ectopic telomerase expression in an in vitro bovine adrenocortical cell model. Telomerase-immortalized cells showed an increased ability for proliferation and survival in minimal essential medium above cells transgenic for GFP. cDNA microarray analyses revealed an altered cell state indicative of increased adrenocortical cell proliferation regulated by the IGF2 pathway and alterations in members of the TGF-B family. As well, we identified alterations in genes associated with development and wound healing that support a model that high telomerase expression induces a highly adaptable, progenitor-like state.

  6. Bilateral Adrenocortical Masses Producing Aldosterone and Cortisol Independently

    PubMed Central

    Lee, Seung-Eun; Lee, You-Bin; Seok, Hyeri; Shin, In Seub; Eun, Yeong Hee; Kim, Jung-Han; Oh, Young Lyun

    2015-01-01

    A 31-year-old woman was referred to our hospital with symptoms of hypertension and bilateral adrenocortical masses with no feature of Cushing syndrome. The serum aldosterone/renin ratio was elevated and the saline loading test showed no suppression of the plasma aldosterone level, consistent with a diagnosis of primary hyperaldosteronism. Overnight and low-dose dexamethasone suppression tests showed no suppression of serum cortisol, indicating a secondary diagnosis of subclinical Cushing syndrome. Adrenal vein sampling during the low-dose dexamethasone suppression test demonstrated excess secretion of cortisol from the left adrenal mass. A partial right adrenalectomy was performed, resulting in normalization of blood pressure, hypokalemia, and high aldosterone level, implying that the right adrenal mass was the main cause of the hyperaldosteronism. A total adrenalectomy for the left adrenal mass was later performed, resulting in a normalization of cortisol level. The final diagnosis was bilateral adrenocortical adenomas, which were secreting aldosterone and cortisol independently. This case is the first report of a concurrent cortisol-producing left adrenal adenoma and an aldosterone-producing right adrenal adenoma in Korea, as demonstrated by adrenal vein sampling and sequential removal of adrenal masses. PMID:26248855

  7. Postnatal foraging demands alter adrenocortical activity and psychosocial development.

    PubMed

    Lyons, D M; Kim, S; Schatzberg, A F; Levine, S

    1998-05-01

    Mother squirrel monkeys stop carrying infants at earlier ages in high-demand (HD) conditions where food is difficult to find relative to low-demand (LD) conditions. To characterize these transitions in psychosocial development, from 10- to 21-weeks postpartum we collected measures of behavior, adrenocortical activity, and social transactions coded for initiator (mother or infant), goal (make-contact or break-contact), and outcome (success or failure). Make-contact attempts were most often initiated by HD infants, but mothers often opposed these attempts and less than 50% were successful. Break-contact attempts were most often initiated by LD infants, but mothers often opposed these attempts and fewer LD than HD infant break-contact attempts were successful. Plasma levels of cortisol were significantly higher in HD than LD mothers, but differences in adrenocortical activity were less consistent in their infants. HD and LD infants also spent similar amounts of time nursing on their mothers and feeding on solid foods. By rescheduling some transitions in development (carry-->self-transport), and not others (nursing-->self-feeding), mothers may have partially protected infants from the immediate impact of an otherwise stressful foraging task. PMID:9589217

  8. Bilateral Adrenocortical Masses Producing Aldosterone and Cortisol Independently.

    PubMed

    Lee, Seung Eun; Kim, Jae Hyeon; Lee, You Bin; Seok, Hyeri; Shin, In Seub; Eun, Yeong Hee; Kim, Jung Han; Oh, Young Lyun

    2015-12-01

    A 31-year-old woman was referred to our hospital with symptoms of hypertension and bilateral adrenocortical masses with no feature of Cushing syndrome. The serum aldosterone/renin ratio was elevated and the saline loading test showed no suppression of the plasma aldosterone level, consistent with a diagnosis of primary hyperaldosteronism. Overnight and low-dose dexamethasone suppression tests showed no suppression of serum cortisol, indicating a secondary diagnosis of subclinical Cushing syndrome. Adrenal vein sampling during the low-dose dexamethasone suppression test demonstrated excess secretion of cortisol from the left adrenal mass. A partial right adrenalectomy was performed, resulting in normalization of blood pressure, hypokalemia, and high aldosterone level, implying that the right adrenal mass was the main cause of the hyperaldosteronism. A total adrenalectomy for the left adrenal mass was later performed, resulting in a normalization of cortisol level. The final diagnosis was bilateral adrenocortical adenomas, which were secreting aldosterone and cortisol independently. This case is the first report of a concurrent cortisol-producing left adrenal adenoma and an aldosterone-producing right adrenal adenoma in Korea, as demonstrated by adrenal vein sampling and sequential removal of adrenal masses. PMID:26248855

  9. Intrarenal Adrenocortical Adenoma Treated by Robotic Partial Nephrectomy with Adrenalectomy

    PubMed Central

    Sulek, Jay; Smith, Steven C.; Hampton, Lance J.

    2016-01-01

    Abstract Background: We present an intrarenal adrenocortical adenoma discovered incidentally after robot-assisted partial nephrectomy and total adrenalectomy for a suspicious renal mass. Current literature describes the rare occurrence of an adrenocortical adenoma arising from a renal–adrenal fusion. This case represents an uncommon, benign pathology that should be considered in the differential diagnosis of an enhancing renal mass. Case Presentation: The patient is a 62-year-old female found to have an enhancing mass at the anterolateral aspect of the upper pole of the right kidney concerning for renal-cell carcinoma. CT imaging was performed to work up a cause for hyperparathyroidism. During robot-assisted partial nephrectomy, the lesion was found to be partially adherent to the lateral limb of the right adrenal gland. Microscopic evaluation with Melan-A staining showed the mass to be of adrenal origin with benign features and lack of capsulation, indicating an adrenal adenoma arising from intrarenal ectopic adrenal rests. Conclusion: An intrarenal adrenal adenoma arising from ectopic adrenal tissue is a unique pathology that represents a benign differential diagnosis in the evaluation of an enhancing renal mass. However, it cannot be differentiated from renal-cell carcinoma based on cross-sectional imaging alone and requires postoperative pathologic assessment to confirm the diagnosis. PMID:27579413

  10. Mechanism of adrenocortical toxicity induced by quinocetone and its bidesoxy-quinocetone metabolite in porcine adrenocortical cells in vitro.

    PubMed

    Wang, Xu; Wan, Dan; Ihsan, Awais; Liu, Qianying; Cheng, Guyue; Li, Juan; Liu, Zhenli; Yuan, Zonghui

    2015-10-01

    Quinocetone (QCT) is a new feeding antibacterial agent in the QdNOs family. The mechanism of its adrenal toxicity is far from clear. This study was conducted to estimate the adrenal cell damage induced by QCT and its bidesoxy-quinocetone (B-QCT) metabolite and to further investigate their mechanisms. Following doses of QCT increasing from 5 to 50 μM, cell apoptosis and necrosis, mitochondrial dysfunction and redox imbalance were observed in porcine adrenocortical cells. The mRNA levels of the six components of intermediary enzymes and the adrenal renin-angiotensin-aldosterone system (RAAS) displayed a dysregulation induced by QCT, indicating that QCT might influence aldosterone secretion not only through the upstream of the production but also through the downstream of the adrenal RAAS pathway. In contrast, B-QCT had few toxic effects on the cell apoptosis, mitochondrial dysfunction and redox imbalance. Moreover, LCMS-IT-TOF analysis showed that no desoxy metabolites of QCT were found in either cell lysate or supernatant samples. In conclusion, we reported on the cytotoxicity in porcine adrenocortical cells exposed to QCT via oxidative stress, which raised awareness that its toxic effects resulted from N→O groups, and its toxic mechanism might involve the interference of the steroid hormone biosynthesis pathway. PMID:26296292

  11. Ion transport in pigmentation

    PubMed Central

    Bellono, Nicholas W.; Oancea, Elena V.

    2014-01-01

    Skin melanocytes and ocular pigment cells contain specialized organelles called melanosomes, which are responsible for the synthesis of melanin, the major pigment in mammals. Defects in the complex mechanisms involved in melanin synthesis and regulation result in vision and pigmentation deficits, impaired development of the visual system,, and increased susceptibility to skin and eye cancers. Ion transport across cellular membranes is critical for many biological processes, including pigmentation, but the molecular mechanisms by which it regulates melanin synthesis, storage, and transfer are not understood. In this review we first discuss ion channels and transporters that function at the plasma membrane of melanocytes; in the second part we consider ion transport across the membrane of intracellular organelles, with emphasis on melanosomes. We discuss recently characterized lysosomal and endosomal ion channels and transporters associated with pigmentation phenotypes. We then review the evidence for melanosomal channels and transporters critical for pigmentation, discussing potential molecular mechanisms mediating their function. The studies investigating ion transport in pigmentation physiology open new avenues for future research and could reveal novel molecular mechanisms underlying melanogenesis. PMID:25034214

  12. Tuberculoid nodular thelitis in a dairy goat flock.

    PubMed

    Chartier, Christophe; Albaric, Olivier; Cesbron, Nora; Despres, Jérôme; Hoogveld, Charlotte; Michelet, Lorraine; Boschiroli, Maria-Laura

    2016-03-01

    An unusual outbreak of teat/udder skin lesions occurred in a dairy goat flock in France. Lesions first appeared as circular, indurated, erythematous areas of skin and progressed to form dark raised haemorrhagic crusts and ulcerative plaques. Histopathological examination revealed marked granulomatous dermatitis with multifocal ulceration. The granulomatous inflammation, with frequent Langhans type multinucleated cells and central caseous necrosis, was indicative of mycobacterial infection. The presence of non-cultivable mycobacteria was confirmed by sequencing PCR products from DNA extracted directly from the lesions and sequences matched a novel mycobacterial pathogen closely related to M. leprae and M. lepromatosis and previously identified in cattle thelitis. The association of nodular gross lesions and tuberculoid granulomas on the teat and lower udder, and the presence of mycobacteria DNA support a diagnosis of tuberculoid nodular thelitis in goats due to mycobacterial infection. PMID:26831157

  13. A case of giant nodular posterior scleritis mimicking choroidal malignancy

    PubMed Central

    Liu, Andrea T; Luk, Fiona O; Chan, Carmen K

    2015-01-01

    To report a case of giant nodular posterior scleritis mimicking a choroidal tumor. A 42-year-old lady with systemic hypertension presented with a 1-week history of unilateral visual loss, pain and redness in her left eye. Examination showed sectoral anterior episcleritis in her left eye as well as a dome-shaped choroidal mass at the inferior-temporal periphery, associated with retinal hemorrhages and subretinal fluid. Systemic evaluation and imaging of the choroidal mass were performed and could not rule out amelanotic choroidal melanoma. At the same time, she was prescribed a 2-week course of oral nonsteroidal anti-inflammatory drug (NSAID) for her sectoral anterior episcleritis. The choroidal mass was found to have resolved completely right before her scheduled fine needle biospy. Diagnosis of nodular posterior scleritis and a trial of oral NSAID can be considered in patients presenting with a choroidal mass before any invasive procedure. PMID:26862098

  14. Pictures of focal nodular hyperplasia and hepatocellular adenomas

    PubMed Central

    Sempoux, Christine; Balabaud, Charles; Bioulac-Sage, Paulette

    2014-01-01

    This practical atlas aims to help liver and non liver pathologists to recognize benign hepatocellular nodules on resected specimen. Macroscopic and microscopic views together with immunohistochemical stains illustrate typical and atypical aspects of focal nodular hyperplasia and of hepatocellular adenoma, including hepatocellular adenomas subtypes with references to clinical and imaging data. Each step is important to make a correct diagnosis. The specimen including the nodule and the non-tumoral liver should be sliced, photographed and all different looking areas adequately sampled for paraffin inclusion. Routine histology includes HE, trichrome and cytokeratin 7. Immunohistochemistry includes glutamine synthase and according to the above results additional markers such as liver fatty acid binding protein, C reactive protein and beta catenin may be realized to differentiate focal nodular hyperplasia from hepatocellular adenoma subtypes. Clues for differential diagnosis and pitfalls are explained and illustrated. PMID:25232451

  15. Focal nodular hyperplasia with major sinusoidal dilatation: a misleading entity

    PubMed Central

    Laumonier, Hervé; Frulio, Nora; Laurent, Christophe; Balabaud, Charles; Zucman-Rossi, Jessica; Bioulac-Sage, Paulette

    2010-01-01

    Focal nodular hyperplasia (FNH) is a benign liver lesion thought to be a non-specific response to locally increased blood flow. Although the diagnosis of FNH and hepatocellular adenoma (HCA) has made great progress over the last few years using modern imaging techniques, there are still in daily practice some difficulties concerning some atypical nodules. Here, the authors report the case of a 47-year-old woman with a single liver lesion thought to be, by imaging, an inflammatory HCA with major sinusoidal congestion. This nodule was revealed to be, at the microscopical level and after specific immunostaining and molecular analysis, an FNH with sinusoidal dilatation (so-called telangiectatic focal nodular hyperplasia). PMID:22798311

  16. H295R Human Adrenocortical Carcinoma Cells as a Screening Platform for Steroidogenesis (NC SOT)

    EPA Science Inventory

    Proper biosynthesis and metabolism of steroid hormones is essential for development and reproduction. Disruption of steroidogenesis by environmental toxicants results in altered hormone levels causing adverse reproductive and developmental effects. H295R human adrenocortical carc...

  17. Epidemiology of nodular goitre. Influence of iodine intake.

    PubMed

    Carlé, Allan; Krejbjerg, Anne; Laurberg, Peter

    2014-08-01

    More than one tenth of the world population is to some degree affected by goitre and most of these harbour nodules. The large differences in thyroid disease prevalence between populations may be caused by genetic and environmental factors. Among the latter, iodine deficiency seems by far to be the most important risk factor. Thus, nodular goitre is a condition predominantly seen in iodine deficient areas of the world. In the present review, we evaluated in detail autopsy and ultrasound studies of the thyroid gland. In autopsy studies, large thyroid volumes and high frequencies of goitres have been reported in countries affected by iodine deficiency. Many cross-sectional studies using thyroid ultrasound investigations have been performed world-wide and reported high thyroid volumes and goitre prevalences, and to some extent also high prevalences of thyroid nodules in iodine-deficient countries. Most of these goitres were classified as nodular goitres. On the other hand, few studies have shown that abundant iodine intake may lead to development of diffuse goitres, but world-wide this has been a minor problem compared with development of nodular goitres. In the past century we have observed a trend towards smaller thyroid glands, and hopefully less than 10% of the world population will experience goitre within a few decades. PMID:25047199

  18. Nodular scabies: a classical case report in an adolescent boy.

    PubMed

    Ramachandra Reddy, Damodara; Ramachandra Reddy, Prathap

    2015-09-01

    This case report presents a classical case of nodular scabies in a 12 year boy who complained of itching for 20-21 days before presentation to the hospital. Application of Betnovate ointment (Betamethasone valerate 0.1 %) before presentation to the hospital had provided only 2-3 days of relief from itching. Dermatological examination revealed skin colored to erythematous papule of 3-4 mm on the body with predilection for web space of fingers and flexural areas and nodules on the scrotum and groin. Based on this, clinical diagnosis of scabies with nodular scabies was made on the child. The scraping obtained from the web-space of the child showed mite under the light microscope, which confirms the diagnosis. Treatment with topical permethrin 5 % lotion resulted in 50-70 % subsidence of itching within a day, and improvement in impetigo lesions of his father in 5 days. However, the scrotal and groin nodular lesion of the child persisted with severe itching. Treatment with topical steroid and tacrolimus 0.1 % ointment did not show much improvement. Intralesional injection of triamcinolone (5 mg/ml) on the nodule resulted in 30-40 % subsidence in itching and 50-60 % reduction in the size of the lesion over 2-3 weeks. PMID:26345076

  19. Solitary Nodular Lesion of Tongue- A Rare Entity

    PubMed Central

    Sarada, P.; Reddy, C.H. Sampath; A.K, Patil; Kurra, Saritha

    2014-01-01

    The solitary, nodular lesions of the oral mucosa present a diagnostic dilemma to the dentist with their analogous presentation. The lesions that appear on the tongue, a soft muscular organ are distinct and even rarer with varied manifestations. Oral mucosa presents lesions of the tongue in all age groups that may range from a small nodular swelling and ulcer formation in an infant of a few days old to an ulcer or a lesion in a 70-year-old. The reason for the appearance of an ulcer may be trauma to the soft tissues in an infant may be due to the presence of natal teeth to the presence of a sharp tooth in the older individuals. These lesions have to be clinically and histologically correlated for the final outcome of the diagnosis, so that there is no chance of any recurrence. We present a unique case of a solitary nodular lesion on the ventral surface of tongue On a 6 year female, where there was a recurrence after surgical excision and after an unusual therapy of non surgical resolution, no recurrence was observed. PMID:24701550

  20. Solitary nodular lesion of tongue- a rare entity.

    PubMed

    Sarada, P; Reddy, C H Sampath; A K, Patil; Kurra, Saritha

    2014-02-01

    The solitary, nodular lesions of the oral mucosa present a diagnostic dilemma to the dentist with their analogous presentation. The lesions that appear on the tongue, a soft muscular organ are distinct and even rarer with varied manifestations. Oral mucosa presents lesions of the tongue in all age groups that may range from a small nodular swelling and ulcer formation in an infant of a few days old to an ulcer or a lesion in a 70-year-old. The reason for the appearance of an ulcer may be trauma to the soft tissues in an infant may be due to the presence of natal teeth to the presence of a sharp tooth in the older individuals. These lesions have to be clinically and histologically correlated for the final outcome of the diagnosis, so that there is no chance of any recurrence. We present a unique case of a solitary nodular lesion on the ventral surface of tongue On a 6 year female, where there was a recurrence after surgical excision and after an unusual therapy of non surgical resolution, no recurrence was observed. PMID:24701550

  1. Hepatocyte Growth Factor/cMET Pathway Activation Enhances Cancer Hallmarks in Adrenocortical Carcinoma.

    PubMed

    Phan, Liem M; Fuentes-Mattei, Enrique; Wu, Weixin; Velazquez-Torres, Guermarie; Sircar, Kanishka; Wood, Christopher G; Hai, Tao; Jimenez, Camilo; Cote, Gilbert J; Ozsari, Levent; Hofmann, Marie-Claude; Zheng, Siyuan; Verhaak, Roeland; Pagliaro, Lance; Cortez, Maria Angelica; Lee, Mong-Hong; Yeung, Sai-Ching J; Habra, Mouhammed Amir

    2015-10-01

    Adrenocortical carcinoma is a rare malignancy with poor prognosis and limited response to chemotherapy. Hepatocyte growth factor (HGF) and its receptor cMET augment cancer growth and resistance to chemotherapy, but their role in adrenocortical carcinoma has not been examined. In this study, we investigated the association between HGF/cMET expression and cancer hallmarks of adrenocortical carcinoma. Transcriptomic and immunohistochemical analyses indicated that increased HGF/cMET expression in human adrenocortical carcinoma samples was positively associated with cancer-related biologic processes, including proliferation and angiogenesis, and negatively correlated with apoptosis. Accordingly, treatment of adrenocortical carcinoma cells with exogenous HGF resulted in increased cell proliferation in vitro and in vivo while short hairpin RNA-mediated knockdown or pharmacologic inhibition of cMET suppressed cell proliferation and tumor growth. Moreover, exposure of cells to mitotane, cisplatin, or radiation rapidly induced pro-cMET expression and was associated with an enrichment of genes (e.g., CYP450 family) related to therapy resistance, further implicating cMET in the anticancer drug response. Together, these data suggest an important role for HGF/cMET signaling in adrenocortical carcinoma growth and resistance to commonly used treatments. Targeting cMET, alone or in combination with other drugs, could provide a breakthrough in the management of this aggressive cancer. PMID:26282167

  2. Pathway Implications of Aberrant Global Methylation in Adrenocortical Cancer

    PubMed Central

    Legendre, Christophe R.; Demeure, Michael J.; Whitsett, Timothy G.; Gooden, Gerald C.; Bussey, Kimberly J.; Jung, Sungwon; Waibhav, Tembe; Kim, Seungchan; Salhia, Bodour

    2016-01-01

    Context Adrenocortical carcinomas (ACC) are a rare tumor type with a poor five-year survival rate and limited treatment options. Objective Understanding of the molecular pathogenesis of this disease has been aided by genomic analyses highlighting alterations in TP53, WNT, and IGF signaling pathways. Further elucidation is needed to reveal therapeutically actionable targets in ACC. Design In this study, global DNA methylation levels were assessed by the Infinium HumanMethylation450 BeadChip Array on 18 ACC tumors and 6 normal adrenal tissues. A new, non-linear correlation approach, the discretization method, assessed the relationship between DNA methylation/gene expression across ACC tumors. Results This correlation analysis revealed epigenetic regulation of genes known to modulate TP53, WNT, and IGF signaling, as well as silencing of the tumor suppressor MARCKS, previously unreported in ACC. Conclusions DNA methylation may regulate genes known to play a role in ACC pathogenesis as well as known tumor suppressors. PMID:26963385

  3. Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma.

    PubMed

    Zheng, Siyuan; Cherniack, Andrew D; Dewal, Ninad; Moffitt, Richard A; Danilova, Ludmila; Murray, Bradley A; Lerario, Antonio M; Else, Tobias; Knijnenburg, Theo A; Ciriello, Giovanni; Kim, Seungchan; Assie, Guillaume; Morozova, Olena; Akbani, Rehan; Shih, Juliann; Hoadley, Katherine A; Choueiri, Toni K; Waldmann, Jens; Mete, Ozgur; Robertson, A Gordon; Wu, Hsin-Ta; Raphael, Benjamin J; Shao, Lina; Meyerson, Matthew; Demeure, Michael J; Beuschlein, Felix; Gill, Anthony J; Sidhu, Stan B; Almeida, Madson Q; Fragoso, Maria C B V; Cope, Leslie M; Kebebew, Electron; Habra, Mouhammed A; Whitsett, Timothy G; Bussey, Kimberly J; Rainey, William E; Asa, Sylvia L; Bertherat, Jérôme; Fassnacht, Martin; Wheeler, David A; Hammer, Gary D; Giordano, Thomas J; Verhaak, Roel G W

    2016-05-01

    We describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers. PMID:27165744

  4. An endocrinologist's view on relative adrenocortical insufficiency in rheumatoid arthritis.

    PubMed

    Imrich, Richard; Vlcek, Miroslav; Aldag, Jean C; Kerlik, Jana; Radikova, Zofia; Rovensky, Jozef; Vigas, Milan; Masi, Alfonse T

    2010-04-01

    The concept of relative adrenal insufficiency (RAI) has been originally introduced to describe a situation in which critically ill patients, without any prior risk or evidence for adrenal insufficiency, have total serum cortisol levels inadequate for the severity of patients' illness. The concept provided a framework for other disease states, in which higher than normal adrenal function could be expected, such as in chronic inflammation. An intense research in RAI field highlighted some new methodological aspects that significantly improved assessment of adrenal function in chronic illness. Measurement of salivary cortisol may provide additional information on locally available cortisol in target tissues. Low levels of dehydroepiandrosterone (DHEAS) for given age and gender were confirmed as a simple and reliable indicator of decreased adrenal function, even in subjects with normal baseline cortisol or normal corticotropin-stimulated cortisol response. Combined lower DHEAS and lower baseline cortisol levels could be an example of hypocompetence of adrenocortical function, yet clinically not apparent. PMID:20398019

  5. Virilizing adrenocortical carcinoma advancing to central precocious puberty after surgery.

    PubMed

    Kim, Min Sun; Yang, Eu Jeen; Cho, Dong Hyu; Hwang, Pyung Han; Lee, Dae-Yeol

    2015-05-01

    Adrenocortical carcinoma (ACC) in pediatric and adolescent patients is rare, and it is associated with various clinical symptoms. We introduce the case of an 8-year-old boy with ACC who presented with peripheral precocious puberty at his first visit. He displayed penis enlargement with pubic hair and facial acne. His serum adrenal androgen levels were elevated, and abdominal computed tomography revealed a right suprarenal mass. After complete surgical resection, the histological diagnosis was ACC. Two months after surgical removal of the mass, he subsequently developed central precocious puberty. He was treated with a gonadotropin-releasing hormone agonist to delay further pubertal progression. In patients with functioning ACC and surgical removal, clinical follow-up and hormonal marker examination for the secondary effects of excessive hormone secretion may be a useful option at least every 2 or 3 months after surgery. PMID:26019766

  6. Ultrastructure of the adrenocortical homologue in dexamethasone-treated eels.

    PubMed Central

    Bhattacharyya, T K; Butler, D G

    1980-01-01

    The ultrastructural modifications of the adrenocortical homologue (AH) in the North American eel (Anguilla rostrata) were studied following a 10 day treatment with dexamethasone (20 mg/day). The principal changes were: disorganization of smooth endoplasmic reticlum, regression and fragmentation of the Golgi apparatus, and a lowering of matrix density in the mitochondria. Steroid treatment also induced the appearance of numerous cytoplasmic inclusions: (a) lamellated bodies with electron-lucent cores; (b) membranous whorls isolating cytoplasmic regions containing smooth endoplasmic reticulum and mitochondria and (c) complex aggregates showing whorls of membranes, residues of cytoplasmic organelles, and dense matrix. The non-accumulation of lipid droplets in repressed AH cells was noteworthy. These subcellular changes indicate endogenous cellular autophagy in the AH as a result of steroid-induced suppression of ACTH production by the pituitary. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 PMID:7400039

  7. Pigment-protein complexes

    SciTech Connect

    Siegelman, H W

    1980-01-01

    The photosynthetically-active pigment protein complexes of procaryotes and eucaryotes include chlorophyll proteins, carotenochlorophyll proteins, and biliproteins. They are either integral components or attached to photosynthetic membranes. Detergents are frequently required to solubilize the pigment-protein complexes. The membrane localization and detergent solubilization strongly suggest that the pigment-protein complexes are bound to the membranes by hydrophobic interactions. Hydrophobic interactions of proteins are characterized by an increase in entropy. Their bonding energy is directly related to temperature and ionic strength. Hydrophobic-interaction chromatography, a relatively new separation procedure, can furnish an important method for the purification of pigment-protein complexes. Phycobilisome purification and properties provide an example of the need to maintain hydrophobic interactions to preserve structure and function.

  8. Methylation of IGF2 regulatory regions to diagnose adrenocortical carcinomas.

    PubMed

    Creemers, S G; van Koetsveld, P M; van Kemenade, F J; Papathomas, T G; Franssen, G J H; Dogan, F; Eekhoff, E M W; van der Valk, P; de Herder, W W; Janssen, J A M J L; Feelders, R A; Hofland, L J

    2016-09-01

    Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. Discrimination of ACCs from adrenocortical adenomas (ACAs) is challenging on both imaging and histopathological grounds. High IGF2 expression is associated with malignancy, but shows large variability. In this study, we investigate whether specific methylation patterns of IGF2 regulatory regions could serve as a valuable biomarker in distinguishing ACCs from ACAs. Pyrosequencing was used to analyse methylation percentages in DMR0, DMR2, imprinting control region (ICR) (consisting of CTCF3 and CTCF6) and the H19 promoter. Expression of IGF2 and H19 mRNA was assessed by real-time quantitative PCR. Analyses were performed in 24 ACCs, 14 ACAs and 11 normal adrenals. Using receiver operating characteristic (ROC) analysis, we evaluated which regions showed the best predictive value for diagnosis of ACC and determined the diagnostic accuracy of these regions. In ACCs, the DMR0, CTCF3, CTCF6 and the H19 promoter were positively correlated with IGF2 mRNA expression (P<0.05). Methylation in the most discriminating regions distinguished ACCs from ACAs with a sensitivity of 96%, specificity of 100% and an area under the curve (AUC) of 0.997±0.005. Our findings were validated in an independent cohort of 9 ACCs and 13 ACAs, resulting in a sensitivity of 89% and a specificity of 92%. Thus, methylation patterns of IGF2 regulatory regions can discriminate ACCs from ACAs with high diagnostic accuracy. This proposed test may become the first objective diagnostic tool to assess malignancy in adrenal tumours and facilitate the choice of therapeutic strategies in this group of patients. PMID:27535174

  9. Adrenocortical function in cane toads from different environments.

    PubMed

    Hernández, Sandra E; Sernia, Conrad; Bradley, Adrian J

    2016-05-01

    The adrenocortical function of cane toads (Rhinella marina) exposed to different experimental procedures, as well as captured from different environments, was assessed by challenging the hypothalamic-pituitary-adrenal (HPA) axis. It was found that restriction stress as well as cannulation increased plasma corticosterone (B) levels for up to 12h. A single dose of dexamethasone (DEX 2mg/kg) significantly reduced B levels demonstrating its potential for use in the evaluation of the HPA axis in amphibia. We also demonstrate that 0.05 IU/g BW (im) of synthetic adrenocorticotropic hormone (ACTH) significantly increased plasma B levels in cane toads. Changes in size area of the cortical cells were positively associated with total levels of B after ACTH administration. We also found differences in adrenal activity between populations. This was assessed by a DEX-ACTH test. The animals captured from the field and maintained in captivity for one year at the animal house (AH) present the highest levels of total and free B after ACTH administration. We also found that animals from the front line of dispersion in Western Australia (WA) present the weakest adrenal response to a DEX-ACTH test. The animals categorized as long established in Queensland Australia (QL), and native in Mexico (MX), do not shown a marked difference in the HPA activity. Finally we found that in response to ACTH administration, females reach significantly higher levels of plasma B than males. For the first time the adrenocortical response in cane toads exposed to different experimental procedures, as well as from different populations was assessed systematically. PMID:26877241

  10. Photosynthetic Pigments in Diatoms.

    PubMed

    Kuczynska, Paulina; Jemiola-Rzeminska, Malgorzata; Strzalka, Kazimierz

    2015-09-01

    Photosynthetic pigments are bioactive compounds of great importance for the food, cosmetic, and pharmaceutical industries. They are not only responsible for capturing solar energy to carry out photosynthesis, but also play a role in photoprotective processes and display antioxidant activity, all of which contribute to effective biomass and oxygen production. Diatoms are organisms of a distinct pigment composition, substantially different from that present in plants. Apart from light-harvesting pigments such as chlorophyll a, chlorophyll c, and fucoxanthin, there is a group of photoprotective carotenoids which includes β-carotene and the xanthophylls, diatoxanthin, diadinoxanthin, violaxanthin, antheraxanthin, and zeaxanthin, which are engaged in the xanthophyll cycle. Additionally, some intermediate products of biosynthetic pathways have been identified in diatoms as well as unusual pigments, e.g., marennine. Marine algae have become widely recognized as a source of unique bioactive compounds for potential industrial, pharmaceutical, and medical applications. In this review, we summarize current knowledge on diatom photosynthetic pigments complemented by some new insights regarding their physico-chemical properties, biological role, and biosynthetic pathways, as well as the regulation of pigment level in the cell, methods of purification, and significance in industries. PMID:26389924

  11. Photosynthetic Pigments in Diatoms

    PubMed Central

    Kuczynska, Paulina; Jemiola-Rzeminska, Malgorzata; Strzalka, Kazimierz

    2015-01-01

    Photosynthetic pigments are bioactive compounds of great importance for the food, cosmetic, and pharmaceutical industries. They are not only responsible for capturing solar energy to carry out photosynthesis, but also play a role in photoprotective processes and display antioxidant activity, all of which contribute to effective biomass and oxygen production. Diatoms are organisms of a distinct pigment composition, substantially different from that present in plants. Apart from light-harvesting pigments such as chlorophyll a, chlorophyll c, and fucoxanthin, there is a group of photoprotective carotenoids which includes β-carotene and the xanthophylls, diatoxanthin, diadinoxanthin, violaxanthin, antheraxanthin, and zeaxanthin, which are engaged in the xanthophyll cycle. Additionally, some intermediate products of biosynthetic pathways have been identified in diatoms as well as unusual pigments, e.g., marennine. Marine algae have become widely recognized as a source of unique bioactive compounds for potential industrial, pharmaceutical, and medical applications. In this review, we summarize current knowledge on diatom photosynthetic pigments complemented by some new insights regarding their physico-chemical properties, biological role, and biosynthetic pathways, as well as the regulation of pigment level in the cell, methods of purification, and significance in industries. PMID:26389924

  12. Skin pigmentation evaluation in broilers fed natural and synthetic pigments.

    PubMed

    Castañeda, M P; Hirschler, E M; Sams, A R

    2005-01-01

    Broiler carcass skin color is important in the United States and Mexico. This study evaluated the use of natural and synthetic pigments in broiler diets at commercial levels. Birds were fed natural or synthetic pigments at low or high levels, simulating US and Mexican commercial practices. Skin color was measured during live production (3 to 7 wk of age) and after slaughter and chilling. The natural pigments had consistently greater skin b* values (yellowness) than the synthetic pigments. The high levels produced greater skin b* values than the low levels, regardless of source. The synthetic pigments had a slower increase in skin b* but reached the same level as the natural low by 7 wk. There was no difference in skin a* values (redness) due to pigment source or level or the age of the bird. By 7 wk, all pigment sources approached plateau levels in the blood, but the synthetic pigment diet produced higher blood levels of yellow and red pigments than the natural pigment diets. Processing intensified skin yellowness and reduced skin redness. These data suggest that although synthetic pigments might have been absorbed better than natural ones, natural pigments were more efficient at increasing skin yellowness and there were only small differences between high and low levels for each pigment source. This finding may allow reduction in pigment use and feed cost to achieve the same skin acceptance by the consumer. PMID:15685954

  13. Pigmented Villonodular Synovitis Presenting as a Popliteal Cyst

    PubMed Central

    Gokhale, Nikhil; Purohit, Shaligam; Bhosale, Pradeep B

    2015-01-01

    Introduction: Pigmented villonodular synovitis is an uncommon disease characterized by hyperplastic synovium, large effusions and bone erosions. It commonly mimics other conditions. As a result, the diagnosis may remain elusive, as the classic signs of tenderness and effusion are not specific. Occasionally, PVNS presents as a popliteal cyst, which may divert attention from intra-articular pathology. In this article, we describe a case of pigmented villonodular synovitis that presented with a popliteal cyst as the chief problem. Case Report: A twelve year old boy presented to us with a history of a gradually enlarging mass in the left popliteal fossa since eighteen months. He complained of restriction of terminal knee flexion, but he had no pain. After clinical examination and imaging the mass was interpreted as being either a popliteal cyst or chronic hematoma without ruling out the possibility of soft tissue sarcoma. An open excisional biopsy of the lesion was performed which revealed a reddish-brown cystic-nodular mass communicating with the knee joint. The histology was consistent with that of pigmented villonodular synovitis. We performed an arthroscopic synovectomy 3 weeks later. Abnormal synovium found in all compartments of the knee was removed. Histology from the intra-articular lesion was also consistent with a diagnosis of pigmented villonodular synovitis. Conclusion: A swelling in the popliteal region may be due to various etiologies. The cause should be thoroughly investigated. Along with clinical examination and imaging the tissue must be subjected to histopathological examination. Pigmented villonodular synovitis can rarely present as a popliteal cyst. In such a situation, treatment consists of dealing with intra-articular and extra-articular pathology. PMID:27299073

  14. Biology of pigmentation

    SciTech Connect

    Parker, F.

    1981-01-01

    The many factors involved in the normal pigmentation of human skin are highly complex involving anatomic, biochemical, and genetic aspects of melanocytes in the skin and the influence of UV light and various hormones on the melanocytes. It is probably more than just coincidence that the melanocytes, which are of neurogenic origin, are so responsive to several trophic hormones produced in the brain. Understanding of the various factors involved in the normal pigmentary process is crucial to explaining the many alterations and anomalies in human pigmentation.

  15. Reciprocal influences among adrenocortical activation, psychosocial processes, and the behavioral adjustment of clinic-referred children.

    PubMed

    Granger, D A; Weisz, J R; McCracken, J T; Ikeda, S C; Douglas, P

    1996-12-01

    The reciprocal effects among cognitive-behavioral, environmental, and biological influences on clinic-referred children's (N = 64; 34 boys; M age 12.71 years) short-term psychological and psychiatric adjustment were studied. At clinic intake and 6 months later, standardized measures of adjustment and control-related beliefs were assessed. Before and after conflict-oriented parent-child interaction tasks the children's saliva was sampled. Adrenocortical responses (i.e., increases in salivary cortisol) to the social conflict task predicted children's internalizing problem behaviors and anxiety disorders at follow-up. Consistently high adrenocortical reactivity at intake and follow-up was associated with deflated social competence over the 6-month period. Also, specific patterns of discontinuity in children's internalizing behavior problems predicted individual differences in their subsequent adrenocortical responsiveness. Specifically, rising behavior problem levels across time predicted higher and declining behavior problem levels predicted lower adrenocortical reactivity at follow-up. Findings are among the first to suggest links among internalizing behavior problems, adrenocortical responsiveness to social challenge, and clinic-referred children's short-term cognitive-behavioral and emotional adjustment. PMID:9071780

  16. Molecular pathways of human adrenocortical carcinoma - translating cell signalling knowledge into diagnostic and treatment options.

    PubMed

    Szyszka, Paulina; Grossman, Ashley B; Diaz-Cano, Salvador; Sworczak, Krzysztof; Dworakowska, Dorota

    2016-01-01

    Adrenocortical carcinoma is associated with a low cure rate and a high recurrence rate. The prognosis is poor, and at diagnosis 30-40% of cases are already metastatic. The current therapeutic options (surgical resection, followed by adjuvant mitotane treatment +/- chemotherapy) are limited, and the results remain unsatisfactory. Key molecular events that contribute to formation of adrenocortical cancer are IGF2 overexpression, TP53-inactivating mutations, and constitutive activation of the Wnt/b-catenin signalling pathway via activating mutations of the b-catenin gene. The underlying genetic causes of inherited tumour syndromes have provided insights into molecular pathogenesis. The increased occurrence of adrenocortical tumours in Li-Fraumeni and Beckwith-Wiedemann syndromes, and Carney complex, has highlighted the roles of specific susceptibility genes: TP53, IGF2, and PRKAR1A, respectively. Further studies have confirmed that these genes are also involved in sporadic tumour cases. Crucially, transcriptome-wide studies have determined the differences between malignant and benign adrenocortical tumours, providing potential diagnostic tools. In conclusion, enhancing our understanding of the molecular events of adrenocortical tumourigenesis, especially with regard to the signalling pathways that may be disrupted, will greatly contribute to improving a range of available diagnostic, prognostic, and treatment approaches. (Endokrynol Pol 2016; 67 (4): 427-440). PMID:27387247

  17. Androgen receptor-mediated regulation of adrenocortical activity in the sand rat, Psammomys obesus.

    PubMed

    Benmouloud, Abdelouafi; Amirat, Zaina; Khammar, Farida; Patchev, Alexandre V; Exbrayat, Jean M; Almeida, Osborne F X

    2014-12-01

    The wild sand rat, Psammomys obesus, displays seasonal variations in adrenocortical activity that parallel those of testicular activity, indicating functional cross-talk between the hypothalamo-pituitary-adrenal and hypothalamo-pituitary-gonadal axes. In the present study, we examined androgen receptor (AR)-mediated actions of testicular steroids in the regulation of adrenocortical function in the sand rat. Specifically, we examined the expression of AR in the adrenal cortex, as well as adrenal apoptosis in male sand rats that had been surgically castrated or castrated and supplemented with testosterone; biochemical indices of adrenocortical function and hormone profiles were also measured. Orchiectomy was followed by an increase in adrenocorticotropic hormone secretion from the anterior pituitary and subsequently, increased adrenocortical activity; the latter was evidenced by orchiectomy-induced increases in the adrenal content of cholesterol and lipids as well as adrenal hypertrophy (seen as an elevation of the RNA/DNA ratio). Further, androgen deprivation respectively up- and downregulated the incidence of apoptosis within the glucocorticoid-producing zona fasciculata and sex steroid-producing zona reticularis. Interestingly, orchiectomy resulted in increased expression of AR in the zona fasciculata. All of the orchiectomy-induced cellular and biochemical responses were reversible after testosterone substitution therapy. Together, these data suggest that adrenocortical activity in the sand rat is seasonally modulated by testicular androgens that act through AR located in the adrenal cortex itself. PMID:25179180

  18. Alpha-interferon in the treatment of nodular lymphomas.

    PubMed

    Urba, W J; Longo, D L

    1986-12-01

    Patients with nodular lymphoma initially respond to a number of therapies but relapse is common and inexorable with time, and despite further therapy, most patients will ultimately die of their lymphoma. The recent demonstration of their sensitivity to alpha-interferon is promising. The importance of this human antitumor effect is that it is presumably based on mechanisms different from conventional agents. Phase I trials of various doses and schedules of recombinant alpha-interferon have shown that effective serum levels can be obtained by intramuscular (IM), intravenous (IV), or subcutaneous (SC) routes. Virtually all patients experienced some degree of acute toxicity manifested by fever, chills, myalgia, and headache. Tolerance usually developed to acute adverse effects within the first few weeks of therapy, regardless of dose or schedule. Fatigue and anorexia were the most important adverse reactions, occurring during the first two weeks of treatment and generally persisting for the duration of therapy. Occasional adverse effects relating to the central nervous and cardiovascular systems have been reported. Primary laboratory abnormalities observed during treatment include decreases in hematologic parameters and elevations of liver function tests. The clinical efficacy of alpha-interferon, both natural and recombinant, has been demonstrated in both untreated and heavily pretreated patients with nodular lymphoma. The response rate has approached 50% in recent studies; however, less than half were complete responders. Future directions include combination of interferon with cytotoxic agents or other biological response modifiers and use as adjuvant therapy. PMID:3541218

  19. Nodular amyloidosis at the sites of insulin injections.

    PubMed

    Bernárdez, Claudia; Schärer, Leo; Molina-Ruiz, Ana María; Requena, Luis

    2015-07-01

    Amyloid is characterized by its fibrillary ultrastructure, and more than 20 proteins have been described to date as possible precursors. Among them, insulin and enfuvirtide represent the only medications described as amyloidogenic substances. We describe two diabetic patients, who were undergoing long-standing subcutaneous insulin treatment, who developed subcutaneous nodules at the sites of insulin injections. Histopathologic examination showed the presence of eosinophilic and amorphous masses in deep dermis, which stained positive with Congo red, amyloid P substance and anti-human insulin antibody. Whether the type of injected insulin played a role or not in the pathogenesis of the process is still uncertain, because all described patients used both fast-acting and slow-acting insulins at the same injection sites. Our second case showed nodular insulin-derived amyloid tumors only at the sites where exclusively fast-acting insulin was injected, which supports the notion that fast-acting insulin may also be the cause of this disorder. Insulin-derived nodular amyloidosis is probably underdiagnosed because of the small body of literature in comparison with the prevalence of insulin dependent diabetic patients. This underdiagnosis probably is because of its clinical similarity with the lesions of lipohypertrophy at the sites of insulin injections, which is rarely biopsied. PMID:25953111

  20. [Typing of infiltration cells in primary, localized, nodular, cutaneous amyloidosis].

    PubMed

    Sepp, N; Grünewald, K; Soyer, H P; Kerl, H; Breathnach, S M; Fritsch, P; Hintner, H

    1992-04-01

    Amyloid tumours in two patients with primary localized nodular cutaneous amyloidosis contained very dense infiltrates consisting mainly of plasma cells and lymphocytes. In one case IgM was detected on many cells of the infiltrate, while in the other IgA was found in morphologically apparently normal plasma cells. Immunohistochemical investigations did not reveal any immunoglobulin light chain restriction in either of the tumours. Numerous cells expressed B cell markers, such as CD20 or CD38. Rearrangement studies on material from the amyloid tumour of one of the patients confirmed the monoclonality of plasma cells. This observation indicates that the nodules of primary localized nodular cutaneous amyloidosis indeed represent an extramedullary plasmocytoma, which consists of amyloid-producing plasma cells. Of special interest was the unexpectedly high proportion of cells expressing T cell markers (CD3, CD5, CD4 greater than CD8) in the amyloid nodules of both patients. After excluding co-expression of B and T cell markers on identical cells by immunohistochemical studies on serial sections and also after molecular biological studies, we assume that this is a separate T cell population that may have a regulatory effect on the production of amyloid. PMID:1597370

  1. Partial KCNQ1OT1 hypomethylation: A disguised familial Beckwith-Wiedemann syndrome as a sporadic adrenocortical tumor.

    PubMed

    H'mida Ben-Brahim, Dorra; Hammami, Sabeur; Haddaji Mastouri, Marwa; Trabelsi, Saoussen; Chourabi, Maroua; Sassi, Sihem; Mougou, Soumaya; Gribaa, Moez; Zakhama, Abdelfattah; Guédiche, Mohamed Neji; Saad, Ali

    2015-03-01

    Beckwith-Wiedemann syndrome has a wide spectrum of complications such as embryonal tumors, namely adrenocortical tumor. Tumor predisposition is one of the most challenging manifestations of this syndrome. A 45-day old female with a family history of adrenocortical tumor presented with adrenocortical tumor. The case raised suspicion of a hereditary Beckwith-Wiedemann syndrome, therefore molecular analysis was undertaken. The results revealed partial KCNQ1OT1 hypomethylation in the infant's blood DNA which was associated with a complete loss of methylation in the infant's adrenocortical tumor tissue. It is unique for familial Beckwith-Wiedemann syndrome caused by KCNQ1OT1 partial hypomethylation to manifest solely through adrenocortical tumor. Incomplete penetrance and specific tissue mosaicism could provide explanations to this novel hereditary Beckwith-Wiedemann syndrome presentation. PMID:26937341

  2. [Comparative clinical analysis of histological systems of adrenocortical tumors diagnosis].

    PubMed

    Bokhyan, V Yu; Stilidi, I S; Pavlovskaya, A I

    2015-01-01

    Differential diagnosis of adrenocortical cancer (ACC) and cortical adenoma presents certain difficulties since there is no specific histological criterion allowing to distinguish tumors of the adrenal cortex with malignant clinical course. Currently there are offered several systems, and the most widely spread have the index Weiss (IW) and the modified index Weiss (MIW). The accuracy of one or another of the proposed systems remains a matter of debate. There was analyzed own experience on the use of IW and MIW in the diagnosis of 91 cases of the ACC and 13 cases of cortex adenomas of the size at least 5 cm. For the diagnosis of large adenomas sensitivity IW was 77%, MIW--100%. For the diagnosis of metastatic and non-metastatic ACC--100% and 97%, 100% and 86%, respectively (p > 0.05). In multivariate analysis of life expectancy of patients the definition of IW and MIW had a prognostic significance. MIW was less subjective, more simple and convenient to be used and it showed a great informative value at the reclassification of certain "adenomas" into ACC. However to use it on their own, without IW, was impractical as MIW had wider gray area and did not reach the threshold value in some cases of ACC. For the diagnosis of tumors of the adrenal cortex IW remains a standard; when a value was equal of 2 or in cases of doubt it was necessary to calculate MIW as well. PMID:26995980

  3. Regulation of the adrenocortical stem cell niche: implications for disease

    PubMed Central

    Walczak, Elisabeth M.; Hammer, Gary D.

    2015-01-01

    Stem cells are endowed with the potential for self-renewal and multipotency. Pluripotent embryonic stem cells have an early role in the formation of the three germ layers (ectoderm, mesoderm and endoderm), whereas adult tissue stem cells and progenitor cells are critical mediators of organ homeostasis. The adrenal cortex is an exceptionally dynamic endocrine organ that is homeostatically maintained by paracrine and endocrine signals throughout postnatal life. In the past decade, much has been learned about the stem and progenitor cells of the adrenal cortex and the multiple roles that these cell populations have in normal development and homeostasis of the adrenal gland and in adrenal diseases. In this Review, we discuss the evidence for the presence of adrenocortical stem cells, as well as the various signalling molecules and transcriptional networks that are critical for the embryological establishment and postnatal maintenance of this vital population of cells. The implications of these pathways and cells in the pathophysiology of disease are also addressed. PMID:25287283

  4. Paracrine control of steroidogenesis by serotonin in adrenocortical neoplasms.

    PubMed

    Lefebvre, H; Duparc, C; Prévost, G; Zennaro, M C; Bertherat, J; Louiset, E

    2015-06-15

    Serotonin (5-hydroxytryptamine; 5-HT) is able to activate the hypothalamo-pituitary-adrenal axis via multiple actions at different levels. In the human adrenal gland, 5-HT, released by subcapsular mast cells, stimulates corticosteroid production through a paracrine mode of communication which involves 5-HT receptor type 4 (5-HT4) primarily located in zona glomerulosa. As a result, 5-HT is much more efficient to stimulate aldosterone secretion than cortisol release in vitro and administration of 5-HT4 receptor agonists to healthy individuals is followed by an increase in plasma aldosterone levels without any change in plasma cortisol concentrations. Interestingly, adrenocortical hyperplasias and tumors responsible for corticosteroid hypersecretion exhibit various cellular and molecular defects which tend to reinforce the intraadrenal serotonergic tone. These pathophysiological mechanisms, which are summarized in the present review, include an increase in adrenal 5-HT production and overexpression of 5-HT receptors in adrenal neoplastic tissues. Altogether, these data support the concept of adrenal serotonergic paracrinopathy and suggest that 5-HT and its receptors may constitute valuable targets for pharmacological treatments of primary adrenal diseases. PMID:25433205

  5. Brain Metastasis in Patients With Adrenocortical Carcinoma: A Clinical Series

    PubMed Central

    Tageja, Nishant; Rosenberg, Avi; Mahalingam, Sowmya; Quezado, Martha; Velarde, Margarita; Edgerly, Maureen; Fojo, Tito

    2015-01-01

    Introduction: Adrenocortical carcinoma (ACC) is a heterogeneous and rare disease. At presentation or at the time of a recurrence, the disease commonly spreads to the liver, lungs, lymph nodes, and bones. The brain has only rarely been reported as a site of metastases. Objective: The aims of this report were to describe the clinical characteristics of patients with ACC who developed brain metastasis and were evaluated at the National Cancer Institute. Methods: We describe the history and clinical presentation of six patients with ACC and metastatic disease in the brain. Images of the six patients and pathology slides were reviewed when available. Results: The median age at the time of the diagnosis of ACC was 42 years. The median time from the initial diagnosis until the presentation of brain metastasis was 43 months. As a group the patients had previously received multiples lines of chemotherapy (median of three), and they presented with one to three metastatic brain lesions. Four patients underwent metastasectomy, one had radiosurgery, and one had both modalities. Two patients are still alive, three died, between 2 and 14 months after the diagnosis of brain metastases, and one was lost to follow-up. Conclusion: Patients with advanced ACC can rarely present with metastasis to the brain, most often long after the initial diagnosis. Timely diagnosis of brain metastasis with appropriate intervention after discussion in a multidisciplinary meeting can improve the prognosis in this particular scenario. PMID:25412413

  6. Temperature and adrenocortical responses in rhesus monkeys exposed to microwaves

    SciTech Connect

    Lotz, W.G.; Podgorski, R.P.

    1982-12-01

    To determine if the endocrine response to microwave exposure was similar in a primate to that reported for other animals, rectal temperature and plasma levels of cortisol, thyroxine (T4), and growth hormone (GH) were measured in rhesus monkeys exposed to 1.29-GHz microwave radiation. Exposures were carried out under far-field conditions with the monkey restrained in a chair. Incident power densities of 0, 20, 28, and 38 mW/sq cm were used, with corresponding specific absorption rates of 0, 2.1, 3.0, and 4.1 W/kg. Blood samples were taken hourly via an indwelling jugular venous catheter over a 24-h period before, during, and after an 8-h exposure. Rectal temperature increased an average of 0.5, 0.7, and 1.7 C for the three intensities used. No changes in T4 or GH were observed. Cortisol levels were increased during exposure to 38 mW/sq cm. It was concluded that the temperature and adrenocortical responses to microwave exposure of the rhesus monkey are similar to the corresponding responses of other animals.

  7. Familial Adrenocortical Carcinoma in Association With Lynch Syndrome

    PubMed Central

    Challis, Benjamin G.; Kandasamy, Narayanan; Powlson, Andrew S.; Koulouri, Olympia; Annamalai, Anand Kumar; Happerfield, Lisa; Marker, Alison J.; Arends, Mark J.; Nik-Zainal, Serena

    2016-01-01

    Context: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. Although the majority of childhood ACC arises in the context of inherited cancer susceptibility syndromes, it remains less clear whether a hereditary tumor predisposition exists for the development of ACC in adults. Here, we report the first occurrence of familial ACC in a kindred with Lynch syndrome resulting from a pathogenic germline MSH2 mutation. Case: A 54-year-old female with a history of ovarian and colorectal malignancy was found to have an ACC. A detailed family history revealed her mother had died of ACC and her sister had previously been diagnosed with endometrial and colorectal cancers. A unifying diagnosis of Lynch syndrome was considered, and immunohistochemical analyses demonstrated loss of MSH2 and MSH6 expression in both AACs (proband and her mother) and in the endometrial carcinoma of her sister. Subsequent genetic screening confirmed the presence of a germline MSH2 mutation (resulting in deletions of exons 1–3) in the proband and her sister. Conclusion: Our findings provide strong support for the recent proposal that ACC should be considered a Lynch syndrome-associated tumor and included in the Amsterdam II clinical diagnostic criteria. We also suggest that screening for ACC should be considered in cancer surveillance strategies directed at individuals with germline mutations in DNA mismatch repair genes. PMID:27144940

  8. Network analysis reveals potential markers for pediatric adrenocortical carcinoma

    PubMed Central

    Kulshrestha, Anurag; Suman, Shikha; Ranjan, Rakesh

    2016-01-01

    Pediatric adrenocortical carcinoma (ACC) is a rare malignancy with a poor outcome. Molecular mechanisms of pediatric ACC oncogenesis and advancement are not well understood. Accurate and timely diagnosis of the disease requires identification of new markers for pediatric ACC. Differentially expressed genes (DEGs) were identified from the gene expression profile of pediatric ACC and obtained from Gene Expression Omnibus. Gene Ontology functional and pathway enrichment analysis was implemented to recognize the functions of DEGs. A protein–protein interaction (PPI) and gene–gene functional interaction (GGI) network of DEGs was constructed. Hub gene detection and enrichment analysis of functional modules were performed. Furthermore, a gene regulatory network incorporating DEGs–microRNAs–transcription factors was constructed and analyzed. A total of 431 DEGs including 228 upregulated and 203 downregulated DEGs were screened. These genes were largely involved in cell cycle, steroid biosynthesis, and p53 signaling pathways. Upregulated genes, CDK1, CCNB1, CDC20, and BUB1B, were identified as the common hubs of PPI and GGI networks. All the four common hub genes were also part of modules of the PPI network. Moreover, all the four genes were also present in the largest module of GGI network. A gene regulatory network consisting of 82 microRNAs and 100 transcription factors was also constructed. CDK1, CCNB1, CDC20, and BUB1B may serve as potential biomarker of pediatric ACC and as potential targets for therapeutic approach, although experimental studies are required to authenticate our findings. PMID:27555782

  9. Fibroepithelioma of Pinkus in continuity with nodular basal cell carcinoma: A rare presentation

    PubMed Central

    Dongre, Atul M.; Khopkar, Uday S.; Kalyanpad, Yogesh N.; Gole, Prachi V.

    2016-01-01

    Fibroepithelioma of Pinkus and nodular basal cell carcinoma (BCC) are different morphological variants of BCC. It is very rare to see both the variants together in a single lesion. Here we report a case of a 56-year-old female who presented with a nodule on the trunk, which on biopsy showed features of both nodular BCC and fibroepithelioma of Pinkus. PMID:27559504

  10. Fibroepithelioma of Pinkus in continuity with nodular basal cell carcinoma: A rare presentation.

    PubMed

    Dongre, Atul M; Khopkar, Uday S; Kalyanpad, Yogesh N; Gole, Prachi V

    2016-01-01

    Fibroepithelioma of Pinkus and nodular basal cell carcinoma (BCC) are different morphological variants of BCC. It is very rare to see both the variants together in a single lesion. Here we report a case of a 56-year-old female who presented with a nodule on the trunk, which on biopsy showed features of both nodular BCC and fibroepithelioma of Pinkus. PMID:27559504

  11. Interparental Aggression and Adolescent Adjustment: The Role of Emotional Insecurity and Adrenocortical Activity

    PubMed Central

    Bergman, Kathleen N.; Cummings, E. Mark; Davies, Patrick T.

    2013-01-01

    Adolescents exposed to interparental aggression are at increased risk for developing adjustment problems. The present study explored intervening variables in these pathways in a community sample that included 266 adolescents between 12 and 16 years old (M = 13.82; 52.5% boys, 47.5% girls). A moderated mediation model examined the moderating role of adrenocortical reactivity on the meditational capacity of their emotional insecurity in this context. Information from multiple reporters and adolescents’ adrenocortical response to conflict were obtained during laboratory sessions attended by mothers, fathers and their adolescent child. A direct relationship was found between marital aggression and adolescents’ internalizing behavior problems. Adolescents’ emotional insecurity mediated the relationship between marital aggression and adolescents’ depression and anxiety. Adrenocortical reactivity moderated the pathway between emotional insecurity and adolescent adjustment. The implications for further understanding the psychological and physiological effects of adolescents’ exposure to interparental aggression and violence are discussed. PMID:25360061

  12. The role of mothers’ and fathers’ adrenocortical reactivity in spillover between interparental conflict and parenting practices

    PubMed Central

    Sturge-Apple, Melissa L.; Davies, Patrick T.; Cicchetti, Dante; Cummings, E. Mark

    2010-01-01

    Guided by the affective spillover hypothesis, the present study examined the mediational role of parental adrenocortical reactivity to interparental conflict in explaining associations between interparental conflict and subsequent changes in mothers’ and fathers’ parenting practices over a 2 year period in a sample of 202 parents and their six year old children. Results of autoregressive, path models indicated that marital withdrawal was associated with increases in adrenocortical reactivity to conflict for mothers but not fathers. Furthermore, elevated adrenocortical reactivity in turn predicted greater psychologically controlling parenting practices and inconsistent discipline over time for mothers, but was not associated with changes in maternal warmth. Implications for clinicians and therapists working with maritally distressed parents and families are discussed. PMID:19364215

  13. A Rare Case of Functioning Adrenocortical Oncocytoma Presenting as Cushing Syndrome

    PubMed Central

    Tartaglia, Nicola; Cianci, Pasquale; Altamura, Amedeo; Lizzi, Vincenzo; Vovola, Fernanda; Fersini, Alberto; Ambrosi, Antonio; Neri, Vincenzo

    2016-01-01

    Functioning adrenocortical oncocytoma is very rare neoplasm. It is usually nonfunctional and benign and incidentally detected. Generally, these tumors originate in the kidneys, thyroid, parathyroid, and salivary or pituitary glands; they have also been reported in other sites including choroid plexus, respiratory tract, and larynx. Histologically, they are characterized by cells with eosinophilic granular cytoplasm and numerous packed mitochondria. We reported a case of a 44-year-old female who presented with Cushing syndrome for hypersecretion of cortisol due to adrenocortical oncocytoma. Magnetic resonance of abdomen revealed a right adrenal mass. Laparoscopic adrenalectomy was performed and the tumor was pathologically confirmed as benign adrenocortical oncocytoma. After surgical treatment, Cushing's syndrome resolved. PMID:26989553

  14. A Rare Case of Functioning Adrenocortical Oncocytoma Presenting as Cushing Syndrome.

    PubMed

    Tartaglia, Nicola; Cianci, Pasquale; Altamura, Amedeo; Lizzi, Vincenzo; Vovola, Fernanda; Fersini, Alberto; Ambrosi, Antonio; Neri, Vincenzo

    2016-01-01

    Functioning adrenocortical oncocytoma is very rare neoplasm. It is usually nonfunctional and benign and incidentally detected. Generally, these tumors originate in the kidneys, thyroid, parathyroid, and salivary or pituitary glands; they have also been reported in other sites including choroid plexus, respiratory tract, and larynx. Histologically, they are characterized by cells with eosinophilic granular cytoplasm and numerous packed mitochondria. We reported a case of a 44-year-old female who presented with Cushing syndrome for hypersecretion of cortisol due to adrenocortical oncocytoma. Magnetic resonance of abdomen revealed a right adrenal mass. Laparoscopic adrenalectomy was performed and the tumor was pathologically confirmed as benign adrenocortical oncocytoma. After surgical treatment, Cushing's syndrome resolved. PMID:26989553

  15. Adrenocortical Tumors and Hyperplasias in Childhood - Etiology, Genetics, Clinical Presentation and Therapy

    PubMed Central

    Sutter, Jennifer A.; Grimberg, Adda

    2007-01-01

    Adrenocortical tumors are rare in children and are associated with a poor prognosis when malignant. The fund of knowledge regarding etiology, presentation and clinical outcomes remains limited. Evaluation of genetic disorders associated with the development of adrenocortical disorders has allowed researchers to identify a number of mutations that may be involved in tumorigenesis, including alterations in the GNAS1, PRKAR1A, TP53 and IGF2 genes. Clinical presentation in children is associated most commonly with young age, female gender and symptoms of virilization. Most children have localized disease at presentation which may be associated with a better prognosis when compared to adults. Surgical resection remains the only potentially curative treatment and mitotane, the most frequently used chemotherapeutic agent, has a poor response rate and is highly toxic. Broader participation in multi-center research, such as the International Pediatric Adrenocortical Tumor Registry, is needed to collect sufficient data to better guide our clinical management. PMID:17021581

  16. Adrenocortical Oncocytic Carcinoma: A Case Report and Review of the Histopathologic Diagnostic Criteria.

    PubMed

    Arik, Deniz; Canaz, Funda; Dündar, Emine

    2016-01-01

    Oncocytic tumors are rare in the adrenal gland. The histopathological diagnosis of adrenocortical carcinoma is difficult due to the lack of precise diagnostic criteria for malignancy. A 44-year-old man was admitted to our hospital with left flank pain. Radiologically an adrenal mass was detected. After the excision and histopathologic evaluation of the mass, a diagnosis of adrenocortical oncocytic carcinoma was made. At least one of the features of more than 5 mitoses in 50 high power fields, atypical mitotic figures or venous invasion is required for the diagnosis of malignancy in adrenocortical tumors. It has been suggested that tumors that have more than one of the minor criteria of large size ( > 10 cm or > 200 gr), necrosis, capsular or sinusoidal invasion, should be evaluated as having uncertain malignant potential. PMID:27562395

  17. Familial predisposition to adrenocortical tumors: clinical and biological features and management strategies.

    PubMed

    Ribeiro, Raul C; Pinto, Emilia M; Zambetti, Gerard P

    2010-06-01

    The incidence of adrenocortical tumors (ACTs) is increased in several familial cancer syndromes resulting from abnormalities in genes that encode transcription factors implicated in cell proliferation, differentiation, senescence, apoptosis, and genomic instability. These include P53, MEN1, APC, and PRKAR1A. Adenomas are the most common ACTs, but adrenocortical carcinomas occur rarely as well. The clinical manifestations of ACTs, which result from increased secretion of adrenocortical hormones, are similar in the familial and sporadic forms of the disease. However, their management may differ because of unique aspects of the constitutional syndromes. The analysis of gene expression profiles of ACTs in these constitutional syndromes have contributed to our understanding of adrenal tumorigenesis and revealed new molecular diagnostic and prognostic markers and candidate genes for targeted therapies. This chapter summarizes the clinical and biological features, pathogenesis, and management strategies for ACTs that develop in patients with familial cancer syndrome. PMID:20833338

  18. Helsinki score-a novel model for prediction of metastases in adrenocortical carcinomas.

    PubMed

    Pennanen, Mirkka; Heiskanen, Ilkka; Sane, Timo; Remes, Satu; Mustonen, Harri; Haglund, Caj; Arola, Johanna

    2015-03-01

    Histopathologic diagnosis of adrenocortical tumors is based on adverse features that indicate malignant potential. Proliferation index has served as a supplemental tool in assessing the malignant potential of adrenocortical tumors. None of the current histologic classification systems can sufficiently accurately predict tumors' metastatic potential. We studied 177 consecutive adult patients with primary adrenocortical tumors operated on at Helsinki University Central Hospital between 1990 and 2003, all patients with a minimum follow-up of 5 years. We determined for each tumor the Weiss score and the Weiss revisited score by Aubert. Proliferation index was measured by computer-assisted image analysis. Each of the 9 Weiss criteria and the proliferation index were then used to establish a scoring system to predict the metastatic potential of adrenocortical tumors. Use of stepwise regression analysis led us to propose a calculation: 3 × mitotic rate (>5/50 high-power fields) + 5 × presence of necrosis + proliferation index in the most proliferative area of the tumor. Using a cutoff value of 8.5, the new scoring system was able to diagnose metastatic adrenocortical carcinoma with 100% sensitivity (confidence interval [CI], 76.8%-100%) and 99.4% specificity (CI, 96.6%-100%). The corresponding sensitivity of the Weiss system was 100% (CI, 76.8%-100%), and specificity, 90.2% (CI, 84.6%-94.3%), with sensitivity of the Weiss revisited system at 100% (CI, 76.8%-100%) and specificity at 96.9% (CI, 93.0%-99.0%). The new Helsinki score thus was accurate in predicting the metastatic potential of adrenocortical tumors. PMID:25582500

  19. Adrenocortical neoplasia: evolving concepts in tumorigenesis with an emphasis on adrenal cortical carcinoma variants.

    PubMed

    de Krijger, Ronald R; Papathomas, Thomas G

    2012-01-01

    Adrenocortical carcinoma (ACC) is a rare, heterogeneous malignancy with a poor prognosis. According to WHO classification 2004, ACC variants include oncocytic ACCs, myxoid ACCs and ACCs with sarcomatous areas. Herein, we provide a comprehensive review of these rare subtypes of adrenocortical malignancy and emphasize their clinicopathological features with the aim of elucidating aspects of diagnostic categorization, differential diagnostics and biological behavior. The issue of current terminology, applied to biphasic tumors with pleomorphic, sarcomatous or sarcomatoid elements arising in adrenal cortex, is also discussed. We additionally present emerging evidence concerning the adrenal cortical tumorigenesis and the putative adenoma-carcinoma sequence as well. PMID:22086150

  20. Medical and Surgical Management of Carney Complex.

    PubMed

    Siordia, Juan A

    2015-07-01

    Carney complex is a rare, autosomal dominant genetic disorder that consists of multiple myxomatous lesions and endocrine abnormalities, including skin lesions, cardiac myxomas, primary pigmented nodular adrenocortical disease, and acromegaly. This review discusses the medical and surgical treatment of patients with Carney complex. PMID:25996461

  1. [Localized nodular pulmonary amyloidosis; report of a case].

    PubMed

    Shimada, Kazuyoshi; Tsubochi, H; Isogami, K; Kobayashi, S

    2006-12-01

    A 66-year-old female was admitted to our hospital because of chest abnormal shadow. Chest X-ray and chest computed tomography (CT) on admission showed a nodule in the right middle lobe. The nodule was not diagnosed preoperatively by a bronchoscopy. She underwent partial lung resection including the nodule with video-assisted thoracoscopic surgery. The pathological diagnosis was amyloidosis, and we diagnosed her illness as localized nodular pulmonary amyloidosis, since the amyloid substance was type AL. In addition, electron microscopy showed amyloid as straightly fibrous materials in alveolus. It is difficult to differentiate amyloidosis from lung cancer by radiology, and the lung biopsy with video-assisted thoracoscopic surgery is useful and a safety way to establish diagnosis. PMID:17163218

  2. Regression of nodular liver lesions in Wilson's disease.

    PubMed

    Kozic, D; Svetel, M; Petrovic, I; Sener, R N; Kostic, V S

    2006-09-01

    Long-term follow-up abdominal imaging studies have not been reported previously in patients with the hepatic form of Wilson's disease (WD). This paper reports the case of a 35-year-old woman with symptoms dating back several months and with multiple, nodular liver lesions. The lesions were hyperdense on non-enhanced computed tomography and hypointense on T2-weighted magnetic resonance (MR) images. A diagnosis of WD was established several weeks after her admission to hospital, and chelating treatment was commenced promptly. No abnormalities were found on follow-up MR examinations of the abdomen and brain 4.5 years later. These imaging features suggest that so long as WD is diagnosed in the initial stages, liver nodules can regress with time and complete healing can be achieved with continuous decoppering treatment. PMID:16950693

  3. Nodular fasciitis on temple area resulting in surgical trauma.

    PubMed

    Choi, Hwan Jun; Jung, Kyu Hwa; Lee, Hyun Ju

    2014-11-01

    Nodular fasciitis (NF) is a pseudosarcomatous reactive proliferative lesion that commonly occurs as a solitary, well-circumscribed, painful, rapidly growing soft tissue mass. It appears at any age, but incidence peaks in the third decade, with a slight predilection for women. It is most commonly located on the extremities, followed by the chest and trunk. Although a common site in the pediatric population, NF is found on the head and neck only in 7% to 20% in the adult population and includes the cheek, parotid region, zygoma, periorbital area, eyelid, forehead, and intraoral sites. The cause of NF is unknown, but an association with trauma may be present. A case of NF over the temple area in a 28-year-old man who has no trauma history but has surgical incisional biopsy history and tenderness on palpation is reported. PMID:25364967

  4. Nodular lymphocyte predominant hodgkin lymphoma: biology, diagnosis and treatment.

    PubMed

    Goel, Anupama; Fan, Wen; Patel, Amit A; Devabhaktuni, Madhuri; Grossbard, Michael L

    2014-08-01

    Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an uncommon variant of classical Hodgkin lymphoma. It is characterized histologically by presence of lymphohistiocytic cells which have B-cell phenotype, are positive for CD19, CD20, CD45, CD79a, BOB.1, Oct.2, and negative for CD15 and CD30. Patients often present with early stage of disease and do not have classical B symptoms. The clinical behavior appears to mimic that of an indolent non-Hodgkin lymphoma more than that of classical Hodgkin disease. The purpose of the present report is to define the biology of NLPHL, review its clinical presentation, and summarize the available clinical data regarding treatment. PMID:24650975

  5. Nodular mucinosis misdiagnosed as non-responsive secondary syphilis.

    PubMed

    Patrício, Catarina; Campos, Sara; João, Alexandre; Serrão, Vasco

    2015-01-01

    A previously healthy 24-year-old man presented with an erythematous, non-pruritic and painless papulonodular skin rash affecting the trunk, upper arms (excluding palms), neck, face, forehead and scalp. He had a penile ulcer for the past 2 weeks, almost healed at the time of observation. The patient tested positive for syphilis and HIV-1; he claimed being negative for HIV 6 months earlier. As the palms were not affected, we performed a skin biopsy for the differential diagnosis between secondary lues and acute HIV seroconversion reaction. Benzathine penicillin (2,400,000 units) was administrated and antiretroviral therapy started. Although the skin biopsy was compatible with secondary syphilis, there was no change in the skin rash 3 weeks after the first penicillin administration. Another 2 doses of penicillin were given but 4 weeks later the rash persisted. A second biopsy revealed a mucinous skin infiltration, compatible with nodular mucinosis. PMID:26311009

  6. A clinical and immunological study of adrenocortical insufficiency (Addison's disease)

    PubMed Central

    Irvine, W. J.; Stewart, A. G.; Scarth, Laura

    1967-01-01

    Fifty-one patients with adrenocortical insufficiency were subdivided into three groups according to the nature of their adrenal disease; twelve patients with idiopathic, twenty-three patients with probable idiopathic and sixteen patients with tuberculous adrenal insufficiency. The importance of objective confirmation of a clinical diagnosis of adrenal insufficiency is stressed and the difficulties of classification of many patients with adult onset adrenal insufficiency are discussed. Idiopathic and probable idiopathic adrenal insufficiency had a sex ratio that was predominantly female (2·5:1) with a mean age of onset of 33 years. Antibodies to adrenal cortex were detected by the methods of immunofluorescence and complement fixation. They were detected in the serum of 80% (20:25) of the females with idiopathic or probable idiopathic adrenal insufficiency and in only 10% (1:10) of the males. The titre of the adrenal antibody was low (≤32) as tested either by immunofluorescence or complement fixation. The serum of only one patient with tuberculous adrenal insufficiency reacted with adrenal tissue in the complement fixation test but the immunofluorescence method showed that this serum reacted with the vascular endothelium and not the secretory cells. No correlation was observed between the duration of the clinical illness and the presence, or absence, or titre of the adrenal antibody. Adrenal antibody was not detected in the sera of fifty-one control subjects matched for age and sex. Four of sixty-nine patients with lymphadenoid goitre, one out of ninety-three patients with diabetes mellitus and none of 230 patients with thyrotoxicosis, primary hypothyroidism or pernicious anaemia had antibody in the serum specific for adrenocortical secretory cells. There is a clinical and immunological overlap between idiopathic adrenal insufficiency and other diseases associated with autoimmune phenomena— thyroid disease, atrophic gastritis and hypoparathyroidism. It is

  7. Adrenocortical cancer (ACC) - literature overview and own experience.

    PubMed

    Dworakowska, Dorota; Drabarek, Agata; Wenzel, Ingrid; Babińska, Anna; Świątkowska-Stodulska, Renata; Sworczak, Krzysztof

    2014-01-01

    Adrenocortical carcinoma (ACC) is a malignant endocrine tumour. The rarity of the disease has stymied therapeutic development. Age distribution shows two peaks: the first and fifth decades of life, with children and women more frequently affected. Although 60-70% of ACCs are biochemically found to overproduce hormones, it is not clinically apparent in many cases. If present, endocrine symptoms include signs of hypercortisolaemia, virilisation or gynaecomastia. ACC carries a poor prognosis, and a cure can be achieved only by complete surgical resection. Mitotane is used both as an adjuvant treatment and also in non-operative patients. The role of radio- and chemotherapy is still controversial. The post-operative disease free survival is low and oscillates around 30% due to high tumour recurrence rate. The diagnosis is based on tumour histological assessment with the use of the Weiss score, however urinary steroid profiling (if available) can serve to differentiate between ACC and other adrenal tumours. Conventional prognostic markers in ACC include stage and grade of disease, and, as currently reported, the presence of hypercortisolaemia. Molecular analysis has had a significant impact on the understanding of the pathogenetic mechanism of ACC development and the evaluation of prognostic and predictive markers, among which alterations of the IGF system, the Wnt pathway, p53 and molecules involved in cancer cell invasion properties and angiogenesis seem to be very promising. We here summarise our own experience related to the management of ACC and present a literature overview. We have not aimed to include a detailed summary of the molecular alterations biology described in ACC, as this has already been addressed in other papers. PMID:25554619

  8. Regulation of the hypothalamic-pituitary-adrenocortical stress response

    PubMed Central

    Herman, James P.; McKlveen, Jessica M.; Ghosal, Sriparna; Kopp, Brittany; Wulsin, Aynara; Makinson, Ryan; Scheimann, Jessie; Myers, Brent

    2016-01-01

    The hypothalamo-pituitary-adrenocortical (HPA axis) is required for stress adaptation. Activation of the HPA axis causes secretion of glucocorticoids, which act on multiple organ systems to redirect energy resources to meet real or anticipated demand. The HPA stress response is driven primarily by neural mechanisms, invoking corticotrophin releasing hormone (CRH) release from hypothalamic paraventricular nucleus (PVN) neurons. Pathways activating CRH release are stressor dependent: reactive responses to homeostatic disruption frequently involve direct noradrenergic or peptidergic drive of PVN neurons by sensory relays, whereas anticipatory responses use oligosynaptic pathways originating in upstream limbic structures. Anticipatory responses are driven largely by disinhibition, mediated by trans-synaptic silencing of tonic PVN inhibition via GABAergic neurons in the amygdala. Stress responses are inhibited by negative feedback mechanisms, whereby glucocorticoids act to diminish drive (brainstem), promote trans-synaptic inhibition by limbic structures (e.g, hippocampus). Glucocorticoids also act at the PVN to rapidly inhibit CRH neuronal activity via membrane glucocorticoid receptors. Chronic stress-induced activation of the HPA axis takes many forms (chronic basal hypersecretion, sensitized stress responses, even adrenal exhaustion), with manifestation dependent upon factors such as stressor chronicity, intensity, frequency and modality. Neural mechanisms driving chronic stress responses can be distinct from those controlling acute reactions, including recruitment of novel limbic, hypothalamic and brainstem circuits. Importantly, an individual’s response to acute or chronic stress is determined by numerous factors, including genetics, early life experience, environmental conditions, sex and age. The context in which stressors occur will determine whether an individual’s acute or chronic stress responses are adaptive or maladaptive (pathological). PMID:27065163

  9. Nodular Scleroderma Revisited: Systemic Sclerosis Presenting as Annular Keloidal Sclerotic Plaques

    PubMed Central

    Lortscher, David N.; Cohen, Philip R.; Bangert, Carolyn A.

    2016-01-01

    Background: Nodular scleroderma, also known as keloidal scleroderma, is a rare variant of systemic sclerosis. Purpose: The clinical features, pathologic findings and postulated pathogenesis of nodular scleroderma are discussed. Methods: A woman with previously undiagnosed systemic sclerosis who presented with nodular scleroderma is described. Using the PubMed database, a literature search was performed on keloidal scleroderma, nodular scleroderma, and systemic sclerosis. Results: Nodular scleroderma is characterized by firm plaques or nodules, which can mimic a keloid, that are typically located on the anterior orposterior upper trunk and the arms; they show pathologic changes of scleroderma, keloid, or hypertrophic scar. Akeloidal response of inflamed skin that is involved in an active fibrotic process inherent to systemic sclerosis, in individuals who are genetically predisposed to keloid formation, is the hypothesized pathogenesis. Conclusion: Nodular scleroderma is rare. The authors’ patient presented with diarrhea, dysphagia, fatigue, Raynaud’s phenomenon, shortness of breath, and annular keloidal plaques of morphea whose biopsy showed features of hypertrophic scar; additional studies confirmed the diagnosis of the nodular scleroderma variant of systemic sclerosis. The possibility of systemic sclerosis should be entertained in patients who present with nodularor keloidal plaques that morphologically resemble morphea and have histologic findings of a scar or a keloid—especially if there are associated symptoms suggestive for systemic sclerosis. PMID:27386053

  10. Evening Activities as a Potential Confound in Research on the Adrenocortical System in Children

    ERIC Educational Resources Information Center

    Kertes, Darlene A.; Gunnar, Megan R.

    2004-01-01

    The relation among children's evening activities, behavioral characteristics, and activity of the hypothalamic-pituitary-adrenocortical axis was assessed in normally developing children ages 7 to 10 years. Salivary cortisol at bedtime was compared on evenings when children had structured activities outside of the home with unstructured evenings at…

  11. Emotional and Adrenocortical Regulation in Early Adolescence: Prediction by Attachment Security and Disorganization in Infancy

    ERIC Educational Resources Information Center

    Spangler, Gottfried; Zimmermann, Peter

    2014-01-01

    The aim of the present study was to examine differences in emotion expression and emotion regulation in emotion-eliciting situations in early adolescence from a bio-psycho-social perspective, specifically investigating the influence of early mother-infant attachment and attachment disorganization on behavioural and adrenocortical responses. The…

  12. Metastatic congenital adrenocortical carcinoma: a case report with tumor remission at 3 1/2 years.

    PubMed

    Godil, M A; Atlas, M P; Parker, R I; Priebe, C J; Zerah, M M; Kane, P; Tsung, J; Wilson, T A

    2000-11-01

    We describe a case of metastasizing congenital adrenocortical carcinoma and a follow-up of 3 1/2 yr. Treatment with surgery and mitotane was associated with multiple complications. The patient was in remission at 3 1/2 yr. Because of the rarity of this condition, we discuss step-by-step problems encountered during management. PMID:11095414

  13. The Effects of Morning Naps, Car Trips, and Maternal Separation on Adrenocortical Activity in Human Infants.

    ERIC Educational Resources Information Center

    Larson, Mary C.; And Others

    1991-01-01

    Three studies examined adrenocortical activity in infants. Morning naps were associated with decreases in salivary cortisol. Riding for 40 minutes in a car lowered salivary cortisol concentrations. Thirty minutes of maternal separation in the laboratory resulted in higher salivary cortisol concentrations than did 30 minutes of play with the mother…

  14. Novel markers of gonadectomy-induced adrenocortical neoplasia in the mouse and ferret

    PubMed Central

    Schillebeeckx, Maximiliaan; Pihlajoki, Marjut; Gretzinger, Elisabeth; Yang, Wei; Thol, Franziska; Hiller, Theresa; Löbs, Ann-Kathrin; Röhrig, Theresa; Schrade, Anja; Cochran, Rebecca; Jay, Patrick Y.; Heikinheimo, Markku; Mitra, Robi D.; Wilson, David B.

    2014-01-01

    Gonadectomy (GDX) induces sex steroid-producing adrenocortical tumors in certain mouse strains and in the domestic ferret. Transcriptome analysis and DNA methylation mapping were used to identify novel genetic and epigenetic markers of GDX-induced adrenocortical neoplasia in female DBA/2J mice. Markers were validated using a combination of laser capture microdissection, quantitative RT-PCR, in situ hybridization, and immunohistochemistry. Microarray expression profiling of whole adrenal mRNA from ovariectomized vs. intact mice demonstrated selective upregulation of gonadal-like genes including Spinlw1 and Insl3 in GDX-induced adrenocortical tumors of the mouse. A complementary candidate gene approach identified Foxl2 as another gonadal-like marker expressed in GDX-induced neoplasms of the mouse and ferret. That both “male-specific” (Spinlw1) and “female-specific” (Foxl2) markers were identified is noteworthy and implies that the neoplasms exhibit mixed characteristics of male and female gonadal somatic cells. Genome-wide methylation analysis showed that two genes with hypomethylated promoters, Igfbp6 and Foxs1, are upregulated in GDX-induced adrenocortical neoplasms. These new genetic and epigenetic markers may prove useful for studies of steroidogenic cell development and for diagnostic testing. PMID:25289806

  15. Maternal-child adrenocortical attunement in early childhood: continuity and change.

    PubMed

    Hibel, Leah C; Granger, Douglas A; Blair, Clancy; Finegood, Eric D

    2015-01-01

    This study evaluated continuity and change in maternal-child hypothalamic-pituitary-adrenal axis attunement in early childhood. Participants were drawn from a prospective study of 1,292 mother-child dyads, which were racially diverse, predominantly low-income, and non-urban. Child focused stress tasks designed to elicit anger, fear, and frustration were administered during early infancy, later infancy, and toddlerhood. Mothers' and children's saliva samples (later assayed for cortisol) were collected before and after the tasks. The strength of mother-child adrenocortical attunement was conserved across infancy and toddlerhood. The magnitude of maternal-child adrenocortical attunement decreased in response to the child-focused stress tasks. Maternal sensitivity and the child's task-related emotional reactivity moderated adrenocortical attunement across the task, with greater maternal sensitivity during a free-play, and lower levels of child emotional reactivity during the stress tasks, stabilizing attunement from pre- to post-task levels. The findings advance our understanding of individual differences in the social regulation of adrenocortical activity in early childhood. PMID:25417896

  16. 2D-DIGE proteomic analysis identifies new potential therapeutic targets for adrenocortical carcinoma

    PubMed Central

    Armignacco, Roberta; Ercolino, Tonino; Canu, Letizia; Baroni, Gianna; Nesi, Gabriella; Galli, Andrea; Mannelli, Massimo; Luconi, Michaela

    2015-01-01

    Adrenocortical carcinoma (ACC) is a rare aggressive tumor with poor prognosis when metastatic at diagnosis. The tumor biology is still mostly unclear, justifying the limited specificity and efficacy of the anti-cancer drugs currently available. This study reports the first proteomic analysis of ACC by using two-dimensional-differential-in-gel-electrophoresis (2D-DIGE) to evaluate a differential protein expression profile between adrenocortical carcinoma and normal adrenal. Mass spectrometry, associated with 2D-DIGE analysis of carcinomas and normal adrenals, identified 22 proteins in 27 differentially expressed 2D spots, mostly overexpressed in ACC. Gene ontology analysis revealed that most of the proteins concurs towards a metabolic shift, called the Warburg effect, in adrenocortical cancer. The differential expression was validated by Western blot for Aldehyde-dehydrogenase-6-A1,Transferrin, Fascin-1,Lamin A/C,Adenylate-cyclase-associated-protein-1 and Ferredoxin-reductase. Moreover, immunohistochemistry performed on paraffin-embedded ACC and normal adrenal specimens confirmed marked positive staining for all 6 proteins diffusely expressed by neoplastic cells, compared with normal adrenal cortex. In conclusion, our preliminary findings reveal a different proteomic profile in adrenocortical carcinoma compared with normal adrenal cortex characterized by overexpression of mainly metabolic enzymes, thus suggesting the Warburg effect also occurs in ACC. These proteins may represent promising novel ACC biomarkers and potential therapeutic targets if validated in larger cohorts of patients. PMID:25691058

  17. Open adrenalectomy for medium sized adrenocortical tumour: How I do it?

    PubMed Central

    Sameh, Wael M.; Kotb, Ahmed Fouad

    2015-01-01

    Introduction: The aim of our work was to report our experience in managing cases with medium-sized adrenocortical carcinoma by the high retroperitoneal extra pleural approach. Methods: During the past 2 years, 10 patients with suspected adrenocortical carcinoma were managed by our technique: the high supra 10th rib, retroperitoneal extra pleural approach. We included cases with 5 to 10 cm adrenal masses, suspected as adrenocortical carcinoma. Results: The mean patient age was 38 years (range: 26–44), the median tumour volume was 7 cm (range: 5–8). Of the 10 patients, 7 were female. Of the patients, 6 had right- and 4 had left-sided tumours. Intraoperatively, all cases had proper surgical removal, with no apparent residual tumour tissue. No single patient required a chest tube or developed respiratory problems. There were no major vascular injuries during surgery. We did not compare our findings to the standard lateral or subcostal approaches, as in our institution we adopt this high lateral approach for medium-sized tumours, while managing larger tumours with transperitoneal subcostal approach and smaller tumours laparoscopically. Conclusion: The high supra 10th lateral retroperitoneal, extra pleural approach is a safe, doable technique, allowing easy access to medium-sized suprarenal tumours and its vasculature, for cases suspected to be adrenocortical carcinoma. PMID:26029297

  18. The Relations between Bullying Exposures in Middle Childhood, Anxiety, and Adrenocortical Activity

    ERIC Educational Resources Information Center

    Carney, JoLynn V.; Hazler, Richard J.; Oh, Insoo; Hibel, Leah C.; Granger, Douglas A.

    2010-01-01

    This exploratory study investigated how exposure to bullying at school in middle childhood is associated with student anxiety levels and adrenocortical activity at a time preceding lunch when anxiety about potential bullying would potentially be higher. Ninety-one sixth-grade students (55 female and 36 male) reported being exposed one or more…

  19. Raman Spectroscopy of Microbial Pigments

    PubMed Central

    Edwards, Howell G. M.; Oren, Aharon

    2014-01-01

    Raman spectroscopy is a rapid nondestructive technique providing spectroscopic and structural information on both organic and inorganic molecular compounds. Extensive applications for the method in the characterization of pigments have been found. Due to the high sensitivity of Raman spectroscopy for the detection of chlorophylls, carotenoids, scytonemin, and a range of other pigments found in the microbial world, it is an excellent technique to monitor the presence of such pigments, both in pure cultures and in environmental samples. Miniaturized portable handheld instruments are available; these instruments can be used to detect pigments in microbiological samples of different types and origins under field conditions. PMID:24682303

  20. Nodular renal blastoma in kidney with multicystic dysplasia. Report of a case.

    PubMed

    Corsi, A; Boldrini, R; Caione, P; Bosman, C

    1995-04-01

    The clinico-pathologic association of nodular renal blastema, multicystic kidney and obstructive uropathy has been recently identified. We report on a female patient diagnosed as having unilater multicystic dysplasia by prenatal ultrasonography. The patient was nephrectomized at the age of 6 1/2 months. Examination of the resected kidney revealed multiple unilocular cysts in the cortex and hypoplasia of the homolateral ureter; histological study confirmed the presence of multiple cysts limited to the renal cortex, and revealed, among them, multiple cortical metanephric blastema cells islands. Our case supports a relationship between nodular renal blastema, cortical cysts and obstructive uropathy; ureter hypoplasia could cause intraluminal back pressure, with consequent abnormal development of the ampullae, normally endowed in nephronic anlagens induction, cystic tubular ectasia and persistence of nodular renal blastema. The peripheral location of renal nodular blastema and cysts supports a late error in nephrogenesis, at the time of formation of the last generation of nephrons. PMID:8532415

  1. Nodular Vasculitis That Developed during Etanercept (Enbrel) Treatment in a Patient with Psoriasis

    PubMed Central

    Park, Seung-Bae; Chang, In-Kyu; Im, Myung; Lee, Young; Kim, Chang-Deok; Seo, Young-Joon

    2015-01-01

    Nodular vasculitis was introduced by Montgomery for cases of erythema induratum-like lesions that were not associated with tuberculosis. Nodular vasculitis has been associated with both nontuberculous infections and noninfectious conditions. However, there has been no report on the development of nodular vasculitis during tumor necrosis factor-α inhibitor treatment. A 28-year-old man visited our clinic for the treatment of severe psoriasis with a 20-year history. Subcutaneous injection of etanercept (25 mg, twice weekly) was started. One year later, erythematous nodules developed on his lower leg. A skin biopsy showed lobular panniculitis with extensive necrosis and vasculitis. To exclude latent tuberculosis, an assay specific for Mycobacterium tuberculosis antigens was performed, with a negative result. After stopping etanercept under the diagnosis of nodular vasculitis associated with etanercept, the lesions gradually disappeared, leaving depressed scars in 3 months. There has been no recurrence after 6 months of follow-up. PMID:26512176

  2. Advanced diagnostic approaches and current medical management of insulinomas and adrenocortical disease in ferrets (Mustela putorius furo).

    PubMed

    Chen, Sue

    2010-09-01

    Endocrine neoplasia is the most common tumor type in domestic ferrets, especially in middle-aged to older ferrets. Islet cell tumors and adrenocortical tumors constitute the major types of endocrine neoplasms. Insulinoma is a tumor that produces and releases excessive amounts of insulin. Evaluation of fasted blood glucose levels provides a quick diagnostic assessment for the detection of insulinomas. Use of glucocorticoids, diazoxide, and diet modification are some of the medical treatment options for insulinomas. Adrenocortical neoplasia in ferrets usually overproduces one or more sex hormones. Sex hormones which can result in progressive alopecia, vulvar swelling in females, and prostagomegaly in males. Abdominal ultrasonography and sex hormone assays can be used to diagnose adrenocortical neoplasms. Drugs such as leuprolide acetate, deslorelin acetate, and the hormone melatonin can be used to treat adrenocortical neoplasms in ferrets when surgery is not an option. PMID:20682429

  3. Effects of ToxCast Phase I Chemicals on Steroidogenesis in H295R Human Adrenocortical Carcinoma cells (SOT)

    EPA Science Inventory

    Steroid hormones are essential for proper development and reproduction. Disruption of steroidogenesis by environmental toxicants results in altered hormone levels causing adverse reproductive and developmental effects. H295R human adrenocortical carcinoma cells were used to evalu...

  4. Hepatic focal nodular hyperplasia with congenital portosystemic shunt.

    PubMed

    Cho, Yuki; Shimono, Taro; Morikawa, Hiroyasu; Shintaku, Haruo; Tokuhara, Daisuke

    2014-12-01

    Hepatic focal nodular hyperplasia (FNH) is a rare benign tumor in children. Vascular anomalies have been identified as pathological features of FNH, but the etiology remains unclear. We describe a rare case including the time course of formation of hepatic FNH in response to congenital portosystemic shunt (PSS). A 4-month-old girl was identified on newborn mass screening to have hypergalactosemia, but no inherited deficiencies in galactose-metabolizing enzymes were found. Ultrasonography and per-rectal portal scintigraphy showed intrahepatic PSS of the right lobe as a cause of the hypergalactosemia. At age 12 months, the patient had elevated hepatic enzymes and small hypoechoic hepatic lesions around the shunt. On abdominal contrast-enhanced ultrasonography spoke-wheel sign and central stellate scar were seen, which are typical features of hepatic FNH without biopsy. Congenital intrahepatic PSS should be evaluated on abdominal contrast-enhanced ultrasonography and observed over time because of its potential to develop into hepatic FNH. PMID:25521987

  5. Thermo-Metallurgical Modeling of Nodular Cast Iron Cooling Process

    NASA Astrophysics Data System (ADS)

    Carazo, Fernando D.; Dardati, Patricia M.; Celentano, Diego J.; Godoy, Luis A.

    2012-12-01

    A new numerical model to describe the microstructural evolution of a eutectic nodular cast iron during its cooling is presented. In particular, equiaxial solidification assuming an independent nucleation of austenite and graphite nodules is considered. In this context, the austenite has dendritic growth whereas the graphite grows with a spherical shape. After solidification occurs, the model assumes that the graphite nodules present in the cast iron continue growing since the carbon content in austenite decreases. Once the stable eutectoid temperature is reached, the alloy undergoes the austenite-ferrite transformation. The nucleation of the ferrite takes place at the contour of the spherical graphite nodules where austenite has low carbon concentration. A ferrite shell surrounding the graphite nodules is formed afterward by means of a process governed by carbon diffusion. Then, a ferrite-pearlite competitive transformation occurs when the temperature is below the metastable temperature. This thermo-metallurgical model is discretized and solved by means of the finite element method. The model allows the computation of cooling curves, fraction evolution for each component, and size and distribution of graphite nodules. The present numerical results are compared with experiments using standardized Quick-cup-type cups, and satisfactory numerical predictions of the final microstructure and cooling curves are achieved.

  6. Retroperitoneal nodular fasciitis: a benign etiology on the differential diagnosis of malignant gastric outlet obstruction

    PubMed Central

    Jiang, Wei; Coben, Robert M.

    2015-01-01

    Nodular fasciitis is a relatively rare, benign and proliferative lesion that is not typically found in the retroperitoneal (RP) space and has not been previously reported as a cause of gastric outlet obstruction (GOO). GOOs are frequently associated with malignancies, however, benign etiologies should be considered as well. We report the first case of GOO secondary to nodular fasciitis in the form of a spontaneously regressing RP mass that was initially concerning for malignancy. PMID:25830048

  7. Retroperitoneal nodular fasciitis: a benign etiology on the differential diagnosis of malignant gastric outlet obstruction.

    PubMed

    Kistler, C Andrew; Jiang, Wei; Coben, Robert M

    2015-04-01

    Nodular fasciitis is a relatively rare, benign and proliferative lesion that is not typically found in the retroperitoneal (RP) space and has not been previously reported as a cause of gastric outlet obstruction (GOO). GOOs are frequently associated with malignancies, however, benign etiologies should be considered as well. We report the first case of GOO secondary to nodular fasciitis in the form of a spontaneously regressing RP mass that was initially concerning for malignancy. PMID:25830048

  8. A Weeping Tumor in a Young Girl: An Unusual Presentation of Nodular Hidradenoma.

    PubMed

    Das, Anupam; Gayen, Tirthankar; Podder, Indrashis; Shome, Kaushik; Bandyopadhyay, Debabrata

    2016-01-01

    A 10-year-old girl presented with a swelling on her left thigh that was associated with dripping of serous fluid from the lesion. Based on histological features of the excised tumor, a diagnosis of nodular hidradenoma was made. Atypical features including large size of the tumor, location on the lower limb, a weeping presentation, and histological finding of a nodular hidradenoma with an unusually large cystic cavity discharging fluid prompted us to report the case. PMID:27293255

  9. A Weeping Tumor in a Young Girl: An Unusual Presentation of Nodular Hidradenoma

    PubMed Central

    Das, Anupam; Gayen, Tirthankar; Podder, Indrashis; Shome, Kaushik; Bandyopadhyay, Debabrata

    2016-01-01

    A 10-year-old girl presented with a swelling on her left thigh that was associated with dripping of serous fluid from the lesion. Based on histological features of the excised tumor, a diagnosis of nodular hidradenoma was made. Atypical features including large size of the tumor, location on the lower limb, a weeping presentation, and histological finding of a nodular hidradenoma with an unusually large cystic cavity discharging fluid prompted us to report the case. PMID:27293255

  10. Nonphotosynthetic pigments as potential biosignatures.

    PubMed

    Schwieterman, Edward W; Cockell, Charles S; Meadows, Victoria S

    2015-05-01

    Previous work on possible surface reflectance biosignatures for Earth-like planets has typically focused on analogues to spectral features produced by photosynthetic organisms on Earth, such as the vegetation red edge. Although oxygenic photosynthesis, facilitated by pigments evolved to capture photons, is the dominant metabolism on our planet, pigmentation has evolved for multiple purposes to adapt organisms to their environment. We present an interdisciplinary study of the diversity and detectability of nonphotosynthetic pigments as biosignatures, which includes a description of environments that host nonphotosynthetic biologically pigmented surfaces, and a lab-based experimental analysis of the spectral and broadband color diversity of pigmented organisms on Earth. We test the utility of broadband color to distinguish between Earth-like planets with significant coverage of nonphotosynthetic pigments and those with photosynthetic or nonbiological surfaces, using both 1-D and 3-D spectral models. We demonstrate that, given sufficient surface coverage, nonphotosynthetic pigments could significantly impact the disk-averaged spectrum of a planet. However, we find that due to the possible diversity of organisms and environments, and the confounding effects of the atmosphere and clouds, determination of substantial coverage by biologically produced pigments would be difficult with broadband colors alone and would likely require spectrally resolved data. PMID:25941875

  11. Comparative chromatography of chloroplast pigment

    NASA Technical Reports Server (NTRS)

    Grandolfo, M.; Sherma, J.; Strain, H. H.

    1969-01-01

    Methods for isolation of low concentration pigments of the cocklebur species are described. The methods entail two step chromatography so that the different sorption properties of the various pigments in varying column parameters can be utilized. Columnar and thin layer methods are compared. Many conditions influence separability of the chloroplasts.

  12. Nonphotosynthetic Pigments as Potential Biosignatures

    PubMed Central

    Cockell, Charles S.; Meadows, Victoria S.

    2015-01-01

    Abstract Previous work on possible surface reflectance biosignatures for Earth-like planets has typically focused on analogues to spectral features produced by photosynthetic organisms on Earth, such as the vegetation red edge. Although oxygenic photosynthesis, facilitated by pigments evolved to capture photons, is the dominant metabolism on our planet, pigmentation has evolved for multiple purposes to adapt organisms to their environment. We present an interdisciplinary study of the diversity and detectability of nonphotosynthetic pigments as biosignatures, which includes a description of environments that host nonphotosynthetic biologically pigmented surfaces, and a lab-based experimental analysis of the spectral and broadband color diversity of pigmented organisms on Earth. We test the utility of broadband color to distinguish between Earth-like planets with significant coverage of nonphotosynthetic pigments and those with photosynthetic or nonbiological surfaces, using both 1-D and 3-D spectral models. We demonstrate that, given sufficient surface coverage, nonphotosynthetic pigments could significantly impact the disk-averaged spectrum of a planet. However, we find that due to the possible diversity of organisms and environments, and the confounding effects of the atmosphere and clouds, determination of substantial coverage by biologically produced pigments would be difficult with broadband colors alone and would likely require spectrally resolved data. Key Words: Biosignatures—Exoplanets—Halophiles—Pigmentation—Reflectance spectroscopy—Spectral models. Astrobiology 15, 341–361. PMID:25941875

  13. 5th International ACC Symposium: Classification of Adrenocortical Cancers from Pathology to Integrated Genomics: Real Advances or Lost in Translation?

    PubMed

    de Krijger, Ronald E; Bertherat, Jérôme

    2016-02-01

    For the clinician, despite its rarity, adrenocortical cancer is a heterogeneous tumor both in term of steroid excess and tumor evolution. For patient management, it is crucial to have an accurate vision of this heterogeneity, in order to use a correct tumor classification. Pathology is the best way to classify operated adrenocortical tumors: to recognize their adrenocortical nature and to differentiate benign from malignant tumors. Among malignant tumors pathology also aims at prognosis assessment. Although progress has being made for prognosis assessment, there is still a need for improvement. Recent studies have established the value of Ki67 for adrenocortical cancer (ACC) prognostication, aiming also at standardization to reduce variability. The use of genomics to study adrenocortical tumors gives a very new insight in their pathogenesis and molecular classification. Genomics studies of ACC give now a clear description of the mRNA (transcriptome) and miRNA expression profile, as well as chromosomal and methylation alterations. Exome sequencing also established firmly the list of the main ACC driver genes. Interestingly, genomics study of ACC also revealed subtypes of malignant tumors with different pattern of molecular alterations, associated with different outcome. This leads to a new vision of adrenocortical tumors classification based on molecular analysis. Interestingly, these molecular classifications meet also the results of pathological analysis. This opens new perspectives on the development and use of various molecular tools to classify, along with pathological analysis, ACC, and guides patient management at the area of precision medicine. PMID:26676358

  14. New directions in phthalocyanine pigments

    NASA Technical Reports Server (NTRS)

    Trinh, Diep VO

    1994-01-01

    Phthalocyanines have been used as a pigment in coatings and related applications for many years. These pigments are some of the most stable organic pigments known. The phthalo blue and green pigments have been known to be ultraviolet (UV) stable and thermally stable to over 400 C. These phthalocyanines are both a semiconductor and photoconductor, exhibiting catalytic activity and photostabilization capability of polymers. Many metal free and metallic phthalocyanine derivatives have been prepared. Development of the new classes of phthalocyanine pigment could be used as coating on NASA spacecraft material such as glass to decrease the optical degradation from UV light, the outside of the space station modules for UV protection, and coating on solar cells to increase lifetime and efficiency.

  15. [INHERITANCE OF EPIDERMIS PIGMENTATION IN SUNFLOWER ACHENES].

    PubMed

    Gorohivets, N A; Vedmedeva, E V

    2016-01-01

    Inheritance of epidermis pigmentation in the pericarp of sunflower seeds was studied. Inheritance of pigmentation was confirmed by three alleles Ew (epidermis devoid of pigmentation), Estr (epidermal pigmentation in strips), Edg (solid pigmentation). Dominance of the lack of epidermis pigmentation over striped epidermis and striped epidermis over solid pigmentation was established. It was shown that the striped epidermis pigmentation and the presence of testa layer are controlled by two genes, expression of which is independent from each other. Yellowish hypodermis was discovered in the sample I2K2218, which is inherited monogenically dominantly. PMID:27281924

  16. Thyroid nodularity and cancer among Chernobyl cleanup workers from Estonia

    SciTech Connect

    Inskip, P.D.; Boice, J.D. Jr.; Tekkel, M.

    1997-02-01

    Thyroid examinations, including palpation, ultrasound and, selectively, fine-needle aspiration biopsy, were conducted on nearly 2,000 Chernobyl cleanup workers from Estonia to evaluate the occurrence of thyroid cancer and nodular thyroid disease among men with protracted exposure to ionizing radiation. The examinations were conducted in four cities in Estonia during March-April 1995, 9 years after the reactor accident. The study population was selected from a predefined cohort of 4,833 cleanup workers from Estonia under surveillance for cancer incidence. These men had been sent to Chernobyl between 1986 and 1991 to entomb the damaged reactor, remove radioactive debris and perform related cleanup activities. A total of 2,997 men were invited for thyroid screening and 1,984 (66%) were examined. Estimates of radiation dose from external sources were obtained from military or other institutional records, and details about service dates and types of work performed while at Chernobyl were obtained from a self-administered questionnaire. Blood samples were collected for assay of chromosomal translocations in circulating lymphocytes and loss of expression of the glycophorin A (GPA) gene in erythrocytes. The primary outcome measure was the presence or absence of thyroid nodules as determined by the ultrasound examination. Of the screened workers, 1,247 (63%) were sent to Chernobyl in 1986, including 603 (30%) sent in April or May, soon after the accident. Workers served at Chernobyl for an average of 3 months. The average age was 32 years at the time of arrival at Chernobyl and 40 years at the time of thyroid examination. The mean documented radiation dose from external sources was 10.8 cGy. Biological indicators of exposure showed low correlations with documented dose, but did not indicate that the mean dose for the population was higher than the average documented dose. 47 refs., 1 fig., 9 tabs.

  17. Hepatic adenoma and focal nodular hyperplasia: differential diagnosis and treatment.

    PubMed

    Herman, P; Pugliese, V; Machado, M A; Montagnini, A L; Salem, M Z; Bacchella, T; D'Albuquerque, L A; Saad, W A; Machado, M C; Pinotti, H W

    2000-03-01

    The diagnosis of benign hepatic tumors as hepatic adenoma (HA) and focal nodular hyperplasia (FNH) remains a challenge for clinicians and surgeons. The importance of differentiating between these lesions is based on the fact that HA must be surgically resected and FNH can be only observed. A series of 23 female patients with benign liver tumors (13 FNH, 10 HA) were evaluated, and a radiologic diagnostic algorithm was employed with the aim of establishing preoperative criteria for the differential diagnosis. All patients were submitted to surgical biopsy or hepatic resection to confirm the diagnosis. Based only on clinical and laboratory data, distinction was not possible. According to the investigative algorithm, the diagnosis was correct in 82.6% of the cases; but even with the development of imaging methods, which were used in combination, the differentiation was not possible in four patients. For FNH cases scintigraphy presented a sensitivity of 38.4% and specificity of 100%, whereas for HA the sensitivity reached 60% and specificity 85.7%. Magnetic resonance imaging, employed when scintigraphic findings were not typical, presented sensitivities of 71.4% and 80% and specificities of 100% and 100% for FNH and HA, respectively. Preoperative diagnosis of FNH was possible in 10 of 13 (76.9%) patients and was confirmed by histology in all of them. In one case, FNH was misdiagnosed as HA. The diagnosis of HA was possible in 9 of 10 (90%) adenoma cases. Surgical biopsy remains the best method for the differential diagnosis between HA and FNH and must be performed in all doubtful cases. Surgical resection is the treatment of choice for all patients with adenoma and can be performed safely. With the evolution of imaging methods it seems that the preoperative diagnosis of FNH may be considered reliable, thereby avoiding unnecessary surgical resection. PMID:10658075

  18. Treatment of Nodular Fasciitis Occurring on the Face

    PubMed Central

    Oh, Byung Ho; Kim, Jihee; Zheng, Zhenlong; Roh, Mi Ryung

    2015-01-01

    Background Surgical excision is generally recommended for the treatment of nodular fasciitis (NF) to rule out sarcoma. However, in cases of NF occurring on the face, the reported recurrence rate is higher and the surgical approach may result in considerable aesthetic concern. Objective To describe our experience with NF occurring on the face and evaluate the outcomes of surgical and nonsurgical methods of treatment. Methods We performed a retrospective review of 16 patients with NF on the face. The patients were treated with surgical excision or nonsurgical methods such as triamcinolone intralesional injection (TA ILI) and pinhole method with a carbon dioxide (CO2) laser. Results Among the 16 patients, surgical treatment was performed in 9 and recurrence occurred in 7 of these 9 patients (77.8%). The recurred lesions showed regression after repeated TA ILI. On the other hand, five patients underwent nonsurgical treatment after the histologic exclusion of malignancy. Their lesions showed regression after repeated pinhole treatment and TA ILI. In one case, NF spontaneously regressed. On a visual analogue scale, the nonsurgical approach showed superior results. However, the values were not statistically significant (6.90±1.56 vs. 5.61±1.36; p=0.163). The satisfaction level was lower in patients who experienced recurrence after surgical excision. Conclusion Surgical treatment for NF on the face showed a noticeable recurrence rate and resulted in scarring. Therefore, considering the possibility of spontaneous regression, the nonsurgical method can be considered as an alternative treatment option for NF on the face. PMID:26719638

  19. The role of periventricular nodular heterotopia in epileptogenesis.

    PubMed

    Aghakhani, Yahya; Kinay, Demet; Gotman, Jean; Soualmi, Lahbib; Andermann, Frederick; Olivier, André; Dubeau, François

    2005-03-01

    A temporal resection in patients with periventricular nodular heterotopia (PNH) and intractable focal seizures yields poor results. To define the role of heterotopic grey matter tissue in epileptogenesis and to improve outcome, we performed stereoencephalography (SEEG) recordings in eight patients with uni- or bilateral PNH and intractable focal epilepsy. The SEEG studies aimed to evaluate the most epileptogenic areas and included the allo- and neocortex and at least one nodule of grey matter. Interictal spiking activity was found in ectopic grey matter in three patients, in the cortex overlying the nodules in five and in the mesial temporal structures in all. At least one heterotopion was involved at seizure onset in six patients, synchronous with the overlying neocortex or ipsilateral hippocampus. Two patients had their seizures originating in the mesial temporal structures only. Six patients had surgery and the resected areas included the seizure onset, with follow-up from 1 to 8 years. An amygdalo-hippocampectomy was performed in two (Engel class Id and III), an amygdalo-hippocampectomy plus removal of an adjacent heterotopion in two (class Ia), and a resection of two contiguous nodules plus a small rim of overlying occipital cortex in one patient (class Id). One patient with bilateral PNH had three adjacent nodules resected and an ipsilateral amygdalo-hippocampectomy resulting in a reduction of the number of seizures by 25-50%. The best predictor of surgical outcome is the presence of a focal epileptic generator; this generator may or may not include the PNH. Invasive recording is required in patients with PNH; it improves localization and is the key to better outcome. PMID:15659421

  20. Natural pigments and sacred art

    NASA Astrophysics Data System (ADS)

    Kelekian, Lena, ,, Lady

    2010-05-01

    Since the dawn of mankind, cavemen has expressed himself through art. The earliest known cave paintings date to some 32,000 years ago and used 4 colours derived from the earth. These pigments were iron oxides and known as ochres, blacks and whites. All pigments known by the Egyptians, the Greeks, the Romans and Renaissance man were natural and it was not until the 18th century that synthetic pigments were made and widely used. Until that time all art, be it sacred or secular used only natural pigments, of which the preparation of many have been lost or rarely used because of their tedious preparation. As a geologist, a mineralogist and an artist specializing in iconography, I have been able to rediscover 89 natural pigments extracted from minerals. I use these pigments to paint my icons in the traditional Byzantine manner and also to restore old icons, bringing back their glamour and conserving them for years to come. The use of the natural pigments in its proper way also helps to preserve the traditional skills of the iconographer. In the ancient past, pigments were extremely precious. Many took an exceedingly long journey to reach the artists, and came from remote countries. Research into these pigments is the work of history, geography and anthropology. It is an interesting journey in itself to discover that the blue aquamarines came from Afghanistan, the reds from Spain, the greens Africa, and so on. In this contribution I will be describing the origins, preparation and use of some natural pigments, together with their history and provenance. Additionally, I will show how the natural pigments are used in the creation of an icon. Being a geologist iconographer, for me, is a sacrement that transforms that which is earthly, material and natural into a thing of beauty that is sacred. As bread and wine in the Eucharist, water during baptism and oil in Holy Union transmit sanctification to the beholder, natural pigments do the same when one considers an icon. The

  1. [Sepsis caused by pigmented and no pigmented Chromobacterium violaceum].

    PubMed

    Guevara, Armando; Salomón, Marlly; Oliveros, María; Guevara, Esmirna; Guevara, Milarys; Medina, Laida

    2007-10-01

    Chromobacterium violaceum sepsis is rare but associated with a high mortality rate. We report a fatal case of C. violaceum sepsis in a 6 years old Venezuelan indian boy. Clinical manifestations were fever and swelling in the right inguinal region. The initial diagnosis was an appendicular plastron. Appendicectomy was performed and during surgery a right psoas abscess was identified that resulted culture positive for pigmented C. violaceum. Blood cultures were positive for a pigmented and non pigmented C. violaceum strain. Imipenem and amikacin were administered despite of which the child died 9 days after hospital admission. PMID:17989847

  2. Familial cytomegalic adrenocortical hypoplasia: an X-linked syndrome of pubertal failure.

    PubMed Central

    Hay, I D; Smail, P J; Forsyth, C C

    1981-01-01

    Five boys with familial cytomegalic adrenocortical hypoplasia have been followed up for an average of 19 years. Despite treatment with replacement corticosteroids, all 5 failed to show a spontaneous onset of puberty and, when assessed at ages 13 to 19 years, all had both sexual infantilism and skeletal immaturity. Hypogonadism was confirmed by low levels of plasma testosterone, and pituitary reserve of gonadotrophin was shown to be inadequate by testing with gonadotrophin-releasing hormone. Two boys, both with adequate testosterone output on human chorionic gonadotrophin stimulation, were given gonadotrophin therapy, whereas the other 3 were treated with parenterally administered testosterone. With treatment, all 5 patients showed advances in pubertal staging. Although the mechanism of the hypogonadotropism remains unclear, the association of hypogonadotrophic hypogonadism with familial cytomegalic adrenocortical hypoplasia appears to be a constant one and may be considered as a treatable inherited syndrome of pubertal failure. PMID:7197507

  3. Adrenocortical Stem and Progenitor Cells: Unifying Model of Two Proposed Origins

    PubMed Central

    Wood, Michelle A.; Hammer, Gary D.

    2010-01-01

    The origins of our understanding of the cellular and molecular mechanisms by which signaling pathways and downstream transcription factors coordinate the specification of adrenocortical cells within the adrenal gland have arisen from studies on the role of Sf1 in steroidogenesis and adrenal development initiated 20 years ago in the laboratory of Dr. Keith Parker. Adrenocortical stem/progenitor cells have been predicted to be undifferentiated and quiescent cells that remain at the periphery of the cortex until needed to replenish the organ, at which time they undergo proliferation and terminal differentiation. Identification of these stem/progenitor cells has only recently been explored. Recent efforts have examined signaling molecules, including Wnt, Shh, and Dax1, which may coordinate intricate lineage and signaling relationships between the adrenal capsule (stem cell niche) and underlying cortex (progenitor cell pool) to maintain organ homeostasis in the adrenal gland. PMID:21094677

  4. A genetic and molecular update on adrenocortical causes of Cushing syndrome.

    PubMed

    Lodish, Maya; Stratakis, Constantine A

    2016-05-01

    Primary adrenal Cushing syndrome is the result of cortisol hypersecretion mainly by adenomas and, rarely, by bilateral micronodular or macronodular adrenocortical hyperplasia. cAMP-dependent protein kinase A (PKA) signalling is the major activator of cortisol secretion in the adrenal cortex. Many adenomas and hyperplasias associated with primary hypercortisolism carry somatic or germline mutations in genes that encode constituents of the cAMP-PKA pathway. In this Review, we discuss Cushing syndrome and its linkage to dysregulated cAMP-PKA signalling, with a focus on genetic findings in the past few years. In addition, we discuss the presence of germline inactivating mutations in ARMC5 in patients with primary bilateral macronodular adrenocortical hyperplasia. This finding has implications for genetic counselling of affected patients; hitherto, most patients with this form of adrenal hyperplasia and Cushing syndrome were thought to have a sporadic and not a familial disorder. PMID:26965378

  5. Low DICER1 expression is associated with poor clinical outcome in adrenocortical carcinoma

    PubMed Central

    de Sousa, Gabriela Resende Vieira; Ribeiro, Tamaya C.; Faria, Andre M.; Mariani, Beatriz M.P.; Lerario, Antonio M.; Zerbini, Maria Claudia N.; Soares, Iberê C.; Wakamatsu, Alda; Alves, Venancio A.F.; Mendonca, Berenice B.; Fragoso, Maria Candida B.V.; Latronico, Ana Claudia; Almeida, Madson Q.

    2015-01-01

    Low DICER1 expression was associated with poor outcome in several cancers. Recently, hot-spot DICER1 mutations were found in ovarian tumors, and TARBP2 truncating mutations in tumor cell lines with microsatellite instability. In this study, we assessed DICER1 e TRBP protein expression in 154 adult adrenocortical tumors (75 adenomas and 79 carcinomas). Expression of DICER1 and TARBP2 gene was assessed in a subgroup of 61 tumors. Additionally, we investigated mutations in metal biding sites located at the RNase IIIb domain of DICER1 and in the exon 5 of TARBP2 in 61 tumors. A strong DICER1 expression was demonstrated in 32% of adenomas and in 51% of carcinomas (p = 0.028). Similarly, DICER1 gene overexpression was more frequent in carcinomas (60%) than in adenomas (23%, p = 0.006). But, among adrenocortical carcinomas, a weak DICER1 expression was significantly more frequent in metastatic than in non-metastatic adrenocortical carcinomas (66% vs. 31%; p = 0.002). Additionally, a weak DICER1 expression was significantly correlated with a reduced overall (p = 0.004) and disease-free (p = 0.005) survival. In the multivariate analysis, a weak DICER1 expression (p = 0.048) remained as independent predictor of recurrence. Regarding TARBP2 gene, its protein and gene expression did not correlate with histopathological and clinical parameters. No variant was identified in hot spot areas of DICER1 and TARBP2. In conclusion, a weak DICER1 protein expression was associated with reduced disease-free and overall survival and was a predictor of recurrence in adrenocortical carcinomas. PMID:26087193

  6. Paediatric Nonfunctioning Adrenocortical Carcinoma with Extension up to Right-Side Heart: Cardiac Surgery Approach

    PubMed Central

    Quarti, Andrea; Surace, Chiara; Pozzi, Marco

    2016-01-01

    Adrenocortical carcinoma is a rare malignancy. Due to late diagnosis and no adequate effective adjuvant treatment, prognosis remains poor. Only approximately 30% of these malignancies are confined to the adrenal gland when they are diagnosed, as these tumors tend to be found years after their genesis. Cardiac involvement of adrenal carcinoma is very rare. We report a rare case of a 7-year-old female with right adrenal cortical carcinoma, involving the right-side heart. PMID:27493811

  7. Die Pigmente der antiken Malerei

    NASA Astrophysics Data System (ADS)

    Riederer, J.

    1982-02-01

    Scientific analysis of painted antique objects provides us with information about the pigments used in earlier periods of history. Beginning in prehistoric times, coloured earths and minerals were used exclusively until the 3rd millenium B.C. when an extensive production of artificial pigments started. Following Egyptian Blue, a potassium copper chloride, cobalt blue, and a cobalt aluminium oxide was invented but used only over a short period, until it was reinvented 200 years ago. In the Greecian and Roman times the palette was considerably enlarged by the use of other coloured minerals and artificially prepared pigments.

  8. High-density lipoprotein is a potential growth factor for adrenocortical cells

    SciTech Connect

    Murao, Koji . E-mail: mkoji@kms.ac.jp; Imachi, Hitomi; Cao, Wenming; Yu, Xiao; Li, Junhua; Yoshida, Kazuya; Ahmed, Rania A.M.; Matsumoto, Kensuke; Nishiuchi, Takamasa; Ishida, Toshihiko; Wong, Norman C.W.

    2006-05-26

    The entry of cholesterol contained within high-density lipoprotein (HDL) into adrenocortical cells is mediated by a human homologue of SR-BI, CD36, and LIMPII Analogous-1 (CLA-1) and thus augmenting their growth. To address the role of CLA-1, we created a mutant mCLA that lacked the C-terminal tail. HDL CE selective uptake by cells carrying the mCLA-1 receptor was fully active and equivalent to those transfected with full-length CLA-1 (fCLA-1). Expression of mCLA inhibited the proliferation of an adrenocortical cell line and the incorporation of [{sup 3}H]thymidine into the cells. This effect was sensitive to wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K). Our transcriptional studies revealed that the inhibitory action of mCLA required the transcriptional factor AP-1 and the effect of HDL on AP-1 activation was also abrogated by wortmannin. These findings raise the possibility that the inhibitors of the effects of HDL may be of therapeutic value for adrenocortical tumor.

  9. Small-Conductance Ca2+-Activated Potassium Channels Negatively Regulate Aldosterone Secretion in Human Adrenocortical Cells.

    PubMed

    Yang, Tingting; Zhang, Hai-Liang; Liang, Qingnan; Shi, Yingtang; Mei, Yan-Ai; Barrett, Paula Q; Hu, Changlong

    2016-09-01

    Aldosterone, which plays a key role in maintaining water and electrolyte balance, is produced by zona glomerulosa cells of the adrenal cortex. Autonomous overproduction of aldosterone from zona glomerulosa cells causes primary hyperaldosteronism. Recent clinical studies have highlighted the pathological role of the KCNJ5 potassium channel in primary hyperaldosteronism. Our objective was to determine whether small-conductance Ca(2+)-activated potassium (SK) channels may also regulate aldosterone secretion in human adrenocortical cells. We found that apamin, the prototypic inhibitor of SK channels, decreased membrane voltage, raised intracellular Ca(2+) and dose dependently increased aldosterone secretion from human adrenocortical H295R cells. By contrast, 1-Ethyl-2-benzimidazolinone, an agonist of SK channels, antagonized apamin's action and decreased aldosterone secretion. Commensurate with an increase in aldosterone production, apamin increased mRNA expression of steroidogenic acute regulatory protein and aldosterone synthase that control the early and late rate-limiting steps in aldosterone biosynthesis, respectively. In addition, apamin increased angiotensin II-stimulated aldosterone secretion, whereas 1-Ethyl-2-benzimidazolinone suppressed both angiotensin II- and high K(+)-stimulated production of aldosterone in H295R cells. These findings were supported by apamin-modulation of basal and angiotensin II-stimulated aldosterone secretion from acutely prepared slices of human adrenals. We conclude that SK channel activity negatively regulates aldosterone secretion in human adrenocortical cells. Genetic association studies are necessary to determine whether mutations in SK channel subtype 2 genes may also drive aldosterone excess in primary hyperaldosteronism. PMID:27432863

  10. Ultrastructural Localization of Endogenous Exchange Factor for ARF6 in Adrenocortical Cells In Situ of Mice

    PubMed Central

    Chomphoo, Surang; Mothong, Wilaiwan; Sawatpanich, Tarinee; Kanla, Pipatphong; Sakagami, Hiroyuki; Kondo, Hisatake; Hipkaeo, Wiphawi

    2016-01-01

    EFA6 (exchange factor for ARF6) activates Arf6 (ADP ribosylation factor 6) by exchanging ADP to ATP, and the resulting activated form of Arf6 is involved in the membrane dynamics and actin re-organization of cells. The present study was attempted to localize EFA6 type D (EFA6D) in mouse adrenocortical cells in situ whose steroid hormone secretion is generally considered not to depend on the vesicle-involved regulatory mechanism. In immunoblotting, an immunoreactive band with the same size as brain EFA6D was detected in homogenates of adrenal cortical tissues almost free of adrenal capsules and medulla. In immuno-light microscopy, EFA6D-immunoreactivity was positive in adrenocortical cells and it was often distinct along the plasmalemma, especially along portions of the cell columns facing the interstitium. In immuno-electron microscopy, the gold-labeling was more dense in the peripheral intracellular domains than the central domain of the immunopositive cells. The labeling was deposited on the plasma membranes in a discontinuous pattern and in cytoplasmic domains rich in filaments. It was also associated with some, but not all, of pleiomorphic vesicles and coated pits/vesicles. No labeling was seen in association with lipid droplets or smooth endoplasmic reticulum. The present finding is in support of the importance of EFA6D for activation of Arf6 in adrenocortical cells. PMID:27462133

  11. Ultrastructural Localization of Endogenous Exchange Factor for ARF6 in Adrenocortical Cells In Situ of Mice.

    PubMed

    Chomphoo, Surang; Mothong, Wilaiwan; Sawatpanich, Tarinee; Kanla, Pipatphong; Sakagami, Hiroyuki; Kondo, Hisatake; Hipkaeo, Wiphawi

    2016-06-28

    EFA6 (exchange factor for ARF6) activates Arf6 (ADP ribosylation factor 6) by exchanging ADP to ATP, and the resulting activated form of Arf6 is involved in the membrane dynamics and actin re-organization of cells. The present study was attempted to localize EFA6 type D (EFA6D) in mouse adrenocortical cells in situ whose steroid hormone secretion is generally considered not to depend on the vesicle-involved regulatory mechanism. In immunoblotting, an immunoreactive band with the same size as brain EFA6D was detected in homogenates of adrenal cortical tissues almost free of adrenal capsules and medulla. In immuno-light microscopy, EFA6D-immunoreactivity was positive in adrenocortical cells and it was often distinct along the plasmalemma, especially along portions of the cell columns facing the interstitium. In immuno-electron microscopy, the gold-labeling was more dense in the peripheral intracellular domains than the central domain of the immunopositive cells. The labeling was deposited on the plasma membranes in a discontinuous pattern and in cytoplasmic domains rich in filaments. It was also associated with some, but not all, of pleiomorphic vesicles and coated pits/vesicles. No labeling was seen in association with lipid droplets or smooth endoplasmic reticulum. The present finding is in support of the importance of EFA6D for activation of Arf6 in adrenocortical cells. PMID:27462133

  12. Morphological changes in the pituitary-adrenocortical axis in natives of La Paz

    NASA Astrophysics Data System (ADS)

    Gosney, John; Heath, Donald; Williams, David; Rios-Dalenz, Jaime

    1991-03-01

    Increased activity of the hypothalamic-pituitary-adrenocortical axis is part of the response to the stress of initial exposure to hypoxia, but there is evidence to suggest that it persists after homeostatic stability has been regained and acclimatization achieved. The adrenal glands of five lifelong residents of La Paz, Bolivia, who had lived at altitudes in the range 3600 3800 m, were significantly larger than those in age-matched controls from sea level (15.3g vs 10.4g; P<0.001) and appeared hyperplastic. The pituitary glands of the highlanders were not significantly different in size from those of the controls (0.67 g vs 0.51 g), but contained larger populations of corticotrophs expressed in terms of the total cell population of their anterior lobes (25.6% vs 19.4%; P<0.001). In conjunction with other studies of this endocrine axis in man and animals exposed to a hypoxic environment, these data suggest that greater amounts of adrenocorticotrophic hormone (ACTH) are required to maintain normal adrenocortical function under such circumstances, probably as a result of hypoxic inhibition of adrenocortical sensitivity to stimulation. Physiological hyperplasia of the adrenal cortex may be common in people living at high altitude.

  13. Nesfatin-1 inhibits proliferation and enhances apoptosis of human adrenocortical H295R cells.

    PubMed

    Ramanjaneya, Manjunath; Tan, Bee K; Rucinski, Marcin; Kawan, Mohamed; Hu, Jiamiao; Kaur, Jaspreet; Patel, Vanlata H; Malendowicz, Ludwik K; Komarowska, Hanna; Lehnert, Hendrik; Randeva, Harpal S

    2015-07-01

    NUCB2/nesfatin and its proteolytically cleaved product nesfatin-1 are recently discovered anorexigenic hypothalamic neuroproteins involved in energy homeostasis. It is expressed both centrally and in peripheral tissues, and appears to have potent metabolic actions. NUCB2/nesfatin neurons are activated in response to stress. Central nesfatin-1 administration elevates circulating ACTH and corticosterone levels. Bilateral adrenalectomy increased NUCB2/nesfatin mRNA levels in rat paraventricular nuclei. To date, studies have not assessed the effects of nesfatin-1 stimulation on human adrenocortical cells. Therefore, we investigated the expression and effects of nesfatin-1 in a human adrenocortical cell model (H295R). Our findings demonstrate that NUCB2 and nesfatin-1 are expressed in human adrenal gland and human adrenocortical cells (H295R). Stimulation with nesfatin-1 inhibits the growth of H295R cells and promotes apoptosis, potentially via the involvement of Bax, BCL-XL and BCL-2 genes as well as ERK1/2, p38 and JNK1/2 signalling cascades. This has implications for understanding the role of NUCB2/nesfatin in adrenal zonal development. NUCB2/nesfatin may also be a therapeutic target for adrenal cancer. However, further studies using in vivo models are needed to clarify these concepts. PMID:25869615

  14. Neuromedin-U stimulates enucleation-induced adrenocortical regeneration in the rat.

    PubMed

    Trejter, Marcin; Neri, Giuliano; Rucinski, Marcin; Majchrzak, Mariola; Nussdorfer, Gastone G; Malendowicz, Ludwik K

    2008-06-01

    Neuromedin-U (NMU) is a brain-gut peptide, which has been previously found to stimulate hypothalamic-pituitary-adrenal axis in the rat. Enucleation-induced adrenal regeneration in rats with contralateral adrenalectomy is a well-established model of adrenal growth, that not only depends on the compensatory ACTH hypersecretion, but is also modulated by several regulatory peptides. Hence, we investigated whether NMU may be included in this group of bioactive molecules. Reverse transcription-polymerase chain reaction and immunocytochemistry showed that regenerating rat adrenocortical cells at days 5 and 8 after surgery express the NMU receptor NMUR1 as mRNA and protein. NMU8 administration to rats bearing regenerating adrenals markedly raised the plasma concentration of corticosterone and notably enhanced proliferative activity of adrenocortical cells. ACTH blood level was unchanged at day 5 and significantly decreased at day 8. The conclusion is drawn that NMU stimulates regeneration of rat adrenal cortex, via a mechanism independent of pituitary ACTH and involving the activation of NMUR1 located on adrenocortical cells. PMID:18506360

  15. Toying with fate: Redirecting the differentiation of adrenocortical progenitor cells into gonadal-like tissue

    PubMed Central

    Röhrig, Theresa; Pihlajoki, Marjut; Ziegler, Ricarda; Cochran, Rebecca S.; Schrade, Anja; Schillebeeckx, Maximiliaan; Mitra, Robi D.; Heikinheimo, Markku; Wilson, David B.

    2014-01-01

    Cell fate decisions are integral to zonation and remodeling of the adrenal cortex. Animal models exhibiting ectopic differentiation of gonadal-like cells in the adrenal cortex can shed light on the molecular mechanisms regulating steroidogenic cell fate. In one such model, prepubertal gonadectomy (GDX) of mice triggers the formation of adrenocortical neoplasms that resemble luteinized ovarian stroma. Transcriptomic analysis and genome-wide DNA methylation mapping have identified genetic and epi-genetic markers of GDX-induced adrenocortical neoplasia. Members of the GATA transcription factor family have emerged as key regulators of cell fate in this model. Expression of Gata4 is pivotal for the accumulation of gonadal-like cells in the adrenal glands of gonadectomized mice, whereas expression of Gata6 limits the spontaneous and GDX-induced differentiation of gonadal-like cells in the adrenal cortex. Additionally, Gata6 is essential for proper development of the adrenal X-zone, a layer analogous to the fetal zone of the human adrenal cortex. The relevance of these observations to developmental signaling pathways in the adrenal cortex, to other animal models of altered adrenocortical cell fate, and to human diseases is discussed. PMID:25498963

  16. EFFECT OF BILATERAL OOPHORECTOMY ON ADRENOCORTICAL FUNCTION IN WOMEN WITH POLYCYSTIC OVARY SYNDROME (PCOS)

    PubMed Central

    Azziz, Ricardo; Chang, Wendy Y.; Stanczyk, Frank Z.; Woods, Keslie

    2012-01-01

    Objective To determine the impact of ovary-secreted products on adrenocortical function in women with PCOS by studying the adrenocortical response to acute adrenocorticotropic-stimulating hormone (ACTH) stimulation before and after bilateral oophorectomy. Design Prospective study. Setting Tertiary care medical center Participants Fourteen women with PCOS scheduled for bilateral oophorectomy for benign indications, on transdermal estradiol (E2) postoperatively. Interventions Physical exam, blood sampling before and after oophorectomy, measurement of hormone levels. Basal (Steroid0), maximum stimulated (Steroid60), and net increment (ΔSteroid) levels of androstenedione (A4), dehydroepiandrosterone (DHEA), and cortisol (F) before and after ACTH-1–24 stimulation were assessed. Main Outcome Measures Pre- and post-operative basal and ACTH(1–24)-stimulated hormonal levels. Results Total testosterone, free testosterone, and estrone levels decreased, and FSH levels increased significantly following oophorectomy. No significant differences in E2, DHEA sulfate (DHEAS) or sex hormone binding globulin levels were detected. Basal and ACTH-stimulated A4 levels decreased significantly following oophorectomy, and ΔA4 was significantly increased. No significant differences in DHEA0, DHEA60, or F0 levels were detected; F60 and ΔF levels tended to increase following oophorectomy, but the differencesdid not reach significance. Conclusions Ovarian factors do not appear to contribute significantly to the adrenocortical dysfunction of PCOS. PMID:23122827

  17. Upregulation of TSHR, TTF-1, and PAX8 in Nodular Goiter Is Associated with Iodine Deficiency in the Follicular Lumen

    PubMed Central

    Chen, Lijun; Liang, Bo; Cai, Huiyao; Cai, Qingyan; Shi, Yaxiong

    2016-01-01

    Objective. It has been testified that iodine regulates thyroid function by controlling thyroid-restricted genes expression and is closely related to diffuse goiter and thyroid dysfunction. However, the effects of follicular lumen iodine, the main form of iodine reserve in the body, on thyroid-restricted genes in nodular goiter are poorly understood. In this study, correlations between follicular lumen iodine and the expressions of thyroid stimulating hormone receptor (TSHR), its transcription factors TTF-1, and PAX8 in nodular goiter were investigated. Patients. In this study, 30 resection specimens clinically histopathologically confirmed to have nodular goiter and 30 normal thyroid specimens from adjacent tissues of nodular goiter are used. Measurement. Western blot immunohistochemistry was performed to assay TSHR, TTF-1, and PAX8 in thyrocytes of nodular goiter as well as in extranodular normal thyroid tissues. Meanwhile, follicular lumen iodine of both nodular goiter and extranodular normal thyroid tissues was detected as well. Results. The TSHR, TTF-1, and PAX8 in nodular goiter were significantly higher than those in the controls. The iodine content in nodular goiter was significantly lower than those in control tissues. Conclusion. Upregulation of TSHR, TTF-1, and PAX8 is associated with low follicular lumen iodine content in nodular goiter. PMID:27525008

  18. Yolk pigments of the Mexican leaf frog.

    PubMed

    Marinetti, G V; Bagnara, J T

    1983-02-25

    Eggs of the Mexican leaf frog contain blue and yellow pigments identified as biliverdin and lutein, respectively. Both pigments are bound to proteins that occur in crystalline form in the yolk platelet. The major blue pigment is biliverdin IX alpha. The eggs vary in color from brilliant blue to pale yellow-green depending on the amount of each pigment. These pigments may provide protective coloration to the eggs. PMID:6681678

  19. Relapsing nodular lesions in the course of adult pulmonary Langerhans cell histiocytosis.

    PubMed

    Tazi, A; Montcelly, L; Bergeron, A; Valeyre, D; Battesti, J P; Hance, A J

    1998-06-01

    In most patients with pulmonary Langerhans cell histiocytosis (LCH), clinical and radiological abnormalities initially either stabilize or regress, often without treatment. Little information is available, however, concerning the subsequent evolution of disease in patients who initially follow a benign course. We describe four patients with biopsy-confirmed pulmonary LCH whose initial course was characterized by regression of parenchymal nodular lesions, but who subsequently developed one or more episodes of active disease 7 mo to 7.5 yr after their initial presentation. In each case, the subsequent episodes of active disease were characterized by the reappearance or marked increase in nodular radiographic abnormalities, whose presence was confirmed by high-resolution computed tomography (HRCT). Thus, initial regression of nodular lesions in pulmonary LCH does not preclude the reappearance of one or more episodes of active disease, and may have important consequences on the long-term prognosis of these patients. PMID:9620939

  20. Nodular Fasciitis of the Hand Over the Metacarpophalangeal Joint: A Case Report

    PubMed Central

    Sailon, Alexander M; Cappuccino, Guy; Hameed, Meera; Fleegler, Earl J

    2008-01-01

    Objective: This study describes a case of nodular fasciitis involving the hand and reviews the neoplasm's pertinent clinical, histologic, and pathologic features. Methods: The patient's chart, operative record, histologic specimens, and relevant literature were reviewed. Results: We report a case of nodular fasciitis involving the hand of a 55-year-old woman that was treated with marginal excision. Conclusions: Nodular fasciitis is a self-limited, benign soft tissue tumor composed of fibroblasts and myofibroblasts that typically afflicts younger patients and rarely presents in the hand. Because of its presentation, it can be easily mistaken for a malignant neoplasm. However, most cases represent a reactive and therefore a polyclonal process. Marginal excision generally provides definitive treatment. PMID:18725954

  1. Effects of Type 1 Insulin-Like Growth Factor Receptor Silencing in a Human Adrenocortical Cell Line.

    PubMed

    Ribeiro, T C; Jorge, A A; Montenegro, L R; Almeida, M Q; Ferraz-de-Souza, B; Nishi, M Y; Mendonca, B B; Latronico, A C

    2016-07-01

    Type 1 insulin-like growth factor receptor (IGF-1R) is overexpressed in a variety of human cancers, including adrenocortical tumors. The aim of the work was to investigate the effects of IGF-1R downregulation in a human adrenocortical cell line by small interfering RNA (siRNA). The human adrenocortical tumor cell line NCI H295R was transfected with 2 specific IGF1R siRNAs (# 1 and # 2) and compared with untreated cells and a negative control siRNA. IGF1R expression was determined by quantitative reverse-transcription PCR (qRTPCR) and Western blot. The effects of IGF-1R downregulation on cell proliferation and apoptosis were assessed. IGF-1R levels were significantly decreased in cells treated with IGF-1R siRNA # 1 or # 2. Relative expression of IGF1R mRNA decreased approximately 50% and Western blot analysis revealed a 30% of reduction in IGF-1R protein. Downregulation of this gene resulted in 40% reduction in cell growth in vitro and 45% increase in apoptosis using siRNA # 2. These findings demonstrate that decreasing IGF-1R mRNA and protein expression in NCI H295R cells can partially inhibit adrenal tumor cell growth in vitro. Targeting IGF1R is a promising therapy for pediatric malignant adrenocortical tumor and can still be an option for adult adrenocortical cancer based on personalized genomic tumor profiling. PMID:27246621

  2. Coexistence of Solid (Nodular) and Differentiated (Adenoid) Basal Cell Carcinoma at the Same Anatomical Site

    PubMed Central

    Rao, Angoori Gnaneshwar

    2015-01-01

    Coexistence of two different histopathological types of basal cell carcinomas (BCCs) in the same anatomical site is rare and interesting. Herein, we report a case of coexistence of nodular and adenoid BCC in a 78-year-old peasant who presented with a plaque and a globular swelling on left paranasal region of few years duration. Histopathology of skin biopsy with immunohistochemistry study using antibodies to S100, epithelial membrane antigen (EMA) and cytokeratin 7 (CK 7) from the margin of the ulcer and globular swelling confirmed the diagnosis that revealed features of nodular and adenoid basal cell carcinoma, respectively. Investigative work up did not reveal evidence of metastasis. PMID:26538745

  3. Drug-induced Hypersensitivity Syndrome Accompanied by Pulmonary Lesions Exhibiting Centrilobular Nodular Shadows.

    PubMed

    Sawata, Tetsuro; Bando, Masashi; Kogawara, Haruna; Nakayama, Masayuki; Mato, Naoko; Yamasawa, Hideaki; Takemura, Tamiko; Sugiyama, Yukihiko

    2016-01-01

    A 51-year-old woman diagnosed with Crohn's disease developed drug-induced hypersensitivity syndrome (DIHS) 12 and six weeks after starting the oral intake of mesalazine and trimethoprim/sulfamethoxazole, respectively. Chest CT showed centrilobular nodular shadows and a transbronchial lung biopsy (TBLB) revealed infiltration of inflammatory cells predominantly in the small pulmonary artery walls and bronchiolar walls. Regarding pulmonary lesions of DIHS, infiltrative shadows have sometimes been reported, whereas nodular shadows have rarely been documented. This is a valuable case report for considering the mechanism underlying the development of pulmonary lesions in case of DIHS. PMID:27150872

  4. Intraneural nodular fasciitis of the radial nerve with rapidly progressive motor symptoms

    PubMed Central

    Sundar, Swetha J.; Healy, Andrew T.; Shook, Steven J.; Kamian, Kambiz

    2016-01-01

    Background: Nodular fasciitis is a benign mesenchymal tumor arising from fascia that typically presents as a rapidly growing, subcutaneous mass. Intraneural cases are very rare and can present with neurological symptoms, requiring surgical resection. Case Description: A 31-year-old woman presented to us with painful paresthesias in her elbow and progressive motor deficits, for which she underwent surgery. Conclusion: The authors report the first case of intraneural nodular fasciitis occurring in the radial nerve and highlight the possibility of rapidly progressive motor deficit in patients presenting with this rare clinical entity. PMID:27114852

  5. [Antibodies to phospholipids and the vascular endothelium in nodular polyarteritis].

    PubMed

    Kirdianov, S Iu; Baranov, A A; Nasonov, E L; Salozhin, K V; Gur'eva, M S; Abaĭtova, N E; Bazhina, O V

    2001-01-01

    Clinical significance of antibodies to phospholipids (aPL) and vascular endothelium (aVE) was evaluated in 20 patients (9 women and 11 men aged 36 +/- 10.8 years) with nodular polyarteritis (NP) corresponding to classification criteria of the USA Rheumatology College. Antibodies to cardiolipin (aCL) (IgG and IgM) and to beta 2-glycoprotein (beta 2-GP1) (IgG) were titered by solid-phase enzyme immunoassay. Total serum level of aVE (IgG + IgM + IgA) was measured by solid-phase enzyme immunoassay using Eahy. 926 endothelial hybrydoma cell culture. Anticardiolipin antibodies were detected in 11 (55%) of 20 patients, 3 of these had IgG aCL, 4 IgM aCL, and 4 both antibody isotypes. Serum titers of all aCL were moderate in all cases. No antibodies to beta 2-GP1 were detected in any of the patients. Total serum endothelial activity varied from 0 to 89.7% in patients with NP. Mean aVE level was 24.45 +/- 21.2%, which was significantly higher than in donors (p < 0.001). In 4 (26.7%) of 15 patients with NP total level of aVE surpassed the upper threshold normal value. The presence of aCL directly correlated with the presence of reticular livedo (r = 0.54, p < 0.05), but not with any other clinical laboratory manifestations of the disease, including thrombotic complications (deep thrombosis of lower limb veins, stroke, myocardial infarction), renal involvement, increased erythrocyte sedimentation rate, increased concentrations of von Willebrand factor antigen and C-reactive protein, or angiitis activity. Vascular endothelial antibodies directly correlated with renal involvement (r = 1.00, p < 0.01), distal gangrene of the limb (r = 0.83, p < 0.01), and angiitis activity (r = 0.78, p < 0.001), with high level of von Willebrand factor antigen and increased erythrocyte sedimentation rate (r = 0.66 and r = 0.64, respectively; p < 0.01), but not with aCL (r = 0.43, p > 0.05) of any isotype (aCL IgG r = -0.01; r = 0.34; p < 0.05). All patients with aVE had aCL in the serum (aCL Ig

  6. Multiple pigmented basal cell carcinomas.

    PubMed

    Shoji, T; Lee, J; Hong, S H; Oh, C H; Kim, W K; Bhawan, J

    1998-04-01

    Basal cell carcinoma is the most common of all skin cancers and the most prevalent one among Caucasians. Rarely, these tumors are seen in other races. We report a 77-year-old Korean woman who presented with multiple darkly pigmented enlarging nodules on her scalp, face, trunk, and extremities. The patient had first noted a 6-mm pigmented lesion on her left eyebrow 10 years previously. Since then, other lesions had appeared in many locations on her body. She had been otherwise healthy and without a history of exposure to arsenic or radiation. There was no family history of skin cancer, xeroderma pigmentosum, or basal cell nevus syndrome. On physical examination, multiple darkly pigmented dome-shaped papules and nodules were present on her scalp, face, right forearm, lower abdomen, and inguinal areas. They ranged in size from 0.5 mm to 2 cm. The larger ones showed central ulceration. Multiple biopsy specimens from different sites showed pigmented basal cell carcinomas. Clinically, there was no evidence of nevus sebaceus, xeroderma pigmentosum, basal cell nevus syndrome, or immunodeficiency. Clinical workup including chest radiography, abdominal ultrasound, bone scan, and brain computerized axial tomography scan did not demonstrate primary or secondary tumors. The results of serologic and hematologic tests were also within normal limits. This is an unusual case report of multiple pigmented basal cell carcinomas in an Asian woman without any predisposing risk factors. PMID:9557792

  7. Exogenous pigment in Peyer's patches

    SciTech Connect

    Shepherd, N.A.; Crocker, P.R.; Smith, A.P.; Levison, D.A.

    1987-01-01

    Dark brown granular pigment was found consistently in macrophages in the deep aspect of adult Peyer's patches. Tissue sections from intestinal resections of 35 patients with a variety of pathologic diagnoses and of seven postmortem cases with no evidence of gastrointestinal disease were examined for the presence of this pigment. It was found in all patients over the age of 6 years (34 cases) but was not found in any children below that age (eight cases). Scanning electron microscopy with secondary and backscattered electron imaging and x-ray energy spectroscopy were performed on routine histologic sections. The pigmented macrophages contained aluminum and silicon, diffusely present throughout the cytoplasm, and numerous discrete foci of titanium. Pigment containing these same elements has also been found around dilated submucosal lymphatics, in mesenteric lymph nodes, and in some transmural inflammatory aggregates of Crohn's disease. The pigment probably is derived from the diet and actively taken up by Peyer's patches, which are able to incorporate inert particulate matter.

  8. Pigment Analysis of Chloroplast Pigment-Protein Complexes in Wheat

    PubMed Central

    Eskins, Kenneth; Duysen, Murray E.; Olson, Linda

    1983-01-01

    Pigment-protein complexes separated from wheat (Triticum aestivum L. selection ND96-25 by two gel electrophoresis techniques were analyzed by high-performance liquid chromatography for chlorophylls and carotenoids. The two techniques are compared, and pigment analyses are given for the major reaction centers and light-harvesting complexes. Reaction centers contain mostly chlorophyll a, carotene, and lutein, whereas light-harvesting complexes contain chlorophyll a, chlorophyll b, lutein, and neoxanthin. The amounts of violaxanthin are variable. Images Fig. 1 PMID:16662906

  9. Pigmented Porokeratosis. A Further Variant?

    PubMed

    Tan, Tracy S P; Tallon, Ben

    2016-03-01

    Porokeratosis is a clonal disorder of keratinization characterized by the presence of the cornoid lamella. A number of variants of porokeratosis have been described, based on the clinical features and histologic features of the lesions. The authors present a case of porokeratosis with prominent melanocytic hyperplasia, which was biopsied to clinically exclude melanoma. The authors retrospectively studied cases of porokeratosis to look for the presence of melanocytic hyperplasia. Melanocytic hyperplasia was identified in 8 of 31 cases (25.8%). All of the cases except the index case were clinically nonpigmented but arose in solar damaged skin. This case represents a distinct variant of porokeratosis, and the authors propose the designation pigmented porokeratosis. Melanocytic hyperplasia is a benign condition, and it is important that this is not histologically confused with melanoma in situ, particularly in a context of clinically pigmented lesion. Increased recognition of pigmented porokeratosis is essential to avoid an erroneous diagnosis of melanoma in situ. PMID:26894774

  10. Microprobe analysis of chlorpromazine pigmentation

    SciTech Connect

    Benning, T.L.; McCormack, K.M.; Ingram, P.; Kaplan, D.L.; Shelburne, J.D.

    1988-10-01

    We describe the histochemical, ultrastructural, and microanalytical features of a skin biopsy specimen obtained from a patient with chlorpromazine pigmentation. Golden-brown pigment granules were present in the dermis, predominantly in a perivascular arrangement. The granules stained positively with the Fontana-Masson stain for silver-reducing substances and negatively with Perl's stain for iron. Electron microscopy revealed dense inclusion bodies in dermal histiocytes, pericytes, endothelial cells, and Schwann cells, as well as lying free in the extracellular matrix. These ''chlorpromazine bodies'' were quite dense even in unosmicated, unstained ultrathin sections, indicating that the pigmentation is related, at least in part, to the inclusions. Microprobe analysis of the chlorpromazine bodies revealed a striking peak for sulfur, which strongly suggests the presence of the drug or its metabolite within these inclusions.

  11. Molecular Imaging in the Management of Adrenocortical Cancer: A Systematic Review.

    PubMed

    Wong, Ka Kit; Miller, Barbra S; Viglianti, Benjamin L; Dwamena, Ben A; Gauger, Paul G; Cook, Gary J; Colletti, Patrick M; Rubello, Domenico; Gross, Milton D

    2016-08-01

    Adrenocortical cancer (ACC) is an uncommon primary neoplasm of the adrenal cortex with dismal prognosis. It often presents with symptoms and signs of adrenal cortical hormone hypersecretion and abdominal mass effect or is incidentally detected as an adrenal mass on imaging performed for other indications. Endocrine evaluation, comprehensive staging, and meticulous resection are crucial to ensure the best possible outcome. Despite extensive initial surgical resection, local and distant metastases are not uncommon with disappointing 5-year survival, although progress is being made at high-volume centers. Accurate restaging of recurrent disease is important to guide further management. Mitotane, external beam radiation and chemotherapy, and newer anticancer systemic treatments are used as adjunctives for inoperable disease and distant metastases. Contrast-enhanced CT and MRI are first-line imaging modalities for evaluation of ACC to characterize adrenal masses and to determine tumor resectability. Emerging literature supports F-FDG PET/CT use to determine the malignant potential of adrenal masses. In patients with a diagnosis of ACC, FDG PET/CT is sensitive for detecting metastatic disease, and its tumor accumulation has been correlated to pathology, Weiss scores, and prognosis. Metomidate, labeled with C for PET or with I for SPECT/CT, allows characterization of an adrenal mass as being of adrenocortical origin with high specificity. Taking advantage of its adrenocortical avidity, metomidate has been labeled with I for radionuclide therapy in a subset of ACC. In this review, we describe how nuclear medicine imaging, and specifically PET, can assist surgical management of ACC. PMID:26825212

  12. Acid Ceramidase (ASAH1) Is a Global Regulator of Steroidogenic Capacity and Adrenocortical Gene Expression

    PubMed Central

    Lucki, Natasha C.; Bandyopadhyay, Sibali; Wang, Elaine; Merrill, Alfred H.

    2012-01-01

    In H295R human adrenocortical cells, ACTH rapidly activates ceramide (Cer) and sphingosine (SPH) turnover with a concomitant increase in SPH-1-phosphate secretion. These bioactive lipids modulate adrenocortical steroidogenesis, primarily by acting as second messengers in the protein kinase A/cAMP-dependent pathway. Acid ceramidase (ASAH1) directly regulates the intracellular balance of Cer, SPH, and SPH-1-phosphate by catalyzing the hydrolysis of Cer into SPH. ACTH/cAMP signaling stimulates ASAH1 transcription and activity, supporting a role for this enzyme in glucocorticoid production. Here, the role of ASAH1 in regulating steroidogenic capacity was examined using a tetracycline-inducible ASAH1 short hairpin RNA H295R human adrenocortical stable cell line. We show that ASAH1 suppression increases the transcription of multiple steroidogenic genes, including Cytochrome P450 monooxygenase (CYP)17A1, CYP11B1/2, CYP21A2, steroidogenic acute regulatory protein, hormone-sensitive lipase, 18-kDa translocator protein, and the melanocortin-2 receptor. Induced gene expression positively correlated with enhanced histone H3 acetylation at target promoters. Repression of ASAH1 expression also induced the expression of members of the nuclear receptor nuclear receptor subfamily 4 (NR4A) family while concomitantly suppressing the expression of dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1. ASAH1 knockdown altered the expression of genes involved in sphingolipid metabolism and changed the cellular amounts of distinct sphingolipid species. Finally, ASAH1 silencing increased basal and cAMP-dependent cortisol and dehydroepiandrosterone secretion, establishing ASAH1 as a pivotal regulator of steroidogenic capacity in the human adrenal cortex. PMID:22261821

  13. microRNAs as Potential Biomarkers in Adrenocortical Cancer: Progress and Challenges

    PubMed Central

    Cherradi, Nadia

    2016-01-01

    Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis and limited therapeutic options. Over the last decade, pan-genomic analyses of genetic and epigenetic alterations and genome-wide expression profile studies allowed major advances in the understanding of the molecular genetics of ACC. Besides the well-known dysfunctional molecular pathways in adrenocortical tumors, such as the IGF2 pathway, the Wnt pathway, and TP53, high-throughput technologies enabled a more comprehensive genomic characterization of adrenocortical cancer. Integration of expression profile data with exome sequencing, SNP array analysis, methylation, and microRNA (miRNA) profiling led to the identification of subgroups of malignant tumors with distinct molecular alterations and clinical outcomes. miRNAs post-transcriptionally silence their target gene expression either by degrading mRNA or by inhibiting translation. Although our knowledge of the contribution of deregulated miRNAs to the pathogenesis of ACC is still in its infancy, recent studies support their relevance in gene expression alterations in these tumors. Some miRNAs have been shown to carry potential diagnostic and prognostic values, while others may be good candidates for therapeutic interventions. With the emergence of disease-specific blood-borne miRNAs signatures, analyses of small cohorts of patients with ACC suggest that circulating miRNAs represent promising non-invasive biomarkers of malignancy or recurrence. However, some technical challenges still remain, and most of the miRNAs reported in the literature have not yet been validated in sufficiently powered and longitudinal studies. In this review, we discuss the current knowledge regarding the deregulation of tumor-associated and circulating miRNAs in ACC patients, while emphasizing their potential significance in pathogenic pathways in light of recent insights into the role of miRNAs in shaping the tumor microenvironment. PMID:26834703

  14. The reticulin algorithm for adrenocortical tumor diagnosis: a multicentric validation study on 245 unpublished cases.

    PubMed

    Duregon, Eleonora; Fassina, Ambrogio; Volante, Marco; Nesi, Gabriella; Santi, Raffaella; Gatti, Gaia; Cappellesso, Rocco; Dalino Ciaramella, Paolo; Ventura, Laura; Gambacorta, Marcello; Dei Tos, Angelo Paolo; Loli, Paola; Mannelli, Massimo; Mantero, Franco; Berruti, Alfredo; Terzolo, Massimo; Papotti, Mauro

    2013-09-01

    The pathologic diagnosis of adrenocortical carcinoma (ACC) still needs to be improved, because the renowned Weiss Score (WS) system has a poor reproducibility of some parameters and is difficult to apply in borderline cases and in ACC variants. The "reticulin algorithm" (RA) defines malignancy through an altered reticulin framework associated with 1 of the 3 following parameter: necrosis, high mitotic rate, and vascular invasion. This study aimed at validating the interobserver reproducibility of reticulin stain evaluation in an unpublished series of 245 adrenocortical tumors (61 adenomas and 184 carcinomas) from 5 Italian centers, classified according to the WS. Eight pathologists reviewed all reticulin-stained slides. After training, a second round of evaluation on discordant cases was performed 10 weeks later. The RA reclassified 67 cases (27%) as adenomas, including 44 with no reticulin alterations and 23 with an altered reticulin framework but lacking the subsequent parameters of the triad. The other 178 cases (73%) were carcinomas according to the above-mentioned criteria. A complete (8/8 pathologists) interobserver agreement was reached in 75% of cases (κ=0.702), irrespective of case derivation, pathologists' experience, and histologic variants, and was further improved when only those cases with high WS and clinically malignant behavior were considered. After the training, the overall agreement increased to 86%. We conclude that reticulin staining is a reliable technique and an easy-to-interpret system in adrenocortical tumors; moreover, it has a high interobserver reproducibility, which supports the notion of using such a method in the proposed 2-step RA approach for ACC diagnosis. PMID:23774167

  15. Autonomic and adrenocortical reactivity and buccal cell telomere length in kindergarten children

    PubMed Central

    Kroenke, Candyce H; Epel, Elissa; Adler, Nancy; Bush, Nicole R.; Obradović, Jelena; Lin, Jue; Blackburn, Elizabeth; Stamperdahl, Juliet Lise; Boyce, W. Thomas

    2011-01-01

    Objective To examine associations between autonomic nervous system and adrenocortical reactivity to laboratory stressors and buccal cell telomere length (BTL) in children. Methods The study sample comprised 78 five- and six-year-old children from a longitudinal cohort study of kindergarten social hierarchies, biological responses to adversity, and child health. Buccal cell samples and reactivity measures were collected in the spring of the kindergarten year. BTL was measured by realtime PCR, as the telomere-to-single copy gene (T/S) ratio. Parents provided demographic information; parents and teachers reported children’s internalizing and externalizing behavior problems. Components of children’s autonomic (heart rate (HR), respiratory sinus arrhythmia (RSA), pre-ejection period (PEP)) and adrenocortical (salivary cortisol) responses were monitored during standardized laboratory challenges. We examined relations between reactivity, internalizing and externalizing behavior, and BTL, adjusted for age, race, and gender. Results Heart rate and cortisol reactivity were inversely related to BTL, PEP was positively related to BTL, and RSA was unrelated. Internalizing behaviors were also inversely related to BTL (standardized β=−0.33, p=0.004). Split at the median of reactivity parameters, children with high sympathetic activation (decreasing PEP) and high parasympathetic withdrawal (decreasing RSA) did not differ with regard to BTL. However, children with both this profile and high cortisol reactivity (N=12) had significantly shorter BTL (0.80 vs. 1.00, χ2=7.6, p=0.006), compared with other children. Conclusions Autonomic and adrenocortical reactivity in combination were associated with shorter buccal cell telomere length in children. These data suggest that psychophysiological processes may influence, and that BTL may be a useful marker of, early biological aging. PMID:21873585

  16. Massive nodular pseudoangiomatous stromal hyperplasia (PASH) of the breast arising simultaneously in the axilla and vulva.

    PubMed

    Jordan, Adrienne C; Jaffer, Shabnam; Mercer, Stephen E

    2011-02-01

    The authors describe a 52-year-old woman with a history of bilateral mastectomies for macromastia caused by massive nodular pseudoangiomatous stromal hyperplasia (PASH), who presented with 2 large growths in her left axilla and groin. These masses had been increasing in size for nearly a year. When excised, the axillary mass had dimensions of 14.0 × 14.0 × 5.5 cm(3) and weighed 664 g. The groin mass was slightly smaller at 14.5 × 11.0 × 5.0 cm(3) and 518 g. Microscopic examination of both masses revealed breast tissue expanded by a hyalinized stroma with prominent slit-like pseudovascular spaces, consistent with PASH. Small incidental foci of PASH are common findings in breast excisions; however, large nodular foci are rare. Furthermore, nodular foci in accessory breast tissue are exceedingly rarer and can raise clinical concerns for malignancy. Histopathologically, PASH can be mistaken for low-grade angiosarcoma. To the authors' knowledge, the present case appears to be the first description of multiple simultaneous foci of massive nodular PASH arising in accessory breast tissue. PMID:21285079

  17. Characteristics of autoclave and in-reactor nodular corrosion of Zircaloys

    SciTech Connect

    Jeong, Y.H.; Rheem, K.S. ); Chung, H.M. )

    1990-11-01

    Nodular corrosion characteristics of recrystallized Zircaloy-4 were investigated in static autoclave tests at 500{degree}C and 10.3 MPa. The roles of annealing temperature, cooling rate after beta-treating at 1050{degree}C, cold work, and surface treatment in corrosion tests were correlated with the results of microstructural characterization by scanning and transmission electron microscopies. A good correlation was obtained between average size of intermetallic precipitates and weight gain, in contrast to nodule coverage and nodule number density. These results could be best explained by the hypothesis that nodules nucleate in local regions that are depleted of Fe and Cr alloying elements. Some observations were inconsistent with the premise that nodules nucleate on or near intermetallic precipitates. Nodular corrosion characteristics and microstructures of commercial Zircaloy-2 cladding of fuel and gadolinia rods, obtained from several BWRs after burnup of 11--30 MWd/kgU, were also examined. Partial amorphization of intermetallic precipitates in BWR Zircaloy-2, and virtual dissolution and in an extreme case spinodal- like fluctuations of dissolved alloying elements in PWR Zircaloy-4 cladding were observed. Occurrence of nodular oxidation of Zircaloy-2 in BWRs could best be correlated to average size of intermetallic precipitates before irradiation and to fuel cladding operating temperature. For an intermetallic size range of 250--700 nm, nodular oxides were observed at 288{degree}C, but only thick uniform oxide was observed at 307{degree}C. 53 refs., 14 figs., 1 tab.

  18. Adrenocortical tumor with precocious puberty in a 2-month-old girl.

    PubMed

    Marret, Jean-Baptiste; Raffoul, Lara; Ribault, Virginie; Ravasse, Philippe; Rod, Julien

    2015-10-01

    Adrenocortical tumor is a rare childhood tumor with a median age at onset of 3.2 years. Virilization is the most common sign. Laparotomy is the reference treatment and has a favorable course. The diagnosis of adrenal tumor can be difficult. The main parameters of malignant tumors are size and metastasis. Analysis of TP53 mutation can facilitate final diagnosis. We report a case of virilizing adrenal tumor that developed in a 2-month-old girl, and which was treated with laparoscopic adrenalectomy. PMID:26508188

  19. Ghrelin and obestatin inhibit enucleation-induced adrenocortical proliferation in the rat.

    PubMed

    Rucinski, Marcin; Trejter, Marcin; Ziolkowska, Agnieszka; Tyczewska, Marianna; Malendowicz, Ludwik K

    2010-05-01

    Studies involving the role of ghrelin (GHREL) in regulating the proliferative activity of various cell types have obtained variable results depending primarily on the experimental model applied. It was recently reported that neither GHREL nor obestatin (OBS) affected the proliferative activity of cultured rat adrenocortical cells. In view of the conflicting results, we investigated the effects of GHREL and OBS on the proliferative activity of rat adrenocortical cells in a model of bilateral enucleation-induced adrenocortical regeneration in the rat. Rats were sacrificed 5 or 8 days after surgery. Twenty-four hours before being sacrificed, the appropriate groups were infused with 3 nmol GHREL or OBS/100 g. The mitotic index was assessed using the stachmokinetic method with vincristine. In comparison with intact rats, expression levels of ppGHREL, BAX, JUN-B and JUN-C genes were notably higher in regenerating adrenals, and neither GHREL nor OBS infusion affected these levels. Expression levels of the GHS-R, GPR39v2 and FOS genes were affected neither by adrenal enucleation nor GHREL or OBS infusion. Expression of only two studied genes, GPR39v1 and EGR1, was regulated by OBS. In the regenerating adrenal glands, GPR39v1 and EGR1 mRNA levels were higher than the levels in intact animals. GHREL infusion had no effect while OBS infusion notably stimulated GPR39v1 mRNA levels in the regenerating adrenal gland and evoked an opposite effect on EGR1 mRNA. OBS administration resulted in a potent decrease in the mitotic index of the studied cells, an effect found at both days 5 and 8 of the experiment. GHREL exerted a similar effect only at day 5 of adrenocortical regeneration. Neither GHREL nor OBS had an effect on blood aldosterone concentrations. GHREL infusion lowered plasma corticosterone concentration at day 5 but not 8 of the experiment, while OBS administration was ineffective. Thus, this study is the first to demonstrate that, in vivo, both GHREL and OBS inhibit the

  20. Characterizing adrenocortical activity in zoo-housed southern three-banded armadillos (Tolypeutes matacus).

    PubMed

    Howell-Stephens, Jennifer A; Brown, Joel S; Bernier, David; Mulkerin, Diane; Santymire, Rachel M

    2012-08-01

    Improving the husbandry in the southern three-banded armadillo (Tolypeutes matacus) through gaining knowledge of its stress physiology is imperative to maintaining a healthy, zoo-housed population. Our objectives were to: 1) validate the use of fecal hormone analysis for monitoring adrenocortical activity using both an adrenocorticotropic hormone (ACTH) challenge and biological events; and 2) characterize longitudinal adrenocortical activity in male and female southern three-banded armadillos. An ACTH injection was given intra-muscularly to one male (4IU/kg; 5.6IU total) and one female (5.5IU/kg; 8IU total) southern three-banded armadillo. Fecal samples were collected 1 day pre- and continued 5 days post-ACTH to capture the physiological response measured by elevated fecal glucocorticoid metabolites (FGM) to validate these techniques. Additionally, natural and routine events, including pairing individuals for breeding and veterinary procedures/handling, were used to biologically validate these techniques. To characterize adrenocortical activity, fecal samples (∼3025 total; n=275/animal/yr) were collected from 11 (5 males; 6 females) southern three-banded armadillos 5-7 times a week for 1 year at Lincoln Park Zoo (Chicago, IL). A cortisol enzyme immunoassay was used for FGM analysis. The ACTH challenge in the male resulted in a twofold increase of FGM (1123.2±36.2 ng/g dry feces) above baseline (675.7±10.0 ng/g dry feces) at approximately 54-94h post- injection. The female exhibited a twofold increase (1635.4 ng/g dry feces) over baseline FGMs (608.5±12.3 ng/g dry feces) approximately 30h post-injection. Reproductive behaviors and veterinary procedures resulted in elevated FGM concentrations from all individuals except for one male. The longitudinal characterization demonstrated that sex and season did not influence (P<0.05) FGM concentrations. Individuals were highly variable with mean FGM concentration of 2010.1±862.4 ng/g dry feces (range, 816.3-7889.1 ng

  1. Properties and requirements for production of a macrophage product which suppresses steroid production by adrenocortical cells.

    PubMed Central

    Mathison, J C; La Forest, A C; Ulevitch, R J

    1984-01-01

    Lipopolysaccharide-treated murine peritoneal exudate macrophages (PEM) release a factor or factors into the supernatant that suppress adrenocorticotropic hormone-induced steroidogenesis in explanted rabbit adrenocortical cells (J. C. Mathison et al., J. Immunol. 130:2757-2762, 1983). To determine the requirements for suppression, PEM supernatants (30 microliters) were added to explanted rabbit adrenocortical cells in a final volume of 120 microliters with 10 mU of adrenocorticotropic hormone per ml, and after 18 h at 37 degrees C, steroid concentrations were measured by a fluorometric assay. Supernatant from proteose peptone-elicited C3HeB/FeJ PEM (5 X 10(6) PEM per 3.5-cm well, 10 micrograms of Salmonella minnesota Re595 LPS per ml, 18 h) suppressed steroid production ca. 50%, and kinetic studies demonstrated that the appearance of suppressive activity in the supernatant was gradual over 4 to 18 h. Release of suppressive activity was not associated with decreased viability of the PEM (assessed by fluorescein diacetate staining and measurement of lactic dehydrogenase in the supernatant). Suppression was not observed when the PEM supernatant was diluted 10-fold before addition to the adrenocortical cells, whereas supernatant concentrated 20-fold (prepared with a 10,000-molecular-weight-cutoff filter) produced 75 to 80% suppression. The suppressive activity was stable at pH 4, pH 11, or 70 degrees C for 30 min but was inactivated at 100 degrees C (10 min). Suppressive activity was also induced in C3HeB/FeJ PEM by O111:B4 lipopolysaccharide or heat-killed Listeria monocytogenes. In contrast, PEM from C3H/HeJ mice did not produce detectable suppressive activity in response to Re595 lipopolysaccharide or heat-killed L. monocytogenes. Thus, these results provide additional support for the inducible, selective release of a macrophage product that could affect the host response to lipopolysaccharide by regulation of the adrenocortical response to adrenocorticotropic

  2. Adrenocortical response to open-field test in rats with anterodorsal thalami nuclei lesion.

    PubMed

    Suárez, M; Perassi, N; Dal Zotto, S

    1996-01-01

    The influence of limbic anterodorsal thalami nuclei (ADTN) on adrenocortical activity and on emotional reactivity were investigated in male and female rats. The emotional reactivity was evaluated by means of the open-field test and the corticoadrenal function by means of plasma and adrenal corticosterone concentration. The results demonstrate that ADTN lesion does not affect the behavioural patterns in the open-field test on the 29th and 30th day after lesion nor adrenal response when animals are exposed to a novel situation. PMID:8724884

  3. 5th International ACC Symposium: The New Genetics of Benign Adrenocortical Neoplasia: Hyperplasias, Adenomas, and Their Implications for Progression into Cancer.

    PubMed

    Kirschner, Lawrence S; Stratakis, Constantine A

    2016-02-01

    Genetic tools for the analysis of human tumors have developed rapidly over the past 20 years. Adrenocortical neoplasms have been subject to multiple analyses using these new genetic tools. Analysis of adrenocortical carcinomas (ACCs) has been complicated by the fact that these tumors tend to exhibit multiple somatic abnormalities, so that identifying driver mutations is complex task. In contrast, benign adrenocortical neoplasms have proven to be a fertile ground for the identification of the genetic causes of adrenocortical adenomas, as well as a variety of adrenocortical hyperplasia. Analysis of cortisol-producing adrenocortical adenomas has revealed alterations leading to enhanced signaling through the cAMP-dependent protein kinase (PKA) pathway. In contrast, macronodular cortisol-producing neoplasias have been shown to result from mutations in the ARMC5 gene, whose function is not yet quite so clear. In contrast, adrenal tumors resulting in excess production of the blood pressure hormone aldosterone almost always result from abnormalities of calcium handling, both in single adenomas and in bilateral hyperplasias. In both cases, there is elevation of a signaling pathway responsible both for hormone secretion and for gland growth and maintenance, thus confirming the linkage of these two output of cellular physiology. The connection between the benign hyperplasia observed in these states and adrenocortical carcinogenesis is not nearly as clear, although genetic studies are beginning to elucidate the relationship between benign and malignant tumors of this gland. PMID:26684645

  4. Clofazimine-induced Hair Pigmentation.

    PubMed

    Philip, Mariam; Samson, Joan Felicita; Simi, Puthenveedu Salahudeen

    2012-07-01

    A 45-year-old man was treated with WHO multibacillary multidrug therapy for borderline leprosy and high dose daily Clofazimine for lepra reaction. Along with the expected side effect of skin pigmentation, the patient also noticed darkening of previously grey hair. This colour persisted eight months after completing multibacillary multidrug therapy. PMID:23180930

  5. 21 CFR 178.3725 - Pigment dispersants.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Pigment dispersants. 178.3725 Section 178.3725... Certain Adjuvants and Production Aids § 178.3725 Pigment dispersants. Subject to the provisions of this regulation, the substances listed in this section may be safely used as pigment dispersants in...

  6. 21 CFR 178.3725 - Pigment dispersants.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Pigment dispersants. 178.3725 Section 178.3725 Food... Certain Adjuvants and Production Aids § 178.3725 Pigment dispersants. Subject to the provisions of this regulation, the substances listed in this section may be safely used as pigment dispersants in...

  7. 21 CFR 178.3725 - Pigment dispersants.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Pigment dispersants. 178.3725 Section 178.3725... Certain Adjuvants and Production Aids § 178.3725 Pigment dispersants. Subject to the provisions of this regulation, the substances listed in this section may be safely used as pigment dispersants in...

  8. 21 CFR 178.3725 - Pigment dispersants.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Pigment dispersants. 178.3725 Section 178.3725... § 178.3725 Pigment dispersants. Subject to the provisions of this regulation, the substances listed in this section may be safely used as pigment dispersants in food-contact materials....

  9. 21 CFR 178.3725 - Pigment dispersants.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Pigment dispersants. 178.3725 Section 178.3725... Certain Adjuvants and Production Aids § 178.3725 Pigment dispersants. Subject to the provisions of this regulation, the substances listed in this section may be safely used as pigment dispersants in...

  10. 21 CFR 73.352 - Paracoccus pigment.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Paracoccus pigment. 73.352 Section 73.352 Food and... ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.352 Paracoccus pigment. (a) Identity. (1) The color additive paracoccus pigment consists of the heat-killed, dried cells of a nonpathogenic and nontoxicogenic strain...

  11. 21 CFR 73.352 - Paracoccus pigment.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Paracoccus pigment. 73.352 Section 73.352 Food and... ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.352 Paracoccus pigment. (a) Identity. (1) The color additive paracoccus pigment consists of the heat-killed, dried cells of a nonpathogenic and nontoxicogenic strain...

  12. 21 CFR 73.352 - Paracoccus pigment.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Paracoccus pigment. 73.352 Section 73.352 Food and... ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.352 Paracoccus pigment. (a) Identity. (1) The color additive paracoccus pigment consists of the heat-killed, dried cells of a nonpathogenic and nontoxicogenic strain...

  13. 21 CFR 73.352 - Paracoccus pigment.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Paracoccus pigment. 73.352 Section 73.352 Food and... ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.352 Paracoccus pigment. (a) Identity. (1) The color additive paracoccus pigment consists of the heat-killed, dried cells of a nonpathogenic and nontoxicogenic strain...

  14. 21 CFR 73.352 - Paracoccus pigment.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Paracoccus pigment. 73.352 Section 73.352 Food and... ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.352 Paracoccus pigment. (a) Identity. (1) The color additive paracoccus pigment consists of the heat-killed, dried cells of a nonpathogenic and nontoxicogenic strain...

  15. Adrenocortical function of Arctic-breeding glaucous gulls in relation to persistent organic pollutants.

    PubMed

    Verboven, Nanette; Verreault, Jonathan; Letcher, Robert J; Gabrielsen, Geir W; Evans, Neil P

    2010-03-01

    Unpredictable changes in the environment stimulate the avian hypothalamo-pituitary-adrenal axis to produce corticosterone, which induces behavioural and metabolic changes that enhance survival in the face of adverse environmental conditions. In addition to profound environmental perturbations, such as severe weather conditions and unpredictable food shortages, many Arctic-breeding birds are also confronted with chronic exposure to persistent organic pollutants (POPs), some of which are known to disrupt endocrine processes. This study investigated the adrenocortical function of a top predator in the Arctic marine environment, the glaucous gull (Larus hyperboreus). High concentrations of organochlorines, brominated flame retardants and metabolically-derived products in blood plasma of incubating glaucous gulls were associated with high baseline corticosterone concentrations in both sexes and a reduced stress response in males. Contaminant-related changes in corticosterone concentration occurred over and above differences in body condition and seasonal variation. Chronically high corticosterone concentrations and/or a compromised adrenocortical response to stress can have negative effects on the health of an individual. The results of the present study suggest that exposure to POPs may increase the vulnerability of glaucous gulls to environmental stressors and thus could potentially compromise their ability to adapt to the rapidly changing environmental conditions associated with climate change that are currently seen in the Arctic. PMID:19932109

  16. Estrogen related receptor α (ERRα) a promising target for the therapy of adrenocortical carcinoma (ACC).

    PubMed

    Casaburi, Ivan; Avena, Paola; De Luca, Arianna; Chimento, Adele; Sirianni, Rosa; Malivindi, Rocco; Rago, Vittoria; Fiorillo, Marco; Domanico, Francesco; Campana, Carmela; Cappello, Anna Rita; Sotgia, Federica; Lisanti, Michael P; Pezzi, Vincenzo

    2015-09-22

    The pathogenesis of the adrenocortical cancer (ACC) involves integration of molecular signals and the interplay of different downstream pathways (i.e. IGFII/IGF1R, β-catenin, Wnt, ESR1). This tumor is characterized by limited therapeutic options and unsuccessful treatments. A useful strategy to develop an effective therapy for ACC is to identify a common downstream target of these multiple pathways. A good candidate could be the transcription factor estrogen-related receptor alpha (ERRα) because of its ability to regulate energy metabolism, mitochondrial biogenesis and signalings related to cancer progression. In this study we tested the effect of ERRα inverse agonist, XCT790, on the proliferation of H295R adrenocortical cancer cell line. Results from in vitro and in vivo experiments showed that XCT790 reduced H295R cell growth. The inhibitory effect was associated with impaired cell cycle progression which was not followed by any apoptotic event. Instead, incomplete autophagy and cell death by a necrotic processes, as a consequence of the cell energy failure, induced by pharmacological reduction of ERRα was evidenced. Our results indicate that therapeutic strategies targeting key factors such as ERRα that control the activity and signaling of bioenergetics processes in high-energy demanding tumors could represent an innovative/alternative therapy for the treatment of ACC. PMID:26312764

  17. Environmental enrichment affects adrenocortical stress responses in the endangered black-footed ferret.

    PubMed

    Poessel, Sharon A; Biggins, Dean E; Santymire, Rachel M; Livieri, Travis M; Crooks, Kevin R; Angeloni, Lisa

    2011-07-01

    Potential stressors of wildlife living in captivity, such as artificial living conditions and frequent human contact, may lead to a higher occurrence of disease and reduced reproductive function. One successful method used by wildlife managers to improve general well-being is the provision of environmental enrichment, which is the practice of providing animals under managed care with environmental stimuli. The black-footed ferret (Mustela nigripes) is a highly-endangered carnivore species that was rescued from extinction by removal of the last remaining individuals from the wild to begin an ex situ breeding program. Our goal was to examine the effect of environmental enrichment on adrenocortical activity in ferrets by monitoring fecal glucocorticoid metabolites (FGM). Results demonstrated that enrichment lowered FGM in juvenile male ferrets, while increasing it in adult females; enrichment had no effect on FGM in juvenile females and adult males. These results correspond with our findings that juvenile males interacted more with the enrichment items than did adult females. However, we did not detect an impact of FGM on the incidence of disease or on the ability of ferrets to become reproductive during the following breeding season. We conclude that an environmental enrichment program could benefit captive juvenile male ferrets by reducing adrenocortical activity. PMID:21549121

  18. Hormonal regulation of focal adhesions in bovine adrenocortical cells: induction of paxillin dephosphorylation by adrenocorticotropic hormone.

    PubMed Central

    Vilgrain, I; Chinn, A; Gaillard, I; Chambaz, E M; Feige, J J

    1998-01-01

    A study of bovine adrenocortical cell shape on adrenocorticotropic hormone (ACTH) challenge showed that the cells round up and develop arborized processes. This effect was found to be (1) specific for ACTH because angiotensin II and basic fibroblast growth factor have no effect; (2) mediated by a cAMP-dependent pathway because forskolin reproduces the effect of the hormone; (3) inhibited by sodium orthovanadate, a phosphotyrosine phosphatase inhibitor, but unchanged by okadaic acid, a serine/threonine phosphatase inhibitor; and (4) correlated with a complete loss of focal adhesions. Biochemical studies of the focal-adhesion-associated proteins showed that pp125fak, vinculin (110 kDa) and paxillin (70 kDa) were detected in the Triton X-100-insoluble fraction from adrenocortical cells. During cell adhesion on fibronectin as substratum, two major phosphotyrosine-containing proteins of molecular masses 125 and 68 kDa were immunodetected in the same fraction. A dramatic decrease in the extent of tyrosine phosphorylation of these proteins was observed within 60 min after treatment with ACTH. No change in pp125fak tyrosine phosphorylation nor in Src activity was detected. In contrast, paxillin was found to be tyrosine-dephosphorylated in a time-dependent manner in ACTH-treated cells. Sodium orthovanadate completely prevented the effect of ACTH. These observations suggest a possible role for phosphotyrosine phosphatases in hormone-dependent cellular regulatory processes. PMID:9601084

  19. An unusual case of adrenocortical carcinoma with liver metastasis that occurred at 23 years after surgery.

    PubMed

    Bergeat, Damien; Rayar, Michel; Beuzit, Luc; Levi Sandri, Giovanni Battista; Dagher, Julien; Merdrignac, Aude; Tanguy, Laetitia; Boudjema, Karim; Sulpice, Laurent; Meunier, Bernard

    2016-06-01

    Adrenocortical carcinoma (ACC) is an uncommon and aggressive cancer occurring more frequently in women; local or distant recurrences occur in 80% of cases, typically within 1 year after curative resection. Liver is the preferred metastatic site. Herein, we report the case of a unique liver metastasis from ACC occurring 23 years after the curative prior tumor surgery. A 45-year-old woman was operated in 1991 for adrenocortical stage II without microvascular involvement or capsular infiltration. At that time, no adjuvant treatment was indicated. The initial surgery consisted on a left adrenalectomy with contemporaneous left nephrectomy and regional lymphadenectomy. Five years after surgery, the patient was considered cured. However, 23 years later, the patient presented an atypical right subcostal pain. A 4 cm liver ACC metastasis involving the segment 4 and initially diagnosed as a hemangioma was discovered. A curative resection of the segment 4 was performed. Final pathological examination confirmed the diagnosis of ACC metastasis with a complete R0 resection; no lymph node metastases were observed. This case is the latest metachronous ACC metastasis ever reported in literature. To date, the patient is alive with no signs of recurrence after a post-surgical follow-up of 13 months. PMID:27275470

  20. An unusual case of adrenocortical carcinoma with liver metastasis that occurred at 23 years after surgery

    PubMed Central

    Rayar, Michel; Beuzit, Luc; Levi Sandri, Giovanni Battista; Dagher, Julien; Merdrignac, Aude; Tanguy, Laetitia; Boudjema, Karim; Sulpice, Laurent; Meunier, Bernard

    2016-01-01

    Adrenocortical carcinoma (ACC) is an uncommon and aggressive cancer occurring more frequently in women; local or distant recurrences occur in 80% of cases, typically within 1 year after curative resection. Liver is the preferred metastatic site. Herein, we report the case of a unique liver metastasis from ACC occurring 23 years after the curative prior tumor surgery. A 45-year-old woman was operated in 1991 for adrenocortical stage II without microvascular involvement or capsular infiltration. At that time, no adjuvant treatment was indicated. The initial surgery consisted on a left adrenalectomy with contemporaneous left nephrectomy and regional lymphadenectomy. Five years after surgery, the patient was considered cured. However, 23 years later, the patient presented an atypical right subcostal pain. A 4 cm liver ACC metastasis involving the segment 4 and initially diagnosed as a hemangioma was discovered. A curative resection of the segment 4 was performed. Final pathological examination confirmed the diagnosis of ACC metastasis with a complete R0 resection; no lymph node metastases were observed. This case is the latest metachronous ACC metastasis ever reported in literature. To date, the patient is alive with no signs of recurrence after a post-surgical follow-up of 13 months.

  1. Estrogen related receptor α (ERRα) a promising target for the therapy of adrenocortical carcinoma (ACC)

    PubMed Central

    Chimento, Adele; Sirianni, Rosa; Malivindi, Rocco; Rago, Vittoria; Fiorillo, Marco; Domanico, Francesco; Campana, Carmela; Cappello, Anna Rita; Sotgia, Federica; Lisanti, Michael P.; Pezzi, Vincenzo

    2015-01-01

    The pathogenesis of the adrenocortical cancer (ACC) involves integration of molecular signals and the interplay of different downstream pathways (i.e. IGFII/IGF1R, β-catenin, Wnt, ESR1). This tumor is characterized by limited therapeutic options and unsuccessful treatments. A useful strategy to develop an effective therapy for ACC is to identify a common downstream target of these multiple pathways. A good candidate could be the transcription factor estrogen-related receptor alpha (ERRα) because of its ability to regulate energy metabolism, mitochondrial biogenesis and signalings related to cancer progression. In this study we tested the effect of ERRα inverse agonist, XCT790, on the proliferation of H295R adrenocortical cancer cell line. Results from in vitro and in vivo experiments showed that XCT790 reduced H295R cell growth. The inhibitory effect was associated with impaired cell cycle progression which was not followed by any apoptotic event. Instead, incomplete autophagy and cell death by a necrotic processes, as a consequence of the cell energy failure, induced by pharmacological reduction of ERRα was evidenced. Our results indicate that therapeutic strategies targeting key factors such as ERRα that control the activity and signaling of bioenergetics processes in high-energy demanding tumors could represent an innovative/alternative therapy for the treatment of ACC. PMID:26312764

  2. The Role of gsp Mutations on the Development of Adrenocortical Tumors and Adrenal Hyperplasia

    PubMed Central

    Villares Fragoso, Maria Candida Barisson; Wanichi, Ingrid Quevedo; Cavalcante, Isadora Pontes; Mariani, Beatriz Marinho de Paula

    2016-01-01

    Somatic GNAS point mutations, commonly known as gsp mutations, are involved in the pathogenesis of McCune–Albright syndrome (MAS) 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. 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. 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 MAS. 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. PMID:27512387

  3. Environmental enrichment affects adrenocortical stress responses in the endangered black-footed ferret

    USGS Publications Warehouse

    Poessel, S.A.; Biggins, D.E.; Santymire, R.M.; Livieri, T.M.; Crooks, K.R.; Angeloni, L.

    2011-01-01

    Potential stressors of wildlife living in captivity, such as artificial living conditions and frequent human contact, may lead to a higher occurrence of disease and reduced reproductive function. One successful method used by wildlife managers to improve general well-being is the provision of environmental enrichment, which is the practice of providing animals under managed care with environmental stimuli. The black-footed ferret (Mustela nigripes) is a highly-endangered carnivore species that was rescued from extinction by removal of the last remaining individuals from the wild to begin an ex situ breeding program. Our goal was to examine the effect of environmental enrichment on adrenocortical activity in ferrets by monitoring fecal glucocorticoid metabolites (FGM). Results demonstrated that enrichment lowered FGM in juvenile male ferrets, while increasing it in adult females; enrichment had no effect on FGM in juvenile females and adult males. These results correspond with our findings that juvenile males interacted more with the enrichment items than did adult females. However, we did not detect an impact of FGM on the incidence of disease or on the ability of ferrets to become reproductive during the following breeding season. We conclude that an environmental enrichment program could benefit captive juvenile male ferrets by reducing adrenocortical activity. ?? 2011 Elsevier Inc.

  4. INFLUENCE OF CHLORDIMEFORM ON ALPHA-ADRENERGIC RECEPTOR-ASSOCIATED MECHANISMS OF HORMONAL REGULATIONS: PITUITARY AND ADRENOCORTICAL SECRETION

    EPA Science Inventory

    The acaricide chlordimeform (CDF) has been reported to have effects on the central nervous system that appear to involve an interaction with adrenergic receptor mediated mechanisms of neurotransmission. The present study examined the influence of CDF on pituitary-adrenocortical h...

  5. Genome-wide paternal uniparental disomy as a cause of Beckwith-Wiedemann syndrome associated with recurrent virilizing adrenocortical tumors.

    PubMed

    Bertoin, F; Letouzé, E; Grignani, P; Patey, M; Rossignol, S; Libé, R; Pasqual, C; Lardière-Deguelte, S; Hoeffel-Fornes, C; Gaillard, D; Previderè, C; Delemer, B; Lalli, E

    2015-06-01

    Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome characterized by fetal macrosomia, macroglossia, and abdominal wall defects. BWS patients are at risk to develop Wilms tumor, neuroblastoma, hepatoblastoma, and adrenal tumors. A young woman with BWS features, but with inconclusive genetic evidence for the disease, came to clinical observation for signs of virilization at the age of 16 years. An adrenocortical tumor was diagnosed and surgically resected. The tumor underwent 2 local relapses that were also surgically treated. The patient was also operated to remove a breast fibroadenoma. SNP arrays were used to analyze chromosome abnormalities in normal and tumor samples from the patient and her parents. The patient presented genome-wide mosaic paternal uniparental disomy (patUPD) both in the adrenocortical and the breast tumors, with different degrees of loss of heterozygosity (LOH). The more recent relapses of the adrenocortical tumor showed a loss of part of chromosome 17p that was absent in the first tumor. Analysis of a skin biopsy sample also showed mosaic patUPD with partial LOH, while no LOH was detected in leukocyte DNA. This case shows that virilizing adrenocortical tumors may be a clinical feature of patients with BWS. The SNP array technology is useful to diagnose genome-wide patUPD mosaicism in BWS patients with an inconclusive molecular diagnosis and underlines the tumorigenic potential of the absence of the maternal genome combined with an excess of the paternal genome. PMID:25365508

  6. High-throughput screening of chemical effects on steroidogenesis using H295R human adrenocortical carcinoma cells

    EPA Science Inventory

    Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. A high-throughput assay using H295R human adrenocortical carcinoma cells was used to evaluate the effect of 2,060 chemical samples...

  7. Chronic stress increases the opioid-mediated inhibition of the pituitary-adrenocortical response to acute stress in pigs.

    PubMed

    Janssens, C J; Helmond, F A; Loyens, L W; Schouten, W G; Wiegant, V M

    1995-04-01

    The role of endogenous opioid mechanisms in the pituitary-adrenocortical response to acute stress was investigated in a longitudinal study in cyclic female pigs before and after exposure to chronic stress (long term tethered housing). Challenge of loose-housed pigs with acute nose-sling stress for 15 min induced an activation of the hypothalamic-pituitary-adrenocortical axis, evidenced by a transient increase in plasma ACTH (peak height above basal, 98 +/- 12 pg/ml; mean +/- SEM) and cortisol (54 +/- 3 ng/ml) concentrations. Pretreatment with the opioid receptor antagonist naloxone (0.5 mg/kg BW, iv bolus) increased the challenge-induced ACTH and cortisol responses to 244 +/- 36 pg/ml and 65 +/- 5 ng/ml, respectively. This indicates that during acute nose-sling stress, endogenous opioid systems are activated that inhibit the pituitary-adrenocortical response. After exposure of the pigs to chronic stress (10-11 weeks of tethered housing), the challenge-induced ACTH response was attenuated, whereas the cortisol response remained unchanged, suggesting an increased adrenocortical sensitivity to circulating ACTH. In addition, pretreatment with naloxone induced a greater increment in the ACTH and cortisol responses in tethered pigs than in loose-housed pigs. As no such changes were found in control animals housed loose during the entire experimental period, this indicates that the impact of opioid systems had increased due to chronic stress. The increased impact of opioid systems during chronic stress may prevent excessive hypothalamic-pituitary-adrenocortical responses to acute stressors and, thus, may be of adaptive value. PMID:7895656

  8. Availability and Utilization of Pigments from Microalgae.

    PubMed

    Begum, Hasina; Yusoff, Fatimah Md; Banerjee, Sanjoy; Khatoon, Helena; Shariff, Mohamed

    2016-10-01

    Microalgae are the major photosynthesizers on earth and produce important pigments that include chlorophyll a, b and c, β-carotene, astaxanthin, xanthophylls, and phycobiliproteins. Presently, synthetic colorants are used in food, cosmetic, nutraceutical, and pharmaceutical industries. However, due to problems associated with the harmful effects of synthetic colorants, exploitation of microalgal pigments as a source of natural colors becomes an attractive option. There are various factors such as nutrient availability, salinity, pH, temperature, light wavelength, and light intensity that affect pigment production in microalgae. This paper reviews the availability and characteristics of microalgal pigments, factors affecting pigment production, and the application of pigments produced from microalgae. The potential of microalgal pigments as a source of natural colors is enormous as an alternative to synthetic coloring agents, which has limited applications due to regulatory practice for health reasons. PMID:25674822

  9. A 65-year-old man with persistent cough and large nodular opacity.

    PubMed

    Grimes, Brandon S; Albores, Jeffrey; Barjaktarevic, Igor

    2015-01-01

    A 65-year-old Asian man with a history of chronic hepatitis B infection presented to our pulmonary clinic for second opinion of his chronic, persistent, nonproductive cough. He was evaluated 10 months earlier with chest CT scan, which revealed a large lingular nodular opacity that was diagnosed as nodular cryptogenic organizing pneumonia by CT scan-guided percutaneous lung biopsy. Systemic corticosteroids were initiated and continued over the next 10 months. The dry cough persisted, and he developed intermittent left-sided pleuritic chest pain. He denied fevers, night sweats, hemoptysis, weight loss, or dyspnea. He was a lifelong nonsmoker and moved to the United States from China during childhood. PMID:25560867

  10. Low-Dose Involved-Field Radiotherapy as Alternative Treatment of Nodular Lymphocyte Predominance Hodgkin's Lymphoma

    SciTech Connect

    Haas, Rick L.M. Girinsky, Theo; Aleman, Berthe; Henry-Amar, Michel; Boer, Jan-Paul de; Jong, Daphne de

    2009-07-15

    Purpose: Nodular lymphocyte predominance Hodgkin's lymphoma is a very rare disease, characterized by an indolent clinical course, with sometimes very late relapses occurring in a minority of all patients. Considerable discussion is ongoing on the treatment of primary and relapsed disease. Patients and Methods: A group of 9 patients were irradiated to a dose of 4 Gy on involved areas only. Results: After a median follow-up of 37 months (range, 6-66), the overall response rate was 89%. Six patients had complete remission (67%), two had partial remission (22%), and one had stable disease (11%). Of 8 patients, 5 developed local relapse 9-57 months after radiotherapy. No toxicity was noted. Conclusion: In nodular lymphocyte predominance Hodgkin's lymphoma, low-dose radiotherapy provided excellent response rates and lasting remissions without significant toxicity.

  11. Nodular and diffuse fibrous proliferation of the penis and tunica vaginalis.

    PubMed

    Musulen, Eva; Carvia-Ponsaille, Rafael Esteban; Fernandez-Figueras, Maria Teresa; Barranco-Garcia, Juan de Dios; Ariza, Aurelio

    2008-04-01

    Fibrous benign proliferations of the testis and paratesticular tissues are an uncommon and heterogeneous group of lesions that can mimic true neoplasms. Among them, those considered to be reactive proliferations have been included in the category of fibrous pseudotumors and are often associated with trauma, hydrocele, or infection. We report 2 cases of nodular and diffuse fibrous proliferation. This condition is part of the spectrum of reactive benign fibrous lesions and has previously been described in the testicular tunics and paratesticular region only. One of our 2 cases had the peculiarity of being located in the penile shaft, whereas the other involved the tunica vaginalis. To the best of our knowledge, this is the first report of a diffuse and nodular fibrous tumor involving the penis. PMID:18360130

  12. Pulmonary epithelioid hemangioendothelioma coexisting with pulmonary nodular amyloidosis: case discussion and review of the literature

    PubMed Central

    Yi, Lingling; Cheng, Dan; Shi, Huimin; Zhang, Kan; Liao, Yongde; Ao, Qilin; Zhen, Guohua

    2014-01-01

    A 38-year-old female was found to have multiple bilateral lung nodules in a routine chest X-ray examination. Thoracoscopy was performed with biopsy of three nodules from the right lower lobe and Congo red staining showed typical amyloid pattern. Initial diagnosis of pulmonary nodular amyloidosis was made. However, one nodule in the right upper lobe enlarged as detected by follow-up CT scan. The patient underwent F-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET)/CT and a significant high FDG uptake in the largest nodule in right upper lobe was observed while the uptake was normal or mildly increased in the other nodules. Meanwhile, right hilar and mediastinal lymph nodes adenopathy was noted. Right upper lobe was resected by thoracotomy. Surprisingly, histopathological findings showed pulmonary epithelioid hemangioendothelioma (PEH) with metastasis of hilar and mediastinal lymph nodes. To our knowledge, this is the first described case of PEH coexisting with pulmonary nodular amyloidosis. PMID:25126197

  13. Holographic films from carotenoid pigments

    NASA Astrophysics Data System (ADS)

    Toxqui-López, S.; Lecona-Sánchez, J. F.; Santacruz-Vázquez, C.; Olivares-Pérez, A.; Fuentes-Tapia, I.

    2014-02-01

    Carotenoids pigments presents in pineapple can be more than just natural dyes, which is one of the applications that now at day gives the chemical industry. In this research shown that can be used in implementing of holographic recording Films. Therefore we describe the technique how to obtain this kind of pigments trough spay drying of natural pineapple juice, which are then dissolved with water in a proportion of 0.1g to 1mL. The obtained sample is poured into glass substrates using the gravity method, after a drying of 24 hours in laboratory normal conditions the films are ready. The films are characterized by recording transmission holographic gratings (LSR 445 NL 445 nm) and measuring the diffraction efficiency holographic parameter. This recording material has good diffraction efficiency and environmental stability.

  14. Laser-induced interstitial thermotherapy in treatment of recurrent nodular goiter and thyroid cancer

    NASA Astrophysics Data System (ADS)

    Seliverstov, Oleg V.; Privalov, Valeriy A.; Lappa, Alexander V.; Demidov, A. K.; Faizrakhmanov, Alexey B.; Yarovoy, Nicolay N.

    2001-10-01

    Laser-induced interstitial thermotherapy was performed in 29 patients with recurrent nodular and multinodular goiter, and in 3 patients with recurrent inoperable thyroid cancer. There were used transcutaneous puncture under ultrasonic control, diode lasers with wavelength 805, 980, and 1060 nm, quartz monofibers, special computerized thermometer with microthermocouples. Disappearance or significant reduction of nodes in the most goiter cases, and regress of tumor in the cancer cases were marked during observation period (0.5 - 2.5 years).

  15. Cutaneous metastatic pigmented breast carcinoma.

    PubMed

    Gaitan-Gaona, Francisco; Said, Mirra C; Valdes-Rodriguez, Rodrigo

    2016-01-01

    A 66-year-old woman presented with a 3 cm black, ulcerated nodule located on the skin of the upper abdomen, just below the breast. The lesion was painful to the touch, but the patient reported no other associated symptoms and was otherwise healthy. A 4-mm punch biopsy of the affected skin was obtained and the histological diagnosis was cutaneous metastatic pigmented breast carcinoma. PMID:27136637

  16. Nanoscience of an ancient pigment.

    PubMed

    Johnson-McDaniel, Darrah; Barrett, Christopher A; Sharafi, Asma; Salguero, Tina T

    2013-02-01

    We describe monolayer nanosheets of calcium copper tetrasilicate, CaCuSi(4)O(10), which have strong near-IR luminescence and are amenable to solution processing methods. The facile exfoliation of bulk CaCuSi(4)O(10) into nanosheets is especially surprising in view of the long history of this material as the colored component of Egyptian blue, a well-known pigment from ancient times. PMID:23215240

  17. A comparison of nodular defect seed geometeries from different deposition techniques

    SciTech Connect

    Stolz, C.J.; Tench, R.J.; Kozlowski, M.R.; Fornier, A.

    1995-12-29

    A focused ion-beam milling instrument commonly utilized in the semiconductor industry for failure analysis and IC repair, is capable of cross-sectioning nodular defects. Utilizing the instrument`s scanning on beam, high-resolution imaging of the seeds that initiate nodular defect growth is possible. In an attempt to understand the origins of these seeds, HfO{sub 2}/SiO{sub 2} and Ta{sub 2}O{sub 5}/SiO{sub 2} coatings were prepared by a variety of coating vendors and different deposition processes including e-beam, magnetron sputtering, and ion beam sputtering. By studying the shape, depth, and composition of the seed, inferences of its origin can be drawn. The boundaries between the nodule and thin film provide insight into the mechanical stability of the nodule. Significant differences in the seed composition, geometry of nodular growth and mechanical stability of the defects for sputtered versus e-beam coatings are reported. Differences in seed shape were also observed from different coating vendors using e-beam deposition of HfO{sub 2}/SiO{sub 2} coatings.

  18. Nodular Scleritis Associated with Herpes Zoster Virus: An Infectious and Immune-Mediated Process.

    PubMed

    Loureiro, Mónica; Rothwell, Renata; Fonseca, Sofia

    2016-01-01

    Purpose. To describe a case of anterior nodular scleritis, preceded by an anterior hypertensive uveitis, which was primarily caused by varicella zoster virus (VZV). Case Report. A 54-year-old woman presented with anterior uveitis of the right eye presumably caused by herpetic viral disease and was successfully treated. Two months later, she developed a nodular scleritis and started oral nonsteroidal anti-inflammatory without effect. A complete laboratory workup revealed positivity for HLA-B27; the infectious workup was negative. Therapy was changed to oral prednisolone and an incomplete improvement occurred. Therefore, a diagnostic anterior paracentesis was performed and the polymerase chain reaction (PCR) analysis revealed VZV. She was treated with valacyclovir and the oral prednisolone began to decrease; however, a marked worsening of the scleritis occurred with the reduction of the daily dose; subsequently, methotrexate was introduced allowing the suspension of the prednisolone and led to clinical resolution of the scleritis. Conclusion. This report of anterior nodular scleritis caused by VZV argues in favor of an underlying immune-mediated component, requiring immunosuppressive therapy for clinical resolution. The PCR analysis of the aqueous humor was revealed to be a valuable technique and should be considered in cases of scleritis with poor response to treatment. PMID:27298747

  19. Nodular Scleritis Associated with Herpes Zoster Virus: An Infectious and Immune-Mediated Process

    PubMed Central

    Loureiro, Mónica; Rothwell, Renata; Fonseca, Sofia

    2016-01-01

    Purpose. To describe a case of anterior nodular scleritis, preceded by an anterior hypertensive uveitis, which was primarily caused by varicella zoster virus (VZV). Case Report. A 54-year-old woman presented with anterior uveitis of the right eye presumably caused by herpetic viral disease and was successfully treated. Two months later, she developed a nodular scleritis and started oral nonsteroidal anti-inflammatory without effect. A complete laboratory workup revealed positivity for HLA-B27; the infectious workup was negative. Therapy was changed to oral prednisolone and an incomplete improvement occurred. Therefore, a diagnostic anterior paracentesis was performed and the polymerase chain reaction (PCR) analysis revealed VZV. She was treated with valacyclovir and the oral prednisolone began to decrease; however, a marked worsening of the scleritis occurred with the reduction of the daily dose; subsequently, methotrexate was introduced allowing the suspension of the prednisolone and led to clinical resolution of the scleritis. Conclusion. This report of anterior nodular scleritis caused by VZV argues in favor of an underlying immune-mediated component, requiring immunosuppressive therapy for clinical resolution. The PCR analysis of the aqueous humor was revealed to be a valuable technique and should be considered in cases of scleritis with poor response to treatment. PMID:27298747

  20. Benign hepatocellular nodules of healthy liver: focal nodular hyperplasia and hepatocellular adenoma

    PubMed Central

    Roncalli, Massimo; Sciarra, Amedeo; Tommaso, Luca Di

    2016-01-01

    Owing to the progress of imaging techniques, benign hepatocellular nodules are increasingly discovered in the clinical practice. This group of lesions mostly arises in the context of a putatively normal healthy liver and includes either pseudotumoral and tumoral nodules. Focal nodular hyperplasia and hepatocellular adenoma are prototypical examples of these two categories of nodules. In this review we aim to report the main pathological criteria of differential diagnosis between focal nodular hyperplasia and hepatocellular adenoma, which mainly rests upon morphological and phenotypical features. We also emphasize that for a correct diagnosis the clinical context such as sex, age, assumption of oral contraceptives, associated metabolic or vascular disturbances is of paramount importance. While focal nodular hyperplasia is a single entity epidemiologically more frequent than adenoma, the latter is representative of a more heterogeneous group which has been recently and extensively characterized from a clinical, morphological, phenotypical and molecular profile. The use of the liver biopsy in addition to imaging and the clinical context are important diagnostic tools of these lesions. In this review we will survey their systematic pathobiology and propose a diagnostic algorithm helpful to increase the diagnostic accuracy of not dedicated liver pathologists. The differential diagnosis between so-called typical and atypical adenoma and well differentiated hepatocellular carcinoma will also be discussed. PMID:27189732

  1. Treatment of recurrent nodular goiters with percutaneous ethanol injection: a clinical study of twelve patients.

    PubMed

    Solymosi, Tamas; Gál, Istvan

    2003-03-01

    Twelve patients who had previously undergone thyroid surgery received percutaneous ethanol injection (PEI) treatment because of recurrent nodular goiter (3 with a toxic [TN], 2 with a nontoxic cystic [NCN], and 7 with a nontoxic solid nodule [NSN]). Two of the 12 had recurrent nerve palsy contralateral to the nodule. Each patient received a mean total dose of 0.88 mL of ethanol per milliliter of nodular volume. Ethanol was injected in a mean of 3.5 sessions for solid and 3 sessions for NCN. In most cases, a slight to moderate burning pain was experienced during and for 12-48 hours after PEI treatment, and one patient experienced temporary hoarseness. One patient with TN and 2 patients with NSN became hypothyroid, 7 patients with nontoxic nodules remained euthyroid, 1 with TN became euthyroid, and a previously hyperthyroid patient with TN became subclinically hyperthyroid 1-year posttherapy. The nodule shrank by more than 50% of the pretreatment volume in all patients (8.6 +/- 2.6 vs. 2.9 +/- 1.2 mL in TN, and 12.3 +/- 4.9 vs. 4.16 +/- 2.54 mL in nontoxic nodules, pretreatment vs. 1 year posttreatment volume, respectively). With regard to the increased risk of reoperation, PEI treatment can be proposed for patients with recurrent nodular goiter requiring surgery. PMID:12729476

  2. Nestin expression is associated with aggressive cutaneous melanoma of the nodular type.

    PubMed

    Ladstein, Rita G; Bachmann, Ingeborg M; Straume, Oddbjørn; Akslen, Lars A

    2014-03-01

    The intermediate filament nestin, a neural stem-cell marker, is reported to be expressed more strongly in melanomas compared with benign melanocytic lesions, and increasingly expressed in advanced melanoma stages. However, the prognostic impact of nestin on melanoma has not been well elucidated. The aim of the present study was to evaluate the prognostic influence of nestin expression in cutaneous melanoma in comparison with standard clinico-pathologic variables. In a large series of nodular cutaneous melanoma (n=348), nestin expression was assessed by immunohistochemistry using tissue microarray (TMA) sections. For comparison, nestin staining in corresponding metastases as well as in superficial spreading melanomas and benign nevi was also examined. Nestin was expressed to varying degrees in a majority of nodular melanomas (92%), and was significantly associated with increased tumor thickness, high mitotic count, and the presence of ulceration and tumor necrosis. Also, expression was stronger in the nodular type than in superficial spreading melanomas and benign nevi, but without significant difference when compared with matched metastases from the former. Importantly, strong expression of nestin was significantly associated with reduced survival in multivariate analysis. In conclusion, increased nestin expression was associated with aggressive melanoma features, with independent prognostic impact on multivariate survival analysis when compared with clinico-pathologic factors. PMID:24030749

  3. Glucose-dependent insulinotropic peptide receptor overexpression in adrenocortical hyperplasia in MEN1 syndrome without loss of heterozygosity at the 11q13 locus

    PubMed Central

    Costa, Marcia Helena Soares; Domenice, Sorahia; Toledo, Rodrigo Almeida; Lourenço, Delmar Muniz; Latronico, Ana Claudia; Pinto, Emilia Modolo; Toledo, Sergio Pereira Almeida; Mendonca, Berenice Bilharinho; Fragoso, Maria Candida Barisson Villares

    2011-01-01

    BACKGROUND: The molecular mechanisms involved in the genesis of the adrenocortical lesions seen in MEN1 syndrome (ACL-MEN1) remain poorly understood; loss of heterozygosity at 11q13 and somatic mutations of MEN1 are not usually found in these lesions. Thus, additional genes must be involved in MEN1 adrenocortical disorders. Overexpression of the glucose-dependent insulinotropic peptide receptor has been shown to promote adrenocortical tumorigenesis in a mice model and has also been associated with ACTH-independent Cushing syndrome in humans. However, to our knowledge, the status of glucose-dependent insulinotropic peptide receptor expression in adrenocortical lesions in MEN1 has not been previously investigated. OBJECTIVE: To evaluate glucose-dependent insulinotropic peptide receptor expression in adrenocortical hyperplasia associated with MEN1 syndrome. MATERIALS/METHODS: Three adrenocortical tissue samples were obtained from patients with previously known MEN1 germline mutations and in whom the presence of a second molecular event (a new MEN1 somatic mutation or an 11q13 loss of heterozygosity) had been excluded. The expression of the glucose-dependent insulinotropic peptide receptor was quantified by qPCR using the ΔΔCT method, and β-actin was used as an endogenous control. RESULTS: The median of glucose-dependent insulinotropic peptide receptor expression in the adrenocortical lesions associated with MEN1 syndrome was 2.6-fold (range 1.2 to 4.8) higher than the normal adrenal controls (p = 0.02). CONCLUSION: The current study represents the first investigation of glucose-dependent insulinotropic peptide receptor expression in adrenocortical lesions without 11q13 loss of heterozygosity in MEN1 syndrome patients. Although we studied a limited number of cases of MEN1 adrenocortical lesions retrospectively, our preliminary data suggest an involvement of glucose-dependent insulinotropic peptide receptor overexpression in the etiology of adrenocortical

  4. Methylprednisolone Pulse Treatment of Graves' Ophthalmopathy Is Not Associated with Secondary Adrenocortical Insufficiency

    PubMed Central

    Jespersen, Sofie; Nygaard, Birte; Kristensen, Lars Østergaard

    2015-01-01

    Objective Graves' ophthalmopathy (GO) is an inflammatory disease in the orbital region. The first-line medical treatment is glucocorticoids. An important potential side effect of glucocorticoid treatment is suppression of the hypothalamic-pituitary-adrenal (HPA) axis with impairment of endogenous cortisol production, implicating symptoms of adrenocortical insufficiency, especially in the period after cessation of therapy with possible risks in cases of intercurrent illness. The aim of this study was to evaluate HPA axis function before and after methylprednisolone pulse treatment of GO. Study Design HPA axis function was evaluated by measurements of plasma ACTH and an ACTH stimulation test with plasma cortisol measurements at 0 and 30 min after an intravenous bolus of synthetic ACTH (Synacthen® 250 µg). This was done in 12 patients with GO before and at cessation of methylprednisolone pulse treatment (500 mg i.v. per week for 6 weeks followed by 250 mg i.v. per week for an additional 6 weeks). Results All patients included fulfilled the criteria of intact HPA axis function before and at cessation of methylprednisolone pulse treatment. Data are given as medians (with ranges). Before glucocorticoid treatment basal plasma cortisol was 290 nM (196-579) and 786 nM (612-1,050) after ACTH stimulation. At cessation of therapy the corresponding values were 309 nM (88-718) and 852 nM (524-1,011), respectively. Thus, all patients passed a 30-min stimulated plasma cortisol of 500 nM. Before treatment plasma ACTH was 4.2 pmol/l (4-16) and at cessation of therapy the corresponding value was 4.8 pmol/l (2-9; p = 0.27). Conclusion Transient suppression of the HPA axis with secondary adrenocortical insufficiency does not seem to be a common phenomenon after intravenous methylprednisolone pulse therapy for GO. Therefore, routine precautions are not necessary. However, our results do not exclude that transient secondary adrenocortical insufficiency might occur occasionally. PMID

  5. Benign nodular hepatocellular lesions caused by abnormal hepatic circulation: etiological analysis and introduction of a new concept.

    PubMed

    Kondo, F

    2001-12-01

    Problems in definitive diagnosis and etiology of various benign nodular hepatocellular lesions were evaluated. Of these lesions, focal nodular hyperplasia (FNH), nodular regenerative hyperplasia (NRH), nodular lesions associated with idiopathic portal hypertension (IPH), non-cirrhotic large regenerative nodules (LRN), hepatocellular adenoma (HA)-like hyperplastic nodules, and partial nodular transformation (PNT) have been suggested to be related to abnormal hepatic circulation. However, the following points are considered to need further clarification: (i) is the abnormal circulation caused by thrombosis, vasculitis, or congenital anomaly?; (ii) is thrombosis a cause or a result of congestion?; (iii) are impaired blood vessels primarily the portal veins or arteries?; (iv) how are these disorders related to various syndromes, immunological abnormalities and abnormal blood flow of other organs, which are reported to coexist with these lesions often?; and (v) how should non-typical cases, which differ from typical cases, be interpreted? In addition, a concept that may lead to solving these problems (anomalous portal tract syndrome; a hypothesis that congenital vascular anomaly is the origin of these benign nodular hepatocellular lesions) was introduced. PMID:11851827

  6. Amplification of the Insulin-Like Growth Factor 1 Receptor Gene Is a Rare Event in Adrenocortical Adenocarcinomas: Searching for Potential Mechanisms of Overexpression

    PubMed Central

    Ribeiro, Tamaya Castro; Jorge, Alexander Augusto; Almeida, Madson Q.; Mariani, Beatriz Marinho de Paula; Nishi, Mirian Yumi; Mendonca, Berenice Bilharinho; Fragoso, Maria Candida Barisson Villares

    2014-01-01

    Context. IGF1R overexpression appears to be a prognostic biomarker of metastatic pediatric adrenocortical tumors. However, the molecular mechanisms that are implicated in its upregulation remain unknown. Aim. To investigate the potential mechanisms involved in IGF1R overexpression. Patients and Methods. We studied 64 adrenocortical tumors. IGF1R copy number variation was determined in all patients using MLPA and confirmed using real time PCR. In a subgroup of 32 patients, automatic sequencing was used to identify IGF1R allelic variants and the expression of microRNAs involved in IGF1R regulation by real time PCR. Results. IGF1R amplification was detected in an adrenocortical carcinoma that was diagnosed in a 46-year-old woman with Cushing's syndrome and virilization. IGF1R overexpression was demonstrated in this case. In addition, gene amplification of other loci was identified in this adrenocortical malignant tumor, but no IGF1R copy number variation was evidenced in the remaining cases. Automatic sequencing revealed three known polymorphisms but they did not correlate with its expression. Expression of miR-100, miR-145, miR-375, and miR-126 did not correlate with IGF1R expression. Conclusion. We demonstrated amplification and overexpression of IGF1R gene in only one adrenocortical carcinoma, suggesting that these combined events are uncommon. In addition, IGF1R polymorphisms and abnormal microRNA expression did not correlate with IGF1R upregulation in adrenocortical tumors. PMID:25110710

  7. Adrenocortical hemorrhagic necrosis: the role of catecholamines and retrograde medullary-cell embolism

    SciTech Connect

    Szabo, S.; McComb, D.J.; Kovacs, K.; Huettner, I.

    1981-10-01

    We investigated the pathogenesis of adrenal necrosis using animal models of the disease (induced by administration of acrylonitrile, cysteamine, or pyrazole) and human cases. Results of electron-microscopic and histochemical time-response studies with rat models revealed an early, retrograde embolization of medullary cells and cell fragments in the cortical capillaries that showed prominent endothelial injury. The experimental adrenal lesions were prevented by surgical removal of the medulla one month before administration of adrenocorticolytic chemicals, or by the administration of the alpha-adrenergic antagonist phenoxybenzamine hydrochloride. Histochemical staining for medullary (argyrophil) granules in human cases of adrenal necrosis demonstrated tissue fragments that stained positively for silver in vascular cortical spaces in nine of ten autopsy specimens and in all four surgical cases we reviewed. Thus, catecholamines released from the adrenal medulla and from the retrograde medullary emboli in the cortex may have a role in the pathogenesis of adrenocortical necrosis.

  8. Effects of neuromedin-U on immature rat adrenocortical cells: in vitro and in vivo studies.

    PubMed

    Ziolkowska, Agnieszka; Macchi, Carlo; Trejter, Marcin; Rucinski, Marcin; Nowak, Magdalena; Nussdorfer, Gastone G; Malendowicz, Ludwik K

    2008-03-01

    Neuromedin U (NMU) is a brain-gut peptide, that in the peripheral organs and tissues acts via a G protein-coupled receptor, called NMUR1. Reverse transcription-polymerase chain reaction showed the expression of NMUR1 mRNA in either cortex and medulla or dispersed zona glomerulosa and zona fasciculata-reticularis cells of the immature rat adrenals. Accordingly, immunocytochemistry demonstrated the presence of NMUR1-like immunoreactivity in the cortex and medulla of immature adrenals. NMU8 administration to immature rats was found to raise aldosterone, but not corticosterone, plasma concentration, without altering adrenal growth. Conversely, the exposure to NMU8 markedly enhanced the proliferative activity of immature rat inner adrenocortical cells in primary in vitro culture, without significantly affecting their corticosterone secretion. Collectively, our findings suggest that adrenals of immature rats may be a target for circulating NMU. However, the physiological significance and relevance of the adrenal effects of NMU remain to be ascertained. PMID:18288377

  9. Interparental Aggression and Infant Patterns of Adrenocortical and Behavioral Stress Responses

    PubMed Central

    Towe-Goodman, Nissa R.; Stifter, Cynthia A.; Mills-Koonce, W. Roger; Granger, Douglas A.

    2011-01-01

    Drawing on emotional security theory, this study examined linkages between interparental aggression, infant self-regulatory behaviors, and patterns of physiological and behavioral stress responses in a diverse sample of 735 infants residing in predominately low-income, nonmetropolitan communities. Latent profile analysis revealed four classes of adrenocortical and behavioral stress response patterns at 7-months of age, using assessments of behavioral and cortisol reactivity to an emotion eliciting challenge, as well as global ratings of the child’s negative affect and basal cortisol levels. The addition of covariates within the latent profile model suggested that children with more violence in the home and who used less caregiver-oriented regulation strategies were more likely to exhibit a pattern of high cortisol reactivity with moderate signs of distress rather than the average stress response, suggesting possible patterns of adaptation in violent households. PMID:22127795

  10. Androgen secreting giant adrenocortical carcinoma with no metastases: A case report and review of the literature

    PubMed Central

    Uruc, Fatih; Urkmez, Ahmet; Yuksel, Ozgur Haki; Sahin, Aytac; Verit, Ayhan

    2015-01-01

    Functional adrenocortical carcinoma (ACC) is a very rare disease with a poor prognosis. Over half (60%) of ACCs bigger than 6 cm synthesize hormones; hormone-secreting ACCs generally include virilization, feminization or Cushing syndrome. Besides, 82% of ACCs are metastatic at the time of diagnosis. While a 48-year-old female patient was examined for abdominal pain and flushing, we detected a non-metastasizing mass (23 × 18 × 16 cm) in the adrenal lodge. The mass was extracted en bloc during open exploration and its histopathology was reported as ACC. We review the literature and report the largest androgen-producing, clinically silent ACC mass cited in the literature so far. PMID:26425231

  11. Simultaneous adrenocortical carcinoma and ganglioneuroblastoma in a child with Turner syndrome and germline p53 mutation.

    PubMed Central

    Pivnick, E K; Furman, W L; Velagaleti, G V; Jenkins, J J; Chase, N A; Ribeiro, R C

    1998-01-01

    The predisposition to malignancy that is dominantly inherited in Li-Fraumeni syndrome is associated with germline mutations of the tumour suppressor gene p53. Although second malignant neoplasms have been described in children with p53 mutations, the synchronous occurrence of two embryologically different tumours in these children has not been reported. A 20 month old girl with failure to thrive and congenital heart defects was found to have unilateral adrenal masses which, at surgical removal, proved to be an adrenocortical carcinoma and a ganglioneuroblastoma. Further investigation showed a germline p53 mutation and Turner syndrome. It remains to be determined what effect the 45,X chromosomal complement may have on the expression of neoplasms seen in patients with p53 germline mutations. Images PMID:9598730

  12. PKA catalytic subunit mutations in adrenocortical Cushing's adenoma impair association with the regulatory subunit.

    PubMed

    Calebiro, Davide; Hannawacker, Annette; Lyga, Sandra; Bathon, Kerstin; Zabel, Ulrike; Ronchi, Cristina; Beuschlein, Felix; Reincke, Martin; Lorenz, Kristina; Allolio, Bruno; Kisker, Caroline; Fassnacht, Martin; Lohse, Martin J

    2014-01-01

    We recently identified a high prevalence of mutations affecting the catalytic (Cα) subunit of protein kinase A (PKA) in cortisol-secreting adrenocortical adenomas. The two identified mutations (Leu206Arg and Leu199_Cys200insTrp) are associated with increased PKA catalytic activity, but the underlying mechanisms are highly controversial. Here we utilize a combination of biochemical and optical assays, including fluorescence resonance energy transfer in living cells, to analyze the consequences of the two mutations with respect to the formation of the PKA holoenzyme and its regulation by cAMP. Our results indicate that neither mutant can form a stable PKA complex, due to the location of the mutations at the interface between the catalytic and the regulatory subunits. We conclude that the two mutations cause high basal catalytic activity and lack of regulation by cAMP through interference of complex formation between the regulatory and the catalytic subunits of PKA. PMID:25477193

  13. 5th International ACC Symposium: Future and Current Therapeutic Trials in Adrenocortical Carcinoma.

    PubMed

    Hoff, Ana O; Berruti, Alfredo

    2016-02-01

    Adrenocortical carcinoma (ACC) is a rare and complex disease associated with a high mortality rate. Despite intensive translational and clinical research, prognosis remains poor. Over the past decade, a significant effort has been made to develop multinational, collaborative studies to better understand the pathogenesis and clinical features of this rare disease in attempt to improve the therapeutic strategies and patient outcome. The results of both standard and newer treatments are discussed in this review as well as the recent discovery of pathways involved in ACC pathogenesis that provide the rationale to introduce new molecular target therapies. Finally, remaining issues regarding how to improve available therapies in adjuvant setting are raised and addressed. PMID:26728470

  14. Clinical, Biochemical, and Molecular Characterization of Macronodular Adrenocortical Hyperplasia of the Zona Reticularis: A New Syndrome

    PubMed Central

    Ghayee, Hans K.; Rege, Juilee; Watumull, Lori M.; Nwariaku, Fiemu E.; Carrick, Kelley S.; Rainey, William E.; Miller, Walter L.

    2011-01-01

    Context: Macronodular adrenocortical hyperplasia classically presents with progressive hypercortisolemia and Cushing syndrome. We describe a 29-yr-old man with massive macronodular adrenocortical hyperplasia without hypercortisolemia but rather markedly elevated and nonsuppressible production of dehydroepiandrosterone (DHEA) and its sulfate (DHEAS). Objective: To characterize the clinical and molecular features of this case and to determine whether the tissue biochemically resembles the zona reticularis or fetal adrenal. Setting: University clinic, hospital, and laboratories. Design: Static and dynamic blood and urine testing were performed preoperatively. Tissue was studied by light microscopy, immunoblot, RNA microarray, and enzyme assay. Participant: A 29-yr-old man with incidentally discovered bilateral adrenal enlargement. Intervention: Bilateral adrenalectomy. Main Outcome Measures: Molecular studies compared with control samples. Results: Hypercortisolism and 21-hydroxylase deficiency were excluded. DHEA, DHEAS, and 17-hydroxypregnenolone were markedly elevated and did not suppress with dexamethasone 2 mg/d for 4 d. Homogenates of the adrenals demonstrated high 17-hydroxylase, good 17,20-lyase, and low or absent 21-hydroxylase and 3β-hydroxysteroid dehydrogenase activities. Immunoblots confirmed robust expression of cytochrome P450c17 and AKR1C3 but not P450c21. Microarray analysis demonstrated high CYP11A1 and CYP17A1 expression but low or absent HSD3B1, HSD3B2, and CYP21A2 expression. Expression of mRNA for cytochrome b5 (CYB5A) and AKR1C3, markers of the zona reticularis, were markedly elevated. Conclusion: This is the first case of macronodular hyperplasia of the adrenal zona reticularis confirmed with studies of enzyme activity, mRNA expression, and protein identification. We speculate that this condition can be clinically silent in men but might cause severe hyperandrogenemia in women. PMID:21084398

  15. Effect of corticosteroid binding proteins on the steroidogenic activity of bovine adrenocortical cell suspensions.

    PubMed

    Basset, M; Rostaing-Metz, B; Chambaz, E M

    1982-07-01

    The possible role of steroid binding proteins in the hormonal secretion process of a steroidogenic tissue was examined using bovine adrenocortical cell suspensions, either under basal conditions or in the presence of half-maximally active concentration (1 x 10(-9) M) of synthetic adrenocorticotropic hormone (ACTH). Three types of plasma cortisol binding proteins were used, namely bovine serum albumine (BSA), purified transcortin (CBG) and purified anticortisol immunoglobulins (IgG). When added to the incubation medium, CBG (at 1 x 10(-10) to 2 x 10(-9) M cortisol binding sites) and anticortisol IgG (at 4.8 x 10(-10) to 3 x 10(-9) M cortisol binding sites) did not influence either the basal nor the ACTH-stimulated net cortisol production of the cell preparations. Whereas crystallized and delipidated BSA showed also no effect, crude commercial BSA preparation (Cohn fraction V) exhibited an ACTH-like cofactor effect which resulted in a marked increase in the net cortisol production by stimulated cells. These observations might be explained by the presence in crude BSA of lipoprotein-cholesterol complexes, possibly acting as an extracellular source of cholesterol available for corticosteroidogenesis. It may be concluded that specific high affinity cortisol binding systems present outside adrenocortical steroidogenic cells do not influence their secretory activity under short term in vitro condition. In addition, it can be stressed that use of ill defined protein preparations (e.g. crude BSA) may lead to artifactual observations in the study of the differentiated functions of isolated steroidogenic cells. PMID:6287106

  16. DAX1 Overexpression in Pediatric Adrenocortical Tumors: A Synergic Role with SF1 in Tumorigenesis.

    PubMed

    de Sousa, G R V; Soares, I C; Faria, A M; Domingues, V B; Wakamatsu, A; Lerario, A M; Alves, V A F; Zerbini, M C N; Mendonca, B B; Fragoso, M C B V; Latronico, A C; Almeida, M Q

    2015-08-01

    DAX1 transcription factor is a key determinant of adrenogonadal development, acting as a repressor of SF1 targets in steroidogenesis. It was recently demonstrated that DAX1 regulates pluripotency and differentiation in murine embryonic stem cells. In this study, we investigated DAX1 expression in adrenocortical tumors (ACTs) and correlated it with SF1 expression and clinical parameters. DAX1 and SF1 protein expression were assessed in 104 ACTs from 34 children (25 clinically benign and 9 malignant) and 70 adults (40 adenomas and 30 carcinomas). DAX1 gene expression was studied in 49 ACTs by quantitative real-time PCR. A strong DAX1 protein expression was demonstrated in 74% (25 out of 34) and 24% (17 out of 70) of pediatric and adult ACTs, respectively (χ(2)=10.1, p=0.002). In the pediatric group, ACTs with a strong DAX1 expression were diagnosed at earlier ages than ACTs with weak expression [median 1.2 (range, 0.5-4.5) vs. 2.2 (0.9-9.4), p=0.038]. DAX1 expression was not associated with functional status in ACTs. Interestingly, a positive correlation was observed between DAX1 and SF1 protein expression in both pediatric and adult ACTs (r=0.55 for each group separately; p<0.0001). In addition, DAX1 gene expression was significantly correlated with SF1 gene expression (p<0.0001, r=0.54). In conclusion, DAX1 strong protein expression was more frequent in pediatric than in adult ACTs. Additionally, DAX1 and SF1 expression positively correlated in ACTs, suggesting that these transcription factors might cooperate in adrenocortical tumorigenesis. PMID:25985323

  17. Non-Invasive Measurement of Adrenocortical Activity in Blue-Fronted Parrots (Amazona aestiva, Linnaeus, 1758)

    PubMed Central

    Ferreira, João C. P.; Fujihara, Caroline J.; Fruhvald, Erika; Trevisol, Eduardo; Destro, Flavia C.; Teixeira, Carlos R.; Pantoja, José C. F.; Schmidt, Elizabeth M. S.; Palme, Rupert

    2015-01-01

    Parrots kept in zoos and private households often develop psychological and behavioural disorders. Despite knowing that such disorders have a multifactorial aetiology and that chronic stress is involved, little is known about their development mainly due to a poor understanding of the parrots’ physiology and the lack of validated methods to measure stress in these species. In birds, blood corticosterone concentrations provide information about adrenocortical activity. However, blood sampling techniques are difficult, highly invasive and inappropriate to investigate stressful situations and welfare conditions. Thus, a non-invasive method to measure steroid hormones is critically needed. Aiming to perform a physiological validation of a cortisone enzyme immunoassay (EIA) to measure glucocorticoid metabolites (GCM) in droppings of 24 Blue-fronted parrots (Amazona aestiva), two experiments were designed. During the experiments all droppings were collected at 3-h intervals. Initially, birds were sampled for 24 h (experiment 1) and one week later assigned to four different treatments (experiment 2): Control (undisturbed), Saline (0.2 mL of 0.9% NaCl IM), Dexamethasone (1 mg/kg IM) and Adrenocorticotropic hormone (ACTH; 25 IU IM). Treatments (always one week apart) were applied to all animals in a cross-over study design. A daily rhythm pattern in GCM excretion was detected but there were no sex differences (first experiment). Saline and dexamethasone treatments had no effect on GCM (not different from control concentrations). Following ACTH injection, GCM concentration increased about 13.1-fold (median) at the peak (after 3–9 h), and then dropped to pre-treatment concentrations. By a successful physiological validation, we demonstrated the suitability of the cortisone EIA to non-invasively monitor increased adrenocortical activity, and thus, stress in the Blue-fronted parrot. This method opens up new perspectives for investigating the connection between behavioural

  18. The effect of pioglitazone on aldosterone and cortisol production in HAC15 human adrenocortical carcinoma cells.

    PubMed

    Pan, Zhi-qiang; Xie, Ding; Choudhary, Vivek; Seremwe, Mutsa; Tsai, Ying-Ying; Olala, Lawrence; Chen, Xunsheng; Bollag, Wendy B

    2014-08-25

    Pioglitazone belongs to the class of drugs called thiazolidinediones (TZDs), which are widely used as insulin sensitizers in the treatment of diabetes. A major side effect of TZDs is fluid retention. The steroid hormone aldosterone also promotes sodium and fluid retention; however, the effect of pioglitazone on aldosterone production is controversial. We analyzed the effect of pioglitazone alone and in combination with angiotensin II (AngII) on the late rate-limiting step of adrenocortical steroidogenesis in human adrenocortical carcinoma HAC15 cells. Treatment with pioglitazone for 24 h significantly increased the expression of CYP11B2 and enhanced AngII-induced CYP11B2 expression. Despite the observed changes in mRNA levels, pioglitazone significantly inhibited AngII-induced aldosterone production and CYP11B2 protein levels. On the other hand, pioglitazone stimulated the expression of the unfolded protein response (UPR) marker DDIT3, with this effect occurring at early times and inhibitable by the PPARγ antagonist GW9962. The levels of DDIT3 (CHOP) and phospho-eIF2α (Ser51), a UPR-induced event that inhibits protein translation, were also increased. Thus, pioglitazone promotes CYP11B2 expression but nevertheless inhibits aldosterone production in AngII-treated HAC15 cells, likely by blocking global protein translation initiation through DDIT3 and phospho-eIF2α. In contrast, pioglitazone promoted AngII-induced CYP11B1 expression and cortisol production. Since cortisol enhances lipolysis, this result suggests the possibility that PPARs, activated by products of fatty acid oxidation, stimulate cortisol secretion to promote utilization of fatty acids during fasting. In turn, the ability of pioglitazone to stimulate cortisol production could potentially underlie the effects of this drug on fluid retention. PMID:25038520

  19. Non-invasive assessment of adrenocortical function in captive Nile crocodiles (Crocodylus niloticus).

    PubMed

    Ganswindt, Stefanie B; Myburgh, Jan G; Cameron, Elissa Z; Ganswindt, Andre

    2014-11-01

    The occurrence of stress-inducing factors in captive crocodilians is a concern, since chronic stress can negatively affect animal health and reproduction, and hence production. Monitoring stress in wild crocodiles could also be beneficial for assessing the state of health in populations which are potentially threatened by environmental pollution. In both cases, a non-invasive approach to assess adrenocortical function as a measure of stress would be preferable, as animals are not disturbed during sample collection, and therefore sampling is feedback-free. So far, however, such a non-invasive method has not been established for any crocodilian species. As an initial step, we therefore examined the suitability of two enzyme-immunoassays, detecting faecal glucocorticoid metabolites (FGMs) with a 11β,21-diol-20-one and 5β-3α-ol-11-one structure, respectively, for monitoring stress-related physiological responses in captive Nile crocodiles (Crocodylus niloticus). An adrenocorticotropic hormone (ACTH) challenge was performed on 10 sub-adult crocodiles, resulting in an overall increase in serum corticosterone levels of 272% above the pre-injection levels 5h post-injection. Saline-treated control animals (n=8) showed an overall increase of 156% in serum corticosterone levels 5h post-administration. Faecal samples pre- and post-injection could be obtained from three of the six individually housed crocodiles, resulting in FGM concentrations 136-380% above pre-injection levels, always detected in the first sample collected post-treatment (7-15 days post-injection). FGM concentrations seem comparatively stable at ambient temperatures for up to 72 h post-defaecation. In conclusion, non-invasive hormone monitoring can be used for assessing adrenocortical function in captive Nile crocodiles based on FGM analysis. PMID:25066028

  20. IGF2 and IGF1R in pediatric adrenocortical tumors: roles in metastasis and steroidogenesis.

    PubMed

    Peixoto Lira, Régia Caroline; Fedatto, Paola Fernanda; Marco Antonio, David Santos; Leal, Letícia Ferro; Martinelli, Carlos Eduardo; de Castro, Margaret; Tucci, Silvio; Neder, Luciano; Ramalho, Leandra; Seidinger, Ana Luiza; Cardinalli, Izilda; Mastellaro, Maria José; Yunes, José Andres; Brandalise, Silvia Regina; Tone, Luiz Gonzaga; Rauber Antonini, Sonir Roberto; Scrideli, Carlos Alberto

    2015-06-01

    Deregulation of the IGF system observed in human tumors indicates a role in malignant cell transformation and in tumor cell proliferation. Although overexpression of the IGF2 and IGF1R genes was described in adrenocortical tumors (ACTs), few studies reported their profiles in pediatric ACTs. In this study, the IGF2 and IGF1R expression was evaluated by RT-qPCR according to the patient's clinical/pathological features in 60 pediatric ACT samples, and IGF1R protein was investigated in 45 samples by immunohistochemistry (IHC). Whole transcriptome and functional assays were conducted after IGF1R inhibition with OSI-906 in NCI-H295A cell line. Significant IGF2 overexpression was found in tumor samples when compared with non-neoplastic samples (P<0.001), significantly higher levels of IGF1R in patients with relapse/metastasis (P=0.031) and moderate/strong IGF1R immunostaining in 62.2% of ACTs, but no other relationship with patient survival and clinical/pathological features was observed. OSI-906 treatment downregulated genes associated with MAPK activity, induced limited reduction of cell viability and increased the apoptosis rate. After 24h, the treatment also decreased the expression of genes related to the steroid biosynthetic process, the protein levels of the steroidogenic acute regulatory protein (STAR), and androgen secretion in cell medium, supporting the role of IGF1R in steroidogenesis of adrenocortical carcinoma cells. Our data showed that the IGF1R overexpression could be indicative of aggressive ACTs in children. However, in vitro treatments with high concentrations of OSI-906 (>1μM) showed limited reduction of cell viability, suggesting that OSI-906 alone could not be a suitable therapy to abolish carcinoma cell growth. PMID:27185872

  1. Non-Invasive Measurement of Adrenocortical Activity in Blue-Fronted Parrots (Amazona aestiva, Linnaeus, 1758).

    PubMed

    Ferreira, João C P; Fujihara, Caroline J; Fruhvald, Erika; Trevisol, Eduardo; Destro, Flavia C; Teixeira, Carlos R; Pantoja, José C F; Schmidt, Elizabeth M S; Palme, Rupert

    2015-01-01

    Parrots kept in zoos and private households often develop psychological and behavioural disorders. Despite knowing that such disorders have a multifactorial aetiology and that chronic stress is involved, little is known about their development mainly due to a poor understanding of the parrots' physiology and the lack of validated methods to measure stress in these species. In birds, blood corticosterone concentrations provide information about adrenocortical activity. However, blood sampling techniques are difficult, highly invasive and inappropriate to investigate stressful situations and welfare conditions. Thus, a non-invasive method to measure steroid hormones is critically needed. Aiming to perform a physiological validation of a cortisone enzyme immunoassay (EIA) to measure glucocorticoid metabolites (GCM) in droppings of 24 Blue-fronted parrots (Amazona aestiva), two experiments were designed. During the experiments all droppings were collected at 3-h intervals. Initially, birds were sampled for 24 h (experiment 1) and one week later assigned to four different treatments (experiment 2): Control (undisturbed), Saline (0.2 mL of 0.9% NaCl IM), Dexamethasone (1 mg/kg IM) and Adrenocorticotropic hormone (ACTH; 25 IU IM). Treatments (always one week apart) were applied to all animals in a cross-over study design. A daily rhythm pattern in GCM excretion was detected but there were no sex differences (first experiment). Saline and dexamethasone treatments had no effect on GCM (not different from control concentrations). Following ACTH injection, GCM concentration increased about 13.1-fold (median) at the peak (after 3-9 h), and then dropped to pre-treatment concentrations. By a successful physiological validation, we demonstrated the suitability of the cortisone EIA to non-invasively monitor increased adrenocortical activity, and thus, stress in the Blue-fronted parrot. This method opens up new perspectives for investigating the connection between behavioural

  2. Adrenocortical response to low-dose ACTH test in female patients with rheumatoid arthritis.

    PubMed

    Radikova, Zofia; Rovensky, Jozef; Vlcek, Miroslav; Penesova, Adela; Kerlik, Jana; Vigas, Milan; Imrich, Richard

    2008-12-01

    Alterations in adrenal steroid production have been suggested in females with rheumatoid arthritis (RA). The aim of the present study was to assess adrenocortical function in RA females. We examined 11 female RA patients (RA: age 30 +/- 2 years, BMI 21.0 +/- 0.7 kg/m(2)) and 10 matched healthy controls (C: age 31 +/- 1 years, BMI 21.6 +/- 0.6 kg/m(2)). Low-dose adrenocorticotropic hormone (ACTH) test (i.v. bolus of 1 microg synthetic ACTH) was performed at 10.00 h with blood sampling every 15 min for 90 min. Cortisol, 17-OH-progesterone (17OHP), androstenedione (ASD), and dehydroepiandrosterone (DHEA) were assayed in plasma. Baseline cortisol levels were higher in RA patients (RA: 385 +/- 38 versus C: 229 +/- 28 nmol/L, P= 0.007). In both study groups, ACTH administration increased all the four steroids measured (P < 0.001). Cortisol response to ACTH administration was diminished in RA patients when compared to controls (Delta(max): 284 +/- 24 in RA versus 424 +/- 31 nmol/L in C, P= 0.002). ACTH-induced maximal rise in plasma DHEA was significantly lower in RA patients when compared to controls (Delta(max): 2.59 +/- 0.68 in RA versus 5.57 +/- 1.25 ng/mL in C, P= 0.015). No significant between-groups differences were found in responses of ASD or 17OHP. The molar ratio of ASD:cortisol was significantly lower (P < 0.05) in RA patients at base line, but did not differ during ACTH test. After ACTH bolus, the cortisol:17OHP ratio decreased significantly in the RA group (P < 0.001), whereas there was no change in the control group. The present results show decreased secretion of cortisol and DHEA in RA patients in response to ACTH, suggesting a subtle HPA hypofunction at the adrenocortical level. PMID:19120158

  3. The effect of pioglitazone on aldosterone and cortisol production in HAC15 human adrenocortical carcinoma cells

    PubMed Central

    Pan, Zhi-qiang; Xie, Ding; Choudhary, Vivek; Seremwe, Mutsa; Tsai, Ying-Ying; Olala, Lawrence; Chen, Xunsheng; Bollag, Wendy B.

    2014-01-01

    Pioglitazone belongs to the class of drugs called thiazolidinediones (TZDs), which are widely used as insulin sensitizers in the treatment of diabetes. A major side effect of TZDs is fluid retention. The steroid hormone aldosterone also promotes sodium and fluid retention; however, the effect of pioglitazone on aldosterone production is controversial. We analyzed the effect of pioglitazone alone and in combination with angiotensin II (AngII) on the late rate-limiting step of adrenocortical steroidogenesis in human adrenocortical carcinoma HAC15 cells. Treatment with pioglitazone for 24hr significantly increased the expression of CYP11B2 and enhanced AngII-induced CYP11B2 expression. Despite the observed changes in mRNA levels, pioglitazone significantly inhibited AngII-induced aldosterone production and CYP11B2 protein levels. On the other hand, pioglitazone stimulated the expression of the unfolded protein response (UPR) marker DDIT3, with this effect occurring at early times and inhibitable by the PPARγ antagonist GW9962. The levels of DDIT3 (CHOP) and phospho-eIF2α (Ser51), a UPR-induced event that inhibits protein translation, were also increased. Thus, pioglitazone promotes CYP11B2 expression but nevertheless inhibits aldosterone production in AngII-treated HAC15 cells, likely by blocking global protein translation initiation through DDIT3 and phospho-eIF2α. In contrast, pioglitazone promoted AngII-induced CYP11B1 expression and cortisol production. Since cortisol enhances lipolysis, this result suggests the possibility that PPARs, activated by products of fatty acid oxidation, stimulate cortisol secretion to promote utilization of fatty acids during fasting. In turn, the ability of pioglitazone to stimulate cortisol production could potentially underlie the effects of this drug on fluid retention. PMID:25038520

  4. Evaluation of 9-cis retinoic acid and mitotane as antitumoral agents in an adrenocortical xenograft model

    PubMed Central

    Nagy, Zoltán; Baghy, Kornélia; Hunyadi-Gulyás, Éva; Micsik, Tamás; Nyírő, Gábor; Rácz, Gergely; Butz, Henriett; Perge, Pál; Kovalszky, Ilona; Medzihradszky, Katalin F; Rácz, Károly; Patócs, Attila; Igaz, Peter

    2015-01-01

    The available drug treatment options for adrenocortical carcinoma (ACC) are limited. In our previous studies, the in vitro activity of 9-cis retinoic acid (9-cisRA) on adrenocortical NCI-H295R cells was shown along with its antitumoral effects in a small pilot xenograft study. Our aim was to dissect the antitumoral effects of 9-cisRA on ACC in a large-scale xenograft study involving mitotane, 9-cisRA and their combination. 43 male SCID mice inoculated with NCI-H295R cells were treated in four groups (i. control, ii. 9-cisRA, iii. mitotane, iv. 9-cisRA + mitotane) for 28 days. Tumor size follow-up, histological and immunohistochemical (Ki-67) analysis, tissue gene expression microarray, quantitative real-time-PCR for the validation of microarray results and to detect circulating microRNAs were performed. Protein expression was studied by proteomics and Western-blot validation. Only mitotane alone and the combination of 9-cisRA and mitotane resulted in significant tumor size reduction. The Ki-67 index was significantly reduced in both 9-cisRA and 9-cisRA+mitotane groups. Only modest changes at the mRNA level were found: the 9-cisRA-induced overexpression of apolipoprotein A4 and down-regulation of phosphodiesterase 4A was validated. The expression of circulating hsa-miR-483-5p was significantly reduced in the combined treatment group. The SET protein was validated as being significantly down-regulated in the combined mitotane+9-cisRA group. 9-cisRA might be a helpful additive agent in the treatment of ACC in combination with mitotane. Circulating hsa-miR-483-5p could be utilized for monitoring the treatment efficacy in ACC patients, and the treatment-induced reduction in protein SET expression might raise its relevance in ACC biology. PMID:26885453

  5. Non-photosynthetic pigments as potential biosignatures

    NASA Astrophysics Data System (ADS)

    Schwieterman, E. W.; Cockell, C. S.; Meadows, V. S.

    2014-03-01

    Photosynthetic organisms on Earth produce potentially detectable surface reflectance biosignatures due in part to the spectral location and strength of pigment absorption. However, life on Earth uses pigments for a multitude of purposes other than photosynthesis, including coping with extreme environments. Macroscopic environments exist on Earth where the surface reflectance is significantly altered by a nonphotosynthetic pigment, such as the case of hypersaline lakes and ponds (Oren et al. 1992). Here we explore the nature and potential detectability of non-photosynthetic pigments in disk-averaged planetary observations using a combination of laboratory measurements and archival reflectance spectra, along with simulated broadband photometry and spectra. The in vivo visible reflectance spectra of a cross section of pigmented microorganisms are presented to illustrate the spectral diversity of biologically produced pigments. Synthetic broadband colors are generated to show a significant spread in color space. A 1D radiative transfer model (Meadows & Crisp 1996; Crisp 1997) is used to approximate the spectra of scenarios where pigmented organisms are widespread on planets with Earth-like atmospheres. Broadband colors are revisited to show that colors due to surface reflectivity are not robust to the addition of scattering and absorption effects from the atmosphere. We consider a èbest case' plausible scenario for the detection of nonphotosynthetic pigments by using the Virtual Planetary Laboratory's 3D spectral Earth model (Robinson et al. 2011) to explore the detectability of the surface biosignature produced by pigmented halophiles that are widespread on an Earth-analog planet.

  6. Pigmented Lesion of Buccal Mucosa

    PubMed Central

    Bajpai, Manas; Kumar, Malay; Kumar, Manish; Agarwal, Deshant

    2014-01-01

    Pigmented lesions are commonly found in the mouth. Such lesions represent a variety of clinical entities, ranging from physiologic changes to manifestation of systemic illness and malignant neoplasm. Diagnosis of such lesions requires a proper case history, extraoral and intraoral examination, and, in some cases, biopsy, aspiration cytology, and laboratory investigations. Here we present a case of purple lesion on the buccal mucosa of a 34-year-old male patient which was provisionally diagnosed as mucocele but on the basis of histopathological picture it was finally diagnosed as angiofibroma, and we also discuss the clinical and histopathological differential diagnosis. PMID:25161669

  7. Melanin pigmented solar absorbing surfaces

    SciTech Connect

    Gallas, J.M.; Eisner, M.

    1980-01-01

    Selectivity enhancement is shown to result for melanin, a black biopolymer pigment, for sufficiently low sample density. The effect is proposed to follow from a consideration of the evanescent waves associated with the total internal reflection phenomenon. A relationship is discussed among powder density, pH and the paramagnetic properties of melanin; this relationship is shown to be consistent with, and offer support to an amino-acid side group proposed earlier as part of the melanin structure. A brief discussion is also presented on the optical properties of melanin and the relative importance of quinhydrone, a change transfer complex believed to exist in the polymeric structure of melanin.

  8. Pigmented lesion of buccal mucosa.

    PubMed

    Bajpai, Manas; Kumar, Malay; Kumar, Manish; Agarwal, Deshant

    2014-01-01

    Pigmented lesions are commonly found in the mouth. Such lesions represent a variety of clinical entities, ranging from physiologic changes to manifestation of systemic illness and malignant neoplasm. Diagnosis of such lesions requires a proper case history, extraoral and intraoral examination, and, in some cases, biopsy, aspiration cytology, and laboratory investigations. Here we present a case of purple lesion on the buccal mucosa of a 34-year-old male patient which was provisionally diagnosed as mucocele but on the basis of histopathological picture it was finally diagnosed as angiofibroma, and we also discuss the clinical and histopathological differential diagnosis. PMID:25161669

  9. Adrenocortical carcinoma

    MedlinePlus

    ... increased aldosterone are the same as symptoms of low potassium, and include: Muscle cramps Weakness ... will be high. Cortisol level will be high. Potassium level will be low. Male or female hormones may be abnormally high. ...

  10. IGF1-R inhibition and liposomal doxorubicin: Progress in preclinical evaluation for the treatment of adrenocortical carcinoma.

    PubMed

    Beuschlein, Felix; Jakoby, Judith; Mentz, Susanne; Zambetti, Gerard; Jung, Sara; Reincke, Martin; Süss, Regine; Hantel, Constanze

    2016-06-15

    Adrenocortical carcinoma (ACC) is a tumor with poor prognosis and limited therapeutic options. Therefore, in addition to multi-chemotherapeutic regimens IGF-1 receptor (IGF-1R) targeting approaches have been evaluated including immunoliposomal (IL) preparations utilizing an IGF-1R inhibiting antibody. In the current study, we extended our experiments by long-term treatment regimens in the classical adrenocortical NCIH295R xenograft model as well as by short-term experiments in two novel xenograft models, which all displayed different levels of IGF-1R and IGF-2 expression. Interestingly, these experiments reveal sub-group dependent differences in therapeutic outcome, reflecting clinical observations and indicate, thus, that implementation of this panel of tumor models might be helpful for clinical translation of novel therapeutic regimens in the future. PMID:26994514

  11. Genotype analysis of the human endostatin variant p.D104N in benign and malignant adrenocortical tumors

    PubMed Central

    de Paula Mariani, Beatriz Marinho; Trarbach, Ericka Barbosa; Ribeiro, Tamaya Castro; Pereira, Maria Adelaide Albergaria; Mendonca, Berenice Bilharinho; Fragoso, Maria Candida Barisson Villares

    2012-01-01

    OBJECTIVE: Endostatin is a potent endogenous inhibitor of angiogenesis. It is derived from the proteolytic cleavage of collagen XVIII, which is encoded by the COL18A1 gene. A polymorphic COL18A1 allele encoding the functional polymorphism p.D104N impairs the activity of endostatin, resulting in a decreased ability to inhibit angiogenesis. This polymorphism has been previously analyzed in many types of cancer and has been considered a phenotype modulator in some benign and malignant tumors. However, these data are controversial, and different results have been reported for the same tumor types, such as prostate and breast cancer. The purpose of this study was to genotype the p.D104N variant in a cohort of pediatric and adult patients with adrenocortical tumors and to determine its possible association with the biological behavior of adrenocortical tumors. METHODS: DNA samples were obtained from 38 pediatric and 56 adult patients (0.6–75 yrs) with adrenocortical tumors. The DNA samples were obtained from peripheral blood, frozen tissue or paraffin-embedded tumor blocks when blood samples or fresh frozen tissue samples were unavailable. Restriction fragment length polymorphism analysis was used to genotype the patients and 150 controls. The potential associations of the p.D104N polymorphism with clinical and histopathological features and oncologic outcome (age of onset, tumor size, malignant tumor behavior, and clinical syndrome) were analyzed. RESULTS: Both the patient group and the control group were in Hardy–Weinberg equilibrium. The frequencies of the p.D104N polymorphism in the patient group were 81.9% (DD), 15.9% (DN) and 2.2% (NN). In the controls, these frequencies were 80.6%, 17.3% and 2.0%, respectively. We did not observe any association of this variant with clinical or histopathological features or oncologic outcome in our cohort of pediatric and adult patients with adrenocortical tumors. PMID:22358232

  12. Fetal adrenal capsular cells serve as progenitor cells for steroidogenic and stromal adrenocortical cell lineages in M. musculus

    PubMed Central

    Wood, Michelle A.; Acharya, Asha; Finco, Isabella; Swonger, Jessica M.; Elston, Marlee J.; Tallquist, Michelle D.; Hammer, Gary D.

    2013-01-01

    The lineage relationships of fetal adrenal cells and adrenal capsular cells to the differentiated adrenal cortex are not fully understood. Existing data support a role for each cell type as a progenitor for cells of the adult cortex. This report reveals that subsets of capsular cells are descendants of fetal adrenocortical cells that once expressed Nr5a1. These fetal adrenocortical cell descendants within the adrenal capsule express Gli1, a known marker of progenitors of steroidogenic adrenal cells. The capsule is also populated by cells that express Tcf21, a known inhibitor of Nr5a1 gene expression. We demonstrate that Tcf21-expressing cells give rise to Nr5a1-expressing cells but only before capsular formation. After the capsule has formed, capsular Tcf21-expressing cells give rise only to non-steroidogenic stromal adrenocortical cells, which also express collagen 1a1, desmin and platelet-derived growth factor (alpha polypeptide) but not Nr5a1. These observations integrate prior observations that define two separate origins of adult adrenocortical steroidogenic cells (fetal adrenal cortex and/or the adrenal capsule). Thus, these observations predict a unique temporal and/or spatial role of adult cortical cells that arise directly from either fetal cortical cells or from fetal cortex-derived capsular cells. Last, the data uncover the mechanism by which two populations of fetal cells (fetal cortex derived Gli1-expressing cells and mesenchymal Tcf21-expressing mesenchymal cells) participate in the establishment of the homeostatic capsular progenitor cell niche of the adult cortex. PMID:24131628

  13. Expression of the spexin gene in the rat adrenal gland and evidences suggesting that spexin inhibits adrenocortical cell proliferation.

    PubMed

    Rucinski, Marcin; Porzionato, Andrea; Ziolkowska, Agnieszka; Szyszka, Marta; Macchi, Veronica; De Caro, Raffaele; Malendowicz, Ludwik K

    2010-04-01

    Spexin (SPX, also called NPQ) is a recently identified, highly conserved peptide which is processed and secreted. We analysed the SPX gene and its protein product in the rat adrenal gland to ascertain whether SPX is involved in the regulation of corticosteroid secretion of and growth of adrenocortical cells. In adult rat adrenal glands the highest levels of SPX mRNA were present in the glomerulosa (ZG) and fasciculate/reticularis (ZF/R) zones. High SPX gene expression levels were found in freshly isolated adult rat ZG and ZF/R cells. In cultured adrenocortical cells the levels of SPX mRNA were lower than in freshly isolated cells. SPX mRNA expression levels were found to be 2-3 times higher during days 90-540 of postnatal development than found during days 2-45. Prolonged ACTH administration lowered and dexamethasone increased adrenal SPX mRNA levels in vivo. Adrenal enucleation produced a significant linear increase in SPX mRNA levels, with the highest value occurring at day 8 after surgery, with control values taken on day 30 after enucleation. Immunohistochemistry revealed SPX-like immunoreactivity in the entire cortex of the adult male rat and in enucleation-induced regenerating cortex. A concentration of 10-6M SPX peptide stimulated basal aldosterone secretion by freshly isolated ZG. In prolonged exposure of adrenocortical cell primary cultures to SPX (10-6M) resulted in a small increase in corticosterone secretion and a notable decrease in BrdU incorporation. The results suggest the direct involvement of SPX in the regulation of adrenocortical cell proliferation; however, the mechanism of action remains unknown. PMID:20045034

  14. The Adrenocortical Response of Greater Sage Grouse (Centrocercus urophasianus) to Capture, ACTH Injection, and Confinement, as Measured in Fecal Samples

    PubMed Central

    Jankowski, M. D.; Wittwer, D. J.; Heisey, D. M.; Franson, J. C.; Hofmeister, E. K.

    2009-01-01

    Investigators of wildlife populations often utilize demographic indicators to understand the relationship between habitat characteristics and population viability. Assessments of corticosterone may enable earlier detection of populations at risk of decline because physiological adjustments to habitat disturbance occur before reproductive diminutions. Noninvasive methods to accomplish these assesments are important in species of concern, such as the greater sage grouse (GRSG). Therefore, we validated a radioimmunoassay that measures immunoreactive corticosterone metabolites (ICM) in fecal samples and used it to characterize the adrenocortical response of 15 GRSG exposed to capture, intravenous injection of 50 IU/kg adrenocorticotrophic hormone (ACTH) or saline, and 22 h of confinement. Those animals injected with ACTH exhibited a more sustained (P = 0.0139) and less variable (P = 0.0012) response than those injected with saline, indicating different levels of adrenocortical activity. We also found that potential field-collection protocols of fecal samples did not alter ICM concentrations: samples held at 4°C for up to 16 h contained similar levels of ICM as those frozen (−20°C) immediately. This study demonstrates a multiphasic adrenocortical response that varied with the level of stimulation and indicates that the assay used to measure this phenomenon is applicable for studies of wild GRSG. PMID:19199814

  15. The adrenocortical response of greater sage grouse (Centrocercus urophasianus) to capture, ACTH injection, and confinement, as measured in fecal samples

    USGS Publications Warehouse

    Jankowski, M.D.; Wittwer, D.J.; Heisey, D.M.; Franson, J.C.; Hofmeister, E.K.

    2009-01-01

    Investigators of wildlife populations often utilize demographic indicators to understand the relationship between habitat characteristics and population viability. Assessments of corticosterone may enable earlier detection of populations at risk of decline because physiological adjustments to habitat disturbance occur before reproductive diminutions. Noninvasive methods to accomplish these assesments are important in species of concern, such as the greater sage grouse (GRSG). Therefore, we validated a radioimmunoassay that measures immunoreactive corticosterone metabolites (ICM) in fecal samples and used it to characterize the adrenocortical response of 15 GRSG exposed to capture, intravenous injection of 50 IU/kg adrenocorticotrophic hormone (ACTH) or saline, and 22 h of confinement. Those animals injected with ACTH exhibited a more sustained (P = 0.0139) and less variable (P = 0.0012) response than those injected with saline, indicating different levels of adrenocortical activity. We also found that potential field-collection protocols of fecal samples did not alter ICM concentrations: samples held at 4??C for up to 16 h contained similar levels of ICM as those frozen (-20??C) immediately. This study demonstrates a multiphasic adrenocortical response that varied with the level of stimulation and indicates that the assay used to measure this phenomenon is applicable for studies of wild GRSG. ?? 2009 by The University of Chicago. All rights reserved.

  16. Rosiglitazone induces autophagy in H295R and cell cycle deregulation in SW13 adrenocortical cancer cells

    SciTech Connect

    Cerquetti, Lidia; Sampaoli, Camilla; Amendola, Donatella; Bucci, Barbara; Masuelli, Laura; Marchese, Rodolfo; Misiti, Silvia; De Venanzi, Agostino; Poggi, Maurizio; Toscano, Vincenzo; Stigliano, Antonio

    2011-06-10

    Thiazolidinediones, specific peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}) ligands, used in type-2 diabetes therapy, show favourable effects in several cancer cells. In this study we demonstrate that the growth of H295R and SW13 adrenocortical cancer cells is inhibited by rosiglitazone, a thiazolidinediones member, even though the mechanisms underlying this effect appeared to be cell-specific. Treatment with GW9662, a selective PPAR-{gamma}-inhibitor, showed that rosiglitazone acts through both PPAR-{gamma}-dependent and -independent mechanisms in H295R, while in SW13 cells the effect seems to be independent of PPAR-{gamma}. H295R cells treated with rosiglitazone undergo an autophagic process, leading to morphological changes detectable by electron microscopy and an increased expression of specific proteins such as AMPK{alpha} and beclin-1. The autophagy seems to be independent of PPAR-{gamma} activation and could be related to an increase in oxidative stress mediated by reactive oxygen species production with the disruption of the mitochondrial membrane potential, triggered by rosiglitazone. In SW13 cells, flow cytometry analysis showed an arrest in the G0/G1 phase of the cell cycle with a decrease of cyclin E and cdk2 activity, following the administration of rosiglitazone. Our data show the potential role of rosiglitazone in the therapeutic approach to adrenocortical carcinoma and indicate the molecular mechanisms at the base of its antiproliferative effects, which appear to be manifold and cell-specific in adrenocortical cancer lines.

  17. The adrenocortical response of greater sage grouse (Centrocercus urophasianus) to capture, ACTH injection, and confinement, as measured in fecal samples.

    PubMed

    Jankowski, M D; Wittwer, D J; Heisey, D M; Franson, J C; Hofmeister, E K

    2009-01-01

    Investigators of wildlife populations often utilize demographic indicators to understand the relationship between habitat characteristics and population viability. Assessments of corticosterone may enable earlier detection of populations at risk of decline because physiological adjustments to habitat disturbance occur before reproductive diminutions. Noninvasive methods to accomplish these assessments are important in species of concern, such as the greater sage grouse (GRSG). Therefore, we validated a radioimmunoassay that measures immunoreactive corticosterone metabolites (ICM) in fecal samples and used it to characterize the adrenocortical response of 15 GRSG exposed to capture, intravenous injection of 50 IU/kg adrenocorticotrophic hormone (ACTH) or saline, and 22 h of confinement. Those animals injected with ACTH exhibited a more sustained (P = 0.0139) and less variable (P = 0.0012) response than those injected with saline, indicating different levels of adrenocortical activity. We also found that potential field-collection protocols of fecal samples did not alter ICM concentrations: samples held at 4 degrees C for up to 16 h contained similar levels of ICM as those frozen (-20 degrees C) immediately. This study demonstrates a multiphasic adrenocortical response that varied with the level of stimulation and indicates that the assay used to measure this phenomenon is applicable for studies of wild GRSG. PMID:19199814

  18. Efficacy and safety of electronic brachytherapy for superficial and nodular basal cell carcinoma

    PubMed Central

    Pons-Llanas, Olga; Candela-Juan, Cristian; Celada-Alvarez, Francisco Javier; de Unamuno-Bustos, Blanca; Llavador-Ros, Margarita; Ballesta-Cuñat, Antonio; Barker, Christopher A.; Tormo-Mico, Alejandro; Botella-Estrada, Rafael; Perez-Calatayud, Jose

    2015-01-01

    Purpose Surface electronic brachytherapy (EBT) is an alternative radiotherapy solution to external beam electron radiotherapy and high-dose-rate radionuclide-based brachytherapy. In fact, it is also an alternative solution to surgery for a subgroup of patients. The objective of this work is to confirm the clinical efficacy, toxicity and cosmesis of a new EBT system, namely Esteya® in the treatment of nodular and superficial basal cell carcinoma (BCC). Material and methods This is a prospective single-center, non-randomized pilot study to assess the efficacy and safety of EBT in nodular and superficial BCC using the Esteya® system. The study was conducted from June 2014 to February 2015. The follow up time was 6 months for all cases. Results Twenty patients with 23 lesions were included. A complete response was documented in all lesions (100%). A low level of toxicity was observed after the 4th fraction in all cases. Erythema was the most frequent adverse event. Cosmesis was excellent, with more than 60% of cases without skin alteration and with subtle changes in the rest. Conclusions Electronic brachytherapy with Esteya® appears to be an effective, simple, safe, and comfortable treatment for nodular and superficial BCC associated with excellent cosmesis. It could be a good choice for elderly patients, patients with contraindications for surgery (due to comorbidities or anticoagulant drugs) or patients where surgery would result in a more disfiguring outcome. A longer follow-up and more studies are needed to confirm these preliminary results. PMID:26207112

  19. Mammotome biopsy under ultrasound control in the diagnostics and treatment of nodular breast lesions - own experience.

    PubMed

    Kibil, Wojciech; Hodorowicz-Zaniewska, Diana; Kulig, Jan

    2012-05-01

    Mammotome biopsy is an effective, minimally invasive, novel technique used in the verification of breast lesions.The aim of the study was to assess the value of ultrasound-guided vacuum-assisted core needle biopsy (mammotome biopsy) in the diagnostics and treatment of nodular breast lesions, considering own data.Material and methods. Analysis comprised 1183 mammotome biopsies under ultrasound control performed in 1177 female patients during the period between 2000 and 2010, at the Regional Clinic for Early Diagnostics and Treatment of Breast Lesions, I Chair and Department of General Surgery, Jagiellonian University, Collegium Medicum.Results. The average patient age amounted to 41.7 years. The size of the investigated lesions ranged between 4 and 65 mm (mean - 12 mm). The histopathological examination result was as follows: fibrocystic lesions (n=285), adenofibroma (n=477), adenosis sclerosans (n=188), hyperplasia without atypy (n=58), phyllode tumor (n=2), papilloma (n=14), hamartoma (n=1), atypical hyperplasia (n=25), in situ ductal carcinoma (n=4), in situ lobular carcinoma (n=5), infiltrating ductal carcinoma (n=114), infiltrating lobular carcinoma (n=4), non-diagnostic result (n=6). The histopathological diagnosis was obtained in 99.5% of cases. Patients diagnosed with atypical hyperplasia or cancer were qualified for surgery, according to accepted standards. The presence of a hematoma was the most common complication after the biopsy, observed in 16.5% of patients.Conclusions. The obtained results confirmed the high value of ultrasound-guided biopsies in the diagnostics of nodular breast lesions. The method is safe, minimally invasive, with few complications, providing a good cosmetic effect. In case of benign lesions with a diameter of less than 15 mm the mammotome biopsy enables to completely excise the lesions, being an alternative to open surgical biopsies. The mammotome biopsy should become the method of choice considering the diagnostics of nodular

  20. Thyroid nodularity and chromosome aberrations among women in areas of high background radiation in China

    SciTech Connect

    Wang, Z.Y.; Boice, J.D. Jr.; Wei, L.X.; Beebe, G.W.; Zha, Y.R.; Kaplan, M.M.; Tao, Z.F.; Maxon, H.R. III; Zhang, S.Z.; Schneider, A.B. )

    1990-03-21

    Thyroid nodularity following continuous low-dose radiation exposure in China was determined in 1,001 women aged 50-65 years who resided in areas of high background radiation (330 mR/yr) their entire lives, and in 1,005 comparison subjects exposed to normal levels of radiation (114 mR/yr). Cumulative doses to the thyroid were estimated to be of the order of 14 cGy and 5 cGy, respectively. Personal interviews and physical examinations were conducted, and measurements were made of serum thyroid hormone levels, urinary iodine concentrations, and chromosome aberrations in circulating lymphocytes. For all nodular disease, the prevalences in the high background and control areas were 9.5% and 9.3%, respectively. For single nodules, the prevalences were 7.4% in the high background area and 6.6% in the control area (prevalence ratio = 1.13; 95% confidence interval = 0.82-1.55). There were no differences found in serum levels of thyroid hormones. Women in the high background region, however, had significantly lower concentrations of urinary iodine and significantly higher frequencies of stable and unstable chromosome aberrations. Increased intake of allium vegetables such as garlic and onions was associated with a decreased risk of nodular disease, which seems consistent with experimental studies suggesting that allium compounds can inhibit tumor growth and proliferation. The prevalence of mild diffuse goiter was higher in the high background radiation region, perhaps related to a low dietary intake of iodine. These data suggest that continuous exposure to low-level radiation throughout life is unlikely to appreciably increase the risk of thyroid cancer. However, such exposure may cause chromosomal damage.

  1. Thyroid nodularity and chromosome aberrations among women in areas of high background radiation in China.

    PubMed

    Wang, Z Y; Boice, J D; Wei, L X; Beebe, G W; Zha, Y R; Kaplan, M M; Tao, Z F; Maxon, H R; Zhang, S Z; Schneider, A B

    1990-03-21

    Thyroid nodularity following continuous low-dose radiation exposure in China was determined in 1,001 women aged 50-65 years who resided in areas of high background radiation (330 mR/yr) their entire lives, and in 1,005 comparison subjects exposed to normal levels of radiation (114 mR/yr). Cumulative doses to the thyroid were estimated to be of the order of 14 cGy and 5 cGy, respectively. Personal interviews and physical examinations were conducted, and measurements were made of serum thyroid hormone levels, urinary iodine concentrations, and chromosome aberrations in circulating lymphocytes. For all nodular disease, the prevalences in the high background and control areas were 9.5% and 9.3%, respectively. For single nodules, the prevalences were 7.4% in the high background area and 6.6% in the control area (prevalence ratio = 1.13; 95% confidence interval = 0.82-1.55). There were no differences found in serum levels of thyroid hormones. Women in the high background region, however, had significantly lower concentrations of urinary iodine and significantly higher frequencies of stable and unstable chromosome aberrations. Increased intake of allium vegetables such as garlic and onions was associated with a decreased risk of nodular disease, which seems consistent with experimental studies suggesting that allium compounds can inhibit tumor growth and proliferation. The prevalence of mild diffuse goiter was higher in the high background radiation region, perhaps related to a low dietary intake of iodine. These data suggest that continuous exposure to low-level radiation throughout life is unlikely to appreciably increase the risk of thyroid cancer. However, such exposure may cause chromosomal damage. PMID:2313719

  2. Ultraviolet pigments in birds evolved from violet pigments by a single amino acid change

    PubMed Central

    Yokoyama, Shozo; Radlwimmer, F. Bernhard; Blow, Nathan S.

    2000-01-01

    UV vision has profound effects on the evolution of organisms by affecting such behaviors as mating preference and foraging strategies. Despite its importance, the molecular basis of UV vision is not known. Here, we have transformed the zebra finch UV pigment into a violet pigment by incorporating one amino acid change, C84S. By incorporating the reverse mutations, we have also constructed UV pigments from the orthologous violet pigments of the pigeon and chicken. These results and comparative amino acid sequence analyses of the pigments in vertebrates demonstrate that many avian species have achieved their UV vision by S84C. PMID:10861005

  3. Management of Thyroid Nodular Disease: Current Cytopathology Classifications and Genetic Testing.

    PubMed

    Kuo, Lindsay E; Kelz, Rachel R

    2016-01-01

    Preoperative diagnosis and operative planning for patients with thyroid nodules has improved over the last decade. The Bethesda criteria for cytopathologic classification of thyroid nodule aspirate has enhanced communication between pathologists and clinicians. Multiple genetic tests, including molecular markers and the Afirma gene expression classifier, have been developed and validated. The tests, along with clinical and radiologic information, are most useful in the setting of indeterminate cytology. The development of an updated diagnostic and treatment algorithm incorporating all available tests will help standardize the management of patients with nodular thyroid disease and reduce variation and inefficiencies in care. PMID:26610771

  4. Nodular regenerative hyperplasia related portal hypertension in a patient with hypogammaglobulinaemia

    PubMed Central

    Lal, Barun Kumar; Stanley, Adrian

    2013-01-01

    Nodular regenerative hyperplasia (NRH) of liver is a relatively rare liver disorder, but a frequent cause of noncirrhotic portal hypertension. We present a lady with common variable immune deficiency who presented with upper gastrointestinal bleeding and deranged liver function tests but preserved synthetic function. Upper gastrointestinal endoscope showed bleeding gastric varices and non-bleeding oesophageal varices. Although her oesophageal varices were eradicated by repeated endoscopic band ligation, the gastric varices failed to resolve after repeated endoscopic histocryl injection and she eventually needed transjugular intrahepatic portosystemic shunt placement. Liver biopsy showed NRH. We review the association of hypogammaglobinaemia and NRH and discuss the appropriate management of portal hypertension in NRH. PMID:23801845

  5. Nodular regenerative hyperplasia related portal hypertension in a patient with hypogammaglobulinaemia.

    PubMed

    Lal, Barun Kumar; Stanley, Adrian

    2013-06-14

    Nodular regenerative hyperplasia (NRH) of liver is a relatively rare liver disorder, but a frequent cause of noncirrhotic portal hypertension. We present a lady with common variable immune deficiency who presented with upper gastrointestinal bleeding and deranged liver function tests but preserved synthetic function. Upper gastrointestinal endoscope showed bleeding gastric varices and non-bleeding oesophageal varices. Although her oesophageal varices were eradicated by repeated endoscopic band ligation, the gastric varices failed to resolve after repeated endoscopic histocryl injection and she eventually needed transjugular intrahepatic portosystemic shunt placement. Liver biopsy showed NRH. We review the association of hypogammaglobinaemia and NRH and discuss the appropriate management of portal hypertension in NRH. PMID:23801845

  6. Reactive Nodular Fibrous Pseudotumor: Case Report and Review of the Literature

    PubMed Central

    Salihi, Rawand; Moerman, Philippe; Timmerman, Dirk; Van Schoubroeck, Dominique; Op de beeck, Katya; Vergote, Ignace

    2014-01-01

    We will describe a case of a patient diagnosed with a rare identity of a benign lesion, “reactive nodular fibrous pseudotumor” (RNFP). It is a tumor which preoperatively can present as a malignant tumor and is only reported in 19 cases. According to the very limited amount of information on this tumor in the literature it is mostly seen after trauma or intraperitoneal inflammation. Our case is the second one of RNFP associated with endometriosis, which is a frequently seen intraperitoneal inflammation process in women. Knowledge that these large pseudotumoral lesions can occur is important to direct the management of these patients. PMID:24800089

  7. Nodular fasciitis in finger simulating soft tissue malignancy☆☆☆

    PubMed Central

    Monteiro, Soraya Silveira; Ribeiro, Diva Helena; Rodrigues, Tatiane Cantarelli; Junior, Gerson Ferreira Gontijo; Arruda, Kylza; Fernandes, Eloy De Avila

    2014-01-01

    Nodular fasciitis (NF) is a rare fibroblastic proliferative lesion, characterized clinically as a solitary mass of hardened and slightly painful on palpation, fast growing and no gender preference. The objective of this study is to report the case of a patient with NF in third finger of left hand, describe the findings of plain radiography, computed tomography and magnetic resonance imaging and correlate with the literature. Since the diagnosis of NF is a challenge, being necessary to conciliate the clinical, radiological and pathological. PMID:26229780

  8. Giant benign nodular hidradenoma of the shoulder: A rare tumor in orthopedic practice

    PubMed Central

    Singhal, Vibhore; Sharma, Sansar C.; Anil, Juyal; Sachan, P. K.; Harsh, Meena; Singhal, Surina; Raghuvanshi, Shailendra

    2010-01-01

    A clear cell hidradenoma is a rare dermal tumor, which is believed to originate from the apical portion of the sweat glands. The usual size reported is 5–30 mm. It is generally found in the head, face, and upper extremity regions. This lesion has not been reported to be large enough to impinge a joint range of motion. Hence, its description in the orthopedic literature is extremely rare. We present a giant benign nodular hidradenoma presenting as painful restriction of the right shoulder joint in a 35-year-old male. PMID:21655004

  9. [Pigmented lesions of the oral cavity].

    PubMed

    Brocheriou, C; Kuffer, R; Verola, O

    1985-01-01

    Pigmented lesions of the oral cavity are of multiple origin. They can be subdivided as follows: non tumoral pigmentations, non melanin pigmented tumors or tumor-like lesions, benign melanin pigmented tumors and malignant melanomas. Among non tumoral pigmented lesions, some of them show melanin deposits: they can be associated with a systemic disease (Peutz Jeghers syndrome, Addison's disease) or have a medicamentous origin, or belong to a lichen migricans. Non tumoral and non melanin pigmentations are principally due to a heavy metal accumulation or an accidental tatoo arising after tooth treatment. Peripheral giant cell granuloma, so-called giant cell epulis is the major non pigmented non melanin pseudotumoral lesion; pigmentation is due to hemosiderin deposits. In the oral cavity nevi are principally of the intramucosal type. Blue nevus, the second type in frequency, is usually located on the hard palate. Primary malignant melanomas are rare in the oral cavity, but it is--because its very bad prognosis--the most important lesion. In order to improve the survival it is necessary to do the diagnosis as early as possible. PMID:3833244

  10. Endocrine factors as effectors of integumental pigmentation.

    PubMed

    Abdel-Malek, Z A

    1988-04-01

    Normal and malignant pigment cells are known targets for many hormones. Besides alpha-melanocyte-stimulating hormone and the steroidal hormones estrogen, testosterone, and glucocorticoids, factors produced by other epidermal cells can affect melanization and proliferation of pigment cells. Among those factors are the prostaglandins, vitamin D3, ETAF, and interleukin-1. PMID:3132340

  11. Thin Layer Chromatography (TLC) of Chlorophyll Pigments.

    ERIC Educational Resources Information Center

    Foote, Jerry

    1984-01-01

    Background information, list of materials needed, procedures used, and discussion of typical results are provided for an experiment on the thin layer chromatography of chlorophyll pigments. The experiment works well in high school, since the chemicals used are the same as those used in paper chromatography of plant pigments. (JN)

  12. ORGANIC DYES AND PIGMENTS DATA BASE

    EPA Science Inventory

    The objective of this research program was to compile a data base covering all the commercially significant dyes and pigments produced or imported in the United States. The Organic Dyes and Pigments Data Base (ODPDB) contains the following data elements: chemical-related data (co...

  13. The bioefficacy of microemulsified natural pigments in egg yolk pigmentation.

    PubMed

    Chow, P Y; Gue, S Z; Leow, S K; Goh, L B

    2014-01-01

    1. This study was designed to test the hypothesis that microemulsified carotenoid products show improved bioavailability over corresponding regular preparations, leading to greater yolk pigmentation at lower dosages. 2. The first trial was conducted using a maize-soya bean basal diet supplemented with either 0.25, 0.5, 0.75, 1.0 and 1.25 g/kg of microemulsified Red or non-microemulsified Red. The second trial involved feeding microemulsified Yellow or non-microemulsified Yellow using a similar dosage range. The layers were divided into 4 replicates of 8 layers each (32 layers per treatment). The 8 cages of layers were fed from a single feed trough. Feed and water were provided ad libitum throughout the trial. Each week, the eggs were collected. The whole liquid egg colour was determined by means of a commercially available yolk colour fan. Where required, HPLC-(high-performance liquid chromatography) based analysis of trans-capsanthin or trans-lutein equivalents using the Association of Analytical Communities method was carried out. Data were statistically analysed by one-way ANOVA method using Statgraphics. 3. Results showed that the colour and carotenoid content of the egg yolk increased with increasing amount of carotenoids in the diet. The colour of egg yolks from layers fed similar concentrations of microemulsified versus the regular preparation was significantly different. At the commercial recommended dose of one g/kg regular Yellow or Red product, the microemulsified pigmenter is able to provide the equivalent yolk colour at a 20-30% lower dose. 4. In conclusion, the trial results supported the hypothesis that a desired yolk colour score is achievable at a significantly lower inclusion rate when carotenoid molecules are emulsified using the microemulsion nanotechnology. PMID:24783946

  14. Developing fungal pigments for "painting" vascular plants.

    PubMed

    Robinson, Sara C

    2012-02-01

    The use of fungal pigments as color additives to wood as a method to increase forest revenue is a relatively new, but quickly developing field. Sugar maple (Acer saccharum) is currently the primary utilized hardwood for spalting and appears to be the best suited North American hardwood for such purposes. The combination of Trametes versicolor and Bjerkandera adusta has been identified in several instances as a strong fungal pairing for zone line production; however, Xylaria polymorpha is capable of creating zone lines without the antagonism of a secondary fungus. Few fungal pigments have been developed for reliable use; Scytalidium cuboideum is capable of producing a penetrating pink/red stain, as well as a blue pigment after extended incubation, and Chlorociboria sp. produces a blue/green pigment if grown on aspen (Populus tremuloides). Several opportunities exist for stimulation of fungal pigments including the use of copper sulfate and changes in wood pH. PMID:22237673

  15. Combined Use of Etomidate and Dexmedetomidine Produces an Additive Effect in Inhibiting the Secretion of Human Adrenocortical Hormones.

    PubMed

    Gu, Hongbin; Zhang, Mazhong; Cai, Meihua; Liu, Jinfen

    2015-01-01

    BACKGROUND The direct effects of etomidate were investigated on the secretion of cortisol and its precursors by dispersed cells from the adrenal cortex of human of animals. Dexmedetomidine (DEX) is an anesthetic agent that may interfere with cortisol secretion via an unknown mechanism, such as involving inhibition of 11b-hydroxylase and the cholesterol side-chain cleavage enzyme system. The aim of this study was to determine whether dexmedetomidine (DEX) has a similar inhibitory effect on adrenocortical function, and whether combined use of etomidate (ETO) and DEX could produce a synergistic action in inhibiting the secretion of human adrenocortical hormones. MATERIAL AND METHODS Human adrenocortical cells were exposed to different concentrations of ETO and DEX. The dose-effect model between the ETO concentration and the mean secretion of cortisone (CORT) and aldosterone (ALDO) per hour was estimated. RESULTS Hill's equation well-described the dose-effect correlation between the ETO concentration and the amount of ALDO and CORT secretion. When the DEX concentration was introduced into the model by using E0 (basal secretion) as the covariate, the goodness of fit of the ETO-CORT dose-effect model was improved significantly and the objective function value was reduced by 4.55 points (P<0.05). The parameters of the final ETO-ALDO pharmacodynamics model were EC50=9.74, Emax=1.20, E0=1.33, and γ=18.5; the parameters of the final ETO-CORT pharmacodynamics model were EC50=9.49, Emax=8.16, E0=8.57, and γ=37.0. In the presence of DEX, E0 was 8.57-0.0247×(CDEX-4.6), and the other parameters remained unchanged. All parameters but γ were natural logarithm conversion values. CONCLUSIONS Combined use of DEX and ETO reduced ETO's inhibitory E0 (basal secretion) of CORT from human adrenocortical cells in a dose-dependent manner, suggesting that combined use of ETO and DEX produced an additive effect in inhibiting the secretion of human adrenocortical hormones. PMID:26568275

  16. Combined Use of Etomidate and Dexmedetomidine Produces an Additive Effect in Inhibiting the Secretion of Human Adrenocortical Hormones

    PubMed Central

    Gu, Hongbin; Zhang, Mazhong; Cai, Meihua; Liu, Jinfen

    2015-01-01

    Background The direct effects of etomidate were investigated on the secretion of cortisol and its precursors by dispersed cells from the adrenal cortex of human of animals. Dexmedetomidine (DEX) is an anesthetic agent that may interfere with cortisol secretion via an unknown mechanism, such as involving inhibition of 11β-hydroxylase and the cholesterol side-chain cleavage enzyme system. The aim of this study was to determine whether dexmedetomidine (DEX) has a similar inhibitory effect on adrenocortical function, and whether combined use of etomidate (ETO) and DEX could produce a synergistic action in inhibiting the secretion of human adrenocortical hormones. Material/Methods Human adrenocortical cells were exposed to different concentrations of ETO and DEX. The dose-effect model between the ETO concentration and the mean secretion of cortisone (CORT) and aldosterone (ALDO) per hour was estimated. Results Hill’s equation well-described the dose-effect correlation between the ETO concentration and the amount of ALDO and CORT secretion. When the DEX concentration was introduced into the model by using E0 (basal secretion) as the covariate, the goodness of fit of the ETO-CORT dose-effect model was improved significantly and the objective function value was reduced by 4.55 points (P<0.05). The parameters of the final ETO-ALDO pharmacodynamics model were EC50=9.74, Emax=1.20, E0=1.33, and γ=18.5; the parameters of the final ETO-CORT pharmacodynamics model were EC50=9.49, Emax=8.16, E0=8.57, and γ=37.0. In the presence of DEX, E0 was 8.57–0.0247×(CDEX–4.6), and the other parameters remained unchanged. All parameters but γ were natural logarithm conversion values. Conclusions Combined use of DEX and ETO reduced ETO’s inhibitory E0 (basal secretion) of CORT from human adrenocortical cells in a dose-dependent manner, suggesting that combined use of ETO and DEX produced an additive effect in inhibiting the secretion of human adrenocortical hormones. PMID

  17. Structure of plant bile pigments

    SciTech Connect

    Schoenleber, R.W.

    1983-12-01

    Selective peptide cleavage has provided a general procedure for the study of the structure, including stereochemistry, of plant bile pigments. The information derived from the synthesis and spectral analysis of a series of 2,3-dihydrodioxobilins allows the determination of the trans relative stereochemistry for ring A of the ..beta../sub 1/-phycocyanobilin from C-phycocyanin as well as for ring A of phytochrome. A complete structure proof of the five phycoerythrobilins attached to the ..cap alpha.. and ..beta.. subunits of B-phycoerythrin is described. One of these tetrapyrroles is doubly-peptide linked to a single peptide chain through two thioethers at the C-3' and C-18' positions. The four remaining phycoerythrobilins are singly-linked to the protein through thioethers at the C-3' position and all possess the probable stereochemistry C-2(R), C-3(R), C-3'(R), and C-16(R).

  18. The role of microRNA deregulation in the pathogenesis of adrenocortical carcinoma

    PubMed Central

    Özata, Deniz M; Caramuta, Stefano; Velázquez-Fernández, David; Akçakaya, Pinar; Xie, Hong; Höög, Anders; Zedenius, Jan; Bäckdahl, Martin; Larsson, Catharina; Lui, Weng-Onn

    2011-01-01

    Adrenocortical carcinoma (ACC) is an aggressive tumor showing frequent metastatic spread and poor survival. Although recent genome-wide studies of ACC have contributed to our understanding of the disease, major challenges remain for both diagnostic and prognostic assessments. The aim of this study was to identify specific microRNAs (miRNAs) associated with malignancy and survival of ACC patients. miRNA expression profiles were determined in a series of ACC, adenoma, and normal cortices using microarray. A subset of miRNAs showed distinct expression patterns in the ACC compared with adrenal cortices and adenomas. Among others, miR-483-3p, miR-483-5p, miR-210, and miR-21 were found overexpressed, while miR-195, miR-497, and miR-1974 were underexpressed in ACC. Inhibition of miR-483-3p or miR-483-5p and overexpression of miR-195 or miR-497 reduced cell proliferation in human NCI-H295R ACC cells. In addition, downregulation of miR-483-3p, but not miR-483-5p, and increased expression of miR-195 or miR-497 led to significant induction of cell death. Protein expression of p53 upregulated modulator of apoptosis (PUMA), a potential target of miR-483-3p, was significantly decreased in ACC, and inversely correlated with miR-483-3p expression. In addition, high expression of miR-503, miR-1202, and miR-1275 were found significantly associated with shorter overall survival among patients with ACC (P values: 0.006, 0.005, and 0.042 respectively). In summary, we identified additional miRNAs associated with ACC, elucidated the functional role of four miRNAs in the pathogenesis of ACC cells, demonstrated the potential involvement of the pro-apoptotic factor PUMA (a miR-483-3p target) in adrenocortical tumors, and found novel miRNAs associated with survival in ACC. PMID:21859927

  19. Electric-Field Enhancement by Nodular Defects in Multilayer Coatings Irradiated at Normal and 45 (degree) Incidence

    SciTech Connect

    Stolz, C J; Genin, F Y; Pistor,T V

    2003-09-18

    The standing-wave electric-field profile within multilayer coatings is significantly perturbated by a nodular defect. The intensity, which is proportional to the electric field squared, is increased in the high index material by {>=}3x at normal incidence and {>=}12x at 45 degrees incidence angle. Therefore it is not surprising that nodular defects are initiation sites of laser-induced damage. In this study, the impact of reflectance-band centering and incident angle are explored for a 1 {micro}m diameter nodular defect seed overcoated with a 24 layer high-reflector constructed of quarter-wave thick alternating layers of hafnia and silica. The modeling was performed using a three-dimensional finite-element analysis code.

  20. Flat pigmented macules on sun-damaged skin of the head/neck: junctional nevus, atypical lentiginous nevus, or melanoma in situ?

    PubMed

    Zalaudek, Iris; Cota, Carlo; Ferrara, Gerardo; Moscarella, Elvira; Guitera, Pascale; Longo, Caterina; Piana, Simonetta; Argenziano, Giuseppe

    2014-01-01

    The clinical recognition of lentigo maligna (LM) in the mottled chronic sun-damaged skin can be challenging, because it shares many clinical features with other pigmented macules that commonly arise on sun-damaged skin. These include solar lentigo, flat seborrheic keratosis, and pigmented actinic keratosis, but almost never "nevus." The reason nevus is not included in the differential diagnosis of LM can be explained by the fact that the stereotypical appearance of a facial nevus differs remarkably from that of an LM. Facial nevi in adults are usually nodular, dome-shaped, well-defined, and hypopigmented (i.e., intradermal nevus of the Miescher type), whereas LM typically appears as a flat, ill-defined, and pigmented macule. Although this concept based on clinical observations sounds reasonable, clinicians apply it often only unconsciously and accept a given histopathologic diagnosis of a "junctional or lentiginous nevus" of a flat pigmented facial macule without the necessary criticism about its clinicopathologic validity. PMID:24314381

  1. Biology, clinical course and management of nodular lymphocyte-predominant hodgkin lymphoma.

    PubMed

    Nogová, Lucia; Rudiger, Thomas; Engert, Andreas

    2006-01-01

    Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) differs in histological and clinical presentation from classical Hodgkin lymphoma (cHL). The typical morphologic signs of NLPHL are atypical "lymphocytic and histiocytic" (L&H) cells, which are surrounded by a non-neoplastic nodular background of small lymphocytes of B-cell origin. The NLPHL cells are positive for CD45, CD19, CD20, CD22 and CD79a, but lack expression of CD15 and CD30, the typical markers for cHL. NLPHL patients are predominantly of male gender with a median age of 37 years. Patients often present in early stages (63%) and rarely have B-symptoms (9%). Treatment of NLPHL patients using standard Hodgkin lymphoma (HL) protocols leads to complete remission (CR) in more than 95% of patients. Survival and freedom from treatment failure (FFTF) are worse in advanced-stage patients than in early-stage patients. Thus, patients in advanced and in early stages with unfavorable risk factors are treated similarly to cHL patients. In contrast, patients with early-stage NLPHL without risk factors can be sufficiently treated with reduced intensity programs having less severe adverse effects. As a result, treatment of early NLPHL is less clearly defined, including radiotherapy in extended field (EF) or involved field (IF) technique, combined modality treatment, and, more recently, monoclonal antibody rituximab. Watch and wait strategy plays an important role in pediatric oncology to avoid adverse effects associated with therapy. PMID:17124071

  2. Potentiation of fibroblast growth by nodular sclerosing Hodgkin's disease cell cultures.

    PubMed

    Newcom, S R; O'Rourke, L

    1982-07-01

    Cell cultures were established from 8 lymph nodes replaced by nodular sclerosing Hodgkin's disease. Serum-containing and serum-free conditioned media from these cultures potentiated fibroblast growth and were found to be consistently more potent than fibroblast growth factor, 100 ng/ml, every other day. Both a proliferative response and transformation-like growth were observed using BALB/c 3T3 cells, human diploid fibroblasts, and human embryonic fibroblasts as target cells. The Hodgkin's disease growth factor(s) was not produced by fibroblasts or lymphocytes in the Hodgkin's cultures and was most potent when the Hodgkin's cultures had been enriched with Hodgkin's giant cells. Removal of normal macrophages decreased the proliferative activity but did not eliminate it or nonadherent growth of 3T3 cells in agar. Control cultures of 6 nonmalignant lymph nodes, a Lennert's lymphoma, a mixed cellularity Hodgkin's disease lymph node, and a malignant histiocytosis cell line suggested that among lymph node disorders, this feature may be relatively specific for nodular sclerosing Hodgkin's disease. PMID:6211204

  3. Primary localized cutaneous nodular amyloidosis of the feet: a case report and review of the literature.

    PubMed

    Ritchie, Simon A; Beachkofsky, Thomas; Schreml, Stephan; Gaspari, Anthony; Hivnor, Chad M

    2014-02-01

    Primary localized cutaneous nodular amyloidosis (PLCNA) is a rare disorder that manifests as the cutaneous formation of nodules composed of light-chain amyloid. Although the type of amyloid deposit is similar to primary systemic amyloidosis, there seems to be little, if any, crossover between the 2 diseases. Because reports of PLCNA are sparse, there is no established protocol for treating this disease. This case report presents a 42-year-old man with a visually striking presentation of PLCNA on both feet with some of the lesions possibly being secondary to trauma, a rare phenomenon. The lesions had been present for more than 4 years, and there were no signs or symptoms of systemic amyloidosis. The lesions responded well to a combination of complete curettage followed by CO2; laser ablation. Primary localized cutaneous nodular amyloidosis is rare and difficult to treat, with high rates of recurrence and a concern for progression to systemic amyloidosis. The diagnosis, workup, treatment, and monitoring of PLCNA also are discussed. PMID:24605345

  4. Nodular thyroid disease in children and adolescents: a high incidence of carcinoma

    SciTech Connect

    McHenry, C.; Smith, M.; Lawrence, A.M.; Jarosz, H.; Paloyan, E.

    1988-07-01

    Over a period of 32 years from 1954 to 1986, 65 patients under the age of 21 years, 52 girls and 13 boys, were operated for nodular thyroids: the overall incidence of carcinoma was 37 per cent. It was 46 per cent in those patients presenting with a solitary nodule. Among the 24 patients with a malignancy, the carcinoma was of the papillary variety in 63 per cent, follicular in 25 per cent and medullary in 12 per cent. Two thirds of the patients had metastatic disease at the time of presentation. All patients with thyroid carcinoma were treated with total thyroidectomy. Other measures included neck dissection and radioactive iodine. When the eight patients with a history of head and neck irradiation and the three patients with medullary carcinoma were excluded, the incidence of carcinoma was 28 per cent. In summary, in spite of the decline in radiation associated cases, the incidence of carcinoma in nodular thyroid disease in the population under 21 years, remains at the relatively high figure of 28 per cent.

  5. Physical insight toward electric field enhancement at nodular defects in optical coatings.

    PubMed

    Cheng, Xinbin; Tuniyazi, Abudusalamu; Wei, Zeyong; Zhang, Jinlong; Ding, Tao; Jiao, Hongfei; Ma, Bin; Li, Hongqiang; Li, Tongbao; Wang, Zhanshan

    2015-04-01

    Although the finite-difference time-domain (FDTD) technique has been prevailingly used to calculate the electric field intensity (EFI) enhancement at nodular defects in high-reflection (HR) coatings, the physical insight as to how the nodular features contribute to the intensified EFI is not explicitly revealed yet, which in turn limits the solutions that improve the laser-induced damage threshold (LIDT) of nodules by decreasing the EFI enhancement. Here, a simplified model is proposed to describe the intensified EFI in nodules: 1) the nodule works as a microlens and its focal length can be predicted using a simple formula, 2) the portion of incident light that penetrates through the HR coating can be estimated by knowing the angular dependent transmittance (ADT) of the nodule, 3) strong EFI enhancement is created when the focal point is within the nodule and simultaneously a certain portion of light penetrates to the focal position. In the light of the proposed model, a broadband HR coating was used to reduce the EFI enhancement at the seed by a factor about 10, which leads to a 20 times increment of the LIDT. This work therefore not only deepens the physical understanding of EFI enhancement at nodules but also provides a new way to increase the LIDT of multilayer reflective optics. PMID:25968699

  6. Knockdown of SF-1 and RNF31 Affects Components of Steroidogenesis, TGFβ, and Wnt/β-catenin Signaling in Adrenocortical Carcinoma Cells

    PubMed Central

    Ehrlund, Anna; Jonsson, Philip; Vedin, Lise-Lotte; Williams, Cecilia; Gustafsson, Jan-Åke; Treuter, Eckardt

    2012-01-01

    The orphan nuclear receptor Steroidogenic Factor-1 (SF-1, NR5A1) is a critical regulator of development and homeostasis of the adrenal cortex and gonads. We recently showed that a complex containing E3 ubiquitin ligase RNF31 and the known SF-1 corepressor DAX-1 (NR0B1) interacts with SF-1 on target promoters and represses transcription of steroidogenic acute regulatory protein (StAR) and aromatase (CYP19) genes. To further evaluate the role of SF-1 in the adrenal cortex and the involvement of RNF31 in SF-1-dependent pathways, we performed genome-wide gene-expression analysis of adrenocortical NCI-H295R cells where SF-1 or RNF31 had been knocked down using RNA interference. We find RNF31 to be deeply connected to cholesterol metabolism and steroid hormone synthesis, strengthening its role as an SF-1 coregulator. We also find intriguing evidence of negative crosstalk between SF-1 and both transforming growth factor (TGF) β and Wnt/β-catenin signaling. This crosstalk could be of importance for adrenogonadal development, maintenance of adrenocortical progenitor cells and the development of adrenocortical carcinoma. Finally, the SF-1 gene profile can be used to distinguish malignant from benign adrenocortical tumors, a finding that implicates SF-1 in the development of malignant adrenocortical carcinoma. PMID:22427816

  7. Surgical Management of Iatrogenic Pigment Dispersion Glaucoma

    PubMed Central

    Mierlo, Camille Van; Pinto, Luis Abegão

    2015-01-01

    ABSTRACT Introduction: Iatrogenic pigment dispersion syndrome generally originates from a repetitive, mechanical trauma to the pigmented posterior epithelium of the iris. This trauma can arise after intraocular surgery, most commonly due to an abnormal contact between the intraocular lens (IOL) and the iris. Whether surgical removal of this primary insult can lead to a successful intraocular pressure (IOP) control remains unclear. Methods: Case-series. Patients with IOP elevation and clinical signs of pigment dispersion were screened for a diagnosis of iatrogenic IOL-related pigment dispersion. Results: Three patients in which the IOL or the IOL-bag complex caused a pigment dispersion through a repetitive iris chafing were selected. In two cases, replacement of a sulcus-based single-piece IOL (patient 1) or a sub-luxated in-the-bag IOL (patient 2) by an anterior-chamber (AC) iris-fixed IOL led to a sustained decrease in IOP. In the third case, extensive iris atrophy and poor anatomical AC parameters for IOL implantation precluded further surgical intervention. Conclusion: IOL-exchange appears to be a useful tool in the management of iatrogenic pigment dispersion glaucoma due to inappropriate IOL implantation. This cause-oriented approach seems to be effective in controlling IOP, but should be offered only if safety criteria are met. How to cite this article: Van Mierlo C, Abegao Pinto L, Stalmans I. Surgical Management of Iatrogenic Pigment Dispersion Glaucoma. J Curr Glaucoma Pract 2015;9(1):28-32. PMID:26997830

  8. Surface modification for aluminium pigment inhibition.

    PubMed

    Karlsson, Philip; Palmqvist, Anders E C; Holmberg, Krister

    2006-12-21

    This review concerns surface treatment of aluminium pigments for use in water borne coatings. Aluminium pigments are commonly used in coatings to give a silvery and shiny lustre to the substrate. Such paints and inks have traditionally been solvent borne, since aluminium pigment particles react with water. For environmental and health reasons solvent borne coatings are being replaced by water borne and the aluminium pigments then need to be surface modified in order to stand exposure to water. This process is called inhibition and both organic and inorganic substances are used as inhibiting agents. The organic inhibiting agents range from low molecular weight substances, such as phenols and aromatic acids, via surfactants, in particular alkyl phosphates and other anionic amphiphiles, to high molecular weight compounds, such as polyelectrolytes. A common denominator for them all is that they contain a functional group that interacts specifically with aluminium at the surface. A particularly strong interaction is obtained if the inhibiting agent contains functional groups that form chelating complex with surface Al(III). Encapsulation of the pigment can be made by in situ polymerization at the surface of the pigment and a recent approach is to have the polymerization occur within a double layer of adsorbed surfactant. The inorganic route is dominated by coating with silica, and recent progress has been made using an alkoxide, such as tetraethoxysilane as silica precursor. Such silica coated aluminium pigments are comparable in performance to chromate inhibited pigments and thus offer a possible heavy metal-free alternative. There are obvious connections between surface modifications made to prevent the pigment to react with water and inhibition of corrosion of macroscopic aluminium surfaces. PMID:17239333

  9. Exosomes released by keratinocytes modulate melanocyte pigmentation

    PubMed Central

    Cicero, Alessandra Lo; Delevoye, Cédric; Gilles-Marsens, Floriane; Loew, Damarys; Dingli, Florent; Guéré, Christelle; André, Nathalie; Vié, Katell; van Niel, Guillaume; Raposo, Graça

    2015-01-01

    Cells secrete extracellular vesicles (EVs), exosomes and microvesicles, which transfer proteins, lipids and RNAs to regulate recipient cell functions. Skin pigmentation relies on a tight dialogue between keratinocytes and melanocytes in the epidermis. Here we report that exosomes secreted by keratinocytes enhance melanin synthesis by increasing both the expression and activity of melanosomal proteins. Furthermore, we show that the function of keratinocyte-derived exosomes is phototype-dependent and is modulated by ultraviolet B. In sum, this study uncovers an important physiological function for exosomes in human pigmentation and opens new avenues in our understanding of how pigmentation is regulated by intercellular communication in both healthy and diseased states. PMID:26103923

  10. Exosomes released by keratinocytes modulate melanocyte pigmentation.

    PubMed

    Lo Cicero, Alessandra; Delevoye, Cédric; Gilles-Marsens, Floriane; Loew, Damarys; Dingli, Florent; Guéré, Christelle; André, Nathalie; Vié, Katell; van Niel, Guillaume; Raposo, Graça

    2015-01-01

    Cells secrete extracellular vesicles (EVs), exosomes and microvesicles, which transfer proteins, lipids and RNAs to regulate recipient cell functions. Skin pigmentation relies on a tight dialogue between keratinocytes and melanocytes in the epidermis. Here we report that exosomes secreted by keratinocytes enhance melanin synthesis by increasing both the expression and activity of melanosomal proteins. Furthermore, we show that the function of keratinocyte-derived exosomes is phototype-dependent and is modulated by ultraviolet B. In sum, this study uncovers an important physiological function for exosomes in human pigmentation and opens new avenues in our understanding of how pigmentation is regulated by intercellular communication in both healthy and diseased states. PMID:26103923

  11. [From the history of endocrinology: reminiscence of the discovery of adrenocortical hormones].

    PubMed

    Pura, M; Kreze, A

    2005-01-01

    In the article authors describe the milestones in history of discoveries of the adrenocortical hormones. Preparation of the adrenal extract cortine was the first experimental contribution. Cortine prolonged life of animals whose adrenals have been removed and had beneficial effects in patients with Addison disease (AD). It was mixture of compounds comprising carbon, hydrogen and oxygen that belong to the steroids. From those deoxycorticosterone had impact on mineral metabolism, substances that Kendall termed as compounds A, B, E, and F influenced metabolism of saccharides and proteins. In 1929 Dr. Hench had observed that the painful symptoms of rheumatoid arthritis (RA) were relieved in a patient who developed jaundice and in 1931 he remarked favourable effects of pregnancy to the course of RA. He suggested that some agent (substance X) was present during jaundice and in pregnancy through that the symptoms of RA were relieved. In 1941 interest concerned to the compound A, however, this was almost ineffective in patients with AD. In 1948 compound E was successfully administered to patients with AD and RA for the first time. Concerning the relation between vitamin E Kendall and Hench gave compound E distinctive name cortisone. Consequently it was confirmed that compound F (hydrocortisone) is the final product of the adrenal cortex. Appreciating the work of the most significant groups was awarding the Nobel Prize to Edward Kendall, Tadeusz Reichstein and Philip Hench in 1950. PMID:16193947

  12. microRNA-7 as a tumor suppressor and novel therapeutic for adrenocortical carcinoma

    PubMed Central

    Gill, Anthony J.; Weiss, Jocelyn; Mugridge, Nancy; Kim, Edward; Feeney, Alex L.; Ip, Julian C.; Reid, Glen; Clarke, Stephen; Soon, Patsy S.H.; Robinson, Bruce G.; Brahmbhatt, Himanshu; MacDiarmid, Jennifer A.; Sidhu, Stan B.

    2015-01-01

    Adrenocortical carcinoma (ACC) has a poor prognosis with significant unmet clinical need due to late diagnosis, high rates of recurrence/metastasis and poor response to conventional treatment. Replacing tumor suppressor microRNAs (miRNAs) offer a novel therapy, however systemic delivery remains challenging. A number of miRNAs have been described to be under-expressed in ACC however it is not known if they form a part of ACC pathogenesis. Here we report that microRNA-7–5p (miR-7) reduces cell proliferation in vitro and induces G1 cell cycle arrest. Systemic miR-7 administration in a targeted, clinically safe delivery vesicle (EGFREDVTM nanocells) reduces ACC xenograft growth originating from both ACC cell lines and primary ACC cells. Mechanistically, miR-7 targets Raf-1 proto-oncogene serine/threonine kinase (RAF1) and mechanistic target of rapamycin (MTOR). Additionally, miR-7 therapy in vivo leads to inhibition of cyclin dependent kinase 1 (CDK1). In patient ACC samples, CDK1 is overexpressed and miR-7 expression inversely related. In summary, miR-7 inhibits multiple oncogenic pathways and reduces ACC growth when systemically delivered using EDVTM nanoparticles. This data is the first study in ACC investigating the possibility of miRNAs replacement as a novel therapy. PMID:26452132

  13. Blunted Opiate Modulation of Hypothalamic-Pituitary-Adrenocortical Activity in Men and Women Who Smoke

    PubMed Central

    al’Absi, Mustafa; Wittmers, Lorentz E.; Hatsukami, Dorothy; Westra, Ruth

    2016-01-01

    Objective To examine the extent to which nicotine dependence alters endogenous opioid regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis functions. Endogenous opiates play an important role in regulating mood, pain, and drug reward. They also regulate the HPA functions. Previous work has demonstrated an abnormal HPA response to psychological stress among dependent smokers. Methods Smokers and nonsmokers (total n = 48 participants) completed two sessions during which a placebo or 50 mg of naltrexone was administered, using a double-blind design. Blood and saliva samples, cardiovascular and mood measures were obtained during a resting absorption period, after exposure to two noxious stimuli, and during an extended recovery period. Thermal pain threshold and tolerance were assessed in both sessions. Participants also rated pain during a 90-second cold pressor test. Results Opioid blockade increased adrenocorticotropin, plasma cortisol, and salivary cortisol levels; these increases were enhanced by exposure to the noxious stimuli. These responses were blunted in smokers relative to nonsmokers. Smokers tended to report less pain than nonsmokers, and women reported more pain during both pain procedures, although sex differences in pain were significant only among nonsmokers. Conclusions We conclude that nicotine dependence is associated with attenuated opioid modulation of the HPA. This dysregulation may play a role in the previously observed blunted responses to stress among dependent smokers. PMID:18799426

  14. Role of ALADIN in Human Adrenocortical Cells for Oxidative Stress Response and Steroidogenesis

    PubMed Central

    Jühlen, Ramona; Idkowiak, Jan; Taylor, Angela E.; Kind, Barbara; Arlt, Wiebke; Huebner, Angela; Koehler, Katrin

    2015-01-01

    Triple A syndrome is caused by mutations in AAAS encoding the protein ALADIN. We investigated the role of ALADIN in the human adrenocortical cell line NCI-H295R1 by either over-expression or down-regulation of ALADIN. Our findings indicate that AAAS knock-down induces a down-regulation of genes coding for type II microsomal cytochrome P450 hydroxylases CYP17A1 and CYP21A2 and their electron donor enzyme cytochrome P450 oxidoreductase, thereby decreasing biosynthesis of precursor metabolites required for glucocorticoid and androgen production. Furthermore we demonstrate that ALADIN deficiency leads to increased susceptibility to oxidative stress and alteration in redox homeostasis after paraquat treatment. Finally, we show significantly impaired nuclear import of DNA ligase 1, aprataxin and ferritin heavy chain 1 in ALADIN knock-down cells. We conclude that down-regulating ALADIN results in decreased oxidative stress response leading to alteration in steroidogenesis, highlighting our knock-down cell model as an important in-vitro tool for studying the adrenal phenotype in triple A syndrome. PMID:25867024

  15. ATR-101 disrupts mitochondrial functions in adrenocortical carcinoma cells and in vivo.

    PubMed

    Cheng, Yunhui; Kerppola, Raili Emilia; Kerppola, Tom Klaus

    2016-04-01

    Adrenocortical carcinoma (ACC) generally has poor prognosis. Existing treatments provide limited benefit for most patients with locally advanced or metastatic tumors. We investigated the mechanisms for the cytotoxicity, xenograft suppression, and adrenalytic activity of ATR-101 (PD132301-02), a prospective agent for ACC treatment. Oral administration of ATR-101 inhibited the establishment and impeded the growth of ACC-derived H295R cell xenografts in mice. ATR-101 induced H295R cell apoptosis in culture and in xenografts. ATR-101 caused mitochondrial hyperpolarization, reactive oxygen release, and ATP depletion within hours after exposure, followed by cytochrome c release, caspase-3/7 activation, and membrane permeabilization. The increase in mitochondrial membrane potential occurred concurrently with the decrease in cellular ATP levels. When combined with ATR-101, lipophilic free radical scavengers suppressed the reactive oxygen release, and glycolytic precursors prevented the ATP depletion, abrogating ATR-101 cytotoxicity. ATR-101 directly inhibited F1F0-ATPase activity and suppressed ATP synthesis in mitochondrial fractions. ATR-101 administration to guinea pigs caused oxidized lipofuscin accumulation in thezona fasciculatalayer of the adrenal cortex, implicating reactive oxygen release in the adrenalytic effect of ATR-101. These results support the development of ATR-101 and other adrenalytic compounds for the treatment of ACC. PMID:26843528

  16. Chloroquine alleviates etoposide-induced centrosome amplification by inhibiting CDK2 in adrenocortical tumor cells

    PubMed Central

    Chen, T-Y; Syu, J-S; Lin, T-C; Cheng, H-l; Lu, F-l; Wang, C-Y

    2015-01-01

    The antitumor drug etoposide (ETO) is widely used in treating several cancers, including adrenocortical tumor (ACT). However, when used at sublethal doses, tumor cells still survive and are more susceptible to the recurring tumor due to centrosome amplification. Here, we checked the effect of sublethal dose of ETO in ACT cells. Sublethal dose of ETO treatment did not induce cell death but arrested the ACT cells in G2/M phase. This resulted in centrosome amplification and aberrant mitotic spindle formation leading to genomic instability and cellular senescence. Under such conditions, Chk2, cyclin A/CDK2 and ERK1/2 were aberrantly activated. Pharmacological inactivation of Chk2, CDK2 or ERK1/2 or depletion of CDK2 or Chk2 inhibited the centrosome amplification in ETO-treated ACT cells. In addition, autophagy was activated by ETO and was required for ACT cell survival. Chloroquine, the autophagy inhibitor, reduced ACT cell growth and inhibited ETO-induced centrosome amplification. Chloroquine alleviated CDK2 and ERK, but not Chk2, activation and thus inhibited centrosome amplification in either ETO- or hydroxyurea-treated ACT cells. In addition, chloroquine also inhibited centrosome amplification in osteosarcoma U2OS cell lines when treated with ETO or hydroxyurea. In summary, we have demonstrated that chloroquine inhibited ACT cell growth and alleviated DNA damage-induced centrosome amplification by inhibiting CDK2 and ERK activity, thus preventing genomic instability and recurrence of ACT. PMID:26690546

  17. Adrenocortical effects of oral estrogens and soy isoflavones in female monkeys.

    PubMed

    Wood, Charles E; Cline, J Mark; Anthony, Mary S; Register, Thomas C; Kaplan, Jay R

    2004-05-01

    The goal of this study was to evaluate the long-term adrenocortical effects of premenopausal oral contraceptives (OC) and postmenopausal conjugated equine estrogens (CEE) and soy isoflavones in a female cynomolgus monkey model. Half of the animals received a triphasic OC for a period of 26 months, after which all monkeys were ovariectomized and randomized to one of three diet groups for 36 months: 1). isoflavone-depleted soy protein (control) (n = 54); 2). soy protein with isoflavones (129 mg/d equivalent) (SPI+) (n = 56); or 3). isoflavone-depleted soy protein with CEE (0.625 mg/d equivalent) (n = 59). In the premenopausal phase, OC treatment resulted in significantly higher cortisol (F) and lower dehydroepiandrosterone sulfate, androstenedione, and testosterone relative to intact controls. In the postmenopausal phase, CEE treatment resulted in significantly higher basal F and lower dehydroepiandrosterone sulfate, androstenedione, and testosterone when compared with control and SPI+ diets. Serum F and androgens in the SPI+ group did not differ significantly from the control group. The SPI+ group had significantly lower adrenal weight than either control or CEE groups, and this effect was localized primarily to the zona fasciculata region of the adrenal cortex. These findings suggest that long-term estrogen treatment may contribute to an androgen-deficient and hypercortisolemic state. PMID:15126559

  18. Steroidogenic Acute Regulatory Protein Overexpression Correlates with Protein Kinase A Activation in Adrenocortical Adenoma.

    PubMed

    Zhou, Weiwei; Wu, Luming; Xie, Jing; Su, Tingwei; Jiang, Lei; Jiang, Yiran; Cao, Yanan; Liu, Jianmin; Ning, Guang; Wang, Weiqing

    2016-01-01

    The association of pathological features of cortisol-producing adrenocortical adenomas (ACAs) with somatic driver mutations and their molecular classification remain unclear. In this study, we explored the association between steroidogenic acute regulatory protein (StAR) expression and the driver mutations activating cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling to identify the pathological markers of ACAs. Immunohistochemical staining for StAR and mutations in the protein kinase cAMP-activated catalytic subunit alpha (PRKACA), protein kinase cAMP-dependent type I regulatory subunit alpha (PRKAR1A) and guanine nucleotide binding protein, alpha stimulating (GNAS) genes were examined in 97 ACAs. The association of StAR expression with the clinical and mutational features of the ACAs was analyzed. ACAs with mutations in PRKACA, GNAS, and PRKAR1A showed strong immunopositive staining for StAR. The concordance between high StAR expression and mutations activating cAMP/PKA signaling in the ACAs was 99.0%. ACAs with high expression of StAR had significantly smaller tumor volume (P < 0.001) and higher urinary cortisol per tumor volume (P = 0.032) than those with low expression of StAR. Our findings suggest that immunohistochemical staining for StAR is a reliable pathological approach for the diagnosis and classification of ACAs with cAMP/PKA signaling-activating mutations. PMID:27606678

  19. The Social Buffering of the Hypothalamic-Pituitary-Adrenocortical Axis in Humans: Developmental and Experiential Determinants

    PubMed Central

    Gunnar, Megan R.; Hostinar, Camelia E.

    2015-01-01

    Social buffering, a subset of social support, is the process through which the availability of a conspecific reduces the activity of stress-mediating neurobiological systems. While its role in coping and resilience is significant, we know little about its developmental history in humans. This brief review presents an integrative developmental account of the social buffering of hypothalamic-pituitary-adrenocortical (HPA) stress reactivity in humans, from infancy to adulthood. During infancy, parents are powerful stress-regulators for children, but child temperament also plays a role and interacts with parenting quality to predict the magnitude of stress responses to fear or pain stimuli. Recent work indicates that parental support remains a potent stress buffer into late childhood, but that it loses its effectiveness as a buffer of the HPA axis by adolescence. Puberty may be the switch that alters the potency of parental buffering. In Beginning in middle childhood, friends may serve as stress buffers, particularly when other peers are the source of stress. By adulthood romantic partners assume this protective role, though studies often reveal sex differences that are currently not well understood. Translational research across species will be critical for developing a mechanistic understanding of social buffering and the processes involved in developmental changes noted in this review. PMID:26230646

  20. GPER agonist G-1 decreases adrenocortical carcinoma (ACC) cell growth in vitro and in vivo

    PubMed Central

    Zolea, Fabiana; Rizza, Pietro; Avena, Paola; Malivindi, Rocco; De Luca, Arianna; Campana, Carmela; Martire, Emilia; Domanico, Francesco; Fallo, Francesco; Carpinelli, Giulia; Cerquetti, Lidia; Amendola, Donatella; Stigliano, Antonio; Pezzi, Vincenzo

    2015-01-01

    We have previously demonstrated that estrogen receptor (ER) alpha (ESR1) increases proliferation of adrenocortical carcinoma (ACC) through both an estrogen-dependent and -independent (induced by IGF-II/IGF1R pathways) manner. Then, the use of tamoxifen, a selective estrogen receptor modulator (SERM), appears effective in reducing ACC growth in vitro and in vivo. However, tamoxifen not only exerts antiestrogenic activity, but also acts as full agonist on the G protein-coupled estrogen receptor (GPER). Aim of this study was to investigate the effect of a non-steroidal GPER agonist G-1 in modulating ACC cell growth. We found that G-1 is able to exert a growth inhibitory effect on H295R cells both in vitro and, as xenograft model, in vivo. Treatment of H295R cells with G-1 induced cell cycle arrest, DNA damage and cell death by the activation of the intrinsic apoptotic mechanism. These events required sustained extracellular regulated kinase (ERK) 1/2 activation. Silencing of GPER by a specific shRNA partially reversed G-1-mediated cell growth inhibition without affecting ERK activation. These data suggest the existence of G-1 activated but GPER-independent effects that remain to be clarified. In conclusion, this study provides a rational to further study G-1 mechanism of action in order to include this drug as a treatment option to the limited therapy of ACC. PMID:26131713

  1. GPER agonist G-1 decreases adrenocortical carcinoma (ACC) cell growth in vitro and in vivo.

    PubMed

    Chimento, Adele; Sirianni, Rosa; Casaburi, Ivan; Zolea, Fabiana; Rizza, Pietro; Avena, Paola; Malivindi, Rocco; De Luca, Arianna; Campana, Carmela; Martire, Emilia; Domanico, Francesco; Fallo, Francesco; Carpinelli, Giulia; Cerquetti, Lidia; Amendola, Donatella; Stigliano, Antonio; Pezzi, Vincenzo

    2015-08-01

    We have previously demonstrated that estrogen receptor (ER) alpha (ESR1) increases proliferation of adrenocortical carcinoma (ACC) through both an estrogen-dependent and -independent (induced by IGF-II/IGF1R pathways) manner. Then, the use of tamoxifen, a selective estrogen receptor modulator (SERM), appears effective in reducing ACC growth in vitro and in vivo. However, tamoxifen not only exerts antiestrogenic activity, but also acts as full agonist on the G protein-coupled estrogen receptor (GPER). Aim of this study was to investigate the effect of a non-steroidal GPER agonist G-1 in modulating ACC cell growth. We found that G-1 is able to exert a growth inhibitory effect on H295R cells both in vitro and, as xenograft model, in vivo. Treatment of H295R cells with G-1 induced cell cycle arrest, DNA damage and cell death by the activation of the intrinsic apoptotic mechanism. These events required sustained extracellular regulated kinase (ERK) 1/2 activation. Silencing of GPER by a specific shRNA partially reversed G-1-mediated cell growth inhibition without affecting ERK activation. These data suggest the existence of G-1 activated but GPER-independent effects that remain to be clarified. In conclusion, this study provides a rational to further study G-1 mechanism of action in order to include this drug as a treatment option to the limited therapy of ACC. PMID:26131713

  2. Rapid and Complete Remission of Metastatic Adrenocortical Carcinoma Persisting 10 Years After Treatment With Mitotane Monotherapy

    PubMed Central

    Ghorayeb, Nada El; Rondeau, Geneviève; Latour, Mathieu; Cohade, Christian; Olney, Harold; Lacroix, André; Perrotte, Paul; Sabourin, Alexis; Mazzuco, Tania L; Bourdeau, Isabelle

    2016-01-01

    Abstract Mitotane has been used for more than 5 decades as therapy for adrenocortical carcinoma (ACC). However its mechanism of action and the extent of tumor response remain incompletely understood. To date no cases of rapid and complete remission of metastatic ACC with mitotane monotherapy has been reported. A 52-year-old French Canadian man presented with metastatic disease 2 years following a right adrenalectomy for stage III nonsecreting ACC. He was started on mitotane which was well tolerated despite rapid escalation of the dose. The patient course was exceptional as he responded to mitotane monotherapy after only few months of treatment. Initiation of chemotherapy was not needed and he remained disease-free with good quality of life on low maintenance dose of mitotane during the following 10 years. A germline heterozygous TP53 exon 4 polymorphism c.215C>G (p. Pro72Arg) was found. Immunohistochemical stainings for IGF-2 and cytoplasmic β-catenin were positive. Advanced ACC is an aggressive disease with poor prognosis and the current therapeutic options remain limited. These findings suggest that mitotane is a good option for the treatment of metastatic ACC and might result in rapid complete remission in selected patients. PMID:27043680

  3. Adrenocortical suppression in workers employed in manufacturing synthetic glucocorticosteroids: solutions to a problem.

    PubMed Central

    Newton, R W; Browning, M C; Nicholson, P C; Mowat, D A

    1982-01-01

    Earlier studies showed gross adrenocortical suppression in three workers employed in manufacturing synthetic glucocorticoids. A further nine had either recognisable abnormalities of their responses to tetracosactrin or evidence of chronic skin contact with glucocorticoids. By 1978 the mean morning cortisol concentration of 20 workers employed in active steroid processes was 235 nmol/1 +/- 28.6 (8.5 microgram/ml +/- 1.04), which was significantly lower than the value of 428 nmol/l +/- 37.7 (15.5 microgram/ml +/- 1.40) obtained in a control group of 19 men (p less than 0.005). The mean morning cortisol of workers employed in processing steroids believed to be physiologically inactive, 306 nmol/l +/- 22.4 (11.1 microgram/ml +/- 0.81), was also significantly lower than this control group (0.01 greater than p greater than 0.005). Improvement of protection for workers together with operational and plant changes resulted in a significant rise in the mean morning cortisol values of workers until, in 1979, men employed in all steroid processes had concentrations that did not differ from those of a control group. PMID:6461351

  4. A comparison between the equine and bovine hypothalamus-pituitary-adrenocortical axis.

    PubMed

    van der Kolk, J H; Fouché, N; Gross, J J; Gerber, V; Bruckmaier, R M

    2016-07-01

    In this review, we address the function of the hypothalamus-pituitary-adrenocortical (HPA) axis with special emphasis on the comparison between the bovine and equine species. The pars intermedia of the pituitary gland is particularly well developed in horses and cattle. However, its function is not well appreciated in cattle yet. The Wulzen's cone of the adenohypophysis is a special feature of ruminants. Total basal cortisol concentration is much higher in horses than that in cows with similar free cortisol fractions. Corticotropin-releasing factor (CRF) concentrations in equine pituitary venous blood are lower compared with other species, whereas plasma ACTH concentrations in cows are higher than those in horses. A CRF challenge test induced a more pronounced cortisol response in horses compared with cattle, whereas regarding ACTH challenge testing, the opposite seems true. Based on data from literature, the bovine species is characterized by relatively high basal blood CRF and ACTH and low cortisol and glucose concentrations. Obviously, further lowering of blood cortisol in cattle is easily prevented by the high sensitivity to ACTH, and as a consequence, subsequent increased gluconeogenesis prevents imminent hypoglycemia. Hypoglycemia is less likely in horses given their high muscle glycogen content and their relatively high cortisol concentration. When assessing HPA axis reactivity, response patterns to exogenous ACTH or CRH might be used as a reliable indicator of animal welfare status in cows and horses, respectively, although it is emphasized that considerable caution should be exercised in using measures of HPA activity solely to assess animal welfare. PMID:27345307

  5. Bilateral Periventricular Nodular Heterotopia and Lissencephaly in an Infant with Unbalanced t(12;17)(q24.31; p13.3) Translocation

    ERIC Educational Resources Information Center

    Grosso, Salvatore; Fichera, Marco; Galesi, Ornella; Luciano, Daniela; Pucci, Lucia; Giardini, Francesca; Berardi, Rosario; Balestri, Paolo

    2008-01-01

    Periventricular nodular heterotopia and Miller-Dieker syndrome are two different disorders of brain development. Miller-Dieker syndrome exhibits classical lissencephaly and is related to defects in the lissencephaly gene ("LIS1"). Periventricular nodular heterotopia is characterized by aggregates of grey matter adjacent to the lateral ventricle…

  6. The Immunophenotype of Nodular Variant of Medullary Carcinoma of the Breast.

    PubMed

    Reyes, Carolina; Nadji, Mehrdad

    2015-10-01

    The histologic and immunohistochemical profile of typical medullary carcinomas (TMC) of the breast are well established. Among the strict histologic criteria for the diagnosis of TMC is complete circumscription of tumor with pushing borders. Those tumors that do not fulfill all morphologic requirements of TMC are designated as atypical medullary carcinomas (AMC). We herewith describe the histology and immunophenotype of a heretofore undescribed variant of TMC composed of multiple distinctly separate nodules that otherwise meet all other histologic and immunohistochemical phenotypes of TMC. Among 2952 cases of infiltrating mammary carcinomas, 111 (3.8%) met the strict criteria for TMC, including positivity for HLA-DR. Nine of these tumors were composed of multiple separate noncoalescing nodules. Immunohistochemical stains for ER, PR, HER2, and HLA-DR, as well as for p53 and Ki-67 were repeated on these nodular forms. Staining for p63 was used to identify possible intraductal components of these tumors. The age of patients ranged from 34 to 53 years. All 9 patients had negative sentinel lymph nodes. Tumors ranged in the overall size from 2.2 to 3.9 cm and were composed of 3 to 6 distinct nodules ranging in size from 0.2 to 1.1 cm surrounding a larger main tumor nodule. The nodules were composed of syncytial groups of large cells with atypical nuclei and prominent nucleoli. A lymphoplasmacytic infiltrate was present within and around each satellite nodule. Serial sections did not show coalescing of the nodules into a single tumor mass. Similarly, staining for p63 failed to support the possibility of nodules representing intraductal components of main tumor. All tumors were negative for ER, PR, and HER2, but positive for HLA-DR. Eight of 9 tumors were diffusely positive for p53 and all 9 showed a high proliferation index in >70% of tumor cells with Ki-67. We conclude that the nodular variants of medullary carcinomas (nTMC) of the breast are uncommon forms of TMC. They

  7. Production of platelet-activating factor is a component of the angiotensin II-protein kinase C activation pathway in bovine adrenocortical cells.

    PubMed

    Pelosin, J M; Keramidas, M; Chambaz, E M

    1991-08-15

    Lyso-platelet-activating factor (lyso-PAF): acetyl-CoA acetyltransferase (EC 2.3.1.67) enzyme activity was characterized for the first time in bovine adrenocortical tissue. It was found to be associated with the microsomal membrane fraction, in which it exhibited a specific activity of 0.4 nmol/min per mg of protein and catalytic properties similar to those described in other cell types. The adrenocortical acetyltransferase activity was increased by 2-3-fold on incubation of the preparation with purified protein kinase C (PKC) under phosphorylating condition. This activation was optimal after 5 min of incubation and paralleled an increase in PKC-catalysed 32P incorporation into microsomal proteins. Both acetyltransferase activation and protein phosphorylation were dependent on the presence of Ca2+ and phospholipids, and were blocked in the presence of the potent PKC inhibitor H-7. In the intact adrenocortical cell, angiotensin II and a potent phorbol ester (phorbol 12-myristate 13-acetate) were able to rapidly induce an increase in the biosynthesis of PAF, which was mostly released into the extracellular medium. These data suggest that bovine adrenocortical lyso-PAF acetyltransferase may be regulated by a PKC-dependent activation pathway, whereas no evidence for an additional adrenocorticotropin/cyclic AMP-dependent stimulation process was obtained in this cell type. Bovine adrenocortical cell membrane preparations were shown to possess high-affinity PAF-binding sites (Kd approximately 0.5 nM). Altogether, these observations suggest that PAF production and release may play a role in the autocrine or paracrine control of adrenocortical cell activation. PMID:1883337

  8. Conservation of the chromatophore pigment response.

    PubMed

    Dukovcic, Stephanie R; Hutchison, Janine R; Trempy, Janine E

    2010-08-01

    Toxicant sensing technology has evolved to include biological sensors, such as cell-based biosensors, which rely on viable cells to convey a measurable physiological signal. Chromatophores are a class of pigment cells that have been investigated as cell-based biosensors. We report the characterization of Oncorhynchus tshawytscha melanophores and describe the melanophore pigment response to neurotransmitters in terms of pigment area occupied. Compared with the previously described model, Betta splendens erythrophores, O. tshawytscha melanophores responded similarly, indicating that pigment responses are biologically conserved between these two species. Additionally, melanophores responded to mercuric chloride and sodium arsenite, similar to B. splendens erythrophores, suggesting that melanophores can be used as detectors for environmental toxicants. This report highlights the potential of O. tshawytscha melanophores to be used as cell-based biosensors to address environmental toxicity, and warrants a continued investigation to strengthen this technology and its applications. PMID:20809546

  9. Optically variable films, pigments, and inks

    NASA Astrophysics Data System (ADS)

    Phillips, Roger W.

    1990-12-01

    Optically variable thin film coatings have been prepared on rolls of polyester film by depositing thin multi-layers in a vacuum roll coater. Such coatings can be removed from the polyester film and ground into optically variable pigments for printing inks. Various printing inks including gravure, flexographic, and Intaglio inks have been prepared from these pigments, and printed images using these inks have been obtained from commercial printing presses. These optically variable systems have been used on various security documents to prevent counterfeiting with color copiers. Unique colors, color shifting effects, and other optical properties have been obtained by combining non-optically variable pigment and dyes with this light interference pigment. The merits of this new ink relative to other optically variable systems are color uniformity, print quality, its ready use on existing printing presses, and high security.

  10. Pigments of fly agaric (Amanita muscaria).

    PubMed

    Stintzing, Florian; Schliemann, Willibald

    2007-01-01

    The complex pigment pattern of fly agaric (Amanita muscaria) cap skins has been studied by LC-DAD and mass spectrometry. Among the betaxanthins the corresponding derivatives of serine, threonine, ethanolamine, alanine, Dopa, phenylalanine and tryptophan are reported for the first time to contribute to the pigment pattern of fly agarics. Betalamic acid, the chromophoric precursor of betaxanthins and betacyanins, muscaflavin and seco-dopas were also detected. Furthermore, the red-purple muscapurpurin and the red muscarubrin were tentatively assigned while further six betacyanin-like components could not be structurally allocated. Stability studies indicated a high susceptibility of pigment extracts to degradation which led to rapid colour loss thus rendering a complete characterization of betacyanin-like compounds impossible at present. Taking into account these difficulties the presented results may be a starting point for a comprehensive characterization of the pigment composition of fly agarics. PMID:18274277

  11. A Case of Pigmented Mammary Paget's Disease

    PubMed Central

    Kim, Ji Eun; Kang, Myung Seung; Kim, Joung Soo

    2008-01-01

    Pigmented mammary Paget's disease is a uncommon clinicopathologic variant of mammary Paget's disease, and this mimics malignant melanoma both clinically and histopathologically. Herein, we report on a rare case of pigmented mammary Paget's disease. An 81-year-old woman presented with 2.5×1 cm sized, red and brown, eczematous plaque on her right areola, and she'd had this lesion for 3 years. Histopathology showed large, atypical cells with large nuclei and abundant pale cytoplasm throughout the epidermis. Dispersed melanocytes were noted in the epidermis and some of the Paget's cells contained melanin within their cytoplasm. Immunohistochemical studies demonstrated that the intraepidermal pagetoid cells were positive for cytokeratin 7; in contrast, they were negative for S-100, Periodic-acid Schiff (PAS), Alcian blue at PH 2.5, HMB-45 and carninoembryonic antigen (CEA). We recommend that pigmented mammary Paget's disease should be included in the differential diagnosis of pigmented lesions on the nipple. PMID:27303202

  12. New Directions in Phthalocyanine Pigments

    NASA Technical Reports Server (NTRS)

    Vandemark, Michael R.

    1992-01-01

    The objectives were the following: (1) investigation of the synthesis of new phthalocyanines; (2) characterization of the new phthalocyanines synthesized; (3) investigate the properties of the newly synthesized phthalocyanines with emphasis on UV protection of plastics and coatings; and (4) utilize quantum mechanics to evaluate the structural relationships with possible properties and synthetic approaches. The proposed research targeted the synthesis of phthalocyanines containing an aromatic bridge between two phthalocyanine rings. The goal was to synthesize pigments which would protect plastics when exposed to the photodegradation effects of the sun in space. The stability and extended conjugation of the phthalocyanines offer a unique opportunity for energy absorption and numerous radiative and non-radiative energy loss mechanisms. Although the original targeted phthalocyanines were changed early in the project, several new and unique phthalocyanine compounds were prepared. The basic goals of this work were met and some unique and unexpected outcomes of the work were the result of the integral use of quantum mechanics and molecular modeling with the synthetic effort.

  13. Draft Genome Sequence of Helicobacter suis Strain SNTW101, Isolated from a Japanese Patient with Nodular Gastritis.

    PubMed

    Matsui, Hidenori; Takahashi, Tetsufumi; Murayama, Somay Y; Uchiyama, Ikuo; Yamaguchi, Katsushi; Shigenobu, Shuji; Suzuki, Masato; Rimbara, Emiko; Shibayama, Keigo; Øverby, Anders; Nakamura, Masahiko

    2016-01-01

    We present here the draft whole-genome shotgun sequence of an uncultivated strain SNTW101 of Helicobacter suis, which has been maintained in the stomachs of mice. This strain was originally isolated from gastric biopsy specimens of a urea breath test-negative Japanese patient suffering from nodular gastritis. PMID:27609915

  14. Phenolic compounds and bioactivities of pigmented rice.

    PubMed

    Deng, Gui-Fang; Xu, Xiang-Rong; Zhang, Yuan; Li, Dan; Gan, Ren-You; Li, Hua-Bin

    2013-01-01

    The pigmented rice has been consumed in China, Japan, and Korea for a long time. It has been used for strengthening kidney function, treating anemia, promoting blood circulation, removing blood stasis, treating diabetes, and ameliorating sight in traditional Chinese medicine. The extracts from pigmented rice are used as natural food colorants in bread, ice cream, and liquor as well as functional food. The pigmented rice is mainly black, red, and dark purple rice, and contains a variety of flavones, tannin, phenolics, sterols, tocols, γ-oryzanols, amino acids, and essential oils. Anthocyanins are thought as major functional components of pigmented rice. Several anthocyanins have been isolated and identified from the pigmented rice, including cyanidin 3-glucoside, cyanidin 3-galactoside, cyanidin 3-rutinoside, cyanidin 3,5-diglucoside, malvidin 3-galactoside, peonidin 3-glucoside, and pelargonidin 3,5-diglucoside. This review provides up-to-date coverage of pigmented rice in regard to bioactive constituents, extraction and analytical methods, and bioactivities. Special attention is paid to the bioactivities including antioxidant and free radical scavenging, antitumor, antiatherosclerosis, hypoglycemic, and antiallergic activities. PMID:23216001

  15. FTIR study of primate color visual pigments

    PubMed Central

    Katayama, Kota; Kandori, Hideki

    2015-01-01

    How do we distinguish colors? Humans possess three color pigments; red-, green-, and blue-sensitive proteins, which have maximum absorbance (λmax) at 560, 530, and 420 nm, respectively, and contribute to normal human trichromatic vision (RGB). Each color pigments consists of a different opsin protein bound to a common chromophore molecule, 11-cis-retinal, whereas different chromophore-protein interactions allow preferential absorption of different colors. However, detailed experimental structural data to explain the molecular basis of spectral tuning of color pigments are lacking, mainly because of the difficulty in sample preparation. We thus started structural studies of primate color visual pigments using low-temperature Fourier-transform infrared (FTIR) spectroscopy, which needs only 0.3 mg protein for a single measurement. Here we report the first structural data of monkey red- (MR) and green- (MG) sensitive pigments, in which the information about the protein, retinal chromophore, and internal water molecules is contained. Molecular mechanism of color discrimination between red and green pigments will be discussed based on the structural data by FTIR spectroscopy. PMID:27493516

  16. Microspectrophotometry of arthropod visual screening pigments.

    PubMed

    Strother, G K; Casella, A J

    1972-05-01

    Absorption spectra of visual screening pigments obtained in vitro with a microspectrophotometer using frozen sections are given for the insects Musca domestica, Phormia regina, Libellula luctuosa, Apis mellifera (worker honeybee only), Drosophila melanogaster (wild type only) and the arachnids Lycosa baltimoriana and Lycosa miami. The spectral range covered is 260-700 nm for Lycosa and Drosophila and 310-700 nm for the remainder of the arthropods. A complete description of the instrumentation is given. For the flies, Phormia and Musca, light absorption by the yellow and red pigments is high from 310 to about 610 nm. This implies that for these insects there should be no wavelength shift in electroretinogram (ERG) results due to light leakage among neighboring ommatidia for this wavelength range. The same comment applies to Calliphora erythrocephala, which is known to have similar screening pigments. For some of the insects studied a close correspondence is noted between screening pigment absorption spectra and spectral sensitivity curves for individual photoreceptors, available in the literature. In some cases the screening pigment absorption spectra can be related to chemical extraction results, with the general observation that some of the in vitro absorption peaks are shifted to the red. The Lycosa, Apis, and Libellula dark red pigments absorb strongly over a wide spectral range and therefore prevent chemical identification. PMID:4623852

  17. Dermoscopic Features of Facial Pigmented Skin Lesions

    PubMed Central

    Goncharova, Yana; Attia, Enas A. S.; Souid, Khawla; Vasilenko, Inna V.

    2013-01-01

    Four types of facial pigmented skin lesions (FPSLs) constitute diagnostic challenge to dermatologists; early seborrheic keratosis (SK), pigmented actinic keratosis (AK), lentigo maligna (LM), and solar lentigo (SL). A retrospective analysis of dermoscopic images of histopathologically diagnosed clinically-challenging 64 flat FPSLs was conducted to establish the dermoscopic findings corresponding to each of SK, pigmented AK, LM, and SL. Four main dermoscopic features were evaluated: sharp demarcation, pigment pattern, follicular/epidermal pattern, and vascular pattern. In SK, the most specific dermoscopic features are follicular/epidermal pattern (cerebriform pattern; 100% of lesions, milia-like cysts; 50%, and comedo-like openings; 37.50%), and sharp demarcation (54.17%). AK and LM showed a composite characteristic pattern named “strawberry pattern” in 41.18% and 25% of lesions respectively, characterized by a background erythema and red pseudo-network, associated with prominent follicular openings surrounded by a white halo. However, in LM “strawberry pattern” is widely covered by psewdonetwork (87.5%), homogenous structureless pigmentation (75%) and other vascular patterns. In SL, structureless homogenous pigmentation was recognized in all lesions (100%). From the above mentioned data, we developed an algorithm to guide in dermoscopic features of FPSLs. PMID:23431466

  18. Apogeotropic central positional nystagmus as a sole sign of nodular infarction.

    PubMed

    Kim, Hyun-Ah; Yi, Hyon-Ah; Lee, Hyung

    2012-10-01

    Positional vertigo and nystagmus without associated neurological symptoms and signs are characteristic features of benign paroxysmal positional vertigo (BPPV). Although positional nystagmus may occur with caudal cerebellar infarction including the nodulus, positional nystagmus is usually associated with other neurological signs such as spontaneous or gaze-evoked nystagmus, perverted head-shaking nystagmus, cerebellar dysmetria, or severe gait ataxia with falling. We present a patient with nodular infarction who had positional vertigo with nystagmus as a sole manifestation. Video-oculography showed apogeotropic positional horizontal nystagmus during head turning while supine, which was consistent with apogeotropic BPPV involving the horizontal canal. MRI disclosed acute infarct in the nodulus. Nodulus infarction should be considered in a patient with positional nystagmus, especially when the presenting symptoms and signs are consistent with BPPV involving the horizontal canal. PMID:22187336

  19. Reduction of Nodular Growth Pattern of Metastatic Uveal Melanoma after Radioembolization of Hepatic Metastases

    PubMed Central

    Halenda, Kevin M.; Kudchadkar, Ragini R.; Lawson, David H.; Kies, Darren D.; Zhelnin, Kristen E.; Krasinskas, Alyssa M.; Grossniklaus, Hans E.

    2016-01-01

    Aim The aim of this study was to report a case of metastatic uveal melanoma in which radioembolized nodular liver metastases decreased in size while infiltrative sinusoidal metastases progressed, leading to jaundice without obstruction of the biliary ducts. Methods The relevant clinical features, imaging, and histopathologic findings of this case are reviewed. Results A 61-year-old Caucasian male with a history of uveal melanoma of the left eye status post plaque brachytherapy developed numerous liver metastases. After progression on systemic therapies, he underwent palliative radioembolization. Despite some radiographic improvement in the liver metastases, he developed hyperbilirubinemia without biliary tract obstruction or signs of liver failure. A biopsy of radiographically normal liver demonstrated extensive sinusoidal infiltration with melanoma. Conclusions Distinct angiographic and histopathologic growth patterns of metastatic uveal melanoma differ in their amenability to radioembolization. Sinusoidal infiltration may lead to hyperbilirubinemia in the absence of overt obstruction or liver failure. PMID:27239458

  20. Graves Disease Induced by Radioiodine Therapy for Toxic Nodular Goiter: A Case Report.

    PubMed

    Yürekli, Yakup; Cengiz, Arzu; Güney, Engin

    2015-10-01

    Graves' disease (GD) may be observed as an infrequent adverse effect after radioiodine therapy (RAIT) for toxic thyroid adenoma (TA) and toxic multi nodular goiter (MNG). We present a case of a 55-year-old male with a toxic nodule who was treated with RAI. After therapy, the patient's serum free triiodothyronine (fT3) and free thyroxine (fT4) levels gradually increased. Antithyroid peroxidase (TPOAb), antithyroglobulin (TgAb) and TSH-receptor antibodies (TRAb) were also positive. Thyroid scintigraphy revealed diffuse intense uptake after four months of RAIT. Radiation-induced GD should be considered in patients with aggravated hyperthyroidism 3-4 months after therapy. PMID:27529890

  1. PPP6R3-USP6 amplification: Novel oncogenic mechanism in malignant nodular fasciitis.

    PubMed

    Guo, Ruifeng; Wang, Xiaoke; Chou, Margaret M; Asmann, Yan; Wenger, Doris E; Al-Ibraheemi, Alyaa; Molavi, Diana W; Aboulafia, Albert; Jin, Long; Fritchie, Karen; Oliveira, Jennifer L; Jenkins, Robert B; Westendorf, Jennifer J; Dong, Jie; Oliveira, Andre M

    2016-08-01

    Nodular fasciitis (NF) is a clonal self-limited neoplastic proliferation characterized by rearrangements of the USP6 locus in most examples. To our knowledge well-documented malignant behavior has never been previously observed in NF. In this report we present an unusual case of NF with classical histologic features that showed a protracted clinical course characterized by multiple recurrences and eventual metastatic behavior over a period of 10 years. Molecular analyses revealed the presence and amplification of the novel PPPR6-USP6 gene fusion, which resulted in USP6 mRNA transcriptional upregulation. These findings further support the oncogenic role of the USP6 protease in mesenchymal neoplasia and expand the biologic potential of NF. © 2016 Wiley Periodicals, Inc. PMID:27113271

  2. Von Meyenburg complexes mimicking metastatic disease at laparotomy for focal nodular hyperplasia

    PubMed Central

    Bieze, Matthanja; Verheij, Joanne; Phoa, Saffire S; van Gulik, Thomas M

    2013-01-01

    A 44-year-old woman presented with symptoms of fatigue and increasing abdominal discomfort. MRI with the hepatobiliary contrast Gd-EOB-DTPA (Primovist) was performed showing a 6 cm lesion in segment 2/3 of the liver typical for focal nodular hyperplasia (FNH). Because of severe complaints attributed to the lesion, the patient was scheduled for resection. At laparotomy multiple small white lesions were found throughout the liver with enlarged locoregional lymph nodes. Macroscopically, the findings could be consistent with widespread metastases and the surgeon felt compelled to determine the nature of these lesions before continuing resection. Final diagnosis revealed multiple bile duct hamartomas and an FNH lesion as was expected. PMID:23814126

  3. Von Meyenburg complexes mimicking metastatic disease at laparotomy for focal nodular hyperplasia.

    PubMed

    Bieze, Matthanja; Verheij, Joanne; Phoa, Saffire S; van Gulik, Thomas M

    2013-01-01

    A 44-year-old woman presented with symptoms of fatigue and increasing abdominal discomfort. MRI with the hepatobiliary contrast Gd-EOB-DTPA (Primovist) was performed showing a 6 cm lesion in segment 2/3 of the liver typical for focal nodular hyperplasia (FNH). Because of severe complaints attributed to the lesion, the patient was scheduled for resection. At laparotomy multiple small white lesions were found throughout the liver with enlarged locoregional lymph nodes. Macroscopically, the findings could be consistent with widespread metastases and the surgeon felt compelled to determine the nature of these lesions before continuing resection. Final diagnosis revealed multiple bile duct hamartomas and an FNH lesion as was expected. PMID:23814126

  4. Sclerosing angiomatoid nodular transformation of the spleen during pregnancy: Diagnostic challenges and clinical management.

    PubMed

    Corrado, Giacomo; Tabanelli, Valentina; Biffi, Roberto; Petralia, Giuseppe; Tinelli, Andrea; Peccatori, Fedro A

    2016-08-01

    We report the first case of sclerosing angiomatoid nodular transformation (SANT) of the spleen diagnosed during pregnancy, discussing differential diagnosis, immunohistochemical profile and treatment. A G2P1 37-year-old woman presented during the 19th week of gestation because of pruritus at lower limbs. To exclude cholestasis, an abdominal ultrasound and whole body magnetic resonance were performed and a single solid lesion with intrinsic vascularization was identified. Therefore, at 22 weeks gestation, after normal fetal assessment, the patient was referred for a splenectomy. No further treatment was suggested and the patient gave birth at 42 weeks gestation with a spontaneous delivery. Distinguishing SANT from other vascular neoplasms of the spleen during pregnancy is a difficult task. Surgical excision should be performed to exclude malignancy and to resolve symptoms, if present. PMID:27080826

  5. Nodular immunocyte-derived (AL) amyloidosis in the trachea of a dog.

    PubMed

    Besancon, M Faulkner; Stacy, Brian A; Kyles, Andrew E; Moore, Peter F; Vernau, William; Smarick, Sean D; Rasor, Liberty A

    2004-04-15

    A 7-year-old castrated male Miniature Schnauzer was examined because of labored breathing and episodes of respiratory distress that progressed to collapse. On cervical radiographs, a focal soft tissue mass in the caudal cervical portion of the trachea was observed, and during tracheoscopy, a 1 x 1 cm, pedunculated, multinodular, pink, intraluminal mass extending from the dorsal tracheal membrane and obstructing approximately 80% of the tracheal lumen was seen. Tracheal resection and anastomosis was performed to remove the mass, and the dog recovered without complications. On histologic examination, the mass consisted of a large accumulation of homogeneous, faintly fibrillar eosinophilic material admixed with a predominantly plasma cell infiltrate; examination of sections stained with thioflavin T and Congo red stain confirmed that the eosinophilic material was amyloid. A diagnosis of nodular, immunocyte-derived (AL) amyloidosis was made. Seventeen months after surgery, the dog had a relapse of respiratory distress because of an extramedullary plasmacytoma involving the trachea. PMID:15112779

  6. Ultrasonic cavitation erosion of nodular cast iron with ferrite-pearlite microstructure.

    PubMed

    Mitelea, Ion; Bordeaşu, Ilare; Pelle, Marius; Crăciunescu, Corneliu

    2015-03-01

    The cavitation erosion of ductile cast iron with ferrite-pearlite microstructure was analyzed based on ultrasonic experiments performed according to ASTM G32-2010 and the resistance was compared to the C45 steel with similar hardness. The microstructural observation of the surface for different exposure times to the ultrasonic cavitation reveals the fact that the process initiates at the nodular graphite-ferrite interface and is controlled by micro-galvanic activities and mechanical factors. The cavitation erosion resistance was evaluated based on the evolution of the mean depth erosion and the mean depth erosion rate as a function of the cavitation time. The cavitation erosion rate of the cast iron is up to 1.32 times higher than the one of the C 45 steel with similar hardness. This is explained by the occurrence of stress concentrators due to the expulsion of the graphite from the metallic matrix. PMID:25465881

  7. Graves Disease Induced by Radioiodine Therapy for Toxic Nodular Goiter: A Case Report

    PubMed Central

    Yürekli, Yakup; Cengiz, Arzu; Güney, Engin

    2015-01-01

    Graves’ disease (GD) may be observed as an infrequent adverse effect after radioiodine therapy (RAIT) for toxic thyroid adenoma (TA) and toxic multi nodular goiter (MNG). We present a case of a 55-year-old male with a toxic nodule who was treated with RAI. After therapy, the patient’s serum free triiodothyronine (fT3) and free thyroxine (fT4) levels gradually increased. Antithyroid peroxidase (TPOAb), antithyroglobulin (TgAb) and TSH-receptor antibodies (TRAb) were also positive. Thyroid scintigraphy revealed diffuse intense uptake after four months of RAIT. Radiation-induced GD should be considered in patients with aggravated hyperthyroidism 3-4 months after therapy.

  8. Oesophageal variceal bleeding in Felty's syndrome associated with nodular regenerative hyperplasia.

    PubMed Central

    Blendis, L M; Lovell, D; Barnes, C G; Ritland, S; Cattan, D; Vesin, P

    1978-01-01

    Four patients with Felty's syndrome developed massive upper gastrointestinal bleeding due to oesophageal varices. The underlying hepatic pathology in all 4 was nodular regenerative hyperplasia. This appears to be a difficult histological diagnosis to make, having been initially reported as normal on percutaneous biopsy or as fibrosis or cirrhosis on wedge biopsy. This series brings the total number of cases reported in the English literature of this association to 12, suggesting a definite symptom complex. The portal hypertension seems to be due to a combination of increased splenic blood flow and postsinusoidal resistance. The clinical importance of this syndrome is that the appropriate therapy for bleeding oesophageal varices appears to be shunt procedure such as a splenorenal shunt with splenectomy, which should be well tolerated. Images PMID:306226

  9. Sclerosing angiomatoid nodular transformation of the spleen: A case report and literature review

    PubMed Central

    Wang, Tian-Bao; Hu, Bao-Guang; Liu, Da-Wei; Gao, Zhen-Hua; Shi, Han-Ping; Dong, Wen-Guang

    2016-01-01

    Sclerosing angiomatoid nodular transformation (SANT) is a rare benign splenic vascular lesion. Since it was first defined in 2004, a total of 132 cases of SANT have been reported in ~50 studies in the English literature. However, it remains difficult to form a definitive pre-operative differential diagnosis of SANT compared with other splenic tumors or malignant lesions. The present study reports a pathologically proven case of SANT in a 29-year-old man who initially presented with left upper quadrant and back discomfort. The study also provides a review of the current knowledge on the condition, including the clinical profile, imaging features, cytological features, differential diagnosis and treatment of SANT. The most important distinguishing features of SANT are its typical vascular character and lack of other features that are typical of a granuloma. A splenectomy is required and the diagnosis is based on pathological analysis. PMID:27446372

  10. Assessment of adrenocortical activity and behavior of the collared anteater (Tamandua tetradactyla) in response to food-based environmental enrichment.

    PubMed

    Eguizábal, Gabina V; Palme, Rupert; Villarreal, Daniel; Dal Borgo, Carla; Di Rienzo, Julio A; Busso, Juan M

    2013-01-01

    One of the current standard approaches to the study of animal welfare is measuring hypothalamic-pituitary-adrenal activity, frequently in association with behavioral assessment. We studied the effects of food-based environmental enrichment on adrenocortical activity and behavior in zoo-housed collared anteaters (Tamandua tetradactyla; n = 5). We successfully validated measurements of fecal cortisol metabolites (FCMs) using an 11-oxoetiocholanolone enzyme immunoassay by stimulating (ACTH injection) and suppressing (dexamethasone administration) adrenocortical activity. Three months later, we subjected animals to an ABA-type experiment (three 6-week periods): pre-enrichment (routine diet: A), enrichment (modified diet: B), and post-enrichment (routine diet: A) periods. We assessed adrenocortical activity by collecting individual feces three times a week (total number of samples: 228), and evaluated behavior by performing 3 days of behavioral observations per period (with a total of 3,600 behavioral data points for the individuals studied). Statistical analysis revealed changes in FCM concentrations (µg/g) over the periods (3.04 ± 0.68, 2.98 ± 0.66, and 4.04 ± 0.90, respectively). Additionally, it showed that the number of FCM peaks was highly reduced during enrichment; meanwhile active natural behaviors were significantly increased. We consider that these changes in response to food-based environmental enrichment improved the welfare of individual zoo-housed collared anteaters. This research might contribute to in situ and ex situ studies on the physiology and behavior of this endemic South American species. PMID:24307059

  11. Temperament moderates the influence of periadolescent social experience on behavior and adrenocortical activity in adult male rats

    PubMed Central

    Caruso, M.J.; McClintock, M.K.; Cavigelli, S.A.

    2014-01-01

    Adolescence is a period of significant behavioral and physiological maturation, particularly related to stress responses. Animal studies that have tested the influence of adolescent social experiences on stress-related behavioral and physiological development have led to complex results. We used a rodent model of neophobia to test the hypothesis that the influence of adolescent social experience on adult behavior and adrenocortical function is modulated by preadolescent temperament. Exploratory activity was assessed in 53 male Sprague-Dawley rats to classify temperament and then they were housed in one of three conditions during postnatal days (PND) 28-46: (1) with familiar kin, (2) with novel social partners, or (3) individually with no social partners. Effects on adult adrenocortical function were evaluated from fecal samples collected while rats were individually-housed and exposed to a 1-hour novel social challenge during PND 110-114. Adolescent-housing with novel or no social partners led to reduced adult glucocorticoid production compared to adolescent-housing with familiar littermates. Additionally, highly-exploratory pre-weanling rats that were housed with novel social partners during adolescence exhibited increased exploratory behavior and a more rapid return to basal glucocorticoid production in adulthood compared to those housed with familiar or no social partners during adolescence and compared to low-exploratory rats exposed to novel social partners. In sum, relatively short-term adolescent social experiences can cause transient changes in temperament and potentially longer-term changes in recovery of glucocorticoid production in response to adult social challenges. Furthermore, early temperament may modulate the influence of adolescent experiences on adult behavioral and adrenocortical function. PMID:25066485

  12. A gene expression signature that distinguishes desmoid tumours from nodular fasciitis.

    PubMed

    Bacac, M; Migliavacca, E; Stehle, J-C; McKee, T; Delorenzi, M; Coindre, J-M; Guillou, L; Stamenkovic, I

    2006-03-01

    Nodular fasciitis (NF) is a rapidly growing cellular mass composed of fibroblasts/myofibroblasts, usually localized in subcutaneous tissues, that typically undergoes fibrosis and almost never recurs. Desmoid tumours (DTs) are rare forms of fibroblastic/myofibroblastic growth that arise in deep soft tissues, display a propensity for local infiltration and recurrence, but fail to metastasize. Given that both entities are primarily fibroblastic/myofibroblastic lesions with overlapping histological features, their gene expression profiles were compared to identify differentially expressed genes that may provide not only potential diagnostic markers, but also clues as to the pathogenesis of each disorder. Differentially expressed transcripts (89 clones displaying increased expression in DTs and 246 clones displaying increased expression in NF) included genes encoding several receptor and non-receptor tyrosine kinases (EPHB3, PTPRF, GNAZ, SYK, LYN, EPHA4, BIRC3), transcription factors (TWIST1, PITX2, EYA2, OAS1, MITF, TCF20), and members of the Wnt signalling pathway (AXIN2, WISP1, SFRP). Remarkably, almost one-quarter of the differentially expressed genes encode proteins associated with inflammation and tissue remodelling, including members of the interferon (IFN), tumour necrosis factor (TNF), and transforming growth factor beta (TGF-beta) signalling pathways as well as metalloproteinases (MMP1, 9, 13, 23), urokinase plasminogen activator (PLAU), and cathepsins. The observations provide the first comparative molecular characterization of desmoid tumours and nodular fasciitis and suggest that selected tyrosine kinases, transcription factors, and members of the Wnt, TGF-beta, IFN, and TNF signalling pathways may be implicated in influencing and distinguishing their fate. PMID:16440290

  13. Adrenocorticotropic hormone in serial cerebrospinal fluid in man - Subject to acute regulation by the hypothalamic-pituitary-adrenocortical system?

    PubMed

    Kellner, Michael; Wortmann, Viola; Salzwedel, Cornelie; Kober, Daniel; Petzoldt, Martin; Urbanowicz, Tatiana; Pulic, Mersija; Boelmans, Kai; Yassouridis, Alexander; Wiedemann, Klaus

    2016-05-30

    Acute regulation of adrenocorticotropic hormone (ACTH) in cerebrospinal fluid (CSF) by the hypothalamic-pituitary-adrenocortical system has not been investigated in man. In a pilot study in healthy male volunteers we measured ACTH every twenty minutes in serial CSF for three hours after an intravenous placebo, hydrocortisone (100mg) or insulin (2mg/kg) injection. No acute inhibitory or stimulatory effects of these interventions were discovered. Our results corroborate previous findings in rhesus monkeys. The regulation of CSF ACTH and its potential relevance for behavioral alterations in health and disease (e.g. major depression or anorexia nervosa) in humans need further study. PMID:27031591

  14. Adrenocortical response in rats subjected to a stress of restraint by immobilization whether accompanied by hypothermia or not

    NASA Technical Reports Server (NTRS)

    Buchel, L.; Prioux-Guyonneau, M.; Libian, L.

    1980-01-01

    The restraint associated with hypothermia which increases the adrenal activity in rats was investigated. In rats with nomothermia or light hypothermia, the plasma and adrenal corticosterone levels increase at least threefold whatever the duration of restraint. Their return to normal values depends on the duration of the restraint. Exposure to cold produces in free rats a light hypothermia with an increase of the plasma and adrenal corticosterone levels, and in restraint animals an important hypothermia which does not potentiate the stimulation of adrenocortical activity induced by the restraint alone.

  15. The Contingency of Cocaine Administration Accounts for Structural and Functional Medial Prefrontal Deficits and Increased Adrenocortical Activation

    PubMed Central

    Anderson, Rachel M.; Cosme, Caitlin V.; Glanz, Ryan M.; Miller, Mary C.; Romig-Martin, Sara A.; LaLumiere, Ryan T.

    2015-01-01

    The prelimbic region (PL) of the medial prefrontal cortex (mPFC) is implicated in the relapse of drug-seeking behavior. Optimal mPFC functioning relies on synaptic connections involving dendritic spines in pyramidal neurons, whereas prefrontal dysfunction resulting from elevated glucocorticoids, stress, aging, and mental illness are each linked to decreased apical dendritic branching and spine density in pyramidal neurons in these cortical fields. The fact that cocaine use induces activation of the stress-responsive hypothalamo-pituitary-adrenal axis raises the possibility that cocaine-related impairments in mPFC functioning may be manifested by similar changes in neuronal architecture in mPFC. Nevertheless, previous studies have generally identified increases, rather than decreases, in structural plasticity in mPFC after cocaine self-administration. Here, we use 3D imaging and analysis of dendritic spine morphometry to show that chronic cocaine self-administration leads to mild decreases of apical dendritic branching, prominent dendritic spine attrition in PL pyramidal neurons, and working memory deficits. Importantly, these impairments were largely accounted for in groups of rats that self-administered cocaine compared with yoked-cocaine- and saline-matched counterparts. Follow-up experiments failed to demonstrate any effects of either experimenter-administered cocaine or food self-administration on structural alterations in PL neurons. Finally, we verified that the cocaine self-administration group was distinguished by more protracted increases in adrenocortical activity compared with yoked-cocaine- and saline-matched controls. These studies suggest a mechanism whereby increased adrenocortical activity resulting from chronic cocaine self-administration may contribute to regressive prefrontal structural and functional plasticity. SIGNIFICANCE STATEMENT Stress, aging, and mental illness are each linked to decreased prefrontal plasticity. Here, we show that chronic

  16. Differential regulation of glucocorticoid synthesis in murine intestinal epithelial versus adrenocortical cell lines.

    PubMed

    Mueller, Matthias; Atanasov, Atanas; Cima, Igor; Corazza, Nadia; Schoonjans, Kristina; Brunner, Thomas

    2007-03-01

    Glucocorticoids are steroid hormones with important functions in development, immune regulation, and glucose metabolism. The adrenal glands are the predominant source of glucocorticoids; however, there is increasing evidence for extraadrenal glucocorticoid synthesis in thymus, brain, skin, and vascular endothelium. We recently identified intestinal epithelial cells as an important source of glucocorticoids, which regulate the activation of local intestinal immune cells. The molecular regulation of intestinal glucocorticoid synthesis is currently unexplored. In this study we investigated the transcriptional regulation of the steroidogenic enzymes P450 side-chain cleavage enzyme and 11beta-hydroxylase, and the production of corticosterone in the murine intestinal epithelial cell line mICcl2 and compared it with that in the adrenocortical cell line Y1. Surprisingly, we observed a reciprocal stimulation pattern in these two cell lines. Elevation of intracellular cAMP induced the expression of steroidogenic enzymes in Y1 cells, whereas it inhibited steroidogenesis in mICcl2 cells. In contrast, phorbol ester induced steroidogenic enzymes in intestinal epithelial cells, which was synergistically enhanced upon transfection of cells with the nuclear receptors steroidogenic factor-1 (NR5A1) and liver receptor homolog-1 (NR5A2). Finally, we observed that basal and liver receptor homolog-1/phorbol ester-induced expression of steroidogenic enzymes in mICcl2 cells was inhibited by the antagonistic nuclear receptor small heterodimer partner. We conclude that the molecular basis of glucocorticoid synthesis in intestinal epithelial cells is distinct from that in adrenal cells, most likely representing an adaptation to the local environment and different requirements. PMID:17170096

  17. Steroidogenic enzyme profile in an androgen-secreting adrenocortical oncocytoma associated with hirsustism

    PubMed Central

    Tetsi Nomigni, Milène; Ouzounian, Sophie; Benoit, Alice; Vadrot, Jacqueline; Tissier, Frédérique; Renouf, Sylvie; Lefebvre, Hervé; Christin-Maitre, Sophie; Louiset, Estelle

    2015-01-01

    Hirsutism induced by hyperandrogenism can be associated with polycystic ovary syndrome, 21-hydroxylase (OH) deficiency or androgen-secreting tumors, including ovarian and adrenal tumors. Adrenal androgen-secreting tumors are frequently malignant. Adrenal oncocytomas represent rare causes of hyperandrogenism. The aim of the study was to investigate steroidogenic enzyme expression and steroid secretion in an androgen-secreting adrenal oncocytoma in a young woman presenting with hirsutism. Hyperandrogenism was diagnosed on the basis of elevated plasma Δ4-androstenedione and testosterone levels. Pelvic ultrasound was normal, CT scanning revealed a right adrenal mass. Androgens were assessed in adrenal and ovarian vein samples and proved a right adrenal origin. Adrenalectomy normalized androgen levels and the adrenal tumor was diagnosed as an oncocytoma. Real time-PCR, immunohistochemistry and cell culture studies were performed on tumor explants to investigate the steroid secretion profile. Among enzymes required for cortisol synthesis, 17α-OH and 3β-hydroxysteroid dehydrogenase 2 (3β-HSD2) were highly expressed whereas 21-OH and 11β-OH were weakly produced at the mRNA and/or protein levels. Enzymes involved in testosterone production, 17β-HSD5 and 17β-HSD3, were also detected. ACTH receptor was present in the tissue. Cortisol, Δ4-androstenedione and testosterone secretions by cultured cells were increased by ACTH. These results provide the first demonstration, to our knowledge, of abnormal expression profile of steroidogenic enzymes in an adrenocortical oncocytoma. Our results also indicate that Δ4-androstenedione hypersecretion resulted from high 17α-OH and 3β-HSD2 expression in combination with low expression of 21-OH and 11β-OH. Testosterone production was ascribed to occurrence of 17β-HSD5 and 17β-HSD3. Finally, our results indicate that androgen secretion was stimulated by ACTH. PMID:26034121

  18. Loner or socializer? Ravens' adrenocortical response to individual separation depends on social integration.

    PubMed

    Stocker, Martina; Munteanu, Alexandru; Stöwe, Mareike; Schwab, Christine; Palme, Rupert; Bugnyar, Thomas

    2016-02-01

    Non-breeding common ravens (Corvus corax) live in complex social groups with a high degree of fission-fusion dynamics. They form valuable relationships and alliances with some conspecifics, while taking coordinated action against others. In ravens, affiliates reconcile their conflicts, console each other after conflicts with a third party, and provide each other with social support - all behaviors that presumably reduce corticosterone levels and alleviate stress. However, how well an individual is socially integrated in a (sub)group might vary substantially. This raises the question whether the social integration of a raven affects its stress responses to fission-fusion dynamics. The present study aims to investigate this effect experimentally by separating single ravens (n=16) individually from their group for four days and subsequently reintroducing them. To determine stress response patterns in the separated individuals we measured the amounts of immunoreactive corticosterone metabolites (CM) in droppings. We compared two enzyme immunoassays, which we validated by conducting an ACTH challenge, and finally decided to apply an 11-oxoetiocholanolone enzyme immunoassay. Additionally, we determined levels of social integration using focal observations. Our findings suggest that a strong social integration is related to low CM levels when the individuals are within the group and high levels during separations, implying that separation leads to stress in these birds. In contrast, poorly socially integrated ravens seem to exhibit the opposite pattern, indicating that to them group living is more stressful than being temporarily separated. We, therefore, conclude that the birds' adrenocortical activity is modulated by their social integration. PMID:26631484

  19. Minireview: Hair Cortisol: A Novel Biomarker of Hypothalamic-Pituitary-Adrenocortical Activity

    PubMed Central

    Novak, Melinda A.

    2012-01-01

    Activity of the hypothalamic-pituitary-adrenocortical (HPA) axis is commonly assessed by measuring glucocorticoids such as cortisol (CORT). For many years, CORT was obtained primarily from blood plasma or urine, whereas later approaches added saliva and feces for noninvasive monitoring of HPA functioning. Despite the value of all these sample matrices for answering many research questions, they remain limited in the temporal range of assessment. Plasma and saliva are point samples that vary as a function of circadian rhythmicity and are susceptible to confounding by environmental disturbances. Even urine and feces generally assess HPA activity over a period of only 24 h or less. We and others have recently developed and validated methods for measuring the concentration of CORT in the body hair of animals (e.g. rhesus monkeys) and scalp hair of humans. CORT is constantly deposited in the growing hair shaft, as a consequence of which such deposition can serve as a biomarker of integrated HPA activity over weeks and months instead of minutes or hours. Since the advent of this methodological advance, hair CORT has already been used as an index of chronic HPA activity and stress in human clinical and nonclinical populations, in a variety of laboratory-housed and wild-living animal species, and in archival specimens that are many decades or even centuries old. Moreover, because human hair is known to grow at an average rate of about 1 cm/month, several studies suggest that CORT levels in hair segments that differ in proximity to the scalp can, under certain conditions, be used as a retrospective calendar of HPA activity during specific time periods preceding sample collection. PMID:22778226

  20. Prevalence of Germline TP53 Mutations in a Prospective Series of Unselected Patients with Adrenocortical Carcinoma

    PubMed Central

    Else, Tobias; Everett, Jessica N.; Long, Jessica M.; Gruber, Stephen B.; Hammer, Gary D.

    2013-01-01

    Purpose: Adrenocortical carcinoma (ACC) is a hallmark cancer in families with Li Fraumeni syndrome (LFS) caused by mutations in the TP53 gene. The prevalence of germline TP53 mutations in children diagnosed with ACC ranges from 50–97%. Although existing criteria advocate for TP53 testing in all patients with ACC regardless of age at diagnosis, the overall prevalence of germline mutations in patients diagnosed with ACC has not been well studied. Patients and Methods: A total of 114 patients with confirmed ACC evaluated in the University of Michigan Endocrine Oncology Clinic were prospectively offered genetic counseling and TP53 genetic testing, regardless of age at diagnosis or family history. Ninety-four of the 114 patients met with a genetic counselor (82.5%), with 53 of 94 (56.4%) completing TP53 testing; 9.6% (nine of 94) declined testing. The remainder (32 of 94; 34%) expressed interest in testing but did not pursue it for various reasons. Results: Four of 53 patients in this prospective, unselected series were found to have a TP53 mutation (7.5%). The prevalence of mutations in those diagnosed over age 18 was 5.8% (three of 52). There were insufficient data to estimate the prevalence in those diagnosed under age 18. None of these patients met clinical diagnostic criteria for classic LFS. Three of the families met criteria for Li Fraumeni-like syndrome; one patient met no existing clinical criteria for LFS or Li Fraumeni-like syndrome. Three of the four patients with mutations were diagnosed with ACC after age 45. Conclusions: Genetic counseling and germline testing for TP53 should be offered to all patients with ACC. Restriction on age at diagnosis or strength of the family history would fail to identify mutation carriers. PMID:23175693

  1. Cloacal gland, endocrine testicular, and adrenocortical photoresponsiveness in male Japanese quail exposed to short days.

    PubMed

    Busso, J M; Dominchin, M F; Marin, R H; Palme, R

    2013-04-01

    Photoperiod is the most important "noise-free" seasonal environmental cue for synchronizing physiological states (such as reproductive activity) in birds. However, in photoperiodic birds such as Japanese quail, the effect of photoperiod on adrenocortical activity remains unclear, particularly in males with differences in cloacal gland photoresponsiveness. At 8 wk of age, birds (n = 55) were either assigned to a short photoperiod (8L:16D; SD) or maintained under long photoperiod (16L:8D; LD; control). After 5 wk of SD exposure, males were classified as nonresponsive (SD-NR; with foam production) or responsive (SD-R; with no foam production) to short days, depending on the cloacal gland volume was above or below 1,000 mm(3). At 14 wk of age, droppings were collected during 3 consecutive days to determine corticosterone (CMs) and androgen metabolites (AMs) by enzyme immunoassays. Male Japanese quail under LD showed significantly higher concentrations of CMs (300 ± 10 ng/g) and AMs (1,257 ± 115 ng/g) than birds kept under SD. Under short days, SD-NR and SD-R showed differences (P < 0.0001), both in CM (153 ± 8 ng/g and 98 ± 6 ng/g, respectively) and AM concentrations (1,294 ± 309 ng/g and 275 ± 53 ng/g, respectively). Interestingly, although SD-NR males exhibited no cloacal gland arrest (according to cloacal gland volume and foam production) and similar testicular activity (AM values) to LD males, they showed lower concentrations of CMs compared with males that remained on LD (P < 0.05). Our findings suggest length of photoperiod affected hypothalamic-pituitary-adrenal activity; however, that was not the only factor involved, because birds subjected to shorter days but whose hypothalamic-pituitary-gonadal axis failed to respond had intermediate CM values. Further research is required to elucidate the underlying mechanisms of this interesting finding. PMID:23411012

  2. Vincristine, cisplatin, teniposide, and cyclophosphamide combination in the treatment of recurrent or metastatic adrenocortical cancer.

    PubMed

    Khan, Tanweera S; Sundin, Anders; Juhlin, Claes; Wilander, Erik; Oberg, Kjell; Eriksson, Barbro

    2004-01-01

    The efficacy and tolerability of a combination of vincristine, cisplatin, teniposide, and cyclophosphamide (OPEC) in 11 patients (median age, 45 yr) with recurrent and/or metastatic adrenocortical cancer (ACC) (seven functional and four nonfunctional) were evaluated. All patients received this regimen after the failure of streptozocin and o,p'-DDD (SO) combination therapy. The regimen comprised cyclophosphamide, 600 mg/m2, and vincristine, 1.5 mg/m2, maximum dose 2.0 mg (d 1); cisplatin, 100 mg/m2 (d 2) and teniposide, 150 mg/m2 (d 4). Cycles were repeated every 4 wk. One to eight cycles (median, six cycles) of OPEC were administered to each patient. The median duration of treatment was 6 mo. The overall 2-yr survival rate was 82% and the median survival since diagnosis was 44 mo while it was 21 mo since start of OPEC therapy. Responses were obtained in nine patients: partial response in two patients, and stable disease in seven patients. The median duration of response was 6.75 mo. A total of 60 cycles of chemotherapy were given to all patients; grade 1-2 toxicity occurred in 57 cycles, while grade 3 toxicity was observed only in two cycles, according to NCI's Common Toxicity Criteria. We conclude that the OPEC regimen may be considered in recurrent or metastatic ACC as a second-line medical treatment. However, the combination is accompanied by considerable side effects and dose modifications are necessary in order to be able to recommend the treatment. This regimen needs further evaluation compared with SO therapy preferably in a randomized multicenter trial. PMID:15299189

  3. Molecular Profiling of Refractory Adrenocortical Cancers and Predictive Biomarkers to Therapy

    PubMed Central

    Millis, Sherri Z.; Ejadi, Samuel; Demeure, Michael J.

    2015-01-01

    PURPOSE Current first-line chemotherapy for patients with metastatic adrenocortical cancer (ACC) includes doxorubicin, etoposide, cisplatin, and mitotane with a reported response rate of only 23.2%. New therapeutic leads for patients with refractory tumors are needed; there is no standard second-line treatment. METHODS Samples from 135 ACC tumors were analyzed by immunohistochemistry, in situ hybridization (FISH or CISH), and/or gene sequencing at a single commercial reference laboratory (Caris Life Sciences) to identify markers associated with drug sensitivity and resistance. RESULTS Overexpression of proteins related to demonstrated chemotherapy sensitivity or resistance included topoisomerase 1, progesterone receptor, and topoisomerase 2-alpha in 46%, 63%, and 42% of cases, respectively. Loss of excision repair cross-complementary group 1 (ERCC1), phosophatase and tensin homolog, O(6)-methylguanine-methyltransferase, and ribonucleotide reductase M1 (RRM1) was identified in 56%, 59%, 71%, and 58% of cases, respectively. Other aberrations included overexpression of programmed death-ligand 1 or programmed cell death protein 1 tumor-infiltrating lymphocytes in >40% of cases. In all, 35% of cases had a mutation in the canonical Wnt signaling pathway (either CTNNB1 or APC) and 48% had a mutation in TP53. No other genomic alterations were identified. CONCLUSION Biomarker alterations in ACC may be used to direct therapies, including recommendations for and potential resistance of some patients to traditional chemotherapies, which may explain the low response rate in the unselected population. Limited outcomes data support the use of mitotane and platinum therapies for patients with low levels of the proteins RRM1 and ERCC1. PMID:26715866

  4. Combined steroidogenic characters of fetal adrenal and Leydig cells in childhood adrenocortical carcinoma.

    PubMed

    Fujisawa, Yasuko; Sakaguchi, Kimiyoshi; Ono, Hiroyuki; Yamaguchi, Rie; Kato, Fumiko; Kagami, Masayo; Fukami, Maki; Ogata, Tsutomu

    2016-05-01

    Although childhood adrenocortical carcinomas (c-ACCs) with a TP53 mutation are known to produce androgens, detailed steroidogenic characters have not been clarified. Here, we examined steroid metabolite profiles and expression patterns of steroidogenic genes in a c-ACC removed from the left adrenal position of a 2-year-old Brazilian boy with precocious puberty, using an atrophic left adrenal gland removed at the time of tumorectomy as a control. The c-ACC produced not only abundant dehydroepiandrosterone-sulfate but also a large amount of testosterone via the Δ5 pathway with Δ5-androstenediol rather than Δ4-androstenedione as the primary intermediate metabolite. Furthermore, the c-ACC was associated with elevated expressions of CYP11A1, CYP17A1, POR, HSD17B3, and SULT2A1, a low but similar expression of CYB5A, and reduced expressions of AKR1C3 (HSD17B5) and HSD3B2. Notably, a Leydig cell marker INSL3 was expressed at a low but detectable level in the c-ACC. Furthermore, molecular studies revealed a maternally inherited heterozygous germline TP53 mutation, and several post-zygotic genetic aberrations in the c-ACC including loss of paternally derived chromosome 17 with a wildtype TP53 and loss of maternally inherited chromosome 11 and resultant marked hyperexpression of paternally expressed growth promoting gene IGF2 and drastic hypoexpression of maternally expressed growth suppressing gene CDKN1C. These results imply the presence of combined steroidogenic properties of fetal adrenal and Leydig cells in this patient's c-ACC with a germline TP53 mutation and several postzygotic carcinogenic events. PMID:26940356

  5. Effects of long-term voluntary exercise on the mouse hypothalamic-pituitary-adrenocortical axis.

    PubMed

    Droste, Susanne K; Gesing, Angela; Ulbricht, Sabine; Müller, Marianne B; Linthorst, Astrid C E; Reul, Johannes M H M

    2003-07-01

    We studied the effects of long-term (i.e. 4 wk) voluntary exercise on the hypothalamic-pituitary-adrenocortical (HPA) axis in male mice. Voluntary exercise was provided by giving mice access to a running wheel, in which they indeed ran for about 4 km/d. Exercising mice showed similar body weights as control animals but presented less abdominal fat, lighter thymuses, and heavier adrenal glands. Exercise resulted in asymmetric structural changes in the adrenal glands. Whereas control mice had larger left than right adrenals, this condition was abolished in exercising animals, mainly because of enlargement of the right adrenal cortex. Tyrosine hydroxylase mRNA expression in the adrenal medullas of exercising mice was increased. In exercising mice, early-morning baseline plasma ACTH levels were decreased, whereas plasma corticosterone levels at the start of the dark phase were twice as high as those in control animals. To forced swimming and restraint stress, exercising mice responded with higher corticosterone levels than those of the control animals but with similar ACTH levels. However, if exposed to a novel environment, then exercising mice presented decreased ACTH responses. Interestingly, exercising mice showed a decreased corticosterone response to novelty only when the novel environment contained a functioning running wheel. Glucocorticoid receptor levels were unchanged, whereas mineralocorticoid receptor levels were decreased, in hippocampus of exercising animals. Corticotropin-releasing factor mRNA levels in the paraventricular nucleus were lower in exercising mice. Thus, voluntary exercise results in complex, adaptive changes at various levels within the HPA axis as well as in sympathoadrenomedullary and limbic/neocortical afferent control mechanisms. These changes seem to underlie the differential responsiveness of the HPA axis to physical vs. emotional challenges. PMID:12810557

  6. Need for Comprehensive Hormonal Workup in the Management of Adrenocortical Tumors in Children

    PubMed Central

    Gönç, E. Nazlı; Özön, Zeynep Alev; Çakır, Meltem Didem; Alikaşifoğlu, Ayfer; Kandemir, Nurgün

    2014-01-01

    Ob­jec­ti­ve: Clinical findings do not reflect the excess hormonal status in adrenocortical tumors (ACTs) in children. Identification of abnormal hormone secretion may help provide the tumor marker and delineate those patients with a risk of adrenal suppression following tumor removal. To analyze the impact of complete hormonal assessment regardless of the clinical presentation in hormone-secreting ACTs in childhood. Methods: Association of hormonal workup at diagnosis with the clinical findings and frequency of adrenal suppression postoperatively were analyzed in 18 children with ACT. Results: Seventeen of the 18 patients had functional ACT. Clinical findings suggested isolated virilization and isolated Cushing’s syndrome in 38.8% and 17.6% of patients, respectively. Hormonal workup revealed a frequency of 83.3% for hyperandrogenism. The majority of the tumors (50%) had mixed type hormonal secretion. Hypercortisolism existed in 28.5% of children with isolated virilization and hyperandrogenism was found in 2/3 of children with isolated Cushing’s syndrome. Various androgens other than dehydroepiandrosterone sulfate were also determined to be high in hyperandrogenism. Increased testosterone was a highly prevalent tumor marker. Nine patients (3 with no signs of hypercortisolism) had adrenal suppression following tumor removal which lasted 1-24 months. Conclusion: Complete hormonal workup showed the predominance of mixed hormone-secreting type of tumor in the patients who lacked the appropriate clinical findings and also showed that patients lacking signs of Cushing’s syndrome could have postoperative adrenal suppression. Clinical findings may not reflect the abnormal hormone secretion in all cases and tumor markers as well as risk of postoperative adrenal suppression can best be determined by complete hormonal evaluation at the time of diagnosis. PMID:24932598

  7. Loner or socializer? Ravens’ adrenocortical response to individual separation depends on social integration

    PubMed Central

    Stocker, Martina; Munteanu, Alexandru; Stöwe, Mareike; Schwab, Christine; Palme, Rupert; Bugnyar, Thomas

    2016-01-01

    Non-breeding common ravens (Corvus corax) live in complex social groups with a high degree of fission–fusion dynamics. They form valuable relationships and alliances with some conspecifics, while taking coordinated action against others. In ravens, affiliates reconcile their conflicts, console each other after conflicts with a third party, and provide each other with social support — all behaviors that presumably reduce corticosterone levels and alleviate stress. However, how well an individual is socially integrated in a (sub)group might vary substantially. This raises the question whether the social integration of a raven affects its stress responses to fission–fusion dynamics. The present study aims to investigate this effect experimentally by separating single ravens (n = 16) individually from their group for four days and subsequently reintroducing them. To determine stress response patterns in the separated individuals we measured the amounts of immunoreactive corticosterone metabolites (CM) in droppings. We compared two enzyme immunoassays, which we validated by conducting an ACTH challenge, and finally decided to apply an 11-oxoetiocholanolone enzyme immunoassay. Additionally, we determined levels of social integration using focal observations. Our findings suggest that a strong social integration is related to low CM levels when the individuals are within the group and high levels during separations, implying that separation leads to stress in these birds. In contrast, poorly socially integrated ravens seem to exhibit the opposite pattern, indicating that to them group living is more stressful than being temporarily separated. We, therefore, conclude that the birds’ adrenocortical activity is modulated by their social integration. PMID:26631484

  8. Chloroquine enhances the efficacy of cisplatin by suppressing autophagy in human adrenocortical carcinoma treatment

    PubMed Central

    Qin, Liang; Xu, Tianyuan; Xia, Leilei; Wang, Xianjin; Zhang, Xiang; Zhang, Xiaohua; Zhu, Zhaowei; Zhong, Shan; Wang, Chuandong; Shen, Zhoujun

    2016-01-01

    Background It has been demonstrated that chloroquine (CQ) enhances the efficacy of chemotherapy. However, little is known about whether CQ could enhance the efficacy of cisplatin (DDP) in the treatment of adrenocortical carcinoma (ACC). In this study, we explore the efficacy and mechanism by which CQ affects DDP sensitivity in human ACC in vitro and in vivo. Methods The autophagic gene Beclin-1 expression was detected by immunohistochemistry, and the protein levels were analyzed using immunoblotting assays of ACC tissues and normal adrenal cortex tissues. The ACC SW13 cells were treated with DDP and/or CQ. The cell viability assay was performed using the MTT method. Qualitative autophagy detection was performed by monodansylcadaverine staining of autophagic vacuoles. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to count cell apoptosis by flow cytometry. The autophagy-related protein (Beclin-1, LC3, and p62) and apoptosis relative protein (Bax and Bcl-2) levels were evaluated with Western blot analysis. Furthermore, a murine model of nude BALB/c mice bearing SW13 cell xenografts was established to evaluate the efficacy of concomitant therapy. Results The expression of the autophagic gene Beclin-1 was significantly downregulated in ACC tissues compared to normal adrenal cortex tissues. The Beclin-1 protein level in ACC tissues was lower than that in normal adrenal cortex tissues (P<0.05). In vitro concomitant therapy (DDP and CQ) was more effective in restraining SW13 cell proliferation. DDP could promote cell apoptosis and induce autophagy in SW13 cells. Concomitant therapy further promoted cell apoptosis by inhibiting autophagy. In vivo, we found that concomitant therapy was more potent than DDP monotherapy in inhibiting the growth of xenografted tumors and prolonging the survival of tumor-bearing mice. Conclusion The antitumor ability of DDP was related to autophagy activity, and the concomitant therapy (DDP and CQ) could be an

  9. Betalain: a particular class of antioxidant pigment.

    PubMed

    El Gharras, Hasna

    2011-10-01

    We have analyzed the stability of betalains in juices prepared from Moroccan yellow cactus pears (Opuntia ficus indica (L.) Mill.) as a function of temperature and pH. The experiments were carried out at temperatures ranging from 80 to 100 degrees C with juices at pH 3.5, 5 and 6.5. The degree of pigment retention decreased when the temperature increased. The degradation constant rates were determined for thermal degradation rates of pseudo-first order. The Arrhenius plot obtained for the degradation of betaxanthin from the yellow fruits was not linear. Regardless of the temperature of treatment, the lowest degradation was obtained for pH 5. When some stabilizers were tested for the protection of pigments, the results showed that ascorbic acid was a better protective agent at pH 3.5, increasing the protection by 40%. The inhibitive action of betalain pigments extracted from cactus pears towards corrosion of stainless steel in phosphoric acid was investigated using electrochemical polarization and electrochemical impedance spectroscopy (EIS) methods. It was found that the presence of natural pigments reduces the corrosion rate of the tested metal, especially on addition of the red pigments (97%). The inhibition efficiency increases as the pigment concentration of extracts increases. It was also found that the pigments tested act as mixed inhibitors. The inhibitive action of the extracts is discussed in term of adsorption and that such adsorption follows a Langmuir adsorption isotherm. The calculated values of the free energy of adsorption indicated that the adsorption process is spontaneous. PMID:22164774

  10. Combined transcriptome studies identify AFF3 as a mediator of the oncogenic effects of β-catenin in adrenocortical carcinoma

    PubMed Central

    Lefèvre, L; Omeiri, H; Drougat, L; Hantel, C; Giraud, M; Val, P; Rodriguez, S; Perlemoine, K; Blugeon, C; Beuschlein, F; de Reyniès, A; Rizk-Rabin, M; Bertherat, J; Ragazzon, B

    2015-01-01

    Adrenocortical cancer (ACC) is a very aggressive tumor, and genomics studies demonstrate that the most frequent alterations of driver genes in these cancers activate the Wnt/β-catenin signaling pathway. However, the adrenal-specific targets of oncogenic β-catenin-mediating tumorigenesis have not being established. A combined transcriptomic analysis from two series of human tumors and the human ACC cell line H295R harboring a spontaneous β-catenin activating mutation was done to identify the Wnt/β-catenin targets. Seven genes were consistently identified in the three studies. Among these genes, we found that AFF3 mediates the oncogenic effects of β-catenin in ACC. The Wnt response element site located at nucleotide position −1408 of the AFF3 transcriptional start sites (TSS) mediates the regulation by the Wnt/β-catenin signaling pathway. AFF3 silencing decreases cell proliferation and increases apoptosis in the ACC cell line H295R. AFF3 is located in nuclear speckles, which play an important role in RNA splicing. AFF3 overexpression in adrenocortical cells interferes with the organization and/or biogenesis of these nuclear speckles and alters the distribution of CDK9 and cyclin T1 such that they accumulate at the sites of AFF3/speckles. We demonstrate that AFF3 is a new target of Wnt/β-catenin pathway involved in ACC, acting on transcription and RNA splicing. PMID:26214578

  11. Maya blue: a clay-organic pigment?

    PubMed

    Van Olphen, H

    1966-11-01

    Maya Blue, a pigment used by the Mayas in Yucatan, is remarkably stable: the color is not destroyed by hot concentrated mineral acids or by heating to about 250 degrees C. The principal constituent is the colorless mineral attapulgite. It is proposed that the pigment is an adsorption complex of attapulgite and natural indigo; a synthetic equivalent may be prepared from attapulgite and either indoxylester or indigo, or by applying the vat-dyeing technique, with reduced indigo.The low dye content of the pigment (less than 0.5 percent) indicates that the dye is absorbed only on the external surfaces of the attapulgite particles and not throughout the channels in their structures. The complex as such is not stable to acids, but the stability displayed by Maya Blue is achieved simply by heating the complex to from 75 degrees to 150 degrees C for several days. An analogous stable pigment can be prepared from sepiolite and indigo. No stable pigments could be prepared from clays with platelike structures or from zeolites. PMID:17778806

  12. Recreating a functional ancestral archosaur visual pigment.

    PubMed

    Chang, Belinda S W; Jönsson, Karolina; Kazmi, Manija A; Donoghue, Michael J; Sakmar, Thomas P

    2002-09-01

    The ancestors of the archosaurs, a major branch of the diapsid reptiles, originated more than 240 MYA near the dawn of the Triassic Period. We used maximum likelihood phylogenetic ancestral reconstruction methods and explored different models of evolution for inferring the amino acid sequence of a putative ancestral archosaur visual pigment. Three different types of maximum likelihood models were used: nucleotide-based, amino acid-based, and codon-based models. Where possible, within each type of model, likelihood ratio tests were used to determine which model best fit the data. Ancestral reconstructions of the ancestral archosaur node using the best-fitting models of each type were found to be in agreement, except for three amino acid residues at which one reconstruction differed from the other two. To determine if these ancestral pigments would be functionally active, the corresponding genes were chemically synthesized and then expressed in a mammalian cell line in tissue culture. The expressed artificial genes were all found to bind to 11-cis-retinal to yield stable photoactive pigments with lambda(max) values of about 508 nm, which is slightly redshifted relative to that of extant vertebrate pigments. The ancestral archosaur pigments also activated the retinal G protein transducin, as measured in a fluorescence assay. Our results show that ancestral genes from ancient organisms can be reconstructed de novo and tested for function using a combination of phylogenetic and biochemical methods. PMID:12200476

  13. Iris pigment epithelial cysts in a newborn

    PubMed Central

    Zargar, Shabnam; Prendiville, Kevin John; Martinez, Eladio

    2016-01-01

    Purpose: We report a case of iris pigment epithelial cysts in a newborn and discuss the importance of an accurate diagnosis for prevention of amblyopia. Methods: We describe a case of an abnormal red reflex seen on a newborn exam. Results: A full-term female born via normal spontaneous vaginal delivery without any complications was seen in the newborn nursery. She was noted to have an abnormal eye exam. Pupils were large with circular dark excrescences of the iris pigment epithelium. She was referred to a pediatric ophthalmologist where she was noted to fixate and follow faces. No afferent pupillary defect was seen. OD red reflex was normal whereas OS red reflex was blocked mostly by dark excrescences. A 2–3 mm dark brown lesion was seen in the OD iris and a 3–5 mm dark brown lesion was seen in the OS iris, consistent with a pupillary iris pigment epithelial cyst. Central visual axis was clear OU. Glaucoma was not present and patching was not performed. Observations and clinical photographs were recommended with follow-up in three months. Conclusion: Iris pigment epithelial cysts are uncommonly seen in children. The primary care provider first seeing a newborn must be aware of lesions obscuring a red reflex with appropriate follow-up. Follow-up in three months with IOP measurements is recommended. Iris pigment epithelial cysts in children may be a cause of amblyopia, thus prompt evaluation is important for prognostic purposes and the prevention of amblyopia. PMID:27625966

  14. Pigments in avocado tissue and oil.

    PubMed

    Ashton, Ofelia B O; Wong, Marie; McGhie, Tony K; Vather, Rosheila; Wang, Yan; Requejo-Jackman, Cecilia; Ramankutty, Padmaja; Woolf, Allan B

    2006-12-27

    Pigments are important contributors to the appearance and healthful properties of both avocado fruits and the oils extracted from these fruits. This study determined carotenoid and chlorophyll pigment concentrations in the skin and three sections of the flesh (outer dark green, middle pale green, and inner yellow flesh-nearest the seed) and anthocyanin concentrations in the skin of Hass avocado during ripening at 20 degrees C. Pigments were extracted from frozen tissue with acetone and measured using high-performance liquid chromatography. Pigments were also measured in the oil extracted from freeze-dried tissue sections by an accelerated solvent extraction system using hexane. Carotenoids and chlorophylls identified in the skin, flesh, and oil were lutein, alpha-carotene, beta-carotene, neoxanthin, violaxanthin, zeaxanthin, antheraxanthin, chlorophylls a and b, and pheophytins a and b with the highest concentrations of all pigments in the skin. Chlorophyllides a and b were identified in the skin and flesh tissues only. As the fruit ripened and softened, the skin changed from green to purple/black, corresponding to changes in skin hue angle, and a concomitant increase in cyanidin 3-O-glucoside and the loss of chlorophyllide a. In flesh tissue, chroma and lightness values decreased with ripening, with no changes in hue angle. The levels of carotenoids and chlorophylls did not change significantly during ripening. As fruit ripened, the total chlorophyll level in the oil from the flesh sections remained constant but declined in the oil extracted from the skin. PMID:17177553

  15. Inadvertent polychlorinated biphenyls in commercial paint pigments.

    PubMed

    Hu, Dingfei; Hornbuckle, Keri C

    2010-04-15

    A polychlorinated biphenyl (PCB) that was not produced as part of the Aroclor mixtures banned in the 1980s was recently reported in air samples collected in Chicago, Philadelphia, the Arctic, and several sites around the Great Lakes. In Chicago, the congener 3,3'-dichlorobiphenyl or PCB11 was found to be the fifth most concentrated congener and ubiquitous throughout the city. The congener exhibited strong seasonal concentration trends that suggest volatilization of this compound from common outdoor surfaces. Due to these findings and also the compound's presence in waters that received waste from paint manufacturing facilities, we hypothesized that PCB11 may be present in current commercial paint. In this study we measured PCBs in paint sold on the current retail market. We tested 33 commercial paint pigments purchased from three local paint stores. The pigment samples were analyzed for all 209 PCB congeners using gas chromatography with tandem mass spectrometry (GC-MS/MS). More than 50 PCB congeners including several dioxin-like PCBs were detected, and the PCB profiles varied due to different types of pigments and different manufacturing processes. PCB congeners were detected in azo and phthalocyanine pigments which are commonly used in paint but also in inks, textiles, paper, cosmetics, leather, plastics, food and other materials. Our findings suggest several possible mechanisms for the inadvertent production of specific PCB congeners during the manufacturing of paint pigments. PMID:19957996

  16. Investigations of biomimetic light energy harvesting pigments

    SciTech Connect

    Van Patten, P.G.; Donohoe, R.J.; Lindsey, J.S.; Bocian, D.F.

    1998-12-01

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). Nature uses chlorophyll and other porphyrinic pigments to capture and transfer light energy as a preliminary step in photosynthesis. The design of synthetic assemblies of light harvesting and energy directing pigments has been explored through synthesis and characterization of porphyrin oligomers. In this project, pigment electronic and vibrational structures have been explored by electrochemistry and dynamic and static optical measurements. Transient absorption data reveal energy transfer between pigments with lifetimes on the order of 20--200 picoseconds, while Raman data reveal that the basic porphyrin core structure is unperturbed relative to the individual monomer units. These two findings, along with an extensive series of experiments on the oxidized oligomers, reveal that coupling between the pigments is fundamentally weak, but sufficient to allow facile energy transfer as the predominant excited state process. Modeling of the expected quantum yields for energy transfer within a variety of arrays was accomplished, thereby providing a tool to guide synthetic goals.

  17. PROFILING GENE EXPRESSION IN HUMAN H295R ADRENOCORTICAL CARCINOMA CELLS AND RAT TESTES TO IDENTIFY PATHWAYS OF TOXICITY FOR CONAZOLE FUNGICIDES

    EPA Science Inventory

    Profiling Gene Expression in Human H295R Adrenocortical Carcinoma Cells and Rat Testes to Identify Pathways of Toxicity for Conazole Fungicides
    Ren1, H., Schmid1, J., Retief2, J., Turpaz2, Y.,Zhang3, X.,Jones3, P., Newsted3, J.,Giesy3, J., Wolf1, D.,Wood1, C., Bao1, W., Dix1, ...

  18. Prenatal Maternal Stress Predicts Methylation of Genes Regulating the Hypothalamic-Pituitary-Adrenocortical System in Mothers and Newborns in the Democratic Republic of Congo

    ERIC Educational Resources Information Center

    Kertes, Darlene A.; Kamin, Hayley S.; Hughes, David A.; Rodney, Nicole C.; Bhatt, Samarth; Mulligan, Connie J.

    2016-01-01

    Exposure to stress early in life permanently shapes activity of the hypothalamic-pituitary-adrenocortical (HPA) axis and the brain. Prenatally, glucocorticoids pass through the placenta to the fetus with postnatal impacts on brain development, birth weight (BW), and HPA axis functioning. Little is known about the biological mechanisms by which…

  19. Pigments which reflect infrared radiation from fire

    DOEpatents

    Berdahl, P.H.

    1998-09-22

    Conventional paints transmit or absorb most of the intense infrared (IR) radiation emitted by fire, causing them to contribute to the spread of fire. The present invention comprises a fire retardant paint additive that reflects the thermal IR radiation emitted by fire in the 1 to 20 micrometer ({micro}m) wavelength range. The important spectral ranges for fire control are typically about 1 to about 8 {micro}m or, for cool smoky fires, about 2 {micro}m to about 16 {micro}m. The improved inventive coatings reflect adverse electromagnetic energy and slow the spread of fire. Specific IR reflective pigments include titanium dioxide (rutile) and red iron oxide pigments with diameters of about 1 {micro}m to about 2 {micro}m and thin leafing aluminum flake pigments. 4 figs.

  20. Pigments which reflect infrared radiation from fire

    DOEpatents

    Berdahl, Paul H.

    1998-01-01

    Conventional paints transmit or absorb most of the intense infrared (IR) radiation emitted by fire, causing them to contribute to the spread of fire. The present invention comprises a fire retardant paint additive that reflects the thermal IR radiation emitted by fire in the 1 to 20 micrometer (.mu.m) wavelength range. The important spectral ranges for fire control are typically about 1 to about 8 .mu.m or, for cool smoky fires, about 2 .mu.m to about 16 .mu.m. The improved inventive coatings reflect adverse electromagnetic energy and slow the spread of fire. Specific IR reflective pigments include titanium dioxide (rutile) and red iron oxide pigments with diameters of about 1 .mu.m to about 2 .mu.m and thin leafing aluminum flake pigments.

  1. Reversible Conjunctival Pigmentation Associated With Prostaglandin Use.

    PubMed

    Choi, Daniel Y; Chang, Robert T; Yegnashankaran, Krishnan; Friedman, Neil J

    2016-01-01

    A 54-year-old Indian male with a diagnosis of ocular hypertension was started on a prostaglandin analog (PGA) in both eyes to lower intraocular pressure. Six years later, he developed progressively increasing bilateral limbal conjunctival hyperpigmentation. Travoprost was discontinued and replaced with brinzolamide and over the next year, the patient's conjunctival pigmentation improved significantly in both the eyes. This case report documents with slit-lamp photography the first case of conjunctival pigmentation associated with PGA use that has been shown to have reversal with discontinuation of the PGA. Because of the widespread use of PGAs, and the evolving nature of the conjunctival pigmentation, clinicians should be aware of this reversible condition when considering biopsy or removal of conjunctival melanocytic lesions. PMID:25967530

  2. Predicting phenotype from genotype: normal pigmentation.

    PubMed

    Valenzuela, Robert K; Henderson, Miquia S; Walsh, Monica H; Garrison, Nanibaa' A; Kelch, Jessica T; Cohen-Barak, Orit; Erickson, Drew T; John Meaney, F; Bruce Walsh, J; Cheng, Keith C; Ito, Shosuke; Wakamatsu, Kazumasa; Frudakis, Tony; Thomas, Matthew; Brilliant, Murray H

    2010-03-01

    Genetic information in forensic studies is largely limited to CODIS data and the ability to match samples and assign them to an individual. However, there are circumstances, in which a given DNA sample does not match anyone in the CODIS database, and no other information about the donor is available. In this study, we determined 75 SNPs in 24 genes (previously implicated in human or animal pigmentation studies) for the analysis of single- and multi-locus associations with hair, skin, and eye color in 789 individuals of various ethnic backgrounds. Using multiple linear regression modeling, five SNPs in five genes were found to account for large proportions of pigmentation variation in hair, skin, and eyes in our across-population analyses. Thus, these models may be of predictive value to determine an individual's pigmentation type from a forensic sample, independent of ethnic origin. PMID:20158590

  3. Mesangial cell hillocks. Nodular foci of exaggerated growth of cells and matrix in prolonged culture.

    PubMed Central

    Sterzel, R. B.; Lovett, D. H.; Foellmer, H. G.; Perfetto, M.; Biemesderfer, D.; Kashgarian, M.

    1986-01-01

    To examine the capability of glomerular mesangial cells (MCs) to produce extracellular matrix, the authors studied MCs in culture by light and electron microscopy as well as immunocytochemistry. MCs were obtained from isolated rat glomeruli and maintained up to 12 weeks in medium containing 20% fetal calf serum. MC outgrowth of primary culture and of up to three subcultures showed characteristic organization consisting of bands of elongated or stellate intertwined cells. After confluency at 10-16 days, MCs continued to grow in irregular multilayers. MCs produced extracellular matrix material within 2-4 days after plating, and large amounts of matrix accumulated with time. By 2-3 weeks, foci of exaggerated MC proliferation, matrix secretion, and necrotic cell debris formed nodular protrusions, which gradually produced large hillocks. Immunocytochemical studies of MC outgrowths were performed on culture plates or on sectioned material with the use of specific rabbit polyclonal antibodies to isolated matrix proteins and FITC-conjugated, affinity-purified second antibodies. Within 3 days of culture, MCs elaborated fibronectin and collagen Types I, III, IV, and V. With time, strands of matrix, notably in the central mass of hillocks, stained extensively for these constituents. Staining for laminin was less pronounced. Smooth muscle cell myosin was regularly found on distinct intracellular fibrils and in the extracellular material of hillocks. Electron microscopy revealed the hillocks to be composed of elongated cells on the surface and stellate cells intermingled with matrix and necrotic cell debris in the core. The results show that proliferating MCs can be maintained in homogeneous culture for a prolonged time period. MCs produce large amounts of the extracellular matrix proteins (Type IV and V collagen, fibronectin, laminin), which are found in normal glomeruli. Cultured MCs also produce interstitial collagen Types I and III. MC hillocks show the nodular accumulation

  4. Adrenocorticotrophic hormone stimulates phosphotyrosine phosphatase SHP2 in bovine adrenocortical cells: phosphorylation and activation by cAMP-dependent protein kinase.

    PubMed Central

    Rocchi, S; Gaillard, I; van Obberghen, E; Chambaz, E M; Vilgrain, I

    2000-01-01

    During activation of adrenocortical cells by adrenocorticotrophic hormone (ACTH), tyrosine dephosphorylation of paxillin is stimulated and this correlates with protrusion of filopodial structures and a decreased number of focal adhesions. These effects are inhibited by Na(3)VO(4), a phosphotyrosine phosphatase inhibitor [Vilgrain, Chinn, Gaillard, Chambaz and Feige (1998) Biochem. J. 332, 533-540]. However, the tyrosine phosphatases involved in these processes remain to be identified. In this study, we provide evidence that the Src homology domain (SH)2-containing phosphotyrosine phosphatase (SHP)2, but not SHP1, is expressed in adrenocortical cells and is phosphorylated upon ACTH challenge. ACTH (10(-8) M) treatment of (32)P-labelled adrenocortical cells resulted in an increase in phosphorylated SHP2. By probing SHP2-containing immunoprecipitates with an antibody to phosphoserine we found that SHP2 was phosphorylated on serine in ACTH-treated cells in a dose- and time-dependent manner. Furthermore, using an in vitro kinase assay, we showed that SHP2 was a target for cAMP-dependent protein kinase (PKA). Serine was identified as the only target amino acid phosphorylated in SHP2. Phosphorylation of SHP2 by PKA resulted in a dramatic stimulation of phosphatase activity measured either with insulin receptor substrate-1 or with the synthetic peptide [(32)P]poly(Glu/Tyr) as substrate. In an in-gel assay of SHP2-containing immunoprecipitates, phosphorylated in vitro by PKA or isolated from adrenocortical cells treated with 10 nM ACTH, a pronounced activation of SHP2 activity was shown. These observations clearly support the idea that a PKA-mediated signal transduction pathway contributes to SHP2 regulation in adrenocortical cells and point to SHP2 as a possible mediator of the effects of ACTH. PMID:11085942

  5. Mycosis fungoides presenting as pigmented purpuric dermatitis.

    PubMed

    Hanna, Shannon; Walsh, Noreen; D'Intino, Yolanda; Langley, Richard G B

    2006-01-01

    Mycosis fungoides, a cutaneous T-cell lymphoma, typically presents as indolent, progressive, and persistent erythematous patches or plaques with mild scaling and over time can evolve into tumor stage with tumor nodules. Other presentations include eczematous, psoriasiform, poikilodermatous, and hypopigmented patches. We report Mycosis fungoides in a 14-year-old boy presenting as pigmented purpuric dermatitis and review the relevant literature. This is a rare presentation of a condition that is uncommon in the pediatric population. In our patient, histologic features were typical of Mycosis fungoides presenting as pigmented purpuric dermatitis. The clinical features, pathology, molecular biology, and the relationship between these two entities are discussed. PMID:16918631

  6. Pseudoepitheliomatous Hyperplasia in a Red Pigment Tattoo

    PubMed Central

    Kazlouskaya, Viktoryia

    2015-01-01

    Red pigment tattoos are known to cause pseudoepitheliomatous hyperplasia in the skin, frequently simulating squamous cell carcinoma or keratoacanthoma. Herein, the authors present two additional cases of red pigment tattoo pseudoepitheliomatous hyperplasia in which they noted a lichenoid tissue reaction. They reviewed the previously published cases and observed a lichenoid reaction in the histopathological images similar to hypertrophic lichen planus. The authors suggest that these reactions might best be referred to as “lichenoid reaction with pseudoepitheliomatous hyperplasia” or “hypertrophic lichen planus-like reaction.” Accordingly, recognition of an inflammatory component may allow additional treatment options. PMID:26705448

  7. Green pigments of the Pompeian artists' palette

    NASA Astrophysics Data System (ADS)

    Aliatis, Irene; Bersani, Danilo; Campani, Elisa; Casoli, Antonella; Lottici, Pier Paolo; Mantovan, Silvia; Marino, Iari-Gabriel; Ospitali, Francesca

    2009-08-01

    Green colored samples on wall paintings and green powder from a pigment pot found in Pompeii area are investigated by micro-Raman, FT-IR and, for one sample, SEM-EDX. To obtain the green color, green earths and malachite were used, together with mixture of Egyptian blue and yellow ochre. The mineralogical identification of the green earths has been attempted through the comparison of the vibrational features, discriminating between celadonite and glauconite spectra. Traces of a modern synthetic pigment containing copper phthalocyanine were found in a fresco fragment.

  8. A Case of Oncocytic Adrenocortical Neoplasm of Borderline (Uncertain) Malignant Potential.

    PubMed

    Shenouda, Mina; Brown, Linda G; Denning, Krista L; Pacioles, Toni

    2016-01-01

    Oncocytic neoplasms are tumors composed predominantly or exclusively of oncocytes (large polygonal cells with granular eosinophilic cytoplasm due to abnormal mitochondrial accumulation). These tumors are frequently reported in the thyroid, kidneys, and salivary glands. However, they are distinctly rare in the adrenal cortex. Oncocytic adrenocortical neoplasms (OAN) are classified regarding their biological behavior by their histological features according to the Lin-Weiss-Bisceglia system (LWB). Here, we report a case of OAN of borderline or uncertain malignant potential (BMP) with subsequently identified papillary thyroid carcinoma (PTC). A 34-year-old female with a nine-month history of fatigue presented with chest pain. A right adrenal mass was incidentally found while ruling out pulmonary embolism. A CT-guided adrenal biopsy, although not routinely indicated, was performed and interpreted as malignant with no definitive origin. Hormonal workup was unremarkable. PET-scan showed hypermetabolic adrenal mass with peak standardized uptake value of 15, suspicious of malignancy. A hypermetabolic thyroid nodule was also identified, but there was no evidence of metastatic disease. The patient underwent adrenalectomy, and the initial pathology report was interpreted as atypical pink cell tumor. A second pathology report from another laboratory favored OAN based on the morphology and immunohistochemical staining. While the histologic criteria of malignancy were not met, the large tumor size makes it compatible with BMP according to LWB criteria. A follow-up thyroid ultrasound revealed a complex thyroid nodule. A total thyroidectomy was performed, and pathology was consistent with PTC. Of interest, PTC frequently shows an increase in mitochondrial content, which is characteristic of oncocytic tumors. This case illustrates that OAN, although rare, should be considered in the differential diagnosis of adrenal masses. When OAN is identified, it should be classified

  9. Incidence and Risk Factors Associated with Readmission After Surgical Treatment for Adrenocortical Carcinoma

    PubMed Central

    Valero-Elizondo, Javier; Kim, Yuhree; Prescott, Jason D.; Margonis, Georgios A.; Tran, Thuy B.; Postlewait, Lauren M.; Maithel, Shishir K.; Wang, Tracy S.; Glenn, Jason A.; Hatzaras, Ioannis; Shenoy, Rivfka; Phay, John E.; Keplinger, Kara; Fields, Ryan C.; Jin, Linda X.; Weber, Sharon M.; Salem, Ahmed; Sicklick, Jason K.; Gad, Shady; Yopp, Adam C.; Mansour, John C.; Duh, Quan-Yang; Seiser, Natalie; Solorzano, Carmen C.; Kiernan, Colleen M.; Votanopoulos, Konstantinos I.; Levine, Edward A.; Poultsides, George A.

    2016-01-01

    Background Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. Given the lack of data on readmission after resection of ACC, the objective of the current study was to define the incidence of readmission, as well as identify risk factors associated with readmission among patients with ACC who underwent surgical resection. Methods Two hundred nine patients who underwent resection of ACC between January 1993 and December 2014 at 1 of 13 major centers in the USA were identified. Demographic and clinicopathological data were collected and analyzed relative to readmission. Results Median patient age was 52 years, and 62 % of the patients were female. Median tumor size was 12 cm, and the majority of patients had an American Society of Anesthesiologists (ASA) class of 3–4 (n=85, 56 %). The overall incidence of readmission within 90 days from surgery was 18 % (n=38). Factors associated with readmission included high ASA class (odds ratio (OR), 4.88 (95 % confidence interval (CI), 1.75–13.61); P=0.002), metastatic disease on presentation (OR, 2.98 (95 % CI, 1.37–6.46); P=0.006), EBL (>700 mL: OR, 2.75 (95 % CI, 1.16–6.51); P=0.02), complication (OR, 1.91 (95 % CI, 1.20–3.05); P=0.007), and prolonged length of stay (LOS; ≥9 days: OR, 4.12 (95 % CI, 1.88–9.01); P<0.001). On multivariate logistic regression, a high ASA class (OR, 4.01 (95 % CI, 1.44–11.17); P=0.008) and metastatic disease on presentation (OR, 3.44 (95 % CI, 1.34–8.84); P=0.01) remained independently associated with higher odds of readmission. Conclusion Readmission following surgery for ACC was common as one in five patients experienced a readmission. Patients with a high ASA class and metastatic disease on presentation were over four and three times more likely to be readmitted after surgical treatment for ACC, respectively. PMID:26286367

  10. A Case of Oncocytic Adrenocortical Neoplasm of Borderline (Uncertain) Malignant Potential

    PubMed Central

    Brown, Linda G; Denning, Krista L; Pacioles, Toni

    2016-01-01

    Oncocytic neoplasms are tumors composed predominantly or exclusively of oncocytes (large polygonal cells with granular eosinophilic cytoplasm due to abnormal mitochondrial accumulation). These tumors are frequently reported in the thyroid, kidneys, and salivary glands. However, they are distinctly rare in the adrenal cortex. Oncocytic adrenocortical neoplasms (OAN) are classified regarding their biological behavior by their histological features according to the Lin-Weiss-Bisceglia system (LWB). Here, we report a case of OAN of borderline or uncertain malignant potential (BMP) with subsequently identified papillary thyroid carcinoma (PTC). A 34-year-old female with a nine-month history of fatigue presented with chest pain. A right adrenal mass was incidentally found while ruling out pulmonary embolism. A CT-guided adrenal biopsy, although not routinely indicated, was performed and interpreted as malignant with no definitive origin. Hormonal workup was unremarkable. PET-scan showed hypermetabolic adrenal mass with peak standardized uptake value of 15, suspicious of malignancy. A hypermetabolic thyroid nodule was also identified, but there was no evidence of metastatic disease. The patient underwent adrenalectomy, and the initial pathology report was interpreted as atypical pink cell tumor. A second pathology report from another laboratory favored OAN based on the morphology and immunohistochemical staining. While the histologic criteria of malignancy were not met, the large tumor size makes it compatible with BMP according to LWB criteria. A follow-up thyroid ultrasound revealed a complex thyroid nodule. A total thyroidectomy was performed, and pathology was consistent with PTC. Of interest, PTC frequently shows an increase in mitochondrial content, which is characteristic of oncocytic tumors. This case illustrates that OAN, although rare, should be considered in the differential diagnosis of adrenal masses. When OAN is identified, it should be classified

  11. Curative Resection of Adrenocortical Carcinoma: Rates and Patterns of Postoperative Recurrence

    PubMed Central

    Amini, Neda; Margonis, Georgios Antonios; Kim, Yuhree; Tran, Thuy B.; Postlewait, Lauren M.; Maithel, Shishir K.; Wang, Tracy S.; Evans, Douglas B.; Hatzaras, Ioannis; Shenoy, Rivfka; Phay, John E.; Keplinger, Kara; Fields, Ryan C.; Jin, Linda X.; Weber, Sharon M.; Salem, Ahmed; Sicklick, Jason K.; Gad, Shady; Yopp, Adam C.; Mansour, John C.; Duh, Quan-Yang; Seiser, Natalie; Solorzano, Carmen C.; Kiernan, Colleen M.; Votanopoulos, Konstantinos I.; Levine, Edward A.; Poultsides, George A.; Pawlik, Timothy M.

    2016-01-01

    Background Adrenocortical carcinoma (ACC) is a rare malignancy. The aim of this study was to determine the incidence and patterns of recurrence after curative-intent surgery for ACC. Methods Patients who underwent curative-intent resection for ACC between 1993 and 2014 were identified from 13 academic institutions participating in the United States ACC study group. Patients with metastasis or an R2 margin were excluded. Patterns and rates of recurrence were determined and classified as locoregional and distant recurrence. Results A total of 180 patients with a median age of 52 years (interquartile range 43–61) were identified. Most patients underwent open surgery (n = 111, 64.5 %) and had an R0 resection margin (n = 117, 75.0 %). At last followup, 116 patients (64.4 %) had experienced recurrence (locoregional only, n = 41, 36.3 %; distant only, n = 51, 45.1 %; locoregional and distant, n = 21, 18.6 %). Median time to recurrence was 18.8 months. Several factors were associated with locoregional recurrence, including left-sided ACC location (odds ratio [OR] 2.71, 95 % confidence interval [CI] 1.06–6.89) and T3/T4 disease (reference T1/T2, OR 3.04, 95 % CI 1.19–7.80) (both p < 0.05). Distant recurrence was associated with larger tumor size (OR 1.11, 95 % CI 1.01–1.24) and T3/T4 disease (reference T1/T2, OR 5.23, 95 % CI 1.70–16.10) (both p < 0.05). Patients with combined locoregional and distant recurrence had worse survival (3- and 5-year survival: 39.5, 19.7 %) versus patients with distant-only (3- and 5-year survival 55.1, 43.3 %) or locoregional-only recurrence (3- and 5-year survival 81.4, 64.1 %) (p = 0.01). Conclusions Nearly two-thirds of patients experienced disease recurrence after resection of ACC. Although a subset of patients experienced recurrence with locoregional disease only, many patients experienced recurrence with distant disease as a component of recurrence and had a poor prognosis. PMID:26282907

  12. Diffuse nodular lymphoid hyperplasia of the small bowel associated with common variable immunodeficiency and giardiasis: a rare case report.

    PubMed

    Olmez, Sehmus; Aslan, Mehmet; Yavuz, Alpaslan; Bulut, Gulay; Dulger, Ahmet Cumhur

    2014-05-01

    Diffuse nodular lymphoid hyperplasia (DNLH) of the intestine is an extremely rare lymphoproliferative disorder of uncertain etiology. Typically, numerous polypoid nodules composed of hyperplastic benign lymphoid tissue are present in the small and/or large intestinal mucosa. DNLH has been observed in association with common variable immunodeficiency (CVID). A 38-years-old man was admitted to our clinic due to dyspeptic complaints. An upper gastrointestinal system endoscopic examination revealed DNLH in the duodenum. A biopsy specimen showed the presence of nodular lymphoid hyperplasia and a Giardia lamblia infection in the duodenum. CVID was suspected, and the diagnosis was established by demonstrating a significant reduction in the serum gamma-globulin levels. DNLH is a rare benign condition with regards to diagnosis and treatment of unknown etiology. In patients with DNLH, screening for the immune deficiencies is being important in addition to histopathological examinations. PMID:24647448

  13. The feasibility of low-G grey solidification of nodular iron in the F-104 experimental furnace package

    NASA Technical Reports Server (NTRS)

    Curreri, P. A.; Smith, G. A.; Workman, G.

    1983-01-01

    The rationale for low-g experiments with cast iron and the need for solidification in the grey form during these experiments are reviewed. The factors which determine whether an iron melt will solidify grey or white are discussed. Cooling rate versus microstructure was studied for a nodular iron candidate material for F-104 low-g solidification. The study determined that low-g grey solidification, using the present F-104 furnace system, of the nodular iron composition studied is not feasible. Specimen microstructure strongly suggested that the F-104 furnace's gas cooling system was causing excessive localized chill resulting in the nucleation of the unwanted iron carbide phase. A change is suggested, in the quench system design, that could possibly overcome this problem.

  14. Identification of a Mycobacterium sp. as the causative agent of orange nodular lesions in the Atlantic sea scallop Placopecten magellanicus.

    PubMed

    Grimm, Catherine; Huntsberger, Carl; Markey, Kathryn; Inglis, Susan; Smolowitz, Roxanna

    2016-03-30

    The Atlantic sea scallop Placopecten magellanicus is an economically important species in the offshore fisheries on the east coast of the USA. Recently, animals collected from waters ranging from Massachusetts to Maryland have shown variably sized (up to 1 cm in diameter) orange nodular foci, predominantly in the adductor muscle tissue, but also in other organs. Histological evaluation of the nodular lesions showed rod-shaped bacteria that stain acid-fast positive and Gram-positive. PCR methodology was employed to identify the causative organism of the nodules as a Mycobacterium sp. using analysis of the partial 16S gene and the 16S-23S internal transcribed spacer region. Based upon genotypic findings, the causative bacterium fits well into the genus Mycobacterium. PMID:27025312

  15. Idiopathic nodular glomerulosclerosis in a never-smoking, normotensive, non-obese, normal-glucose-tolerant middle-aged woman.

    PubMed

    Uchida, Takahiro; Oda, Takashi; Watanabe, Atsushi; Higashi, Keishi; Katsurada, Yuka; Shimazaki, Hideyuki; Tamai, Seiichi; Kumagai, Hiroo

    2012-10-01

    A 53-year-old woman with a history of dyslipidemia presented with medium-grade proteinuria and several years of progressive renal dysfunction. Renal biopsy showed diffuse and global Kimmelstiel-Wilson nodule like nodular mesangial sclerosis, but she had no history of diabetes mellitus, no diabetic retinopathy and normal oral glucose tolerance. Congo red staining was negative, and immunofluorescence staining showed no immunoglobulin deposition including kappa or lambda light chains. Electron microscopy showed no electron dense deposits or organized deposits. Thus, we diagnosed idiopathic nodular glomerulosclerosis (ING). ING is a recently established clinicopathologic disease entity linked to longstanding cigarette smoking and hypertension. Obesity is also listed as a contributing factor. However, none of these factors was documented in this case. This is a valuable case of ING that suggests the existence of as-yet unknown causative factors of ING other than smoking, hypertention or obesity. PMID:26019825

  16. Pigment oligomers as natural and artificial photosynthetic antennas

    SciTech Connect

    Blankenship, R.E.

    1996-12-31

    Green photosynthetic bacteria contain antenna complexes known as chlorosomes. These complexes are appressed to the cytoplasmic side of the inner cell membrane and function to absorb light and transfer the energy to the photochemical reaction center, where photochemical energy storage takes place. Chlorosomes differ from all other known photosynthetic antenna complexes in that the geometrical arrangement of pigments is determined primarily by pigment-pigment interactions instead of pigment-protein interactions. The bacteriochlorophyll c, d or e pigments found in chlorosomes form large oligomers with characteristic spectral properties significantly perturbed from those exhibited by monomeric pigments. Because of their close spatial interaction, the pigments are thought to be strongly coupled electronically, and many of the optical properties result from exciton interactions. This presentation will summarize existing knowledge on the chemical composition and properties of chlorosomes, the evidence for the oligomeric nature of chlorosome pigment organization and proposed structures for the oligomers, and the kinetics and mechanisms of energy transfer in chlorosomes.

  17. Separation of Chloroplast Pigments Using Reverse Phase Chromatography.

    ERIC Educational Resources Information Center

    Reese, R. Neil

    1997-01-01

    Presents a protocol that uses reverse phase chromatography for the separation of chloroplast pigments. Provides a simple and relatively safe procedure for use in teaching laboratories. Discusses pigment extraction, chromatography, results, and advantages of the process. (JRH)

  18. Paternal inheritance of classic X-linked bilateral periventricular nodular heterotopia.

    PubMed

    Kasper, Burkhard S; Kurzbuch, Katrin; Chang, Bernard S; Pauli, Elisabeth; Hamer, Hajo M; Winkler, Jürgen; Hehr, Ute

    2013-06-01

    Periventricular nodular heterotopia (PNH) is a developmental disorder of the central nervous system, characterized by heterotopic nodules of gray matter resulting from disturbed neuronal migration. The most common form of bilateral PNH is X-linked dominant inherited, caused by mutations in the Filamin A gene (FLNA) and associated with a wide variety of other clinical findings including congenital heart disease. The typical patient with FLNA-associated PNH is female and presents with difficult to treat seizures. In contrast, hemizygous FLNA loss of function mutations in males are reported to be perinatally lethal. In X-linked dominant traits like FLNA-associated PNH the causal mutation is commonly inherited from the mother. Here, we present an exceptional family with paternal transmission of classic bilateral FLNA-associated PNH from a mildly affected father with somatic and germline mosaicism for a c.5686G>A FLNA splice mutation to both daughters with strikingly variable clinical manifestation and PNH extent in cerebral MR imaging. Our observations emphasize the importance to consider in genetic counseling and risk assessment the rare genetic constellation of paternal transmission for families with X-linked dominant inherited FLNA-associated PNH. PMID:23636902

  19. [A Case of Early Gastric Cancer with Nodular Tumor-like Scalp Metastasis].

    PubMed

    Song, Young Wook; Kim, Woo Sub; Yun, Gee Young; Park, Sun Wook; Kang, Sun Hyung; Moon, Hee Seok; Sung, Jae Kyu; Jeong, Hyun Yong

    2016-07-25

    Many neoplasms, including lung cancer, breast cancer, melanoma, and gastrointestinal tract malignancy, possess potential for skin metastasis. Skin metastases can represent the first presentation of such malignancies and may be observed incidentally during routine exam. Skin metastases from gastric adenocarcinoma are uncommon, with a prevalence rate of 0.04-0.8%. Cutaneous metastases from gastric cancer are generally observed as the initial symptom of advanced gastric cancer. Early detection and treatment can increase patient survival. A 42-year-old woman visited our department with nodule about 1 cm in size on the right frontal scalp noticed incidentally after laparoscopy-assisted distal gastrectomy and adjuvant systemic chemo-therapy for early gastric cancer about 16 months prior. The patient was diagnosed with skin metastasis from gastric adenocarcinoma. Complete excision of the skin lesion and additional chemotherapy were performed. Herein, we report a case of nodular tumor-like scalp metastasis from early gastric cancer with a brief review of the literature. PMID:27443622

  20. Differentiation of hepatocellular adenoma and focal nodular hyperplasia using 18F-fluorocholine PET/CT.

    PubMed

    van den Esschert, Jacomina W; Bieze, Matthanja; Beuers, Ulrich H; van Gulik, Thomas M; Bennink, Roelof J

    2011-03-01

    The aim of this pilot study was to evaluate the use of PET/CT with (18)F-fluorocholine in the differentiation of hepatocellular adenoma (HCA) from focal nodular hyperplasia (FNH). Patients with liver lesions larger than 2 cm suspicious for HCA or FNH were prospectively included. All patients underwent PET/CT with (18)F-fluorocholine and histopathological diagnosis was obtained by either liver biopsy or surgery. The ratios between the maximum standardized uptake value (SUV) of the lesion and the mean SUV of normal liver parenchyma were calculated and a receiver operating characteristic (ROC) curve analysis was performed. Ten patients with FNH and 11 with HCA were included. The mean SUV ratio was 1.68±0.29 (±SD) for FNH and 0.88±0.18 for HCA (p<0.001). An SUV ratio cut-off value between 1.12 and 1.22 differentiated patients with FNH from those with HCA with 100% sensitivity and 100% specificity. This pilot study showed that PET/CT with (18)F-fluorocholine can differentiate HCA from FNH. PMID:20717825

  1. Differentiation of hepatocellular adenoma and focal nodular hyperplasia using 18F-fluorocholine PET/CT

    PubMed Central

    van den Esschert, Jacomina W.; Bieze, Matthanja; Beuers, Ulrich H.; Bennink, Roelof J.

    2010-01-01

    The aim of this pilot study was to evaluate the use of PET/CT with 18F-fluorocholine in the differentiation of hepatocellular adenoma (HCA) from focal nodular hyperplasia (FNH). Patients with liver lesions larger than 2 cm suspicious for HCA or FNH were prospectively included. All patients underwent PET/CT with 18F-fluorocholine and histopathological diagnosis was obtained by either liver biopsy or surgery. The ratios between the maximum standardized uptake value (SUV) of the lesion and the mean SUV of normal liver parenchyma were calculated and a receiver operating characteristic (ROC) curve analysis was performed. Ten patients with FNH and 11 with HCA were included. The mean SUV ratio was 1.68±0.29 (±SD) for FNH and 0.88±0.18 for HCA (p<0.001). An SUV ratio cut-off value between 1.12 and 1.22 differentiated patients with FNH from those with HCA with 100% sensitivity and 100% specificity. This pilot study showed that PET/CT with 18F-fluorocholine can differentiate HCA from FNH. PMID:20717825

  2. Adenoma or atypical hepatic focal nodular hyperplasia: role of preoperative imaging and laparoscopic treatment.

    PubMed

    Di Carlo, Isidoro; Pulvirenti, Elia; Toro, Adriana; Priolo, Gian Domenico

    2010-06-01

    Differentiation of focal nodular hyperplasia (FNH) and other hypervascular liver lesions, such as hepatocellular adenoma (HCA), is important because of the drastically different therapeutic approach. However, FNH can be well distinguished only if it shows a typical aspect; alternatively, in the case of atypical FNH, imaging findings are not specific enough to provide a secure diagnosis and histologic verification of the lesion is required. In addition, HCA cannot be identified conclusively by any current available imaging technique and it can be at best suspected strongly, and this suspicion may lead to liver resection. Herein we report a case of a patient with an unusual FNH nodule presenting at ultrasonographic scanning as an isoechoic mass arising from hepatic segment 4b; the diagnostic indecision between FNH and HCA was not definitively solved even after computed tomography scan and magnetic resonance imaging and the patient was scheduled for a laparoscopic resection. The pathologic examination diagnosed an atypical FNH nodule. The clinical doubt between FNH and HCA remains a problem affecting the clinicians, and more effort should be made in the direction of a better preoperative differentiation of such different conditions. Surgical resection should not be considered as the failure of the preoperative diagnostic attempt, but as the mainstay for a definitive and sure diagnosis. PMID:20551788

  3. Influence of Heat Treatment on Microstructural and Mechanical Properties of Nodular Cast Iron

    NASA Astrophysics Data System (ADS)

    Kruthiventi, S.; Basavakumar, K. G.; Nambala, S.; Subramanyacharyulu, G.

    2014-04-01

    Spheroidal Graphite Iron (SG Iron) is popularly known as ductile iron or nodular cast iron which is a special case of cast iron having carbon content of more than 3 wt% in volume and graphite is in the form of spherical tiny sized particles. Since the last three decades, the demand for SG Iron has been increasing due to its superior mechanical properties such as high strength and toughness, this nature leads to the usage of SG Iron in numerous industrial applications. From the earlier studies, it has been proved that addition of alloying elements to SG Iron leads to change in properties such as increased tensile strength and hardness. Heat-treatment of alloys is one of the valuable methods to achieve better properties. In the present study, the microstructures and mechanical properties of SG Iron were studied after various heat treatments beyond the limits, and tests were done to measure its mechanical properties like tensile strength, hardness, impact strength. Digital microphotographs, scanning electron microphotographs were analysed before and after the heat treatment. Results indicated great change in mechanical properties after the heat-treatment. From the results it can be concluded that the heat treatment of SG Iron results in changed composition of alloys, which also leads to economical growth of SG Iron.

  4. Case report of nodular melanoma within congenital melanocytic nevus- primary closure challenge

    PubMed Central

    Eljuga, Domagoj; Milas, Ivan; Kirac, Iva; Stanec, Mladen; Vrdoljak, Danko Velimir

    2016-01-01

    Introduction Congenital melanocytic nevi (CMN) are present in 1–2% of newborn infants. The size of CMN defines the risk of developing melanoma which is estimated from 5–10%, especially in lesions that are located across the spine. Presentation of case Herein we report a case where nodular melanoma was discovered on the periphery of medium sized CMN in a high risk patient. After complete excision, the defect was reconstructed with random pattern, triple rhomboid flap. Discussion Melanoma that arose within medium sized CMN would leave a complex posterior lower trunk defect. We used a triple Limberg flap which was proven to be straightforward and simple method when large defects are to be covered with vital tissue. We have also showed that this type of reconstruction is suitable for high risk patients that could not withstand any complex procedures. Conclusion In our case, the method we choose to reconstruct the defect proved to be simple, safe and easy, especially when surgery is performed in a high risk patient. PMID:26826932

  5. Magnetic resonance imaging findings of nodular fasciitis in the mental region.

    PubMed

    Katada, Tsutomu; Tsuchimochi, Makoto; Oda, Takaaki; Sasaki, Yoshihiko; Toyama, Michio; Katagiri, Masataka

    2004-09-01

    Nodular fasciitis (NF) is a benign reactive lesion of the soft tissues related to the fascia and characterized by fibroblastic proliferation. The most common site is the upper extremities (46%), followed by the head and neck region (20%). In the orofacial region, the lesion typically develops within the subcutaneous structures overlying the angle and inferior border of the mandible and the zygoma. Magnetic resonance imaging (MRI) findings of NF in the orofacial region are almost unreported in the literature. In the present case report, we describe MRI findings of mental NF in a 19-year-old woman. MRI revealed a well-defined, round soft-tissue mass lying on the mentum. On T1-weighted MRI, the lesion was isointense to skeletal muscle; it was hyperintense to skeletal muscle on T2-weighted MRI, and was enhanced by Gd-diethylenetriamine pentaacetic acid (DTPA). Histologic examination revealed abundant myxoid degeneration dispersed in the lesion. The T2-weighted higher heterogeneous signal intensity was likely due to abundant myxoid degeneration or the cellular component of the lesion. A strong bright signal intensity belt appeared in the periphery of the lesion on Gd-DTPA enhancement. This rim enhancement appeared to represent small arterioles and venules that were visible in the peripheral area on histologic examination. PMID:15490310

  6. Undifferentiated metastatic renal cell carcinoma presenting as a cutaneous nodular lesion.

    PubMed

    Paolino, Giovanni; Lido, Paolo; Bei, Roberto; Polisca, Patrizio

    2015-12-01

    Cutaneous metastases may be the first sign of clinically silent visceral cancer. Approximately 30% of patients with primary renal cell carcinoma present with metastatic disease, and only 8% of them have skin metastases. We present the case of a 59-year-old male patient with a subcutaneous nodular on the upper chest extending to the jugular region. The lesion appeared skin colored and was not painful and 5 cm × 3.5 cm in diameter. The histological examination of the cutaneous biopsy showed an infiltration of undifferentiated epithelial cells positive to cytokeratins AE1/AE3, whereas they were negative to CK-20, CK5/6, cluster of differentiation 10, vimentin, thyroid transcription factor-1, S-100, human melanoma black-45, hepatocyte-specific antigen, carcinoembryonic antigen, and chromogranin A. A total-body computed tomography (CT) showed the presence of a tumoral lesion in the left kidney with multiple metastases in the lung, brain, and bones. According to the cutaneous biopsy and total-body CT, a final diagnosis of an undifferentiated renal carcinoma presenting as a subcutaneous metastasis was made. A chemotherapeutic treatment with gemcitabine and cisplatin resulted in the stabilization of the renal and metastatic lesions with an improvement in the quality of life of the patient. Considering that the prognosis of patients with cutaneous metastases is very poor, it is necessary to obtain an appropriate diagnosis in order to identify patients with treatable disease with the purpose of starting a therapeutic protocol. PMID:26623153

  7. Characterization of Hepatic Adenoma and Focal Nodular Hyperplasia with Gadoxetic Acid

    PubMed Central

    Mohajer, Kiyarash; Frydrychowicz, Alex; Robbins, Jessica B.; Loeffler, Agnes G.; Reed, Thomas D; Reeder, Scott B.

    2013-01-01

    Purpose To characterize imaging features of histologically proven hepatic adenoma (HA) as well as histologically and/or radiologically proven focal nodular hyperplasia (FNH) using delayed hepatobiliary MR imaging with 0.05mmol/kg gadoxetic acid. Materials and Methods Five patients with six HAs with histological correlation were retrospectively identified on liver MRI studies performed with gadoxetic acid, and T1-weighted imaging acquired during the delayed hepatobiliary phase. Additionally, 23 patients with 34 radiologically diagnosed FNH lesions (interpreted without consideration of delayed imaging) were identified, two of which also had histological confirmation. Signal intensity ratios relative to adjacent liver were measured on selected imaging sequences. Results All six hepatic adenomas (100%), which had histological confirmation, demonstrated hypointensity relative to adjacent liver on delayed imaging. Further, all of the FNH (including 34 radiologically proven, 2 of which were also histologically proven) were either hyperintense (23/34, 68%) or isointense (11/34, 32%) relative to the adjacent liver on delayed imaging. None of the FNHs were hypointense relative to liver. Conclusion Distinct imaging characteristics of HA versus FNH on delayed gadoxetic acid-enhanced MRI, with adenomas being hypointense and FNH being iso- or hyperintense on delayed imaging may improve specificity for characterization, and aid in the differentiation of these two lesions. PMID:22674623

  8. Ultrasonographic Differentiation Between Nodular Hyperplasia and Neoplastic Follicular-Patterned Lesions of the Thyroid Gland.

    PubMed

    Song, Yong Sub; Kim, Ji-Hoon; Na, Dong Gyu; Min, Hye Sook; Won, Jae-Kyung; Yun, Tae Jin; Choi, Seung Hong; Sohn, Chul-Ho

    2016-08-01

    We evaluate the gray-scale ultrasonographic characteristics that differentiate between nodular hyperplasia (NH) and neoplastic follicular-patterned lesions (NFPLs) of the thyroid gland. Ultrasonographic features of 750 patients with 832 thyroid nodules (NH, n = 361; or NFPLs, follicular adenoma, n = 123; follicular carcinoma, n = 159; and follicular variant papillary carcinoma, n = 189) were analyzed. Except for echogenicity, over two-thirds of the cases of NH and NFPLs share the ultrasonographic characteristics of solid internal content, a well-defined smooth margin and round-to-ovoid shape. Independent predictors for NH were non-solid internal content (sensitivity 27.1%, specificity 90.2%), isoechogenicity (sensitivity 69.5%, specificity 63.5%) and an ill-defined margin (sensitivity 18.8%, specificity 94.5%). Independent predictors for NFPLs were hypoechogenicity (sensitivity 60.5%, specificity 70.4%), marked hypoechogenicity (sensitivity 2.8%, specificity 99.4%) and taller-than-wide shape (sensitivity 6.6%, specificity 98.1%). Although NH and NFPLs commonly share ultrasonographic characteristics, non-solid internal content and ill-defined margin are specific to NH and marked hypoechogenicity and taller-than-wide shape are specific to NFPLs. PMID:27166018

  9. Highly recurrent mutations of SGK1, DUSP2 and JUNB in nodular lymphocyte predominant Hodgkin lymphoma.

    PubMed

    Hartmann, S; Schuhmacher, B; Rausch, T; Fuller, L; Döring, C; Weniger, M; Lollies, A; Weiser, C; Thurner, L; Rengstl, B; Brunnberg, U; Vornanen, M; Pfreundschuh, M; Benes, V; Küppers, R; Newrzela, S; Hansmann, M-L

    2016-04-01

    Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)-a subtype of Hodgkin lymphoma (HL)-is characterized by a low content of tumor cells, the lymphocyte predominant (LP) cells. Transformation into diffuse large B-cell lymphoma (DLBCL) occurs in about 10% of patients. We performed whole-genome mutation analysis of the DLBCL components from two composite lymphomas consisting of clonally related NLPHL and DLBCL as a means to identify candidate tumor suppressor genes and oncogenes in NLPHL. The analysis of LP cells for selected mutations of the DLBCL revealed that most mutations are also present in the LP cells, indicating a close relationship between the two components. The analysis of 62 selected genes in NLPHL by targeted ultra-deep sequencing revealed three novel highly recurrently mutated genes (each mutated in ~50% of cases), that is, DUSP2, SGK1 and JUNB. SGK1 was expressed in the LP cells of primary NLPHL cases and in the NLPHL cell line DEV. Administration of an SGK1 inhibitor induced apoptosis in the NLPHL cell line DEV and the DLBCL cell line Farage, suggesting a pathogenetic role of SGK1 in the LP and DLBCL cells. In summary, the present study identifies SGK1, DUSP2 and JUNB as novel key players in the pathogenesis of NLPHL. PMID:26658840

  10. Midkine: A Novel Biomarker to Predict Malignancy in Patients with Nodular Thyroid Disease

    PubMed Central

    Kuzu, Fatih; Arpaci, Dilek; Altas, Ayfer; Haytaoglu, Gürkan; Can, Murat; Barut, Figen; Kokturk, Furuzan; Ilikhan, Sevil Uygun; Bayraktaroglu, Taner

    2016-01-01

    Background. Midkine (MK), a new heparin-binding growth factor, plays important roles in a variety of biological phenomena such as carcinogenesis, inflammation, and angiogenesis. In this study, we aimed to evaluate serum midkine (SMK) and nodular midkine (NMK) levels in patients with thyroid nodules to predict malignancy and whether there was any association between. Methods. A total of 105 patients (74 women, 31 men) with thyroid nodules were enrolled. The levels of SMK and NMK were measured. Any possible correlation between SMK, NMK, and biochemical, cytopathological, or radiological variables was investigated. Results. Both SMK and NMK were found to be higher in hypoechoic nodules with an irregular border and without a halo (p < 0.05). Serum MK levels were significantly higher in nodules with microcalcifications than nodules with macrocalcification or without calcification (p = 0.001). SMK levels were found to be correlated with NMK levels (SMK 0.63 ng/ml versus 1.04 ng/mL and NMK 0.55 ng/mL versus 0.55 ng/mL, r2 = 0.54, p < 0.001). Conclusion. Both SMK and NMK can predict tumorigenesis of highly malignant/suspicious thyroid cytopathology and also well correlated with sonographic features of thyroid nodules. We suggest that MK levels may serve as an alternative biomarker, in conjunction with the cytopathological results in preoperative assessment of thyroid nodules. PMID:27446208

  11. Focal nodular hyperplasia of the liver: an emerging complication of hematopoietic SCT in children.

    PubMed

    Pillon, M; Carucci, N S; Mainardi, C; Carraro, E; Zuliani, M; Chemello, L; Calore, E; Tumino, M; Varotto, S; Toffolutti, T; Destro, R; Gazzola, M V; Alaggio, R; Basso, G; Messina, C

    2015-03-01

    Hepatic focal nodular hyperplasia (FNH) is a nonmalignant condition rarely affecting children previously treated for cancer, especially those who received hematopoietic SCT (HSCT). Some aspects of its pathogenesis still remain unclear and a strong association with specific risk factors has not yet been identified. We report here a single institution's case series of 17 patients who underwent HSCT and were diagnosed with FNH, analyzing retrospectively their clinical features and the radiological appearance of their hepatic lesions. We aimed to compare the diagnostic accuracy of ultrasound (US) and magnetic resonance imaging (MRI) and to explore the role of transient elastography (FibroScan) to evaluate the degree of hepatic fibrosis in FNH patients. Our analysis showed an association of FNH with age at transplant ⩽12 years (hazard ratio (HR) 9.10); chronic GVHD (HR 2.99); hormone-replacement therapy (HR 4.02) and abdominal radiotherapy (HR 4.37). MRI proved to be a more accurate diagnostic tool compared with US. Nine out of 12 patients who underwent FibroScan showed hepatic fibrosis. Our study points out that FNH is an emerging complication of HSCT, which requires a lifelong surveillance to follow its course in cancer patients. PMID:25581411

  12. [Current status of diagnostic imaging of focal nodular hyperplasia of the liver].

    PubMed

    Uggowitzer, M M; Kugler, C; Ruppert-Kohlmayr, A; Groell, R; Raith, J; Schreyer, H

    2000-09-01

    Ranging behind hemangiomas, focal nodular hyperplasias (FNH) are the second most common benign solid liver lesions. Women between the age of 20 and 50 years are predominantly affected. In rare cases FNH may occur in children. Etiologically, an arteriovenous vascular malformation of the liver is discussed, which causes pseudotumorous growth of the surrounding liver parenchyma. Morphological features such as the presence of a radial vascular architecture and feeding arteries within a central scar are characteristic for the presence of FNH. Imaging techniques which enable the depiction of the arterial blood supply with a characteristic centrifugal filling pattern, the contrast enhancement in the early arterial phase, the absence of calcifications and of a tumour capsule and the typical enhancement of the central scar, are of particular importance. Knowledge of these features is important in order to differentiate FNH from other hypervascular focal liver lesions with tendency of scar formation, such as hepatic adenomas, giant hemangiomas, hepatocellular and fibrolamellar carcinomas, and metastases. Diagnosis and differential diagnosis of FNH will be enabled by a combined modality approach consisting of (Doppler) sonography and triphasic CT. To confirm the diagnosis of FNH, dynamic MRI is advisable. Because of the invasiveness of angiography as well as the limited sensitivity and spatial resolution of the various scintigraphic methods, these modalities no longer play a role in the diagnostic work-up of FNH. Lesions lacking typical features diagnostic for FNH remain subjects for biopsy and histological examination. PMID:11079084

  13. Nodular regenerative hyperplasia: Evolving concepts on underdiagnosed cause of portal hypertension

    PubMed Central

    Hartleb, Marek; Gutkowski, Krzysztof; Milkiewicz, Piotr

    2011-01-01

    Nodular regenerative hyperplasia (NRH) is a rare liver condition characterized by a widespread benign transformation of the hepatic parenchyma into small regenerative nodules. NRH may lead to the development of non-cirrhotic portal hypertension. There are no published systematic population studies on NRH and our current knowledge is limited to case reports and case series. NRH may develop via autoimmune, hematological, infectious, neoplastic, or drug-related causes. The disease is usually asymptomatic, slowly or non-progressive unless complications of portal hypertension develop. Accurate diagnosis is made by histopathology, which demonstrates diffuse micronodular transformation without fibrous septa. Lack of perinuclear collagen tissue distinguishes NRH from typical regenerative nodules in the cirrhotic liver. While the initial treatment is to address the underlying disease, ultimately the therapy is directed to the management of portal hypertension. The prognosis of NRH depends on both the severity of the underlying illness and the prevention of secondary complications of portal hypertension. In this review we detail the epidemiology, pathogenesis, diagnosis, management, and prognosis of NRH. PMID:21472097

  14. Multifocal Nodular Fatty Infiltration of the Liver: A Case Report of a Challenging Diagnostic Problem

    PubMed Central

    Tebala, Giovanni Domenico; Jwad, Anees; Khan, Abdul Quyyum; Long, Ervine; Sissons, Guy

    2016-01-01

    Patient: Female, 59 Final Diagnosis: Multifocal nodular fatty infiltration of the liver Symptoms: None Medication: — Clinical Procedure: Laparoscopy Specialty: Surgery Objective: Rare disease Background: Fatty infiltration of the liver usually has a diffuse pattern, but in very rare cases it presents as multiple focal lesions of the liver, mimicking metastases. A correct diagnosis is crucial to address prognosis and eventual treatment. Case Report: We present the case of a completely fit and asymptomatic patient referred for multiple bilateral liver metastases of unknown origin. She had no previous history of malignancy. She was extensively investigated with all locally available methods, including ultrasound scan, computed tomography, magnetic resonance imaging, upper and lower gastrointestinal endoscopy, and diagnostic laparoscopy. Imaging-guided biopsy and laparoscopic biopsy confirmed the diagnosis of multifocal fatty infiltration of the liver. Conclusions: The diagnosis of this condition can be challenging and an accurate initial clinical history must be part of a thorough clinical examination. Multimodal imaging is mandatory, but diagnostic laparoscopy with direct macrobiopsy may be necessary to clear all doubts. PMID:27017525

  15. Subcutaneous Panniculitis-Like T Cell Lymphoma Mimicking Early-Onset Nodular Panniculitis

    PubMed Central

    Shen, Guifen; Dong, Lingli; Zhang, Shengtao

    2016-01-01

    Patient: Male, 24 Final Diagnosis: Subcutaneous panniculitis-like T-cell lymphoma Symptoms: Fever • skin nodules Medication: — Clinical Procedure: Skin biopsy • PET-CT Specialty: Hematology Objective: Rare disease Background: Subcutaneous panniculitis-like T cell lymphoma is a very uncommon subtype of cutaneous T cell lymphoma. The manifestations of this rare disease are atypical at onset, and may mimic some rheumatic or dermatologic diseases, which causes the delay of diagnosis and treatment. Case Report: We report a 24-year-old man suffering from intermittent fever and skin nodules on the left anterior chest wall, who was initially misdiagnosed with nodular panniculitis and finally diagnosed with subcutaneous panniculitis-like T cell lymphoma through repeat examination of biopsy of the skin nodule. Positron emission tomography revealed extracutaneous adipose tissue involvement. Subsequently, hemophagocytic syndrome occurred while under a conventional dose of glucocorticoid, but remission was induced by treatment with cyclosporine A and high doses of dexamethasone. Conclusions: In order to avoid the delay diagnosis and inappropriate treatment of subcutaneous panniculitis-like T cell lymphoma, in addition to a thorough physical examination, PET-CT and disease-specific pathologic, immunophenotypic, and T cell receptor tests of the skin biopsy should be performed. Extracutaneous involvement, especially hemophagocytic syndrome, indicated worse prognosis. Even so, cyclosporine A plus high-dose corticosteroid could be an option of treatment. PMID:27342380

  16. A de novo frameshift in HNRNPK causing a Kabuki-like syndrome with nodular heterotopia.

    PubMed

    Lange, L; Pagnamenta, A T; Lise, S; Clasper, S; Stewart, H; Akha, E S; Quaghebeur, G; Knight, S J L; Keays, D A; Taylor, J C; Kini, U

    2016-09-01

    Kabuki syndrome is a heterogeneous condition characterized by distinctive facial features, intellectual disability, growth retardation, skeletal abnormalities and a range of organ malformations. Although at least two major causative genes have been identified, these do not explain all cases. Here we describe a patient with a complex Kabuki-like syndrome that included nodular heterotopia, in whom testing for several single-gene disorders had proved negative. Exome sequencing uncovered a de novo c.931_932insTT variant in HNRNPK (heterogeneous nuclear ribonucleoprotein K). Although this variant was identified in March 2012, its clinical relevance could only be confirmed following the August 2015 publication of two cases with HNRNPK mutations and an overlapping phenotype that included intellectual disability, distinctive facial dysmorphism and skeletal/connective tissue abnormalities. Whilst we had attempted (unsuccessfully) to identify additional cases through existing collaborators, the two published cases were 'matched' using GeneMatcher, a web-based tool for connecting researchers and clinicians working on identical genes. Our report therefore exemplifies the importance of such online tools in clinical genetics research and the benefits of periodically reviewing cases with variants of unproven significance. Our study also suggests that loss of function variants in HNRNPK should be considered as a molecular basis for patients with Kabuki-like syndrome. PMID:26954065

  17. Cellular localization of CIP2A determines its prognostic impact in superficial spreading and nodular melanoma.

    PubMed

    Flørenes, Vivi Ann; Emilsen, Elisabeth; Dong, Hiep Phuc; Førsund, Mette; Holm, Ruth; Slipicevic, Ana

    2015-06-01

    Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an important oncogene contributing to cancer progression partially by regulating cMYC and AKT. We examined CIP2A expression in cutaneous melanomas, its association with clinicopathological parameters and mapped molecular mechanisms regulated by CIP2A in vitro. CIP2A expression was analyzed by immunohistochemistry in 17 nevi, 132 primary melanomas and 49 metastases. Effects of siRNA-mediated down-regulation on proliferation, apoptosis and signaling pathways were assessed in melanoma cell lines. In superficial spreading melanomas (SSM), high nuclear CIP2A expression was associated with poor overall survival (OS) (P = 0.0018). Surprisingly, high cytoplasmic expression was related to improved relapse-free (P = 0.031) and OS (P = 0.014) in nodular melanomas (NM). In vitro experiments revealed that CIP2A can regulate proliferation and/or apoptosis partially through the PI3K/AKT pathway but also independently. In summary, CIP2A could represent a potential therapeutic target in SSM. However, in NM cytoplasmic CIP2A is associated with improved prognosis indicating that CIP2A has distinct, complex functions dependent on the molecular context and histological subtype. As seen in other cancer types, CIP2A can influence cMYC and AKT, but our data also suggest that in melanoma it has additional targets which need to be identified. PMID:25663244

  18. The Use of HPLC for the Characterization of Phytoplankton Pigments.

    PubMed

    Garrido, José L; Roy, Suzanne

    2015-01-01

    HPLC is still the technique of choice for the analysis and characterization of phytoplankton pigments. In this chapter we describe procedures for sample preparation and pigment extraction, and the use of octyl silica columns and pyridine-containing mobile phases to separate chlorophylls and carotenoids. The identification of pigments on the basis of their retention times and visible spectra, the preparation of pigment standards, and the quantitative analysis by either external or internal standard procedures are also described. PMID:26108510

  19. The peripheral clock regulates human pigmentation.

    PubMed

    Hardman, Jonathan A; Tobin, Desmond J; Haslam, Iain S; Farjo, Nilofer; Farjo, Bessam; Al-Nuaimi, Yusur; Grimaldi, Benedetto; Paus, Ralf

    2015-04-01

    Although the regulation of pigmentation is well characterized, it remains unclear whether cell-autonomous controls regulate the cyclic on-off switching of pigmentation in the hair follicle (HF). As human HFs and epidermal melanocytes express clock genes and proteins, and given that core clock genes (PER1, BMAL1) modulate human HF cycling, we investigated whether peripheral clock activity influences human HF pigmentation. We found that silencing BMAL1 or PER1 in human HFs increased HF melanin content. Furthermore, tyrosinase expression and activity, as well as TYRP1 and TYRP2 mRNA levels, gp100 protein expression, melanocyte dendricity, and the number gp100+ HF melanocytes, were all significantly increased in BMAL1 and/or PER1-silenced HFs. BMAL1 or PER1 silencing also increased epidermal melanin content, gp100 protein expression, and tyrosinase activity in human skin. These effects reflect direct modulation of melanocytes, as BMAL1 and/or PER1 silencing in isolated melanocytes increased tyrosinase activity and TYRP1/2 expression. Mechanistically, BMAL1 knockdown reduces PER1 transcription, and PER1 silencing induces phosphorylation of the master regulator of melanogenesis, microphthalmia-associated transcription factor, thus stimulating human melanogenesis and melanocyte activity in situ and in vitro. Therefore, the molecular clock operates as a cell-autonomous modulator of human pigmentation and may be targeted for future therapeutic strategies. PMID:25310406

  20. Human pigmentation genes under environmental selection

    PubMed Central

    2012-01-01

    Genome-wide association studies and comparative genomics have established major loci and specific polymorphisms affecting human skin, hair and eye color. Environmental changes have had an impact on selected pigmentation genes as populations have expanded into different regions of the globe. PMID:23110848

  1. "Dry-column" chromatography of plant pigments

    NASA Technical Reports Server (NTRS)

    Woeller, F. H.; Lehwalt, M. F.; Oyama, V. I.

    1973-01-01

    Separation of plant pigments which can be accomplished on thin-layer silica plates with mixture of petroleum ether, halocarbon, acetone, and polar solvent can be readily translated into dry-column technique that yields reproducible chromatograms after elution in fashion of liquid chromatography with fluorimeter as detector. Best solvent system was found to be mixture of petroleum ether, dichloromethane, acetone, and ethyl acetate.

  2. Retinal pigment epithelial hamartoma--unusual manifestations.

    PubMed Central

    Rosenberg, P. R.; Walsh, J. B.

    1984-01-01

    Hamartoma of the retinal pigment epithelium is an uncommon tumour of young adults. We have seen 2 patients with this clinical diagnosis, both with unusual manifestations. In one patient growth of the tumour was observed over a 5-year period. In the second patient arterial-arterial anastomoses were detected at a site distal to the tumour. Images PMID:6722077

  3. Production of a Sporulation Pigment by Streptomyces venezuelae

    PubMed Central

    Scribner, H. E.; Tang, Terry; Bradley, S. G.

    1973-01-01

    Streptomyces venezuelae S13 produced a pH-indicating sporulation pigment on a glucose-salts-agar medium consisting of glucose, KNO3, MgSO4, and Na2HPO4, pH 7. Pigmentation on this medium appeared to be closely associated with sporulation, which normally required 5 to 7 days at 30 C. The pigment was soluble in water as well as in a number of organic solvents. Butanol-extracted pigment exhibited absorption maxima at 430 and 520 nm at pH 3 and 12, respectively. Although many salts of organic acids and amino acids could replace glucose as the sole carbon source in basal salts-agar medium for growth and pigmentation, most sugars that were tested supported good growth but negligible pigmentation. Among the nitrogenous substances tested, KNO3 was most desirable for pigmentation. The organism did not exhibit any specific requirements for divalent cations with respect to growth and pigmentation. In the absence of MgSO4, however, glucose-salts-agar prepared by autoclaving all components together failed to support growth. The production of the sporulation pigment on glucose-salts-agar was comparable to that obtained on tomato paste-oatmeal-agar medium. Incorporation of partially purified pigment material into broth medium that did not normally support sporulation induced sporulation, and amino acid-salts-agar medium could induce vegetative mycelia to pigment when transferred from medium that did not support either pigmentation or sporulation. Images PMID:4577487

  4. Neurotized Congenital Melanocytic Nevus Resembling a Pigmented Neurofibroma

    PubMed Central

    Singh, Nidhi; Chandrashekar, Laxmisha; Kar, Rakhee; Sylvia, Mary Theresa; Thappa, Devinder Mohan

    2015-01-01

    Neurotized congenital melanocytic nevus and pigmented neurofibroma (PNF) are close mimics and pose a clinicopathological challenge. We present a case of pigmented hypertrichotic plaque over lumbosacral region and discuss the differential diagnosis and its clinical, histopathological and immunohistochemistry features which may aid in differentiation. We highlight the difficulties faced in differentiating neurotized congenital melanocytic nevus from pigmented neurofibroma. PMID:25657396

  5. The determination and optimization of (rutile) pigment particle size distributions

    NASA Technical Reports Server (NTRS)

    Richards, L. W.

    1972-01-01

    A light scattering particle size test which can be used with materials having a broad particle size distribution is described. This test is useful for pigments. The relation between the particle size distribution of a rutile pigment and its optical performance in a gray tint test at low pigment concentration is calculated and compared with experimental data.

  6. 21 CFR 73.3128 - Mica-based pearlescent pigments.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Mica-based pearlescent pigments. 73.3128 Section... pigments. (a) Identity and specifications. The color additive is formed by depositing titanium or iron... pigments listed in paragraph (a) of this section may be used as a color additive in contact lenses...

  7. 21 CFR 73.350 - Mica-based pearlescent pigments.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Mica-based pearlescent pigments. 73.350 Section 73... LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.350 Mica-based pearlescent pigments. (a... pearlescent pigments may contain only those diluents listed in this subpart as safe and suitable for use...

  8. 21 CFR 73.3128 - Mica-based pearlescent pigments.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Mica-based pearlescent pigments. 73.3128 Section... pigments. (a) Identity and specifications. The color additive is formed by depositing titanium or iron... pigments listed in paragraph (a) of this section may be used as a color additive in contact lenses...

  9. 21 CFR 73.350 - Mica-based pearlescent pigments.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Mica-based pearlescent pigments. 73.350 Section 73... LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.350 Mica-based pearlescent pigments. (a... pearlescent pigments may contain only those diluents listed in this subpart as safe and suitable for use...

  10. 21 CFR 73.1350 - Mica-based pearlescent pigments.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Mica-based pearlescent pigments. 73.1350 Section... LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1350 Mica-based pearlescent pigments. (a...-based pearlescent pigments may contain only those diluents listed in this subpart as safe and...

  11. 21 CFR 73.1350 - Mica-based pearlescent pigments.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Mica-based pearlescent pigments. 73.1350 Section... LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1350 Mica-based pearlescent pigments. (a...-based pearlescent pigments may contain only those diluents listed in this subpart as safe and...

  12. Dimerization of visual pigments in vivo.

    PubMed

    Zhang, Tao; Cao, Li-Hui; Kumar, Sandeep; Enemchukwu, Nduka O; Zhang, Ning; Lambert, Alyssia; Zhao, Xuchen; Jones, Alex; Wang, Shixian; Dennis, Emily M; Fnu, Amrita; Ham, Sam; Rainier, Jon; Yau, King-Wai; Fu, Yingbin

    2016-08-01

    It is a deeply engrained notion that the visual pigment rhodopsin signals light as a monomer, even though many G protein-coupled receptors are now known to exist and function as dimers. Nonetheless, recent studies (albeit all in vitro) have suggested that rhodopsin and its chromophore-free apoprotein, R-opsin, may indeed exist as a homodimer in rod disk membranes. Given the overwhelmingly strong historical context, the crucial remaining question, therefore, is whether pigment dimerization truly exists naturally and what function this dimerization may serve. We addressed this question in vivo with a unique mouse line (S-opsin(+)Lrat(-/-)) expressing, transgenically, short-wavelength-sensitive cone opsin (S-opsin) in rods and also lacking chromophore to exploit the fact that cone opsins, but not R-opsin, require chromophore for proper folding and trafficking to the photoreceptor's outer segment. In R-opsin's absence, S-opsin in these transgenic rods without chromophore was mislocalized; in R-opsin's presence, however, S-opsin trafficked normally to the rod outer segment and produced functional S-pigment upon subsequent chromophore restoration. Introducing a competing R-opsin transmembrane helix H1 or helix H8 peptide, but not helix H4 or helix H5 peptide, into these transgenic rods caused mislocalization of R-opsin and S-opsin to the perinuclear endoplasmic reticulum. Importantly, a similar peptide-competition effect was observed even in WT rods. Our work provides convincing evidence for visual pigment dimerization in vivo under physiological conditions and for its role in pigment maturation and targeting. Our work raises new questions regarding a potential mechanistic role of dimerization in rhodopsin signaling. PMID:27462111

  13. Pediatric Adrenocortical Tumors: What They Can Tell Us on Adrenal Development and Comparison with Adult Adrenal Tumors

    PubMed Central

    Lalli, Enzo; Figueiredo, Bonald C.

    2015-01-01

    Adrenocortical tumors (ACT) in children are very rare and are most frequently diagnosed in the context of the Li-Fraumeni syndrome, a multiple cancer syndrome linked to germline mutations of the tumor suppressor gene TP53 with loss of heterozygosity in the tumors. A peak of children ACT incidence is present in the states of southern Brazil, where they are linked to the high prevalence in the population of a specific TP53 mutation (R337H). Children ACT have specific features distinguishing them from adult tumors in their pathogenetic mechanisms, genomic profiles, and prognosis. Epidemiological and molecular evidence suggests that in most cases they are derived from the fetal adrenal. PMID:25741319

  14. Adrenocortical function during prolonged treatment with clobetasone butyrate in children with chronic atopic dermatitis and elevated IgE levels.

    PubMed

    Boner, A L; Richelli, C; De Stefano, G; Antolini, I; Aprili, F; Mengoni, M

    1985-01-01

    Twelve children with chronic atopic dermatitis and elevated IgE levels (age range: 2-13 years; mean age = 8.2 +/- 3.5 years) were selected for the study and treated with clobetasone butyrate (0.05% cream) thrice daily during the first week, then twice daily for three weeks. Adrenocortical function was evaluated at the beginning and the end of treatment period. The results show that there was no statistically significant change in adrenal function during the study period (tetracosactrin test). The results of the immunological studies, namely total IgE using the paper disc radioimmunoassay technique, specific IgE using the radioallergosorbent test and immunoglobulin levels are given. PMID:4018942

  15. Differential Effects of Etomidate and its Pyrrole Analogue Carboetomidate on the Adrenocortical and Cytokine Responses to Endotoxemia

    PubMed Central

    Pejo, Ervin; Feng, Yan; Chao, Wei; Cotten, Joseph F; Ge, Ri Le; Raines, Douglas E

    2011-01-01

    Objective We developed a novel pyrrole analogue of etomidate, (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate), which retains etomidate’s desirable anesthetic and hemodynamic properties but lacks its potent inhibitory affect on adrenocorticotropic hormone-stimulated steroid synthesis. The objective of this study was to test the hypothesis that in contrast to etomidate, carboetomidate neither suppresses the adrenocortical response to endotoxemia nor enhances the accompanying production of pro-inflammatory cytokines. Design Animal study Setting University research laboratory Subjects Male Sprague-Dawley rats Interventions For both single and multiple anesthetic dose studies, rats were injected with Escherichia coli lipopolysaccharide immediately followed by a hypnotic dose of etomidate, carboetomidate or vehicle alone (dimethyl sulfoxide) as a control. For single dose studies, no additional anesthetic (or vehicle) was administered. For multiple anesthetic dose studies, additional doses of anesthetic (or vehicle) were administered every 15 min for a total of eight anesthetic (or vehicle) doses. Measurements and Main Results Plasma adrenocorticotropic hormone, corticosterone, and cytokine concentrations were measured before lipopolysaccharide administration and intermittently throughout the 5 hour experiment. In single anesthetic dose studies, plasma adrenocorticotropic hormone and cytokine concentrations were not different at any time point among the etomidate, carboetomidate, and vehicle groups whereas plasma corticosterone concentrations were briefly (60–120 min) reduced in the etomidate group. In multiple anesthetic dose studies, plasma corticosterone concentrations were persistently lower and peak plasma IL-1β and IL-6 concentrations were higher in the etomidate group versus the carboetomidate and control groups. Peak plasma IL-10 concentrations were similarly elevated in the etomidate and carboetomidate groups versus the control group

  16. Assessment of adrenocortical activity by non-invasive measurement of faecal cortisol metabolites in dromedary camels (Camelus dromedarius).

    PubMed

    Sid-Ahmed, Omer-Elfaroug; Sanhouri, Ahmed; Elwaseela, Badr-Eldin; Fadllalah, Imad; Mohammed, Galal-Eldin Elazhari; Möstl, Erich

    2013-08-01

    The aim of this study was to determine whether glucocorticoid production could be monitored non-invasively in dromedary camels by measuring faecal cortisol metabolites (FCMs). Five Sudanese dromedaries, two males and three females, were injected with a synthetic adrenocorticotropic hormone (ACTH) analogue. Blood samples were collected pre- and post-ACTH injection. Faeces were sampled after spontaneous defecation for five consecutive days (2 days before and 3 days after ACTH injection). Baseline plasma cortisol values ranged from 0.6 to 10.8 ng/ml in males and from 1.1 to 16.6 ng/ml in females, while peak values after ACTH injection were 10.9-41.9 in males and 10-42.2 ng/ml in females. Peak blood cortisol values were reached between 1.5 and 2.0 h after ACTH injection. The concentration of FCMs increased after ACTH injection in the faeces of both sexes, although steroid levels peaked earlier in males [24 h; (286.7-2,559.7 ng/g faeces)] than in females [36-48 h; (1,182.6-5,169.1 ng/g faeces)], reflecting increases of 3.1-8.3- and 4.3-8-fold above baseline levels. To detect chromatographic patterns of immunoreactive FCMs, faecal samples with high FCM concentrations from both sexes were pooled and subjected to reverse phase high performance liquid chromatography (RP-HPLC). RP-HPLC analysis revealed sex differences in the polarity of FCMs, with females showing more polar FCMs than males. We concluded that stimulation of adrenocortical activity by ACTH injection resulted in a measurable increase in blood cortisol that was reliably paralleled by increases in FCM levels. Thus, measurement of FCMs is a powerful tool for monitoring the adrenocortical responses of dromedaries to stressors in field conditions. PMID:23430659

  17. Validation of a Fecal Glucocorticoid Assay to Assess Adrenocortical Activity in Meerkats Using Physiological and Biological Stimuli

    PubMed Central

    Heistermann, Michael; Santema, Peter; Dantzer, Ben; Mausbach, Jelena; Ganswindt, Andre; Manser, Marta B.

    2016-01-01

    In mammals, glucocorticoid (i.e. GC) levels have been associated with specific life-history stages and transitions, reproductive strategies, and a plethora of behaviors. Assessment of adrenocortical activity via measurement of glucocorticoid metabolites in feces (FGCM) has greatly facilitated data collection from wild animals, due to its non-invasive nature, and thus has become an established tool in behavioral ecology and conservation biology. The aim of our study was to validate a fecal glucocorticoid assay for assessing adrenocortical activity in meerkats (Suricata suricatta), by comparing the suitability of three GC enzyme immunoassays (corticosterone, 11β-hydroxyetiocholanolone and 11oxo-etiocholanolone) in detecting FGCM increases in adult males and females following a pharmacological challenge with adrenocorticotropic hormone (ACTH) and biological stimuli. In addition, we investigated the time course characterizing FGCM excretion, the effect of age, sex and time of day on FGCM levels and assessed the potential effects of soil contamination (sand) on FGCM patterns. Our results show that the group specific 11β-hydroxyetiocholanolone assay was most sensitive to FGCM alterations, detecting significant and most distinctive elevations in FGCM levels around 25 h after ACTH administration. We found no age and sex differences in basal FGCM or on peak response levels to ACTH, but a marked diurnal pattern, with FGCM levels being substantially higher in the morning than later during the day. Soil contamination did not significantly affect FGCM patterns. Our results emphasize the importance of conducting assay validations to characterize species-specific endocrine excretion patterns, a crucial step to all animal endocrinology studies using a non-invasive approach. PMID:27077741

  18. Regulation of corticotropin receptor number and messenger RNA in cultured human adrenocortical cells by corticotropin and angiotensin II.

    PubMed Central

    Lebrethon, M C; Naville, D; Begeot, M; Saez, J M

    1994-01-01

    The regulation of ACTH receptor binding sites and mRNA by ACTH and angiotensin II (A-II) was studied using cultured human adrenal fasciculata reticularis cells (HAC). These cells expressed two major ACTH receptor transcripts of 1.8 and 3.4 kb and three minor ones of 4, 7, and 11 kb. ACTH increased the levels of all these transcripts in a time- and dose-dependent manner. At a maximal concentration of 10(-8) M, ACTH enhanced 21- and 4-fold the level of ACTH receptor mRNA and the number of receptors per cell, respectively. Pretreatment of HAC with A-II produced a dose-dependent enhancement of ACTH receptor mRNA that was associated with an increase of both ACTH receptor number and responsiveness to this hormone. The effects of A-II were completely blocked by an AT1 receptor subtype antagonist but not by an AT2 antagonist. The effects of ACTH together with A-II on ACTH receptor mRNA were greater than those induced by each hormone alone. These results show that ACTH receptor number and mRNA are positively regulated by the two main hormones (ACTH and A-II) which, in vivo, regulate adrenocortical functions. In addition, they also show that HAC are a target for A-II. Thus, regulation of ACTH receptors may be one mechanism by which ACTH and A-II regulate adrenocortical functions under both normal and pathological conditions. Images PMID:8163681

  19. Age-related variation in the adrenocortical response to stress in nestling white storks (Ciconia ciconia) supports the developmental hypothesis.

    PubMed

    Blas, Julio; Baos, Raquel; Bortolotti, Gary R; Marchant, Tracy A; Hiraldo, Fernando

    2006-09-01

    The post-natal development of the adrenocortical response to stress was investigated in European white storks. Sixty wild nestlings aged 24-59 days old were subjected to a standardized capture and restraint protocol, and the time-course pattern of the response to stress was assessed through determination of circulating corticosterone in blood samples collected at five fixed times during the 45-min period following capture. The time course of the response was best fit to a third-order function of handling time, and showed a strong effect of age. Although age did not affect baseline titers and all birds showed a positive post-capture increase in circulating corticosterone, age had a positive effect on the relative increase from baseline titer, the recorded time to reach maximum level, and the acute concentration after 10 min following capture and restraint. While young nestlings displayed very little response to capture, the response near fledging resembled the typical adrenocortical pattern widely reported in fully developed birds. Our results concur with those found in altricial and semi-altricial species, and suggest that non-precocial birds follow a similar mode of development of the hypothalamic-pituitary-adrenal (HPA) axis. The fact that HPA sensitivity to stress is functional suggests that young storks gradually develop emergency responses of adaptive value and are able to overcome acute perturbations in spite of their parental dependence, at least during the last two-thirds of post-natal development. According to the Developmental Hypothesis, such gradual changes would allow nestlings to respond to perturbations as a function of the specific behavioral and physiological abilities of their age. The potential sources of stress that nestlings have to face during development (i.e., weather conditions, dietary restrictions, and social competition) are discussed according to developmental changes in behavioral and physiological abilities. PMID:16624312

  20. Validation of a Fecal Glucocorticoid Assay to Assess Adrenocortical Activity in Meerkats Using Physiological and Biological Stimuli.

    PubMed

    Braga Goncalves, Ines; Heistermann, Michael; Santema, Peter; Dantzer, Ben; Mausbach, Jelena; Ganswindt, Andre; Manser, Marta B

    2016-01-01

    In mammals, glucocorticoid (i.e. GC) levels have been associated with specific life-history stages and transitions, reproductive strategies, and a plethora of behaviors. Assessment of adrenocortical activity via measurement of glucocorticoid metabolites in feces (FGCM) has greatly facilitated data collection from wild animals, due to its non-invasive nature, and thus has become an established tool in behavioral ecology and conservation biology. The aim of our study was to validate a fecal glucocorticoid assay for assessing adrenocortical activity in meerkats (Suricata suricatta), by comparing the suitability of three GC enzyme immunoassays (corticosterone, 11β-hydroxyetiocholanolone and 11oxo-etiocholanolone) in detecting FGCM increases in adult males and females following a pharmacological challenge with adrenocorticotropic hormone (ACTH) and biological stimuli. In addition, we investigated the time course characterizing FGCM excretion, the effect of age, sex and time of day on FGCM levels and assessed the potential effects of soil contamination (sand) on FGCM patterns. Our results show that the group specific 11β-hydroxyetiocholanolone assay was most sensitive to FGCM alterations, detecting significant and most distinctive elevations in FGCM levels around 25 h after ACTH administration. We found no age and sex differences in basal FGCM or on peak response levels to ACTH, but a marked diurnal pattern, with FGCM levels being substantially higher in the morning than later during the day. Soil contamination did not significantly affect FGCM patterns. Our results emphasize the importance of conducting assay validations to characterize species-specific endocrine excretion patterns, a crucial step to all animal endocrinology studies using a non-invasive approach. PMID:27077741

  1. Clonality and allelotype analyses of focal nodular hyperplasia compared with hepatocellular adenoma and carcinoma

    PubMed Central

    Cai, Yi-Ran; Gong, Li; Teng, Xiao-Ying; Zhang, Hong-Tu; Wang, Cheng-Feng; Wei, Guo-Lian; Guo, Lei; Ding, Fang; Liu, Zhi-Hua; Pan, Qin-Jing; Su, Qin

    2009-01-01

    AIM: To identify clonality and genetic alterations in focal nodular hyperplasia (FNH) and the nodules derived from it. METHODS: Twelve FNH lesions were examined. Twelve hepatocellular adenomas (HCAs) and 22 hepatocellular carcinomas (HCCs) were used as references. Nodules of different types were identified and isolated from FNH by microdissection. An X-chromosome inactivation assay was employed to describe their clonality status. Loss of heterozygosity (LOH) was detected, using 57 markers, for genetic alterations. RESULTS: Nodules of altered hepatocytes (NAH), the putative precursors of HCA and HCC, were found in all the FNH lesions. Polyclonality was revealed in 10 FNH lesions from female patients, and LOH was not detected in any of the six FNH lesions examined, the results apparently showing their polyclonal nature. In contrast, monoclonality was demonstrated in all the eight HCAs and in four of the HCCs from females, and allelic imbalances were found in the HCAs (9/9) and HCCs (15/18), with chromosomal arms 11p, 13q and 17p affected in the former, and 6q, 8p, 11p, 16q and 17p affected in the latter lesions in high frequencies (≥ 30%). Monoclonality was revealed in 21 (40%) of the 52 microdissected NAH, but was not found in any of the five ordinary nodules. LOH was found in all of the 13 NAH tested, being highly frequent at six loci on 8p, 11p, 13q and 17p. CONCLUSION: FNH, as a whole, is polyclonal, but some of the NAH lesions derived from it are already neoplastic and harbor similar allelic imbalances as HCAs. PMID:19787833

  2. A glial origin for periventricular nodular heterotopia caused by impaired expression of Filamin-A.

    PubMed

    Carabalona, Aurelie; Beguin, Shirley; Pallesi-Pocachard, Emilie; Buhler, Emmanuelle; Pellegrino, Christophe; Arnaud, Karen; Hubert, Philippe; Oualha, Mehdi; Siffroi, Jean Pierre; Khantane, Sabrina; Coupry, Isabelle; Goizet, Cyril; Gelot, Antoinette Bernabe; Represa, Alfonso; Cardoso, Carlos

    2012-03-01

    Periventricular nodular heterotopia (PH) is a human brain malformation caused by defective neuronal migration that results in ectopic neuronal nodules lining the lateral ventricles beneath a normal appearing cortex. Most affected patients have seizures and their cognitive level varies from normal to severely impaired. Mutations in the Filamin-A (or FLNA) gene are the main cause of PH, but the underlying pathological mechanism remains unknown. Although two FlnA knockout mouse strains have been generated, none of them showed the presence of ectopic nodules. To recapitulate the loss of FlnA function in the developing rat brain, we used an in utero RNA interference-mediated knockdown approach and successfully reproduced a PH phenotype in rats comparable with that observed in human patients. In FlnA-knockdown rats, we report that PH results from a disruption of the polarized radial glial scaffold in the ventricular zone altering progression of neural progenitors through the cell cycle and impairing migration of neurons into the cortical plate. Similar alterations of radial glia are observed in human PH brains of a 35-week fetus and a 3-month-old child, harboring distinct FLNA mutations not previously reported. Finally, juvenile FlnA-knockdown rats are highly susceptible to seizures, confirming the reliability of this novel animal model of PH. Our findings suggest that the disorganization of radial glia is the leading cause of PH pathogenesis associated with FLNA mutations. Rattus norvegicus FlnA mRNA (GenBank accession number FJ416060). PMID:22076441

  3. Outcomes of liver resection in hepatocellular adenoma and focal nodular hyperplasia

    PubMed Central

    Bieze, Matthanja; Busch, Olivier R C; Tanis, Pieter J; Verheij, Joanne; Phoa, Saffire S K S; Gouma, Dirk J; van Gulik, Thomas M

    2014-01-01

    Objectives: The clinical management of hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH) is still subject to controversy, especially with respect to patient selection for surgery. The aim of this prospective cohort study was to assess the outcomes of surgical intervention. Methods: Between January 2008 and September 2012, patients diagnosed with FNH or HCA based on magnetic resonance imaging or computed tomography were enrolled in this prospective study. Resection was undertaken in patients with HCA of >5 cm or symptomatic lesions. Lesion characteristics, extent of liver resection (minor: fewer than three segments; major: three or more segments), morbidity (by Dindo–Clavien class), mortality, postoperative length of stay and symptoms [McGill Pain Questionnaire, including a visual analogue scale (VAS)] were evaluated. Results: A total of 110 patients (106 female; median age: 39 years) were included; 51 patients had HCA and 59 had FNH. Of the 110 patients, 49 underwent resection (33 HCA patients; 16 FNH patients). Laparoscopic minor resection was performed in five HCA and five FNH patients; open minor resection was performed in 19 HCA and seven FNH patients, and open major resection was performed in nine HCA and four FNH patients. Severe postoperative complications were observed in four patients (Grade III, n = 3; Grade IV, n = 1). Median baseline scores on the VAS were 6 in FNH patients and 7 in HCA patients; the median VAS score after resection was 0 (P = 0.008). Conclusions: If patients with HCA and FNH require surgery, limited resection can be carried out with low morbidity and without mortality. Patients with preoperative symptoms show a high rate of postoperative symptom relief. PMID:23509949

  4. Focal nodular hyperplasia: characterisation at gadoxetic acid-enhanced MRI and diffusion-weighted MRI

    PubMed Central

    An, H S; Kim, Y J; Jung, S I; Jeon, H J

    2013-01-01

    Purpose: The aim of this study was to assess the enhancement patterns of hepatic focal nodular hyperplasia (FNH) on gadoxetic acid-enhanced MRI and diffusion-weighted (DW) MRI. Methods: This retrospective study had institutional review board approval. Gadoxetic acid-enhanced and DW MR images were evaluated in 23 patients with 30 FNHs (26 histologically proven and 4 radiologically diagnosed). The lesion enhancement patterns of the hepatobiliary phase images were classified as heterogeneous or homogeneous signal intensity (SI), and as dominantly high/iso or low SI compared with those of adjacent liver parenchyma. Heterogeneous (any) SI lesions and homogeneous low SI lesions were categorised into the fibrosis group, whereas homogeneous high/iso SI lesions were categorised into the non-fibrosis group. Additionally, lesion SI on T2 weighted images, DW images and apparent diffusion coefficient (ADC) values were compared between the two groups. Results: The lesions showed heterogeneous high/iso SI (n=16), heterogeneous low SI (n=5), homogeneous high/iso SI (n=7) or homogeneous low SI (n=2) at the hepatobiliary phase MR images. The fibrosis group lesions were more likely to show high SI on DW images and T2 weighted images compared with those in the non-fibrosis group (p<0.05). ADC values tended to be lower in the fibrosis group than those in the non-fibrosis group without significance. Conclusion: FNH showed variable enhancement patterns on hepatobiliary phase images during gadoxetic acid-enhanced MRI. SI on DW and T2 weighted images differed according to the fibrosis component contained in the lesion. Advances in knowledge: FNH shows a wide spectrum of imaging findings on gadoxetic acid-enhanced MRI and DW MRI. PMID:23873903

  5. Intrasinusoidal cytotoxic CD8+ T cells in nodular regenerative hyperplasia of the liver.

    PubMed

    Ziol, Marianne; Poirel, Helene; Kountchou, Gisele N; Boyer, Olivier; Mohand, Djamila; Mouthon, Luc; Tepper, Maryline; Guillet, Jean-Gerard; Guettier, Catherine; Raphael, Martine; Beaugrand, Michel

    2004-10-01

    Diffuse nodular regenerative hyperplasia (NRH) of the liver is an acquired architectural disturbance that can lead to portal hypertension. Although frequently associated with autoimmune or hematologic malignancies, its exact pathogenesis remains largely unknown. We observed CD8+ cytotoxic T cells in the liver sinusoids of 14 of 44 NRH patients and explored possible relationships between these lymphocytes and vascular damage. The immunophenotype of intrahepatic lymphocytes was determined using immunohistochemical analysis and endothelial injury using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method for apoptosis combined with endothelial cell labeling. Controls for the quantitative analysis of liver-infiltrating lymphocytes consisted of patients with chronic hepatitis C or normal liver (n = 13 and n = 6, respectively). Liver specimens from the 14 patients dislayed intrasinusoidal infiltrate composed of CD3+ and CD8+ lymphocytes, located near atrophic liver cell plates. Significantly more granzyme B+ and CD57+ lymphocytes were observed in NRH than chronic hepatitis C samples with quantitatively similar CD8+ infiltrates. Double-labeling revealed apoptotic endothelial sinusoidal cells in CD8+ T-cell-infiltrated areas in all NRH samples but never in chronic hepatitis C or normal livers. T-cell receptor rearrangement or immunoscope analysis suggested liver-specific polyclonal or oligoclonal T-cell expansions. Clinical and biological characteristics of the 14 patients were similar to those observed in the 30 patients with NRH devoid of lymphocytic infiltration. We report here that CD8+ cytotoxic T cells infiltrated the liver sinusoids of a high percentage (32%) of NRH patients and suggest that some NRH cases might result from chronic, cytotoxic CD8+ T-lymphocyte targeting of sinusoidal endothelial cells. PMID:15492992

  6. Morphometric changes in subcortical structures of the central auditory pathway in mice with bilateral nodular heterotopia.

    PubMed

    Truong, Dongnhu T; Rendall, Amanda R; Rosen, Glenn D; Fitch, R Holly

    2015-04-01

    Malformations of cortical development (MCD) have been observed in human reading and language impaired populations. Injury-induced MCD in rodent models of reading disability show morphological changes in the auditory thalamic nucleus (medial geniculate nucleus; MGN) and auditory processing impairments, thus suggesting a link between MCD, MGN, and auditory processing behavior. Previous neuroanatomical examination of a BXD29 recombinant inbred strain (BXD29-Tlr4(lps-2J)/J) revealed MCD consisting of bilateral subcortical nodular heterotopia with partial callosal agenesis. Subsequent behavioral characterization showed a severe impairment in auditory processing-a deficient behavioral phenotype seen across both male and female BXD29-Tlr4(lps-2J)/J mice. In the present study we expanded upon the neuroanatomical findings in the BXD29-Tlr4(lps-2J)/J mutant mouse by investigating whether subcortical changes in cellular morphology are present in neural structures critical to central auditory processing (MGN, and the ventral and dorsal subdivisions of the cochlear nucleus; VCN and DCN, respectively). Stereological assessment of brain tissue of male and female BXD29-Tlr4(lps-2J)/J mice previously tested on an auditory processing battery revealed overall smaller neurons in the MGN of BXD29-Tlr4(lps-2J)/J mutant mice in comparison to BXD29/Ty coisogenic controls, regardless of sex. Interestingly, examination of the VCN and DCN revealed sexually dimorphic changes in neuronal size, with a distribution shift toward larger neurons in female BXD29-Tlr4(lps-2J)/J brains. These effects were not seen in males. Together, the combined data set supports and further expands the observed co-occurrence of MCD, auditory processing impairments, and changes in subcortical anatomy of the central auditory pathway. The current stereological findings also highlight sex differences in neuroanatomical presentation in the presence of a common auditory behavioral phenotype. PMID:25549859

  7. Nodular amyloidoma and primary pulmonary lymphoma with amyloid production: a differential diagnostic problem.

    PubMed

    Dacic, S; Colby, T V; Yousem, S A

    2000-09-01

    Nodular amyloidomas (NA) of the lung are non-neoplastic inflammatory nodules containing eosinophilic amyloid deposits and a lymphoplasmacytic infiltrate. In some instances, the extensive amyloid deposits may obscure an underlying lymphoproliferative disorder. The histologic and immunohistologic features that discriminate these two differential diagnostic possibilities were studied in this series of six cases of NA and five cases of primary low-grade malignant lymphomas of lung with secondary amyloid deposits (ML). Two of lymphoma cases showed histopathologic and immunophenotypic features of B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-cell CLL/SLL), and three cases were low-grade B-cell lymphoma derived from mucosa associated lymphoid tissue (MALT lymphoma). Key discriminating morphologic features between NA and ML included lymphatic tracking of the cellular infiltrate (3/5 ML; 1/6 NA), pleural infiltration (3/5 ML; 0/6 NA), sheet-like masses of plasma cells (5/5 ML; 0/6 NA) and reactive follicles (4/5 ML; 1/6 NA). Lesional circumscription, vascular and bronchial destruction, lymphoepithelial lesions, and granulomas were not helpful discriminators. Immunohistochemical features indicating a dominant CD20+, CD79a+ B-cell population (5/5 ML; 0/6 NA), light chain restriction (4/5 ML; 0/6 NA), and aberrant antigen expression of CD20/CD43 (2/5 ML; 0/6 NA) were helpful. Amyloid tumors with a reactive lymphoplasmacytic infiltrate can be separated from low-grade malignant lymphomas utilizing both histologic and immunohistochemical features. PMID:11007032

  8. Nomograms to Predict Recurrence-Free and Overall Survival After Curative Resection of Adrenocortical Carcinoma

    PubMed Central

    Kim, Yuhree; Margonis, Georgios A.; Prescott, Jason D.; Tran, Thuy B.; Postlewait, Lauren M.; Maithel, Shishir K.; Wang, Tracy S.; Evans, Douglas B.; Hatzaras, Ioannis; Shenoy, Rivfka; Phay, John E.; Keplinger, Kara; Fields, Ryan C.; Jin, Linda X.; Weber, Sharon M.; Salem, Ahmed I.; Sicklick, Jason K.; Gad, Shady; Yopp, Adam C.; Mansour, John C.; Duh, Quan-Yang; Seiser, Natalie; Solorzano, Carmen C.; Kiernan, Colleen M.; Votanopoulos, Konstantinos I.; Levine, Edward A.; Poultsides, George A.; Pawlik, Timothy M.

    2016-01-01

    IMPORTANCE Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor, and the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined. OBJECTIVES To define clinicopathological variables associated with recurrence-free survival (RFS) and overall survival (OS) after curative surgical resection of ACC and to propose nomograms for individual risk prediction. DESIGN, SETTING, AND PARTICIPANTS Nomograms to predict RFS and OS after surgical resection of ACC were proposed using a multi-institutional cohort of patients who underwent curative-intent surgery for ACC at 13 major institutions in the United States between March 17, 1994, and December 22, 2014. The dates of our study analysis were April 15, 2015, to May 12, 2015. MAIN OUTCOMES AND MEASURES The discriminative ability and calibration of the nomograms to predict RFS and OS were tested using C statistics, calibration plots, and Kaplan-Meier curves. RESULTS In total, 148 patients who underwent surgery for ACC were included in the study. The median patient age was 53 years, and 65.5% (97 of 148) of the patients were female. One-third of the patients (35.1% [52 of 148]) had a functional tumor, and the median tumor size was 11.2 cm. Most patients (77.7% [115 of 148]) underwent R0 resection, and 8.8% (13 of 148) of the patients had N1 disease. Using backward stepwise selection of clinically important variables with the Akaike information criterion, the following variables were incorporated in the prediction of RFS: tumor size of at least 12 cm (hazard ratio [HR], 3.00; 95% CI, 1.63–5.70; P < .001), positive nodal status (HR, 4.78; 95% CI, 1.47–15.50; P = .01), stage III/IV (HR, 1.80; 95% CI, 0.95–3.39; P = .07), cortisol-secreting tumor (HR, 2.38; 95% CI, 1.27–4.48; P = .01), and capsular invasion (HR, 1.96; 95% CI, 1.02–3.74; P = .04). Factors selected as predicting OS were tumor size of at least 12 cm (HR, 1.78; 95% CI, 1.00–3.17; P = .05), positive

  9. Color me bad: microbial pigments as virulence factors.

    PubMed

    Liu, George Y; Nizet, Victor

    2009-09-01

    A hallmark feature of several pathogenic microbes is the distinctive color of their colonies when propagated in the clinical laboratory. Such pigmentation comes in a variety of hues, and has often proven useful in presumptive clinical diagnosis. Recent advances in microbial pigment biochemistry and the genetic basis of pigment production have sometimes revealed a more sinister aspect to these curious materials that change the color of reflected light by selective light absorbance. In many cases, the microbial pigment contributes to disease pathogenesis by interfering with host immune clearance mechanisms or by exhibiting pro-inflammatory or cytotoxic properties. We review several examples of pigments that promote microbial virulence, including the golden staphyloxanthin of Staphylococcusaureus, the blue-green pyocyanin of Pseudomonas spp., and the dark brown or black melanin pigments of Cryptococcus neoformans and Aspergillus spp. Targeted pigment neutralisation might represent a viable concept to enhance treatment of certain difficult infectious disease conditions. PMID:19726196

  10. Activation of visual pigments by light and heat.

    PubMed

    Luo, Dong-Gen; Yue, Wendy W S; Ala-Laurila, Petri; Yau, King-Wai

    2011-06-10

    Vision begins with photoisomerization of visual pigments. Thermal energy can complement photon energy to drive photoisomerization, but it also triggers spontaneous pigment activation as noise that interferes with light detection. For half a century, the mechanism underlying this dark noise has remained controversial. We report here a quantitative relation between a pigment's photoactivation energy and its peak-absorption wavelength, λ(max). Using this relation and assuming that pigment activations by light and heat go through the same ground-state isomerization energy barrier, we can predict the relative noise of diverse pigments with multi-vibrational-mode thermal statistics. The agreement between predictions and our measurements strongly suggests that pigment noise arises from canonical isomerization. The predicted high noise for pigments with λ(max) in the infrared presumably explains why they apparently do not exist in nature. PMID:21659602

  11. Age-associated glycopeptide pigment in human costal cartilage.

    PubMed Central

    van der Korst, J. K.; Willekens, F. L.; Lansink, A. G.; Henrichs, A. M.

    1977-01-01

    Age-associated pigmentation of human costal cartilage is caused by the accumulation of a brown water-soluble substance which can be only be extracted after proteolytic disruption of the cartilage. After isolation by gel filtration and ion exchange chromatography, the compound was identified as an acid glycopeptide. In contrast to ochronotic pigment and an artificial pigment derived by oxidation of homogentistic acid in alkaline solution, the age-associated cartilage pigment was strongly fluorescent and did not form insoluble complexes with cetylpyridinium chloride. Moreover, age-associated cartilage pigment is alkali resistant, in contrast to the ochronotic pigment. The pigment differs from lipofuscin in being strongly hydrophilic and having no affinity for fat stains. The unidentified chromophore could not be separated from the glycopeptide molecule. PMID:596418

  12. Cone visual pigments of monotremes: filling the phylogenetic gap.

    PubMed

    Wakefield, Matthew J; Anderson, Mark; Chang, Ellen; Wei, Ke-Jun; Kaul, Rajinder; Graves, Jennifer A Marshall; Grützner, Frank; Deeb, Samir S

    2008-01-01

    We have determined the sequence and genomic organization of the genes encoding the cone visual pigment of the platypus (Ornithorhynchus anatinus) and the echidna (Tachyglossus aculeatus), and inferred their spectral properties and evolutionary pathways. We prepared platypus and echidna retinal RNA and used primers of the middle-wave-sensitive (MWS), long-wave-sensitive (LWS), and short-wave sensitive (SWS1) pigments corresponding to coding sequences that are highly conserved among mammals; to PCR amplify the corresponding pigment sequences. Amplification from the retinal RNA revealed the expression of LWS pigment mRNA that is homologous in sequence and spectral properties to the primate LWS visual pigments. However, we were unable to amplify the mammalian SWS1 pigment from these two species, indicating this gene was lost prior to the echidna-platypus divergence (21 MYA). Subsequently, when the platypus genome sequence became available, we found an LWS pigment gene in a conserved genomic arrangement that resembles the primate pigment, but, surprisingly we found an adjacent (20 kb) SWS2 pigment gene within this conserved genomic arrangement. We obtained the same result after sequencing the echidna genes. The encoded SWS2 pigment is predicted to have a wavelength of maximal absorption of about 440 nm, and is paralogous to SWS pigments typically found in reptiles, birds, and fish but not in mammals. This study suggests the locus control region (LCR) has played an important role in the conservation of photo receptor gene arrays and the control of their spatial and temporal expression in the retina in all mammals. In conclusion, a duplication event of an ancestral cone visual pigment gene, followed by sequence divergence and selection gave rise to the LWS and SWS2 visual pigments. So far, the echidna and platypus are the only mammals that share the gene structure of the LWS-SWS2 pigment gene complex with reptiles, birds and fishes. PMID:18598396

  13. Bleached pigment activates transduction in salamander cones

    PubMed Central

    1995-01-01

    We have used suction electrode recording together with rapid steps into 0.5 mM IBMX solution to investigate changes in guanylyl cyclase velocity produced by pigment bleaching in isolated cones of the salamander Ambystoma tigrinum. Both backgrounds and bleaches accelerate the time course of current increase during steps into IBMX. We interpret this as evidence that the velocity of the guanylyl cyclase is increased in background light or after bleaching. Our results indicate that cyclase velocity increases nearly linearly with increasing percent pigment bleached but nonlinearly (and may saturate) with increasing back-ground intensity. In cones (as previously demonstrated for rods), light-activated pigment and bleached pigment appear to have somewhat different effects on the transduction cascade. The effect of bleaching on cyclase rate is maintained for at least 15-20 min after the light is removed, much longer than is required after a bleach for circulating current and sensitivity to stabilize in an isolated cone. The effect on the cyclase rate can be completely reversed by treatment with liposomes containing 11-cis retinal. The effects of bleaching can also be partially reversed by beta-ionone, an analogue of the chromophore 11- cis-retinal which does not form a covalent attachment to opsin. Perfusion of a bleached cone with beta-ionone produces a rapid increase in circulating current and sensitivity, which rapidly reverses when the beta-ionone is removed. Perfusion with beta-ionone also causes a partial reversal of the bleach-induced acceleration of cyclase velocity. We conclude that bleaching produces an "equivalent background" excitation of the transduction cascade in cones, perhaps by a mechanism similar to that in rods. PMID:8786347

  14. Practice and Educational Gaps in Abnormal Pigmentation.

    PubMed

    Mohammad, Tasneem F; Hamzavi, Iltefat H

    2016-07-01

    Dyschromia refers to abnormal pigmentation and is one of the most common diagnoses in dermatology. However, there are many educational and practice gaps in this area, specifically in melasma, postinflammatory hyperpigmentation, and vitiligo. This article aims to review the gold standard of care for these conditions as well as highlight common educational and practice gaps in these areas. Finally, possible solutions to these gaps are addressed. PMID:27363886

  15. Diet-induced pigmented purpuric dermatosis.

    PubMed

    Weiß, Katharina T; Karrer, Sigrid; Landthaler, Michael; Babilas, Philipp; Schreml, Stephan

    2014-08-01

    Pigmented purpuric dermatoses (PPD) are chronic and relapsing disorders characterised by a localised or generalised purpuric rash. Even though the clinical presentation of PPD subtypes varies, they have a similar histopathology. The aetiology is largely unknown, but trigger factors, such as drugs, infections and systemic illnesses have been described. To our knowledge, this is the only case showing widespread PPD lesions not only induced but also rapidly provoked by dietary factors, namely Coca Cola and apple-cherry fruit spritzer. PMID:23574037

  16. Skin pigmentation, biogeographical ancestry and admixture mapping.

    PubMed

    Shriver, Mark D; Parra, Esteban J; Dios, Sonia; Bonilla, Carolina; Norton, Heather; Jovel, Celina; Pfaff, Carrie; Jones, Cecily; Massac, Aisha; Cameron, Neil; Baron, Archie; Jackson, Tabitha; Argyropoulos, George; Jin, Li; Hoggart, Clive J; McKeigue, Paul M; Kittles, Rick A

    2003-04-01

    Ancestry informative markers (AIMs) are genetic loci showing alleles with large frequency differences between populations. AIMs can be used to estimate biogeographical ancestry at the level of the population, subgroup (e.g. cases and controls) and individual. Ancestry estimates at both the subgroup and individual level can be directly instructive regarding the genetics of the phenotypes that differ qualitatively or in frequency between populations. These estimates can provide a compelling foundation for the use of admixture mapping (AM) methods to identify the genes underlying these traits. We present details of a panel of 34 AIMs and demonstrate how such studies can proceed, by using skin pigmentation as a model phenotype. We have genotyped these markers in two population samples with primarily African ancestry, viz. African Americans from Washington D.C. and an African Caribbean sample from Britain, and in a sample of European Americans from Pennsylvania. In the two African population samples, we observed significant correlations between estimates of individual ancestry and skin pigmentation as measured by reflectometry (R(2)=0.21, P<0.0001 for the African-American sample and R(2)=0.16, P<0.0001 for the British African-Caribbean sample). These correlations confirm the validity of the ancestry estimates and also indicate the high level of population structure related to admixture, a level that characterizes these populations and that is detectable by using other tests to identify genetic structure. We have also applied two methods of admixture mapping to test for the effects of three candidate genes (TYR, OCA2, MC1R) on pigmentation. We show that TYR and OCA2 have measurable effects on skin pigmentation differences between the west African and west European parental populations. This work indicates that it is possible to estimate the individual ancestry of a person based on DNA analysis with a reasonable number of well-defined genetic markers. The implications and

  17. An intracellular anion channel critical for pigmentation

    PubMed Central

    Bellono, Nicholas W; Escobar, Iliana E; Lefkovith, Ariel J; Marks, Michael S; Oancea, Elena

    2014-01-01

    Intracellular ion channels are essential regulators of organellar and cellular function, yet the molecular identity and physiological role of many of these channels remains elusive. In particular, no ion channel has been characterized in melanosomes, organelles that produce and store the major mammalian pigment melanin. Defects in melanosome function cause albinism, characterized by vision and pigmentation deficits, impaired retinal development, and increased susceptibility to skin and eye cancers. The most common form of albinism is caused by mutations in oculocutaneous albinism II (OCA2), a melanosome-specific transmembrane protein with unknown function. Here we used direct patch-clamp of skin and eye melanosomes to identify a novel chloride-selective anion conductance mediated by OCA2 and required for melanin production. Expression of OCA2 increases organelle pH, suggesting that the chloride channel might regulate melanin synthesis by modulating melanosome pH. Thus, a melanosomal anion channel that requires OCA2 is essential for skin and eye pigmentation. DOI: http://dx.doi.org/10.7554/eLife.04543.001 PMID:25513726

  18. Optical tomography of pigmented human skin biopsies

    NASA Astrophysics Data System (ADS)

    Riemann, Iris; Fischer, Peter; Kaatz, Martin; Fischer, Tobias W.; Elsner, Peter; Dimitrov, Enrico; Reif, Annette; Konig, Karsten

    2004-07-01

    The novel femtosecond NIR (near infrared) laser based high resolution imaging system DermaInspect was used for non-invasive diagnostics of pigmented skin. The system provides fluorescence and SHG images of high spatial submicron resolution (3D) and 250 ps temporal resolution (4D) based on time resolved single photon counting (TCSPC). Pigmented tissue biopsies from patients with nevi and melanoma have been investigated using the tunable 80 MHz femtosecond laser MaiTai with laser wavelengths in the range of 750 - 850 nm. The autofluorescence patterns of different intratissue cell types and structures were determined. The non-linear induced autofluorescence originates from naturally endogenous fluorophores and protein structures like NAD(P)H, flavins, elastin, collagen, phorphyrins and melanin. In addition to autofluorescence, SHG (second harmonic generation) was used to detect dermal collagen structures. Interestingly, pigmented cells showed intense luminescence signals. Further characterization of tissue components was performed via 4D measurements of the fluorescence lifetime (x, y, z, τ). The novel multiphoton technique offers the possibility of a painless high resolution non invasive diagnostic method (optical biopsy), in particular for the early detection of skin cancer.

  19. An intracellular anion channel critical for pigmentation.

    PubMed

    Bellono, Nicholas W; Escobar, Iliana E; Lefkovith, Ariel J; Marks, Michael S; Oancea, Elena

    2014-01-01

    Intracellular ion channels are essential regulators of organellar and cellular function, yet the molecular identity and physiological role of many of these channels remains elusive. In particular, no ion channel has been characterized in melanosomes, organelles that produce and store the major mammalian pigment melanin. Defects in melanosome function cause albinism, characterized by vision and pigmentation deficits, impaired retinal development, and increased susceptibility to skin and eye cancers. The most common form of albinism is caused by mutations in oculocutaneous albinism II (OCA2), a melanosome-specific transmembrane protein with unknown function. Here we used direct patch-clamp of skin and eye melanosomes to identify a novel chloride-selective anion conductance mediated by OCA2 and required for melanin production. Expression of OCA2 increases organelle pH, suggesting that the chloride channel might regulate melanin synthesis by modulating melanosome pH. Thus, a melanosomal anion channel that requires OCA2 is essential for skin and eye pigmentation. PMID:25513726

  20. Blackberry pigment (whitlockite) gallstones in uremic patient.

    PubMed

    Cariati, Andrea

    2013-04-01

    Black pigment gallstones represent nearly the 15% of all gallstones and are usually related with the typical "hyperbilirubinbilia" factors as hemolysis, ineffective erythropoiesis, pathologic enterohepatic cycling of unconjugated bilirubin, cirrhosis and with gallbladder mucosa (parietal) factors as adenomyomatosis. During a prospective study on 179 patients who underwent cholecystectomy for gallstone disease a 69-year-old female with predialysis chronic kidney disease was operated for symptomatic gallstone. The removed gallstones were black pigment gallstones, with an irregular (as small blackberry) surface. Analysis of the stones revealed a great amount of whitlockite (Ca Mg)3 (PO4)2. Recent studies on chronic renal failure patients found that chronic uremia is associated with an increased risk of gallstones formation (22%) as it seems in women affected by primary hyperparathyroidism (30%). The presence of calcium phosphate gallstones in these patients have been never described. In conclusion, further studies could be necessary to establish the role of chronic renal failure and of primary and secondary hyperparathyroidism in gallstones formation and, in particular, if dialysis and predialysis patients have an higher risk to develop cholesterol and black pigment gallstones in particular of the "blackberry" (whitlockite) subtype. PMID:22959097