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Sample records for pigmented nodular adrenocortical

  1. [Primary pigmented nodular adrenocortical disease as cause of Cushing's syndrome associated with Carney complex].

    PubMed

    Dumić, Miroslav; Janjanin, Nevena; Uroić, Anita Spehar; Ille, Jasenka; Skegro, Mate; Kusec, Vesna; Marjanac, Igor; Matić, Toni; Jelasić, Drazen

    2006-01-01

    We report a 11-year-old girl and two 14-year-old boys with Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). In these patients, hypercortisolism is a consequence of autonomous cortisol secretion from adrenal glands and is ACTH-independent. Besides PPNAD, the girl had lentigines, spotty pigmentation on her bucal mucosa and lips and she also had schwannoma. One of the reported boys had prolactinoma. Considering this, those two patients fulfill the criteria for Carney complex which is a type of multiple endocrine neoplasia syndromes inherited in an autosomal dominant trait. The other boy had PPNAD but no other obvious signs of Carney complex were noticed. Family study didn't reveal any clinical or laboratory signs of Carney complex in our patients' first relatives. All of our patients underwent bilateral adrenalectomy (in one of the boys laparoscopic surgery was performed). Glucocorticoid and mineralocorticoid substitution has been started. Adrenal glands were macroscopically normal but pathohistological analysis confirmed the diagnosis of PPNAD.

  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. 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.

  4. PKA regulatory subunit 1A inactivating mutation induces serotonin signaling in primary pigmented nodular adrenal disease

    PubMed Central

    Bram, Zakariae; Louiset, Estelle; Renouf, Sylvie; Duparc, Céline; Boutelet, Isabelle; Rizk-Rabin, Marthe; Libé, Rossella; Young, Jacques; Carson, Dennis; Vantyghem, Marie-Christine; Szarek, Eva; Martinez, Antoine; Stratakis, Constantine A.; Bertherat, Jérôme

    2016-01-01

    Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent hypercortisolism. The disease is primarily caused by germline mutations of the protein kinase A (PKA) regulatory subunit 1A (PRKAR1A) gene, which induces constitutive activation of PKA in adrenocortical cells. Hypercortisolism is thought to result from PKA hyperactivity, but PPNAD tissues exhibit features of neuroendocrine differentiation, which may lead to stimulation of steroidogenesis by abnormally expressed neurotransmitters. We hypothesized that serotonin (5-HT) may participate in the pathophysiology of PPNAD-associated hypercortisolism. We show that PPNAD tissues overexpress the 5-HT synthesizing enzyme tryptophan hydroxylase type 2 (Tph2) and the serotonin receptors types 4, 6, and 7, leading to formation of an illicit stimulatory serotonergic loop whose pharmacological inhibition in vitro decreases cortisol production. In the human PPNAD cell line CAR47, the PKA inhibitor H-89 decreases 5-HT4 and 5-HT7 receptor expression. Moreover, in the human adrenocortical cell line H295R, inhibition of PRKAR1A expression increases the expression of Tph2 and 5-HT4/6/7 receptors, an effect that is blocked by H-89. These findings show that the serotonergic process observed in PPNAD tissues results from PKA activation by PRKAR1A mutations. They also suggest that Tph inhibitors may represent efficient treatments of hypercortisolism in patients with PPNAD. PMID:27699247

  5. PKA regulatory subunit 1A inactivating mutation induces serotonin signaling in primary pigmented nodular adrenal disease.

    PubMed

    Bram, Zakariae; Louiset, Estelle; Ragazzon, Bruno; Renouf, Sylvie; Wils, Julien; Duparc, Céline; Boutelet, Isabelle; Rizk-Rabin, Marthe; Libé, Rossella; Young, Jacques; Carson, Dennis; Vantyghem, Marie-Christine; Szarek, Eva; Martinez, Antoine; Stratakis, Constantine A; Bertherat, Jérôme; Lefebvre, Hervé

    2016-09-22

    Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent hypercortisolism. The disease is primarily caused by germline mutations of the protein kinase A (PKA) regulatory subunit 1A (PRKAR1A) gene, which induces constitutive activation of PKA in adrenocortical cells. Hypercortisolism is thought to result from PKA hyperactivity, but PPNAD tissues exhibit features of neuroendocrine differentiation, which may lead to stimulation of steroidogenesis by abnormally expressed neurotransmitters. We hypothesized that serotonin (5-HT) may participate in the pathophysiology of PPNAD-associated hypercortisolism. We show that PPNAD tissues overexpress the 5-HT synthesizing enzyme tryptophan hydroxylase type 2 (Tph2) and the serotonin receptors types 4, 6, and 7, leading to formation of an illicit stimulatory serotonergic loop whose pharmacological inhibition in vitro decreases cortisol production. In the human PPNAD cell line CAR47, the PKA inhibitor H-89 decreases 5-HT4 and 5-HT7 receptor expression. Moreover, in the human adrenocortical cell line H295R, inhibition of PRKAR1A expression increases the expression of Tph2 and 5-HT4/6/7 receptors, an effect that is blocked by H-89. These findings show that the serotonergic process observed in PPNAD tissues results from PKA activation by PRKAR1A mutations. They also suggest that Tph inhibitors may represent efficient treatments of hypercortisolism in patients with PPNAD.

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

    PubMed Central

    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

  7. Adrenocortical carcinoma

    MedlinePlus

    ... Adrenocortical carcinoma (ACC) is a cancer of the adrenal glands . The adrenal glands are two triangle-shaped glands. One gland is ... unknown. Symptoms Symptoms of increased cortisol or other adrenal gland hormones may include: Fatty, rounded hump high on ...

  8. 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

  9. 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

  10. 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

  11. 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.

  12. Adrenocortical reserves in hyperthyroidism.

    PubMed

    Agbaht, Kemal; Gullu, Sevim

    2014-02-01

    Explicit data regarding the changes in adrenocortical reserves during hyperthyroidism do not exist. We aimed to document the capability (response) of adrenal gland to secrete cortisol and DHEA-S during hyperthyroidism compared to euthyroidism, and to describe factors associated with these responses. A standard-dose (0.25 mg/i.v.) ACTH stimulation test was performed to the same patients before hyperthyroidism treatment, and after attainment of euthyroidism. Baseline cortisol (Cor(0)), DHEA-S (DHEA-S(0)), cortisol binding globulin (CBG), ACTH, calculated free cortisol (by Coolen's equation = CFC), free cortisol index (FCI), 60-min cortisol (Cor(60)), and DHEA-S (DHEA-S(60)), delta cortisol (ΔCor), delta DHEA-S (ΔDHEA-S) responses were evaluated. Forty-one patients [22 females, 49.5 ± 15.2 years old, 32 Graves disease, nine toxic nodular goiter] had similar Cor(0), DHEA-S(0), CFC, FCI, and DHEA-S(60) in hyperthyroid and euthyroid states. Cor(60), ΔCor, and ΔDHEA-S were lower in hyperthyroidism. In four (10 %) patients the peak ACTH-stimulated cortisol values were lower than 18 μg/dL. When the test repeated after attainment of euthyroidism, all of the patients had normal cortisol response. Regression analysis demonstrated an independent association of Cor(60) with free T3 in hyperthyroidism. However, the predictors of CFC, FCI, and DHEA-S levels were serum creatinine levels in hyperthyroidism, and both creatinine and transaminase levels in euthyroidism. ACTH-stimulated peak cortisol, delta cortisol, and delta DHEA-S levels are decreased during hyperthyroidism, probably due to increased turnover. Since about 10 % of the subjects with hyperthyroidism are at risk for adrenal insufficiency, clinicians dealing with Graves' disease should be alert to the possibility of adrenal insufficiency during hyperthyroid stage.

  13. 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

  14. 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

  15. Update in adrenocortical carcinoma.

    PubMed

    Fassnacht, Martin; Kroiss, Matthias; Allolio, Bruno

    2013-12-01

    Adrenocortical carcinoma (ACC) is an orphan malignancy that has attracted increasing attention during the last decade. Here we provide an update on advances in the field since our last review published in this journal in 2006. The Wnt/β-catenin pathway and IGF-2 signaling have been confirmed as frequently altered signaling pathways in ACC, but recent data suggest that they are probably not sufficient for malignant transformation. Thus, major players in the pathogenesis are still unknown. For diagnostic workup, comprehensive hormonal assessment and detailed imaging are required because in most ACCs, evidence for autonomous steroid secretion can be found and computed tomography or magnetic resonance imaging (if necessary, combined with functional imaging) can differentiate benign from malignant adrenocortical tumors. Surgery is potentially curative in localized tumors. Thus, we recommend a complete resection including lymphadenectomy by an expert surgeon. The pathology report should demonstrate the adrenocortical origin of the lesion (eg, by steroidogenic factor 1 staining) and provide Weiss score, resection status, and quantitation of the proliferation marker Ki67 to guide further treatment. Even after complete surgery, recurrence is frequent and adjuvant mitotane treatment improves outcome, but uncertainty exists as to whether all patients benefit from this therapy. In advanced ACC, mitotane is still the standard of care. Based on the FIRM-ACT trial, mitotane plus etoposide, doxorubicin, and cisplatin is now the established first-line cytotoxic therapy. However, most patients will experience progress and require salvage therapies. Thus, new treatment concepts are urgently needed. The ongoing international efforts including comprehensive "-omic approaches" and next-generation sequencing will improve our understanding of the pathogenesis and hopefully lead to better therapies.

  16. Scleroderma with Nodular Scleroderma

    PubMed Central

    Srisuttiyakorn, Chutika; Aunhachoke, Kobkul

    2016-01-01

    Background Nodular scleroderma is a rare variant of scleroderma which can occur in connection with systemic sclerosis or morphea. A biopsy from the lesion can demonstrate the scleroderma pattern, i.e., keloid pattern or mixed type. Treatment is challenging, and several treatments modalities have been reported with unsatisfactory results. Main Observations We present a case of systemic sclerosis in a 50-year-old female who developed nodular scleroderma in the absence of deterioration of the scleroderma condition. Although no additional treatment was given, the lesions remained stable without progression. Conclusions Although this condition is rare, it has been reported sporadically, and clinicians should be able to recognize this variant in cases of scleroderma presenting with firm nodules or plaques. PMID:27920682

  17. Mouse models of adrenocortical tumors

    PubMed Central

    Basham, Kaitlin J.; Hung, Holly A.; Lerario, Antonio M.; Hammer, Gary D.

    2016-01-01

    The molecular basis of the organogenesis, homeostasis, and tumorigenesis of the adrenal cortex has been the subject of intense study for many decades. Specifically, characterization of tumor predisposition syndromes with adrenocortical manifestations and molecular profiling of sporadic adrenocortical tumors have led to the discovery of key molecular pathways that promote pathological adrenal growth. However, given the observational nature of such studies, several important questions regarding the molecular pathogenesis of adrenocortical tumors have remained. This review will summarize naturally occurring and genetically engineered mouse models that have provided novel tools to explore the molecular and cellular underpinnings of adrenocortical tumors. New paradigms of cancer initiation, maintenance, and progression that have emerged from this work will be discussed. PMID:26678830

  18. [Adrenocortical tumors--new perspectives].

    PubMed

    Latronico, Ana Claudia; Mendonça, Berenice B de

    2004-10-01

    A high frequency of adrenocortical tumors has been observed in Brazilian children and adults from South and Southwestern regions. The valuable national experience in the management of these tumors have resulted in several and relevant basic and clinical reports. However, the creation of an adrenocortical tumor national registry, the uniformity of approaches and collaborative studies are target to pursue. In this review article, we briefly described the fundamental points which were discussed in two scientific events on adrenocortical tumors: "International Consensus Conference on Treatment of Adrenal Cancer" and "I Simposio de Diagnóstico e Tratamento dos Tumores Adrenocorticais". The task force involving several Brazilian centers will increase the progress in the diagnosis, prognosis and treatment of this devastating disorder.

  19. Adrenocortical Activity and Emotion Regulation.

    ERIC Educational Resources Information Center

    Stansbury, Kathy; Gunnar, Megan R.

    1994-01-01

    This essay argues that the activity of the hypothalamic-pituitary-adrenocortical (HPA) system does not appear to be related to emotion regulation processes in children, although individual differences in emotion processes related to negative emotion temperaments appear to be associated with individual differences in HPA reactivity among normally…

  20. [Adrenocortical carcinoma: Update in 2014].

    PubMed

    Libé, Rossella; Assié, Guillaume

    2014-04-01

    All adrenal masses with atypical characteristics at conventional imaging must be explored as potential adrenocortical cancer. CT scan with delayed contrast media wash-out and/or abdominal MRI including chemical shift and/or wash-out analysis and 18F-FDG PET help to characterize the adrenal mass. Open adrenalectomy is the first step in the treatment of resectables adrenocortical cancer, as potentially curative. It must be complete (R0), without tumoral dissemination. The management of the adrenocortical cancer requires a multidisciplinary approach, including the endocrinologist, oncologist, surgeons, radiologist, nuclear medicine, pathologist, and geneticians in order to guarantee to the patient the best care. At the national level, the French network COMETE (supported by the Institut National du Cancer) and the international level, the European Network for the Study of Adrenal tumors -ENS@T- (supported by ESF and FP7) contribute to improve the clinical management and the understanding of the pathogenesis of the adrenocortical cancers. Recently, a new insight on molecular markers has been done. These approaches will be soon used "in routine".

  1. Nodular Fasciitis of the Orbit.

    PubMed

    Compton, Christopher J; Clark, Jeremy D; Thompson, Matthew P; Lee, Hui Bae H; Nunery, William R

    A 13-month-old boy was presented with new onset proptosis of the right eye. CT scan and MRI showed an enhancing mass in the right superior orbit with local bone remodeling and erosion. A craniotomy was performed for biopsy and sub-total resection. Histopathology and immunohistochemistry confirmed the lesion to be nodular fasciitis. Nodular fasciitis lesions are classically found in the anterior ocular adnexa, especially in pediatric patients. This is the first reported case of nodular fasciitis arising in the posterior orbit of a child younger than 16.

  2. Gene expression and regulation in adrenocortical tumorigenesis.

    PubMed

    Fonseca, Annabelle L; Healy, James; Kunstman, John W; Korah, Reju; Carling, Tobias

    2012-12-27

    Adrenocortical tumors are frequently found in the general population, and may be benign adrenocortical adenomas or malignant adrenocortical carcinomas. Unfortunately the clinical, biochemical and histopathological distinction between benign and malignant adrenocortical tumors may be difficult in the absence of widely invasive or metastatic disease, and hence attention has turned towards a search for molecular markers. The study of rare genetic diseases that are associated with the development of adrenocortical carcinomas has contributed to our understanding of adrenocortical tumorigenesis. In addition, comprehensive genomic hybridization, methylation profiling, and genome wide mRNA and miRNA profiling have led to improvements in our understanding, as well as demonstrated several genes and pathways that may serve as diagnostic or prognostic markers.

  3. Feminizing Adrenocortical Carcinoma with Distinct Histopathological Findings

    PubMed Central

    Hatano, Masako; Takenaka, Yasuhiro; Inoue, Ikuo; Homma, Keiko; Hasegawa, Tomonobu; Sasano, Hisanobu; Awata, Takuya; Katayama, Shigehiro

    2016-01-01

    We herein present a 60-year-old man with adrenocortical carcinoma who had gynecomastia. An endocrinological examination revealed increased levels of serum estradiol and dehydroepiandrosterone-sulfate (DHEA-S) and reduced levels of free testosterone. Magnetic resonance imaging showed an adrenal tumor with heterogeneous intensity. Iodine-131 adosterol scintigraphy showed an increased uptake at the same site. Because feminizing adrenocortical carcinoma was suspected, right adrenalectomy was performed; the pathological diagnosis was adrenocortical carcinoma. The results of immunostaining indicated a virilizing tumor. Aromatase activity was identified on RT-PCR. As disorganized steroidogenesis is pathologically present in adrenocortical carcinoma, this diagnosis should be made with caution. PMID:27853073

  4. Primary bimorphic adrenocortical disease: cause of hypercortisolism in McCune-Albright syndrome.

    PubMed

    Carney, J Aidan; Young, William F; Stratakis, Constantine A

    2011-09-01

    McCune-Albright syndrome (polyostotic fibrous dysplasia, café-au-lait skin spots, and precocious puberty) is a genetically mosaic disorder with populations of mutant and normal cells in affected organs. Cushing syndrome, a rare feature of the condition, usually affects infants and is the result of corticotropin-independent primary bilateral adrenal disease, usually interpreted as nodular adrenocortical hyperplasia. In this study of 9 patients with Cushing syndrome and McCune-Albright syndrome, light microscopy revealed a characteristic bimorphic pattern of diffuse and nodular hyperplasia and a distinctive form of cortical atrophy with apparent zona glomerulosa hyperplasia in 8 patients, all very young. The pattern could be explained by the presence of a mosaic distribution of mutant and normal cells in the adrenal glands. The findings are different from those in inherited or other forms of genetically caused Cushing syndrome. The ninth patient, aged 17 years, had an adrenal adenoma and diffuse cortical hyperplasia in each adrenal gland.

  5. 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.

  6. Treating Nodular Lymphocyte Predominant Hodgkin Disease (NLPHD)

    MedlinePlus

    ... for Hodgkin Disease Treating Classic Hodgkin Disease, by Stage Treating Nodular Lymphocyte Predominant Hodgkin Disease (NLPHD) Treating Hodgkin Disease in Children Hodgkin Disease in Pregnancy Hodgkin Disease Treating Hodgkin Disease Treating Nodular Lymphocyte ...

  7. [Regenerative nodular hyperplasia in HIV].

    PubMed

    González, Ramiro Javier Romo; Chaves, Emiliano; Mullen, Eduardo; Copello, Hercilia

    2011-12-01

    Nodular regenerative hyperplasia of the liver is a rare condition. We describe here the case of a patient with HIV who presented with a clinical syndrome of portal hypertension. After multiple evaluations the diagnosis was recognized by the histology. The findings were attributed to the prolonged use of didanosine.

  8. Feminizing adrenocortical tumors: Literature review

    PubMed Central

    Chentli, Farida; Bekkaye, Ilyes; Azzoug, Said

    2015-01-01

    Feminizing adrenal tumors (FAT) are extremely rare tumors prevailing in males. Clinical manifestations are gynecomastia and/or other hypogonadism features in adults. They are rarer in pediatric population and their main manifestation is peripheral sexual precocity. In women genital bleeding, uterus hypertrophy, high blood pressure and/or abdomen mass may be the only manifestations. On the biological point, estrogen overproduction with or without increase in other adrenal hormones are the main abnormalities. Radiological examination usually shows the tumor, describes its limits and its eventual metastases. Adrenal and endocrine origins are confirmed by biochemical assessments and histology, but that one is unable to distinguish between benign and malignant tumors, except if metastases are already present. Immunostaining using anti-aromatase antibodies is the only tool that distinguishes FAT from other adrenocortical tumors. Abdominal surgery is the best and the first line treatment. For large tumors (≥10 cm), an open access is preferred to coeliosurgery, but for the small ones, or when the surgeon is experienced, endoscopic surgery seems to give excellent results. Surgery can be preceded by adrenolytic agents such as ortho paraprime dichloro diphenyl dichloroethane (Mitotane), ketoconazole or by aromatase inhibitors, but till now there is not any controlled study to compare the benefit of different drugs. New anti-estrogens can be used too, but their results need to be confirmed in malignant tumors resistant to classical chemotherapy and to conventional radiotherapy. Targeted therapy can be used too, as in other adrenocortical tumors, but the results need to be confirmed. PMID:25932386

  9. TCGA analysis of adrenocortical carcinoma - TCGA

    Cancer.gov

    In the most comprehensive molecular characterization to date of adrenocortical carcinoma, a rare cancer of the adrenal cortex, researchers extensively analyzed 91 cases for alterations in the tumor genomes.

  10. Retroperitoneoscopic partial adrenalectomy for large adrenocortical oncocytoma.

    PubMed

    Modi, Pranjal; Goel, Rajiv; Kadam, Gaurang

    2007-04-01

    A young woman had mild hypertension, and on evaluation, a large tumor arising from the right adrenal gland was found. The tumor was hormonally inactive. Retroperitoneoscopic partial adrenalectomy was carried out. The histopathology report described adrenocortical oncocytoma.

  11. Nodular lesions and mesangiolysis in diabetic nephropathy.

    PubMed

    Wada, Takashi; Shimizu, Miho; Yokoyama, Hitoshi; Iwata, Yasunori; Sakai, Yoshio; Kaneko, Shuichi; Furuichi, Kengo

    2013-02-01

    Diabetic nephropathy is a leading cause of end-stage renal failure all over the world. Advanced human diabetic nephropathy is characterized by the presence of specific lesions including nodular lesions, doughnut lesions, and exudative lesions. Thus far, animal models precisely mimicking advanced human diabetic nephropathy, especially nodular lesions, remain to be fully established. Animal models with spontaneous diabetic kidney diseases or with inducible kidney lesions may be useful for investigating the pathogenesis of diabetic nephropathy. Based on pathological features, we previously reported that diabetic glomerular nodular-like lesions were formed during the reconstruction process of mesangiolysis. Recently, we established nodular-like lesions resembling those seen in advanced human diabetic nephropathy through vascular endothelial injury and mesangiolysis by administration of monocrotaline. Here, in this review, we discuss diabetic nodular lesions and its animal models resembling human diabetic kidney lesions, with our hypothesis that endothelial cell injury and mesangiolysis might be required for nodular lesions.

  12. Genetics and epigenetics of adrenocortical tumors.

    PubMed

    Lerario, Antonio M; Moraitis, Andreas; Hammer, Gary D

    2014-04-05

    Adrenocortical tumors are common neoplasms. Most are benign, nonfunctional and clinically irrelevant. However, adrenocortical carcinoma is a rare disease with a dismal prognosis and no effective treatment apart from surgical resection. The molecular genetics of adrenocortical tumors remain poorly understood. For decades, molecular studies relied on a small number of samples and were directed to candidate-genes. This approach, based on the elucidation of the genetics of rare genetic syndromes in which adrenocortical tumors are a manifestation, has led to the discovery of major dysfunctional molecular pathways in adrenocortical tumors, such as the IGF pathway, the Wnt pathway and TP53. However, with the advent of high-throughput methodologies and the organization of international consortiums to obtain a larger number of samples and high-quality clinical data, this paradigm is rapidly changing. In the last decade, genome-wide expression profile studies, microRNA profiling and methylation profiling allowed the identification of subgroups of tumors with distinct genetic markers, molecular pathways activation patterns and clinical behavior. As a consequence, molecular classification of tumors has proven to be superior to traditional histological and clinical methods in prognosis prediction. In addition, this knowledge has also allowed the proposal of molecular-targeted approaches to provide better treatment options for advanced disease. This review aims to summarize the most relevant data on the rapidly evolving field of genetics of adrenal disorders.

  13. 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

  14. NODULAR FORMS OF TUBAL DISEASE

    PubMed Central

    Ries, Emil

    1897-01-01

    The conclusions at which we arrive are the following: 1. Nodular enlargement of the tube can be caused by a number of different pathological conditions. 2. Clinical examination does not enable us to make a diagnosis of the pathological condition existing in an individual case of nodule of the tube. 3. The diagnosis of the nature of a tubal nodule can be made only with the microscope. 4. The conditions causing nodular enlargement of the tube are congenital or acquired, non-inflammatory or inflammatory. 5. Any one of these conditions can exist without the production of nodules. 6. The nodules can be found in all parts of the tube and—taking the peculiar anatomy of each part of the tube into account—show the same structure. 7. The enlargement can be caused by epithelial or epithelioid formations, connective or muscular tissue, by round-cell infiltrations or combinations of two or more of these. 8. The epithelial formations originate in the epithelium of a. the tubal mucous membrane (salpingitis pseudo-follicularis, adenomyoma originating in the tubal epithelium). b. the accessory tubes (intraparietal parasalpinx and hydro-parasalpinx). c. remnants of the Wolffian body (adenomyoma). 9. The epithelioid formations originate in the peritoneal endothelium (peritoneal growths under "relative heterotopy"). 10. The excess of formation of connective tissue is a consequence of inflammatory conditions of the tubal wall (salpingitis interstitialis, Zweifel). 11. The hypertrophy of the muscular tissue is a. non-inflammatory (adenomyoma). b. consequent upon inflammation—Kaltenbach's case (23). 12. The accumulations of round cells are direct evidence of inflammation: a. non-specific (salpingitis interstitialis disseminata, salpingitis abscedens); or b. specific (salpingitis tuberculosa or s. gonorrhoica). 13. The epithelioid formations can occur wherever pseudo-membranes cover organs lined with a serous coat. 14. Extra-uterine pregnancy (abdominal or tubal) produces

  15. The ARMC5 gene shows extensive genetic variance in primary macronodular adrenocortical hyperplasia

    PubMed Central

    Correa, Ricardo; Zilbermint, Mihail; Berthon, Annabel; Espiard, Stephanie; Batsis, Maria; Papadakis, Georgios Z.; Xekouki, Paraskevi; Lodish, Maya B.; Bertherat, Jerome; Faucz, Fabio R.; Stratakis, Constantine A.

    2015-01-01

    Objective Primary macronodular adrenal hyperplasia (PMAH) is a rare type of Cushing’s syndrome (CS) that results in increased cortisol production and bilateral enlargement of the adrenal glands. Recent work showed that the disease may be caused by germline and somatic mutations in the ARMC5 gene, a likely tumor-suppressor gene (TSG). We investigated 20 different adrenal nodules from one patient with PMAH for ARMC5 somatic sequence changes. Design All of the nodules where obtained from a single patient who underwent bilateral adrenalectomy. DNA was extracted by standard protocols and the ARMC5 sequence was determined by the Sanger method. Results Sixteen of 20 adrenocortical nodules harbored, in addition to what appeared to be the germline mutation, a second somatic variant. The p.Trp476* sequence change was present in all 20 nodules, as well as in normal tissue from the adrenal capsule, identifying it as the germline defect; each of the 16 other variants were found in different nodules: 6 were frame shift, 4 were missense, 3 were nonsense, and 1 was a splice site variation. Allelic losses were confirmed in 2 of the nodules. Conclusion This is the most genetic variance of the ARMC5 gene ever described in a single patient with PMAH: each of 16 adrenocortical nodules had a second new, “private”, and -in most cases- completely inactivating ARMC5 defect, in addition to the germline mutation. The data support the notion that ARMC5 is a TSG that needs a second, somatic hit, to mediate tumorigenesis leading to polyclonal nodularity; however, the driver of this extensive genetic variance of the second ARMC5 allele in adrenocortical tissue in the context of a germline defect and PMAH remains a mystery. PMID:26162405

  16. A case of primary aldosteronism caused by unilateral multiple adrenocortical micronodules presenting as muscle cramps at rest: The importance of functional histopathology for identifying a culprit lesion.

    PubMed

    Ito, Atsushi; Yamazaki, Yuto; Sasano, Hironobu; Matsubara, Daisuke; Fukushima, Noriyoshi; Tamba, Mio; Tabata, Kenichi; Ashizawa, Kentaro; Takei, Akihito; Koizumi, Masaru; Sakuma, Yasunaru; Sata, Naohiro; Oshiro, Hisashi

    2017-04-01

    Unilateral multiple adrenocortical micronodules (UMNs) constitute a rare subset of primary aldosteronism (PA) characterized by the hypersecretion of aldosterone derived from multiple small nodules in the zona glomerulosa of the unilateral adrenal grand. This case study describes a 49-year-old man with PA and UMNs who presented with muscle cramps at rest due to hypokalemia. The patient had a 6-year history of hypertension treated with antihypertensive drugs. Imaging studies revealed bilateral adrenal nodules as large as 5 mm. Adrenal venous sampling confirmed unilateral PA; therefore, the patient underwent the removal of the affected adrenal gland. Macroscopically, the removed adrenal gland exhibited irregular adrenocortical thickening accompanied by ill-defined, adrenocortical macronodules as large as 6 mm. The zona glomerulosa was histologically hyperplastic. However, an immunohistochemistry test of the steroidogenic enzymes revealed that these macronodules and the hyperplastic glomerular layer tested negative for CYB11B2. Moreover, we observed adrenocortical micronodules as large as 0.5 mm that tested immunohistochemically positive for CYP11B2 and HSD3B2 but negative for CYP17A1 and CYP11B1. Thus, UMNs were diagnosed. This case instructively indicates that a grossly or histologically detectable nodular lesion is not necessarily a culprit lesion for PA. Therefore, functional histopathology is indispensable for the correct subclassification of PA.

  17. 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. PMID:27625633

  18. 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.

  19. Pigmented basal cell carcinoma mimicking a superficial spreading melanoma.

    PubMed

    Hasbún Acuña, Paula; Cullen Aravena, Roberto; Maturana Donaire, César; Ares Mora, Raúl; Porras Kusmanic, Ninoska

    2016-12-20

    Basal cell carcinoma is the most common form of skin cancer, especially in elderly people. Pigmented basal cell carcinoma is a rare subtype and has been described in the literature as a nodular and hyperpigmented lesion; rarely, it can appear as an extensive pigmented plate, which may be clinically indistinguishable from superficial spreading melanoma and Bowen disease. Dermatoscopy has a high sensitivity in the diagnosis of basal cell carcinoma. When Menzies criteria are used; however, the final diagnosis is made by histopathology. The objective of the present report is to analyze the case of a patient with pigmented basal cell carcinoma simulating a superficial spreading melanoma.

  20. Superficially located enlarged lymphoid follicles characterise nodular gastritis.

    PubMed

    Okamura, Takuma; Sakai, Yasuhiro; Hoshino, Hitomi; Iwaya, Yugo; Tanaka, Eiji; Kobayashi, Motohiro

    2015-01-01

    Nodular gastritis is a form of chronic Helicobacter pylori gastritis affecting the gastric antrum and characterised endoscopically by the presence of small nodular lesions resembling gooseflesh. It is generally accepted that hyperplasia of lymphoid follicles histologically characterises nodular gastritis; however, quantitative analysis in support of this hypothesis has not been reported. Our goal was to determine whether nodular gastritis is characterised by lymphoid follicle hyperplasia.The number, size, and location of lymphoid follicles in nodular gastritis were determined and those properties compared to samples of atrophic gastritis. The percentages of high endothelial venule (HEV)-like vessels were also evaluated.The number of lymphoid follicles was comparable between nodular and atrophic gastritis; however, follicle size in nodular gastritis was significantly greater than that seen in atrophic gastritis. Moreover, lymphoid follicles in nodular gastritis were positioned more superficially than were those in atrophic gastritis. The percentage of MECA-79 HEV-like vessels was greater in areas with gooseflesh-like lesions in nodular versus atrophic gastritis.Superficially located hyperplastic lymphoid follicles characterise nodular gastritis, and these follicles correspond to gooseflesh-like nodular lesions observed endoscopically. These observations suggest that MECA-79 HEV-like vessels could play at least a partial role in the pathogenesis of nodular gastritis.

  1. 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

  2. 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

  3. 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.

  4. Nodular panniculitis in a female toy poodle.

    PubMed

    Post, K

    1983-05-01

    A four month old female toy Poodle showing multiple nodules 2 to 3 cm in diameter, some of which had ruptured over the neck and trunk area, was diagnosed as having nodular panniculitis. The animal had been treated with a course of chloramphenicol and ampicillin for one month with no response. The diagnosis was based on history, clinical signs, laboratory data and dramatic response to the addition of corticosteroid to the antibiotic therapy.

  5. 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.

  6. Unusual Presentation of Multibacillary Nodular Leprosy

    PubMed Central

    Raut, Shweta; Kanade, Swapna; Nataraj, Gita; Mehta, Preeti

    2017-01-01

    Despite India achieving the goal of elimination of leprosy as a public health problem, leprosy is still being transmitted in India. However, due to decreased clinical suspicion of leprosy and atypical case presentations, such cases may be not be diagnosed. We present a case report of an unusual presentation of multibacillary leprosy which presented as nodular lesions. This case report indicates that atypical presentations of leprosy may be missed out by primary care physicians. PMID:28042219

  7. Thyroid peroxidase activity in human nodular goiters.

    PubMed

    Moura, E G; Rosenthal, D; Carvalho-Guimarães, D P

    1989-01-01

    1. Thyroid peroxidase (TPO, iodide-oxidation) activity was evaluated in nodular and paranodular tissue samples from 27 patients with nodular goiter (19 "cold" and 8 "hot" nodules), and compared to 11 diffuse toxic goiter and 9 normal thyroid tissue samples. 2. In terms of U/g digitonin solubilized protein, TPO activity was increased in hot nodules (P less than 0.05), although not as much as in diffuse toxic goiters (P less than 0.01). 3. The mean TPO activity of tissues paranodular to a cold nodule was not different from that of normal thyroids. 4. Both the highest and the lowest TPO activities were found in cold nodules, but their mean value did not differ from those of their paranodular tissues or normal thyroids. 5. Inter-tissue variability was significantly increased (P less than 0.01) in cold nodules and in tissues paranodular to a hot nodule. 6. These data show that heterogeneity both within and among tissues contributes to the wide range of TPO activity detected in nodular goiters.

  8. 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

  9. LOCALIZED PIGMENTED VILLONODULAR SYNOVITIS: CASE REPORT.

    PubMed

    Carvalho Godoy, Fabiola Andrea de; Faustino, Carlos Alberto Cury; Meneses, Cláudio Santos; Nishi, Sergio Tadao; Góes, César Eduardo Giancoli; Canto, Abaeté Leite do

    2011-01-01

    This case concerned a female patient with a complaint of pain in the anterior region of her left knee during and after sports activities, followed by joint blockage three months ago. From imaging examinations, simple radiography of the knee was normal and magnetic resonance showed a solid expansive mass, possibly corresponding to soft-tissue chondroma or focal nodular synovitis. Arthroscopic resection of the lesion was performed, and the diagnosis of diffuse giant cell tumor resembling localized pigmented villonodular synovitis (PVNS) was made from the result of the anatomopathological examination. The patient presented good clinical evolution, with disappearance of symptoms and return to physical activities.

  10. LOCALIZED PIGMENTED VILLONODULAR SYNOVITIS: CASE REPORT

    PubMed Central

    Carvalho Godoy, Fabiola Andrea de; Faustino, Carlos Alberto Cury; Meneses, Cláudio Santos; Nishi, Sergio Tadao; Góes, César Eduardo Giancoli; Canto, Abaeté Leite do

    2015-01-01

    This case concerned a female patient with a complaint of pain in the anterior region of her left knee during and after sports activities, followed by joint blockage three months ago. From imaging examinations, simple radiography of the knee was normal and magnetic resonance showed a solid expansive mass, possibly corresponding to soft-tissue chondroma or focal nodular synovitis. Arthroscopic resection of the lesion was performed, and the diagnosis of diffuse giant cell tumor resembling localized pigmented villonodular synovitis (PVNS) was made from the result of the anatomopathological examination. The patient presented good clinical evolution, with disappearance of symptoms and return to physical activities. PMID:27027040

  11. Steroid sulfatase deficiency with bilateral periventricular nodular heterotopia.

    PubMed

    Ozawa, Hiroshi; Osawa, Maki; Nagai, Toshiro; Sakura, Nobuo

    2006-03-01

    This report presents a case of steroid sulfatase deficiency with bilateral periventricular nodular heterotopia. A 13-year-old male was diagnosed as having steroid sulfatase deficiency because steroid sulfatase activity was not detected in his leukocytes. In deoxyribonucleic acid studies, steroid sulfatase locus and adjacent loci were found to be deleted in his deoxyribonucleic acid. Cranial magnetic resonance imaging revealed periventricular nodular heterotopia, disclosing an irregular contour of the lateral walls of the lateral ventricles due to small nodular masses that were isointense as to the gray matter. In steroid sulfatase deficiency patients, bilateral periventricular nodular heterotopia must be considered.

  12. Treatment of nasal ala nodular congenital melanocytic naevus with carbon dioxide laser and Q-switched Nd:YAG laser.

    PubMed

    Zeng, Ying; Ji, Chenyang; Zhan, Kui; Weng, Weili

    2016-11-01

    Total excision of congenital melanocytic nevi (CMN) is not always feasible. We here present our experience of using carbon dioxide laser and Q-switched neodymium-doped yttrium-aluminum-garnet (Nd:YAG) laser to treat nodular CMN of the nasal ala. Q-switched Nd:YAG laser and/or carbon dioxide laser were used to treat eight cases of nasal ala nodular CMN. Carbon dioxide laser was utilized to ablate all visible melanocytic tissue within one session. Ablation was performed so as to reproduce the original anatomical contours as closely as possible. Recurrences were treated in the same way. Q-switched Nd:YAG laser was also used to irradiate all target lesions to achieve the desired end point within one session. The intervals between treatments were at least 8 weeks. Recurrence of melanocytic tissue, scar formation, pigmentation, depigmentation, and the degree of patient satisfaction were recorded at every visit. Two of the eight patients were treated with Q-switched Nd:YAG laser. Although, the lesion lightened in one of them, the hyperplastic tissue persisted. Eventually, these two patients, along with the remaining six patients, were successfully treated with a carbon dioxide laser. We recommend carbon dioxide laser treatment for nodular nasal CMN. This simple treatment does not involve skin flap transplantation and has good cosmetic outcomes. Although Q-switched Nd:YAG laser does lighten some nasal nodular CMNs, it does not eradicate the hyperplastic tissue, and is therefore not an effective treatment for nodular nasal CMN.

  13. Mitotane treatment for adrenocortical carcinoma: an overview.

    PubMed

    De Francia, S; Ardito, A; Daffara, F; Zaggia, B; Germano, A; Berruti, A; Di Carlo, F

    2012-03-01

    Adrenocortical carcinoma (ACC) is a rare aggressive endocrine neoplasm characterized by a 5-year survival of less than 50%. Due to the widespread use of imaging techniques in clinics, ACC is increasingly recognized as an incidentally discovered tumor. Mostly characterized by poor prognosis, ACC is often diagnosed at an advanced stage of disease. Early diagnosis is uncommon; when diagnosed, ACCs are usually large and have invaded adjacent organs, even if metastatic spread to distant sites can be absent. Complete surgical resection is the only potentially curative treatment for patients with localized disease; however, due to a recurrence rate of 50-70% after apparent radical surgery, there is a strong rationale for a concomitant systemic treatment. Adrenolytic therapy with mitotane (o,p›-DDD), administered alone or in combination with others antineoplastic agents, is the primary treatment for patients with advanced ACC and is increasingly used also in an adjuvant setting, even if controversy exists on this issue due to the limitations of the available literature. Despite being in use for many years, the rarity of ACC precluded the organization of randomized trials; thus, many areas of uncertainty and controversy remain regarding the role of this old drug in the clinical management of patients with ACC. The purpose of this paper is to review the current evidence on mitotane treatment in patients with advanced disease and in ACC patients after complete surgical resection as adjuvant treatment.

  14. Bilateral periventricular nodular heterotopia with megalencephaly: a case report.

    PubMed

    Abe, Yu; Kobayashi, Satoru; Wakusawa, Keisuke; Tanaka, Soichiro; Inui, Takehiko; Yamamoto, Toshiyuki; Kunishima, Shinji; Haginoya, Kazuhiro

    2014-06-01

    Bilateral periventricular nodular heterotopia is a neuronal migration disorder characterized by gray matter cellular rests in the periventricular regions. Megalencephaly has not been reported in children with bilateral periventricular nodular heterotopia. No other disorder with a similar phenotype has been reported. Here we report the case of a 5-year-old Japanese boy with bilateral periventricular nodular heterotopia and megalencephaly. Relative macrocephaly was evident at birth, and bilateral periventricular nodular heterotopia and megalencephaly were noted on magnetic resonance imaging (MRI). However, no hydrocephalus or indication of cerebral cortical dysplasia was seen. A mild intellectual disability was present, but the patient had no history of seizures. Genetic analysis revealed no mutation on the capillary sequences for FLNA, and no pathogenic abnormalities were evident on array comparative genomic hybridization. This case could represent a new disease entity: bilateral periventricular nodular heterotopia with megalencephaly.

  15. 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 ...

  16. Aging effects on oxidative phosphorylation in rat adrenocortical mitochondria.

    PubMed

    Solinas, Paola; Fujioka, Hisashi; Radivoyevitch, Tomas; Tandler, Bernard; Hoppel, Charles L

    2014-06-01

    Does aging in itself lead to alteration in adrenocortical mitochondrial oxidative phosphorylation? Mitochondria from Fischer 344 (F344) rats (6 and 24 months old), Brown Norway rats (6 and 32 months old) and F344-Brown Norway hybrid rats (6 and 30 months old) were compared. Mitochondria were isolated from extirpated adrenal cortex. The yields of mitochondria were quantitatively similar in all rat strains irrespective of age. In order to assess the activity of each mitochondrial complex, several different substrates were tested and the rate of oxidative phosphorylation measured. Aging does not affect mitochondrial activity except in the F344 rat adrenal cortex where the maximal ADP-stimulated oxidative phosphorylation decreased with age. We hypothesize that impaired synthesis of steroid hormones by the adrenal cortex with age in F344 rats might be due to decreased adrenocortical mitochondrial oxidative phosphorylation. We conclude that aging results in adrenocortical mitochondria effects that are non-uniform across different rat strains.

  17. How is Adrenocortical Cancer being Managed in the UK?

    PubMed Central

    Aspinall, Sebastian R; Imisairi, AH; Bliss, RD; Scott-Coombes, D; Harrison, BJ; Lennard, TWJ

    2009-01-01

    INTRODUCTION Adrenocortical carcinomas are rare. This case series is reported to give an overview of how adrenocortical carcinoma is currently managed in the UK. PATIENTS AND METHODS A retrospective review was made of case notes from patients with adrenocortical carcinomas presenting to the authors (TWJL, RDB, BJH, and DS-C) over the past 10 years in Newcastle, Sheffield and Cardiff. RESULTS Newcastle treated twelve, Sheffield eleven and Cardiff seven cases. The median follow-up was 25.5 months (range, 1–102 months). All tumours were greater than 5 cm in diameter. The majority presented with symptoms of hormone excess. Adrenalectomy was performed in 83% – this was radical in 30% and followed by excision of recurrence in 13%. Adjuvant mitotane was given in 64% of patients, in combination with cytotoxic chemotherapy in 20%. One-third of patients did not receive any adjuvant therapy. There was no significant difference in survival between the three centres. The majority of patients (57%) died during the period of follow-up of this study. The median survival was 37 months (range, 2–102 months). CONCLUSIONS The size of tumour, stage and mode of presentation, age and overall survival of patients in this study are comparable to published series of adrenocortical carcinomas from major endocrine surgical centres world-wide. Despite controversies about benefits, adjuvant mitotane was used in the majority of cases, whereas cytotoxic chemotherapy was only used in the minority. The exact role of adjuvant therapy in the management of adrenocortical carcinoma is not as well established as for other more common malignancies. Establishing a database for adrenocortical carcinomas in the UK would contribute to our understanding of the management of this disease. PMID:19558758

  18. Monascus pigments.

    PubMed

    Feng, Yanli; Shao, Yanchun; Chen, Fusheng

    2012-12-01

    Monascus pigments (MPs) as natural food colorants have been widely utilized in food industries in the world, especially in China and Japan. Moreover, MPs possess a range of biological activities, such as anti-mutagenic and anticancer properties, antimicrobial activities, potential anti-obesity activities, and so on. So, in the past two decades, more and more attention has been paid to MPs. Up to now, more than 50 MPs have been identified and studied. However, there have been some reviews about red fermented rice and the secondary metabolites produced by Monascus, but no monograph or review of MPs has been published. This review covers the categories and structures, biosynthetic pathway, production, properties, detection methods, functions, and molecular biology of MPs.

  19. 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.

  20. [Hepatocellular nodular hyperplasias, adenomas and carcinomas].

    PubMed

    Altmann, H W

    1995-01-01

    Nodular hyperplasias ("hyperplasiomas") are new formations whose development as a required and regulated response can be traced either to compensatory reactions to the loss of cells (regeneration in a narrow sense) and to decreased cellular performance, or to primary growth impulses. Included in this group are: the "macroregenerative nodules" after extensive cell losses; solitary nodules of uncertain etiology; and the minute foci of "micronodular transformation" whose origin can be traced to a particular disturbance of the hepatic blood supply. The so-called "adenomatous hyperplasias" of the cirrhotic liver that have a tendency towards carcinomatous change are not included in this group and are perhaps better considered as "hyperplasiogenic adenomas". The so-called "focal nodular hyperplasia" too, it must be stressed, should be separated from the simple hyperplasias, for it is more closely related to the adenomas, but represents a new formation of limited growth potential. Morphologically it is conspicuously subdivided by multiple connective tissue bands and scars, but it is above all characterized by metaplastically derived neoductuli, and hence it is appropriately designated as a "combined nodule". Among the true uninodular adenomas there are several variants differing in their morphology,--the so-called "atypical" or "intermediate" forms, that can give rise to carcinomas. The hepatocellular carcinoma, that may arise in a variety of ways, presents multiple cytological and histological variants, but only the so-called "fibrolamellar carcinoma" presents also a clinical peculiarity. "Hepatoblastomas" differ from the common hepatocellular carcinomas by their origin in early childhood from immature early precursor cells and, in the later phases of life, from redifferentiated cells that can even give rise to mesenchymal elements. There is no evidence of the existence of particular pluripotential stem cells.

  1. Adrenocortical carcinoma (ACC): diagnosis, prognosis, and treatment

    PubMed Central

    Libé, Rossella

    2015-01-01

    Adrenocortical carticnoma (ACC) is a rare malignancy with an incidence of 0.7–2.0 cases/million habitants/year. The diagnosis of malignancy relies on careful investigations of clinical, biological, and imaging features before surgery and pathological examination after tumor removal. Most patients present with steroid hormone excess or abdominal mass effects, but 15% of patients with ACC is initially diagnosed incidentally. After the diagnosis, in order to assess the ACC prognosis and establish an adequate basis for treatment decisions different tools are proposed. The stage classification proposed by the European Network for the Study of Adrenal Tumors (ENSAT) is recommended. Pathology reports define the Weiss score, the resection status and the proliferative index, including the mitotic count and the Ki67 index. As far as the treatment is concerned, in case of tumor limited to the adrenal gland, the complete resection of the tumor is the first option. Most patients benefit from adjuvant mitotane treatment. In metastatic disease, mitotane is the cornerstone of initial treatment, and cytotoxic drugs should be added in case of progression. Recently, the First International Randomized (FIRM-ACT) Trial in metastatic ACC reported the association between mitotane and etoposide/doxorubicin/cisplatin (EDP) as the new standard in first line treatment of ACC. In last years, new targeted therapies, including the IGF-1 receptor inhibitors, have been investigated, but their efficacy remains limited. Thus, new treatment concepts are urgently needed. The ongoing “omic approaches” and next-generation sequencing will improve our understanding of the pathogenesis and hopefully will lead to better therapies. PMID:26191527

  2. 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

  3. Multi-column chromatography of urinary steriods and adrenocortical dysfunction.

    PubMed

    Sayegh, J F; Vestergaard, P

    1978-01-01

    The potential of the multi-column assay for urinary neutral steroids in work with samples from patients with adrenocortical pathology is demonstrated through analyses performed on urine samples from Cushing and congenital adrenal hyperplasia cases, after modification of the routine methodology to include the quantitation of additional steroids of particular importance for pathological samples.

  4. Stress, reproduction, and adrenocortical modulation in amphibians and reptiles.

    PubMed

    Moore, Ignacio T; Jessop, Tim S

    2003-01-01

    While the hypothalamo-pituitary-adrenocortical (HPA) response to stress appears to be conserved in vertebrates, the manner in which it is activated and its actions vary. We examine two trends in the stress biology literature that have been addressed in amphibian and reptilian species: (1). variable interactions among stress, corticosterone, and reproduction and (2). adrenocortical modulation. In the first topic we examine context-dependent interactions among stress, corticosterone, and reproduction. An increasing number of studies report positive associations between reproduction and corticosterone that contradict the generalization that stress inhibits reproduction. Moderately elevated levels of stress hormones appear to facilitate reproduction by mobilizing energy stores. In contrast, pronounced activation of the HPA axis and extremely elevated levels of stress hormones appear to inhibit reproduction. Much of these contrasting effects of stress and reproduction can be explained by expanding the Energetics-Hormone Vocalization Model, proposed for anuran calling behavior, to other taxa. In the second topic, a number of amphibians and reptiles modulate their HPA stress response. Adrenocortical modulation can occur at multiple levels and due to a variety of factors. However, we have little information as to the physiological basis for the variability. We suggest that several ecologically based ideas, such as variability in the length of the breeding season and lifetime reproductive opportunities, can be used to explain the utility of adrenocortical modulation in these taxa.

  5. Laparoscopic bilateral partial adrenalectomy for adrenocortical adenomas causing Cushing's syndrome: report of a case.

    PubMed

    Inoue, Tomoko; Ishiguro, Kiyosuke; Suda, Takako; Ito, Norimasa; Suzuki, Yoshimasa; Taniguchi, Yuji; Ohgi, Shigetsugu

    2006-01-01

    Laparoscopic total adrenalectomy has become a standard technique for small adrenal tumors; however, bilateral adrenalectomy results in postoperative adrenal insufficiency, necessitating lifelong steroid replacement. To preserve adrenocortical function in a 41-year-old woman with bilateral adrenocortical adenoma (BAA) causing Cushing's syndrome, we performed laparoscopic bilateral partial adrenalectomy. We based our preoperative diagnosis of bilateral adrenocortical tumors causing Cushing's syndrome on the results of endocrinological investigations and imaging findings. Thus, we performed lateral transperitoneal laparoscopic bilateral partial adrenalectomy, preserving the adrenal glands, which were normal. Pathological examination of both tumors confirmed the diagnosis of adrenocortical adenoma. The patient had no postoperative complications, and her adrenocortical function was normal without steroid replacement at her 10-month follow-up. This report shows that Cushing's syndrome resulting from bilateral adenomas can be effectively treated by laparoscopic bilateral partial adrenalectomy as a minimally invasive, adrenocortical-preserving operation.

  6. 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).

  7. Benign Nodular Goiter Causing Upper Airway Obstruction

    PubMed Central

    Başoğlu, Mahmut; Öztürk, Gürkan; Aydınlı, Bülent; Yıldırgan, M. İlhan; Atamanalp, S. Selçuk; Celebi, Fehmi

    2009-01-01

    Objective Benign nodular goiter (BNG) can cause narrowing of the upper airway. In some rare cases, obstruction of the upper airway also occurs. The following paper reports our experiences with regard to BNG patients who experienced obstruction of the upper airway. Materials and Methods. We retrospectively investigated the records of 13 patients with acute airway obstruction due to BNG who were admitted to the General Surgery Department of Ataturk University Medical School between January 2000 and December 2007. Results Thirteen patients with airway obstruction secondary to BNG were hospitalized during this period. There were two males and 11 females, and the mean age was 58.5 years (range 37–74 years). For all patients, the primary symptom upon admission was defined as respiratory distress; all patients had varying degrees of respiratory distress upon admission. Three of the patients underwent emergent endotracheal intubation in the emergency room. A preoperative radiological evaluation was performed with thyroid ultrasonography (US) and computed tomography (CT). There were retrosternal or substernal components of the BNG in nine patients. Twelve patients underwent operations, while one patient with mild respiratory distress elected not to be operated on. Ten patients underwent total thyroidectomies, while two patients underwent near-total thyroidectomies. One patient with retrosternal goiter also underwent a median sternotomy. Three patients received a tracheostomy after the operation. Suction drains were utilized in all operations. During the post-operative period, two patients suffered from voice impairment, and seven patients experienced hypocalcemia. Two patients died. Pathological examination of the thyroidectomy tissue revealed BNG in all cases. In addition, two patients had micropapillary carcinomas. Conclusion Although BNG causing upper airway obstruction is rare, it is an important clinical entity because of the need for emergent operation, the

  8. Gallium-67 uptake by a benign adrenocortical adenoma

    SciTech Connect

    Jackson, J.A.; Naul, L.G.; Montgomery, J.L.; Carpentier, W.R.; Roberts, J.W.

    1988-08-01

    A 55-yr-old man presented with an atypical relapsing meningitis and was found to have intense unilateral adrenal uptake by /sup 67/Ga imaging. Computed tomography showed a 4-cm right adrenal mass which was hypointense on the T1-weighted images and mildly hyperintense on the T2-weighted images of a magnetic resonance (MR) scan. At surgery, a coincidental benign adrenocortical adenoma was found. Because /sup 67/Ga uptake is usually associated with inflammatory or malignant lesions and malignant adrenal lesions are hyperintense on T2-weighted MR images, these findings contributed to diagnostic uncertainty in this patient. Thus, a nonhyperfunctional adrenocortical adenoma may be associated with abnormal /sup 67/Ga uptake and atypical MR findings.

  9. 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

  10. Occult Adrenocortical Carcinoma and Unexpected Early Childhood Death.

    PubMed

    Pilla, Mark; Gilbert, John; Moore, Lynette; Byard, Roger W

    2017-01-01

    A four-year-old previously well boy collapsed unexpectedly and was taken immediately to hospital, where he developed seizures and cardiogenic shock with lethal, rapidly progressing multi-organ failure. At autopsy, the height was >90th percentile and there were indications of early virilization. Internally, a friable tumor of the left adrenal gland was identified that had invaded the left renal vein and inferior vena cava. Histology revealed typical features of an adrenocortical carcinoma with aggregated trabeculae of cells containing abundant eosinophilic cytoplasm and large pleomorphic nuclei. There was strong positive cytoplasmic staining for inhibin; mitochondria were shown on electron microscopy to contain prominent electron-dense granules. Death was due to massive pulmonary tumor embolism. Although adrenocortical carcinomas are very rare and are more commonly found in adults, the current case demonstrates that they may also occur in childhood and be responsible for unexpected death by the very unusual mechanism of tumor embolism.

  11. Acute self-suppression of corticosteroidogenesis in isolated adrenocortical cells.

    PubMed

    Carsia, R V; Malamed, S

    1979-10-01

    The relation between steroidogenesis induced by ACTH and that induced by exogenous concentrations of glucocorticoids was studied in isolated adrenocortical cells. Exogenous corticosterone and cortisol, in concentrations within the production capacity of the adrenal gland, suppressed steroidogenesis induced by ACTH in rat and beef cells, respectively. The precursors pregnenolone and progesterone enhanced steroidogenesis in both rat and beef cells. Aldosterone in rat cells and 17 beta-estradiol in rat and beef cells had little if any effect on steroidogenesis. Either suppression or stimulation by exogenous steroids was acute, that is, after 2-h incubation for rat cells and 1-h incubation for beef cells. A direct suppressive action of end product glucocorticoids is indicated. This observed self-suppression of adrenocortical cells suggests the existence of a mechanism for the find adjustment of steroidogenesis that operates in addition to the classical control exerted by the anterior pituitary.

  12. [Irreversible coma following hypoglycemia in Sheehan syndrome with adrenocortical insufficiency].

    PubMed

    Sas, A M; Meynaar, I A; Laven, J S; Bakker, S L; Feelders, R A

    2003-08-23

    A 24-year-old woman of Somali origin delivered at term after an uncomplicated pregnancy. Post-partum haemorrhage resulted in hypovolaemic shock which was treated by hysterectomy. Five days later she became comatose due to unrecognised hypoglycaemia which caused severe irreversible brain damage and status epilepticus. Treatment in the intensive care unit with artificial respiration, prednisolone, desmopressin, inotropic support, barbiturates and an anaesthetic under EEG guidance was unsuccessful. The patient died 28 days post-partum. The hypoglycaemia was due to a combination of (a) inadequate glucose intake and (b) lack of counter-regulatory mechanisms due to a deficiency of steroids and growth hormone as a result of loss of pituitary function (Sheehan syndrome) together with adrenocortical insufficiency. The combination of Sheehan syndrome and primary adrenocortical insufficiency has not been described previously in the literature.

  13. Oral pigmentation: A review.

    PubMed

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

    2015-08-01

    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.

  14. 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

  15. 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

  16. Chylous ascites after resection of giant adrenocortical carcinoma

    PubMed Central

    Karakoyun, Rojbin; Demirci, Erkan; Alikanoglu, Arsenal Sezgin

    2016-01-01

    Postoperative chylous ascites (PCA) is a rare clinical state that occurs during abdominal surgery. Despite its rarity, the need to diagnose and treat PCA is increasing in importance with the increased number of wide resections and lymph node dissections being performed and the serious consequences of treatment. Here we describe the PCA complications we observed after resection for treating a case of giant adrenocortical carcinoma and we have the brief review of the PCA complication. PMID:28149812

  17. Adrenocortical carcinoma: modern management and evolving treatment strategies

    PubMed Central

    McDuffie, Lucas A; Aufforth, Rachel D

    2016-01-01

    Adrenocortical carcinoma (ACC) is a rare cancer with a poor prognosis. Unlike many other cancers, there has been little improvement in patient outcome over the past several decades. However, as scientific advancements are made and our understanding of the molecular genetics involved in ACC improve then progress may be achieved in this devastating disease. This review focuses on recent literature published in the field of ACC from 2010 to 2015 with an emphasis on improving diagnosis, staging and treatment for ACC. PMID:27213037

  18. [Adrenalectomy for preservation of adrenocortical function. Indication and results].

    PubMed

    Walz, M K

    2009-02-01

    The standard procedure for adrenal tumors is total adrenalectomy. In order to preserve adrenocortical function, partial adrenalectomy has become an accepted and proven option in bilateral hereditary pheochromocytomas. For this at least one third of one gland has to be maintained. In unilateral adrenal tumors, partial adrenalectomy has mainly been used in Conn's syndrome. Studies demonstrate results identical to those of total adrenalectomy. All other adrenal tumors are exceptional indications for partial adrenalectomy.

  19. 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...

  20. 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

  1. 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.

  2. Outcomes of Adjuvant Mitotane after Resection of Adrenocortical Carcinoma: A 13-Institution Study by the US Adrenocortical Carcinoma Group

    PubMed Central

    Postlewait, Lauren M; Ethun, Cecilia G; Tran, Thuy B; Prescott, Jason D; Pawlik, Timothy M; Wang, Tracy S; Glenn, Jason; 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; Staley, Charles A; Poultsides, George A; Maithel, Shishir K

    2016-01-01

    BACKGROUND Current treatment guidelines recommend adjuvant mitotane after resection of adrenocortical carcinoma with high-risk features (eg, tumor rupture, positive margins, positive lymph nodes, high grade, elevated mitotic index, and advanced stage). Limited data exist on the outcomes associated with these practice guidelines. STUDY DESIGN Patients who underwent resection of adrenocortical carcinoma from 1993 to 2014 at the 13 academic institutions of the US Adrenocortical Carcinoma Group were included. Factors associated with mitotane administration were determined. Primary end points were recurrence-free survival (RFS) and overall survival (OS). RESULTS Of 207 patients, 88 (43%) received adjuvant mitotane. Receipt of mitotane was associated with hormonal secretion (58% vs 32%; p = 0.001), advanced TNM stage (stage IV: 42% vs 23%; p = 0.021), adjuvant chemotherapy (37% vs 5%; p < 0.001), and adjuvant radiation (17% vs 5%; p = 0.01), but was not associated with tumor rupture, margin status, or N-stage. Median follow-up was 44 months. Adjuvant mitotane was associated with decreased RFS (10.0 vs 27.9 months; p = 0.007) and OS (31.7 vs 58.9 months; p = 0.006). On multivariable analysis, mitotane was not independently associated with RFS or OS, and margin status, advanced TNM stage, and receipt of chemotherapy were associated with survival. After excluding all patients who received chemotherapy, adjuvant mitotane remained associated with decreased RFS and similar OS; multivariable analyses again showed no association with recurrence or survival. Stage-specific analyses in both cohorts revealed no association between adjuvant mitotane and improved RFS or OS. CONCLUSIONS When accounting for stage and adverse tumor and treatment-related factors, adjuvant mitotane after resection of adrenocortical carcinoma is not associated with improved RFS or OS. Current guidelines should be revisited and prospective trials are needed. PMID:26775162

  3. Invasive Ocular Surface Squamous Neoplasia Masquerading as Nodular Scleritis.

    PubMed

    Sharma, Medha; Sundar, Dheepak; Vanathi, Murugesan; Meel, Rachna; Kashyap, Seema; Chawla, Rohan; Tandon, Radhika

    The authors report a rare case of ocular surface squamous neoplasia with intraocular involvement that had an initial masquerade presentation of recurrent anterior nodular scleritis. A 35-year-old male patient presented with right eye recurrent anterior nodular scleritis for which a lamellar patch graft was done. Two months later, the patient presented with recurrence of symptoms. Histopathology review revealed the presence of well-differentiated squamous cell malignancy. A high index of suspicion for malignancy is required in such cases when they do not respond to conventional therapy.

  4. Pregnancy in a patient with adrenocortical carcinoma during treatment with Mitotane - a case report.

    PubMed

    Baszko-Błaszyk, Daria; Ochmańska, Katarzyna; Waśko, Ryszard; Sowiński, Jerzy

    2011-01-01

    We present the case of a female patient with virilising adrenocortical carcinoma treated surgically who conceived during adjuvant treatment with mitotane. We discuss the frequently erroneous routine treatment with oral hormonal contraception without thorough differential diagnosis in female patients with oligo-/amenorrhea and subsequent delay in the proper diagnosis of adrenocortical carcinoma.

  5. Multifocal nodular fasciitis of the hand and shoulder: case report.

    PubMed

    Kotha, Guruvardhan Kumar; Bj, Venkatramana; Maryada, Venkateshwar Reddy; Jawalkar, Harshad

    2014-12-01

    We report a case of nodular fasciitis occurring on the dorsum of the right middle finger, the dorsum of the right hand, and the right upper back associated with cortical erosions of the scapula. Ray amputation of the middle finger and marginal excision of the hand and periscapular masses were performed. There was no recurrence of the tumor at either site a year later.

  6. Hereditary nodular heterotopia accompanied by mega cisterna magna.

    PubMed

    Oda, T; Nagai, Y; Fujimoto, S; Sobajima, H; Kobayashi, M; Togari, H; Wada, Y

    1993-08-15

    This is the first report of hereditary nodular heterotopia accompanied by mega cisterna magna. Magnetic resonance imaging documented multiple bilateral subependymal nodules, which were isointense to gray matter. This disease entity is considered a dominant trait, since the mother and two daughters, half-sisters, were affected.

  7. 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.

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

    PubMed

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

    2015-10-30

    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.

  9. Glucocorticoid control of steroidogenesis in isolated rat adrenocortical cells.

    PubMed

    Carsia, R V; Malamed, S

    1983-08-17

    The role of end-product glucocorticoids in the regulation of corticosteroidogenesis in isolated adrenocortical cells was investigated. Trypsin-isolated cells from male rat adrenal glands were incubated with or without corticotropin (ACTH) and with or without corticosterone. Endogenous corticosterone production was determined by radioimmunoassay at the end of incubation. Cessation of ACTH-induced corticosterone production was apparent after 2-4 h of incubation. The suppression occurred later with lower cell concentrations. Corticosterone production was partially restored after washing the suppressed cells. Supernatant fluid from suppressed cell suspensions also suppressed steroidogenesis of a fresh population of cells. However, the suppressing property of the supernatant fluid was abolished after the removal of corticosterone by charcoal-dextran treatment, suggesting that corticosterone or other steroids caused the suppression. Exogenous corticosterone induced suppression over a wide range of ACTH concentrations, but did not change the half-maximal steroidogenic concentration of ACTH, indicating that the suppression does not change the sensitivity of the cells to ACTH. Suppression occurred within 30-60 min after corticosterone had been added to the incubation medium either at the start of incubation or while steroidogenesis was in progress. Suppression varied directly with the concentration of exogenous corticosterone. These data indicate that glucocorticoids can directly and acutely suppress corticosteroidogenesis and thus control adrenocortical function in concert with other regulators such as ACTH and Ca2+.

  10. 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

  11. 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.

  12. 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

  13. A nodular-ulcerative form of secondary syphilis in AIDS

    PubMed Central

    Owen, Benjamin D.; Balavenkataraman, Arvind; Weinstein, Mitchell R.

    2017-01-01

    An uncommon variant in the pre-AIDS era, lues maligna is a nodular-ulcerative form of secondary syphilis. We present a case of a 41-year-old man with HIV infection who developed fever, chills, nausea, vomiting, right upper quadrant abdominal pain, weight loss, watery diarrhea, and a painless, nonpruritic rash. He had diffuse nodular-ulcerative lesions in various stages of development. He was found to have a CD4 count of 101 cells/mm3 (22%), an HIV viral load of 2,735,060 copies/mL, and a positive rapid plasma reagin at 1:64. He was started on emtricitabine, tenofovir, and dolutegravir, as well as doxycycline. He was given benzathine penicillin 2.4 million units intramuscularly and within hours developed a Jarisch-Herxheimer reaction. Skin lesions showed signs of healing, and constitutional symptoms improved 48 hours later. PMID:28127144

  14. Nodular fasciitis of the hand: excision preserving 'vital' structures.

    PubMed

    Al-Qattan, M M; Arafah, M M

    2014-10-01

    Nodular fasciitis is an extremely rare benign fibrous tumour of the hand. Although benign, the tumour is frequently adherent to tendons/nerves and joints of the hand. However, the tumour may spontaneously regress and does not tend to recur following excision with histologically positive margins. For the last 20 years, the author has adopted a specific management approach for these and other benign fibrous tumours of the hand. Following the clinical/radiological diagnosis, tumour excision is done preserving 'vital' structures within the hand. The diagnosis is confirmed histologically and by immune stains, and the patient is then followed up for local recurrence. Over a 20-year period, the author has treated four cases of nodular fasciitis of the hand using this management approach. Despite the positive margins in all cases, there were no recurrences at a minimum follow-up interval of 3 years.

  15. Nodular fasciitis in finger simulating soft tissue malignancy.

    PubMed

    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.

  16. 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

  17. Ion transport in pigmentation.

    PubMed

    Bellono, Nicholas W; Oancea, Elena V

    2014-12-01

    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.

  18. 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

  19. 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.

  20. Morpho-histodifferentiation of Billbergia Thunb. (Bromeliaceae) nodular cultures.

    PubMed

    de Souza, Thaysi Ventura; Thiesen, Julia Faillace; Lando, Ana Paula; Guerra, Miguel Pedro; Santos, Marisa

    2017-01-01

    Nodule cultures are formed through an intermediate morphogenetic route that lies between organogenesis and somatic embryogenesis. Although well described in many species, different aspects of the morphological and histological development of nodules remain to be clarified. Based on their threatened status and high ornamental value, Billbergia alfonsi-joannis and Billbergia zebrina, two epiphytic bromeliad species endemic to the South American Atlantic Forest, were studied. Nodular cultures were induced to grow from nodal segments taken from etiolated seedlings grown in vitro for 12 weeks in the dark on MS medium supplemented with 1 μM TDZ. Samples were taken for analysis weekly over 8 weeks of growth and analyzed under light, transmission electron, and scanning electron microscopes. Morphological and histological analysis showed that nodular clusters originated from stem pericycles and consisted of a polycenter, cambial tissue, cortical parenchyma, and a covering tissue. The polycenter consisted of an organizational center dispersed in parenchymal tissue. Each organizational center was formed by a vascular system surrounded by a bundle sheath. A cambial tissue surrounded these polycenters, promoting the regeneration of new nodules and leading to the formation of buds and roots. Primary nodules could generate secondary nodules in a repetitive process. Thus, histological analysis revealed the origin and formation of nodular cultures. These new data will support the establishment of micropropagation protocols and regeneration on a large scale for these species.

  1. 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.

  2. Hot spot liver scan in focal nodular hyperplasia

    SciTech Connect

    Piers, D.A.; Houthoff, H.J.; Krom, R.A.F.; Schuur, K.H.; Sikkens, H.; Weits, J.

    1980-12-01

    In scintigraphy of the liver with radiocolloid, space-occupying lesions generally are visualized as regions of decreased accumulation of radioactivity. Rarely focal areas of increased activity are depicted; most are related to altered vascular dynamics in the liver secondary to obstruction of the superior or inferior vena cava or the hepatic veins. There are reports of single cases of focally increased activity due to a hepatic hemangioma, hepatic venoocclusive disease, herniation of a part of the liver, and a liver hot spot found after radiocolloid injection via a malpositioned central venous catheter in one of the hepatic vein branches. In patients with focal nodular hyperplasia, liver scans with solitary defects as well as normal patterns are found. In some cases, increased uptake of colloid in the lesion has been documented. Pasquier and Dorta reported a patient with a palpable mass in the left liver lobe with increased accumulation of radioactivity on the radiocolloid liver scan. The histologic diagnosis was hamartoma, but reviewing the description and considering the confusion in the past concerning the nomenclature, this case is suggestive of focal nodular hyperplasia. We report a patient with focal nodular hyperplasia who had increased radiocolloid uptake in the lesion. The radionuclide studies are compared with angiography, sonography, and computed tomography. An explanation for the localized increased colloid accumulation based on histologic findings is suggested.

  3. Diagnostic accuracy of nodular gastritis for H. pylori infection

    PubMed Central

    Romero-Flores, Juan L; Fernandez-Rivero, Justo A; Marroquín-Fabian, Erika; Téllez-Ávila, Félix I; Sánchez-Jiménez, Beatriz A; Juárez-Hernández, Eva; Uribe, Misael; Chávez-Tapia, Norberto C

    2017-01-01

    Background The term nodular is not included in the Sydney classification and there is no widely accepted histopathological definition. It has been proposed that the presence of antral nodularity could predict Helicobacter pylori (H. pylori) infection. The aim of this study was to determine the diagnostic accuracy of nodular gastritis (NG) for H. pylori infection after a rigorous standardization process, and to describe the associated histopathological characteristics. Materials and methods Endoscopic images of patients submitted to endoscopy with biopsy sampling were included. Endoscopic images were distributed among six endoscopists. The analysis was performed sequentially in three rounds: the first round assessed the interobserver variability, the second evaluated the intraobserver variability, and the third calculated the interobserver variability after training. A correlation analysis between endoscopic and histopathological findings was performed. Results A total of 917 studies were included. In the first analysis of interobserver variability, a poor kappa value (0.078) was obtained. The second evaluation yielded good intraobserver variability, with kappa values of 0.62–0.86. The evaluation of interobserver variability after training revealed an improvement in the kappa value of 0.42. A correlation was found between endoscopic images and histopathological reports. Conclusion There was a strong correlation between NG and H. pylori, but only after rigorous evaluation. The use of the term NG requires extensive standardization before it can be used clinically. PMID:28031716

  4. 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...

  5. Analysis of circulating microRNAs in adrenocortical tumors.

    PubMed

    Szabó, Diana Rita; Luconi, Michaela; Szabó, Peter M; Tóth, Miklós; Szücs, Nikolette; Horányi, János; Nagy, Zoltán; Mannelli, Massimo; Patócs, Attila; Rácz, Károly; Igaz, Peter

    2014-03-01

    Differential diagnosis of adrenocortical adenoma (ACA) and carcinoma is of pivotal clinical relevance, as the prognosis and clinical management of benign and malignant adrenocortical tumors (ACTs) is entirely different. Circulating microRNAs (miRNAs) are promising biomarker candidates of malignancy in several tumors; however, there are still numerous technical problems associated with their analysis. The objective of our study was to investigate circulating miRNAs in ACTs and to evaluate their potential applicability as biomarkers of malignancy. We have also addressed technical questions including the choice of profiling and reference gene used. A total of 25 preoperative plasma samples obtained from patients with ACAs and carcinomas were studied by microarray and quantitative real-time PCR. None of the three miRNAs (hsa-miR-192, hsa-mir-197 and hsa-miR-1281) found as differentially expressed in plasma samples in our microarray screening could be validated by quantitative real-time PCR. In contrast, of the selected eight miRNAs reported in the literature as differentially expressed in ACT tissues, five (hsa-miR-100, hsa-miR-181b, hsa-miR-184, hsa-miR-210 and hsa-miR-483-5p) showed a statistically significant overexpression in adrenocortical cancer vs adenoma when normalized on hsa-miR-16 as a reference gene. Receiver operator characteristic analysis of data revealed that the combination of dCThsa-miR-210 - dCThsa-miR-181b and dCThsa-miR-100/dCThsa-miR-181b showed the highest diagnostic accuracy (area under curve 0.87 and 0.85, respectively). In conclusion, we have found significant differences in expression of circulating miRNAs between ACAs and carcinomas, but their diagnostic accuracy is not yet high enough for clinical application. Further studies on larger cohorts of patients are needed to assess the diagnostic and prognostic potential application of circulating miRNA markers.

  6. 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.

  7. Complex Glycerol Kinase Deficiency and Adrenocortical Insufficiency in Two Neonates

    PubMed Central

    Korkut, Sabriye; Baştuğ, Osman; Raygada, Margarita; Hatipoğlu, Nihal; Kurtoğlu, Selim; Kendirci, Mustafa; Lyssikatos, Charalampos; Stratakis, Constantine A.

    2016-01-01

    Contiguous gene deletions of chromosome Xp21 can lead to glycerol kinase deficiency and severe adrenocortical insufficiency (AI) in a male newborn among other problems. We describe our experience with two such patients who presented with dysmorphic facies, AI, and pseudo-hypertriglyceridemia. Both infants had normal serum 17-hidroxyprogesterone levels, and adrenal glands could not be observed with ultrasonography. Creatine kinase and triglyceride levels were measured to elucidate the etiology of adrenal hypoplasia and were above normal limits in both cases. Both patients required steroid and salt supplementation. They were both found to have Xp21.2 deletions (DMD, NR0B1, GK, IL1RAPL1). We conclude that AI in the context of other genetic abnormalities should prompt chromosomal investigations in the absence of another unifying explanation. PMID:27087023

  8. Complex Glycerol Kinase Deficiency and Adrenocortical Insufficiency in Two Neonates.

    PubMed

    Korkut, Sabriye; Baştuğ, Osman; Raygada, Margarita; Hatipoğlu, Nihal; Kurtoğlu, Selim; Kendirci, Mustafa; Lyssikatos, Charalampos; Stratakis, Constantine A

    2016-12-01

    Contiguous gene deletions of chromosome Xp21 can lead to glycerol kinase deficiency and severe adrenocortical insufficiency (AI) in a male newborn among other problems. We describe our experience with two such patients who presented with dysmorphic facies, AI, and pseudo-hypertriglyceridemia. Both infants had normal serum 17-hidroxyprogesterone levels, and adrenal glands could not be observed with ultrasonography. Creatine kinase and triglyceride levels were measured to elucidate the etiology of adrenal hypoplasia and were above normal limits in both cases. Both patients required steroid and salt supplementation. They were both found to have Xp21.2 deletions (DMD, NR0B1, GK, IL1RAPL1). We conclude that AI in the context of other genetic abnormalities should prompt chromosomal investigations in the absence of another unifying explanation.

  9. 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

  10. Virilizing Adrenocortical Carcinoma Advancing to Central Precocious Puberty after Surgery

    PubMed Central

    Kim, Min Sun; Yang, Eu Jeen; Cho, Dong Hyu; Hwang, Pyung Han

    2015-01-01

    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

  11. 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.

  12. 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.

  13. Current and Emerging Therapeutic Options in Adrenocortical Cancer Treatment

    PubMed Central

    Stigliano, Antonio; Cerquetti, Lidia; Sampaoli, Camilla; Bucci, Barbara; Toscano, Vincenzo

    2012-01-01

    Adrenocortical carcinoma (ACC) is a very rare endocrine tumour, with variable prognosis, depending on tumour stage and time of diagnosis. The overall survival is five years from detection. Radical surgery is considered the therapy of choice in the first stages of ACC. However postoperative disease-free survival at 5 years is only around 30% and recurrence rates are frequent. o,p'DDD (ortho-, para'-, dichloro-, diphenyl-, dichloroethane, or mitotane), an adrenolytic drug with significant toxicity and unpredictable therapeutic response, is used in the treatment of ACC. Unfortunately, treatment for this aggressive cancer is still ineffective. Over the past years, the growing interest in ACC has contributed to the development of therapeutic strategies in order to contrast the neoplastic spread. In this paper we discuss the most promising therapies which can be used in this endocrine neoplasia. PMID:22934112

  14. 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

  15. Photosynthetic Pigments in Diatoms.

    PubMed

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

    2015-09-16

    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.

  16. Actual 10-Year Survivors Following Resection of Adrenocortical Carcinoma

    PubMed Central

    Tran, Thuy B.; Postlewait, Lauren M.; Maithel, Shishir K.; Prescott, Jason D.; Wang, Tracy S.; Glenn, Jason; 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.; Hatzaras, Ioannis; Shenoy, Rivfka; Pawlik, Timothy M.; Norton, Jeffrey A.; Poultsides, George A.

    2017-01-01

    Background Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with limited therapeutic options beyond surgical resection. The characteristics of actual long-term survivors following surgical resection for ACC have not been previously reported. Method Patients who underwent resection for ACC at one of 13 academic institutions participating in the US Adrenocortical Carcinoma Group from 1993 to 2014 were analyzed. Patients were stratified into four groups: early mortality (died within 2 years), late mortality (died within 2–5 years), actual 5-year survivor (survived at least 5 years), and actual 10-year survivor (survived at least 10 years). Patients with less than 5 years of follow-up were excluded. Results Among the 180 patients available for analysis, there were 49 actual 5-year survivors (27%) and 12 actual 10-year survivors (7%). Patients who experienced early mortality had higher rates of cortisol-secreting tumors, nodal metastasis, synchronous distant metastasis, and R1 or R2 resections (all P < 0.05). The need for multi-visceral resection, perioperative blood transfusion, and adjuvant therapy correlated with early mortality. However, nodal involvement, distant metastasis, and R1 resection did not preclude patients from becoming actual 10-year survivors. Ten of twelve actual 10-year survivors were women, and of the seven 10-year survivors who experienced disease recurrence, five had undergone repeat surgery to resect the recurrence. Conclusion Surgery for ACC can offer a 1 in 4 chance of actual 5-year survival and a 1 in 15 chance of actual 10-year survival. Long-term survival was often achieved with repeat resection for local or distant recurrence, further underscoring the important role of surgery in managing patients with ACC. PMID:27633419

  17. Lymphadenectomy for Adrenocortical Carcinoma: Is There a Therapeutic Benefit?

    PubMed Central

    Gerry, Jon M.; Tran, Thuy B.; Postlewait, Lauren M.; Maithel, Shishir K.; Prescott, Jason D.; Wang, Tracy S.; Glenn, Jason A.; 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.; Hatzaras, Ioannis; Shenoy, Rivfka; Pawlik, Timothy M.; Norton, Jeffrey A.; Poultsides, George A.

    2017-01-01

    Background Lymph node metastasis is an established predictor of poor outcome for adrenocortical carcinoma (ACC); however, routine lymphadenectomy during surgical resection of ACC is not widely performed and its therapeutic role remains unclear. Methods Patients undergoing margin-negative resection for localized ACC were identified from a multi-institutional database. Patients were stratified into 2 groups based on the surgeon’s effort or not to perform a lymphadenectomy as documented in the operative note. Clinical, pathologic, and outcome data were compared between the 2 groups. Results Of 120 patients who met inclusion criteria from 1993 to 2014, 32 (27 %) underwent lymphadenectomy. Factors associated with lymphadenectomy were tumor size (12 vs. 9.5 cm; p = .007), palpable mass at presentation (26 vs. 12 %; p = .07), suspicious lymph nodes on preoperative imaging (44 vs. 7 %; p < .001), and need for multivisceral resection (78 vs. 36 %; p <.001). Median number of lymph nodes harvested was higher in the lymphadenectomy group (5.5 vs. 0; p < .001). In-hospital mortality (0 vs. 1.3 %; p =.72) and grade 3/4 complication rates (0 vs. 12 %; p = .061) were not significantly different. Patients who underwent lymphadenectomy had improved overall survival (5-year 76 vs. 59 %; p = .041). The benefit of lymphadenectomy on overall survival persisted on multivariate analysis (HR = 0.17; p = .006) controlling for adverse preoperative and intraoperative factors associated with lymphadenectomy, such as tumor size, palpable mass, irregular tumor edges, suspicious nodes on imaging, and multivisceral resection. Conclusions In this multicenter study of adrenocortical carcinoma patients undergoing R0 resection, the surgeon’s effort to dissect peritumoral lymph nodes was independently associated with improved overall survival. PMID:27590329

  18. Noninvasive monitoring of adrenocortical function in captive jaguars (Panthera onca).

    PubMed

    Conforti, Valéria A; Morato, Ronaldo G; Augusto, Anderson M; de Oliveira e Sousa, Lúcio; de Avila, David M; Brown, Janine L; Reeves, Jerry J

    2012-01-01

    Jaguars are threatened with extinction throughout their range. A sustainable captive population can serve as a hedge against extinction, but only if they are healthy and reproduce. Understanding how jaguars respond to stressors may help improve the captive environment and enhance their wellbeing. Thus, our objectives were to: (1) conduct an adrenocorticotrophic hormone (ACTH) challenge to validate a cortisol radioimmunoassay (RIA) for noninvasive monitoring of adrenocortical function in jaguars; (2) investigate the relationship between fecal corticoid (FCM) and androgen metabolite (FAM) concentrations in males during the ACTH challenge; and (3) establish a range of physiological concentrations of FCMs for the proposed protocol. Seven jaguars (3 M, 4 F) received 500 IU/animal of ACTH. Pre- and post-ACTH fecal samples were assayed for corticoid (M and F) and androgen metabolites (M) by RIA. Concentrations of FCMs increased (P80.01) after ACTH injection (pre-ACTH: 0.90 ± 0.12 µg/g dry feces; post-ACTH: 2.55 ± 0.25 µg/g). Considering pre- and post-ACTH samples, FCM concentrations were higher (P80.01) in males (2.15 ± 0.20 µg/g) than in females (1.30 ± 0.20 µg/g), but the magnitude of the response to ACTH was comparable (P>0.05) between genders. After ACTH injection, FAMs increased in two (of 3) males; in one male, FCMs and FAMs were positively correlated (0.60; P80.01). Excretion of FCMs was assessed in 16 jaguars (7 M, 9 F) and found to be highly variable (range, 80.11-1.56 µg/g). In conclusion, this study presents a cortisol RIA for monitoring adrenocortical function in jaguars noninvasively.

  19. Serum Selenium Levels in Euthyroid Nodular Thyroid Diseases.

    PubMed

    Sakız, Davut; Kaya, Ahmet; Kulaksizoglu, Mustafa

    2016-11-01

    The thyroid gland is susceptible to nodulation. The mechanism responsible for the growth of only some follicular cells, which results in nodule formation, is not yet clear. Selenium deficiency may be a risk factor in the development of thyroid nodules. The aim of this study was to investigate the relationship between selenium levels in patients with euthyroid nodular thyroid disease. Seventy patients with a solitary euthyroid thyroid nodule, 70 patients with more than one euthyroid nodule, and 60 healthy patients without thyroid nodules were included in the study. Venous serum samples were stored at -80°C and analyzed the same day using spectrometry. The selenium levels of patients with multiple thyroid nodules, solitary nodules, and patients without nodules were 57.3 ± 14.8 μg/L; 58.8 ± 15.1 μg/L; and 57.6 ± 13.3 μg/L, respectively. The mean serum selenium level of all patients included in the study was 57.9 ± 14.4 μg/L. Although serum selenium levels were slightly higher in men, a statistically significant difference was not observed. In our study, a significant relationship between serum selenium levels and nodular thyroid disease was not seen. Our study was undertaken in an iodine sufficient region. Mean serum selenium levels were lower compared with many other studies, which may be associated with the low selenium content of the soil. Nodular thyroid disease shows multifactorial features. When our study is considered together with previous studies, serum selenium levels may considered to be effective on structural thyroid diseases if combined with additional factors such as severe iodine deficiency. Further studies are required to assess the role of selenium in thyroid nodule formation.

  20. Wear-resistant nodular iron for automotive piston rings

    NASA Astrophysics Data System (ADS)

    Vatavuk, J.; Mariano, J. R.

    1992-01-01

    Progress in automotive engine development demands new cost-effective materials with higher mechanical properties and improved wear resistance as compared to existing materials. For example, niobium, as niobium carbide, improves the wear resistance of a typical nodular iron used for piston rings. Niobium prompts the precipitation of stable and hard niobium carbides in the liquid; these particles do not interfere with the subsequent heat treatment of the iron. Industrial production of new niobium-alloyed piston rings was accomplished with a minimum of disruption in normal production processes.

  1. Nodular Fasciitis Complicating a Staged Surgical Excision of Dermatofibrosarcoma Protuberans

    PubMed Central

    Goodwin, Brandon; Wagner, Richard F.; Resto, Vicente; Kelly, Brent

    2016-01-01

    Dermatofibrosarcoma protuberans (DFSP) is an unusual spindle cell tumor with a high rate of local recurrence with traditional excision. Fortunately, Mohs micrographic surgery yields excellent cure rates for this neoplasm due to contiguous tumor spread and meticulous tumor mapping and margin analysis. We present the unique case of a patient treated with a modified Mohs technique with an analysis of the final margin with permanent sections, who developed a spindle cell neoplasm in the margins of her second stage excision consistent with nodular fasciitis. Distinguishing residual DFSP from a benign reactive process was an essential and challenging component of this patient's management. PMID:28018683

  2. p53 Mutations in human adrenocortical neoplasms: Immunohistochemical and molecular studies

    SciTech Connect

    Reincke, M.; Allolio, B.; Travis, W.H.; Linehan, H.M.; Karl, M.; Mastorakos, G.; Chrousos, G.P.

    1994-03-01

    p53 is a recessive tumor suppressor gene located on chromosome 17p. Mutations in the p53 gene play an important role in the tumorigenesis of diverse types of human neoplasms including breast and colon cancers. More than 90% of all mutations discovered in such tumors have been detected in 4 hot spot areas that lie between exons 5 and 8. In contrast to wild-type p53, mutant p53 accumulates intracellularly and can be easily detected by immunohistochemistry. The authors therefore investigated the frequency of p53 mutations in human adrenocortical neoplasms using molecular biology and immunohistochemistry techniques. Five patients with adrenocortical adenomas (5 female; ages 39-72 yr), 11 patients with adrenocortical carcinomas (8 female, 3 male; ages 15-50 yr), and two adrenocortical tumor cell lines were studied. After DNA extraction from frozen tumor tissue or paraffin-embedded material, exons 5 through 8 were amplified using the polymerase chain reaction and directly sequenced by the dideoxy termination method. Immunohistochemistry was performed on paraffin-embedded tumor specimens obtained during adrenalectomy using a monoclonal antibody reacting with both wild-type and mutant p53. Prevalence of mutations was adenomas, 0/5, carcinomas, 3/11, and adrenocortical cell lines, 2/2. Single point mutations were detected in 3 cases (exons 5, 6, and 7, respectively), and rearrangements of exon 7/8 and 8 were found in 2 cases. Immunohistochemistry detected strong nuclear and/or cytoplasmic p53 immunoreactivity in all adrenocortical carcinomas with point mutations of the p53 gene but not in adenomas and carcinomas with the wild-type sequence or with deletion/rearrangement of the p53 gene. They conclude that p53 plays a role in the tumorigenesis of adrenocortical carcinomas but is of less importance to benign adenomas. 27 refs., 3 figs., 2 tabs.

  3. Pigmented central neurocytoma.

    PubMed

    Kiehl, Tim-Rasmus; Kalkanis, Steven N; Louis, David N

    2004-06-01

    Central neurocytoma is a low-grade neuronal neoplasm that occurs most often within the lateral ventricles. We report the case of a 60-year-old woman who presented with gait problems, headache and memory loss. Preoperative evaluation demonstrated a heterogeneous, hypervascular and partially cystic mass in the left lateral ventricle. Histopathological examination revealed characteristic features of central neurocytoma, including immunoreactivity for synaptophysin, as well as the unusual feature of abundant pigment in the cytoplasm of tumor cells. Special stains revealed iron, consistent with hemosiderin, but found no evidence of melanin or melanosomes. Previous reports of pigmented central neurocytoma have described the presence of lipofuscin or neuromelanin. To our knowledge, the present case represents the first example of pigmented central neurocytoma secondary to hemosiderin deposition.

  4. 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.

  5. GATA4 Is a Critical Regulator of Gonadectomy-Induced Adrenocortical Tumorigenesis in Mice

    PubMed Central

    Krachulec, Justyna; Vetter, Melanie; Schrade, Anja; Löbs, Ann-Kathrin; Bielinska, Malgorzata; Cochran, Rebecca; Kyrönlahti, Antti; Pihlajoki, Marjut; Parviainen, Helka; Jay, Patrick Y.; Heikinheimo, Markku

    2012-01-01

    In response to gonadectomy certain inbred mouse strains develop sex steroidogenic adrenocortical neoplasms. One of the hallmarks of neoplastic transformation is expression of GATA4, a transcription factor normally present in gonadal but not adrenal steroidogenic cells of the adult mouse. To show that GATA4 directly modulates adrenocortical tumorigenesis and is not merely a marker of gonadal-like differentiation in the neoplasms, we studied mice with germline or conditional loss-of-function mutations in the Gata4 gene. Germline Gata4 haploinsufficiency was associated with attenuated tumor growth and reduced expression of sex steroidogenic genes in the adrenal glands of ovariectomized B6D2F1 and B6AF1 mice. At 12 months after ovariectomy, wild-type B6D2F1 mice had biochemical and histological evidence of adrenocortical estrogen production, whereas Gata4+/− B6D2F1 mice did not. Germline Gata4 haploinsufficiency exacerbated the secondary phenotype of postovariectomy obesity in B6D2F1 mice, presumably by limiting ectopic estrogen production in the adrenal glands. Amhr2-cre-mediated deletion of floxed Gata4 (Gata4F) in nascent adrenocortical neoplasms of ovariectomized B6.129 mice reduced tumor growth and the expression of gonadal-like markers in a Gata4F dose-dependent manner. We conclude that GATA4 is a key modifier of gonadectomy-induced adrenocortical neoplasia, postovariectomy obesity, and sex steroidogenic cell differentiation. PMID:22461617

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

    PubMed Central

    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

    2014-01-01

    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

  7. Like father, like son: periventricular nodular heterotopia and nonverbal learning disorder.

    PubMed

    McCann, Marcia V; Pongonis, Stephen J; Golomb, Meredith R; Edwards-Brown, Mary; Christensen, Celanie K; Sokol, Deborah K

    2008-08-01

    Periventricular nodular heterotopia is a common malformation of cortical development in which the migration of developing neurons destined for the cerebral cortex is abbreviated. Bilateral periventricular nodular heterotopia is most commonly an X-linked disorder that involves mutations in the filamin A (FLNA) gene, but an autosomal recessive form and sporadic forms have been identified. To our knowledge, autosomal dominant transmission of isolated periventricular nodular heterotopia has not been reported. Periventricular nodular heterotopia has a heterogeneous phenotype, associated commonly with seizure disorder, and more recently with reading deficits and visual-spatial deficits in some patients. We present a father and son with bilateral periventricular nodular heterotopia and similar visual-spatial learning deficits, consistent with nonverbal learning disability.

  8. [A patient with muscular torticollis caused by nodular fasciitis in the sternocleidomastoid muscle (SCM)].

    PubMed

    Hemmi, Shoji; Murakami, Tatufumi; Shirabe, Teruo; Sunada, Yoshihide

    2002-09-01

    Nodular fasciitis is a benign pseudosarcomatous proliferative lesion which is frequently misdiagnosed as malignant tumor clinically and microscopically. It usually occurs as a rapidly enlarging subcutaneous mass on the upper extremities, especially on the forearm. Here we report a patient showing muscular torticollis caused by nodular fasciitis in the sternocleidomastoid muscle (SCM). A 17-year-old woman was hospitalized because of rapidly progressive torticollis. The right SCM was markedly enlarged and firm on palpation. Muscle biopsy taken from the right SCM revealed massive proliferation of spindle shaped fibroblasts infiltrating into the endomysium. These findings coincided with the intramuscular nodular fasciitis. However, different from typical nodular fasciitis, no apparent nodule formation was found in this patient. Instead, diffuse proliferative lesion extended widely into the neck soft tissue. To our knowledge, this is the first report of muscular torticollis caused by nodular fasciitis involving the SCM.

  9. 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

  10. Outcomes after resection of cortisol-secreting adrenocortical carcinoma

    PubMed Central

    Margonis, Georgios Antonios; Kim, Yuhree; 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.; Pawlik, Timothy M.

    2016-01-01

    BACKGROUND We sought to define the impact of cortisol-secreting status on outcomes after surgical resection of adrenocortical carcinoma (ACC). METHODS The U.S ACC group database was queried to identify patients who underwent ACC resection between 1993 and 2014. The short-term and long-term outcomes were assessed. RESULTS The incidence of all functional and cortisol-secreting tumors was 40.6% and 22.6%, respectively. On multivariable analysis, cortisol secretion remained associated with an increased risk of postoperative complications (odds ratio = 2.25, 95 % confidence interval = 1.04 to 4.88; P = .04). At a median follow-up of 17.6 months, 118 patients (50.4%) had developed a recurrence. On multivariable analysis, after adjusting for patient and disease-related factors cortisol secretion independently predicted shorter recurrence-free survival (Hazard ratio = 2.05, 95% confidence interval = 1.16 to 3.60; P = .01). CONCLUSIONS Cortisol secretion was associated with an increased risk of postoperative morbidity. Recurrence remains high among patients with ACC after surgery; cortisol secretion was independently associated with a shorter recurrence-free survival. Tailoring postoperative surveillance of ACC patients based on their cortisol secreting status may be important. PMID:26810939

  11. 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

  12. 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.

  13. 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

  14. The challenge of developmental therapeutics for adrenocortical carcinoma

    PubMed Central

    Costa, Ricardo; Carneiro, Benedito A.; Tavora, Fabio; Pai, Sachin G.; Kaplan, Jason B.; Chae, Young Kwang; Chandra, Sunandana; Kopp, Peter A.; Giles, Francis J.

    2016-01-01

    Adrenocortical carcinoma (ACC) is a rare disease with an estimated incidence of only 0.7 new cases per million per year. Approximately 30-70% of the patients present with advanced disease with very poor prognosis and without effective therapeutic options. In the recent years, unprecedented progresses in cancer biology and genomics have fostered the development of numerous targeted therapies for various malignancies. Immunotherapy has also transformed the treatment landscape of malignancies such as melanoma, among others. However, these advances have not brought meaningful benefits for patients with ACC. Extensive genomic analyses of ACC have revealed numerous signal transduction pathway aberrations (e.g., insulin growth factor receptor and Wnt/β-catenin pathways) that play a central role in pathophysiology. These molecular alterations have been explored as potential therapeutic targets for drug development. This manuscript summarizes recent discoveries in ACC biology, reviews the results of early clinical studies with targeted therapies, and provides the rationale for emerging treatment strategies such as immunotherapy. PMID:27102148

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

    PubMed

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

    2014-10-01

    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.

  16. Determination of pigments in vegetables.

    PubMed

    Schoefs, Benoît

    2004-10-29

    Plant pigments are responsible for the shining color of plant tissues. They are also found in animal tissues and, eventually in transformed food products as additives. These pigments have an important impact on the commercial value of products, because the colors establish the first contact with the consumer. In addition plant pigments may have an influence on the health of the consumers. Pigments are labile: they can be easily altered, and even destroyed. Analytical processes have been developed to determine pigment composition. The aim of this paper is to provide a brief overview of these methods.

  17. Terahertz Analysis of Quinacridone Pigments

    NASA Astrophysics Data System (ADS)

    Squires, A. D.; Kelly, M.; Lewis, R. A.

    2017-03-01

    We present terahertz spectroscopy and analysis of two commercially available quinacridone pigments in the 0.5-4.5 THz range. Our results show a clear distinction between quinacridone red and magenta pigments. We reveal four definite absorptions in the terahertz regime common to both pigments, but offset between the pigments by ˜0.2 THz. The lowest-energy line in each pigment is observed to increase in frequency by ˜0.1 THz as the temperature is reduced from 300 to 12 K.

  18. Nodular Lymphocyte Predominant Hodgkin Lymphoma of the Thyroid

    PubMed Central

    Cassis, João; Simões, Helder; Sequeira Duarte, João

    2016-01-01

    Thyroid lymphomas are rare clinical entities that may result from either the primary intrathyroid de novo or secondary thyroid gland involvement of a lymphoma. Among these, the Hodgkin's subtype is quite uncommon, accounting for 0.6–5% of all thyroid malignancies. The authors report on a 76-year-old female presenting with a thyroid nodule that, upon surgical excision, was found to be a nodular lymphocyte predominant Hodgkin lymphoma of the thyroid. So far, thyroid involvement by this variant has never been reported. Upon reporting on this clinical case, the authors emphasize the difficulties usually found in establishing the diagnosis and in defining the best management strategy. A thorough review of the available literature is done. PMID:28044111

  19. Influence of iodization programmes on the epidemiology of nodular goitre.

    PubMed

    Fiore, Emilio; Tonacchera, Massimo; Vitti, Paolo

    2014-08-01

    Iodine is essential for the synthesis of thyroid hormones. Iodine deficiency can affect human health in different ways, and is commonly referred to as iodine deficiency disorders (IDD). These range from defective development of the central nervous system during the fetal-neonatal life, to goitre in the adult. Only a few countries were completely iodine sufficient before 1990. Since then, a major effort has been made to introduce salt iodization to ensure sufficient intake of iodine in deficient areas. Iodine prophylaxis has been shown to exert a pivotal role in abating goitre and other iodine-deficiency disorders, and has also been shown to modulate the pattern of thyroid diseases. An increased frequency of thyroid autoimmunity and of hypothyroidism has been observed after introducing iodization programmes. Nevertheless, available evidence clearly confirms that the benefits of correcting iodine deficiency, consisting mainly of reducing nodular goitre and non-autoimmune hyperthyroidism, far outweigh the risks of iodine supplementation.

  20. Left upper lobe mass and diffuse reticular-nodular infiltrate.

    PubMed

    Jackson, H D; Carney, K J; Knautz, M A; Tenholder, M F

    1994-06-01

    We encountered a clinical problem in a young man who presented with a left upper lobe mass and a diffuse reticular-nodular infiltrate. We thought we had appropriately applied Murphy's Law (the famed bank robber who "went where the money is"), and Ockham's Razor (the philosopher William of Ockham [1285 to 1349]-"Entities are not to be multiplied beyond necessity") as we rapidly diagnosed the lung mass with computed tomography, scintigraphy, and fine-needle aspiration. However, when his invaluable previous chest radiographs arrived, bronchoscopy with transbronchial biopsy, bronchoalveolar lavage, brushings, and postbronchoscopy sputum revealed the more ominous diagnosis in this patient. This case illustrates the complementary nature of current imaging and bronchoscopy techniques; but, even more importantly, it demonstrates the value of the history coupled with the previous radiograph. Even an unusual case can provide lessons in cost containment.

  1. Sclerosing angiomatoid nodular transformation of the spleen. A case report.

    PubMed

    Martínez Martínez, Pedro Jesús; Solbes Vila, Ramón; Bosquet Úbeda, Carlos Javier; Roig Álvaro, José María

    2017-03-01

    A 57 year old woman presenting with heartburn and a one month history of epigastric abdominal pain and left hypochondrium pain. After conducting an ultrasound scan and a CT scan, a low attenuation lesion in the spleen was found, and the definitive diagnosis was sclerosing angiomatoid nodular transformation of the spleen (STANT) which was based on a splenectomy and a pathologic study. SANT is a benign rare vascular disease consisting of proliferation of angiomatoid/vascular nodules which predominantly affects women aged 27 to 68. It is usually detected as a coincidental finding in asymptomatic patients. The presumptive diagnosis is established by imaging tests, especially CT and MR; and the final diagnosis is as well established on the basis of pathology after a splenectomy.

  2. 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.

  3. [Nodular secondary syphilis in a HIV patient mimicking cutaneous lymphoma].

    PubMed

    Baniandrés Rodríguez, O; Nieto Perea, O; Moya Alonso, L; Carrillo Gijón, R; Harto Castaño, A

    2004-05-01

    We report the case of a 61-year old man who, already for a month, had infiltrated plaques on the chest, back, neck and face as well as axilar lymphadenopathy, bearing a striking resemblance to lymphoma. During his stay in the hospital he had fever, sore throat, macules on the palms and soles and a depapilated plaque on the tongue and alopecia. A test for syphilis confirmed the diagnosis. The HIV serology was also positive. The nodular secondary syphilis is an unusual form that was first documented more than 20 years ago. Since then, only a few cases have been reported in which the first diagnosis included lymphoreticular malignancy. This form of secondary syphilis was found in the HIV-infected as well as non-infected patients. We discuss the atypical clinical course, the inappropriate serological reactions and the therapy in HIV infected patients with secondary syphilis.

  4. Periventricular nodular heterotopia in Smith-Magenis syndrome.

    PubMed

    Capra, Valeria; Biancheri, Roberta; Morana, Giovanni; Striano, Pasquale; Novara, Francesca; Ferrero, Giovanni Battista; Boeri, Luca; Celle, Maria Elena; Mancardi, Maria Margherita; Zuffardi, Orsetta; Parrini, Elena; Guerrini, Renzo

    2014-12-01

    Smith-Magenis syndrome (SMS) is caused by an interstitial microdeletion of chromosome 17p11.2. A few patients with the typical SMS phenotype have RAI1 gene mutations. The syndrome is characterized by minor craniofacial anomalies, short stature, sleep disturbances, behavioural and neurocognitive abnormalities, as well as variable multisystemic manifestations. Periventricular nodular heterotopia (PNH) is a genetically heterogeneous neuronal migration disorder characterized by subependymal heterotopic nodules, and is variably associated with other brain malformations, epileptic seizures and intellectual disability. Here we report on two patients harboring deletions of the 17p11.2 region in whom the SMS typical phenotype was associated with bilateral PNH. Our observations expand the spectrum of chromosomal rearrangements associated with PNH and indicate that abnormal neuronal migration may contribute to the neurocognitive phenotype of SMS.

  5. PEROXISOMES IN INNER ADRENOCORTICAL CELLS OF FETAL AND ADULT GUINEA PIGS

    PubMed Central

    Black, Virginia H.; Bogart, Bruce I.

    1973-01-01

    Abundant membrane-bounded granules, 0.1–0.45 µm in diameter, occur among the elements of the smooth-surfaced endoplasmic reticulum in zona fasciculata and zona reticularis adrenocortical cells of guinea pigs. Acid phosphatase cannot be cytochemically demonstrated in them, and they are therefore distinct from lysosomes. Incubation in medium containing 3,3'-diaminobenzidine results in dense staining of the granules, identifying them as peroxisomes. These small peroxisomes increase in number as fetal adrenocortical cells differentiate, and they appear to arise from dilated regions of endoplasmic reticulum. They maintain interconnections with the smooth endoplasmic reticulum and with one another. PMID:4633170

  6. Loss of sensitivity to ACTH of adrenocortical cells isolated from maturing domestic fowl.

    PubMed

    Carsia, R V; Scanes, C G; Malamed, S

    1985-07-01

    Maturation of domestic fowl corticosteroidogenesis was evaluated using purified adrenocortical cells. Basal corticosterone production decreased steadily from 2 days to 26 weeks after hatching. However, maximally stimulated corticosterone production was not changed. In contrast, the half-maximal steroidogenic concentrations (ED50 values or effective doses for 50% maximal effect) of ACTH analogs increased approximately 40 times by 26 weeks, but the ED50 values of 8-bromo-cyclic AMP and pregnenolone were not changed. This suggests that adrenocortical cell sensitivity to ACTH decreases with maturation of the domestic fowl.

  7. Ectopic Adrenocortical Tissue in the Spermatic Cord in a 44-Year-old Man☆

    PubMed Central

    Müllhaupt, Gautier; Mordasini, Livio; Gramann, Tobias; Ertel, Vera; Schmid, Hans-Peter; Abt, Dominik

    2014-01-01

    We report on a 44-year-old man who underwent microsurgical inguinal repair for symptomatic varicocele. As an incidental finding during surgery, a yellowish tumor (9 × 5 × 4 mm) was found in the spermatic cord. Histologic examination revealed ectopic adrenocortical tissue. Ectopic adrenocortical tissue in the spermatic cord is known to appear in children and adolescents but is extremely rare in adults. Surgical removal of the tissue is recommended, although malignant transformation or functional hormonal disorders are very unlikely. PMID:26958477

  8. Quantitative assessment of corpus callosum morphology in periventricular nodular heterotopia.

    PubMed

    Pardoe, Heath R; Mandelstam, Simone A; Hiess, Rebecca Kucharsky; Kuzniecky, Ruben I; Jackson, Graeme D

    2015-01-01

    We investigated systematic differences in corpus callosum morphology in periventricular nodular heterotopia (PVNH). Differences in corpus callosum mid-sagittal area and subregional area changes were measured using an automated software-based method. Heterotopic gray matter deposits were automatically labeled and compared with corpus callosum changes. The spatial pattern of corpus callosum changes were interpreted in the context of the characteristic anterior-posterior development of the corpus callosum in healthy individuals. Individuals with periventricular nodular heterotopia were imaged at the Melbourne Brain Center or as part of the multi-site Epilepsy Phenome Genome project. Whole brain T1 weighted MRI was acquired in cases (n=48) and controls (n=663). The corpus callosum was segmented on the mid-sagittal plane using the software "yuki". Heterotopic gray matter and intracranial brain volume was measured using Freesurfer. Differences in corpus callosum area and subregional areas were assessed, as well as the relationship between corpus callosum area and heterotopic GM volume. The anterior-posterior distribution of corpus callosum changes and heterotopic GM nodules were quantified using a novel metric and compared with each other. Corpus callosum area was reduced by 14% in PVNH (p=1.59×10(-9)). The magnitude of the effect was least in the genu (7% reduction) and greatest in the isthmus and splenium (26% reduction). Individuals with higher heterotopic GM volume had a smaller corpus callosum. Heterotopic GM volume was highest in posterior brain regions, however there was no linear relationship between the anterior-posterior position of corpus callosum changes and PVNH nodules. Reduced corpus callosum area is strongly associated with PVNH, and is probably associated with abnormal brain development in this neurological disorder. The primarily posterior corpus callosum changes may inform our understanding of the etiology of PVNH. Our results suggest that

  9. [Histopathological Study of the Relationship between Lymphoid Follicles and Different Endoscopic Types of Nodular Gastritis].

    PubMed

    Nagata, Takuo; Ishitake, Hisahito; Shimamoto, Fumio; Tamura, Tadamasa; Matsumura, Kazunori; Sumii, Masaharu; Nakai, Shirou

    2014-11-01

    Nodular gastritis is characterized histologically by hyperplasia and enlargement of lymphoid follicles in the lamina propria. With the objective of elucidating the relationship between different endoscopic types of nodular gastritis and lymphoid follicles, distributions of lymphoid follicles in the lamina propria were investigated in young gastric cancer patients with nodular gastritis. For the study, whole-mucosal step sectioning of each resected stomach was performed, the densities of lymphoid follicles of all specimens were measured microscopically, and the horizontal and depth distributions were calculated. For assessment in the horizontal direction, density distribution diagrams of lymphoid follicles were created. For assessment in the depth direction, the different endoscopic types of nodular gastritis were compared in the five different analysis sites. In the assessment of the horizontal distribution, no characteristic distribution tendencies were observed in either the granular type group or the scattered type group; however, it was found that areas with relatively high densities of lymphoid follicles generally coincided with the areas where nodular gastritis was observed endoscopically. These results suggested that hyperplasia and aggregation of lymphoid follicles in the lamina propria are involved at the sites where nodular gastritis is observed endoscopically. In the assessment of the depth distribution, lymphoid follicles tended to be more unevenly distributed in the upper lamina propria in the granular type group than in the scattered type at the three different analysis sites where nodular gastritis was observed endoscopically. These results suggested the possibility of a granular type characteristic.

  10. Adrenocortical adenoma and carcinoma: histopathological and molecular comparative analysis.

    PubMed

    Stojadinovic, Alexander; Brennan, Murray F; Hoos, Axel; Omeroglu, Atilla; Leung, Denis H Y; Dudas, Maria E; Nissan, Aviram; Cordon-Cardo, Carlos; Ghossein, Ronald A

    2003-08-01

    We compared histomorphological features and molecular expression profiles of adrenocortical adenomas (ACAd) and carcinomas (ACCa). A critical histopathological review (mean, 11 slides per patient) was conducted of 37 ACAd and 67 ACCa. Paraffin-embedded tissue cores of ACAd (n = 33) and ACCa (n = 38) were arrayed in triplicate on tissue microarrays. Expression profiles of p53, mdm-2, p21, Bcl-2, cyclin D1, p27, and Ki-67 were investigated by immunohistochemistry and correlated with histopathology and patient outcome using standard statistical methodology. Median follow-up period was 5 years. Tumor necrosis, atypical mitoses, and >1 mitosis per 50 high-power fields were factors that were highly specific for ACCa (P <.001). Number (0 to 4) of unfavorable markers [Ki-67 (+), p21 (+), p27 (+), mdm-2(-)] expressed was significantly associated with mitotic activity and morphologic index (i.e., number of adverse morphologic features) and highly predictive of malignancy (P <.001). Ki-67 overexpression occurred in 0 ACAd and 36% ACCa (P <.001) and was significantly associated with mitotic rate and unfavorable morphologic index (P <.001). Tumor necrosis, atypical mitoses, >5 mitoses per 50 high-power fields, sinusoidal invasion, histologic index of >5, and presence of more than two unfavorable molecular markers were associated significantly with metastasis in ACCa. Well-established histopathologic criteria and Ki-67 can specifically distinguish ACCAd from ACCa. Tumor cell proliferation (Ki-67) correlates with mitotic activity and morphologic index. Tumor morphology is a better predictor of metastatic risk in ACCa than current immunohistochemistry-detected cell cycle regulatory and proliferation-associated proteins.

  11. Sphingosine kinase 1 is overexpressed and promotes adrenocortical carcinoma progression

    PubMed Central

    Huang, Jiwei; Kong, Wen; Xue, Wei; Zhu, Yu; Zhang, Jin; Huang, Yiran

    2016-01-01

    Adrenocortical carcinoma (ACC) is a rare endocrine tumor with a very poor prognosis. Sphingosine kinase 1 (SphK1), an oncogenic kinase, has previously been found to be upregulated in various cancers. However, the role of the SphK1 in ACC has not been investigated. In this study, SphK1 mRNA and protein expression levels as well as clinicopathological significance were evaluated in ACC samples. In vitro siRNA knockdown of SphK1 in two ACC cell lines (H295R and SW13) was used to determine its effect on cellular proliferation and invasion. In addition, we further evaluated the effect of SphK1 antagonist fingolimod (FTY720) in ACC in vitro and in vivo, as a single agent or in combination with mitotane, and attempted to explore its anticarcinogenic mechanisms. Our results show a significant over-expression of SphK1 mRNA and protein expression in the carcinomas compared with adenomas (P < 0.01 for all comparisons). Functionally, konckdown of SphK1 gene expression in ACC cell lines significantly decreased cell proliferation and invasion. FTY720 could result in a decreased cell proliferation and induction of apoptosis, and the combination of mitotane and FTY720 resulted in a greater anti-proliferative effect over single agent treatment in SW13 cells. Furthermore, FTY720 could markedly inhibit tumor growth in ACC xenografts. SphK1 expression is functionally associated to cellular proliferation, apoptosis, invasion and mitotane sensitivity of ACC. Our data suggest that SphK1 might be a potential therapeutic target for the treatment of ACC. PMID:26673009

  12. 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.

  13. Hair cortisol measurement in mitotane-treated adrenocortical cancer patients.

    PubMed

    Manenschijn, L; Quinkler, M; van Rossum, E F C

    2014-04-01

    The only approved drug for the treatment of adrenocortical cancer (ACC) is mitotane. Mitotane is adrenolytic and therefore, hydrocortisone replacement therapy is necessary. Since mitotane increases cortisol binding globulin (CBG) and induces CYP3A4 activity, high doses of hydrocortisone are thought to be required. Evaluation of hydrocortisone therapy in mitotane-treated patients has been difficult since there is no good marker to evaluate hydrocortisone therapy. Measurement of cortisol in scalp hair is a novel method that offers the opportunity to measure long-term cortisol levels. Our aim was to evaluate whether hair cortisol measurements could be useful in evaluating recent hydrocortisone treatment in mitotane-treated ACC patients. Hair cortisol levels were measured in 15 mitotane-treated ACC patients on hydrocortisone substitution and 96 healthy individuals. Cortisol levels were measured in 3 cm hair segments, corresponding to a period of 3 months. Hair cortisol levels were higher in ACC patients compared to healthy individuals (p<0.0001). Seven ACC patients (47%) had hair cortisol levels above the reference range. None of the patients had hair cortisol levels below normal. In contrast to hydrocortisone doses (β=0.03, p=0.93), hair cortisol levels were associated with BMI (β=0.53, p=0.042). There was no correlation between hair cortisol levels and hydrocortisone doses (β=0.41, p=0.13). Almost half of the ACC patients had high hair cortisol levels, suggesting long-term over-substitution of hydrocortisone in some of the patients, whereas none of the patients was under-substituted. Hair cortisol measurements might be useful in long-term monitoring hydrocortisone treatment in mitotane-treated ACC patients.

  14. Intestinal nodular lymphoid hyperplasia and extraintestinal lymphoma--a rare association.

    PubMed

    Monsanto, P; Lérias, C; Almeida, N; Lopes, S; Cabral, J E; Figueiredo, P; Silva, M; Julião, M; Gouveia, H; Sofia, C

    2012-06-01

    Nodular lymphoid hyperplasia of the gastrointestinal tract is characterized by the presence of innumerable small discrete nodules involving a variable segment of the gastrointestinal tract. The association between nodular lymphoid hyperplasia and other benign and malignant diseases has been clearly described, with an increased risk of gastrointestinal tumours, namely gastrointestinal lymphoma. However, the association with extraintestinal lymphoma seems extremely rare. The authors present a clinical case of a patient with nodular lymphoid hyperplasia of the small and large intestine that subsequently developed an extraintestinal lymphoma (diffuse large B-cell lymphoma).

  15. Diffuse Nodular Lymphoid Hyperplasia of the Intestine Caused by Common Variable Immunodeficiency and Refractory Giardiasis

    PubMed Central

    Choi, Jung Hye; Han, Dong Soo; Kim, Jieun; Yi, Kijong; Oh, Young-Ha; Kim, Yongsoo

    2017-01-01

    Diffuse nodular lymphoid hyperplasia of the gastrointestinal tract is a rare disease characterized by numerous small polypoid nodules in the small intestine, large intestine, or both. It is associated with immunodeficiency and infection, such as Giardia lamblia and Helicobacter pylori. Although diffuse nodular lymphoid hyperplasia associated with common variable immunodeficiency (CVID) and giardiasis is already known, a few studies have reported a regression of the lymphoid nodules after the eradication of infection. We herein describe a case of diffuse nodular lymphoid hyperplasia of the intestine associated with CVID and refractory giardiasis that markedly improved after successfully treating giardiasis. PMID:28154271

  16. Diffuse Nodular Lymphoid Hyperplasia of the Intestine Caused by Common Variable Immunodeficiency and Refractory Giardiasis.

    PubMed

    Choi, Jung Hye; Han, Dong Soo; Kim, Jieun; Yi, Kijong; Oh, Young-Ha; Kim, Yongsoo

    2017-01-01

    Diffuse nodular lymphoid hyperplasia of the gastrointestinal tract is a rare disease characterized by numerous small polypoid nodules in the small intestine, large intestine, or both. It is associated with immunodeficiency and infection, such as Giardia lamblia and Helicobacter pylori. Although diffuse nodular lymphoid hyperplasia associated with common variable immunodeficiency (CVID) and giardiasis is already known, a few studies have reported a regression of the lymphoid nodules after the eradication of infection. We herein describe a case of diffuse nodular lymphoid hyperplasia of the intestine associated with CVID and refractory giardiasis that markedly improved after successfully treating giardiasis.

  17. 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…

  18. Reciprocal Influences among Adrenocortical Activation, Psychosocial Processes, and the Behavioral Adjustment of Clinic-Referred Children.

    ERIC Educational Resources Information Center

    Granger, Douglas A.; And Others

    1996-01-01

    Assessed children's adjustment at clinic intake and six months later, and sampled children's saliva before and after a conflict-oriented parent-child interaction. Increases in salivary cortisol predicted children's internalizing problem behaviors and anxiety disorders at follow-up. High adrenocortical reactivity at intake and follow-up was…

  19. 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…

  20. Drinking-induced changes in fowl adrenocortical activity: effect of visual and non-visual stimuli.

    PubMed

    Harvey, S; Klandorf, H; Lam, S K

    1985-02-01

    The deprivation of drinking water for 30 h resulted in increased corticosterone concentrations in the plasma of 8- to 10-week-old chickens. When water-deprived birds were allowed to drink ad libitum the corticosterone concentration declined within 45 min, to the level in hydrated controls, and remained suppressed thereafter. Similar reductions in the corticosterone concentrations were also observed in water-deprived chicks which were allowed to drink for only 5 min, 1 min or 5 s. The involvement of visual stimuli in mediating this adrenocortical response was demonstrated by a comparable decline in the corticosterone concentration in water-deprived birds which were presented with water but not allowed access to it. Non-visual stimuli also appeared to be causally involved in the adrenocortical suppression after drinking, since the intraperitoneal injection of tap water (40 ml per bird) also resulted in a lowering of the corticosterone level. However, in the absence of appropriate reinforcement from metabolic stimuli, a rebound in the corticosterone concentration was observed in birds prevented from drinking, in birds unable to satiate their thirst and in birds rehydrated (orally or intraperitoneally) without feeding. These results demonstrate adrenocortical suppression in water-deprived chickens after free access to food and water and the involvement of visual and non-visual stimuli in mediating this response. The maintenance of adrenocortical suppression is dependent upon metabolic stimuli associated with food and water intake.

  1. 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…

  2. 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…

  3. Adrenocortical responses to repeated parachute jumping and subsequent h-CRH challenge in inexperienced healthy subjects.

    PubMed

    Deinzer, R; Kirschbaum, C; Gresele, C; Hellhammer, D H

    1997-04-01

    The present study examined the adrenocortical response to 3 consecutive parachute jumps and a poststress h-CRH challenge. Fifteen participants in a parachute-jumping course took saliva samples for later cortisol analysis every 20 min throughout the day, when they accomplished their very first 3 parachute jumps and throughout a control day. The effects of an h-CRH challenge on salivary cortisol were assessed in the evening of the jumping day and on a control day. Parachute jumping induced 3 distinct highly significant adrenocortical responses. The respective cortisol increases for the first, second, and third jump were 39.4 +/- 26.5 nmol/1, 31.4 +/- 21.4 nmol/l, and 16.5 +/- 11.9 nmol/l. Cortisol responses to the first and second jump did not differ but the response to the third jump was significantly reduced [t(13) = 3.11; p = 0.008]. Two groups of subjects were identified, "decreasers," whose response decreased from one to the other jump, and "increasers," whose response remained unchanged or increased. The magnitude of the preceding cortisol response of decreasers exceeded that of increasers significantly by about 30 nmol. The mean adrenocortical effects of the poststress h-CRH challenge and the time-matched challenge on a control day did not differ although, in 4 subjects, the poststress adrenocortical response to h-CRH was completely suppressed.

  4. 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

  5. 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.

  6. 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

  7. Nodular Fasciitis of the Orbit: A Case Report Confirmed by Molecular Cytogenetic Analysis.

    PubMed

    Anzeljc, Andrew J; Oliveira, Andre M; Grossniklaus, Hans E; Kim, Hee Joon; Hayek, Brent

    2016-02-12

    Nodular fasciitis is a benign fibroblastic proliferation typically found in the subcutaneous tissue or superficial fascia of the extremities that is often confused for malignancy. These lesions rarely occur on the eyelids and ocular adnexa and are seldom analyzed by ophthalmic pathologists. USP6 gene rearrangement has been recently demonstrated in nodular fasciitis and this rearrangement may lead to the formation of a fusion gene MYH9-USP6 in some cases. Herein, the authors describe a 38-year-old woman with a 6-month history of a progressively enlarging mass beneath her right medial upper eyelid. Histopathologic analysis of the excisional biopsy confirmed classic features of nodular fasciitis. Molecular cytogenetic analysis revealed a rearrangement of the USP6 locus, confirming the diagnosis of benign nodular fasciitis.

  8. Nodular graphite formation in vacuum melted high purity Fe-C-Si alloys

    NASA Astrophysics Data System (ADS)

    Dhindaw, B.; Verhoeven, J. D.

    1980-06-01

    This paper describes a study of the cast structure of vacuum melted high purity Fe-C-Si alloys with emphasis on hypoeutectic and eutectic compositions. Nodular graphite was observed to form at high cooling rates and coral graphite at low cooling rates. This result was also confirmed by a limited study on directional solidification of alloys prepared from the same starting materials. The formation of nodular graphite at the high cooling rates was suppressed to near zero by changing the starting iron from 99.94 pct electrolytic iron to an ultra-pure zone refined iron, or by holding the melt at a low super-heat prior to cooling. Chemical analysis showed only that the impurity responsible for nodular formation was present at the low ppm level. An attempt is made to explain the appearance of the various microstructures in terms of the nucleation and growth of nodular graphite, coral graphite and the carbide structure of white iron.

  9. Intra-muscular Nodular Fasciitis Presenting as Swelling in Neck: Challenging Entity for Diagnosis.

    PubMed

    Sinhasan, Sankappa P; K V, Bharathi; Bhat, Ramachandra V; Hartimath, Basavanandaswamy C

    2014-01-01

    The diagnosis of Nodular Fasciitis is a very challenging on cytological aspirations. Even in histopathological sections, it can be sometimes be mistaken for soft tissue sarcomas due to its high cellularity, presence of mitotic figures, poor circumscription and degenerative myxoid areas. Most commonly, nodular fasciitis is seen on extremities; and sub-cutaneous form is most common. We are hereby reporting a case of nodular fasciitis at a rare site (head and neck area) in its rare form (intra-muscular type: originating within sternocleidomastoid muscle), which was clinically suspected as a malignancy arising from solitary thyroid nodule. Cytological diagnosis was issued as benign spindle cell lesion (where chances of a misdiagnosis as malignant are very high), thereby preventing radical surgery. It was subsequently confirmed as intra-muscular nodular fasciitis after histopathological examination.

  10. Transforming growth factor beta 1: an autocrine regulator of adrenocortical steroidogenesis.

    PubMed

    Feige, J J; Cochet, C; Savona, C; Shi, D L; Keramidas, M; Defaye, G; Chambaz, E M

    1991-01-01

    Transforming growth factor beta 1 (TGF beta 1) is a member of a large family of structurally related regulatory polypeptides which comprises both functionally similar (TGF beta 1, TGF beta 2, TGF beta 3, TGF beta 4 and TGF beta 5) and functionally distinct proteins. In the past few years, TGF beta 1 has emerged as a multifunctional protein. One of its remarkable properties is its capacity to negatively modulate the differentiated, steroidogenic adrenocortical functions. We present here a review of the results from our recent work related to the effects of TGF beta 1 on bovine adrenocortical cell (zona fasciculata-reticularis) functions. We identified the steroid 17 alpha-hydroxylase (P-450 17 alpha) biosynthetic enzyme and the angiotensin II receptor as major targets whose expression are negatively regulated by TGF beta 1 in these cells. We characterized TGF beta 1 receptors at the surface of adrenocortical cells (mainly type I and type III receptors) and observed that their number is increased under ACTH treatment. Furthermore, we could detect the presence of immunoreactive TGF beta 1 in the bovine adrenal cortex whereas it was undetectable in the adrenal medulla and in the capsule. We also observed that adrenocortical cells secrete TGF beta 1 under a latent form together with large amounts of alpha 2-macroglobulin, a protease inhibitor known to be implied in the latency of TGF beta in serum. Taken together, these observations led us to a working hypothesis, proposing TGF beta 1 as an autocrine and/or paracrine regulator of adrenocortical steroidogenic functions. This concept points out the physiological activation of the latent TGF beta 1 complex as the important limiting step controlling its action in the adrenal cortex.

  11. Properties of calcium and potassium currents of clonal adrenocortical cells

    PubMed Central

    1989-01-01

    The ionic currents of clonal Y-1 adrenocortical cells were studied using the whole-cell variant of the patch-clamp technique. These cells had two major current components: a large outward current carried by K ions, and a small inward Ca current. The Ca current depended on the activity of two populations of Ca channels, slow (SD) and fast (FD) deactivating, that could be separated by their different closing time constants (at -80 mV, SD, 3.8 ms, and FD, 0.13 ms). These two kinds of channels also differed in (a) activation threshold (SD, approximately - 50 mV; FD, approximately -20 mV), (b) half-maximal activation (SD, between -15 and -10 mV; FD between +10 and +15 mV), and (c) inactivation time course (SD, fast; FD, slow). The total amplitude of the Ca current and the proportion of SD and FD channels varied from cell to cell. The amplitude of the K current was strongly dependent on the internal [Ca2+] and was almost abolished when internal [Ca2+] was less than 0.001 microM. The K current appeared to be independent, or only slightly dependent, of Ca influx. With an internal [Ca2+] of 0.1 microM, the activation threshold was -20 mV, and at +40 mV the half- time of activation was 9 ms. With 73 mM external K the closing time constant at -70 mV was approximately 3 ms. The outward current was also modulated by internal pH and Mg. At a constant pCa gamma a decrease of pH reduced the current amplitude, whereas the activation kinetics were not much altered. Removal of internal Mg produced a drastic decrease in the amplitude of the Ca-activated K current. It was also found that with internal [Ca2+] over 0.1 microM the K current underwent a time- dependent transformation characterized by a large increase in amplitude and in activation kinetics. PMID:2539432

  12. The role of radioiodine therapy in benign nodular goitre.

    PubMed

    Bonnema, Steen Joop; Fast, Søren; Hegedüs, Laszlo

    2014-08-01

    For treatment of benign nodular goitre the choice usually stands between surgery and (131)I therapy. (131)I therapy, used for 30 years for this condition, leads to a goitre volume reduction of 35-50% within 1-2 years. However, this treatment has limited efficacy if the thyroid (131)I uptake is low or if the goitre is large. Recombinant human TSH (rhTSH)-stimulated (131)I therapy significantly improves goitre reduction, as compared with conventional (131)I therapy without pre-stimulation, and adverse effects are few with rhTSH doses of 0.1 mg or lower. RhTSH-stimulated (131)I therapy reduces the need for additional therapy due to insufficient goitre reduction, but the price is a higher rate of hypothyroidism. Another approach with rhTSH-stimulation is to reduce the administered (131)I activity by a factor that equals the increase in the thyroid (131)I uptake. Using this approach, radiation exposure is considerably reduced while the goitre reduction is similar to that obtained with conventional (131)I therapy.

  13. Pathogenesis of nodular goiter and its implications for surgical management

    SciTech Connect

    Teuscher, J.; Peter, H.J.; Gerber, H.; Berchtold, R.; Studer, H.

    1988-01-01

    Despite sufficient iodine supply, goiter continues to be of considerable surgical significance in formerly endemic countries. It now appears that iodine deficiency and increased thyrotropin stimulation are not the only causes of goiter. Xenotransplantation of human thyroid tissue onto nude mice allowed study of the regulation of growth and function in human goiter tissue. Grafts of human thyroid tissue growing in nude mice could be shown to react to endogenous mouse thyrotropic stimulation and suppression. /sup 131/I autoradiographs of xenotransplanted goiter tissue showed as marked a heterogeneity as did the original goitrous tissue prior to transplantation. There was no firm correlation between the morphologic appearance of a follicle and its iodine metabolism. Scintigraphically cold and hot goiter tissue differed from each other quantitatively but not qualitatively; i.e., both hot and cold tissue were composed of metabolically active and nonactive follicles. Iodine organification was not completely suppressible by thyroxine treatment; this indicates autonomous functional activity. The distribution of proliferating tissue labeled by /sup 3/H-thymidine did not parallel the distribution of functionally active tissue labelled by /sup 131/I. Thyroxine treatment did not completely inhibit /sup 3/H-thymidine incorporation, indicating autonomous growth. Thus, our pathogenetic concept of goiter formation is based on three mainstays: (1) goiter heterogeneity, (2) autonomy of growth and function, and (3) dissociation of growth and function in human goiter tissue. Thus, the surgeon dealing with goiter ought to remove all pathologically altered tissue, i.e., nodular tissue, irrespective of its appearance on scintiscans.

  14. Focal nodular hyperplasia of the liver following hematopoietic SCT.

    PubMed

    Sudour, H; Mainard, L; Baumann, C; Clement, L; Salmon, A; Bordigoni, P

    2009-01-01

    Incidental hepatic regenerating nodules rarely occur after haematopoietic SCT (HSCT). Focal nodular hyperplasia (FNH) is one of these unusual benign tumors with characteristic imaging features. To determine the incidence and the outcome of FNH of the liver and improve the understanding of its pathogenesis, we prospectively surveyed a total of 138 patients who had undergone serial prospective pre- and post-transplantation evaluations of iron biomarkers, including ferritin and liver iron concentration assessed by magnetic resonance imaging (MRI). Seventeen patients with a median delay of 6.4 years (2.2-13.6) developed FNH of the liver. All were children at the time of transplantation. MR images were typical for FNH in 16 patients; only one patient needed a confirmatory biopsy. Sixteen had received a myeloablative conditioning; six received a BU-based preparation and 10 TBI. Three patients experienced sinusoidal obstruction syndrome. Neither complication nor malignant transformation has been reported to date. FNH of the liver seems to be a frequent delayed benign complication following HSCT, probably of iatrogenic vascular origin. Basic clinical and diagnostic imaging follow-up is warranted.

  15. Pigmentation in the sentinel node correlates with increased sentinel node tumor burden in melanoma patients.

    PubMed

    van Lanschot, Cornelia G F; Koljenović, Senada; Grunhagen, Dirk-Jan; Verhoef, Cornelis; van Akkooi, Alexander C J

    2014-06-01

    The prognosis of sentinel node (SN)-positive melanoma patients is predicted by a number of characteristics such as size and site of the metastases in the SN. The pathway and prognosis of strong pigmentation of melanoma metastases in the SN is unclear. The aim of this study is to evaluate the role of pigmentation and growth pattern of metastases in the SN with respect to survival. A total of 389 patients underwent an SN procedure (1997-2011). Ninety-five patients had a positive SN and material from 75 patients was available for review. The median follow-up time was 75 months (range 6-164). Pigmentation was scored from 0 to 2 using the following scale: 0=absent, 1=slight, and 2=strong. Growth pattern was scored as either eccentric (1) or infiltrative (2). SN tumor burden was measured according to the Rotterdam criteria. The primary melanoma had a median Breslow thickness of 2.90 mm (0.8-12.00 mm). Ulceration was present in 34 patients (45.3%). There was a median SN tumor burden of 0.5 mm (0.05-7.00 mm). In a total of 75 patients, 59 patients (79%) had no pigmentation, 13 patients (17%) had slight pigmentation, and three patients (4%) had strong pigmentation in the SN. Because of the small numbers, the classification was modified to either absent 59 (79%) or present 16 (21%) pigmentation, respectively. The SN tumor burden was significantly higher (P=0.031) for patients with pigmentation. Patients with pigmentation had a 5-year melanoma-specific survival (MSS) of 47% and a 10-year MSS of 33%. Patients without pigmentation had a 5-year MSS of 70% and a 10-year MSS of 59% (P=0.06). There was no difference in MSS for patients with an eccentric or an infiltrative growth pattern, nor did it correlate with other prognostic factors. Multivariate analysis for MSS showed five significant factors associated with worse prognosis: male sex (P=0.036), nodular melanoma (P=0.001), truncal site (P=0.0001), SN tumor burden more than 1.0 mm (P=0.022), and positive completion lymph node

  16. 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...

  17. 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

  18. Energy Conserving Coating - Pigment Research

    DTIC Science & Technology

    1991-05-01

    indicated above, changes from yellow to orange. Thermochromic CVL Mixtures Thermochromic dye mixtures were made by reacting specific leuco (colorless...2 Photochromic Pigments and Dyes ................................. 3 Thermochromic Inorganic Pigments...describing the state of the art in color changing materials, from liquid crystals to thermochromic metal complexes to photochromic spiran dyes . The re- search

  19. 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.

  20. Nonphotosynthetic Pigments as Potential Biosignatures

    NASA Astrophysics Data System (ADS)

    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.

  1. 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.

  2. How I manage pulmonary nodular lesions and nodular infiltrates in patients with hematologic malignancies or undergoing hematopoietic cell transplantation.

    PubMed

    Wingard, John R; Hiemenz, John W; Jantz, Michael A

    2012-08-30

    Pulmonary nodules and nodular infiltrates occur frequently during treatment of hematologic malignancies and after hematopoietic cell transplantation. In patients not receiving active immunosuppressive therapy, the most likely culprits are primary lung cancer, chronic infectious or inactive granulomata, or even the underlying hematologic disease itself (especially in patients with lymphoma). In patients receiving active therapy or who are otherwise highly immunosuppressed, there is a wider spectrum of etiologies with infection being most likely, especially by bacteria and fungi. Characterization of the pulmonary lesion by high-resolution CT imaging is a crucial first diagnostic step. Other noninvasive tests can often be useful, but invasive testing by bronchoscopic evaluation or acquisition of tissue by one of several biopsy techniques should be performed for those at risk for malignancy or invasive infection unless contraindicated. The choice of the optimal biopsy technique should be individualized, guided by location of the lesion, suspected etiology, skill and experience of the diagnostic team, procedural risk of complications, and patient status. Although presumptive therapy targeting the most likely etiology is justified in patients suspected of serious infection while evaluation proceeds, a structured evaluation to determine the specific etiology is recommended. Interdisciplinary teamwork is highly desirable to optimize diagnosis and therapy.

  3. 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.

  4. 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.

  5. Iris phenotypes and pigment dispersion caused by genes influencing pigmentation.

    PubMed

    Anderson, Michael G; Hawes, Norman L; Trantow, Colleen M; Chang, Bo; John, Simon W M

    2008-10-01

    Spontaneous mutations altering mouse coat colors have been a classic resource for discovery of numerous molecular pathways. Although often overlooked, the mouse iris is also densely pigmented and easily observed, thus representing a similarly powerful opportunity for studying pigment cell biology. Here, we present an analysis of iris phenotypes among 16 mouse strains with mutations influencing melanosomes. Many of these strains exhibit biologically and medically relevant phenotypes, including pigment dispersion, a common feature of several human ocular diseases. Pigment dispersion was identified in several strains with mutant alleles known to influence melanosomes, including beige, light, and vitiligo. Pigment dispersion was also detected in the recently arising spontaneous coat color variant, nm2798. We have identified the nm2798 mutation as a missense mutation in the Dct gene, an identical re-occurrence of the slaty light mutation. These results suggest that dysregulated events of melanosomes can be potent contributors to the pigment dispersion phenotype. Combined, these findings illustrate the utility of studying iris phenotypes as a means of discovering new pathways, and re-linking old ones, to processes of pigmented cells in health and disease.

  6. [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.

  7. Characterization of the Microenvironment of Nodular Lymphocyte Predominant Hodgkin Lymphoma

    PubMed Central

    Visser, Lydia; Wu, Rui; Rutgers, Bea; Diepstra, Arjan; van den Berg, Anke

    2016-01-01

    Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is characterized by a low percentage of neoplastic lymphocyte predominant (LP) cells in a background of lymphocytes. The goal of this study is to characterize the microenvironment in NLPHL. Ten NLPHL cases and seven reactive lymph nodes (RLN) were analyzed by flow cytometry for the main immune cells and multiple specific subpopulations. To discriminate between cells in or outside the tumor cell area, we used CD26. We observed significantly lower levels of CD20+ B-cells and CD56+ NK cells and higher levels of CD4+ T-cells in NLPHL in comparison to RLN. In the subpopulations, we observed increased numbers of PD-1+CD4+ T follicular helper cells (TFH), CD69+CD4+ and CD69+CD8+ T-cells and CCR7-CD45RA-CD4+ effector memory T-cells, while FoxP3+CD4+ T regulatory cells (Tregs) and CCR7-CD45RA+ terminally differentiated CD4+ T-cells were decreased in NLPHL compared to RLN. CD69+ cells were increased in the tumor cell area in CD4+ and CD8+ T-cells, while FoxP3+CD25+CD4+ Tregs and CD25+CD8+ T-cells were significantly increased outside the tumor area. Thus, we show a markedly altered microenvironment in NLPHL, with lower numbers of NK cells and Tregs. PD-1+CD4+ and CD69+ T-cells were located inside, and Tregs and CD25+CD8+ cells outside the tumor cell area. PMID:27999289

  8. 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.

  9. 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

  10. 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

  11. Pigmented squamous cell carcinoma of the cheek skin probably arising from solar keratosis.

    PubMed

    Terada, Tadashi; Yamagami, Jun; Fugimoto, Atsushi; Tanaka, Kyoko; Sugiura, Makoto

    2003-07-01

    We report a rare case of pigmented squamous cell carcinoma (SCC) of the cheek skin probably arising from solar keratosis. An 80-year-old man was referred to our clinic because of a black skin nodule in the right cheek. The nodular lesion was 1 cm in diameter, dome-shaped, hard, sharply demarcated, partially erosive and telangiectatic at the border. The lesion was completely excised under the clinical diagnosis of probable seborrheic keratosis. Microscopically, cutaneous horn and mildly atypical squamous epithelia suggestive of previous solar keratosis were present in the surface of the lesion. The lesion consisted of atypical squamous cells with keratinization and intercellular bridges, and it was regarded as SCC. The SCC cells were seen to invade lightly into the upper dermis, where lymphocytic infiltrations and melanophages were noted. Characteristically, heavy deposition of melanin pigment was recognized in the SCC cells as well as in proliferated dendritic and pigment blockade melanocytes that were scattered or colonized within the SCC cell nests. Masson-Fontana stain revealed numerous melanin granules in the SCC cells, as well as in dendritic and pigment blockade melanocytes. Immunohistochemically, the SCC cells were positive for cytokeratins and epithelial membrane antigen, and negative for S-100 protein and HMB45 antigen. Dendritic and pigment blockade melanocytes were negative for cytokeratins, epithelial membrane antigen, and HMB45 antigen, but positive for S-100 protein. The present case suggests that SCC cells of the skin may induce proliferation of melanocytes. The differential diagnosis and the histogenesis of pigmented SCC of the skin are discussed.

  12. A morphometric analysis of adrenocortical actin localized by immunoelectron microscopy: the effect of adrenocorticotropin.

    PubMed

    Loesser, K E; Malamed, S

    1987-10-01

    The localization of actin and the effect of ACTH on its concentration was examined in freshly isolated rat adrenocortical cells. Lowicryl K4M-embedded cells were used for the immunoelectron localization of actin; gold was used as a label for immunoreactive sites. Actin was at least 4 times as concentrated at the cortical cytoplasm as in the lipid droplets and at least 5 times as concentrated in the microvilli as in the lipid droplets. ACTH stimulation approximately doubled the concentration of actin in the cortical cytoplasm and increased by 50% the concentration of actin in the microvilli. The microvillar contribution to the cell surface area was 40% higher in ACTH-stimulated cells than it was in unstimulated cells. These results provide quantitative evidence suggesting that actin and the microvilli participate in steroid secretion by the adrenocortical cell.

  13. Aging of the rat adrenocortical cell: response to ACTH and cyclic AMP in vitro.

    PubMed

    Malamed, S; Carsia, R V

    1983-03-01

    To study intrinsic age-related changes in adrenocortical steroid production, cells isolated from rats of different ages (3 to 24 months) were used. Acute (2 hour) corticosterone production in response to stimulation by adrenocorticotrophic hormone (ACTH) and adenosine 3':5'-cyclic monophosphate (cAMP) was measured by radioimmunoassay. With age, adrenocortical cells lose much of their ability to produce corticosterone in the absence or presence of ACTH or cAMP. The loss is progressive from 6 to 24 months of age. Analysis of the data suggests that from 6 to 12 months, an intracellular steroidogenic lesion develops; in addition there may be a loss in ACTH receptors on the plasma membrane. After 12 months these defects increase and are accompanied by a decrease in receptor sensitivity to ACTH.

  14. 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.

  15. Dermoscopy of pigmented skin lesions.

    PubMed

    Soyer, H P; Argenziano, G; Chimenti, S; Ruocco, V

    2001-01-01

    This paper describes the basic concepts of dermoscopy, the various dermoscopic equipments and the standard criteria for diagnosing pigmented skin lesions. In assessing dermoscopic images, both global and local features can be recognized. These features will be systematically described and illustrated in Part I of this article. First, we will focus on 8 morphologically rather distinctive global features that allow a quick, preliminary categorization of a given pigmented skin lesion. Second, we will describe various local features representing the letters of the dermoscopic alphabet. The local features permit a more detailed assessment of pigmented skin lesions.

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

    PubMed

    Iezzi, Federica; 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.

  17. Acanthosis Nigricans Associated with an Adrenocortical Tumor in a Pediatric Patient

    PubMed Central

    Dimitriadi, Filippina Filia; Barrows, Frank; Mostoufi-Moab, Sogol

    2013-01-01

    Malignant acanthosis nigricans (AN) is a rare paraneoplastic syndrome seen primarily in adults with an underlying diagnosis of gastrointestinal adenocarcinoma. Malignant AN is characterized by hyperpigmentation and velvety hyperplasia of the epidermis. This condition is generally not associated with tumors in pediatric populations or in the adrenal gland. We present a case of malignant AN in a pediatric patient with a nonmalignant, functional adrenocortical tumor. PMID:23819073

  18. Acanthosis nigricans associated with an adrenocortical tumor in a pediatric patient.

    PubMed

    Isaacoff, Elizabeth; Dimitriadi, Filippina Filia; Barrows, Frank; Pawel, Bruce; Mattei, Peter; Mostoufi-Moab, Sogol

    2013-01-01

    Malignant acanthosis nigricans (AN) is a rare paraneoplastic syndrome seen primarily in adults with an underlying diagnosis of gastrointestinal adenocarcinoma. Malignant AN is characterized by hyperpigmentation and velvety hyperplasia of the epidermis. This condition is generally not associated with tumors in pediatric populations or in the adrenal gland. We present a case of malignant AN in a pediatric patient with a nonmalignant, functional adrenocortical tumor.

  19. 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

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

    PubMed

    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

    2015-09-08

    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.

  1. ACTH-Independent Cushing’s Syndrome with Bilateral Micronodular Adrenal Hyperplasia and Ectopic Adrenocortical Adenoma

    PubMed Central

    Louiset, Estelle; Gobet, Françoise; Libé, Rossella; Horvath, Anelia; Renouf, Sylvie; Cariou, Juliette; Rothenbuhler, Anya; Bertherat, Jérôme; Clauser, Eric; Grise, Philippe; Stratakis, Constantine A.; Kuhn, Jean-Marc; Lefebvre, Hervé

    2010-01-01

    Context: Bilateral micronodular adrenal hyperplasia and ectopic adrenocortical adenoma are two rare causes of ACTH-independent Cushing’s syndrome. Objective: The aim of the study was to evaluate a 35-yr-old woman with ACTH-independent hypercortisolism associated with both micronodular adrenal hyperplasia and ectopic pararenal adrenocortical adenoma. Design and Setting: In vivo and in vitro studies were performed in a University Hospital Department and academic research laboratories. Intervention: Mutations of the PRKAR1A, PDE8B, and PDE11A genes were searched for in leukocytes and adrenocortical tissues. The ability of adrenal and adenoma tissues to synthesize cortisol was investigated by immunohistochemistry, quantitative PCR, and/or cell culture studies. Main Outcome Measure: Detection of 17α-hydroxylase and 21-hydroxylase immunoreactivities, quantification of CYP11B1 mRNA in adrenal and adenoma tissues, and measurement of cortisol levels in supernatants by radioimmunological assays were the main outcomes. Results: Histological examination of the adrenals revealed nonpigmented micronodular cortical hyperplasia associated with relative atrophy of internodular cortex. No genomic and/or somatic adrenal mutations of the PRKAR1A, PDE8B, and PDE11A genes were detected. 17α-Hydroxylase and 21-hydroxylase immunoreactivities as well as CYP11B1 mRNA were detected in adrenal and adenoma tissues. ACTH and dexamethasone activated cortisol secretion from adenoma cells. The stimulatory action of dexamethasone was mediated by a nongenomic effect involving the protein kinase A pathway. Conclusion: This case suggests that unknown molecular defects can favor both micronodular adrenal hyperplasia and ectopic adrenocortical adenoma associated with Cushing’s syndrome. PMID:19915020

  2. Photosynthetic pigments: perplexing persistent prevalence of 'superfluous' pigment production.

    PubMed

    Beale, Samuel I

    2008-04-22

    Phycobilins function as light-harvesting pigments in most cyanobacteria and red algae. Although green cyanobacteria of the genus Prochlorococcus express genes encoding enzymes that direct the synthesis of phycobilins, these pigments do not appear to play a role in light harvesting in Prochlorococcus. Now, it is shown that cyanophages infecting Prochlorococcus also contain genes for phycobilin-synthesizing enzymes, and these are expressed in Prochlorococcus, raising further questions as to the role of phycobilins in the host and the virus.

  3. Reactive Retinal Astrocytic Tumor (Focal Nodular Gliosis): A Case Report

    PubMed Central

    Hudson, Lauren E.; Mendoza, Pia R.; Yan, Jiong; Grossniklaus, Hans E.

    2017-01-01

    Purpose To report the clinical and histopathological findings of a reactive retinal astrocytic tumor (RRAT) that progressed to massive retinal gliosis. Observations The patient presented with an elevated, white-yellow retinal mass and extensive retinal exudation in the left eye. Progressive enlargement of the mass and proliferative vitreoretinopathy eventually led to phthisis bulbi and enucleation. Histologically, the mass showed a predominant astrocytic component with intense glial fibrillary acidic protein staining, hyperplasia, fibrous metaplasia, and osseous metaplasia of the retinal pigment epithelium. The Ki-67 proliferative index was <5%, and few scattered vascular channels were observed. Conclusions and Importance These findings show that this tumor is the result of a reactive glial process rather than of neoplastic vascular proliferation. Massive retinal gliosis probably represents the advanced stage of RRAT.

  4. Genetic and non-iodine-related factors in the aetiology of nodular goitre.

    PubMed

    Knudsen, Nils; Brix, Thomas Heiberg

    2014-08-01

    Genetic and a large number of environmental non-iodine-related factors play a role in the cause of nodular goitre. Most evidence for the influence of genetic and environmental factors in the cause of goitre is from cross-sectional, population-based studies. Only a few studies have included prospective data on risk factors for nodular goitre, although few prospective data are available on the effect of iodine and tobacco smoking on goitre development. Goitre is not one single phenotype. Many epidemiological studies do not distinguish diffuse from nodular goitre, as the investigated parameter is often thyroid volume or frequency with increased thyroid volume. Moreover, information on the presence and effect of gene-environment, gene-gene, and environment-environment effect modifications is limited. Thus, firm conclusions about the relative contributions and causality of the investigated risk factors should be made with caution. Smoking seems to be an established risk factor for nodular goitre, possibly with effect modification from iodine intake, as the risk associated with smoking is smaller or absent in areas with sufficient iodine intake. The use of oral contraceptives might have protective effects against goitre, and childbirth is an increased risk factor for goitre in areas with non-optimal iodine intake. Insulin resistance is a recently investigated risk factor, and the risk of goitre may be reversible with metformin treatment. Iodine remains the major environmental risk factor for nodular goitre.

  5. 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.

  6. Marked transient hypercholesterolemia caused by low-dose mitotane as adjuvant chemotherapy for adrenocortical carcinoma.

    PubMed

    Tada, Hayato; Nohara, Atsushi; Kawashiri, Masa-Aki; Inazu, Akihiro; Mabuchi, Hiroshi; Yamagishi, Masakazu

    2014-01-01

    We herein report a case of marked transient hypercholesterolemia in a man receiving low-dose mitotane as adjuvant chemotherapy for adrenocortical carcinoma.A 58-year-old man without any clinical symptoms or history of hypercholesterolemia was admitted to our hospital to treat an adrenocortical carcinoma detected on general screening using computed tomography. He reported no chest symptom and did not exhibit any established risk factors for coronary artery disease, such as diabetes, obesity, hypertension or relevant family history, with the exception of current smoking, on admission. A stress electrocardiogram showed negative findings. The left adrenal tumor as well as left kidney, spleen and distal portion of the pancreas were subsequently resected using radical surgery. The histopathological findings confirmed the preoperative diagnosis of adrenocortical carcinoma. After the operation, treatment with low-dose mitotane (1g/day) was introduced as adjuvant chemotherapy. Interestingly, the patient developed marked hyper-LDL cholesterolemia at a level equivalent to that of familial hypercholesterolemia (LDL cholesterol level ~ 300 mg/dL) following the introduction of mitotane, without evidence of primary or secondary hypercholesterolemia due to other causes. A coronary angiogram performed to assess the new-onset angina revealed three-vessel disease, which was later revascularized via percutaneous coronary intervention eight months after the start of mitotane therapy. The cholesterol level normalized with the suspension of mitotane. This case suggests that mitotane can cause severe hypercholesterolemia, potentially resulting in coronary atherosclerosis.

  7. Adrenocortical suppression in highland chick embryos is restored during incubation at sea level.

    PubMed

    Salinas, Carlos E; Villena, Mercedes; Blanco, Carlos E; Giussani, Dino A

    2011-01-01

    By combining the chick embryo model with incubation at high altitude, this study tested the hypothesis that development at high altitude is related to a fetal origin of adrenocortical but not adrenomedullary suppression and that hypoxia is the mechanism underlying the relationship. Fertilized eggs from sea-level or high altitude hens were incubated at sea level or high altitude. Fertilized eggs from sea-level hens were also incubated at altitude with oxygen supplementation. At day 20 of incubation, embryonic blood was taken for measurement of plasma corticotropin, corticosterone, and Po(2). Following biometry, the adrenal glands were collected and frozen for measurement of catecholamine content. Development of chick embryos at high altitude led to pronounced adrenocortical blunting, but an increase in adrenal catecholamine content. These effects were similar whether the fertilized eggs were laid by sea-level or high altitude hens. The effects of high altitude on the stress axes were completely prevented by incubation at high altitude with oxygen supplementation. When chick embryos from high altitude hens were incubated at sea level, plasma hormones and adrenal catecholamine content were partially restored toward levels measured in sea-level chick embryos. There was a significant correlation between adrenocortical blunting and elevated adrenal catecholamine content with both asymmetric growth restriction and fetal hypoxia. The data support the hypothesis tested and provide evidence to isolate the direct contribution of developmental hypoxia to alterations in the stress system.

  8. Visual and metabolic stimuli cause adrenocortical suppression in fasted chickens during refeeding.

    PubMed

    Harvey, S; Klandorf, H; Pinchasov, Y

    1983-07-01

    Concentrations of corticosterone were determined in the plasma of fasted domestic fowl before and at intervals after refeeding. The deprivation of food markedly increased (p less than 0.001) the level of plasma corticosterone. When refed ad libitum the corticosterone concentration declined (by 70%) within 45 min to the level in fed birds and remained at this concentration thereafter. A similar depression in the corticosterone concentration was observed when fasted birds were merely given the sight of the same diet, although the concentration returned to the fasting level within 60 min of food presentation. Refeeding diets with different metabolic energy contents demonstrated that the duration of the feeding-induced adrenocortical suppression was energy related. In fasted birds the presentation of an inert cellulose diet caused a temporary decline in the corticosterone level. In the absence of visual stimuli the administration (by force feeding) of the inert diet had no effect on the corticosterone concentration, whereas force feeding of metabolizable diets still induced adrenocortical suppression. These results demonstrate that adrenocortical suppression occurs in fasted refed birds and both visual and metabolic stimuli are involved in this response.

  9. The importance of a proper selection area to be biopsied in nodular leukoplakia: a case report.

    PubMed

    Pagin, Otávio; Santos, Paulo Sérgio da Silva; Del Neri, Nathalia Bigelli; Gustavo de Lima, Heliton; Lara, Vanessa Soares

    2014-03-01

    Nodular leukoplakia is a non-homogeneous type of oral leukoplakia presenting a white surface with verrucous, nodular, ulcerated or erythematous features with a greater risk of malignant transformation when compared to the homogeneous type. Common sites of involvement include lip commissures, buccal mucosa and soft palate. It is often associated with epithelial dysplasia or carcinoma and requires detailed microscopic assessment and regular follow-up. The importance of a proper selection of the area to be biopsied and the close teamwork between a dentist and oral pathologist is the basis of providing an accurate final diagnosis.

  10. Transcatheter Arterial Embolization as a Safe and Effective Treatment for Focal Nodular Hyperplasia of the Liver

    SciTech Connect

    Terkivatan, Tuerkan; Hussain, Shahid M.; Lameris, Johan S.; Ijzermans, Jan N.M.

    2002-10-15

    When surgical treatment is being considered for focal nodular hyperplasia, the risk of liver surgery must be carefully balanced against the benefit of resection, especially in the case of a large or centrally located lesion. However, when resection is contraindicated or even impossible, transcatheter arterial embolization should be considered as a safe and less invasive alternative treatment.We describe two cases of young women who presented with abdominal pain and a hypervascular enhancing mass with the radiologic features of focal nodular hyperplasia. Arterial embolization was the therapy selected due to the risk of surgery. In both cases the procedure was successful, and the lesion showed shrinkage during follow-up.

  11. Nodular cystic fat necrosis with calcification in a patient with juvenile dermatomyositis.

    PubMed

    Ferenczi, Katalin; Berke, Adrienne; Makkar, Hanspaul S

    2014-01-01

    Nodular cystic fat necrosis is a rare, benign form of encapsulated fat necrosis with distinct histology, characterized by cystic fat necrosis with lipomembranous changes and, in later stages, calcification. We report the case of a 7-year-old child with juvenile dermatomyositis who presented with three asymptomatic, firm, mobile nodules on the arms and neck. Histology was consistent with nodular cystic fat necrosis with prominent calcification. This is an unusual presentation of this entity because it has never been previously reported in association with juvenile dermatomyositis.

  12. Noninvasive monitoring of adrenocortical activity in carnivores by fecal glucocorticoid analyses.

    PubMed

    Young, K M; Walker, S L; Lanthier, C; Waddell, W T; Monfort, S L; Brown, J L

    2004-06-01

    Measurement of glucocorticoid metabolites in feces has become an accepted method for the noninvasive evaluation of adrenocortical activity. The objective of this study was to determine if a simple cortisol enzyme immunoassay (EIA) was suitable for monitoring adrenocortical activity in a variety of carnivore species. Performance of the cortisol EIA was gauged by comparison to a corticosterone radioimmunoassay (RIA) that has been used for measuring glucocorticoid metabolites in feces of numerous species. Tests for parallelism and extraction efficiency were used to compare the cortisol EIA and corticosterone RIA across eight species of carnivores (Himalayan black bear, sloth bear, domestic cat, cheetah, clouded leopard, black-footed ferret, slender-tailed meerkat, and red wolf). The biological relevance of immunoreactive glucocorticoid metabolites in feces was established for at least one species of each Carnivora family studied with an adrenocorticotropic hormone (ACTH) challenge. High performance liquid chromatography (HPLC) analysis of fecal extracts for each species revealed (1) the presence of multiple immunoreactive glucocorticoid metabolites in feces, but (2) the two immunoassays measured different metabolites, and (3) there were differences across species in the number and polarities of metabolites identified between assay systems. ACTH challenge studies revealed increases in fecal metabolite concentrations measured by the cortisol EIA and corticosterone RIA of approximately 228-1145% and approximately 231-4150% above pre-treatment baseline, respectively, within 1-2 days of injection. Concentrations of fecal glucocorticoid metabolites measured by the cortisol EIA and corticosterone RIA during longitudinal evaluation (i.e., >50 days) of several species were significantly correlated (P<0.0025, correlation coefficient range 0.383-0.975). Adrenocortical responses to physical and psychological stressors during longitudinal evaluations varied with the type of

  13. Cytochrome b5 Expression in Gonadectomy-induced Adrenocortical Neoplasms of the Domestic Ferret (Mustela putorius furo)

    PubMed Central

    Wagner, S.; Kiupel, M.; Peterson, R.A.; Heikinheimo, M.; Wilson, D.B.

    2008-01-01

    Whereas the adrenal glands of healthy ferrets produce only limited amounts of androgenic steroids, adrenocortical neoplasms that arise in neutered ferrets typically secrete androgens or their derivative, estrogen. The 17,20-lyase activity of cytochrome P450 17α-hydroxylase/17,20-lyase (P450c17) must increase to permit androgen biosynthesis in neoplastic adrenal tissue. We screened ferret adrenocortical tumor specimens for expression of cytochrome b5 (cyt b5), an allosteric regulator that selectively enhances the 17,20-lyase activity of P450c17. Cyt b5 immunoreactivity was evident in 24 of 25 (96 %) adrenocortical adenomas/carcinomas from ferrets with signs of ectopic sex steroid production. Normal adrenocortical cells lacked cyt b5, which may account for the low production of adrenal androgens in healthy ferrets. Other markers characteristic of gonadal somatic cells, such as luteinizing hormone receptor, aromatase, and GATA4, were co-expressed with cyt b5 in some of the tumors. We conclude that cyt b5 is upregulated during gonadectomy-induced adrenocortical neoplasia and is a marker of androgen synthetic potential in these tumors. PMID:18587089

  14. A case of pediatric virilizing adrenocortical tumor resulting in hypothalamic-pituitary activation and central precocious puberty following surgical removal.

    PubMed

    Miyoshi, Yoko; Oue, Takaharu; Oowari, Mitsugu; Soh, Hideki; Tachibana, Makiko; Kimura, Sadami; Kiyohara, Yuki; Yamada, Hiroyuki; Bessyo, Kazuhiko; Mushiake, Sotaro; Homma, Keiko; Hasegawa, Tomonobu; Sasano, Hironobu; Ozono, Keiichi

    2009-01-01

    We present a 6-year-old boy with a virilizing adrenocortical tumor who initially presented with peripheral precocious puberty. Development of facial acne, pubic hair and a growth spurt were noted at the age of five. A low-pitched voice as well as maturation of external genitalia was noted at the age of six. Both serum and urinary levels of adrenal androgens were elevated. Abdominal computed tomography revealed a large right suprarenal mass and he underwent surgical resection without any complications. The histological diagnosis was adrenocortical carcinoma according to the criteria of Weiss. Following surgical removal of the androgen-producing tumor, the patient subsequently developed hypothalamic-pituitary activation and demonstrated central precocious puberty. He was treated with a gonadotropin-releasing hormone agonist in order to delay further pubertal progression. Clinical follow-up of potential secondary effects of excess hormone secretion after removal is important in some pediatric patients with virilizing adrenocortical tumor.

  15. Nodular Scleritis in Association with Panuveitis in Behçet’s Disease

    PubMed Central

    SAATCI, Ali Osman; AYHAN, Ziya; ONEN, Fatos; OZBEK, Zeynep; DURAK, Ismet

    2016-01-01

    This case report involves a 32-year-old man with Behçet’s disease who had simultaneous bilateral anterior uveitis, unilateral nodular scleritis, and occlusive vasculitis with retinal hemorrhages. Although scleritis is not a classical feature of Behçet’s disease, a diagnosis of Behçet’s disease should be considered in patients with scleritis.

  16. Seasonal changes in nodular nitrogenase activity of Alnus glutinosa and Elaeagnus angustifolia.

    PubMed

    Zitzer, S F; Dawson, J O

    1989-06-01

    Root nodule development, and seasonal patterns of nodular nitrogenase and hydrogenase activities were determined for 5- to 8-year old black alder (Alnus glutinosa (L.) Gaertn.) and Russian olive (Elaeagnus angustifolia L.) interplanted with black walnut (Juglans nigra L.) on bottomland and upland sites in central Illinois, USA. Black alder produced nodules at both sites, but Russian olive did so only at the bottomland site. Nodular nitrogenase activity was detectable in both species over a 220-day period. Maximum, midday rates of nitrogenase activity (acetylene reduction) of 15 to 20 micromoles C(2)H(4) per g dry nodule per hour were maintained by black alder for approximately 150 days at both the upland and bottomland sites. Near maximum rates of nodular nitrogenase activity were maintained for a similar period by Russian olive at the lowland site, although specific nitrogenase activity was approximately 25% lower than in black alder owing to a larger proportion of necrotic nodular tissue in Russian olive. In both species, nitrogenase activity increased exponentially with temperature between 10 degrees C and 20 to 25 degrees C. No net hydrogen evolution by nodules of either species was detected at any time during the assay period, indicating efficient hydrogenase systems were operating under the conditions of the field assay. Height of black walnut interplanted with nodulated black alder and Russian olive was greater than that of black walnut grown in pure stands.

  17. Soybean (Glycine max. L.) and bacteroid glyoxylate cycle activities during nodular senescence.

    PubMed

    Fargeix, Christophe; Gindro, Katia; Widmer, François

    2004-02-01

    Soybean (Glycine max. L.) nodular senescence results in the dismantling of the peribacteroid membrane (PBM) and in an increase of soybean isocitrate lyase (ICL; EC 4.1.3.1) and malate synthase (MS; EC 4.1.3.2) mRNA and protein levels. This suggests that in senescing soybean nodular cells, the specific glyoxylate cycle enzyme activities might be induced to reallocate carbon obtained from the PBM degradation. In order to evaluate as well the carbon metabolism of the nitrogen-fixing Bradyrhizobium japonicum endosymbiotic bacteroids during nodular senescence, their glyoxylate cycle activities were also investigated. To this end, partial DNA sequences were isolated from their icl and ms genes, but the corresponding mRNAs were not detected in the microorganisms. It was also observed that the bacteroid ICL and MS activities were negligible during nodular senescence. This suggests that glyoxylate cycle activities are not reinitiated in the bacteroids under these physiological conditions. In case the microorganisms nevertheless feed on the PBM degradation products, this might occur via the citric acid cycle exclusively.

  18. Animal models of disease: feline hyperthyroidism: an animal model for toxic nodular goiter.

    PubMed

    Peterson, Mark E

    2014-11-01

    Since first discovered just 35 years ago, the incidence of spontaneous feline hyperthyroidism has increased dramatically to the extent that it is now one of the most common disorders seen in middle-aged to senior domestic cats. Hyperthyroid cat goiters contain single or multiple autonomously (i.e. TSH-independent) functioning and growing thyroid nodules. Thus, hyperthyroidism in cats is clinically and histologically similar to toxic nodular goiter in humans. The disease in cats is mechanistically different from Graves' disease, because neither the hyperfunction nor growth of these nodules depends on extrathyroidal circulating stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells, but iodine deficiency, other nutritional goitrogens, or environmental disruptors may play a role in the disease pathogenesis. Clinical features of feline toxic nodular goiter include one or more palpable thyroid nodules, together with signs of hyperthyroidism (e.g. weight loss despite an increased appetite). Diagnosis of feline hyperthyroidism is confirmed by finding the increased serum concentrations of thyroxine and triiodothyronine, undetectable serum TSH concentrations, or increased thyroid uptake of radioiodine. Thyroid scintigraphy demonstrates a heterogeneous pattern of increased radionuclide uptake, most commonly into both thyroid lobes. Treatment options for toxic nodular goiter in cats are similar to that used in humans and include surgical thyroidectomy, radioiodine, and antithyroid drugs. Most authorities agree that ablative therapy with radioiodine is the treatment of choice for most cats with toxic nodular goiter, because the animals are older, and the disease will never go into remission.

  19. In Situ fracture observation and fracture toughness analysis of pearlitic graphite cast irons with different nodularity

    NASA Astrophysics Data System (ADS)

    Han, Seung Youb; Sohn, Seok Su; Shin, Sang Yong; Lee, Sunghak; Suh, Yong Chan

    2013-07-01

    Effects of microstructural modification and microfracture mechanisms on fracture toughness of pearlitic graphite cast irons with different nodularity were investigated by in situ observation of microfracture process. Six pearlitic graphite cast irons were fabricated by adding a small amount of Mg as a nodularizing element for graphite, and their microstructures including pearlite, ferrite, graphite, and eutectic carbide were analyzed. Most of ferrites were observed in a layer shape around graphites because of carbon-depleted zones formed near graphites. As the nodularity and nodule count increased, fracture toughness linearly increased in the cast irons except the iron containing many fine graphites. According to in situ observation of microfracture process, cracks initiated at nodular graphites and carbides even at a small load, and then propagated readily through the adjacent graphites or carbides, thereby resulting in the lowest fracture toughness. The cast iron having widely spaced graphites and ferrite layers thickly formed around graphites showed the highest fracture toughness because of the blocking of crack propagation by ductile ferrite layers and the crack blunting and deflection by graphites, which was also confirmed by the R-curve analysis.

  20. Mycobacterium species related to M. leprae and M. lepromatosis from cows with bovine nodular thelitis.

    PubMed

    Pin, Didier; Guérin-Faublée, Véronique; Garreau, Virginie; Breysse, Franck; Dumitrescu, Oana; Flandrois, Jean-Pierre; Lina, Gerard

    2014-12-01

    Bovine nodular thelitis is a granulomatous dermatitis associated with infection with acid-fast bacteria. To identify the mycobacterium responsible for this infection, we conducted phylogenetic investigations based on partial sequencing of 6 genes. These bacteria were identified as an undescribed Mycobacterium species that was phylogenetically related to M. leprae and M. lepromatosis.

  1. Low SGK1 Expression in Human Adrenocortical Tumors Is Associated with ACTH-Independent Glucocorticoid Secretion and Poor Prognosis

    PubMed Central

    Sbiera, Silviu; Leich, Ellen; Tissier, Frédérique; Steinhauer, Sonja; Deutschbein, Timo; Fassnacht, Martin; Allolio, Bruno

    2012-01-01

    Context: Using single-nucleotide polymorphism analysis, we observed allelic loss of the gene for serum glucocorticoid (GC) kinase 1 (SGK1), a GC-responsive kinase involved in multiple cellular functions, in a subset of cortisol-secreting adenomas. Objective: Our objective was to analyze SGK1 expression in adrenocortical tumors and to further characterize its role in ACTH-independent cortisol secretion, tumor progression, and prognosis. Design and Setting: Gene expression levels of SGK1, SGK3, and CTNNB1 (coding for β-catenin) and protein expression levels of SGK1, nuclear β-catenin, and phosphorylated AKT were determined in adrenocortical tumors and normal adrenal glands. Patients: A total of 227 adrenocortical tumors (40 adenomas and 187 carcinomas) and 25 normal adrenal tissues were included. Among them, 62 frozen tumor samples were used for mRNA analysis and 203 tumors were investigated on tissue microarrays or full standard slides by immunohistochemistry. Main Outcome Measures: We evaluated the relationship between SGK1 mRNA and/or protein levels and clinical parameters. Results: SGK1 mRNA levels were lower in cortisol-secreting than in nonsecreting tumors (P < 0.005). Nonsecreting neoplasias showed a significant correlation between SGK1 and CTNNB1 mRNA levels (P < 0.001; r = 0.57). Low SGK1 protein levels, but not nuclear β-catenin and phosphorylated AKT, were associated with poor overall survival in patients with adrenocortical carcinoma (P < 0.005; hazard ratio = 2.0; 95% confidence interval = 1.24–3.24), independent of tumor stage and GC secretion. Conclusion: Low SGK1 expression is related to ACTH-independent cortisol secretion in adrenocortical tumors and is a new prognostic factor in adrenocortical carcinoma. PMID:23055545

  2. [Radiolucent pigment gallstones (author's transl)].

    PubMed

    Wosiewitz, U; Wolpers, C; Quint, P

    1978-12-01

    Pigment gallstones may be subdivided into three different types: radiolucent and radioopaque stones in the gallbladder and radiolucent stones in the common bile duct. 35 of our patients had radiolucent pigment stones in the gallbladder; 21 of these were followed for years by repeated X-ray examination. There is only little enlargement of these stones as time passes by, however the number of these stones increases continuously. Chemical analysis could be done on such stones in 24 cases. The stones were composed of granular calcium bilirubinate and of asphalt-like products derived from abnormal bilirubin degradation. 5 patients had pigment stones in the common bile duct. These stones contained little cholesterol and exhibited a spongy microstructure characterized by small tubules with a diameter of 1 micrometer. They contained more lipids and bilirubin than the stones collected from the gallbladder and on extraction with organic solvents no asphalt-like residues could be obtained.

  3. 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.

  4. Nodular lymphocyte predominant Hodgkin lymphoma: a Lymphoma Study Association retrospective study

    PubMed Central

    Lazarovici, Julien; Dartigues, Peggy; Brice, Pauline; Obéric, Lucie; Gaillard, Isabelle; Hunault-Berger, Mathilde; Broussais-Guillaumot, Florence; Gyan, Emmanuel; Bologna, Serge; Nicolas-Virelizier, Emmanuelle; Touati, Mohamed; Casasnovas, Olivier; Delarue, Richard; Orsini-Piocelle, Frédérique; Stamatoullas, Aspasia; Gabarre, Jean; Fornecker, Luc-Matthieu; Gastinne, Thomas; Peyrade, Fréderic; Roland, Virginie; Bachy, Emmanuel; André, Marc; Mounier, Nicolas; Fermé, Christophe

    2015-01-01

    Nodular lymphocyte predominant Hodgkin lymphoma represents a distinct entity from classical Hodgkin lymphoma. We conducted a retrospective study to investigate the management of patients with nodular lymphocyte predominant Hodgkin lymphoma. Clinical characteristics, treatment and outcome of adult patients with nodular lymphocyte predominant Hodgkin lymphoma were collected in Lymphoma Study Association centers. Progression-free survival (PFS) and overall survival (OS) were analyzed, and the competing risks formulation of a Cox regression model was used to control the effect of risk factors on relapse or death as competing events. Among 314 evaluable patients, 82.5% had early stage nodular lymphocyte predominant Hodgkin lymphoma. Initial management consisted in watchful waiting (36.3%), radiotherapy (20.1%), rituximab (8.9%), chemotherapy or immuno-chemotherapy (21.7%), combined modality treatment (12.7%), or radiotherapy plus rituximab (0.3%). With a median follow-up of 55.8 months, the 10-year PFS and OS estimates were 44.2% and 94.9%, respectively. The 4-year PFS estimates were 79.6% after radiotherapy, 77.0% after rituximab alone, 78.8% after chemotherapy or immuno-chemotherapy, and 93.9% after combined modality treatment. For the whole population, early treatment with chemotherapy or radiotherapy, but not rituximab alone (Hazard ratio 0.695 [0.320–1.512], P=0.3593) significantly reduced the risk of progression compared to watchful waiting (HR 0.388 [0.234–0.643], P=0.0002). Early treatment appears more beneficial compared to watchful waiting in terms of progression-free survival, but has no impact on overall survival. Radiotherapy in selected early stage nodular lymphocyte predominant Hodgkin lymphoma, and combined modality treatment, chemotherapy or immuno-chemotherapy for other patients, are the main options to treat adult patients with a curative intent. PMID:26430172

  5. Nodular lymphocyte predominant Hodgkin lymphoma: a Lymphoma Study Association retrospective study.

    PubMed

    Lazarovici, Julien; Dartigues, Peggy; Brice, Pauline; Obéric, Lucie; Gaillard, Isabelle; Hunault-Berger, Mathilde; Broussais-Guillaumot, Florence; Gyan, Emmanuel; Bologna, Serge; Nicolas-Virelizier, Emmanuelle; Touati, Mohamed; Casasnovas, Olivier; Delarue, Richard; Orsini-Piocelle, Frédérique; Stamatoullas, Aspasia; Gabarre, Jean; Fornecker, Luc-Matthieu; Gastinne, Thomas; Peyrade, Fréderic; Roland, Virginie; Bachy, Emmanuel; André, Marc; Mounier, Nicolas; Fermé, Christophe

    2015-12-01

    Nodular lymphocyte predominant Hodgkin lymphoma represents a distinct entity from classical Hodgkin lymphoma. We conducted a retrospective study to investigate the management of patients with nodular lymphocyte predominant Hodgkin lymphoma. Clinical characteristics, treatment and outcome of adult patients with nodular lymphocyte predominant Hodgkin lymphoma were collected in Lymphoma Study Association centers. Progression-free survival (PFS) and overall survival (OS) were analyzed, and the competing risks formulation of a Cox regression model was used to control the effect of risk factors on relapse or death as competing events. Among 314 evaluable patients, 82.5% had early stage nodular lymphocyte predominant Hodgkin lymphoma. Initial management consisted in watchful waiting (36.3%), radiotherapy (20.1%), rituximab (8.9%), chemotherapy or immuno-chemotherapy (21.7%), combined modality treatment (12.7%), or radiotherapy plus rituximab (0.3%). With a median follow-up of 55.8 months, the 10-year PFS and OS estimates were 44.2% and 94.9%, respectively. The 4-year PFS estimates were 79.6% after radiotherapy, 77.0% after rituximab alone, 78.8% after chemotherapy or immuno-chemotherapy, and 93.9% after combined modality treatment. For the whole population, early treatment with chemotherapy or radiotherapy, but not rituximab alone (Hazard ratio 0.695 [0.320-1.512], P=0.3593) significantly reduced the risk of progression compared to watchful waiting (HR 0.388 [0.234-0.643], P=0.0002). Early treatment appears more beneficial compared to watchful waiting in terms of progression-free survival, but has no impact on overall survival. Radiotherapy in selected early stage nodular lymphocyte predominant Hodgkin lymphoma, and combined modality treatment, chemotherapy or immuno-chemotherapy for other patients, are the main options to treat adult patients with a curative intent.

  6. ACAT-selective and nonselective DGAT1 inhibition: adrenocortical effects--a cross-species comparison.

    PubMed

    Floettmann, Jan Eike; Buckett, Linda K; Turnbull, Andrew V; Smith, Tim; Hallberg, Carina; Birch, Alan; Lees, David; Jones, Huw B

    2013-01-01

    Acyl-coenzyme A: cholesterol O-Acyltransferase (ACAT) and Acyl-coenzyme A: diacylglycerol O-acyltransferase (DGAT) enzymes play important roles in synthesizing neutral lipids, and inhibitors of these enzymes have been investigated as potential treatments for diabetes and other metabolic diseases. Administration of a Acyl-coenzyme A: diacylglycerol O-acyltransferase 1 (DGAT1) inhibitor with very limited cellular selectivity over ACAT resulted in significant adrenocortical degenerative changes in dogs. These changes included macrosteatotic vacuolation associated with adrenocyte cell death in the zonae glomerulosa and fasciculata and minimal to substantial mixed inflammatory cell infiltration and were similar to those described previously for some ACAT inhibitors in dogs. In the mouse, similar but only transient adrenocortical degenerative changes were seen as well as a distinctive nondegenerative reduction in cortical fine vacuolation. In the marmoset, only the distinctive nondegenerative reduction in cortical fine vacuolation was observed, suggesting that the dog, followed by the mouse, is the most sensitive species for cortical degeneration. Biochemical analysis of adrenal cholesterol and cholesteryl ester indicated that the distinctive reduction in cortical fine vacuolation correlated with a significant reduction in cholesteryl ester in the mouse and marmoset, whereas no significant reduction in cholestryl ester, but an increase in free cholesterol was observed in dogs. Administration of a DGAT1 inhibitor with markedly improved selectivity over ACAT to the marmoset and the mouse resulted in no adrenal pathology at exposures sufficient to cause substantial DGAT1 but not ACAT inhibition, thereby implicating ACAT rather than DGAT1 inhibition as the probable cause of the observed adrenal changes. Recognizing that the distinctive nondegenerative reduction in cortical fine vacuolation in the mouse could be used as a histopathological biomarker for an in vivo model of

  7. P53/Rb inhibition induces metastatic adrenocortical carcinomas in a preclinical transgenic model.

    PubMed

    Batisse-Lignier, M; Sahut-Barnola, I; Tissier, F; Dumontet, T; Mathieu, M; Drelon, C; Pointud, J-C; Damon-Soubeyrand, C; Marceau, G; Kemeny, J-L; Bertherat, J; Tauveron, I; Val, P; Martinez, A; Lefrançois-Martinez, A-M

    2017-04-03

    Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis. Pan-genomic analyses identified p53/Rb and WNT/β-catenin signaling pathways as main contributors to the disease. However, isolated β-catenin constitutive activation failed to induce malignant progression in mouse adrenocortical tumors. Therefore, there still was a need for a relevant animal model to study ACC pathogenesis and to test new therapeutic approaches. Here, we have developed a transgenic mice model with adrenocortical specific expression of SV40 large T-antigen (AdTAg mice), to test the oncogenic potential of p53/Rb inhibition in the adrenal gland. All AdTAg mice develop large adrenal carcinomas that eventually metastasize to the liver and lungs, resulting in decreased overall survival. Consistent with ACC in patients, adrenal tumors in AdTAg mice autonomously produce large amounts of glucocorticoids and spontaneously activate WNT/β-catenin signaling pathway during malignant progression. We show that this activation is associated with downregulation of secreted frizzled related proteins (Sfrp) and Znrf3 that act as inhibitors of the WNT signaling. We also show that mTORC1 pathway activation is an early event during neoplasia expansion and further demonstrate that mTORC1 pathway is activated in ACC patients. Preclinical inhibition of mTORC1 activity induces a marked reduction in tumor size, associated with induction of apoptosis and inhibition of proliferation that results in normalization of corticosterone plasma levels in AdTAg mice. Altogether, these data establish AdTAg mice as the first preclinical model for metastatic ACC.Oncogene advance online publication, 3 April 2017; doi:10.1038/onc.2017.54.

  8. Mitotane alters mitochondrial respiratory chain activity by inducing cytochrome c oxidase defect in human adrenocortical cells.

    PubMed

    Hescot, Ségolène; Slama, Abdelhamid; Lombès, Anne; Paci, Angelo; Remy, Hervé; Leboulleux, Sophie; Chadarevian, Rita; Trabado, Séverine; Amazit, Larbi; Young, Jacques; Baudin, Eric; Lombès, Marc

    2013-06-01

    Mitotane, 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane is the most effective medical therapy for adrenocortical carcinoma, but its molecular mechanism of action remains poorly understood. Although mitotane is known to have mitochondrial (mt) effects, a direct link to mt dysfunction has never been established. We examined the functional consequences of mitotane exposure on proliferation, steroidogenesis, and mt respiratory chain, biogenesis and morphology, in two human adrenocortical cell lines, the steroid-secreting H295R line and the non-secreting SW13 line. Mitotane inhibited cell proliferation in a dose- and a time-dependent manner. At the concentration of 50 μM (14 mg/l), which corresponds to the threshold for therapeutic efficacy, mitotane drastically reduced cortisol and 17-hydroxyprogesterone secretions by 70%. This was accompanied by significant decreases in the expression of genes encoding mt proteins involved in steroidogenesis (STAR, CYP11B1, and CYP11B2). In both H295R and SW13 cells, 50 μM mitotane significantly inhibited (50%) the maximum velocity of the activity of the respiratory chain complex IV (cytochrome c oxidase (COX)). This effect was associated with a drastic reduction in steady-state levels of the whole COX complex as revealed by blue native PAGE and reduced mRNA expression of both mtDNA-encoded COX2 (MT-CO2) and nuclear DNA-encoded COX4 (COX4I1) subunits. In contrast, the activity and expression of respiratory chain complexes II and III were unaffected by mitotane treatment. Lastly, mitotane exposure enhanced mt biogenesis (increase in mtDNA content and PGC1α (PPARGC1A) expression) and triggered fragmentation of the mt network. Altogether, our results provide first evidence that mitotane induced a mt respiratory chain defect in human adrenocortical cells.

  9. Mitotane effects in a H295R xenograft model of adjuvant treatment of adrenocortical cancer.

    PubMed

    Lindhe, O; Skogseid, B

    2010-09-01

    Adrenocortical cancer is one of the most aggressive endocrine malignancies. Growth through the capsule or accidental release of cancer cells during surgery frequently results in metastatic disease. We investigated the antitumoral effect of 2 adrenocorticolytic compounds, O, P'-DDD and MeSO2-DDE, in the adrenocortical cell line H295R both in vitro and as a xenograft model in vivo. H295R cells were injected s. c. in nude mice. O, P'-DDD, MeSO2-DDE, or oil (control) was administered i. p., either simultaneously with cell injection at day 0 (mimicking adjuvant treatment), or at day 48 (established tumors). Accumulation of PET tracers [ (11)C]methionine (MET), [ (11)C] metomidate (MTO), 2-deoxy-2-[ (18)F]fluoro-d-glucose (FDG), and [ (18)F]-l-tyrosine (FLT) in the aggregates were assessed +/- drug treatment in vitro. Tumor growth was significantly inhibited when O, P'-DDD was given at the same time as injection of tumor cells. No significant growth inhibition was observed after treatment with O, P'-DDD at day 48. A significant reduction in FLT uptake and an increased FDG uptake, compared to control, were observed following treatment with 15 microM O, P'-DDD (p<0.01) in vitro. MeSO2-DDE (15 microM) treatment gave rise to a reduced MET and an increased FLT uptake (p<0.01). Both compounds reduced the uptake of MTO compared to control (p<0.01). Treatment with O, P'-DDD simultaneously to inoculation of H295R cells in mice, imitating release of cells during surgery, gave a markedly better effect than treatment of established H295R tumors. We suggest that FLT may be a potential PET biomarker when assessing adrenocortical cancer treatment with O,P'-DDD. Further studies in humans are needed to investigate this.

  10. 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

  11. Cell cycle dependent RRM2 may serve as proliferation marker and pharmaceutical target in adrenocortical cancer

    PubMed Central

    Grolmusz, Vince Kornél; Karászi, Katalin; Micsik, Tamás; Tóth, Eszter Angéla; Mészáros, Katalin; Karvaly, Gellért; Barna, Gábor; Szabó, Péter Márton; Baghy, Kornélia; Matkó, János; Kovalszky, Ilona; Tóth, Miklós; Rácz, Károly; Igaz, Péter; Patócs, Attila

    2016-01-01

    Adrenocortical cancer (ACC) is a rare, but agressive malignancy with poor prognosis. Histopathological diagnosis is challenging and pharmacological options for treatment are limited. By the comparative reanalysis of the transcriptional malignancy signature with the cell cycle dependent transcriptional program of ACC, we aimed to identify novel biomarkers which may be used in the histopathological diagnosis and for the prediction of therapeutical response of ACC. Comparative reanalysis of publicly available microarray datasets included three earlier studies comparing transcriptional differences between ACC and benign adrenocortical adenoma (ACA) and one study presenting the cell cycle dependent gene expressional program of human ACC cell line NCI-H295R. Immunohistochemical analysis was performed on ACC samples. In vitro effects of antineoplastic drugs including gemcitabine, mitotane and 9-cis-retinoic acid alone and in combination were tested in the NCI-H295R adrenocortical cell line. Upon the comparative reanalysis, ribonucleotide reductase subunit 2 (RRM2), responsible for the ribonucleotide dezoxyribonucleotide conversion during the S phase of the cell cycle has been validated as cell cycle dependently expressed. Moreover, its expression was associated with the malignancy signature, as well. Immunohistochemical analysis of RRM2 revealed a strong correlation with Ki67 index in ACC. Among the antiproliferative effects of the investigated compounds, gemcitabine showed a strong inhibition of proliferation and an increase of apoptotic events. Additionally, RRM2 has been upregulated upon gemcitabine treatment. Upon our results, RRM2 might be used as a proliferation marker in ACC. RRM2 upregulation upon gemcitabine treatment might contribute to an emerging chemoresistance against gemcitabine, which is in line with its limited therapeutical efficacy in ACC, and which should be overcome for successful clinical applications. PMID:27725909

  12. 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.

  13. Investigation of N-cadherin/β-catenin expression in adrenocortical tumors.

    PubMed

    Rubin, Beatrice; Regazzo, Daniela; Redaelli, Marco; Mucignat, Carla; Citton, Marilisa; Iacobone, Maurizio; Scaroni, Carla; Betterle, Corrado; Mantero, Franco; Fassina, Ambrogio; Pezzani, Raffaele; Boscaro, Marco

    2016-10-01

    β-catenin is a multifunctional protein; it is a key component of the Wnt signaling, and it plays a central role in cadherin-based adhesions. Cadherin loss promotes tumorigenesis by releasing membrane-bound β-catenin, hence stimulating Wnt signaling. Cadherins seem to be involved in tumor development, but these findings are limited in adrenocortical tumors (ACTs). The objective of this study was to evaluate alterations in key components of cadherin/catenin adhesion system and of Wnt pathway. This study included eight normal adrenal samples (NA) and 95 ACT: 24 adrenocortical carcinomas (ACCs) and 71 adrenocortical adenomas (ACAs). β-catenin mutations were evaluated by sequencing, and β-catenin and cadherin (E-cadherin and N-cadherin) expression was analyzed by quantitative reverse transcription PCR (qRT-PCR) and by immunohistochemistry (IHC). We identified 18 genetic alterations in β-catenin gene. qRT-PCR showed overexpression of β-catenin in 50 % of ACC (12/24) and in 48 % of ACA (21/44). IHC data were in accordance with qRT-PCR results: 47 % of ACC (7/15) and 33 % of ACA (11/33) showed increased cytoplasmic or nuclear β-catenin accumulation. N-cadherin downregulation has been found in 83 % of ACC (20/24) and in 59 % of ACA (26/44). Similar results were obtained by IHC: N-cadherin downregulation was observed in 100 % (15/15) of ACC and in 55 % (18/33) of ACA. β-catenin overexpression together with the aberrant expression of N-cadherin may play important role in ACT tumorigenesis. The study of differentially expressed genes (such as N-cadherin and β-catenin) may enhance our understanding of the biology of ACT and may contribute to the discovery of new diagnostic and prognostic tools.

  14. 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.

  15. Multi-organ resection for locally advanced adrenocortical cancer: surgical strategy and literature review

    PubMed Central

    GUIDA, F.; CLEMENTE, M.; VALVANO, L.; NAPOLITANO, C.

    2015-01-01

    Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy with an estimated worldwide incidence of 0.5–2 per million/year. Complete surgical removal of ACC represents the current treatment of choice for this tumor. A disease-free resection margin (R0) is an important predictor of long-term survival: surgery is demanding and must be performed by a highly experienced surgical team. We report the surgical strategy adopted in a patient with locally advanced ACC and virilization to obtain a R0 resection. PMID:26712261

  16. 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.

  17. Focal nodular hyperplasia of the liver and elevated alpha fetoprotein level in an infant with isolated hemihyperplasia.

    PubMed

    Demir, Hac Ahmet; Varan, Ali; Akçören, Zuhal; Haliloglu, Mithat; Büyükpamukcu, Münevver

    2008-10-01

    A case of focal nodular hyperplasia of the liver in a 43-day-old baby girl with isolated hemihyperplasia and elevated serum alpha-fetoprotein is presented. The child referred to our hospital with bilateral renal masses detected by prenatal and postnatal ultrasonography. A mass lesion was detected in segment 6 of liver and was diagnosed as focal nodular hyperplasia. We present this case to emphasize the presence of focal nodular hyperplasia in a patient with isolated hemihypertrophy and elevated serum alpha-fetoprotein level.

  18. A case of pigmented Bowen's disease*

    PubMed Central

    Vivan, Márcia Maria; Hirata, Sérgio Henrique; do Nascimento, Liliane Santos; Enokihara, Milvia Maria Simões e Silva

    2017-01-01

    Pigmented Bowen's disease is a rare subtype of Bowen's disease. Clinically it presents as a slow-growing, well-defined, hyperpigmented plaque, and should be included as a differential diagnosis of other pigmented lesions. The authors describe a challenging case of pigmented Bowen's disease with non-diagnostic dermscopy findings. PMID:28225972

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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....

  6. 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...

  7. 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...

  8. 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...

  9. BACILLUS PYOCYANEUS AND ITS PIGMENTS

    PubMed Central

    Jordan, Edwin O.

    1899-01-01

    The principal conclusions that seem to me justified are as follows: 1. The fluorescent pigment formed by some varieties of B. pyocyaneus is produced under conditions identical with those governing the production of the pigment by other "fluorescent bacteria." 2. The production of pyocyanin is not dependent upon the presence of either phosphate or sulfate in the culture medium. It is formed in non-proteid as well as in proteid media, but is not a necessary accompaniment of the metabolic activities of the organism (e. g. tartrate solution). 3. The power of producing pyocyanin under conditions of artificial cultivation is lost sooner than the fluorescigenic power. 4. There are greater natural and acquired differences in pyocyanigenic power than in fluorescigenic. 5. The fluorescent pigment may be oxidized slowly by the action of light and air as well as by reagents into a yellow pigment, and pyocyanin may be similarly oxidized into a black pigment. 6. A convenient separation of B. pyocyaneus into four varieties would be the following: var. α, pyocyanigenic and fluorescigenic (most common); var. β, pyocyanigenic only (rare); var. γ, fluorescigenic only (not uncommon, closely related to "B. fluorescens liquefaciens"); var. δ, non-chromogenic. 7. Except for the occasional loss of one or another function the different varieties are not so plastic as sometimes assumed, and cannot be readily converted into one another by subjection to varying conditions of life. 8. The signification and correlation of the almost countless physiological variations among the members of this group in respect to growth in gelatin, behavior to temperature, indol production, etc., remain to be determined. It is not yet clear that the variations in chromogenic power can be in any way correlated with the presence or absence of other physiological functions. PMID:19866929

  10. 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.

  11. Isolated adrenocortical cells of the domestic fowl (Gallus domesticus): steroidogenic and ultrastructural properties.

    PubMed

    Carsia, R V; Scanes, C G; Malamed, S

    1985-02-01

    Isolated adrenocortical cells from White Leghorn chickens (Gallus domesticus) were compared to those from rats (Rattus norvegicus). Cells were prepared from collagenase-dispersed adrenal glands of sexually mature male animals. Corticosterone was measured by radioimmunoassay after incubation for 2 h with steroidogenic agents. Of the four ACTH analogues used, three were 6-17 times more potent with rat cells than with fowl cells (potencies were indicated by half-maximal steroidogenic concentrations). However, 9-tryptophan (O-nitrophenylsulfenyl) ACTH was 8 times more potent with fowl cells than with rat cells, thus suggesting that ACTH receptor differences exist between the two cell types. In addition, cAMP analogues were 10 times more potent with rat cells than with fowl cells suggesting that fowl corticosteroidogenesis is less dependent on cAMP than is rat corticosteroidogenesis. At equal cell concentrations, rat cells secreted 20-40 times more corticosterone than did chicken cells when they were maximally stimulated. Although rat cells converted 8 times more pregnenolone to corticosterone than did fowl cells, the half-maximal steroidogenic concentration for pregnenolone-supported corticosterone synthesis was the same for both cell types (about 5 microM). This suggests that fowl cells have lower steroidogenic enzyme content rather than lower steroidogenic enzyme activity. An unusual feature seen in the isolated fowl adrenocortical cells was an abundance of intracellular filaments.

  12. Steroid control of steroidogenesis in isolated adrenocortical cells: molecular and species specificity.

    PubMed

    Carsia, R V; Macdonald, G J; Malamed, S

    1983-06-01

    The molecular and species specificity of glucocorticoid suppression of corticosteroidogenesis was investigated in isolated adrenocortical cells. Trypsin-isolated cells from male rat, domestic fowl and bovine adrenal glands were incubated with or without steroidogenic agents and with or without steroids. Glucocorticoids were measured by radioimmunoassay or fluorometric assay after 1-2 h incubation. Glucocorticoids suppressed ACTH-induced steroidogenesis of isolated rat cells with the following relative potencies: corticosterone greater than cortisol = cortisone greater than dexamethasone. The mineralocorticoid, aldosterone did not affect steroidogenesis. Suppression by glucocorticoids was acute (within 1-2 h), and varied directly with the glucocorticoid concentration. Testosterone also suppressed ACTH-induced steroidogenesis. Glucocorticoid-type steroids have equivalent suppressive potencies, thus suggesting that these steroids may induce suppression at least partly by a common mechanism. Although corticosterone caused the greatest suppression, testosterone was more potent. The steroid specificity of suppression of cyclic AMP (cAMP)-induced and ACTH-induced steroidogenesis were similar, suggesting that suppression is not solely the result of interference with ACTH receptor function or the induction of adenylate cyclase activity. Exogenous glucocorticoids also suppressed ACTH-induced steroidogenesis of cells isolated from domestic fowl and beef adrenal glands, thus suggesting that this observed suppression may be a general mechanism of adrenocortical cell autoregulation.

  13. 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

  14. Acute effects of ACTH on dissociated adrenocortical cells: quantitative changes in mitochondria and lipid droplets.

    PubMed

    Zoller, L C; Malamed, S

    1975-08-01

    To study the role of certain organelles in steroidogenesis, dissociated rat adrenocortical cells were incubated for two hours with ACTH at a concentration that induces a high level of steroid production. Sections of ACTH treated and untreated cells were photographed in the electron microscope, and morphometric analysis was undertaken to assess possible ACTH-induced changes in total cell volume, volume density and numerical denisty of lipid droplets and mitochondria. There was no change in total cell volume. Lipid droplet volume density and numerical density decreased. Mitochondrial volume density did not change, but numerical density increased. The decrease in lipid droplet volume density indicates a rapid depletion of cholesterol for steroid production. This depletion is almost entirely due to the disappearance of lipid droplets, rather than to an overall diminution in their size, as shown by the decrease in lipid droplet numerical density. The mitochondrial data suggest that the adrenocortical cell has an adedquate mitochondrial apparatus to respond to acute ACTH stimulation with increased steroid output without an increase inmitochondrial volume.

  15. 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. PMID:27275470

  16. Morphofunctional effects of mitotane on mitochondria in human adrenocortical cancer cells.

    PubMed

    Poli, Giada; Guasti, Daniele; Rapizzi, Elena; Fucci, Rossella; Canu, Letizia; Bandini, Alessandra; Cini, Nicoletta; Bani, Daniele; Mannelli, Massimo; Luconi, Michaela

    2013-08-01

    At present, mitotane (MTT) represents the first-line pharmacological approach for the treatment of advanced adrenocortical carcinoma (ACC). Despite clear evidence that the drug can reduce the clinical signs of steroid excess in secreting ACC, the mechanism mediating the possible toxic effect of MTT on tumor cells still remains obscure. This study investigated the intracellular events underlying the toxic effect of MTT by studying qualitative and quantitative alterations in mitochondrial morphology and functions in human adrenocortical cancer cell lines, H295R and SW13. Increasing concentrations of MTT resulted in rapid intracellular accumulation and conversion of the drug. Cytostatic and cytotoxic effects were evident at doses corresponding to the therapeutic window (30-50 μM) through an apoptotic mechanism involving caspase 3/7. Electron microscopic analysis of cell mitochondria displayed MTT-induced dose- and time-dependent alterations in the morphology of the organelle. These alterations were characterized by a marked swelling and a decrease in the number of respiratory cristae, accompanied by a significant depolarization of the mitochondrial membrane potential, finally leading to the disruption of the organelle. A drastic reduction of oxygen consumption was observed due to mitochondrial membrane damage, which was accompanied by a decrease in the levels of VDAC1 integral membrane channel. These findings contribute to better understand the intracellular mechanism of action of MTT in ACC cells, showing that its cytotoxic effect seems to be mainly mediated by an apoptotic process activated by the disruption of mitochondria.

  17. Mitotane enhances doxorubicin cytotoxic activity by inhibiting P-gp in human adrenocortical carcinoma cells.

    PubMed

    Gagliano, Teresa; Gentilin, Erica; Benfini, Katiuscia; Di Pasquale, Carmelina; Tassinari, Martina; Falletta, Simona; Feo, Carlo; Tagliati, Federico; Uberti, Ettore Degli; Zatelli, Maria Chiara

    2014-12-01

    Mitotane is currently employed as adjuvant therapy as well as in the medical treatment of adrenocortical carcinoma (ACC), alone or in combination with chemotherapeutic agents. It was previously demonstrated that mitotane potentiates chemotherapeutic drugs cytotoxicity in cancer cells displaying chemoresistance due to P-glycoprotein (P-gp), an efflux pump involved in cancer multidrug resistance. The majority of ACC expresses high levels of P-gp and is highly chemoresistent. The aim of our study was to explore in vitro whether mitotane, at concentrations lower than those currently reached in vivo, may sensitize ACC cells to the cytotoxic effects of doxorubicin and whether this effect is due to a direct action on P-gp. NCI-H295 and SW13 cell lines as well as 4 adrenocortical neoplasia primary cultures were treated with mitotane and doxorubicin, and cell viability was measured by MTT assay. P-gp activity was measured by calcein and P-gp-Glo assays. P-gp expression was evaluated by Western blot. We found that very low mitotane concentrations sensitize ACC cells to the cytotoxic effects of doxorubicin, depending on P-gp expression. In addition, mitotane directly inhibits P-gp detoxifying function, allowing doxorubicin cytotoxic activity. These data provide the basis for the greater efficacy of combination therapy (mitotane plus chemotherapeutic drugs) on ACC patients. Shedding light on mitotane mechanisms of action could result in an improved design of drug therapy for patients with ACC.

  18. Metastatic virilizing adrenocortical carcinoma: a rare case of cure with surgery and mitotane therapy.

    PubMed

    Chalasani, Sreelatha; Vats, Hemender Singh; Banerjee, Tarit K; McKenzie, Alan K

    2009-06-01

    A 57-year-old white woman with metastases to lungs and liver from virilizing adrenocortical carcinoma (ACC) was treated with radical nephroadrenalectomy followed by oral mitotane 3 to 6 g/day for 5 months. She developed complete response and remained free of disease for more than 25 years. Here we present the case and review the literature. ACC is a rare tumor and may occur at any age. About 60% are functional tumors with hormonal secretions and clinical manifestations due to specific hormone secretions: Cushing's syndrome due to cortisone, virilizing tumor due to androgens, feminizing tumor due to estrogens, or hypertension due to aldosterone. Stage I and II disease is curable with surgery. Stage III and IV disease may benefit from mitotane orally with gradual adjustment of the dosage to a tolerable level. Plasma mitotane level at 14 to 20 g/L results in optimal response both in hormonal secretion and symptom control, as well as tumor regression. Addition of chemotherapy (streptozotocin or a combination of etoposide, cisplatin and doxorubicin) to mitotane also produced responses along with increased survival among responders. An international study has been started by randomizing between two of the above combinations by the Collaborative Group for Adrenocortical Carcinoma Treatment.

  19. Virilizing para-adrenocortical adenoma associated with idiopathic-acquired generalized anhidrosis in an adolescent girl.

    PubMed

    Gumus, Pinar; Luquette, Mark; Haymon, Marie Louise; Valerie, Evans; Morales, Jaime; Vargas, Alfonso

    2011-01-01

    Adrenocortical tumors are rare in childhood and adolescence. Virilization, alone or in combination with signs of overproduction of other adrenal hormones, is the most common clinical presentation. Here we report an unusual case of an African-American female adolescent presenting with idiopathic acquired generalized anhidrosis, dysregulation of body temperature, absence of adult body odor and dry skin in the face of a virilizing para-adrenocortical adenoma. Virilization signs regressed soon after removal of the tumor, but normalization of the 3alpha-androstenediol glucuronide (3alpha-AG) took longer compared to other measurable androgens; accompanied by anhidrosis. The association of remitting anhidrosis with normalized levels of 3alpha-AG suggests it might be a possible mechanism for anhidrosis. High 3alpha-AG levels might implicate the increased peripheral conversion of weak pro-androgens with different biochemical structure. We recommend obtaining 3alpha-AG beside other androgens in virilized patients with atypical dermatological symptoms in the face of hyperandrogenism.

  20. 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.

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

    PubMed

    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.

  2. Feminizing adrenocortical adenoma presenting as heterosexual precocious puberty: report of one case.

    PubMed

    Hsiao, Hui-Pin; Chao, Mei-Chyn; Lin, Chao-Yu; Chen, Hsiu-Lin; Chen, Shiu-Lin; Chiou, Shyh-Shin; Chen, Bai-Hsiun

    2005-01-01

    We report on a case of a 2 2/12-year-old boy with heterosexual precocious puberty secondary to a feminizing adrenocortical adenoma. The boy, with no previous history of disease or treatment, presented with bilateral gynecomastia and pubic hair development (Tanner III breasts and Tanner II pubic hair). Plasma estradiol and testosterone were 410.9 pg/ml and 126.2 ng/dl respectively. Basal plasma LH and FSH levels were within the normal range. Bolus i.v. injection of GnRH showed unresponsiveness of LH and FSH. Abdominal echography and abdominal magnetic resonance imaging revealed a well-defined mass at the left suprarenal region (measuring 4.0 x 2.7 x 3.6 cm in size). After removal of the adrenal tumor, the estradiol and testosterone levels fell to normal in 2 weeks. The gynecomastia and pubic hair regressed with time. The pathology of the tumor showed compact pattern with polygonal cells containing moderate eosinophilic cytoplasm without mitotic figure. These findings were consistent with an adrenocortical adenoma secreting estradiol and testosterone as the cause of the patient's heterosexual precocious puberty.

  3. Species differences in 3-methylsulphonyl-DDE bioactivation by adrenocortical tissue.

    PubMed

    Lindström, Veronica; Brandt, Ingvar; Lindhe, Orjan

    2008-03-01

    The CYP11B1-activated adrenocortical toxicant 3-methylsulphonyl-DDE (3-MeSO2-DDE) is proposed as a lead compound for an improved chemotherapy for adrenocortical carcinoma. We compared the binding of 3-MeSO2-[14C]DDE in the adrenal cortex of four rodent species; hamster, guinea pig, mouse and rat, using a precision-cut adrenal slice culture system ex vivo. Localization and quantification of the bound radioactivity were carried out using light microscopy autoradiography and radioluminography. The results revealed major species differences since 3-MeSO2-[14C]DDE was extensively bound to the hamster adrenal tissue while the guinea pig adrenals were devoid of binding. A high binding in mouse adrenal cortex was confirmed while binding in rat adrenal cortex was very weak. The results support previous observations that metabolic activation of 3-MeSO2-DDE is highly species dependent. Since CYP11B1 could be expressed in tissues other than the adrenal cortex, final toxicological characterization should be carried out in a species that can bioactivate this compound.

  4. Neuropeptides and the hypothalamic-pituitary-adrenocortical (HPA) system: review of recent research strategies in depression.

    PubMed

    Hatzinger, M

    2000-04-01

    Depressed patients show a variety of alterations in hypothalamic-pituitary-adrenocortical (HPA) system regulation which is reflected by increased pituitary-adrenocortical hormone secretion at baseline and a number of aberrant neuroendocrine function tests. The latter include the combined dexamethasone (DEX) suppression/corticotropin-releasing hormone (CRH) challenge test, in which CRH was able to override DEX induced suppression of ACTH and cortisol secretion. Whereas the abnormal HPA activation in these patients improved in parallel with clinical remission, persistent HPA dysregulation was associated with an increased risk of relapse. Moreover, healthy subjects at high genetic risk for depression also showed this phenomenon as a trait marker. In consequence, it has been concluded that HPA alteration and development as well as course of depression may be causally related. As evidenced from clinical and preclinical studies, underlying mechanisms of these abnormalities involve impairment of central corticosteroid receptor function which leads to enhanced activity of hypothalamic neurons synthesising and releasing vasopressin and CRH. These neuropeptides mediate not only neuroendocrine but also behavioural effects. Recent research provided evidence that CRH can induce depression-like symptoms in animals and that these signs are mediated through the CRH1 receptor subtype. Hence, therapeutical application of new compounds acting more specifically on the HPA system such as CRH1 receptor antagonists appear to be a promising approach for future treatment options of depression. In conclusion, research in neuroendocrinology provided new insights into the underlying pathophysiology of depression and, in consequence, may lead to the development of new therapeutic tools.

  5. If It Goes up, Must It Come Down? Chronic Stress and the Hypothalamic-Pituitary Adrenocortical Axis in Humans

    ERIC Educational Resources Information Center

    Miller, Gregory E.; Chen, Edith; Zhou, Eric S.

    2007-01-01

    The notion that chronic stress fosters disease by activating the hypothalamic-pituitary adrenocortical (HPA) axis is featured prominently in many theories. The research linking chronic stress and HPA function is contradictory, however, with some studies reporting increased activation, and others reporting the opposite. This meta-analysis showed…

  6. Endothelial cells regulate β-catenin activity in adrenocortical cells via secretion of basic fibroblast growth factor.

    PubMed

    Schwafertz, Carolin; Schinner, Sven; Kühn, Markus C; Haase, Matthias; Asmus, Amelie; Mülders-Opgenoorth, Birgit; Ansurudeen, Ishrath; Hornsby, Peter J; Morawietz, Henning; Oetjen, Elke; Schott, Matthias; Willenberg, Holger S

    2017-02-05

    Endothelial cell-derived products influence the synthesis of aldosterone and cortisol in human adrenocortical cells by modulating proteins such as steroidogenic acute-regulatory (StAR) protein, steroidogenic factor (SF)-1 and CITED2. However, the potential endothelial cell-derived factors that mediate this effect are still unknown. The current study was perfomed to look into the control of β-catenin activity by endothelial cell-derived factors and to identify a mechanism by which they affect β-catenin activity in adrenocortical NCIH295R cells. Using reporter gene assays and Western blotting, we found that endothelial cell-conditioned medium (ECCM) led to nuclear translocation of β-catenin and an increase in β-catenin-dependent transcription that could be blocked by U0126, an inhibitor of the mitogen-activated protein kinase pathway. Furthermore, we found that a receptor tyrosin kinase (RTK) was involved in ECCM-induced β-catenin-dependent transcription. Through selective inhibition of RTK using Su5402, it was shown that receptors responding to basic fibroblast growth factor (bFGF) mediate the action of ECCM. Adrenocortical cells treated with bFGF showed a significant greater level of bFGF mRNA. In addition, HUVECs secrete bFGF in a density-dependent manner. In conclusion, the data suggest that endothelial cells regulate β-catenin activity in adrenocortical cells also via secretion of basic fibroblast growth factor.

  7. 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...

  8. Combined comparative genomic hybridization and genomic microarray for detection of gene amplifications in pulmonary artery intimal sarcomas and adrenocortical tumors.

    PubMed

    Zhao, Jianming; Roth, Jürgen; Bode-Lesniewska, Beata; Pfaltz, Madeleine; Heitz, Philipp U; Komminoth, Paul

    2002-05-01

    Identification of gene amplifications in human tumors is important for the understanding of tumorigenesis and may lead to discovery of diagnostic and prognostic markers. In this study, we used a microarray-based comparative genomic hybridization (CGH) technique, combined with conventional CGH, to identify gene amplifications in 43 tumors including eight pulmonary artery intimal sarcomas and 35 adrenocortical tumors. Conventional CGH revealed gains or amplifications of 12q13-q15 in six sarcomas and in two adrenocortical carcinomas. Using microarrays, we demonstrated that, among genes located on 12q13-q15, SAS/CDK4 were amplified in six sarcomas, and MDM2 and GLI in five and four sarcomas, respectively. The two adrenocortical tumors showed coamplifications of SAS/CDK4 and MDM2. Furthermore, PDGFRA (located on 4q12) amplification was identified in five sarcomas. Our data demonstrate: (1) amplifications of SAS/CDK4, MDM2, GLI, and PDGFRA are strongly associated with the tumorigenesis of pulmonary artery intimal sarcomas, whereas SAS/CDK4 and MDM2 coamplification may contribute to the progression of adrenocortical tumors; (2) microarray-based CGH is a useful tool for simultaneous detection of multiple gene amplifications, with a high sensitivity and resolution compared to that of conventional CGH.

  9. Diffuse Muscular Pain, Skin Tightening, and Nodular Regenerative Hyperplasia Revealing Paraneoplastic Amyopathic Dermatomyositis due to Testicular Cancer.

    PubMed

    Norrenberg, Sarah; Gangji, Valérie; Del Marmol, Véronique; Soyfoo, Muhammad S

    2012-01-01

    Paraneoplastic dermatomyositis (DM) associated with testicular cancer is extremely rare. We report the case of a patient with skin tightening, polymyalgia, hypereosinophilia, and nodular regenerative hyperplasia revealing seminoma and associated paraneoplastic DM.

  10. Prognostic factors in nodular lymphomas: a multivariate analysis based on the Princess Margaret Hospital experience

    SciTech Connect

    Gospodarowicz, M.K.; Bush, R.S.; Brown, T.C.; Chua, T.

    1984-04-01

    A total of 1,394 patients with non-Hodgkin's lymphoma were treated at the Princess Margaret Hospital between January 1, 1967 and December 31, 1978. Overall actuarial survival of 525 patients with nodular lymphomas was 40% at 12 years; survival of patients with localized (Stage I and III) nodular lymphomas treated with radical radiation therapy was 58%. Significant prognostic factors defined by multivariate analysis included patient's age, stage, histology, tumor bulk, and presence of B symptoms. By combining prognostic factors, distinct prognostic groups have been identified within the overall population. Patients with Stage I and II disease, small or medium bulk, less than 70 years of age achieved 92% 12 year actuarial survival and a 73% relapse-free rate in 12 years of follow-up. These patients represent groups highly curable with irradiation.

  11. 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.

  12. Multiple bilateral pulmonary nodules masquerading as pulmonary metastasis; a case of nodular sarcoidosis

    PubMed Central

    Jafari, Mostafa; Farrokh, Donya; Mohammadpanah, Najmeh

    2016-01-01

    Sarcoidosis is a multi-system inflammatory disorder of unknown etiology that is manifested by the presence of non-caseating granulomas. Multiple pulmonary nodules are rare presentations of sarcoidosis. We report a case of nodular sarcoidosis in a young male of Middle-East origin who had initially presented with bilateral painful ankle edema. His chest X-ray showed multiple bilateral pulmonary nodules. A high resolution computed tomography scan of the chest demonstrated multiple pulmonary nodular lesions and also mediastinal and hilar lymphadenopathy. Subsequent biopsies revealed non-necrotizing granuloma with multi-nucleated giant cells indicative of sarcoidosis. An appropriate work-up was done to confirm the true nature of the nodules and facilitate treatment. PMID:27757192

  13. Nodular transformation of the liver associated with portal and pulmonary arterial hypertension.

    PubMed

    Portmann, B; Stewart, S; Higenbottam, T W; Clayton, P T; Lloyd, J K; Williams, R

    1993-02-01

    A case of multiple focal nodular hyperplasia (FNH) of the liver associated with noncirrhotic portal hypertension and later complicated by pulmonary arterial hypertension leading to death from right heart failure is reported. In retrospect, the portal hypertension diagnosed in early life was most likely due to a congenital hypoplasia of portal vein branches and multiple FNH, a hyperplastic response of the liver parenchyma in association with anomalies of hepatic arterial branches as found within the lesions. This case may represent a form of multiple FNH syndrome restricted to the liver, because neither extrahepatic vascular malformation nor brain tumor was identified at autopsy. The FNH lesions had considerably expanded over the years, and the severe sinusoidal congestion due to chronic right-sided heart failure with subsequent prolonged parenchymal exposure to blood-borne hepatotrophic factors is a likely explanation for both the massive enlargement of FNH lesions and the nodular regenerative hyperplasia observed in the intervening parenchyma.

  14. Availability and Utilization of Pigments from Microalgae.

    PubMed

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

    2016-10-02

    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.

  15. Complexometric determination of magnesium in nodular cast iron and alloyed cast iron roll samples.

    PubMed

    Banerjee, S; Dutta, R K

    1980-02-01

    A complexometric method for the determination of magnesium in nodular cast iron, alloyed cast iron and roll samples has been developed. The bulk of the iron is removed by ether extraction and the phosphate as zirconium phosphate. The other elements are removed by extraction with dithiocarbamate into chloroform. Magnesium is then titrated with EDTA at pH 10, with Eriochrome Black T as indicator. Calcium interferes, but is very rarely present in such cast iron samples.

  16. Laryngeal involvement with fatal outcome in progressive nodular histiocytosis: A rare case report

    PubMed Central

    Salunke, Aarti; Belgaumkar, Vasudha; Chavan, Ravindranath; Dobariya, Rinkesh

    2016-01-01

    Progressive nodular histiocytosis (PNH) represents a very rare type of non-Langerhans cell histiocytosis. It is characterized by progressive appearance of papules and nodules without spontaneous resolution. We report a 60-year-old patient with novel clinical features in the form of extensive noduloulcerative lesions, ichthyotic patches, and laryngeal involvement culminating in fatal outcome prior to therapeutic intervention. Although the presenting features were baffling, histopathology and immunohistochemistry clinched the diagnosis of PNH. PMID:27990389

  17. 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).

  18. 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.

  19. Nodular lymphoid hyperplasia in the gastrointestinal tract in adult patients: A review.

    PubMed

    Albuquerque, Andreia

    2014-11-16

    Nodular lymphoid hyperplasia of the gastrointestinal tract is characterized by the presence of multiple small nodules, normally between between 2 and 10 mm in diameter, distributed along the small intestine (more often), stomach, large intestine, or rectum. The pathogenesis is largely unknown. It can occur in all age groups, but primarily in children and can affect adults with or without immunodeficiency. Some patients have an associated disease, namely, common variable immunodeficiency, selective IgA deficiency, Giardia infection, or, more rarely, human immunodeficiency virus infection, celiac disease, or Helicobacter pylori infection. Nodular lymphoid hyperplasia generally presents as an asymptomatic disease, but it may cause gastrointestinal symptoms like abdominal pain, chronic diarrhea, bleeding or intestinal obstruction. A diagnosis is made at endoscopy or contrast barium studies and should be confirmed by histology. Its histological characteristics include markedly hyperplasic, mitotically active germinal centers and well-defined lymphocyte mantles found in the lamina propria and/or in the superficial submucosa, distributed in a diffuse or focal form. Treatment is directed towards associated conditions because the disorder itself generally requires no intervention. Nodular lymphoid hyperplasia is a risk factor for both intestinal and, very rarely, extraintestinal lymphoma. Some authors recommend surveillance, however, the duration and intervals are undefined.

  20. Cutaneous metastatic pigmented breast carcinoma.

    PubMed

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

    2016-03-16

    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.

  1. Visual Pigments of Goldfish Cones

    PubMed Central

    Hárosi, Ferenc I.; MacNichol, Edward F.

    1974-01-01

    Freshly isolated retinal photoreceptors of goldfish were studied microspectrophotometrically. Absolute absorptance spectra obtained from dark-adapted cone outer segments reaffirm the existence of three spectrally distinct cone types with absorption maxima at 455 ± 3,530 ± 3, and 625 ± 5 nm. These types were found often recognizable by gross cellular morphology. Side-illuminated cone outer segments were dichroic. The measured dichroic ratio for the main absorption band of each type was 2–3:1. Rapidly bleached cells revealed spectral and dichroic transitions in regions near 400–410, 435–455, and 350–360 nm. These photoproducts decay about fivefold as fast as the intermediates in frog rods. The spectral maxima of photoproducts, combined with other evidence, indicate that retinene2 is the chromophore of all three cone pigments. The average specific optical density for goldfish cone outer segments was found to be 0.0124 ± 0.0015/µm. The spectra of the blue-, and green-absorbing cones appeared to match porphyropsin standards with half-band width Δν = 4,832 ± 100 cm–1. The red-absorbing spectrum was found narrower, having Δν = 3,625 ± 100 cm–1. The results are consistent with the notion that visual pigment concentration within the outer segments is about the same for frog rods and goldfish cones, but that the blue-, and green-absorbing pigments possess molar extinctions of 30,000 liter/mol cm. The red-absorbing pigment was found to have extinction of 40,000 liter/mol cm, assuming invariance of oscillator strength among the three cone spectra. PMID:4817352

  2. Nanoscience of an ancient pigment.

    PubMed

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

    2013-02-06

    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.

  3. 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

  4. Adrenocortical carcinoma: An extremely uncommon entity and the role of Immunohistochemistry in its diagnosis

    PubMed Central

    Gogoi, G.; Baruah, Manash P; Borah, P.; Borgohain, M.

    2012-01-01

    Adrenocortcal carcinoma is an extremely uncommon entity with an incidence of two in one millionth population. Here we present a 60 year gentleman with pain in abdomen, nausea, and backache, and weight loss. Contrast enhanced computed tomography (CECT) abdomen revealed a heterogenous well defined mass measuring (15 × 10.3 × 13) cm3 on the left suprarenal region with central necrosis which extended medially up to the midline. Locally, the growth infiltrated the upper pole of left kidney. Initially, the differential diagnosis included that of renal cell carcinoma arising from upper pole of left kidney involving adrenal gland. The patient underwent left radical nephrectomy and left adrenalectomy. Histological evaluation could not differentiate it from of malignant pheochromocytoma, but immunohistochemistry confirmed it as adrenocortical carcinoma. This case highlights the crucial role of immunohistochemistry in establishing the diagnosis like tumors. PMID:23565434

  5. Synchronous adrenocortical neoplasms, paragangliomas, and pheochromocytomas: syndromic considerations regarding an unusual constellation of endocrine tumors.

    PubMed

    LeBlanc, Melissa; Tabrizi, Mohsen; Kapsner, Patricia; Hanson, Joshua Anspach

    2014-12-01

    The most common clinical syndromes presenting with paragangliomas and/or pheochromocytomas as their endocrine components are multiple endocrine neoplasia type 2, neurofibromatosis, Von Hippel-Lindau syndrome, Carney-Stratakis syndrome, Carney triad, and the recently described hereditary paraganglioma syndrome. Only Carney triad is known to also present with adrenocortical adenomas, currently representing the only described syndrome in which all 3 of the aforementioned tumors are found together. In most cases, prototypical lesions of the triad such as gastrointestinal stromal tumor and pulmonary chondromas are also seen. We present a case of a young woman with synchronous paragangliomas, adrenal/extra-adrenal cortical neoplasms, and pheochromocytoma without genetic mutations for multiple endocrine neoplasia 2, Von Hippel-Lindau syndrome, neurofibromatosis, and succinate dehydrogenase. We speculate that this represents a previously undescribed presentation of Carney triad and, at the very least, indicates the need for monitoring for the development of other tumors of the triad.

  6. Structure-activity relations between alkyl nucleophilic chemicals causing duodenal ulcer and adrenocortical necrosis

    SciTech Connect

    Szabo, S.; Reynolds, E.S.; Unger, S.H.

    1982-10-01

    Structure-activity relationships were qualitatively and quantitatively examined for 56 chemicals (e.g., derivatives of propionitrile, acrylonitrile and cysteamine) which caused duodenal ulcer and/or adrenocortical necrosis in rats. For the first time the duodenal ulcerogenic property of numerous chemicals has been studied in a rational and predictive manner. Ulcerogenic activity was most intense in the carbonitriles attached to two or three carbon backbones and diminished by shortening, lengthening, branching, unsaturating, halogenating or hydroxylating the carbon chains. Different modes of action are implied. Adrenocorticolytic potency was associated with unsaturation of the carbon chain and substitution of the nitrile by thiol or amine radicals. An action of these chemicals on the central nervous system has been suggested.

  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. A case report of adrenocortical carcinosarcoma with oncocytic and primitive neuroectodermal-like features.

    PubMed

    Kao, Chia-Sui; Grignon, David J; Ulbright, Thomas M; Idrees, Muhammad T

    2013-09-01

    Adrenocortical carcinosarcomas are rare aggressive neoplasms; only a few have been reported to date, all with dismal prognosis. These were reported as having varying morphology. We have encountered a case of adrenal carcinosarcoma with an undifferentiated component bearing similarities to primitive neuroectodermal tumors and other areas of oncocytic differentiation. The 48-year-old woman patient presented with abdominal pain and unintended, excessive weight loss. Computed tomographic imaging revealed a tumor located adjacent to the liver and kidney necessitating a partial nephrectomy and hepatectomy. Histologically, the tumor exhibited malignant features. Melan-A, inhibin, calretinin, cytokeratin AE1/AE3, synaptophysin, and neuron-specific enolase were positive immunohistochemically. The patient developed metastasis within 2 months of surgery and is currently alive with disease after chemotherapy. Adrenal carcinosarcoma is a rare highly aggressive malignancy with a wide morphologic spectrum. Recognition of variant morphology and applying correct immunohistochemical studies will aid in reaching an accurate diagnosis.

  9. 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.

  10. 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

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

    PubMed

    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.

  12. Co-inhibition of EGFR and IGF1R synergistically impacts therapeutically on adrenocortical carcinoma

    PubMed Central

    Lian, Jianpo; Wang, Xiaojing; Ning, Guang; Wang, Weiqing; Zhu, Yu

    2016-01-01

    Purpose Adrenocortical carcinoma (ACC) is a rare tumor with very poor prognosis and no effective treatment. The aim of this study was to explore a novel therapy co-targeting EGFR and IGF1R in vitro and vivo. Methods The expression of EGFR and IGF1R were evaluated in a series of adrenocortical tumors by immunohistochemistry. Cell viability of ACC cell lines H295R and SW13 were determined by MTT assay after treatment with the combination of EGFR inhibitor Erlotinib and IGF1R inhibitor NVP-AEW541. Apoptosis was assessed by flow cytometry. The mechanism within intracellular signaling pathways was analyzed by Western blot. Mice bearing human ACC xenografts were treated with Erlotinib and NVP-AEW541, and the effects on tumour growth were assessed. Results Our results show a significant over-expression of EGFR (66.67%) and IGF1R (80.0%) in ACC. Besides, the co-overexpression of EGFR and IGF1R was seen in 8/15 ACCs, as compared with ACAs (P<0.05). Erlotinib and NVP-AEW541 significantly inhibited cell viability and induced apoptosis by blocking phosphorylation of MEK/ERK and AKT, respectively. Meanwhile, we found that single inhibition of IGF1R induced compensatory activation of MEK/ERK, leading to sustained activation of mTOR, which represent as aggregation of EGFR and IGF1R downstream components. More importantly, the combination of Erlotinib and NVP-AEW541 enhances anti-tumour efficacy compared to treatment with either agent alone or to untreated control in vitro and vivo. Conclusions In conclusion, coinhibition therapy targeting EGFR and IGF1R may be considerable for treatment of ACC in the future. PMID:27105537

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. Phytochemistry: structure of the blue cornflower pigment.

    PubMed

    Shiono, Masaaki; Matsugaki, Naohiro; Takeda, Kosaku

    2005-08-11

    The same anthocyanin pigment makes roses red but cornflowers blue, a phenomenon that has so far not been entirely explained. Here we describe the X-ray crystal structure of the cornflower pigment, which reveals that its blue colour arises from a complex of six molecules each of anthocyanin and flavone, with one ferric iron, one magnesium and two calcium ions. We believe that this tetrametal complex may represent a previously undiscovered type of supermolecular pigment.

  18. 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.

  19. 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.

  20. Comparison of Clinicopathologic Features and Survival of Histopathologically Amelanotic and Pigmented Melanomas: A Population-Based Study

    PubMed Central

    Thomas, Nancy E.; Kricker, Anne; Waxweiler, Weston T.; Dillon, Patrick M.; Busam, Klaus J.; From, Lynn; Groben, Pamela A.; Armstrong, Bruce K.; Anton-Culver, Hoda; Gruber, Stephen B.; Marrett, Loraine D.; Gallagher, Richard P.; Zanetti, Roberto; Rosso, Stefano; Dwyer, Terence; Venn, Alison; Kanetsky, Peter A.; Orlow, Drs. Irene; Paine, Susan; Ollila, David W.; Reiner, Anne S.; Luo, Li; Hao, Honglin; Frank, Jill S.; Begg, Colin B.; Berwick, Marianne

    2014-01-01

    Importance Previous studies have reported that histopathologically amelanotic melanoma is associated with poorer survival than pigmented melanoma; however, small numbers of amelanotic melanomas, selected populations, lack of centralized pathology review, or no adjustment for stage limit interpretation or generalization of results from prior studies. Objective To compare melanoma-specific survival between patients with histopathologically amelanotic and those with pigmented melanoma in a large international population-based study. Design Survival analysis with median follow-up of 7.6 years. Setting The Genes, Environment, and Melanoma study enrolled incident cases of melanoma diagnosed in 1998-2003 from international population-based cancer registries. Participants A total of 2,995 patients with 3,486 invasive primary melanomas centrally scored for histologic pigmentation. Main Outcomes and Measurements Clinicopathologic predictors and melanoma-specific survival of histologically amelanotic and pigmented melanoma were compared using generalized estimating equations and Cox regression models, respectively. Results Eight percent of melanomas (275 of 3,467) were histopathologically amelanotic. Female sex, nodular and unclassified or other histologic subtypes, increased Breslow thickness, presence of mitoses, severe solar elastosis, and lack of a co-existing nevus were independently associated with amelanotic melanoma (each P < .05). Amelanotic melanoma was generally of a higher American Joint Committee on Cancer (AJCC) tumor stage at diagnosis (P for trend <.001) than pigmented melanoma. Hazard of death from melanoma was higher for amelanotic than pigmented melanoma [hazard ratio (HR), 2.0; 95% confidence interval (CI), 1.4-3.0; P< .001], adjusted for age, sex anatomic site, and study design variables; but survival did not differ once AJCC tumor stage was also taken into account, (HR, 0.8; 95% CI, 0.5-1.2; P = .36). Conclusions and Relevance At the population level

  1. Comparison of clinicopathologic features and survival of histopathologically amelanotic and pigmented melanomas: a population-based study.

    PubMed

    Thomas, Nancy E; Kricker, Anne; Waxweiler, Weston T; Dillon, Patrick M; Busman, Klaus J; From, Lynn; Groben, Pamela A; Armstrong, Bruce K; Anton-Culver, Hoda; Gruber, Stephen B; Marrett, Loraine D; Gallagher, Richard P; Zanetti, Roberto; Rosso, Stefano; Dwyer, Terence; Venn, Alison; Kanetsky, Peter A; Orlow, Irene; Paine, Susan; Ollila, David W; Reiner, Anne S; Luo, Li; Hao, Honglin; Frank, Jill S; Begg, Colin B; Berwick, Marianne

    2014-12-01

    IMPORTANCE Previous studies have reported that histopathologically amelanotic melanoma is associated with poorer survival than pigmented melanoma; however, small numbers of amelanotic melanomas, selected populations, lack of centralized pathologic review, or no adjustment for stage limit the interpretation or generalization of results from prior studies.OBJECTIVE To compare melanoma-specific survival between patients with histopathologically amelanotic and those with pigmented melanoma in a large international population-based study.DESIGN, SETTING, AND PARTICIPANTS Survival analysis with a median follow-up of 7.6 years.The study population comprised 2995 patients with 3486 invasive primary melanomas centrally scored for histologic pigmentation from the Genes, Environment, and Melanoma(GEM) Study, which enrolled incident cases of melanoma diagnosed in 1998 through 2003 from international population-based cancer registries.MAIN OUTCOMES AND MEASURES Clinicopathologic predictors and melanoma-specific survival of histologically amelanotic and pigmented melanoma were compared using generalized estimating equations and Cox regression models, respectively.RESULTS Of 3467 melanomas, 275 (8%) were histopathologically amelanotic. Female sex,nodular and unclassified or other histologic subtypes, increased Breslow thickness, presence of mitoses, severe solar elastosis, and lack of a coexisting nevus were independently associated with amelanotic melanoma (each P < .05). Amelanotic melanoma was generally ofa higher American Joint Committee on Cancer (AJCC) tumor stage at diagnosis (odds ratios[ORs] [95%CIs] between 2.9 [1.8-4.6] and 11.1 [5.8-21.2] for tumor stages between T1b and T3b and ORs [95%CIs] of 24.6 [13.6-44.4] for T4a and 29.1 [15.5-54.9] for T4b relative to T1a;P value for trend, <.001) than pigmented melanoma. Hazard of death from melanoma was higher for amelanotic than for pigmented melanoma (hazard ratio [HR], 2.0; 95%CI, 1.4-3.0)(P < .001), adjusted for age, sex

  2. [Effect of fetal adrenal hormones on the reactivity of the hypothalamo-hypophyseal-adrenocortical system in the adult rat].

    PubMed

    Dygalo, N N; Naumenko, E V

    1984-01-01

    It was found in the experiments on adult males, descendants of the intact or adrenalectomized (prior to mating) female rats which were injected during the pregnancy with adrenaline, hydrocortisone or saline solution, that the reaction of their hypophysial-adrenocortical system to emotional stress or injection of noradrenaline into brain were inversely proportional to the content of corticosteroids, rather than of adrenaline, in the blood of their mothers during the pregnancy. On the other hand, the coupled changes of the levels of corticosteroids and adrenaline in the blood of pregnant mothers only was accompanied by the marked decrease in the sensitivity of brain cholinergic mechanisms in descendants. Hence, the changes of the levels of both adrenaline and corticosterids in the blood of pregnant females modify the reactivity of hypophysial-adrenocortical system of adult descendants, apparently, via the development of brain neurochemical mechanisms in the foetuses. But the role of these hormones is different.

  3. 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.

  4. CagA antibodies in Japanese children with nodular gastritis or peptic ulcer disease.

    PubMed

    Kato, S; Sugiyama, T; Kudo, M; Ohnuma, K; Ozawa, K; Iinuma, K; Asaka, M; Blaser, M J

    2000-01-01

    cagA(+) Helicobacter pylori strains have been linked to more severe gastric inflammation, peptic ulcer disease, and gastric cancer in adults, but there have been few studies of cagA in children. We examined the relationship between H. pylori cagA status and clinical status in Japanese children. Forty H. pylori-positive children were studied: 15 with nodular gastritis, 5 with gastric ulcers, and 20 with duodenal ulcers. H. pylori status was confirmed by biopsy-based tests and serum anti-H. pylori immunoglobulin G (IgG) antibody. As controls, 77 asymptomatic children with sera positive for anti-H. pylori IgG were enrolled. Levels of IgG antibodies to CagA in serum were measured by an antigen-specific enzyme-linked immunosorbent assay. In 16 patients with successful H. pylori eradication, posttreatment levels of CagA and H. pylori IgG antibodies also were studied. The CagA antibody seropositivities of asymptomatic controls (81.8%) and patients with nodular gastritis, gastric ulcers, and duodenal ulcers (80.0 to 95.0%) were not significantly different. Compared with pretreatment levels of CagA antibodies, posttreatment levels decreased progressively and significantly. We conclude that, as in Japanese adults, a high prevalence of cagA(+) H. pylori strains was found in Japanese children, and that there was no association with nodular gastritis or peptic ulcer disease. In the assessment of eradicative therapies, monitoring of serum anti-CagA antibodies does not appear to offer any direct benefit over monitoring of anti-H. pylori antibodies.

  5. Routine calcitonin measurement in nodular thyroid disease management: is it worthwhile?

    PubMed Central

    Turk, Yigit; Ozdemir, Murat; Ertunc, Gozde; Demir, Batuhan; Icoz, Gokhan; Akyildiz, Mahir; Yilmaz, Mustafa

    2017-01-01

    Purpose To evaluate the diagnostic accuracy of routine calcitonin measurement in patients with nodular thyroid disease. Methods Consecutive patients with nodular thyroid disease (n = 640) were studied. Serum calcitonin levels were measured under basal conditions, and when basal values were between 10–100 pg/mL, testing was repeated after pentagastrin (PG) stimulation. Patients with previously diagnosed or familial medullary thyroid cancer (MTC) were excluded. Patients were operated on when basal or stimulated calcitonin >100 pg/mL or when other surgical indications were present. Results Four cases of MTC were identified. MTC was diagnosed in 75% of patients with basal calcitonin >100 pg/mL. One out of 11 patients with basal calcitonin between 10–100 pg/mL was diagnosed with MTC. PG stimulation resulted in elevation in 4 cases, where 1 case was diagnosed with MTC. Positive predictive value for basal calcitonin levels in the preoperative diagnosis of MTC was 5% for values between 10–100 pg/mL and 100% for values >100 pg/mL. Possible reasons for false positivity were papillary thyroid cancer in 17%, renal insufficiency in 8.3%, Hashimoto thyroiditis in 17% and β-blocker use in 33%. Positive predictive value for the PG test (>100 pg/mL) was 25% in the entire series. The cost of adding calcitonin measurement (±PG stimulation) to the preoperative work-up, resulted in €912.68 per MTC patient to detect the disease. Conclusion Basal calcitonin measurement together with PG stimulation in cases of basal calcitonin >10 pg/mL detects MTC in 0.62% of patients with nodular thyroid disease. PMID:28382288

  6. Phenotypic and Imaging Features of FLNA-Negative Patients With Bilateral Periventricular Nodular Heterotopia and Epilepsy

    PubMed Central

    Fallil, Zianka; Pardoe, Heath; Bachman, Robert; Cunningham, Benjamin; Parulkar, Isha; Shain, Catherine; Poduri, Annapurna; Knowlton, Robert; Kuzniecky, Ruben

    2015-01-01

    Purpose Periventricular nodular heterotopia (PVNH) is a malformation of cortical development due to impaired neuronal migration resulting in the formation of nodular masses of neurons and glial cells in close proximity to the ventricular walls. We report the clinical characteristics of the largest case series of FLNA negative patients with seizures and bilateral periventricular heterotopia. Methods Participants were recruited through the Epilepsy Phenome/Genome Project (EPGP), a multicenter collaborative effort to collect detailed phenotypic data and DNA on a large number of individuals with epilepsy, including a cohort with symptomatic epilepsy related to PVNH. Included subjects had epilepsy and MRI confirmed bilateral PVNH. MRI studies were visually and quantitatively reviewed to investigate the topographic extent of PVNH, symmetry and laterality. Key Findings We analyze data on 71 patients with bilateral PVNH. The incidence of febrile seizures was 16.6%. There was at least one other family member with epilepsy in 36.9% of this population. Developmental delay was present in 21.8%. Focal onset seizures were the most common type of seizure presentation (79.3%). High heterotopia burden was strongly associated with female gender and trigonal nodular localization. There was no evidence for differences in brain volume between PVNH subjects and controls. No relationship was observed between heterotopic volume and gender, developmental delay, location of PVNH, ventricular or cerebellar abnormalities, laterality of seizure onset, age at seizure onset and duration of epilepsy. Significance A direct correlation was observed between high heterotopia burden, female gender and trigonal location in this large cohort of FLNA-negative bilateral PVNH patients with epilepsy. Quantitative MRI measurements indicate that this correlation is based on the diffuse nature of the heterotopic nodules rather than on the total volume of abnormal heterotopic tissue. PMID:26340046

  7. 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

  8. Differential effects of transforming growth factor type beta on the growth and function of adrenocortical cells in vitro.

    PubMed Central

    Hotta, M; Baird, A

    1986-01-01

    Transforming growth factor type beta (TGF-beta) suppresses basal as well as corticotropin (ACTH)-stimulated steroid formation by bovine adrenocortical cells in culture. The effect is dose dependent and is not accompanied by any change in adrenocortical cell growth. The minimum effective dose of TGF-beta is 4 X 10(-13) M (10 pg/ml), and maximal inhibition is observed at a concentration of 4 X 10(-11) M (1 ng/ml). A 16- to 20-hr incubation with TGF-beta is required to decrease steroidogenesis, and 12-18 hr are required before cells treated with TGF-beta recover complete responsiveness to corticotropin. Increases in cAMP mediated by corticotropin, forskolin, and isobutylmethylxanthine are not modified by the addition of TGF-beta; thus adenylate cyclase activity is unaffected by TGF-beta. Although TGF-beta inhibits the formation of all of the delta 4-steroids measured (including cortisol, corticosterone, aldosterone, and androstenedione), its effect can be completely reversed by the addition of 25-hydroxycholesterol, pregnenolone, or progesterone to the cells. In contrast, the addition of low density lipoprotein has no effect suggesting that TGF-beta targets the conversion of cholesterol precursors to cholesterol. The results demonstrate a highly potent effect of TGF-beta on the differentiated function of the adrenocortical cell. The inhibition of steroidogenesis can be dissociated from any effect on cell proliferation, and it occurs distal to the formation of cAMP but proximal to the formation of cholesterol. The results suggest that in the adrenal, TGF-beta or TGF-beta-like proteins may be playing an important role in modifying the differentiated state of the adrenocortical cell. PMID:3020557

  9. Nodular amyloidosis of the lung and the breast mimicking breast carcinoma with pulmonary metastasis.

    PubMed

    Liaw, Y S; Kuo, S H; Yang, P C; Chen, C L; Luh, K T

    1995-05-01

    Nodular amyloidosis of the breast and lung is a rare condition of unknown aetiology. The disease runs a benign course, but offers a diagnostic problem due to nonspecific histological features. We describe the case of a 56 year old woman with a 5 year history of multiple nodules of both lungs and left breast, clinically mimicking breast carcinoma with pulmonary metastasis. To our knowledge, this is the first case of cytologically proven amyloidosis diagnosed by ultrasound-guided percutaneous transthoracic fine-needle aspiration of pulmonary nodules.

  10. [Pulmonary Mycobacterium avium-intracellulare complex disease that presented multiple nodular shadows rapidly].

    PubMed

    Fujiwara, Kiyohiro

    2009-09-01

    The patient was 81-year-old woman diagnosed with lung cancer who underwent upper right lobectomy in January 2002. Computed tomography (CT) of the thorax showed a mass shadow presenting rapid-growing in the left S3 in August, 2008. The size of the mass shadow in the left S3 increased on day 16 after hospitalization, and a nodular shadow appeared in the left S(1+2). The bronchial washing specimen showed acid-fast bacilli identified as Mycobacterium intracellulare by deoxyribonucleic acid (DNA) -DNA hybridization (DDH). The patient showed radiological improvement following combination chemotherapy with rifampicin, ethambutol and clarithromycin.

  11. Transition of nodular toxic goiter to autoimmune hyperthyroidism triggered by 131I therapy.

    PubMed

    Nygaard, B; Faber, J; Veje, A; Hegedüs, L; Hansen, J M

    1999-05-01

    The use of 131I treatment in nodular toxic goiter is widely accepted. In this article, we describe transition of nodular toxic goiter into an autoimmune toxic goiter with development of thyrotropin receptor antibodies (TRAb) as a side effect of 131I treatment. In this retrospective study, 149 patients with nodular toxic goiter (100 with multinodular goiter, 49 with a solitary autonomously functioning toxic nodule) were studied. Of these 149 patients 100 became permanently euthryoid after 1 dose of 131I, and due to persistent hyperthyroidism, 32 patients needed 2-5 doses to became euthyroid. After becoming euthyroid, none of these 132 patients had relapse of hyperthyroidism in the follow-up period. Based on evaluation of the thyroid hormone variables, 17 of 149 patients had a distinctly different pattern in the changes in thyroid hormones. They developed an increase in FT4I 3-6 months posttreatment after an initial fall in FT4I. Twelve of these 17 patients were treated with antithyroid drugs before the initial 131I dose. On samples of frozen sera (-20 degrees C) anti-thyroid peroxidase (TPO) and TRAb were followed for 6 months after 131I treatment in these 17 patients. A similar follow-up was done in 20 patients (10 with and 10 without antithyroid drug pretreatment), randomly selected from the patients who did not relapse. In the remaining 112 patients, anti-TPO and TRAb levels were measured only before the 131I treatment. Of the 17 patients with relapse, 6 developed TRAb concomitant with recurrence of hyperthyroidism (4% of the study group). In 5 of the 17 patients TRAb values remained absent throughout the follow-up period. The remaining 6 patients had elevated TRAb values before 131I treatment. Among the 132 patients who did not relapse, an additional 7 cases with presence of TRAb were found. A total of 9% of the study group was found to have TRAb before 131I pretreatment. Anti-TPO was found in 20 of 149 patients (13%) before 131I treatment. Complications, either

  12. Medulloblastoma With Extensive Nodularity: Tailored Therapy in a Low-resource Setting.

    PubMed

    Aristizabal, Paula; Burns, Luke; Rivera-Gomez, Rebeca; Levy, Michael L; Roberts, William; Crawford, John R

    2017-03-06

    Treatment for medulloblastoma carries significant risks, particularly in resource-constrained settings. We report a case of a Mexican infant with desmoplastic/nodular medulloblastoma. Given the nature of her tumor, we developed a tailored regimen following subtotal resection to avoid both radiation therapy and the high-dose cisplatin therapy offered at most centers in the United States. The patient is in remission 4 years after the initial diagnosis. This case suggests an alternative treatment plan for this particular tumor variant that accommodates the limited resources of many centers around the world and avoids the risks associated with radiation therapy at a young age.

  13. 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. Christian; Hofmeister, Erik 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.

  14. Tissue mercury concentrations and adrenocortical responses of female big brown bats (Eptesicus fuscus) near a contaminated river.

    PubMed

    Wada, Haruka; Yates, David E; Evers, David C; Taylor, Robert J; Hopkins, William A

    2010-10-01

    Much of the research on mercury (Hg) in wild vertebrates has focused on piscivores and other animals at high trophic levels. However, recent studies indicated that insectivorous terrestrial vertebrates may also be at risk. In the present study, we examined blood and fur Hg concentrations as well as the adrenocortical responses of insectivorous big brown bats (Eptesicus fuscus) near the Hg-contaminated South River, VA and a nearby reference area. Baseline glucocorticoids and adrenocortical responses to handling have been widely used to assess the influence of environmental stressors because plasma glucocorticoids rise in response to various physical, psychological, and physiological challenges. Female bats captured at the contaminated site had 2.6 times higher blood and fur Hg concentrations than those captured at the reference site (blood: 0.11 vs. 0.04 μg/g wet weight; fur: 28.0 vs. 10.9 μg/g fresh weight). Fur Hg concentrations at the contaminated site were higher than most wild omnivorous and carnivorous mammals reported in the literature. Although fur and blood Hg concentrations were tightly correlated, fur Hg concentrations averaged 260 times higher than concentrations in blood. This suggests that fur may be an important depuration route for bats, just as it is in other mammals. Despite the high Hg concentrations in bat tissue, we did not observe any site difference in adrenocortical responses. Our results suggest that the bats at the contaminated site were exposed to Hg concentrations below those causing adverse effects on their adrenal axis.

  15. 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.

  16. Adrenocortical nuclear progesterone-binding protein: Identification by photoaffinity labeling and evidence for deoxyribonucleic acid binding and stimulation by adrenocorticotropin

    SciTech Connect

    Demura, T.; Driscoll, W.J.; Lee, Y.C.; Strott, C.A. )

    1991-01-01

    Nuclei of the guinea pig adrenal cortex contain a protein that specifically binds progesterone and that, biochemically, is clearly distinct from the classical progesterone receptor. The adrenocortical nuclear progesterone-binding protein has now been purified more than 2000-fold by steroid-affinity chromatography with a 75% yield. The purified protein preparation demonstrated three major bands on sodium dodecyl sulfate-polyacrylamide gel of 79K, 74K, and 50K. To determine which of the three might represent the progesterone-binding protein, steroid photoaffinity labeling was performed which resulted in the specific and exclusive labeling of a 50K band. Thus, the adrenocortical nuclear progesterone-binding protein appears to be distinct from the classical progesterone receptor not only biochemically, but also on the basis of molecular size. To test whether the adrenocortical nuclear progesterone-binding protein can be hormonally stimulated, guinea pigs were treated with ACTH. The chronic administration of ACTH caused a 4- to 6-fold increase in the specific progesterone binding capacity without a change in the binding affinity. There appeared to be no significant difference in nuclear progesterone binding between the zona fasciculata and zona reticularis. This finding suggests a mediating role for the progesterone-binding protein in ACTH action. In addition, the nuclear progesterone-binding protein bound to nonspecific DNA sequences, further suggesting a possible transcriptional regulatory role.

  17. Dermatoscopic findings of pigmented purpuric dermatosis*

    PubMed Central

    Ozkaya, Dilek Biyik; Emiroglu, Nazan; Su, Ozlem; Cengiz, Fatma Pelin; Bahali, Anil Gulsel; Yildiz, Pelin; Demirkesen, Cuyan; Onsun, Nahide

    2016-01-01

    Background Pigmented purpuric dermatosis is a chronic skin disorder of unknown aetiology characterised by symmetrical petechial and pigmented macules, often confined to the lower limbs. The aetiology of pigmented purpuric dermatosis is unknown. Dermatoscopy is a non-invasive diagnostic technique that allows the visualisation of morphological features invisible to the naked eye; it combines a method that renders the corneal layer of the skin translucent with an optical system that magnifies the image projected onto the retina. Objectives The aim of this study is to investigate the dermatoscopic findings of pigmented purpuric dermatosis. Methods This study enrolled patients diagnosed histopathologically with pigmented purpuric dermatosis who had dermatoscopic records. We reviewed the dermatoscopic images of PPD patients who attended the outpatient clinic in the Istanbul Dermatovenereology Department at the Bezmialem Vakıf University Medical Faculty. Results Dermatoscopy showed: coppery-red pigmentation (97%, n = 31) in the background, a brown network (34%, n = 11), linear vessels (22%, n = 7), round to oval red dots, globules, and patches (69%, n = 22; 75%, n = 24; 34%, n = 11; respectively), brown globules (26%, n = 8) and dots (53%, n = 17), linear brown lines (22%, n = 7), and follicular openings (13%, n = 4). Conclusion To our knowledge, this is the first study to report the dermatoscopy of pigmented purpuric dermatosis. In our opinion, dermatoscopy can be useful in the diagnosis of pigmented purpuric dermatosis. PMID:27828629

  18. 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)

  19. Modulation of the adrenocortical response to acute stress with respect to brood value, reproductive success and survival in the Eurasian hoopoe.

    PubMed

    Schmid, Baptiste; Tam-Dafond, Laura; Jenni-Eiermann, Susanne; Arlettaz, Raphaël; Schaub, Michael; Jenni, Lukas

    2013-09-01

    Reproducing parents face the difficult challenge of trading-off investment in current reproduction against presumed future survival and reproduction. Glucocorticoids are supposed to mediate this trade-off because the adrenocortical response to stress disrupts normal reproductive behaviour in favour of self-maintenance and own survival. According to the brood-value hypothesis, individuals with a low survival probability until the next reproductive season have to invest in current reproduction, a process driven by a down-regulation of their adrenocortical response. If the adrenocortical response to stress effectively mediates the trade-off between current reproduction versus future survival and reproduction, we expect a negative relationship with reproductive success and a positive correlation of the adrenocortical stress response with survival. We studied the relationship between corticosterone secretion in parents and their current brood value, reproductive success and survival in a short-lived multi-brooded bird, the Eurasian hoopoe Upupa epops. The adrenocortical response to acute handling stress was correlated with the brood value within the individual (first and second broods of the year) and between individuals. Birds breeding late in the season mounted a lower total corticosterone response to acute stress than birds breeding earlier, while females showed lower levels than males. We observed a negative relationship between the adrenocortical stress response and rearing success or fledging success in females, as predicted by the brood-value hypothesis. However, we could not evidence a clear link between the adrenocortical stress response and survival. Future research testing the brood-value hypothesis and trade-offs between current reproduction and future survival should also measure free corticosterone and carefully differentiate between cross-sectional (i.e. between-individual) and individual-based experimental studies.

  20. 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.

  1. Organic pigments in plastics can cause allergic contact dermatitis.

    PubMed

    Jolanki, R; Kanerva, L; Estlander, T

    1987-01-01

    A short review on organic pigments in plastics as a cause of allergic contact dermatitis is presented. Previously, organic pigments have been reported as provoking allergic pigmented contact dermatitis when used in cosmetics. Here we present the case of a patient who developed allergic contact dermatitis from an organic pigment (Irgalite Orange F2G) in a plastic glove. This shows that organic pigments in plastics can also cause allergic contact dermatitis. The potential sensitizing capacity of organic pigments should be noted.

  2. Syncytial Variant of Nodular Sclerosis Classical Hodgkin Lymphoma of the Terminal Ileum in a Patient with Longstanding Crohn's Disease.

    PubMed

    Gibson, Bradley; Podoll, Mirna Bajramovic; Baumgartner, Erin Marie; Maley, Diana Haninger

    2016-01-01

    Primary Hodgkin lymphoma of the gastrointestinal tract is an uncommon malignancy with few reported cases. Here we describe a rare variant of Hodgkin lymphoma presented in the gastrointestinal tract in association with Crohn's Disease.The patient is a 58 year old male with a 40 year history of formerly well-controlled Crohn's disease who presented with abdominal discomfort and constitutional symptoms. Computed tomography showed a 10 cm thickened segment of ileum and a dilated segment of small bowel. The patient underwent segmental resection, revealing a mass, which was diagnosed by pathology as nodular sclerosis classical Hodgkin lymphoma, syncytial variant.There are only 29 reported cases of syncytial variant of nodular sclerosis classical Hodgkin lymphoma. This is the second documented case of primary gastrointestinal syncytial variant of nodular sclerosis classical Hodgkin lymphoma. Further characterization of this entity is necessary.

  3. Anthocyanins. Plant pigments and beyond.

    PubMed

    Santos-Buelga, Celestino; Mateus, Nuno; De Freitas, Victor

    2014-07-23

    Anthocyanins are plant pigments widespread in nature. They play relevant roles in plant propagation and ecophysiology and plant defense mechanisms and are responsible for the color of fruits and vegetables. A large number of novel anthocyanin structures have been identified, including new families such as pyranoanthocyanins or anthocyanin oligomers; their biosynthesis pathways have been elucidated, and new plants with "a la carte" colors have been created by genetic engineering. Furthermore, evidence about their benefits in human health has accumulated, and processes of anthocyanin absorption and biotransformation in the human organism have started to be ascertained. These advances in anthocyanin research were revised in the Seventh International Workshop on Anthocyanins that took place in Porto (Portugal) on September 9-11, 2013. Some selected papers are collected in this special issue, where aspects such as anthocyanin accumulation in plants, relationship with color expression, stability in plants and food, and bioavailability or biological activity are revised.

  4. 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).

  5. [Nodular regenerative hyperplasia as a complication of thiopurine treatment in a patient with inflammatory bowel disease].

    PubMed

    Cohen-Ezra, Oranit; Avni, Yona; Morgenstern, Sara; Ben-Ari, Ziv

    2012-12-01

    Immunomodulator therapy with thiopurine analogues azathioprine or 6-mercaptopurine is commonly prescribed for the treatment of organ transplantation, inflammatory bowel disease, autoimmune diseases and malignancies. Hepatotoxicity due to thiopurine analogues usually presents as an increase in serum transaminase levels. Toxicity is usually not severe, and a dose reduction is effective in most patients. Nodular regenerative hyperplasia (NRH) is a very rare but potentially severe complication of thiopurine-containing therapy. NRH is often asymptomatic, neither biochemical nor molecular markers are indicative for NRH. The suspicion rises when there are clinical symptoms of portal hypertension or increases in transaminases levels orthrombocytopenia. Liver biopsy is essential for definitive diagnosis. This is a case report of a 40-year-old male patient with Crohn's disease who developed increased serum levels of liver enzymes and thrombocytopenia following the administration of thiopurine. Although treatment with thiopurine was discontinued, he has further progressed and presented with acute variceal bleeding due to portal hypertension. The diagnosis of nodular regenerative hyperplasia was proven by a liver biopsy. In conclusion, NRH is a very rare but potentially severe complication of thiopurine-containing immunosuppressive therapy for IBD.

  6. 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.

  7. Nodular histogenetic type -- the most significant factor for thick melanoma: implications for prevention.

    PubMed

    Bergenmar, M; Ringborg, U; Månsson Brahme, E; Brandberg, Y

    1998-10-01

    Tumour thickness is the most important prognostic factor in malignant melanoma. To reduce the melanoma-related mortality, factors related to the presentation of thick melanoma have to be identified. Three samples of melanoma patients (n=694) were studied for this purpose. Histogenetic type was the only factor which differentiated between 'thin' (< or = 0.8 mm) and 'thick' (> 2.0 mm) lesions. During a 10-year period only 3% of the nodular lesions were 'thin' at diagnosis. Differences in knowledge about melanoma or the location of the lesion (either 'easy' or 'difficult' for the patient to observe) did not explain differences in tumour thickness. The most common tumour site irrespective of histogenetic type and gender was 'back of the trunk'. 'Increase in diameter' and 'bleeding' were the symptoms most frequently reported by patients with 'thick' melanoma. 'Thick' lesions were diagnosed in older age groups and in men to a greater extent. Considering these results, melanoma prevention should also be targeted to older age groups and attention should be paid to symptoms such as 'increase in diameter' even in the absence of other characteristic symptoms of melanoma. An increased proportion of nodular melanoma diagnosed as 'thin' lesions can be interpreted as a step forward in secondary prevention.

  8. Mucinous versus nonmucinous solitary pulmonary nodular bronchioloalveolar carcinoma: CT and FDG PET findings and pathologic comparisons.

    PubMed

    Lee, Ho Yun; Lee, Kyung Soo; Han, Joungho; Kim, Byung-Tae; Cho, Young-Seok; Shim, Young Mog; Kim, Jhingook

    2009-08-01

    We aimed to evaluate the CT, PET, and pathologic findings of solitary pulmonary nodular mucinous and nonmucinous bronchioloalveolar carcinomas (BACs). From August 2003 to March 2008, we saw 24 patients with solitary pulmonary nodular mucinous (n=6) or nonmucinous (n=18) BACs that were resected. CT and PET findings of the lesions were assessed in terms of size, solidity, morphologic characteristics, attenuation and maximum standardized uptake value (mSUV). All nonmucinous BACs appeared as a pure ground-glass opacity (GGO) nodule, whereas mucinous BACs appeared as solid (n=4) or part-solid (n=2) nodules. CT attenuation values were significantly higher for mucinous BACs (-21.0 HU+/-4.9) than for nonmucinous BACs (-491.8 HU+/-172.5) (P<.001). Mean mSUVs were 2.3+/-1.9 for mucinous BACs and 0.5+/-0.8 for nonmucinous BACs (P=.007), but mSUVs were not statistically different after size adjustment (r=0.371, P=.081). Mucinous BACs appear as solid or part-solid nodules at CT, whereas nonmucinous BACs present as pure GGO nodules. Both subtypes of tumors show scant FDG uptake at PET.

  9. Total versus bilateral subtotal thyroidectomy for benign multi-nodular goiter

    PubMed Central

    Ciftci, Fatih; Sakalli, Erdal; Abdurrahman, Ibrahim

    2015-01-01

    Purpose: To compare the postoperative early-stage complications of total and bilateral subtotal thyroidectomy for benign multi-nodular goiter. Material and methods: There were 409 patients. The patients were divided into two groups. A total of 258 (63%) patients underwent total thyroidectomy, and 151 (37%) patients underwent bilateral subtotal thyroidectomy. Results: Recurrent laryngeal nerve palsy occurred in six (2.3%) of the total thyroidectomy patients and in three (1.9%) of the bilateral subtotal thyroidectomy patients (P>0.05). No permanent palsy was observed in either of the thyroidectomy groups. Hypocalcemia occurred in 40 (15.5%) of the total thyroidectomy patients and in 27 (17.8%) of those who underwent bilateral subtotal thyroidectomy (P>0.05). Also, no statistically significant differences were found between the two groups with respect to the development rates of hematoma and incision site infection (P>0.05). Conclusion: Because of its low complication rates, total thyroidectomy is a safe procedure for benign multı-nodular goiter. PMID:26064391

  10. 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

    2015-11-16

    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.

  11. 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…

  12. 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

  13. 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

  14. 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

    2015-06-24

    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.

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

    PubMed Central

    Hayashi, Yuichiro; Al-Eyd, Ghaith; Nakagawa, Ken; Morita, Shinya; Kosaka, Takeo; Oya, Mototsugu; Mitani, Fumiko; Suematsu, Makoto; Kabe, Yasuaki

    2016-01-01

    Background. The immunohistochemical detection of aldosterone synthase (CYP11B2) and steroid 11β-hydroxylase (CYP11B1) has enabled the identification of aldosterone-producing cell clusters (APCCs) in the subcapsular portion of the human adult adrenal cortex. We hypothesized that adrenals have layered zonation in early postnatal stages and are remodeled to possess APCCs over time. Purposes. To investigate changes in human adrenocortical zonation with age. Methods. We retrospectively analyzed adrenal tissues prepared from 33 autopsied patients aged between 0 and 50 years. They were immunostained for CYP11B2 and CYP11B1. The percentage of APCC areas over the whole adrenal area (AA/WAA, %) and the number of APCCs (NOA, APCCs/mm2) were calculated by four examiners. Average values were used in statistical analyses. Results. Adrenals under 11 years old had layered zona glomerulosa (ZG) and zona fasciculata (ZF) without apparent APCCs. Some adrenals had an unstained (CYP11B2/CYP11B1-negative) layer between ZG and ZF, resembling the rat undifferentiated cell zone. Average AA/WAA and NOA correlated with age, suggesting that APCC development is associated with aging. Possible APCC-to-APA transitional lesions were incidentally identified in two adult adrenals. Conclusions. The adrenal cortex with layered zonation remodels to possess APCCs over time. APCC generation may be associated with hypertension in adults. PMID:27721827

  16. Upregulation of TLR2 and TLR4 in the human adrenocortical cells differentially modulates adrenal steroidogenesis.

    PubMed

    Kanczkowski, Waldemar; Tymoszuk, Piotr; Chavakis, Triantafyllos; Janitzky, Volker; Weirich, Torsten; Zacharowski, Kai; Ehrhart-Bornstein, Monika; Bornstein, Stefan R

    2011-04-10

    Rapid activation of adrenal steroid release plays a pivotal role in an organism's first line of defense during sepsis. Adrenal gland function is often suppressed in critically ill patients and negatively impacts the overall survival rate. Increasingly, experimental and clinical evidence suggests that Toll-like receptors (TLRs), components of the innate immune system, play a key role in the mediation of systemic responses to invading pathogens during sepsis. In the present study, we aimed to elucidate the effect of TLR2, TLR4 and CD14 upregulation on adrenocortical cell steroidogenesis. We found that TLR4 and CD14 but not TLR2 overexpression in NCI-H295R cells inhibited basal and acute cortisol and aldosterone production. This effect could be partially explained by reduced expression of enzymes involved in the synthesis of latter steroids--CYP11B1 and CYP11B2. Together, these data suggest that TLR upregulation in the steroid producing cells may be involved in the adrenal gland dysfunction during sepsis.

  17. 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

  18. Contributions of Steroidogenic Factor 1 to the Transcription Landscape of Y1 Mouse Adrenocortical Tumor Cells

    PubMed Central

    Schimmer, Bernard P.; Tsao, Jennivine; Cordova, Martha; Mostafavi, Sara; Morris, Quaid; Scheys, Joshua O.

    2011-01-01

    Summary The contribution of steroidogenic factor 1 (SF–1) to the gene expression profile of Y1 mouse adrenocortical cells was evaluated using short hairpin RNAs to knockdown SF–1. The reduced level of SF–1 RNA was associated with global changes that affected the accumulation of more than 2,000 transcripts. Among the down-regulated transcripts were several with functions in steroidogenesis that were affected to different degrees—i.e., Mc2r >Scarb1 > Star ≥ Hsd3b1 > Cyp11b1. For Star and Cyp11b1, the different levels of expression correlated with the amount of residual SF-1 bound to the proximal promoter regions. The knockdown of SF–1 did not affect the accumulation of Cyp11a1 transcripts even though the amount of SF–1 bound to the proximal promoter of the gene was reduced to background levels. Our results indicate that transcripts with functions in steroidogenesis vary in their dependence on SF–1 for constitutive expression. On a more global scale, SF–1 knockdown affects the accumulation of a large number of transcripts, most of which are not recognizably involved in steroid hormone biosynthesis. PMID:21111771

  19. 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

  20. Minimally Invasive Resection of Adrenocortical Carcinoma: A Multi-Institutional Study of 201 Patients

    PubMed Central

    Lee, Christina W.; Salem, Ahmed I.; Schneider, David F.; Leverson, Glen E.; Tran, Thuy B.; Poultsides, George A.; Postlewait, Lauren M.; Maithel, Shishir K.; Wang, Tracy S.; Hatzaras, Ioannis; Shenoy, Rivfka; Phay, John E.; Shirley, Lawrence; Fields, Ryan C.; Jin, Linda X.; Pawlik, Timothy M.; Prescott, Jason D.; 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.; Weber, Sharon M.

    2016-01-01

    Background and Objectives Minimally invasive surgery for adrenocortical carcinoma (ACC) is controversial. We sought to evaluate the perioperative and long-term outcomes following minimally invasive (MIS) and open resection (OA) of ACC in patients treated with curative intent surgery. Methods Retrospective data from patients who underwent adrenalectomy for primary ACC at 13 tertiary care cancer centers were analyzed, including demographics, clinicopathological, and operative outcomes. Outcomes following MIS were compared to OA. Results A total of 201 patients were evaluated including 47 MIS and 154 OA. There was no difference in utilization of MIS approach among institutions (p=0.24) or 30-day morbidity (29.3%, MIS versus 30.9%, OA, p=0.839). The only preoperatively determined predictor for MIS was smaller tumor size (p<0.001). There was no difference in rates of intraoperative tumor rupture (p=0.612) or R0 resection (p=0.953). Only EBL (p=0.038) and T stage (p=0.045) were independent prognostic indicators of overall survival after adjusting for significant factors. The surgical approach was not associated with overall or disease-free survival. Conclusion MIS adrenalectomy may be utilized for preoperatively determined ACC ≤ 10.0 cm, however OA should be utilized for adrenal masses with either preoperative or intraoperative evidence of local invasion or enlarged lymph nodes, regardless of size. PMID:27770290

  1. 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

  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. Modulation of proteomic profile in H295R adrenocortical cell line induced by mitotane.

    PubMed

    Stigliano, A; Cerquetti, L; Borro, M; Gentile, G; Bucci, B; Misiti, S; Piergrossi, P; Brunetti, E; Simmaco, M; Toscano, V

    2008-03-01

    Mitotane, 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chloro-phenyl) ethane (o,p'-DDD), is a compound that represents the effective agent in the treatment of the adrenocortical carcinoma (ACC), able to block cortisol synthesis. In this type of cancer, the biological mechanism induced by this treatment remains still unknown. In this study, we have already shown a greater impairment in the first steps of the steroidogenesis and recognized a little effect on cell cycle. We also evaluated the variation of proteomic profile of the H295R ACC cell line, either in total cell extract or in mitochondria-enriched fraction after treatment with mitotane. In total cell extracts, triose phosphate isomerase, alpha-enolase, D-3-phosphoglycerate dehydrogenase, peroxiredoxin II and VI, heat shock protein 27, prohibitin, histidine triad nucleotide-binding protein, and profilin-1 showed a different expression. In the mitochondrial fraction, the following proteins appeared to be down regulated: aldolase A, peroxiredoxin I, heterogenous nuclear ribonucleoprotein A2/B1, tubulin-beta isoform II, heat shock cognate 71 kDa protein, and nucleotide diphosphate kinase, whereas adrenodoxin reductase, cathepsin D, and heat shock 70 kDa protein 1A were positively up-regulated. This study represents the first proteomic study on the mitotane effects on ACC. It permits to identify some protein classes affected by the drug involved in energetic metabolism, stress response, cytoskeleton structure, and tumorigenesis.

  4. First case report of an adrenocortical carcinoma caused by a BRCA2 mutation

    PubMed Central

    El Ghorayeb, Nada; Grunenwald, Solange; Nolet, Serge; Primeau, Vanessa; Côté, Stéphanie; Maugard, Christine M.; Lacroix, André; Gaboury, Louis; Bourdeau, Isabelle

    2016-01-01

    Abstract Background: Adrenocortical carcinoma (ACC) may rarely be a component of inherited cancer syndromes such as Li-Fraumeni syndrome and Beckwith-Wiedemann syndrome. ACC caused by a BRCA2 mutation has never been reported. Methods: Nucleotide sequencing of BRCA2 in lymphocyte and tumoral DNA of a 50-year-old male who presented with an androgen-secreting ACC and a strong family history of breast, ovarian, and pancreatic cancers. Results: A germline BRCA2 2 bp heterozygous deletion at nucleotide 8765 (8765delAG) leading to a frameshift mutation (p.Glu2846GlyfsX23) was detected. Only the BRCA2 deleted allele was retained in the ACC tumoral DNA compared with the control DNA supporting a loss of heterozygosity in the tumor. Conclusion: This is the first reported case of a patient with ACC associated with a BRCA2 germline mutation. Loss of heterozygosity in ACC DNA suggests a causal link with the BRCA2 8765delAG mutation. PMID:27603373

  5. Metformin as a new anti-cancer drug in adrenocortical carcinoma

    PubMed Central

    Fucci, Rossella; Santi, Raffaella; Canu, Letizia; Nesi, Gabriella; Mannelli, Massimo; Luconi, Michaela

    2016-01-01

    Adrenocortical carcinoma (ACC) is a rare heterogeneous malignancy with poor prognosis. Since radical surgery is the only available treatment, more specific and effective drugs are urgently required. The anti-diabetic drug metformin has been associated with a decreased cancer prevalence and mortality in several solid tumors, prompting its possible use for ACC treatment. This paper evaluates the in vitro and in vivo anti-cancer effects of metformin using the ACC cell model H295R. Metformin treatment significantly reduces cell viability and proliferation in a dose- and time-dependent manner and associates with a significant inhibition of ERK1/2 and mTOR phosphorylation/activation, as well as with stimulation of AMPK activity. Metformin also triggers the apoptotic pathway, shown by the decreased expression of Bcl-2 and HSP27, HSP60 and HSP70, and enhanced membrane exposure of annexin V, resulting in activation of caspase-3 apoptotic effector. Metformin interferes with the proliferative autocrine loop of IGF2/IGF-1R, which supports adrenal cancer growth. Finally, in the ACC xenograft mouse model, obtained by subcutaneous injection of H295R cells, metformin intraperitoneal administration inhibits tumor growth, confirmed by the significant reduction of Ki67%. Our data suggest that metformin inhibits H295R cell growth both in vitro and in vivo. Further preclinical studies are necessary to validate the potential anti-cancer effect of metformin in patients affected by ACC. PMID:27391065

  6. Adrenocortical responses to offspring-directed threats in two open-nesting birds.

    PubMed

    Butler, Luke K; Bisson, Isabelle-Anne; Hayden, Timothy J; Wikelski, Martin; Romero, L Michael

    2009-07-01

    Dependent young are often easy targets for predators, so for many parent vertebrates, responding to offspring-directed threats is a fundamental part of reproduction. We tested the parental adrenocortical response of the endangered black-capped vireo (Vireo atricapilla) and the common white-eyed vireo (V. griseus) to acute and chronic threats to their offspring. Like many open-nesting birds, our study species experience high offspring mortality. Parents responded behaviorally to a predator decoy or human 1-2m from their nests, but, in contrast to similar studies of cavity-nesting birds, neither these acute threats nor chronic offspring-directed threats altered plasma corticosterone concentrations of parents. Although parents in this study showed no corticosterone response to offspring-directed threats, they always increased corticosterone concentrations in response to capture. To explain these results, we propose that parents perceive their risk of nest-associated death differently depending on nest type, with cavity-nesting adults perceiving greater risk to themselves than open-nesters that can readily detect and escape from offspring-directed threats. Our results agree with previous studies suggesting that the hypothalamic-pituitary-adrenal axis, a major physiological mechanism for coping with threats to survival, probably plays no role in coping with threats to offspring when risks to parents and offspring are not correlated. We extend that paradigm by demonstrating that nest style may influence how adults perceive the correlation between offspring-directed and self-directed threats.

  7. StAR Protein Stability in Y1 and Kin-8 Mouse Adrenocortical Cells.

    PubMed

    Clark, Barbara J; Hudson, Elizabeth A

    2015-03-04

    The steroidogenic acute regulatory protein (STAR) protein expression is required for cholesterol transport into mitochondria to initiate steroidogenesis in the adrenal and gonads. STAR is synthesized as a 37 kDa precursor protein which is targeted to the mitochondria and imported and processed to an intra-mitochondrial 30 kDa protein. Tropic hormone stimulation of the cAMP-dependent protein kinase A (PKA) signaling pathway is the major contributor to the transcriptional and post-transcriptional regulation of STAR synthesis. Many studies have focused on the mechanisms of cAMP-PKA mediated control of STAR synthesis while there are few reports on STAR degradation pathways. The objective of this study was to determine the effect of cAMP-PKA-dependent signaling on STAR protein stability. We have used the cAMP-PKA responsive Y1 mouse adrenocortical cells and the PKA-deficient Kin-8 cells to measure STAR phosphorylation and protein half-life. Western blot analysis and standard radiolabeled pulse-chase experiments were used to determine STAR phosphorylation status and protein half-life, respectively. Our data demonstrate that PKA-dependent STAR phosphorylation does not contribute to 30 kDa STAR protein stability in the mitochondria. We further show that inhibition of the 26S proteasome does not block precursor STAR phosphorylation or steroid production in Y1 cells. These data suggest STAR can maintain function and promote steroidogenesis under conditions of proteasome inhibition.

  8. Two different P2Y receptors linked to steroidogenesis in bovine adrenocortical cells.

    PubMed

    Nishi, H

    1999-10-01

    Both extracellular adenosine 5'-triphosphate (ATP) and uridine 5'-triphosphate (UTP) induced corticoid production (steroidogenesis) concentration-dependently in bovine adrenocortical cells (BA cells). Pertussis toxin (PTX, approx. 2 microg/ml) partially inhibited (approx. 55% inhibition) extracellular ATP (100 microM)-induced steroidogenesis in BA cells. However, PTX did not inhibit extracellular UTP (100 microM)-induced steroidogenesis. Both ATP- and UTP-induced steroidogeneses were significantly inhibited by suramin (50-200 microM). These effects were inhibited significantly by reactive blue-2 (more than 100 microM) and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (more than 100 microM). Both nucleotides (1-100 microM) induced inositol phosphates accumulation and intracellular Ca2+ mobilization, but PTX did not inhibit them. The RT-PCR procedure identified only P2Y2-receptor mRNA in BA cells. These results suggest that extracellular ATP induces steroidogenesis via a unique P2 receptor linked to PTX-sensitive guanine nucleotide-binding protein (G-protein), while extracellular UTP induces steroidogenesis via P2 receptor linked to PTX-insensitive G-protein. Thus, it was concluded that at least two different P2Y-like receptors linking to steroidogenesis exist in BA cells.

  9. 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

  10. Excitatory influence of the locus coeruleus in hypothalamic-pituitary-adrenocortical axis responses to stress.

    PubMed

    Ziegler, D R; Cass, W A; Herman, J P

    1999-05-01

    The locus coeruleus (LC) is a key brainstem region involved in arousal and is highly responsive to alerting/stressful stimuli, including those that activate the hypothalamic-pituitary-adrenocortical (HPA) axis. It is currently unclear whether the LC exerts any regulatory influence on the HPA axis and, consequently, on neuroendocrine responses to stress. The present studies were designed to test the hypothesis that the LC promotes HPA axis responses to acute and chronic stress. Adult male rats received bilateral (6-hydroxydopamine) lesions of the LC that produced severe cell loss in the LC and 80% depletion of noradrenaline in medial prefrontal cortex. Notably, lesions did not affect dopamine-beta-hydroxylase protein content in the parvocellular paraventricular nucleus (PVN), indicating a lack of collateral damage to other ascending noradrenergic pathways. LC lesions significantly reduced peak adrenocorticotropic hormone (ACTH) and corticosterone responses to 30 min acute restraint stress. However, LC lesions did not significantly attenuate neuroendocrine or other physiological responses to a 4-week chronic variable stress regimen. LC lesions did not substantially affect basal concentrations of plasma corticosterone or corticotropin-releasing hormone mRNA expression in the hypothalamic paraventricular nucleus following chronic stress. We conclude that the LC is a HPA-excitatory brain region, promoting neuroendocrine and physiological responses primarily to acute stress. However, a potential role for the LC in the induction of HPA axis hyperactivity following chronic stress can not be ruled out.

  11. 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

  12. A rare case of Cushing's syndrome due to bilateral adrenocortical adenomas.

    PubMed

    Yasuda, Atsushi; Seki, Toshiro; Ito, Kazuko; Takagi, Atsushi; Watanabe, Daisuke; Nakamura, Naoya; Hanai, Kazuya; Terachi, Toshiro; Maekawa, Takashi; Sasano, Hironobu; Fukagawa, Masafumi

    2014-12-20

    We report a rare case of Cushing's syndrome caused by bilateral cortisol-secreting adenomas in a 63-year-old man. Our preoperative diagnosis was based on endocrinological results and imaging findings. Laparoscopic adrenalectomy has become a standard technique for adrenal tumors; however, bilateral adrenalectomy results in postoperative adrenal insufficiency, necessitating lifelong steroid replacement. To preserve adrenal function, the left adrenal gland was completely resected, whereas the right adrenal gland was partially resected laparoscopically. Hydrocortisone supplementation was initiated at a dose of 30 mg/day and was slowly tapered. However, symptoms of adrenal insufficiency developed, and adrenal steroid secretion did not respond to exogenous adrenocorticotropic hormone. Bilateral cortisol-secreting tumors rarely cause Cushing's syndrome. The present study comprised few patients, and the utilized surgical procedures (i.e., total/partial adrenalectomy or bilateral total adrenalectomy) were not uniform. Few cases of bilateral adrenal-preserving surgery have been reported. However, our patient developed adrenal insufficiency after the oral cortisone supplementation was tapered. This report demonstrates that partial adrenalectomy does not necessarily preserve normal adrenocortical function. Therefore, careful postoperative observation is necessary for patients undergoing a partial adrenalectomy.

  13. Next-generation sequencing of adrenocortical carcinoma reveals new routes to targeted therapies

    PubMed Central

    Ross, J S; Wang, K; Rand, J V; Gay, L; Presta, M J; Sheehan, C E; Ali, S M; Elvin, J A; Labrecque, E; Hiemstra, C; Buell, J; Otto, G A; Yelensky, R; Lipson, D; Morosini, D; Chmielecki, J; Miller, V A; Stephens, P J

    2014-01-01

    Aims Adrenocortical carcinoma (ACC) carries a poor prognosis and current systemic cytotoxic therapies result in only modest improvement in overall survival. In this retrospective study, we performed a comprehensive genomic profiling of 29 consecutive ACC samples to identify potential targets of therapy not currently searched for in routine clinical practice. Methods DNA from 29 ACC was sequenced to high, uniform coverage (Illumina HiSeq) and analysed for genomic alterations (GAs). Results At least one GA was found in 22 (76%) ACC (mean 2.6 alterations per ACC). The most frequent GAs were in TP53 (34%), NF1 (14%), CDKN2A (14%), MEN1 (14%), CTNNB1 (10%) and ATM (10%). APC, CCND2, CDK4, DAXX, DNMT3A, KDM5C, LRP1B, MSH2 and RB1 were each altered in two cases (7%) and EGFR, ERBB4, KRAS, MDM2, NRAS, PDGFRB, PIK3CA, PTEN and PTCH1 were each altered in a single case (3%). In 17 (59%) of ACC, at least one GA was associated with an available therapeutic or a mechanism-based clinical trial. Conclusions Next-generation sequencing can discover targets of therapy for relapsed and metastatic ACC and shows promise to improve outcomes for this aggressive form of cancer. PMID:25078331

  14. Social crowding stress diminishes the pituitary-adrenocortical and hypothalamic histamine response to adrenergic stimulation.

    PubMed

    Bugajski, J; Gadek-Michalska, A; Borycz, J

    1993-12-01

    Social stress of crowding almost totally reduced the rise in serum corticosterone elicited by intracerebroventricular administration of isoprenaline, a beta-adrenergic receptor agonist, after 3 and 7 day of crowding and substantially diminished that response after 14 and 21 days. Crowding stress totally abolished the increase in hypothalamic histamine induced by isoprenaline in control rats. Crowding also significantly diminished the increase in serum corticosterone evoked by clonidine, an alpha 2-adrenergic agonist, and abolished the clonidine-induced elevation in hypothalamic histamine levels. The stimulatory effect of phenylephrine, an alpha 1-adrenergic agonist, on corticosterone secretion was only moderately diminished in crowded rats. Neither phenylephrine nor crowding stress changed significantly the hypothalamic histamine levels. These results indicate that social stress of crowding considerably impairs the hypothalamic-pituitary-adrenocortical responsiveness to central beta- and alpha 2-adrenergic receptor stimulation. Crowding also abolishes the rise in hypothalamic histamine induced by beta- and alpha 2-adrenergic agonist, suggesting a role of hypothalamic histamine in the HPA adaptation to the social stress of crowding.

  15. Adrenocortical regulation, eating in the absence of hunger and BMI in young children.

    PubMed

    Francis, L A; Granger, D A; Susman, E J

    2013-05-01

    The purpose of this study was to examine relations among adrenocortical regulation, eating in the absence of hunger, and body mass index (BMI) in children ages 5-9years (N=43). Saliva was collected before and after the Trier Social Stress Test for Children (TSST-C), and was later assayed for cortisol. Area under the curve with respect to increase (AUCi) was used as a measure of changes in cortisol release from baseline to 60min post-TSST-C. Age- and sex-specific BMI scores were calculated from measured height and weight, and eating in the absence of hunger was assessed using weighed food intake during a behavioral procedure. We also included a measure of parents' report of child impulsivity, as well as family demographic information. Participants were stratified by age into younger (5-7years) and older (8-9years) groups. In younger children, parents' reports of child impulsivity were significantly and positively associated with BMI; cortisol AUCi was not associated with BMI or eating in the absence of hunger. In older children, however, greater stress-related cortisol AUCi was related to higher BMI scores and greater energy intake in the absence of hunger. The results suggest that cortisol AUCi in response to psychosocial stress may be linked to problems with energy balance in children, with some variation by age.

  16. Adrenocortical and behavioral attunement in parents with 1-year-old infants.

    PubMed

    van Bakel, Hedwig J A; Riksen-Walraven, J Marianne

    2008-03-01

    Sethre-Hofstad et al. [2002, Psychoneuroendocrinology 27:731-747] found that behaviorally well-attuned or sensitive parents showed better physiological attunement with their 2- to 4-year-old toddlers' adrenocortical responses to a potentially challenging task than less sensitive parents. In the present study we aimed to replicate this finding in a sample of 83 parents with 15-month-old infants. Parental and infant cortisol responses were assessed using saliva samples collected before and 21 min after the child's confrontation with a stranger and a moving robot. Infant behaviors reflecting distress/uncertainty during the stranger-robot session were rated from videotape. Parental sensitivity was observed during a parent-infant teaching episode. Our findings replicate those of Sethre-Hofstad et al. [2002, Psychoneuroendocrinology 27:731-747] by showing correlated parent-infant cortisol responses for sensitive parents but not for less sensitive parents. Furthermore, sensitive parents cortisol responses were associated with their children's distress/uncertainty during the stranger-robot episode, whereas this was not true for less sensitive parents. Results indicate an important connection between behavior and physiology in parent-infant interactions that deserve more research.

  17. Diagnosis and management of facial pigmented macules.

    PubMed

    Lallas, Aimilios; Argenziano, Giuseppe; Moscarella, Elvira; Longo, Caterina; Simonetti, Vito; Zalaudek, Iris

    2014-01-01

    The differential diagnosis of pigmented macules on the mottled chronic sun-damaged skin of the face is challenging and includes lentigo maligna (LM), pigmented actinic (solar) keratosis, solar lentigo, and lichen-planus-like keratosis. Although dermatoscopy improves the diagnostic accuracy of the unaided eye, the accurate diagnosis and management of pigmented facial macules remains one of the most challenging scenarios in daily practice. This is related to the fact that pigmented actinic (solar) keratosis, lichen-planus-like keratosis, and LM may reveal overlapping criteria, making their differential diagnosis clinically difficult. For this reason, practical rules have been introduced, which should help to minimize the risk for inappropriate diagnosis and management of LM.

  18. 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.

  19. Color characterization of coatings with diffraction pigments.

    PubMed

    Ferrero, A; Bernad, B; Campos, J; Perales, E; Velázquez, J L; Martínez-Verdú, F M

    2016-10-01

    Coatings with diffraction pigments present high iridescence, which needs to be characterized in order to describe their appearance. The spectral bidirectional reflectance distribution functions (BRDFs) of six coatings with SpectraFlair diffraction pigments were measured using the robot-arm-based goniospectrophotometer GEFE, designed and developed at CSIC. Principal component analysis has been applied to study the coatings of BRDF data. From data evaluation and based on theoretical considerations, we propose a relevant geometric factor to study the spectral reflectance and color gamut variation of coatings with diffraction pigments. At fixed values of this geometric factor, the spectral BRDF component due to diffraction is almost constant. Commercially available portable goniospectrophotometers, extensively used in several industries (automotive and others), should be provided with more aspecular measurement angles to characterize the complex reflectance of goniochromatic coatings based on diffraction pigments, but they would not require either more than one irradiation angle or additional out-of-plane geometries.

  20. Induction of Yellow Pigmentation in Serratia marcescens

    PubMed Central

    Trias, Joaquim; Viñas, Miquel; Guinea, Jesús; Lorén, José G.

    1988-01-01

    The appearance of yellow pigmentation in nonpigmented strains of Serratia sp. has been demonstrated to be due to the production of a muconic acid, 2-hydroxy-5-carboxymethylmuconic acid semialdehyde. The 3,4-dihydroxyphenylacetate 2,3-dioxygenase responsible for the synthesis of this muconic acid was induced in all strains tested. Another muconic acid, the β-cis-cis-carboxymuconic acid, could also be synthesized from 3,4-dihydroxybenzoate, but this product was not colored. Mutants that were unable to grow on tyrosine and produced yellow pigment were isolated from nonpigmented strains. These mutants had properties similar to those of the yellow-pigmented strains. The ability to produce pigment may be more widespread among Serratia marcescens strains than is currently known. PMID:16347803

  1. 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.

  2. 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. PMID:27529890

  3. Rheumatoid pleural effusion with nodular pleuritis. A rare presentation of rheumatoid arthritis.

    PubMed

    Emmungil, H; Yıldız, F; Gözükara, M Y; Açıkalın, A

    2015-02-01

    Rheumatoid pleural effusion and lung nodules are unusual complications of rheumatoid disease that typically present subsequently to other more common manifestations of rheumatoid illness. However, these complications may occasionally occur before or concurrently with the development of joint manifestations of disease. We report the case of a 41-year-old female patient with rheumatoid pleural effusion and lung nodule arising simultaneously with the onset of joint symptoms. The patient underwent thoracentesis followed by video-assisted thoracoscopic biopsy to result in a diagnosis of rheumatoid pleuritis and nodular disease. A high index of suspicion and coexistence of the cytologic and histopathologic effusion picture characteristic of rheumatoid pleuritis are of clinical importance in making a diagnosis.

  4. Horner's syndrome following a subtotal thyroidectomy for a benign nodular goitre.

    PubMed

    Aslankurt, Murat; Aslan, Lokman; Colak, Mustafa; Aksoy, Adnan

    2013-06-13

    We present a case of Horner's syndrome occurring as a complication of thyroidectomy. A 42-year-old female patient presented with eyelid drop which developed immediately after thyroidectomy for goitre. Ophthalmic examination revealed eyelid ptosis, miosis and anhidrosis. Preoperative ultrasonography showed multiple isohyperechogenic solid nodules in each lobe, consistent with multinodular goitre. Therefore, the patient underwent subtotal thyroidectomy. The ophthalmic findings did not improve at the end of 6 months follow-up. Similar cases have been reported related to neck tumours or their surgery, mediastinum-located goitre and retropharyngeal abscess surgeries, but not after benign nodular goitre surgery. Several possible mechanisms have been proposed to explain this phenomenon; anatomical variations making the patient susceptible to damage to the sympathetic chain seem to be most likely in our patient.

  5. Photodynamic therapy of nodular basal cell carcinoma with multifiber contact light delivery.

    PubMed

    Thompson, Marcelo Soto; Andersson-Engels, Stefan; Svanberg, Sune; Johansson, T; Palsson, Sara; Bendsoe, Niels; Derjabo, A; Kapostins, J; Stenram, Unne; Spigulis, J; Svanberg, Katarina

    2006-01-01

    To overcome the limited treatment depth of superficial photodynamic therapy we investigate interstitial light delivery. In the present work the treatment light was delivered using a system in which three or six clear-cut fibers were placed in direct contact with the tumor area. This placement was thought to represent a step toward general purpose interstitial PDT. Twelve nodular basal cell carcinomas were treated employing delta-aminolevulinic acid and 635 nm laser irradiation. Fluorescence measurements were performed monitoring the buildup and subsequent bleaching of the produced sensitizer protoporphyrin IX. The treatment efficacy, judged at a 28-month follow-up, showed a 100% complete response. Two punch excisions at 7 months converted two partial responses to complete responses. One patient failed to appear at all follow-up sessions. The outcome of the treatments was comparable to superficial photodynamic therapy in terms of histological, clinical, and cosmetic results.

  6. Gray matter volumes and cognitive ability in the epileptogenic brain malformation of periventricular nodular heterotopia.

    PubMed

    Walker, Linsey M; Katzir, Tami; Liu, Tianming; Ly, Jenny; Corriveau, Kathleen; Barzillai, Mirit; Chu, Felicia; O'Connor, Margaret G; Hackney, David B; Chang, Bernard S

    2009-08-01

    Periventricular nodular heterotopia (PNH) is a brain malformation clinically characterized by the triad of epilepsy, normal intelligence, and dyslexia. We investigated the structure-function relationship between cerebral volumes and cognitive ability in this disorder by studying 12 subjects with PNH and 6 controls using volumetric analysis of high-resolution anatomical MRI and neuropsychological testing. Total cerebral volumes and specific brain compartment volumes (gray matter, white matter, and cerebrospinal fluid) in subjects with PNH were comparable to those in controls. There was a negative correlation between heterotopic gray matter volume and cortical gray matter volume. Cerebral and cortical volumes in PNH did not correlate with Full Scale IQ, unlike in normal individuals. Our findings support the idea that heterotopic nodules contain misplaced neurons that would normally have migrated to the cortex, and suggest that structural correlates of normal cognitive ability may be different in the setting of neuronal migration failure.

  7. Programmed death 1 expression in variant immunoarchitectural patterns of nodular lymphocyte predominant Hodgkin lymphoma: comparison with CD57 and lymphomas in the differential diagnosis.

    PubMed

    Churchill, Hywyn R O; Roncador, Giovanna; Warnke, Roger A; Natkunam, Yasodha

    2010-12-01

    Recent studies have exploited an antibody directed against programmed death 1 expressed by follicular helper T-cells in the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma. We had previously described clinically relevant, variant immunoarchitectural patterns of nodular lymphocyte predominant Hodgkin lymphoma and, in this study, sought to address the diagnostic utility of programmed death 1 in comparison with CD57 in variant nodular lymphocyte predominant Hodgkin lymphoma. Immunohistologic staining for programmed death 1 was carried out on biopsies of 67 patients with variant nodular lymphocyte predominant Hodgkin lymphoma. Thirty-four additional cases of nodular lymphocyte predominant Hodgkin lymphoma with associated diffuse areas, de novo T-cell and histiocyte-rich large B-cell lymphoma, and lymphocyte-rich classic Hodgkin lymphoma were also studied. Our results show that programmed death 1 positivity was found in the majority of nodular lymphocyte predominant Hodgkin lymphoma cases with a classic nodular architecture (87%) as compared with 50% for CD57 and was particularly helpful in identifying extranodular large atypical cells. Nodular lymphocyte predominant Hodgkin lymphoma with diffuse areas showed a gradual decrease in programmed death 1 reactivity from nodular to diffuse areas, although a significant proportion (40%-50%) of cases retained programmed death 1 positivity also in diffuse areas. In addition, T-cell and histiocyte-rich large B-cell lymphoma and lymphocyte-rich classic Hodgkin lymphoma displayed programmed death 1 positivity in a significant subset of cases (33%-40%). In conclusion, our study supports the utility of programmed death 1 in the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma and shows greater sensitivity of staining of programmed death 1 as compared with CD57 across all variants of nodular lymphocyte predominant Hodgkin lymphoma. Loss of programmed death 1 reactivity did not correlate with diffuse areas

  8. Genetics of pigmentation and melanoma predisposition.

    PubMed

    Pho, L N; Leachman, S A

    2010-02-01

    About 5-10% of human cutaneous malignant melanoma is hereditary and known to involve rare germline mutations in highly penetrant, autosomal dominant genes. These genes are important in cell cycle control but are not responsible for all familial cases of melanoma. Epidemiologic studies have linked specific phenotypic traits including fair skin, light-colored eyes, and poor tanning ability to melanoma risks. The ability to visually discern and define pigmentary phenotypes in humans and in animal models has permitted elucidation of many genes involved in pigmentation and melanin biosynthesis. Additional genetic epidemiological studies have recently identified a subset of these pigmentation genes that are associated with risk for melanoma and other cutaneous malignancies as well as photosensitivity. Genome-wide association studies (GWAS) have unveiled single nucleotide polymorphisms (SNPs) or genetic variants in MC1R, TPCN2, ASIP, KITLG, NCKX5, TYR, IRF4, OCA2, and TYRP1 pigmentation genes. These findings emphasize the contribution of pigmentation pathways to melanoma predisposition and tumorigenesis through gene-environment interactions. Since pigmentation genes in the melanin synthesis pathway also confer risk for cutaneous malignancy, a better understanding of the operative molecular mechanisms involved in this relationship has the potential to impact individual risk assessment for cutaneous malignant melanoma in the future. This paper is an overview of our current understanding of pigmentation gene modifications that have been associated with melanoma risk and how these genes can enrich clinical management, prevention, and early detection of malignant melanoma.

  9. Macular pigment and lutein supplementation in choroideremia.

    PubMed

    Duncan, Jacque L; Aleman, Tomas S; Gardner, Leigh M; De Castro, Elaine; Marks, Daniel A; Emmons, Jessica M; Bieber, Michelle L; Steinberg, Janet D; Bennett, Jean; Stone, Edwin M; MacDonald, Ian M; Cideciyan, Artur V; Maguire, Maureen G; Jacobson, Samuel G

    2002-03-01

    Choroideremia is an incurable X-linked retinal degeneration caused by mutations in the gene encoding Rab escort protein-1. A group of clinically defined and genotyped patients were studied to determine: (1) the degree of rod and cone dysfunction and structural abnormality in the central retina and the level of macular pigment; and (2) the response of macular pigment and foveal vision to a 6 month trial of supplementation with oral lutein (at 20 mg per day). Rod and cone-mediated function was measured with dark-adapted static perimetry; in vivo retinal structure was determined with optical coherence tomography; and macular pigment optical density was measured with heterochromatic flicker photometry. In this cohort of patients (ages 15-65 years), both rod- and cone-mediated central function declined with age as did central retinal thickness. Macular pigment levels did not differ between patients and male control subjects. Supplementation of oral lutein in a subset of patients led to an increase in serum lutein and macular pigment levels; absolute foveal sensitivity did not change. It is concluded that macular pigment density can be augmented by oral intake of lutein in patients with choroideremia. There was no short-term change in the central vision of the patients on the supplement, but long-term influences of lutein supplementation on disease natural history warrant further study.

  10. Microspectrophotometry of Arthropod Visual Screening Pigments

    PubMed Central

    Strother, G. K.; Casella, A. J.

    1972-01-01

    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

  11. Single nucleotide polymorphism microarray analysis in cortisol-secreting adrenocortical adenomas identifies new candidate genes and pathways.

    PubMed

    Ronchi, Cristina L; Leich, Ellen; Sbiera, Silviu; Weismann, Dirk; Rosenwald, Andreas; Allolio, Bruno; Fassnacht, Martin

    2012-03-01

    The genetic mechanisms underlying adrenocortical tumor development are still largely unknown. We used high-resolution single nucleotide polymorphism microarrays (Affymetrix SNP 6.0) to detect copy number alterations (CNAs) and copy-neutral losses of heterozygosity (cnLOH) in 15 cortisol-secreting adrenocortical adenomas with matched blood samples. We focused on microalterations aiming to discover new candidate genes involved in early tumorigenesis and/or autonomous cortisol secretion. We identified 962 CNAs with a median of 18 CNAs per sample. Half of them involved noncoding regions, 89% were less than 100 kb, and 28% were found in at least two samples. The most frequently gained regions were 5p15.33, 6q16.1, 7p22.3-22.2, 8q24.3, 9q34.2-34.3, 11p15.5, 11q11, 12q12, 16q24.3, 20p11.1-20q21.11, and Xq28 (≥20% of cases), most of them being identified in the same three adenomas. These regions contained among others genes like NOTCH1, CYP11B2, HRAS, and IGF2. Recurrent losses were less common and smaller than gains, being mostly localized at 1p, 6q, and 11q. Pathway analysis revealed that Notch signaling was the most frequently altered. We identified 46 recurrent CNAs that each affected a single gene (31 gains and 15 losses), including genes involved in steroidogenesis (CYP11B1) or tumorigenesis (CTNNB1, EPHA7, SGK1, STIL, FHIT). Finally, 20 small cnLOH in four cases affecting 15 known genes were found. Our findings provide the first high-resolution genome-wide view of chromosomal changes in cortisol-secreting adenomas and identify novel candidate genes, such as HRAS, EPHA7, and SGK1. Furthermore, they implicate that the Notch1 signaling pathway might be involved in the molecular pathogenesis of adrenocortical tumors.

  12. 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.

  13. Inhibition of Human Adrenocortical Cancer Cell Growth by Temozolomide in Vitro and the Role of the MGMT Gene

    PubMed Central

    Creemers, S. G.; van Koetsveld, P. M.; van den Dungen, E. S. R.; Korpershoek, E.; van Kemenade, F. J.; Franssen, G. J. H.; de Herder, W. W.; Feelders, R. A.

    2016-01-01

    Context: Treatment of patients with adrenocortical carcinomas (ACC) with mitotane and/or chemotherapy is often associated with toxicity and poor tumor response. New therapeutic options are urgently needed. Objective: The objectives of the study were to evaluate the therapeutic possibilities of temozolomide (TMZ) in ACC cells and to assess the potential predictive role of the DNA repair gene O6-Methylguanine-DNA methyltransferase (MGMT) in adrenocortical tumors. Methods: Three human ACC cell lines and eight primary ACC cultures were used to assess effects of TMZ in vitro. In the cell lines, 11 normal adrenals, 16 adrenocortical adenomas, and 29 ACC, MGMT promoter methylation and expression were determined. Results: IC50 values of TMZ on cell growth were 39 μM, 38 μM, and 44 μM for H295R, HAC15, and SW13, respectively. TMZ induced apoptosis and provoked cytotoxic and cytostatic effects by reducing the surviving fraction of ACC colonies and the colony size. TMZ thereby induced cell cycle arrests in ACC cell lines. TMZ and mitotane both inhibited growth of ACC cells cultured as three-dimensional spheroids. TMZ inhibited cell amount in five of eight primary ACC cultures and induced apoptosis in seven of eight primary ACC cultures. In ACC cell lines and adrenal tissues, MGMT promoter methylation was low. In ACCs, methylation was inversely correlated with MGMT mRNA expression. MGMT protein expression was not correlated with MGMT methylation. Conclusions: For the first time, we show the therapeutic potential of temozolomide for ACC, offering an urgently needed potential alternative for patients not responding to mitotane alone or with etoposide, doxorubicin, and cisplatin. (Pre-)clinical studies are warranted to assess efficacy in vivo. PMID:27603910

  14. Splenorenal Arterial Bypass: Description of Technique and Case Example in an Instance of Renal Revascularization during Adrenalectomy for Adrenocortical Carcinoma.

    PubMed

    Yozawitz, J; Kissin, M; Szuchmacher, M; Sullivan, J; Nicastro, J; Coppa, G; Molmenti, E

    2016-12-01

    We present a patient with a 16 cm adrenocortical carcinoma that underwent a left adrenalectomy en bloc with resection of the involved segment of the left renal artery. A splenectomy and splenorenal bypass was performed to revascularize the left kidney. To our knowledge, this is the first instance in the literature of a splenorenal arterial bypass being reported for renal revascularization during an extirpative oncologic procedure. A 64-year-old male patient, with history significant for adrenocortical carcinoma, status post prior right adrenalectomy with partial right nephrectomy, presented for an elective left adrenalectomy. Preoperative work-up revealed an 11.4 × 13.2 × 16 cm left adrenal mass, most consistent with an adrenocortical carcinoma. At the time of surgery, the mass was found to be intimately adherent to the aorta at the takeoff of the left renal artery. Moreover, the left renal artery appeared to be coursing directly through the mass. The involved segment of the left renal artery was resected en bloc with the tumor. Because of concerns for a small and likely poorly functioning right renal remnant, a decision was made to attempt to salvage the left kidney. This was accomplished by performing a splenectomy and constructing a splenorenal bypass. Serial Duplex Doppler renal ultrasound studies were obtained over the first three postoperative days and demonstrated improved arterial waveforms. Serum creatinine reached a peak level of 3.76 mg/dL on postoperative day 3, and then began to slowly trend down to 3.37 mg/dL on the day of discharge (postoperative day7).

  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. 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.

  17. 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.

  18. Diagnostic utility and limitations of glutamine synthetase and serum amyloid-associated protein immunohistochemistry in the distinction of focal nodular hyperplasia and inflammatory hepatocellular adenoma.

    PubMed

    Joseph, Nancy M; Ferrell, Linda D; Jain, Dhanpat; Torbenson, Michael S; Wu, Tsung-Teh; Yeh, Matthew M; Kakar, Sanjay

    2014-01-01

    Inflammatory hepatocellular adenoma can show overlapping histological features with focal nodular hyperplasia, including inflammation, fibrous stroma, and ductular reaction. Expression of serum amyloid-associated protein in inflammatory hepatocellular adenoma and map-like pattern of glutamine synthetase in focal nodular hyperplasia can be helpful in this distinction, but the pitfalls and limitations of these markers have not been established. Morphology and immunohistochemistry were analyzed in 54 inflammatory hepatocellular adenomas, 40 focal nodular hyperplasia, and 3 indeterminate lesions. Morphological analysis demonstrated that nodularity, fibrous stroma, dystrophic blood vessels, and ductular reaction were more common in focal nodular hyperplasia, while telangiectasia, hemorrhage, and steatosis were more common in inflammatory hepatocellular adenoma, but there was frequent overlap of morphological features. The majority of inflammatory hepatocellular adenomas demonstrated perivascular and/or patchy glutamine synthetase staining (73.6%), while the remaining cases had diffuse (7.5%), negative (3.8%), or patchy pattern of staining (15%) that showed subtle differences from the classic map-like staining pattern and was designated as pseudo map-like staining. Positive staining for serum amyloid-associated protein was seen in the majority of inflammatory hepatocellular adenomas (92.6%) and in the minority of focal nodular hyperplasia (17.5%). The glutamine synthetase staining pattern was map-like in 90% of focal nodular hyperplasia cases, with the remaining 10% of cases showing pseudo map-like staining. Three cases were labeled as indeterminate and showed focal nodular hyperplasia-like morphology but lacked map-like glutamine synthetase staining pattern; these cases demonstrated a patchy pseudo map-like glutamine synthetase pattern along with the expression of serum amyloid-associated protein. Our results highlight the diagnostic errors that can be caused by variant

  19. 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.

  20. 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

  1. 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

  2. Prognostic markers of survival after combined mitotane- and platinum-based chemotherapy in metastatic adrenocortical carcinoma.

    PubMed

    Malandrino, Pasqualino; Al Ghuzlan, Abir; Castaing, Marine; Young, Jacques; Caillou, Bernard; Travagli, Jean-Paul; Elias, Dominique; de Baere, Thierry; Dromain, Clarisse; Paci, Angelo; Chanson, Philippe; Schlumberger, Martin; Leboulleux, Sophie; Baudin, Eric

    2010-09-01

    To progress in the stratification of the first-line therapeutic management of metastatic adrenocortical carcinoma (ACC), we searched for prognostic parameters of survival in patients treated with combined mitotane- and cisplatinum-based chemotherapy as first-line. We retrospectively studied prospectively collected parameters from 131 consecutive patients with metastatic ACC (44 with a tissue specimen available) treated at the Gustave Roussy Institute with mitotane- and platinum-based chemotherapy. Fifty-five patients with clinical, pathological, and morphological data available together with treatment characteristics including detailed follow-up were enrolled. Plasma mitotane levels and ERCC1 protein staining were analyzed. Response was analyzed according to RECIST criteria as well as overall survival (OS) from the start of cisplatinum-based chemotherapy. Parameters impacting on OS were evaluated by univariate analysis, and then analyzed by multivariate analysis. Using a landmark method, OS according to response to chemotherapy was analyzed. Objective response to combined mitotane- and cisplatinum-based chemotherapy was 27.3%. Median OS was 1 year. In the univariate analysis, resection of the primary, time since diagnosis, mitotane monotherapy as single first-line treatment, number of affected organs, plasma mitotane above 14 mg/l, and objective response were predictors of survival. In the multivariate analysis, mitotane level > or =14 mg/l and objective response to platinum-based chemotherapy were found to be independent predictors of survival (P=0.03 and <0.001). Our study suggests a prognostic role for mitotane therapy and objective response to platinum-based chemotherapy.

  3. Prospective evaluation of mitotane toxicity in adrenocortical cancer patients treated adjuvantly.

    PubMed

    Daffara, Fulvia; De Francia, Silvia; Reimondo, Giuseppe; Zaggia, Barbara; Aroasio, Emiliano; Porpiglia, Francesco; Volante, Marco; Termine, Angela; Di Carlo, Francesco; Dogliotti, Luigi; Angeli, Alberto; Berruti, Alfredo; Terzolo, Massimo

    2008-12-01

    Toxicity of adjuvant mitotane treatment is poorly known; thus, our aim was to assess prospectively the unwanted effects of adjuvant mitotane treatment and correlate the findings with mitotane concentrations. Seventeen consecutive patients who were treated with mitotane after radical resection of adrenocortical cancer (ACC) from 1999 to 2005 underwent physical examination, routine laboratory evaluation, monitoring of mitotane concentrations, and a hormonal work-up at baseline and every 3 months till ACC relapse or study end (December 2007). Mitotane toxicity was graded using NCI CTCAE criteria. All biochemical measurements were performed at our center and plasma mitotane was measured by an in-house HPLC assay. All the patients reached mitotane concentrations >14 mg/l and none of them discontinued definitively mitotane for toxicity; 14 patients maintained consistently elevated mitotane concentrations despite tapering of the drug. Side effects occurred in all patients but were manageable with palliative treatment and adjustment of hormone replacement therapy. Mitotane affected adrenal steroidogenesis with a more remarkable inhibition of cortisol and DHEAS than aldosterone. Mitotane induced either perturbation of thyroid function mimicking central hypothyroidism or, in male patients, inhibition of testosterone secretion. The discrepancy between salivary and serum cortisol, as well as between total and free testosterone, is due to the mitotane-induced increase in hormone-binding proteins which complicates interpretation of hormone measurements. A low-dose monitored regimen of mitotane is tolerable and able to maintain elevated drug concentrations in the long term. Mitotane exerts a complex effect on the endocrine system that may require multiple hormone replacement therapy.

  4. sHDL Nanoparticles: A Novel Therapeutic Strategy for Adrenocortical Carcinomas

    PubMed Central

    Subramanian, Chitra; Kuai, Rui; Zhu, Qing; White, Peter; Moon, James; Schwendeman, Anna; Cohen, Mark S.

    2015-01-01

    Background Chemotherapeutic strategies for adrenocortical carcinoma (ACC) carry significant toxicities. Cholesterol is critical for ACC cell growth and steroidogenesis and ACC cells over-express scavenger receptor BI (SR-BI) that uptakes cholesterol from circulating high-density lipoprotein (HDL). We hypothesize that cholesterol-free synthetic-HDL nanoparticles (sHDL) will deplete cholesterol and synergize with chemotherapeutics to achieve enhanced anticancer effects at lower (less toxic) drug levels. Methods Anti proliferative efficacy of ACC cells for the combinations of sHDL with chemotherapeutics was tested by cell-Titer Glo. Cortisol levels were measured from the culture media. Effect on steroidogenesis was measured by RT-PCR. Induction of apoptosis was evaluated by flow cytometry. Results Combination-Index (CI) for sHDL and either etoposide(E), cisplatin(P) or mitotane(M) demonstrated synergy (CI<1) for anti-proliferation. sHDL alone or in combination with chemo drugs was able to reduce cortisol production by 70-90% compared to cisplatin alone or controls (p<0.01). RT-PCR indicated significant inhibition of steroidogenic enzymes for sHDL (p<0.01 vs. no sHDL). Combination therapy with sHDL increased apoptosis by 30-50% compared to drug or sHDL alone (p<0.03) confirmed by mitochondrial potential decrease. Conclusion sHDL can act synergistically and lower the amount of M/E/P needed for anticancer efficacy in ACC in part due to cholesterol starvation. This novel treatment strategy warrants further investigation translationally. PMID:26582501

  5. Clinical Score Predicting Long-Term Survival after Repeat Resection for Recurrent Adrenocortical Carcinoma

    PubMed Central

    Tran, Thuy B; Maithel, Shishir K; Pawlik, Timothy M; Wang, Tracy S; Hatzaras, Ioannis; Phay, John E; Fields, Ryan C; Weber, Sharon M; Sicklick, Jason K; Yopp, Adam C; Duh, Quan-Yang; Solorzano, Carmen C; Votanopoulos, Konstantinos I; Poultsides, George A

    2017-01-01

    BACKGROUND Adrenocortical carcinoma (ACC) is an aggressive malignancy typically resistant to chemotherapy and radiation. Surgery, even in the setting of locally recurrent or metastatic disease, remains the only potentially curative option. However, the subset of patients who will benefit from repeat resection in this setting remains ill defined. The objective of this study was to propose a prognostic clinical score that facilitates selection of patients for repeat resection of recurrent ACC. STUDY DESIGN Patients who underwent curative-intent repeat resection for recurrent ACC at 1 of 13 academic medical centers participating in the US ACC Study Group were identified. End points included morbidity, mortality, and overall survival. RESULTS Fifty-six patients underwent repeat curative-intent resection for recurrent ACC (representing 21% of 265 patients who underwent resection for primary ACC) from 1997 to 2014. Median age was 52 years. Sites of resected recurrence included locoregional only (54%), lung only (14%), liver only (12%), combined locoregional and lung (4%), combined liver and lung (4%), and other distant sites (12%). Thirty-day morbidity and mortality rates were 40% and 5.4%, respectively. Cox regression analysis revealed that the presence of multifocal recurrence, disease-free interval <12 months, and extrapulmonary distant metastases were independent predictors of poor survival. A clinical score consisting of 1-point each for the 3 variables demonstrated good discrimination in predicting survival after repeat resection (5-year: 72% for 0 points, 32% for 1 point, 0% for 2 or 3 points; p = 0.0006, area under the curve = 0.78). CONCLUSIONS Long-term survival after repeat resection for recurrent ACC is feasible when 2 of the following factors are present: solitary tumor, disease-free interval >12 months, and locoregional or pulmonary recurrence. PMID:27618748

  6. Long noncoding RNA profiles of adrenocortical cancer can be used to predict recurrence.

    PubMed

    Glover, A R; Zhao, J T; Ip, J C; Lee, J C; Robinson, B G; Gill, A J; Soon, P S H; Sidhu, S B

    2015-02-01

    Adrenocortical carcinoma (ACC) is an aggressive malignancy with high rates of recurrence following surgical resection. Long noncoding RNAs (lncRNAs) play an important role in cancer development. Pathogenesis of adrenal tumours have been characterised by mRNA, microRNA and methylation expression signatures, but it is unknown if this extends to lncRNAs. This study describes lncRNA expression signatures in ACC, adrenal cortical adenoma (ACA) and normal adrenal cortex (NAC) and presents lncRNAs associated with ACC recurrence to identify novel prognostic and therapeutic targets. RNA was extracted from freshly frozen tissue with confirmation of diagnosis by histopathology. Focused lncRNA and mRNA transcriptome analysis was performed using the ArrayStar Human LncRNA V3.0 microarray. Differentially expressed lncRNAs were validated using quantitative reverse transcriptase-PCR and correlated with clinical outcomes. Microarray of 21 samples (ten ACCs, five ACAs and six NACs) showed distinct patterns of lncRNA expression between each group. A total of 956 lncRNAs were differentially expressed between ACC and NAC, including known carcinogenesis-related lncRNAs such as H19, GAS5, MALAT1 and PRINS (P≤0.05); 85 lncRNAs were differentially expressed between ACC and ACA (P≤0.05). Hierarchical clustering and heat mapping showed ACC samples correctly grouped compared with NAC and ACA. Sixty-six differentially expressed lncRNAs were found to be associated with ACC recurrence (P≤0.05), one of which, PRINS, was validated in a group of 20 ACCs and also found to be associated with metastatic disease on presentation. The pathogenesis of adrenal tumours extends to lncRNA dysregulation and low expression of the lncRNA PRINS is associated with ACC recurrence.

  7. Targeting heterogeneity of adrenocortical carcinoma: Evaluation and extension of preclinical tumor models to improve clinical translation

    PubMed Central

    Hantel, Constanze; Shapiro, Igor; Poli, Giada; Chiapponi, Costanza; Bidlingmaier, Martin; Reincke, Martin; Luconi, Michaela; Jung, Sara; Beuschlein, Felix

    2016-01-01

    In recent years it has been recognized that clinical translation of novel therapeutic strategies for patients with adrenocortical carcinoma (ACC) often fails. These disappointing results indicate that the currently utilized tumor models only poorly reflect relevant pathophysiology and, thereby, do not predict clinical applicability of novel pharmacological approaches. However, also the development of new preclinical ACC models has remained a challenge with only one human cell line (NCI-H295R) and one recently established human pediatric xenograft model (SJ-ACC3) being available for this highly heterogeneous malignancy. Our current study furthermore reveals a poor reproducibility of therapeutic action between different clones of the most commonly used tumor model NCI-H295R. In an attempt to broaden the current preclinical armamentarium, we aimed at the development of patient-individual tumor models. During these studies, one xenograft (MUC-1) displayed marked engraftment and sustained tumor growth. MUC-1 tumor analysis revealed highly vascularized, proliferating and SF-1 positive xenografts. In a next step, we characterized all currently available human tumor models for ACC for Ki67, SF-1 and EGF-receptor status in comparison with MUC-1-xenografts. In addition, we established a primary culture, which is now viable over 31 passages with sustained nuclear SF-1 and cytoplasmic 3βHSD immuno-positivity. Subsequent investigation of therapeutic responsiveness upon treatment with the current systemic gold standard EDP-M (etoposide, doxorubicin, cisplatin and mitotane) demonstrated maintenance of the clinically observed drug resistance for MUC-1 exclusively. In summary, we provide evidence for a novel patient-derived tumor model with the potential to improve clinical prediction of novel therapeutic strategies for patients with ACC. PMID:27764813

  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. Contralateral adrenal suppression on adrenocortical scintigraphy provides good evidence showing subclinical cortisol overproduction from unilateral adenomas.

    PubMed

    Katabami, Takuyuki; Ishii, Satoshi; Obi, Ryusei; Asai, Shiko; Tanaka, Yasushi

    2016-12-30

    Unilateral and/or predominant uptake on adrenocortical scintigraphy (ACS) may be related to autonomous cortisol overproduction in patients with subclinical Cushing's syndrome (SCS). However, there is no information regarding whether increased tracer uptake on the tumor side or decreased uptake on the contralateral side on ACS is more greatly associated with inappropriate cortisol production. Therefore, we evaluated the relationship between quantitative (131)I-6β-iodomethyl-norcholesterol ((131)I-NP-59) uptake in both adrenal glands and parameters of autonomic cortisol secretion and attempted to set a cut off for SCS detection. The study included 90 patients with unilateral adrenal adenoma who fulfilled strict criteria. The diagnosis of SCS was based on serum cortisol ≥3.0 μg/dL after 1-mg dexamethasone suppression test (DST) with at least 1 other hypothalamus-pituitary-adrenal axis function abnormality. Twenty-two (27.7%) subjects were diagnosed with SCS. The uptake rate on the affected side in the SCS group was comparable to that in the non-functioning adenoma group. In contrast, the uptake rate on the contralateral side was lower and the laterality ratio significantly higher in the SCS group. The two ACS indices were correlated with serum cortisol levels after a 1-mg DST, but uptake on the tumor side was not. Tumor size was also important for the functional statuses of adrenal tumors and NP-59 imaging patterns. The best cut-off point for the laterality ratio to detect SCS was 3.07. These results clearly indicate that contralateral adrenal suppression in ACS is good evidence showing subclinical cortisol overproduction.

  10. 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

  11. Steroidogenic enzyme profile in an androgen-secreting adrenocortical oncocytoma associated with hirsustism.

    PubMed

    Tetsi Nomigni, Milène; Ouzounian, Sophie; Benoit, Alice; Vadrot, Jacqueline; Tissier, Frédérique; Renouf, Sylvie; Lefebvre, Hervé; Christin-Maitre, Sophie; Louiset, Estelle

    2015-06-01

    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.

  12. 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.

  13. Liposomal polychemotherapy improves adrenocortical carcinoma treatment in a preclinical rodent model.

    PubMed

    Hantel, Constanze; Jung, Sara; Mussack, Thomas; Reincke, Martin; Beuschlein, Felix

    2014-06-01

    Owing to high relapse rates and early metastatic spread, prognosis in adrenocortical carcinoma (ACC) patients remains poor, highlighting the importance of developing new treatment alternatives for them. Recently, polychemotherapy regimens including etoposide, doxorubicin, and cisplatin together with mitotane (EDP-M) have been defined as the standard treatment for late-stage disease patients. Nevertheless, the administration of conventional cytostatic drugs is associated with severe and dose-limiting side effects. In an attempt to optimize existing clinical treatment regimens, in this study, we investigated the therapeutic efficacy of EDP-M in comparison with that of a paclitaxel-modified scheme (paclitaxel, doxorubicin, cisplatin plus mitotane (PDP-M)) in preclinical in vitro and in vivo models. In addition, based on an extraordinary uptake phenomenon of liposomes in ACC cells, we further evaluated liposomal variants of these protocols (etoposide, liposomal doxorubicin, liposomal cisplatin plus mitotane (LEDP-M) and nab-paclitaxel, liposomal doxorubicin, liposomal cisplatin plus mitotane (LPDP-M)). In vitro, PDP-M was more potent in the induction of apoptosis and inhibition of cell viability as well as cell proliferation than EDP-M. Following the administration of a single therapeutic cycle, we further demonstrated that LEDP-M and LPDP-M exerted significant antitumoral effects in vivo, which were not as evident upon EDP-M and PDP-M treatments. These results were confirmed in a long-term experiment, in which the highest and sustained antitumoral effects were observed for LEDP-M. In summary, liposomal cytostatic substances could represent a promising option that deserves testing in appropriate clinical protocols for the treatment of ACC patients.

  14. Non pigmented melanocytic nevus of the oral cavity: a case report with emphasis on the surgical excision procedures.

    PubMed

    Porrini, R; Valente, G; Colombo, E; Cannas, M; Sabbatini, M

    2013-01-01

    We report a case of a 37-year-old caucasian woman presenting a 1 cm pinkish nodular asymptomatic lesion of the hard palate, slowly growing in the last years. The lesion underwent to biopsy. Histological analysis showed the nevus tissue layered under a continuous squamous epithelium. The stroma contained nests of medium-sized round cells, with regular monomorphous nuclei. The nevus cells were immunohistochemically positive for S-100 protein, while melanin, visualized by Masson-Fontana silver staining, was absent. Therefore a diagnosis of non pigmented melanocytic nevus was formulated. Because of its rarity and to avoid any risk of malignant transformation, a surgical treatment with wide excision was chosen; the surgical wound was previously covered with a membrane of fibrin and autologous platelets, and subsequently sutured, resulting in a total heal. This procedure seems to be the most reliable to approach melanocytic lesions of the oral cavity. Clinical diagnosis of non-pigmented nevi, either flat or protruding, is difficult, because the nevus shows a pinkish colour that is indistinguishable from that of the surrounding mucosa. Moreover, attention is required when similar clinical evidence occurs, because the localization inside the oral cavity may offer several problems of differential diagnosis.

  15. The etiology and molecular genetics of human pigmentation disorders

    PubMed Central

    Baxter, Laura L.; Pavan, William J.

    2012-01-01

    Pigmentation, defined as the placement of pigment in skin, hair, and eyes for coloration, is distinctive because the location, amount, and type of pigmentation provides a visual manifestation of genetic heterogeneity in pathways regulating the pigment-producing cells, melanocytes. The scope of this genetic heterogeneity in humans ranges from normal to pathological pigmentation phenotypes. Clinically normal human pigmentation encompasses a variety of skin and hair color as well as with punctate pigmentation such as melanocytic nevi (moles) or ephelides (freckles), while clinically abnormal human pigmentation exhibits markedly reduced or increased pigment levels, known as hypopigmentation and hyperpigmentation, respectively. Elucidation of the molecular genetics underlying pigmentation has revealed genes important for melanocyte development and function. Furthermore, many pigmentation disorders show additional defects in cells other than melanocytes, and identification of the genetic insults in these disorders has revealed pleiotropic genes, where a single gene is required for various functions, often in different cell types. Thus unravelling the genetics of easily visualized pigmentation disorders has identified molecular similarities between melanocytes and less visible cell types/tissues, revealing a common cellular origin and/or common genetic regulatory pathways. Herein we discuss notable human pigmentation disorders and their associated genetic alterations, focusing on the fact that the developmental genetics of pigmentation abnormalities is instructive for understanding normal pathways governing development and function of melanocytes. PMID:23799582

  16. Pigmented eccrine poroma: dermoscopic and confocal features

    PubMed Central

    Bombonato, Caterina; Piana, Simonetta; Moscarella, Elvira; Lallas, Aimillios; Argenziano, Giuseppe; Longo, Caterina

    2016-01-01

    Eccrine poroma is a rare benign adnexal tumor of epithelial cells originating from the terminal ductal portion of the sweat glands that is typically located on palms and soles, although other cutaneous sites can be affected [1]. It is usually nonpigmented even if there is a pigmented variant that corresponds to 17% of cases and it is usually underdiagnosed, since it is mistakenly confused with other pigmented tumors [2,3]. Dermoscopy and reflectance confocal microscopy (RCM) may assist in the correct diagnosis of this tumor. Herein, we report one case of pigmented eccrine poroma (PEP) that simulated clinically a cutaneous melanoma or a basal cell carcinoma. Dermoscopy and RCM excluded the possibilities of those two diagnoses; the overall confocal findings were suggestive for a benign epithelial tumor. Histology was fundamental to diagnose this lesion as a pigmented eccrine poroma. Even if the diagnosis of eccrine poroma remains histopathological still, as in this case report, noninvasive tools such as dermoscopy and RCM examinations can be of help to rule out the diagnosis of melanoma. Larger studies on this rare pigmented variant of eccrine poroma could shed new light on the identification of specific diagnostic dermoscopic and confocal features. PMID:27648386

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. A polymorphic form of steroidogenic factor-1 is associated with adrenocorticotropin resistance in y1 mouse adrenocortical tumor cell mutants.

    PubMed

    Frigeri, Claudia; Tsao, Jennivine; Cordova, Martha; Schimmer, Bernard P

    2002-10-01

    ACTH resistance in mutant derivatives of the Y1 mouse adrenocortical tumor cell line results from a defect that affects the activity of steroidogenic factor-1 (SF1), thereby preventing the expression of the melanocortin-2 receptor. In this report, we show that the SF1 genes in ACTH-resistant mutants differ from the gene in ACTH-responsive Y1 cells by two base changes-one that changes an Ala to Ser at codon 172, and one in the third position of codon 3 that does not affect the protein sequence. Furthermore, several of the mutants contain multiple copies of this alternate SF1 gene (SF1(S172)) on acentric chromosome fragments. The SF1(S172) allele represents a polymorphism rather than a spontaneous mutation because the two SF1 alleles can be traced to the hybrid mouse strain (C57L/J x A/HeJ) from which the original adrenal tumor was derived. The SF1(A172) allele also is found in C57Bl/6J and C57Bl/10J mice, whereas the SF1(S172) allele also is found in C3H/HeJ and DBA/2J mice. The two forms of SF1 had only modest differences in activity suggesting that the SF1 polymorphism per se is not directly responsible for ACTH resistance. Our results indicate that the SF1(S172) allele is a marker of ACTH resistance in this family of adrenocortical tumor cells.

  3. Expression of adiponectin receptors in mouse adrenal glands and the adrenocortical Y-1 cell line: adiponectin regulates steroidogenesis.

    PubMed

    Li, Ping; Sun, Fei; Cao, Huang-Ming; Ma, Qin-Yun; Pan, Chun-Ming; Ma, Jun-Hua; Zhang, Xiao-Na; Jiang, He; Song, Huai-Dong; Chen, Ming-Dao

    2009-12-25

    Obesity is frequently associated with malfunctions of the hypothalamus-pituitary-adrenal (HPA) axis and hyperaldosteronism, but the mechanism underlying this association remains unclear. Since the adrenal glands are embedded in adipose tissue, direct cross-talk between adipose tissue and the adrenal gland has been proposed. A previous study found that adiponectin receptor mRNA was expressed in human adrenal glands and aldosterone-producing adenoma (APA). However, the expression of adiponectin receptors in adrenal glands has not been confirmed at the protein level or in other species. Furthermore, it is unclear whether adiponectin receptors expressed in adrenal cells are functional. We found, for the first time, that adiponectin receptor (AdipoR1 and AdipoR2) mRNA and protein were expressed in mouse adrenal and adrenocortical Y-1 cells. However, adiponectin itself was not expressed in mouse adrenal or Y-1 cells. Furthermore, adiponectin acutely reduced basal levels of corticosterone and aldosterone secretion. ACTH-induced steroid secretion was also inhibited by adiponectin, and this was accompanied by a parallel change in the expression of the key genes involved in steroidogenesis. These findings indicate that adiponectin may take part in the modulation of steroidogenesis. Thus, adiponectin is likely to have physiological and/or pathophysiological significance as an endocrine regulator of adrenocortical function.

  4. First Case Report of a Sporadic Adrenocortical Carcinoma With Gastric Metastasis and a Synchronous Gastrointestinal Stromal Tumor of the Stomach.

    PubMed

    Kovecsi, Attila; Jung, Ioan; Bara, Tivadar; Bara, Tivadar; Azamfirei, Leonard; Kovacs, Zsolt; Gurzu, Simona

    2015-09-01

    Adrenocortical carcinoma is a rare tumor with high aggresivity that can associate systemic metastases. A 71-year-old man was hospitalized for gastric cancer. The abdominal computed tomography also revealed a tumor above the right kidney. Total gastrectomy and right adrenalectomy were performed. The encapsulated tumor of the adrenal gland weighed 560 grams and presented diffuse tumor architecture under microscope, with capsular, sinusoidal, and vascular invasion. The large tumor cells had a polygonal shape, with slight basophilic, eosinophilic, or vacuolated cytoplasm, pleomorphic nuclei, and a high mitotic rate. In the stomach, the protruded tumor was covered by normal mucosa; under microscope, the tumor cells were observed only in the submucosal layer. In primary adrenal tumor and gastric metastasis the tumor cells were marked by vimentin, inhibin, synaptophysin, neuron-specific enolase, and calretinin. Based on these criteria, the diagnosis of adrenocortical carcinoma (ACC) with gastric metastasis and no lymph node metastases was established. A synchronous 10 × 10-mm-sized gastrointestinal stromal tumor (GIST) of the stomach, without mitoses, was also identified. So far, as we know, this is the 15th case of ever reported synchronous/metachronous sporadic ACCs; the ACC-related gastric metastases either synchronous ACC and GIST, has not been reported in the literature previously.

  5. Drug interactions with mitotane by induction of CYP3A4 metabolism in the clinical management of adrenocortical carcinoma.

    PubMed

    Kroiss, Matthias; Quinkler, Marcus; Lutz, Werner K; Allolio, Bruno; Fassnacht, Martin

    2011-11-01

    Mitotane [1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane, (o,p'-DDD)] is the only drug approved for the treatment for adrenocortical carcinoma (ACC) and has also been used for various forms of glucocorticoid excess. Through still largely unknown mechanisms, mitotane inhibits adrenal steroid synthesis and adrenocortical cell proliferation. Mitotane increases hepatic metabolism of cortisol, and an increased replacement dose of glucocorticoids is standard of care during mitotane treatment. Recently, sunitinib, a multityrosine kinase inhibitor (TKI), has been found to be rapidly metabolized by CYP3A4 during mitotane treatment, indicating clinically relevant drug interactions with mitotane. We here summarize the current evidence concerning mitotane-induced changes in hepatic monooxygenase expression, list drugs potentially affected by mitotane-related CYP3A4 induction and suggest alternatives. For example, using standard doses of macrolide antibiotics is unlikely to reach sufficient plasma levels, making fluoroquinolones in many cases a superior choice. Similarly, statins such as simvastatin are metabolized by CYP3A4, whereas others like pravastatin are not. Importantly, in the past, several clinical trials using cytotoxic drugs but also targeted therapies in ACC yielded disappointing results. This lack of antineoplastic activity may be explained in part by insufficient drug exposure owing to enhanced drug metabolism induced by mitotane. Thus, induction of CYP3A4 by mitotane needs to be considered in the design of future clinical trials in ACC.

  6. The effect of types I and III interferons on adrenocortical cells and its possible implications for autoimmune Addison's disease.

    PubMed

    Hellesen, A; Edvardsen, K; Breivik, L; Husebye, E S; Bratland, E

    2014-06-01

    Autoimmune Addison's disease (AAD) is caused by selective destruction of the hormone-producing cells of the adrenal cortex. As yet, little is known about the potential role played by environmental factors in this process. Type I and/or type III interferons (IFNs) are signature responses to virus infections, and have also been implicated in the pathogenesis of autoimmune endocrine disorders such as type 1 diabetes and autoimmune thyroiditis. Transient development of AAD and exacerbation of established or subclinical disease, as well as the induction of autoantibodies associated with AAD, have been reported following therapeutic administration of type I IFNs. We therefore hypothesize that exposure to such IFNs could render the adrenal cortex susceptible to autoimmune attack in genetically predisposed individuals. In this study, we investigated possible immunopathological effects of type I and type III IFNs on adrenocortical cells in relation to AAD. Both types I and III IFNs exerted significant cytotoxicity on NCI-H295R adrenocortical carcinoma cells and potentiated IFN-γ- and polyinosine-polycytidylic acid [poly (I : C)]-induced chemokine secretion. Furthermore, we observed increased expression of human leucocyte antigen (HLA) class I molecules and up-regulation of 21-hydroxylase, the primary antigenic target in AAD. We propose that these combined effects could serve to initiate or aggravate an ongoing autoimmune response against the adrenal cortex in AAD.

  7. The Role of the Pituitary-Adrenocortical Axis System in the Regulation of Secretion of Digestive Glands of Wrestlers during Sports and Postsports Ontogenesis

    ERIC Educational Resources Information Center

    Panov, Sergei F.; Panova, Irina P.; Volunskaya, Elena V.; Chebotarev, Andrei V.

    2016-01-01

    According to many researchers its necessary to research a hormonal profile in order to determine mechanisms of regulation of functions of the digestive conveyor during sports activities. In the paper the results of the carried out research on studying of a role of pituitary-adrenocortical axis system of adaptive reactions in activities of the…

  8. 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…

  9. 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, ...

  10. Pretreatment of pigments to prepare liquids for enteric coating.

    PubMed

    Bölcskei, E; Bajdik, J; Müller, J; Knop, K; Kleinebudde, P; Pintye-Hódi, K

    2008-07-01

    Film coating fluids commonly contain different pigments. The objective of this work was a study of the distribution of these particles in the coating film. Different pretreatment forms (pigment suspension, pigment paste and untreated pigments) were applied. They were incorporated into a Eudragit L 30 D-55 dispersion. The surface roughness and the mechanical properties of the free films indicated, that the most homogeneous film was obtained with the pigment paste. The homogeneity of the film was investigated by mechanical testing. The protective effect of the coating did not vary with the application of pigments in different forms, but the appearance of the coated tablets underwent a considerable change.

  11. Detection of Pigment Networks in Dermoscopy Images

    NASA Astrophysics Data System (ADS)

    Eltayef, Khalid; Li, Yongmin; Liu, Xiaohui

    2017-02-01

    One of the most important structures in dermoscopy images is the pigment network, which is also one of the most challenging and fundamental task for dermatologists in early detection of melanoma. This paper presents an automatic system to detect pigment network from dermoscopy images. The design of the proposed algorithm consists of four stages. First, a pre-processing algorithm is carried out in order to remove the noise and improve the quality of the image. Second, a bank of directional filters and morphological connected component analysis are applied to detect the pigment networks. Third, features are extracted from the detected image, which can be used in the subsequent stage. Fourth, the classification process is performed by applying feed-forward neural network, in order to classify the region as either normal or abnormal skin. The method was tested on a dataset of 200 dermoscopy images from Hospital Pedro Hispano (Matosinhos), and better results were produced compared to previous studies.

  12. Predicting Phenotype from Genotype: Normal Pigmentation*

    PubMed Central

    Valenzuela, Robert K.; Henderson, Miquia S.; Walsh, Monica H.; Garrison, Nanibaa’A.; Kelch, Jessica T.; Cohen-Barak, Orit; Erickson, Drew T.; Meaney, F. John; Walsh, J. Bruce; Cheng, Keith C.; Ito, Shosuke; Wakamatsu, Kazumasa; Frudakis, Tony; Thomas, Matthew; Brilliant, Murray H.

    2013-01-01

    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

  13. 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.

  14. 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.

  15. An intracellular anion channel critical for pigmentation.

    PubMed

    Bellono, Nicholas W; Escobar, Iliana E; Lefkovith, Ariel J; Marks, Michael S; Oancea, Elena

    2014-12-16

    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.

  16. Light Chain Deposition Disease Diagnosed with Laser Micro-dissection, Liquid Chromatography, and Tandem Mass Spectrometry of Nodular Glomerular Lesions

    PubMed Central

    Kasagi, Tomomichi; Nobata, Hironobu; Suzuki, Keisuke; Miura, Naoto; Banno, Shogo; Takami, Akiyoshi; Yamashita, Taro; Ando, Yukio; Imai, Hirokazu

    2017-01-01

    A 42-year-old man developed nephrotic syndrome and rapidly progressive renal failure. Kidney biopsy demonstrated nodular glomerulosclerosis, negative Congo red staining, and no deposition of light or heavy chains. Laser micro-dissection and liquid chromatography with tandem mass spectrometry of nodular lesions revealed the presence of a kappa chain constant region and kappa III variable region, which signified light chain deposition disease. Dexamethasone and thalidomide were effective in decreasing the serum levels of free kappa light chain from 147.0 to 38.0 mg/L, eliminating proteinuria, and halting the worsening of the kidney dysfunction, with serum creatinine levels stable around 4.0 mg/dL for 3 years. PMID:28050001

  17. 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.

  18. 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.

  19. Bilateral periventricular nodular heterotopia with mental retardation and syndactyly in boys: a new X-linked mental retardation syndrome.

    PubMed

    Dobyns, W B; Guerrini, R; Czapansky-Beilman, D K; Pierpont, M E; Breningstall, G; Yock, D H; Bonanni, P; Truwit, C L

    1997-10-01

    Bilateral periventricular nodular heterotopia (BPNH) is a recently recognized malformation of neuronal migration, and perhaps proliferation, in which nodular masses of gray matter line the walls of the lateral ventricles. Most affected individuals have epilepsy and normal intelligence with no other congenital anomalies. A striking skew of the sex ratio has been observed because 31 of 38 probands have been female, and one gene associated with BPNH was recently mapped to chromosome Xq28. We report three unrelated boys with a new multiple congenital anomaly-mental retardation syndrome that consists of BPNH, cerebellar hypoplasia, severe mental retardation, epilepsy, and syndactyly. Variable abnormalities included focal or regional cortical dysplasia, cataracts, and hypospadius. We hypothesize that this syndrome involves the same Xq28 locus as isolated BPNH, and we review the expanding number of syndromes associated with BPNH.

  20. 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.

  1. The focal differentiation of pigment cells.

    PubMed

    Whimster, I W

    1979-05-01

    A study has been made of the normal development and of the regeneration after excision of the groups of large pigment cells which form the spotted skin pattern of the gecko Eublepharis macularius, together with the effects of neonatal graft transplantation on this pattern. The results all indicate strongly that such groups of specialized pigment cells are not clones but the product of an induction process. This is then compared with the neural reflex mechanism by which the skin pattern of Chamaeoleo dilepis is formed.

  2. RISK ASSESSMENT FOR THE DYE AND PIGMENT ...

    EPA Pesticide Factsheets

    This risk assessment calculates the maximum loadings of constituents found in dyes and pigment industries waste streams which can be disposed in different types of waste management units without causing health benchmarks to be exceeded at plausible receptor locations. The assessment focuses on potential risks from volatilization and leaching to groundwater of constituents disposed in surface impoundments and landfills with either clay liners or composite liners. This product will be used by EPA decision makers to assist in determining whether certain waste streams generated by the dyes and pigments industries should be designated as hazardous.

  3. Clonal immunoglobulin gene rearrangement in nodular lymphoid hyperplasia of the gastrointestinal tract associated with common variable immunodeficiency.

    PubMed

    Laszewski, M J; Kemp, J D; Goeken, J A; Mitros, F A; Platz, C E; Dick, F R

    1990-09-01

    The authors report a case of common variable immunodeficiency associated with nodular lymphoid hyperplasia of the gastrointestinal tract in which a clonal population of lymphoid cells was detected by immunophenotypic and genotypic studies on tissue obtained by colonoscopic biopsy. The patient has been followed up for more than 50 months without clinical, radiographic, or pathologic evidence of lymphoma. The significance of clonal rearrangement in the setting of immunodeficiency and the role of genotypic studies in defining lymphoid malignancy are discussed.

  4. Chiari type 1 malformation and periventricular nodular heterotopia in a 6-year-old boy with congenital hemiplegia: a case report.

    PubMed

    Kaushik, Jaya Shankar; Sharma, Suvasini; Aneja, Satinder; Kumar, Atin

    2014-01-01

    A 6-year-old boy presented with weakness of the right upper and lower limbs, noted since infancy. Magnetic resonance imaging of the brain revealed periventricular nodular heterotopia lining the trigone and occipital horns of bilateral lateral ventricles along with herniation of the cerebellar tonsils below the foramen magnum suggestive of Chiari type 1 malformation. The association of periventricular nodular heterotopia with Chiari type 1 malformation has not been described earlier in children.

  5. Characterization of nodular and thermal defects in hafnia/silica multilayer coatings using optical, photothermal, and atomic force microscopy

    SciTech Connect

    Stolz, C.J.; Yoshiyama, J.M.; Salleo, A.; Wu, Z.L.; Green, J.; Krupka, R.

    1997-12-24

    Multilayer coatings manufactured from metallic hafnium and silica sources by reactive electron beam deposition, are being developed for high fluence optics in a fusion laser with a wavelength of 1053 nm and a 3 ns pulse length. Damage threshold studies have revealed a correlation between laser damage and nodular defects, but interestingly laser damage is also present in nodule-free regions. Photothermal studies of optical coatings reveal the existence of defects with strong optical absorption in nodule-free regions of the coating. A variety of microscopic techniques were employed to characterize the effects for a better understanding of the thermal properties of nodular defects and role of thermal defects in laser damage. Photothermal microscopy, utilizing the surface thermal lensing technique, was used to map the thermal characteristics of 3 mm x 3 mm areas of the coatings. High resolution subaperture scans, with a 1 pm step size and a 3 um pump beam diameter, W= conducted on the defects to characterize their photothermal properties. Optical and atomic force microscopy was used to visually identify defects and characterize their topography. The defects were then irradiated to determine the role of nodular and thermal defects in limiting the damage threshold of the multilayer.

  6. Nodular sclerosing classical Hodgkin lymphoma masquerading as acute suppurative-necrotizing lymphadenitis.

    PubMed

    Florentine, Barbara D; Cohen, Alen N

    2014-03-01

    The diagnosis of nodular sclerosing classical Hodgkin lymphoma (NSCHL) by fine-needle aspiration (FNA) biopsy has historically been a diagnostic challenge due to the usual paucicellularity of the specimen. This case report, and other previously published reports, suggests that there is another facet to the potentially challenging diagnosis of this particular variant of Hodgkin lymphoma (HL): the presence of suppurative-necrotizing changes mimicking an infectious etiology. The patient presented here underwent FNA biopsy of an acutely enlarged supraclavicular lymph node and cytologic smears showed marked acute inflammation in a background of necrosis. A diagnosis of infectious suppurative lymphadenitis was made at that time. After a negative infectious work-up with infectious disease consultation, an excisional biopsy was performed and the patient was definitively diagnosed with NSCHL. The presence of neoplastic Hodgkin and Reed-Sternberg cells in the purulent exudate was minimal and only appropriately identified after retrospective review. This particular subtype of classical HL represents a potential pitfall in FNA biopsy cytology. Consequently, the cytopathologist and surgeon should always consider this entity in the differential diagnosis of a suppurative, lymphadenitis-like aspirate, and pursue repeat FNA or an excisional biopsy if there is any clinical index of suspicion.

  7. 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

  8. 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

  9. Identification of a duplication of Xq28 associated with bilateral periventricular nodular heterotopia.

    PubMed

    Fink, J M; Dobyns, W B; Guerrini, R; Hirsch, B A

    1997-08-01

    Bilateral periventricular nodular heterotopia (BPNH) is a malformation of neuronal migration and is characterized by nodules of heterotopic gray matter lining the lateral ventricles of the brain. The majority of BPNH patients are female and have epilepsy as a sole clinical manifestation of their disease. Familial BPNH has been mapped to Xq28 by linkage analysis. A multiple congenital anomaly-mental retardation syndrome (BPNH/MR) was recently delineated in three unrelated boys with BPNH, cerebellar hypoplasia, severe mental retardation, epilepsy, and syndactyly. High-resolution chromosome analysis revealed a subtle abnormality of Xq28 in one of the boys with BPNH/MR syndrome. FISH with cosmids and YACs from Xq28 further characterized this abnormality as a 2.25-3.25-Mb inverted duplication. No abnormality of Xq28 was detected by G-banding or FISH in the other two boys. These data support the linkage assignment of BPNH to band Xq28 and narrow the critical region to the distal 2.25-3.25 Mb of Xq28.

  10. 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.

  11. Papillary carcinoma of thyroid with exuberant nodular fasciitis-like stroma. Report of three cases.

    PubMed

    Chan, J K; Carcangiu, M L; Rosai, J

    1991-03-01

    Three examples of an unusual morphologic variant of papillary thyroid carcinoma (PTC) are reported. The presence of a prominent stromal component resulted in low-power microscopic appearances resembling fibroadenoma, phyllodes tumor, or fibrocystic disease of the breast in two cases. The carcinomatous component grew in the form of anastomosing narrow tubules, clustered glands, solid sheets with or without squamous differentiation, and/or papillae, and exhibited the typical nuclear features of PTC. The abundant stroma had a nodular fasciitis-like quality and was composed of short fascicles of spindle cells separated by varying amounts of mucoid matrix, collagen, and extravasated red blood cells; this was interpreted as an exuberant mesenchymal reaction to the carcinoma. The importance of recognizing this variant of PTC is that, when one encounters a fibroproliferative lesion of the thyroid, a diligent search should be made for papillary carcinoma. This variant also must be distinguished from the vastly more aggressive papillary carcinomas with anaplastic transformation and the so-called carcinosarcomas.

  12. Changes of the blood lymphocyte population following /sup 131/I treatment for nodular goiter

    SciTech Connect

    Blomgren, H.; Petrini, B.; Wasserman, J.; Schnell, P.O.; Lundell, G.

    1987-02-01

    The blood lymphocyte population was examined in 34 patients who were treated with /sup 131/I for toxic or atoxic nodular goiter. The patients received one to three doses of 300-550 MBq of /sup 131/I administered at 1 week intervals. Lymphocyte counts were significantly reduced both 1 and 6 weeks after treatment. This reduction was accompanied by a changed composition of the lymphocyte population. The frequency of lymphocytes expressing membrane receptors for C'3 (EAC-rosette forming) was significantly reduced 1 and 6 weeks after /sup 131/I-administration. At 6 weeks there was a slight but statistically significant increase of the frequency of T-cells as identified by Leu 1 monoclonal antibodies. This was largely caused by an increased proportion of helper/induced T-cells as identified by Leu 3a monoclonals. /sup 131/I-treatment also reduced the capacity of lymphocytes to secrete immunoglobulins (Ig) upon PWM-stimulation. The most pronounced effect was observed for IgM. Secretion of IgG and IgA were less reduced. Mitogenic stimulations of lymphocytes with PHA and ConA were not significantly changed. We conclude that these changes observed, with the exception of mitogen reactivity, are essentially similar to those occurring after external radiation therapy for cancer. We speculate that blood lymphocytes passing through the continuously irradiated gland are damaged mainly by emitted beta-particles.

  13. Nodular lymphoid hyperplasia: A marker of low-grade inflammation in irritable bowel syndrome?

    PubMed Central

    Piscaglia, Anna Chiara; Laterza, Lucrezia; Cesario, Valentina; Gerardi, Viviana; Landi, Rosario; Lopetuso, Loris Riccardo; Calò, Giovanni; Fabbretti, Giovanna; Brisigotti, Massimo; Stefanelli, Maria Loredana; Gasbarrini, Antonio

    2016-01-01

    AIM To evaluate the prevalence of nodular lymphoid hyperplasia (NLH) in adult patients undergoing colonoscopy and its association with known diseases. METHODS We selected all cases showing NLH at colonoscopy in a three-year timeframe, and stratified them into symptomatic patients with irritable bowel syndrome (IBS)-type symptoms or suspected inflammatory bowel disease (IBD), and asymptomatic individuals undergoing endoscopy for colorectal cancer screening. Data collection included medical history and final diagnosis. As controls, we considered all colonoscopies performed for the aforementioned indications during the same period. RESULTS One thousand and one hundred fifty colonoscopies were selected. NLH was rare in asymptomatic individuals (only 3%), while it was significantly more prevalent in symptomatic cases (32%). Among organic conditions associated with NLH, the most frequent was IBD, followed by infections and diverticular disease. Interestingly, 31% of IBS patients presented diffuse colonic NLH. NLH cases shared some distinctive clinical features among IBS patients: they were younger, more often female, and had a higher frequency of abdominal pain, bloating, diarrhoea, unspecific inflammation, self-reported lactose intolerance and metal contact dermatitis. CONCLUSION About 1/3 of patients with IBS-type symptoms or suspected IBD presented diffuse colonic NLH, which could be a marker of low-grade inflammation in a conspicuous subset of IBS patients. PMID:28028368

  14. 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

  15. A Case of Oncocytic Adrenocortical Neoplasm of Borderline (Uncertain) Malignant Potential.

    PubMed

    Shenouda, Mina; Brown, Linda G; Denning, Krista L; Pacioles, Toni

    2016-06-13

    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

  16. Preclinical progress and first translational steps for a liposomal chemotherapy protocol against adrenocortical carcinoma.

    PubMed

    Jung, Sara; Nagy, Zoltan; Fassnacht, Martin; Zambetti, Gerard; Weiss, Max; Reincke, Martin; Igaz, Peter; Beuschlein, Felix; Hantel, Constanze

    2016-10-01

    Systemic therapy of adrenocortical carcinoma (ACC) is limited by heterogeneous tumor response and adverse effects. Recently, we demonstrated anti-tumor activity of LEDP-M (etoposide, liposomal doxorubicin, liposomal cisplatin, mitotane), a liposomal variant of EDP-M (etoposide, doxorubicin, cisplatin, mitotane). To improve the therapeutic efficacy and off-target profiles of the clinical gold standard EDP-M, we investigated liposomal EDP-M regimens in different preclinical settings and in a small number of ACC patients with very advanced disease. Short- and long-term experiments were performed on two ACC models (SW-13 and SJ-ACC3) in vivo We evaluated the anti-tumoral effects and off-target profiles of EDP-M, LEDP-M and a novel regimen L(l)EDP-M including liposomal etoposide. Furthermore, the role of plasma microRNA-210 as a therapeutic biomarker and first clinical data were assessed. Classical and liposomal protocols revealed anti-proliferative efficacy against SW-13 (EDP-M P < 0.01; LEDP-M: P < 0.001; L(l)EDP-M: P < 0.001 vs controls), whereas in SJ-ACC3, only EDP-M (P < 0.05 vs controls) was slightly effective. Long-term experiments in SW-13 demonstrated anti-tumor efficacy for all treatment schemes (EDP-M: P < 0.01, LEDP-M: P < 0.05, L(l)EDP-M P < 0.001 vs controls). The analysis of pre-defined criteria leading to study termination revealed significant differences for control (P < 0.0001) and EDP-M (P = 0.003) compared to L(l)EDP-M treatment. Raising its potential for therapy monitoring, we detected elevated levels of circulating microRNA-210 in SW-13 after LEDP-M treatment (P < 0.05). In contrast, no comparable effects were detectable for SJ-ACC3. However, overall histological evaluation demonstrated improved off-target profiles following liposomal regimens. The first clinical data indicate improved tolerability of liposomal EDP-M, thus confirming our results. In summary, liposomal EDP-M regimens represent promising

  17. Prevalence of simple nodular goiter and Hashimoto's thyroiditis in current, previous, and never smokers in a geographical area with mild iodine deficiency.

    PubMed

    Rendina, D; De Palma, D; De Filippo, G; De Pascale, F; Muscariello, R; Ippolito, R; Fazio, V; Fiengo, A; Benvenuto, D; Strazzullo, P; Galletti, F

    2015-03-01

    Simple nodular goiter and Hashimoto's thyroiditis are 2 frequent nonmalignant thyroid diseases. Tobacco smoking has detrimental effects on the endocrine system and in particular on thyroid function and morphology. The objective of this cross-sectional study, involving 1800 Caucasian adults from a geographical area with mild iodine deficiency, was to evaluate the relationship between tobacco smoking, smoking cessation, and the prevalence of simple nodular goiter and Hashimoto's thyroiditis. Thyroid status was evaluated by ultrasonic exploration of the neck, measurement of FT3, FT4, TSH, antibodies against thyroid peroxidase and thyroglobulin, and urinary iodine excretion. The fine-needle aspiration biopsy of significant nodules was also performed. Smoking habits were evaluated by a specific questionnaire and the calculation of number of pack years. Both current and previous smokers showed an increased risk of simple nodular goiter compared to never smokers after adjustment for potential confounders and known goitrogen factors. Interestingly, the simple nodular goiter risk was similar for never smokers and for previous smokers declaring a time since cessation of smoking for more than 69 months. Smoking habit was not associated to an increased risk of Hashimoto's thyroiditis.Smoking appears to be an independent risk factor for simple nodular goiter but not for Hashimoto's thyroiditis in an area with mild iodine deficiency. A prolonged withdrawal of smoking dramatically reduces the risk of simple nodular goiter occurrence.

  18. Locally differentiated cryptic pigmentation in the freshwater isopod Asellus aquaticus.

    PubMed

    Hargeby, A; Stoltz, J; Johansson, J

    2005-05-01

    A repeated pattern of background colour matching in animals is an indication that pigmentation may be cryptic. Here, we examine the relationship between pigmentation of the freshwater isopod Asellus aquaticus and background darkness in 29 lakes, wetlands and ponds in Southern Sweden. The results show that Asellus pigmentation was correlated with substrate darkness across all localities. In seven localities, in which two contrasting substrate types were noted, Asellus populations were differentiated with respect to pigmentation. These findings thus provide phenomenological support for cryptic pigmentation in Asellus. Pigmentation generally increased with body size, but the relationship between pigmentation and size differed among localities, possibly as a result of differences in correlational selection on pigmentation and size. Selection thus appears to have resulted in local differentiation over a small spatial scale, even within lakes and wetlands. This differentiation is a likely cause behind elevated phenotype variation noted in localities with two substrate types, suggesting that habitat heterogeneity promotes genetic diversity.

  19. 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)

  20. Pigmented poroma with unusual location and dermatoscopic features

    PubMed Central

    Kassuga, Luiza E. B. P.; Jeunon, Thiago; Sousa, Maria Auxiliadora Jeunon; Campos-do-Carmo, Gabriella

    2012-01-01

    Poroma is a benign adnexal neoplasm with atn “poroid”/ductal differentiation that mimics benign and malignant skin tumors. Histopathology shows circumscribed proliferation of poroid cells intermingled with a variable number of cuticular cells. We report a case of pigmented poroma located on the face that simulated clinically and dermatoscopically a pigmented basal cell carcinoma. The features of pigmented and non-pigmented poromas were revisited in order to assist in the diagnosis. PMID:23785609

  1. 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.

  2. Prostaglandin-induced iridial pigmentation in primates.

    PubMed

    Selén, G; Stjernschantz, J; Resul, B

    1997-02-01

    Latanoprost, a new ocular hypotensive prostaglandin F2 alpha analogue prodrug, was found to induce increased pigmentation of monkey irides in chronic toxicity studies. This prompted us to investigate the effect of naturally occurring prostaglandins on the monkey iris to determine whether this pigmentary effect is unique for latanoprost or whether it is a class effect of prostaglandins. PGF2 alpha-isopropyl ester (IE), PGE2-IE and latanoprost were applied topically to cynomolgus monkey eyes for 18-44 weeks. One eye of each animal was treated, while the other served as control. In addition, latanoprost was applied to sympathectomized monkey eyes. PGF2 alpha-IE, PGE2-IE, as well as latanoprost, induced increased pigmentation in the monkey eye. The first signs of this effect were seen after about two months of treatment. Latanoprost also induced increased pigmentation in sympathectomized eyes. It is concluded that both naturally occurring prostaglandins and their synthetic analogues can induce increased iridial pigmentation in cynomolgus monkeys, and that the effect does not require the presence of sympathetic nerves.

  3. 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

  4. Pigment Deposition in the Rat Retina.

    PubMed

    Hojman, Anne S; Otzen, Louise W D; Schrøder-Hansen, Lise Maj; Wegener, Karen M

    2015-08-01

    Incidental findings in the rat eye are not uncommon in acute and long-term toxicological studies. These findings can be associated with a number of causes unrelated to treatment with the test article, including congenital malformation, trauma, infection, metabolic disease, genetic predisposition, and age-related changes. The occurrence of pigment deposition in the retina of Wistar Hannover (Crl:WI (Han)) rats in a 4-week toxicity study is reported in this communication. The microscopic examination of the eyes in the 4-week toxicity study revealed focal yellow-brown pigment deposits in the retina, mainly located in the ganglion cell layer. The retinal pigment deposits were randomly distributed in the control and treated groups and were considered incidental. The deposits were clearly positive for ferric iron in the Perls' stain but not for lipofuscin by the Schmorl's and Long Ziehl-Neelsen methods. The iron-containing pigment is likely to represent hemosiderin accumulation after retinal micro-hemorrhage or could be indicative of the normal intraretinal iron transport and turnover.

  5. 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

  6. BRIEF COMMUNICATIONS: Picosecond spectroscopy of pyrrol pigments

    NASA Astrophysics Data System (ADS)

    Lippitsch, M. E.; Leitner, A.; Riegler, M.; Aussenegg, F. R.

    1982-05-01

    Picosecond fluorescence and absorption spectroscopy methods were used to study pyrromethenone, pyrromethene, and biliverdin. These methods made it possible to determine some details of the kinetics of various relaxation mechanisms. The results obtained provided a better understanding of the biological action of pyrrol pigments.

  7. The 503nm pigment of Escherichia coli

    PubMed Central

    Kamitakahara, Joyce R.; Polglase, W. J.

    1970-01-01

    The yield of cell protein was one-third less for streptomycin-dependent Escherichia coli B than for the wild-type parent strain when both were grown aerobically on a medium with limiting glucose, but anaerobically the yield of protein was similar for both strains. The transient pigment absorbing at 503nm that is known to be present in E. coli and other organisms was not detectable in streptomycin-dependent mutants nor in a non-dependent (energy-deficient) revertant. When wild-type E. coli B was grown on limiting glucose–salts medium containing 2,4 dinitrophenol, the yield of cell protein was decreased and formation of the 503nm pigment was inhibited. Fumarase, aconitase and glucose 6-phosphate dehydrogenase were de-repressed in E. coli B cells grown with excess of glucose in a medium containing 2,4-dinitrophenol. In air-oxidized, wild-type E. coli B cells, the 503nm pigment appeared before reduced cytochromes when gluconate was the substrate but failed to appear when succinate was the substrate. The results provide evidence for a role of the 503nm pigment in aerobic energy metabolism, possibly as an electron acceptor from NADPH. PMID:4395501

  8. "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.

  9. Pigment patterns in adult fish result from superimposition of two largely independent pigmentation mechanisms.

    PubMed

    Ceinos, Rosa M; Guillot, Raúl; Kelsh, Robert N; Cerdá-Reverter, José M; Rotllant, Josep

    2015-03-01

    Dorso-ventral pigment pattern differences are the most widespread pigmentary adaptations in vertebrates. In mammals, this pattern is controlled by regulating melanin chemistry in melanocytes using a protein, agouti-signalling peptide (ASIP). In fish, studies of pigment patterning have focused on stripe formation, identifying a core striping mechanism dependent upon interactions between different pigment cell types. In contrast, mechanisms driving the dorso-ventral countershading pattern have been overlooked. Here, we demonstrate that, in fact, zebrafish utilize two distinct adult pigment patterning mechanisms - an ancient dorso-ventral patterning mechanism, and a more recent striping mechanism based on cell-cell interactions; remarkably, the dorso-ventral patterning mechanism also utilizes ASIP. These two mechanisms function largely independently, with resultant patterns superimposed to give the full pattern.

  10. Single Nucleotide Polymorphism Microarray Analysis in Cortisol-Secreting Adrenocortical Adenomas Identifies New Candidate Genes and Pathways1 2

    PubMed Central

    Ronchi, Cristina L; Leich, Ellen; Sbiera, Silviu; Weismann, Dirk; Rosenwald, Andreas; Allolio, Bruno; Fassnacht, Martin

    2012-01-01

    The genetic mechanisms underlying adrenocortical tumor development are still largely unknown. We used high-resolution single nucleotide polymorphism microarrays (Affymetrix SNP 6.0) to detect copy number alterations (CNAs) and copy-neutral losses of heterozygosity (cnLOH) in 15 cortisol-secreting adrenocortical adenomas with matched blood samples. We focused on microalterations aiming to discover new candidate genes involved in early tumorigenesis and/or autonomous cortisol secretion. We identified 962 CNAs with a median of 18 CNAs per sample. Half of them involved noncoding regions, 89% were less than 100 kb, and 28% were found in at least two samples. The most frequently gained regions were 5p15.33, 6q16.1, 7p22.3-22.2, 8q24.3, 9q34.2-34.3, 11p15.5, 11q11, 12q12, 16q24.3, 20p11.1-20q21.11, and Xq28 (≥20% of cases), most of them being identified in the same three adenomas. These regions contained among others genes like NOTCH1, CYP11B2, HRAS, and IGF2. Recurrent losses were less common and smaller than gains, being mostly localized at 1p, 6q, and 11q. Pathway analysis revealed that Notch signaling was the most frequently altered. We identified 46 recurrent CNAs that each affected a single gene (31 gains and 15 losses), including genes involved in steroidogenesis (CYP11B1) or tumorigenesis (CTNNB1, EPHA7, SGK1, STIL, FHIT). Finally, 20 small cnLOH in four cases affecting 15 known genes were found. Our findings provide the first high-resolution genome-wide view of chromosomal changes in cortisol-secreting adenomas and identify novel candidate genes, such as HRAS, EPHA7, and SGK1. Furthermore, they implicate that the Notch1 signaling pathway might be involved in the molecular pathogenesis of adrenocortical tumors. PMID:22496620

  11. Rethinking the History of Artists' Pigments Through Chemical Analysis

    NASA Astrophysics Data System (ADS)

    Berrie, Barbara H.

    2012-07-01

    Following a brief overview of the history of analysis of artists' pigments, I discuss the illustrative example of lead-tin yellow. Recent advances in our knowledge of artists' use of red lakes, glassy pigments, and metallic pigments in works of cultural heritage, particularly European paintings, as determined from chemical analyses are described.

  12. 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.

  13. Origin of adult-type pigment cells forming the asymmetric pigment pattern, in Japanese flounder (Paralichthys olivaceus).

    PubMed

    Yamada, Toshiyuki; Okauchi, Masanori; Araki, Kazuo

    2010-12-01

    The flatfish-specific asymmetric pigment pattern depends on the asymmetric appearance of adult-type pigment cells after the late metamorphic stages. To understand the mechanism enabling the formation of this asymmetric pattern, we investigated the behavior of pigment cell latent precursors in postembryonic Japanese flounder, Paralichthys olivaceus, by analysis of the expression patterns of pigment lineage markers (colony stimulating factor 1 receptor, dopachrome tautomerase, kit) and the DiI (DiO) labeling test for latent precursors. We found that, throughout the larval stages, pigment cell latent precursors were predominantly localized along the dorsal and ventral margins of the flank symmetrically and migrated continuously from these regions to the lateral sides symmetrically, and after late metamorphic stages these precursors differentiated into adult-type pigment cells on the lateral side asymmetrically. We conclude that adult-type pigment cells that form the asymmetric pigment pattern are continuously derived from the dorsal and ventral margins of the flank during larval development.

  14. Dimerization of visual pigments in vivo

    PubMed Central

    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

    2016-01-01

    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

  15. Central posterior capsule pigmentation in a patient with pigment dispersion and previous ocular trauma: a case report.

    PubMed

    Al-Mezaine, Hani S

    2010-01-01

    We report a 55-year-old man with unusually dense, unilateral central posterior capsule pigmentation associated with the characteristic clinical features of pigment dispersion syndrome, including a Krukenberg's spindle and dense trabecular pigmentation in both eyes. A history of an old blunt ocular trauma probably caused separation of the anterior hyaloid from the back of the lens, thereby creating an avenue by which pigment could reach the potential space of Berger's from the posterior chamber.

  16. Lack of long-lasting effects of mitotane adjuvant therapy in a mouse xenograft model of adrenocortical carcinoma.

    PubMed

    Doghman, Mabrouka; Lalli, Enzo

    2013-12-05

    Mitotane is a widely used drug in the therapy of adrenocortical carcinoma (ACC). It is important to set up preclinical protocols to study the possible synergistic effects of its association with new drugs for ACC therapy. We assessed the efficacy of different routes of administration of mitotane (i.p. and oral) in inhibiting growth of H295R ACC cell xenografts in an adjuvant setting. Both formulations of mitotane could inhibit H295R xenografts growth only at short times after carcinoma cells inoculation, even though plasma mitotane levels approached or fell within the therapeutic range in humans. Our results show that mitotane adjuvant therapy is inadequate to antagonize long-term growth of H295R cancer cells xenografts and that care should then be taken in the design of preclinical protocols to evaluate the performance of new drugs in association with mitotane.

  17. 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

  18. Early hepatocellular carcinoma with high-grade atypia in small vaguely nodular lesions.

    PubMed

    Ojima, Hidenori; Masugi, Yohei; Tsujikawa, Hanako; Emoto, Katsura; Fujii-Nishimura, Yoko; Hatano, Mami; Kawaida, Miho; Itano, Osamu; Kitagawa, Yuko; Sakamoto, Michiie

    2016-04-01

    Multistep hepatocarcinogenesis progresses from dysplastic nodules to early hepatocellular carcinoma (eHCC) and to advanced HCC. The aim of the present study was to investigate the detailed histopathological features of eHCC. We investigated 66 small vaguely nodular lesions resected from 40 patients. The degree of cellular and structural atypia and stromal invasion were assessed. The immunohistochemical expression of HCC-related markers adenylate cyclase-associated protein 2 (CAP2), heat shock protein 70 (HSP70), Bmi-1, CD34 and h-caldesmon were evaluated. Of the 66 nodules, 10 were diagnosed as low-grade dysplastic nodules (LGDN), 10 as high-grade dysplastic nodules (HGDN) and 46 as eHCC. Among the 46 eHCC, 18 nodules (39.1%) showed marked stromal invasion and/or the presence of the scirrhous component and were subclassified as high-grade eHCC (HGeHCC). The remaining 28 eHCC, which lacked these features, were subclassified as low-grade eHCC (LGeHCC) and were examined further. HGeHCC showed high levels of cellular and structural atypia and large tumor size. The immunohistochemical expression of CAP2 and the area of sinusoidal vascularization showed increases from LGDN to HGeHCC. The density of arterial tumor vessels was high in HGeHCC compared with other nodule types. Cluster analysis of these parameters subclassified 65 nodules into HGeHCC-dominant, LGeHCC and HGDN-dominant, and LGDN-dominant groups. These results indicate the increased malignant potential of HGeHCC and suggest that it is already a transitional stage to advanced HCC. We consider that our grading classification system may be valuable for considering treatment strategies for eHCC around 2 cm in diameter.

  19. Challenges of identifying eczema in darkly pigmented skin.

    PubMed

    Myers, Joan

    2015-07-01

    There is a paucity of information about the difference in the presentation of eczema in darkly pigmented skin compared to children with fair or white skin. This article describes the possible challenges of diagnosing eczema in children with darkly pigmented skin. The physiological difference in darkly pigmented skin compared with fair or white skin is explored, and how eczema may be manifested and identified in darkly pigmented skin. The author uses the term darkly pigmented skin to describe children of black Caribbean, African or Asian descent.

  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.

  1. 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.

  2. Prevalence and Functional Consequence of TP53 Mutations in Pediatric Adrenocortical Carcinoma: A Children's Oncology Group Study

    PubMed Central

    Wasserman, Jonathan D.; Novokmet, Ana; Eichler-Jonsson, Claudia; Ribeiro, Raul C.; Rodriguez-Galindo, Carlos; Zambetti, Gerard P.; Malkin, David

    2015-01-01

    Purpose Adrenocortical carcinoma (ACC) is a rare pediatric malignancy. It occurs in excess among individuals with the Li-Fraumeni syndrome, which results primarily from germline mutations in the TP53 gene. Prior series exploring frequencies of germline TP53 mutation among children with ACC have been small, geographically limited, or subject to referral bias. The functional consequence of mutations has not been related to phenotype. We provide a genotype-phenotype analysis of TP53 mutations in pediatric ACC and propose a model for tissue-specific effects based on adrenocortical ontogeny. Patients and Methods Eighty-eight consecutive, unrelated children with ACC, unselected for family history, underwent germline TP53 sequencing. Rate and distribution of mutations were identified. Functional analysis was performed for novel TP53 variants. Correlation with the International Agency for Research on Cancer p53 database further delineated mutational distribution, association with family history, and risk for multiple primary malignancies (MPMs). Results Germline mutations were present in 50% of children. These mutations did not correspond to the conventional hotspot mutations. There was a wide range of mutant protein function. Patients bearing alleles encoding protein with higher functionality were less likely to have a strong family cancer history, whereas those with greater loss of function had MPMs and/or positive family history. In patients with MPMs, ACC was the most frequent initial malignancy. Finally, we demonstrated age-dependent rates of TP53 mutation positivity. Conclusion TP53 mutations are prevalent in children with ACC but decline with age. Mutations result in a broad spectrum of functional loss. Effect of individual mutations may predict carrier and familial disease penetrance with potentially broad implications for clinical surveillance and counseling. PMID:25584008

  3. Empowering patients and researchers through a common health information registry: a case example of adrenocortical carcinoma patients and researchers.

    PubMed

    Allwes, Deborah; Popovich, Michael L

    2007-01-01

    Adrenocortical Carcinoma is a rare malignant tumor that forms in the outer layer of tissue of the adrenal gland, which is a small gland situated on the anteriosuperior aspect of the kidneys. These glands produce steroid hormones, adrenaline, and noradrenaline that control heart rate, blood pressure, and other body functions. Because this cancer affects a limited number of patients, it is referred to as an Orphan disease, which is defined as a condition that affects fewer than 200,000 people nationwide. Internationally, there are 5,000-8,000 such diseases affecting an estimated 55 million people. There is often limited medical intervention for many of these conditions. With a small number of patients, and a correspondingly small number of providers and researches, this disease is a candidate for establishing a shareable information system that is used by the patient, provider, and researcher. This resource empowers the patient to support their care and treatment while allowing medical providers and researches to have valuable and broad access to patient activities and behaviors that may impact their treatment. Orphan disease registries are prime candidates for establishing health information resources that support communications between patients, providers, and researchers. As a resource, this information can be used to facilitate treatment protocols to include biomarker identification, testing and monitoring of new drugs. By empowering a common community of individuals that share a common disease, the potential to accelerate research and identify improved treatment options may also increase. This paper presents a strategic plan and design for implementing Orphan disease registries within an e-health environment that specifically links patients and providers with researchers. The Adrenocortical Carcinoma Registry will be used to demonstrate the implementation and potential of these systems.

  4. 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

  5. Mapping of Photosynthetic Pigments in Spanish Reservoirs

    NASA Astrophysics Data System (ADS)

    Peña-Martinez, R.; Domínguez-Gómez, J.-A.; de Hoyos, C.; Ruiz-Verdú, A.

    2004-05-01

    We present the preliminary results of the first stage of the project AO-594, which comprises the development and calibration of algorithms for photosynthetic pigment mapping in Spanish reservoirs. In the years 2001-2002, an extensive field campaign was made in 36 reservoirs and lakes in order to obtain a database of Rrs spectra (400-1000 nm), photosynthetic pigments concentration and phytoplankton composition. The sampled water bodies cover a wide range of environmental conditions, trophic levels and phytoplankton communities. As a first approach in algorithm development, we have explored the relationships between ratios of MERIS bands and pigment concentrations through simple linear regression analysis. The bands have been selected based on the spectral properties of each pigment and a peak analysis of the Rrs spectra. For chlorophyll a, we have found a very good linear relationship (R2 =0.919) using the ratio between bands 9 and 7. Similar results are found using band 8 instead of 7. In any case, the model derived for the whole range of concentrations (0-500 mg m3 ) fails for low values (<15 mg m-3 ). Possible solutions include the use of - non-linear models or the use of two different models depending on the ratio values. For cyanobacteria detection, the ratio between bands 9 and 6 (the later centred at 620 nm) shows a good correlation (R2 =0.723) with phycocyanin concentration measured fluorometrically, and better (R2 =0.945) with zeaxanthin measured using HPLC. The correlation of other indicator pigments with MERIS band ratios is less strong, but is still possible to develop algorithms accurate enough for bloom monitoring. We also discuss the problems found with the L2 MERIS reflectance imagery that we have tried to use for model calibration. We present the results of the study carried on six reservoirs in northeastern Spain. In a date coincident with a MERIS image (June 19th, 2003) we have collected pigment concentration and reflectance data measured from a

  6. 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

  7. Pigmented Pindborg tumor of the maxilla: A case report

    PubMed Central

    Priya, Subashchandrabose; Madanagopaal, Lakshmikanth Ramiah; Sarada, Venkaterwaran

    2016-01-01

    The calcifying epithelial odontogenic tumor (CEOT), also known as the Pindborg tumor, is a benign locally invasive neoplasm. Common variants of CEOT include noncalcifying, Langerhans cell, bone and cementum forming and clear cell, which have a prognostic significance. Pigmented variants are known to occur in other odontogenic tumors. However, a definitive pigmented variant of CEOT has not been reported in literature so far. Here, we report the first case of pigmented Pindborg tumor arising from the maxilla in a young female. The pigment was demonstrated as melanin by staining and confirmed by immunohistochemistry. The pigmented variant of CEOT did not recur within 18 months postsurgery. Our report indicates that it is essential to recognize the pigmented variant. We discuss the common variants of CEOT and potential histogenesis of the pigmented variant. Further studies are required to reveal the histogenesis of melanocytes and their pathological significance in the odontogenic tumors. PMID:27721633

  8. 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.

  9. Animal pigment bilirubin discovered in plants.

    PubMed

    Pirone, Cary; Quirke, J Martin E; Priestap, Horacio A; Lee, David W

    2009-03-04

    The bile pigment bilirubin-IXalpha is the degradative product of heme, distributed among mammals and some other vertebrates. It can be recognized as the pigment responsible for the yellow color of jaundice and healing bruises. In this paper we present the first example of the isolation of bilirubin in plants. The compound was isolated from the brilliant orange-colored arils of Strelitzia nicolai, the white bird of paradise tree, and characterized by HPLC-ESMS, UV-visible, (1)H NMR, and (13)C NMR spectroscopy, as well as comparison with an authentic standard. This discovery indicates that plant cyclic tetrapyrroles may undergo degradation by a previously unknown pathway. Preliminary analyses of related plants, including S. reginae, the bird of paradise, also revealed bilirubin in the arils and flowers, indicating that the occurrence of bilirubin is not limited to a single species or tissue type.

  10. FRUIT AND VEGETABLE PIGMENTS AS INDICATORS.

    PubMed

    Pratt, O B; Swartout, H O

    1930-05-09

    (1) Solutions of many fruit pigments act as indicators. (2) These solutions are easily prepared and stable, and the pH range of their color changes is in most cases conveniently near the neutral point (3) As liquid indicators they can be used in titrating acids, but not bases (4)Their greatest usefulness depends upon the fact that very satisfactory test papers can be made with them in a simple and inexpensive way.

  11. 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.

  12. Treatment of gingival pigmentation: a case series.

    PubMed

    Deepak, Prasad; Sunil, S; Mishra, R; Sheshadri

    2005-01-01

    A smile expresses a feeling of joy, success, sensuality, affection and courtesy, and reveals self confidence and kindness. The harmony of the smile is determined not only by the shape, the position and the color of the teeth but also by the gingival tissues. Gingival health and appearance are essential components of an attractive smile. Gingival pigmentation results from melanin granules, which are produced by melanoblasts. The degree of pigmentation depends on melanoblastic activity. Although melanin pigmentation of the gingiva is completely benign and does not present a medical problem, complaints of 'black gums' are common particularly in patients having a very high smile line (gummy smile). For depigmentation of gingiva different treatment modalities have been reported like- Bur abrasion, scraping, partial thickness flap, cryotherapy, electrosurgery and laser. In the present case series bur abrasion, scraping, partial thickness flap (epithelial excision) cryotherapy and electrosurgery have been tried for depigmentation, which are simple, effective and yield good results, along with good patient satisfaction. The problems encountered with some of these techniques have also been discussed.

  13. 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.

  14. Neurofibromatosis type 1 and pregnancy: The transformation of a nodular to cystic neurofibroma in the cervical region

    PubMed Central

    Ramos-Zúñiga, Rodrigo; Saldaña-Koppel, Daniel Alexander

    2015-01-01

    Background: The peripheral hallmarks of neurofibromatosis type 1 (NF1) are Café au lait and solid nodular neurofibromas. The morphological behavior of these lesions could be susceptible to modification during pregnancy. The present case report describes a case of cystic transformation of a nodular neurofibroma, with progressive growth and mass effect in the anterior cervical region, which was surgically resolved without any complications. Case Description: A 33-year-old female patient with a known personal history of NF1, with annual control of the peripheral neurofibromas and cerebral and spinal magnetic resonance imaging follow-ups. Under genetic counseling, she decides to get pregnant following all the medical advises. Once the pregnancy is confirmed, she starts to notice the growth of one of them adjacent to the left cervical region. Such neurofibroma presented with the progressive gradual increase and in the last month, she presented dysphagia, dysphonia, and postural pain localized by the mass effect. Once the pregnancy concluded, the microsurgical approach was scheduled for resection of the lesion, where a cystic mass was found within the walls of the neurofibroma. The resection was uneventful. Conclusion: The transformation of a nodular to cystic neurofibroma during pregnancy is a very rare presentation, which may exacerbate the clinical symptomatology depending on the topography of the lesion due to the mass effect it may create. This condition may alert to the recommendations and vigilance in patients with NF1, who are pregnant or are planning on a future pregnancy. The neurosurgical resolution in this region is safe and beneficial. PMID:26605110

  15. Contrast-enhanced ultrasonography in nodular splenomegaly associated with type B Niemann-Pick disease: an atypical hemangioma enhancement pattern.

    PubMed

    Benedetti, E; Proietti, A; Miccoli, P; Basolo, F; Ciancia, E; Erba, P A; Galimberti, S; Orsitto, E; Petrini, M

    2009-09-01

    Sommario INTRODUZIONE: La malattia di Niemann-Pick (NPD) tipo A e B è una patologia da accumulo di lipidi. Il tipo A è un disordine fatale dell'infanzia. Il tipo B è una forma non-neuronopatica ossevata sia nei bambini che negli adulti con possibile riscontro di epatomegalia e/o splenomegalia (nodulare) durante un esame ecografico. Il tipo C dipende da un difetto nel trasporto del colesterolo. METODI: Una donna di 21 anni si è presentata al Pronto Soccorso con febbre, faringodinia e dolore al quadrante addominale superiore sinistro. Gli esami ematochimici hanno evidenziato anemia, piastrinopenia, aumento delle AST, ALT, GGT, FA, LDH trigliceridi, colesterolo totale, e ridotto HDL. La PCR per CMV ed EBV era negativa. La radiografia del torace era negativa. L'ecografia transaddominale ha rilevato splenomegalia (>22 cm long axis) con una lesione ipoecogena irregolare subcapsulare al polo superiore compatibile con infarto splenico e la presenza di multiple lesioni nodulari iperecogene con diametro da 1 cm fino a 5. RISULTATI: È stata quindi eseguita una ecografia con mezzo di contrasto con SonoVue (Bracco) che ha confermato la presenza di un infarto splenico. Le lesioni nodulari mostravano un enhancement in fase arteriosa con wash out in fase parenchimatosa tardiva. La F-FDG-PET ha mostrato un uptake nodulare splenico. Nel sospetto di un processo linfoproliferativo è stata eseguita una splenectomia. La diagnosi è stata di NPD tipo B con infarto splenico e le lesioni nodulari sono risulate essere emangiomi. DISCUSSIONE: Concludendo, la CEUS ha confermato la diagnosi e l'estenzione dell'infarto splenico, ma l'enhancement nodulare atipico supportato dalle immagini F-FDG-PET è stato fuorviante, suggerendo l'ipotesi di lesioni linfomatose.

  16. The photochromic effect of bismuth vanadate pigments. Part I: Synthesis, characterization and lightfastness of pigment coatings

    NASA Astrophysics Data System (ADS)

    Tücks, A.; Beck, H. P.

    2005-04-01

    We report on investigations of the photochromic effect of BiVO 4 pigments. Emphasis is placed on an approach widely used in industrial color testing. By means of colorimetry Δ E ab*-values, which measure the perceived color difference, can be calculated from reflectance spectra of non-illuminated and illuminated pigment coatings. Pigments were prepared by either wet-chemical precipitation or solid-state reactions. Depending on the choice of starting compounds, lightfastness was found to vary significantly. Small amounts of impurity phases do not seem to affect photochromism. In contrast, impurities like Fe and Pb cause intense photochromism. The role of Fe is suggested by trace analyses, which (in case of pigments synthesized by precipitation reactions) reveal a correlation between concentration and Δ E ab*. Indications are found that other effects like pigment-lacquer interactions might also be of importance. Difference reflectance spectra turn out to vary in shape depending on the type and concentration of impurities or dopants. For BiVO 4 at least three different mechanisms of photochromism can be assumed.

  17. The photochromic effect of bismuth vanadate pigments. Part I: Synthesis, characterization and lightfastness of pigment coatings

    SciTech Connect

    Tuecks, A.; Beck, H.P. . E-mail: hp.beck@mx.uni-saarland.de

    2005-04-15

    We report on investigations of the photochromic effect of BiVO{sub 4} pigments. Emphasis is placed on an approach widely used in industrial color testing. By means of colorimetry {delta}E{sub ab}*-values, which measure the perceived color difference, can be calculated from reflectance spectra of non-illuminated and illuminated pigment coatings. Pigments were prepared by either wet-chemical precipitation or solid-state reactions. Depending on the choice of starting compounds, lightfastness was found to vary significantly. Small amounts of impurity phases do not seem to affect photochromism. In contrast, impurities like Fe and Pb cause intense photochromism. The role of Fe is suggested by trace analyses, which (in case of pigments synthesized by precipitation reactions) reveal a correlation between concentration and {delta}E{sub ab}*. Indications are found that other effects like pigment-lacquer interactions might also be of importance. Difference reflectance spectra turn out to vary in shape depending on the type and concentration of impurities or dopants. For BiVO{sub 4} at least three different mechanisms of photochromism can be assumed.

  18. Cushing's syndrome caused by nodular adrenal hyperplasia in children with McCune-Albright syndrome.

    PubMed

    Kirk, J M; Brain, C E; Carson, D J; Hyde, J C; Grant, D B

    1999-06-01

    McCune-Albright syndrome consists of fibrous dysplasia of bone, café-au-lait skin pigmentation, and endocrine dysfunction (usually precocious puberty). Other endocrine abnormalities occur in a minority of patients, and of these, Cushing's syndrome is the least often recognized. We present 5 children (4 girls) with features of McCune-Albright syndrome who had Cushing's syndrome in the infantile period (<6 months). In 2 children spontaneous resolution occurred, but the remaining 3 required bilateral adrenalectomy. In addition, all 4 girls have experienced precocious puberty, and 3 children demonstrated radiologic evidence of nephrocalcinosis. Understanding of the underlying defect causing McCune-Albright syndrome emphasizes the importance of searching for other endocrine dysfunction in these children.

  19. Ultrastructural Characterization of Hyperactive Endothelial Cells, Pericytes and Fibroblasts in Hypertrophic and Nodular Port Wine Stain Lesions.

    PubMed

    Gao, L; Yin, R; Wang, H; Guo, W; Song, W; Nelson, J S; Tan, W; Wang, G

    2017-02-09

    Port wine stain (PWS) is a congenital vascular malformation of human skin involving the superficial vascular plexus,(1-4) but the molecular pathogenesis of these lesions remains incompletely understood.(5-8) We herein performed a transmission electron microscopy (TEM) study to determine the main pathological characteristics and ultrastructure of various cell types, including endothelial cells (ECs), pericytes, fibroblasts and keratinocytes, in hypertrophic and nodular PWS. The study was approved by the Investigational Review Board at the Xijing Hospital, Xi'an, China. This article is protected by copyright. All rights reserved.

  20. Periventricular nodular heterotopia, frontonasal encephalocele, corpus callosal dysgenesis and arachnoid cyst: A constellation of abnormalities in a child with epilepsy.

    PubMed

    Krishnan, Prasad; Chattopadhyay, Arijit; Saha, Manash

    2014-01-01

    A 7-year-old male child presented with poorly controlled generalized tonic-clonic seizures. On examination, he was mentally retarded, deaf and had a swelling at the root on the nose. Computed tomography scan done previously revealed a left temporal arachnoid cyst (AC) due to which he was referred for surgery. However, magnetic resonance imaging revealed a constellation of abnormalities - all of which could be responsible for his seizures. The combination of periventricular nodular heterotopias with encepaholcele is rarely described in the literature, and more infrequently so its combination with AC and callosal dysgenesis - the Chudley-Mccullough syndrome. We describe the case and review relevant literature on this subject.

  1. Compositions of sedimentary strata, nodular features and veins at the base of Mount Sharp, Gale crater, Mars: an APXS perspective

    NASA Astrophysics Data System (ADS)

    Thompson, L. M.; Gellert, R.; Spray, J. G.; Berger, J. A.; Boyd, N.; Campbell, J. L.; de Souza, E.; Pavri, B.; Perrett, G. M.; VanBommel, S.; Yen, A. S.

    2015-10-01

    Since the MSL Curiosity rover arrived at the lower most slopes of Mount Sharp, the APXS instrument has encountered four distinct bedrock compositions, two of which have not previously been encountered on the mission, indicating different source regions and/or post -depositional alteration/diagenetic histories. Raised, resistant nodular features are interpreted as diagenetic and exhibit elevated,and positively correlated Mg, S and Ni. Late vein networks and associated resistant fins reveal a complex texture and chemistry, recording multiple fluid flow events.

  2. Comparison of the Effects of PRKAR1A and PRKAR2B Depletion on Signaling Pathways, Cell Growth, and Cell Cycle Control of Adrenocortical Cells

    PubMed Central

    Basso, F.; Rocchetti, F.; Rodriguez, S.; Nesterova, M.; Cormier, F.; Stratakis, C.; Ragazzon, B.; Bertherat, J.; Rizk-Rabin, M.

    2016-01-01

    The cyclic AMP/protein kinase A signaling cascade is one of the main pathways involved in the pathogenesis of adrenocortical tumors. The PKA R1A and R2B proteins are the most abundant regulatory subunits in endocrine tissues. Inactivating mutations of PRKAR1A are associated with Carney complex and a subset of sporadic tumors and the abundance of R2B protein is low in a subset of secreting adrenocortical adenomas. We previously showed that PRKAR1A and PRKAR2B inactivation have anti-apoptotic effects on the adrenocortical carcinoma cell line H295R. The aim of this study was to compare the effects of PRKAR1A and PRKAR2B depletion on cell proliferation, apoptosis, cell signaling pathways, and cell cycle regulation. We found that PRKAR2B depletion is compensated by an upregulation in the abundance of R1A protein, whereas PRKAR1A depletion has no effect on the production of R2B. The depletion of either PRKAR1A or PRKAR2B promotes the expression of Bcl-xL and resistance to apoptosis; and is associated with a high percentage of cells in S and G2 phase, activates PKA and MEK/ERK pathways, and impairs the expression of IkB leading to activate the NF-κB pathway. Nonetheless, we observed differences in the regulation of cyclins. The depletion of PRKAR1A leads to the accumulation of cyclin D1 and p27kip, whereas the depletion of PRKAR2B promotes the accumulation of cyclin A, B, cdk1, cdc2, and p21Cip. In conclusion, although the depletion of PRKAR1A and PRKAR2B in adrenocortical cells has similar effects on cell proliferation and apoptosis; loss of these PKA subunits differentially affects cyclin expression. PMID:25268545

  3. Management of Nodular Lymphocyte Predominant Hodgkin Lymphoma in the Modern Era

    SciTech Connect

    King, Martin T.; Donaldson, Sarah S.; Link, Michael P.; Natkunam, Yasodha; Advani, Ranjana H.; Hoppe, Richard T.

    2015-05-01

    Purpose: To analyze treatment outcomes for nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) at a single institution. Patients and Methods: Patients with newly diagnosed NLPHL between 1996 and 2013 were reviewed retrospectively. Patients treated before 1996 were excluded because the majority received extended field radiation therapy (RT) alone. Results: Fifty-five patients (22 ≤ 21 years old) were identified. The median follow-up time was 6.8 years. Among 37 patients with limited-stage (I-II) disease, treatments included involved field RT at a median dose of 36 Gy (n=9), rituximab monotherapy (n=9), observation (n=3), and response-adaptive therapy (n=16), in which the RT dose was reduced from 25.5 Gy to 15 Gy or was eliminated based on interim imaging after chemotherapy. The 5-year progression-free survival (PFS) was 76.4% (95% confidence interval [CI], 63.1-92.4). Nine patients experienced progression, including 5 receiving rituximab, 2 undergoing observation, and 2 receiving response-adaptive therapy. Rituximab was associated with an inferior PFS compared with RT alone (P=.02). The difference in PFS between response-adaptive therapy and RT alone was not statistically significant (P=.39). Among 18 patients with advanced-stage (III-IV) disease, treatments included chemotherapy alone (n=3), combined modality therapy (CMT) (n=2), response-adaptive therapy (n=2), rituximab (n=7), and observation (n=4). The 5-year PFS was 29.9% (CI, 13.3-67.4). Twelve patients experienced progression, including 1 receiving chemotherapy, 1 receiving CMT, 6 receiving rituximab, and 4 undergoing observation. There was no significant PFS difference between rituximab and non-rituximab therapies (P=.19) within the caveat of small sample sizes. In the entire cohort, 9 patients (3 with limited disease, 6 with advanced disease) experienced large cell transformation (LCT). Seven patients died; of those, 5 died with LCT. Conclusions: For limited disease, response-adaptive therapy

  4. High-contrast enzymatic immunohistochemistry of pigmented tissues

    PubMed Central

    Duncan, Sara M.; Seigel, Gail M.

    2016-01-01

    Historically, standard enzyme immunohistochemistry has been accomplished with brown (DAB, diaminobenzidine) substrate. This can become problematic in pigmented tissues, such as the retina, where brown pigment of retinal pigmented epithelial (RPE) cells can be easily confounded with brown substrate. Although immunofluorescence detection methods can overcome this challenge, fluorescence may fade over a period of weeks, while enzyme substrates allow for more long-lasting, archival results. In this report, we will describe a high-contrast enzyme immunohistochemistry method ideal for pigmented tissues that utilizes purple (VIP) substrate. We compared brown (DAB) and purple (VIP) substrates in enzyme immunohistochemistry experiments using human retina (paraffin sections) and monkey retinal pigmented epithelial cells (frozen sections), both containing brown pigmented cells. We compared substrates using several primary antibodies against markers that can be detected in the retina, including GFAP, VEGF, CD147 (EMMPRIN), RHO (rhodopsin) and PAX6. Methyl green was used as a counterstain for paraffin sections. A side-by-side comparison between DAB and VIP immunohistochemistry showed excellent contrast between pigmented cells and the purple VIP substrate in both human retinal tissue and monkey pigmented epithelial cells for all of the markers tested. This was a marked improvement over DAB staining in pigmented cells and tissues. For both paraffin sections and frozen sections of pigmented tissues, purple VIP substrate is an excellent alternative to brown DAB substrate and non-permanent immunofluorescence methods. PMID:27660801

  5. GREEN FLUORESCENT PIGMENT ACCUMULATED BY A MUTANT OF CELLVIBRIO GILVUS.

    PubMed

    LOVE, S H; HULCHER, F H

    1964-01-01

    Love, Samuel H. (Bowman Gray School of Medicine, Winston-Salem, N.C.), and Frank H. Hulcher. Green fluorescent pigment accumulated by a mutant of Cellvibrio gilvus. J. Bacteriol. 87:39-45. 1964.-A mutant of Cellvibrio gilvus, designated strain 139A, liberated a green, fluorescent pigment into the surrounding culture medium. A study of the factors which affected the accumulation of this pigment led to the development of a chemically defined medium which supported maximal pigment accumulation in aerated, liquid cultures. d-Glucose, glycine or l-serine, l-phenylalanine, l-proline, and l-lysine comprised the organic components of this medium. The visible absorption spectrum of the pigment showed a maximal band at 400 mmu (pH 7.0). A difference spectrum between reduced and oxidized pigment showed loss of the band at 400 mmu upon oxidation. However, a methanol-extractable, flavinelike compound occurred in the wild strain but not in the mutant. Ferric ions added to the defined medium stimulated growth, with a concomitant reduction of pigment accumulation. Pigment was formed at a maximal rate during the stationary growth phase, and the highest yield was obtained by 18 hr. Organic solvents did not extract the pigment from water solutions. One and sometimes two, compounds absorbing at 400 mmu could be eluted by ion-exchange chromatography on Cellex-P (H(+)), which was used to separate the pigment from other components in the culture supernatants so that the radioactivity of the pigment could be measured. The mutant synthesized C(14)-labeled pigment from d-glucose-U-C(14) and from each of four amino acids (glycine-1-C(14), l-phenylalanine-U-C(14), l-proline-U-C(14), and l-lysine-U-C(14). Delta-Amino-levulenic acid-4-C(14) did not contribute C(14) to the pigment.

  6. Origins of adult pigmentation: diversity in pigment stem cell lineages and implications for pattern evolution

    PubMed Central

    Spiewak, Jessica E.

    2014-01-01

    Summary Teleosts comprise about half of all vertebrate species and exhibit an extraordinary diversity of adult pigment patterns that function in shoaling, camouflage and mate choice and have played important roles in speciation. Here, we review recent studies that have identified several distinct neural crest lineages, with distinct genetic requirements, that give rise to adult pigment cells in fishes. These lineages include post-embryonic, peripheral nerve associated stem cells that generate black melanophores and iridescent iridophores, cells derived directly from embryonic neural crest cells that generate yellow-orange xanthophores, and bipotent stem cells that generate both melanophores and xanthophores. This complexity in adult chromatophore lineages has implications for our understanding of adult traits, melanoma, and the evolutionary diversification of pigment cell lineages and patterns. PMID:25421288

  7. Study on the autofluorescence profiles of iris pigment epithelium and retinal pigment epithetlium

    NASA Astrophysics Data System (ADS)

    Xu, Gaixia; Qu, Junle; Chen, Danni; Sun, Yiwen; Zhao, Lingling; Lin, Ziyang; Ding, Zhihua; Niu, Hanben

    2007-05-01

    Transplantation technique of retinal pigment epithelium has been noticeable in recent years and gradually put into clinical practice in treatment of retinal degenerative diseases. Generally, immunological, histochemical, and physical methods are used to study the iris pigment epithelium (IPE) and retinal pigment epithelium (RPE) cells, which need complex sample preparation. In this paper, we provided a simple autofluorescence microscopy to investigate the fresh porcine IPE and RPE cells without any pretreatment. The results showed that the morphology and size of both were similar, round and about 15 μm. The main flourophore in both cells was similar, i.e. lipofuscin. In additional, the autofluorescence spectrum of RPE shifted blue after light-induced damage by laser illuminating. Because it was easier for IPE to be damaged by laser than for RPE, and the power of one scanning operation to get a full image was strong enough to damage IPE sample, we hadn't get any satisfied autofluorescence spectrum of IPE.

  8. Origins of adult pigmentation: diversity in pigment stem cell lineages and implications for pattern evolution.

    PubMed

    Parichy, David M; Spiewak, Jessica E

    2015-01-01

    Teleosts comprise about half of all vertebrate species and exhibit an extraordinary diversity of adult pigment patterns that function in shoaling, camouflage, and mate choice and have played important roles in speciation. Here, we review studies that have identified several distinct neural crest lineages, with distinct genetic requirements, that give rise to adult pigment cells in fishes. These lineages include post-embryonic, peripheral nerve-associated stem cells that generate black melanophores and iridescent iridophores, cells derived directly from embryonic neural crest cells that generate yellow-orange xanthophores, and bipotent stem cells that generate both melanophores and xanthophores. This complexity in adult chromatophore lineages has implications for our understanding of adult traits, melanoma, and the evolutionary diversification of pigment cell lineages and patterns.

  9. Characterization of Sorolla's gouache pigments by means of spectroscopic techniques

    NASA Astrophysics Data System (ADS)

    Roldán, Clodoaldo; Juanes, David; Ferrazza, Livio; Carballo, Jorgelina

    2016-02-01

    This paper presents the characterization of the Joaquín Sorolla's gouache sketches for the oil on canvas series "Vision of Spain" commissioned by A. M. Huntington to decorate the library of the Hispanic Society of America in New York. The analyses were focused on the identification of the elemental composition of the gouache pigments by means of portable EDXRF spectrometry in a non-destructive mode. Additionally, SEM-EDX and FTIR analyses of a selected set of micro-samples were carried out to identify completely the pigments, the paint technique and the binding media. The obtained results have confirmed the identification of lead and zinc white, vermillion, earth pigments, ochre, zinc yellow, chrome yellow, ultramarine, Prussian blue, chromium based and copper-arsenic based green pigments, bone black and carbon based black pigments, and the use of gum arabic as binding media in the gouache pigments.

  10. Analytical Raman spectroscopic discrimination between yellow pigments of the Renaissance.

    PubMed

    Edwards, Howell G M

    2011-10-01

    The Renaissance represented a major advance in painting techniques, subject matter, artistic style and the use of pigments and pigment mixtures. However, most pigments in general use were still mineral-based as most organic dyes were believed to be fugitive; the historical study of artists' palettes and recipes has assumed importance for the attribution of art works to the Renaissance period. Although the application of diagnostic elemental and molecular spectroscopic techniques play vital and complementary roles in the analysis of art works, elemental techniques alone cannot definitively provide the data needed for pigment identification. The advantages and limitations of Raman spectroscopy for the definitive diagnostic characterisation of yellow pigments that were in use during the Renaissance is demonstrated here in consideration of heavy metal oxides and sulphides; these data will be compared with those obtained from analyses of synthetic yellow pigments that were available during the eighteenth and nineteenth Centuries which could have been used in unrecorded restorations of Renaissance paintings.

  11. Oral pigmented lesions: Clinicopathologic features and review of the literature

    PubMed Central

    da Silva-Jorge, Rogério; Jorge, Jacks; Lopes, Márcio A.; Vargas, Pablo A.

    2012-01-01

    Diagnosis of pigmented lesions of the oral cavity and perioral tissues is challenging. Even though epidemiology may be of some help in orientating the clinician and even though some lesions may confidently be diagnosed on clinical grounds alone, the definitive diagnosis usually requires histopathologic evaluation. Oral pigmentation can be physiological or pathological, and exogenous or endogenous. Color, location, distribution, and duration as well as drugs use, family history, and change in pattern are important for the differential diagnosis. Dark or black pigmented lesions can be focal, multifocal or diffuse macules, including entities such as racial pigmentation, melanotic macule, melanocytic nevus, blue nevus, smoker’s melanosis, oral melanoacanthoma, pigmentation by foreign bodies or induced by drugs, Peutz-Jeghers syndrome, Addison´s disease and oral melanoma. The aim of this review is to present the main oral black lesions contributing to better approach of the patients. Key words:Pigmentation, melanin, oral, diagnosis, management. PMID:22549672

  12. Mapping pigment distribution in mud samples through hyperspectral imaging

    NASA Astrophysics Data System (ADS)

    Mehrübeoglu, Mehrube; Nicula, Cosmina; Trombley, Christopher; Smith, Shane W.; Smith, Dustin K.; Shanks, Elizabeth S.; Zimba, Paul V.

    2015-09-01

    Mud samples collected from bodies of water reveal information about the distribution of microorganisms in the local sediments. Hyperspectral imaging has been investigated as a technology to identify phototropic organisms living on sediments collected from the Texas Coastal Bend area based on their spectral pigment profiles and spatial arrangement. The top pigment profiles identified through high-performance liquid chromatography (HPLC) have been correlated with spectral signatures extracted from the hyperspectral data of mud using fast Fourier transform (FFT). Spatial distributions have also been investigated using 2D hyperspectral image processing. 2D pigment distribution maps have been created based on the correlation with pigment profiles in the FFT domain. Among the tested pigments, the results show match among four out of five pigment distribution trends between HPLC and hyperspectral data analysis. Differences are attributed mainly to the difference between area and volume of scale between the HPLC analysis and area covered by hyperspectral imaging.

  13. Clinical, pathological, and molecular data on desmoplastic/nodular medulloblastoma: case studies and a review of the literature

    PubMed Central

    Siegfried, Aurore; Bertozzi, Anne Isabelle; Bourdeaut, Franck; Sevely, Annick; Loukh, Najat; Grison, Camille; Miquel, Catherine; Lafon, Delphine; Sevenet, Nicolas; Pietsch, Torsten; Dufour, Christelle; Delisle, Marie-Bernadette

    2016-01-01

    The aim of this study was to better define the clinical and biopathological features of patients with desmoplastic/nodular medulloblastoma (DNMB) and to further characterize this subgroup. 17 children aged < 5 years, with initial DNMB treated according to the HIT-SKK protocol, were evaluated. A retrospective central radiological review, a pathological and immunohistochemical study, and array-CGH and sequencing of germline SUFU and PTCH1 genes were performed. 15 histologically reviewed cases were confirmed as DNMB including three cases of medulloblastoma with extensive nodularity. Median age at diagnosis was 26 months. Radiology showed five cases with a vermis location and one with T2 hyperintensity. All cases showed a SHH immuno-profile. A 9q deletion was found in 6 cases, a MYCN–MYCL amplification in 1 case, and a SUFU germline mutation in 1 case (/9). The presence of SUFU and PTCH1 germline mutations agreed with previous reports. At 3 years, progression-free survival and overall-survival rates were 72 ± 15% and 85 ± 10%, respectively. The rate of recurrence was relatively high (4 patients). This may have been because chemotherapy was delayed in two cases. Age > 3 years, and residual tumor may also have been an explanation for recurrence. PMID:26857864

  14. Podocyte-Specific VEGF-A Gain of Function Induces Nodular Glomerulosclerosis in eNOS Null Mice

    PubMed Central

    Veron, Delma; Aggarwal, Pardeep K.; Velazquez, Heino; Kashgarian, Michael; Moeckel, Gilbert

    2014-01-01

    VEGF-A and nitric oxide are essential for glomerular filtration barrier homeostasis and are dysregulated in diabetic nephropathy. Here, we examined the effect of excess podocyte VEGF-A on the renal phenotype of endothelial nitric oxide synthase (eNOS) knockout mice. Podocyte-specific VEGF164 gain of function in eNOS−/− mice resulted in nodular glomerulosclerosis, mesangiolysis, microaneurysms, and arteriolar hyalinosis associated with massive proteinuria and renal failure in the absence of diabetic milieu or hypertension. In contrast, podocyte-specific VEGF164 gain of function in wild-type mice resulted in less pronounced albuminuria and increased creatinine clearance. Transmission electron microscopy revealed glomerular basement membrane thickening and podocyte effacement in eNOS−/− mice with podocyte-specific VEGF164 gain of function. Furthermore, glomerular nodules overexpressed collagen IV and laminin extensively. Biotin-switch and proximity ligation assays demonstrated that podocyte-specific VEGF164 gain of function decreased glomerular S-nitrosylation of laminin in eNOS−/− mice. In addition, treatment with VEGF-A decreased S-nitrosylated laminin in cultured podocytes. Collectively, these data indicate that excess glomerular VEGF-A and eNOS deficiency is necessary and sufficient to induce Kimmelstiel-Wilson–like nodular glomerulosclerosis in mice through a process that involves deposition of laminin and collagen IV and de-nitrosylation of laminin. PMID:24578128

  15. Active Mg Estimation Using Thermal Analysis: A Rapid Method to Control Nodularity in Ductile Cast Iron Production

    NASA Astrophysics Data System (ADS)

    Suárez, Ramon; Sertucha, Jon; Larrañaga, Pello; Lacaze, Jacques

    2016-10-01

    Appropriate nodularity in ductile iron castings is strongly associated with the presence of high enough not combined Mg dissolved in the melt to cast. However, the residual Mg which is commonly measured for production control accounts for both dissolved Mg and Mg combined as oxides and sulfides. To account for the uncertainties associated with such a control, it is quite usual to over treat the melt with the risk of porosity appearance. A new methodology based on thermal analysis has been developed in the present work so as to estimate the amount of free Mg dissolved in the melt ready for pouring. A combination of Te mixture and a new "reactive mixture" composed of sulfur plus a commercial inoculant has been prepared for this purpose. This reactive mixture is able to transform the magnesium remaining dissolved in the melt to combined forms of this element. Experiments performed both during start of production (when Mg overtreatment is usual) and during normal mass production indicate that important variations of free Mg occur without relevant changes in residual Mg content as determined by spectrometry. The method developed in the present work has shown to be highly effective to detect those melt batches where active Mg content is not high enough for guaranteeing a correct nodularity of castings. Selection of proper active Mg thresholds and a correct inoculation process are critical to avoid "false"-negative results when using this new method.

  16. Asymptomatic Multiple Myeloma Presenting as a Nodular Hepatic Lesion: A Case Report and Review of the Literature

    PubMed Central

    Huang, Hans; Bazerbachi, Fateh; Mesa, Hector; Gupta, Pankaj

    2015-01-01

    Background Plasma cell myeloma is the most common primary bone malignancy in adults. However, liver involvement in the form of an initial and asymptomatic nodular plasmacytoma is exceedingly rare. Case Report A 64-year-old male was found to have a right hepatic lobe nodule on a routine abdominal ultrasound prior to bariatric surgery. Liver biopsy revealed a plasma cell neoplasm that, given the location of the lesion, was favored to represent a lymphoma with prominent plasmacytic differentiation. Positron emission tomography (PET) demonstrated a hypermetabolic hepatic mass and identified multiple destructive bony lesions. Biopsy of a clavicular lesion revealed sheets of plasma cells and confirmed the diagnosis of multiple myeloma. The patient underwent 6 cycles of chemotherapy with cyclophosphamide, bortezomib, and dexamethasone before transitioning to lenalidomide and dexamethasone because of early disease progression. Although the patient had International Staging System I (low-risk) disease, his disease demonstrated an aggressive clinical course and resistance to multiple lines of therapy. Conclusion Extramedullary nodular hepatic plasmacytoma is exceedingly rare. Nevertheless, extramedullary plasmacytomas should be included in the differential diagnosis of patients with indistinct hepatic lesions visualized on computed tomography scan, especially if PET scans show associated bony lesions. In general, extramedullary plasmacytomas are a poor prognostic sign and a harbinger of an aggressive clinical course in the context of multiple myeloma. PMID:26730235

  17. Ionic dependence of adrenal steroidogenesis and ACTH-induced changes in the membrane potential of adrenocortical cells

    PubMed Central

    Matthews, E. K.; Saffran, M.

    1973-01-01

    1. The effects of changes of ionic environment upon corticosteroid production by rabbit adrenal glands have been investigated in vitro using a superfusion technique and on-line steroid analysis by an automated fluorescence method. In some experiments micro-electrode recordings of adrenocortical transmembrane potentials were made concomitantly with measurement of steroid output. 2. Adrenocorticotrophic hormone (ACTH), 10 m-u./ml., induced a sevenfold increase in corticosteroid production rate in normal Krebs solution. 3. The steroidogenic response to ACTH was not impaired after omission of [K]o for 1 hr but was inhibited following exposure to K+-free medium for 3 hr. Increase of [K]o tenfold to 47 mM increased the basal but not the ACTH-stimulated output of corticosteroid whereas raising [K]o twentyfold to 94 mM enhanced both the basal and ACTH-stimulated steroid production rate. In K+-free solution the adrenocortical cells hyperpolarized from - 67 to - 86 mV; subsequently on addition of ACTH they depolarized. Reintroduction of K+ restored the membrane potential. 4. Omission of Ca2+ partially depolarized the cells but only affected the steroidogenic response to ACTH in the presence of EDTA. A threefold increase of [Ca]o, to 7·68 mM, had no effect on either membrane potentials or steroid formation, but increasing [Ca]o tenfold to 25·6 mM partially blocked ACTH action. Increasing [Mg]o twentyfold to 22·6 mM had little effect on ACTH-stimulated corticosteroid output and Sr 2·56 mM, in substitution for Ca2+, supported ACTH action, but La, 0·25 mM, completely blocked the steroidogenic effect of ACTH. 5. Replacement of NaCl, 118 mM by choline chloride, 118 mM, was without effect on ACTH-induced steroidogenesis, whereas LiCl, 118 mM, reduced it by 50%. NaF, 1 and 10 mM, inhibited ACTH-induced steroidogenesis by approximately 60%. 6. Nupercaine, 10-4 M, inhibited the steroid response to ACTH with no effect upon membrane potentials: increasing the nupercaine

  18. Chlorpromazine-induced skin pigmentation with corneal and lens opacities.

    PubMed

    Huff, Laura S; Prado, Renata; Pederson, Jon F; Dunnick, Cory A; Lucas, Lisa M

    2014-05-01

    Chlorpromazine is known to cause abnormal oculocutaneous pigmentation in sun-exposed areas. We present the case of a psychiatric patient who developed blue-gray pigmentation of the skin as well as corneal and lens opacities following 7 years of chlorpromazine treatment. Ten months after discontinuation of chlorpromazine, the skin discoloration and anterior lens deposits showed partial improvement, but the corneal deposits remained unchanged. A review of the literature on the reversibility of chlorpromazine-induced abnormal oculocutaneous pigmentation also is provided.

  19. BASIS FOR ENHANCED BARRIER FUNCTION OF PIGMENTED SKIN

    PubMed Central

    Man, Mao-Qiang; Lin, Tzu-Kai; Santiago, Juan Luis; Celli, Anna; Zhong, Lily; Huang, Zhi-Ming; Roelandt, Truus; Hupe, Melanie; Sundberg, John P.; Silva, Kathleen A.; Crumrine, Debra; Martin-Ezquerra, Gemma; Trullas, Carles; Sun, Richard; Wakefield, Joan S.; Wei, Maria L.; Feingold, Kenneth R.; Mauro, Theodora M.; Elias, Peter M.

    2014-01-01

    Humans with darkly-pigmented skin display superior permeability barrier function in comparison to humans with lightly-pigmented skin. The reduced pH of the stratum corneum (SC) of darkly-pigmented skin could account for enhanced function, because acidifying lightly-pigmented human SC resets barrier function to darkly-pigmented levels. In SKH1 (non-pigmented) vs. SKH2/J (pigmented) hairless mice, we evaluated how a pigment-dependent reduction in pH could influence epidermal barrier function. Permeability barrier homeostasis is enhanced in SKH2/J vs. SKH1 mice, correlating with a reduced pH in the lower SC that co-localizes with the extrusion of melanin granules. Darkly-pigmented human epidermis also shows substantial melanin extrusion in the outer epidermis. Both acute barrier disruption and topical basic pH challenges accelerate re-acidification of SKH2/J (but not SKH1) SC, while inducing melanin extrusion. SKH2/J mice also display enhanced expression of the SC acidifying enzyme, secretory phospholipase A2f (sPLA2f). Enhanced barrier function of SKH2/J mice could be attributed to enhanced activity of two acidic pH-dependent, ceramide-generating enzymes, β-glucocerebrosidase and acidic sphingomyelinase, leading to accelerated maturation of SC lamellar bilayers. Finally, organotypic cultures of darkly-pigmented-bearing human keratinocytes display enhanced barrier function in comparison to lightly-pigmented cultures. Together, these results suggest that the superior barrier function of pigmented epidermis can be largely attributed to the pH-lowering impact of melanin persistence/extrusion and enhanced sPLA2f expression. PMID:24732399

  20. Production of luteoskyrin, a hepatotoxic pigment, by Penicillium islandicum Sopp.

    PubMed

    Ueno, Y; Ishikawa, I

    1969-09-01

    Various factors affecting the yields of luteoskyrin, a hepatotoxic mycotoxin, and related pigments in the liquid medium were studied. Maximal yields of luteoskyrin (0.13% by isolation) and of other pigments were attained in the late phase of the cultivation. The yield of the pigment was increased by supplying malt extract, malonic acid, glutamic acid, or asparagine. A useful material for preparation of (14)C-labeled luteoskyrin was 2-(14)C-malonate.