JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2010
Lai Wang
Abstract Thyroid hormone regulates terminal differentiation of growth plate chondrocytes in part through modulation of the Wnt/,-catenin signaling pathway. Insulin-like growth factor 1 (IGF-1) has been described as a stabilizer of ,-catenin, and thyroid hormone is a known stimulator of IGF-1 receptor expression. The purpose of this study was to test the hypothesis that IGF-1 signaling is involved in the interaction between the thyroid hormone and the Wnt/,-catenin signaling pathways in regulating growth plate chondrocyte proliferation and differentiation. The results show that IGF-1 and the IGF- receptor (IGF1R) stimulate Wnt-4 expression and ,-catenin activation in growth plate chondrocytes. The positive effects of IGF-1/IGF1R on chondrocyte proliferation and terminal differentiation are partially inhibited by the Wnt antagonists sFRP3 and Dkk1. T3 activates IGF-1/IGF1R signaling and IGF-1-dependent PI3K/Akt/GSK-3, signaling in growth plate chondrocytes undergoing proliferation and differentiation to prehypertrophy. T3 -mediated Wnt-4 expression, ,-catenin activation, cell proliferation, and terminal differentiation of growth plate chondrocytes are partially prevented by the IGF1R inhibitor picropodophyllin as well as by the PI3K/Akt signaling inhibitors LY294002 and Akti1/2. These data indicate that the interactions between thyroid hormone and ,-catenin signaling in regulating growth plate chondrocyte proliferation and terminal differentiation are modulated by IGF-1/IGF1R signaling through both the Wnt and PI3K/Akt signaling pathways. While chondrocyte proliferation may be triggered by the IGF-1/IGF1R-mediated PI3K/Akt/GSK3, pathway, cell hypertrophy is likely due to activation of Wnt/,-catenin signaling, which is at least in part initiated by IGF-1 signaling or the IGF-1-activated PI3K/Akt signaling pathway. © 2010 American Society for Bone and Mineral Research [source]

Cutaneous Manifestations from the Follicular Variant of Papillary Carcinoma of the Thyroid: A Case Report and Literature Review

THE LARYNGOSCOPE, Issue S1 2009
Yoon-Soo Bae BS
No abstract is available for this article. [source]

Testing putative hemichordate homologues of the chordate dorsal nervous system and endostyle: expression of NK2.1 (TTF-1) in the acorn worm Ptychodera flava (Hemichordata, Ptychoderidae)

EVOLUTION AND DEVELOPMENT, Issue 6 2002
Carter M. Takacs
SUMMARY Recent phylogenetic investigations have confirmed that hemichordates and echinoderms are sister taxa. However, hemichordates share several cardinal characteristics with chordates and are thus an important taxon for testing hypotheses of homology between key chordate characters and their putative hemichordate antecedents. The chordate dorsal nervous system (DNS) and endostyle are intriguing characters because both hemichordate larval and adult structures have been hypothesized as homologues. This study attempts to test these purported homologies through examination of the expression pattern of a Ptychodera flava NK2 gene, PfNK2.1, because this gene is expressed both in the DNS and endostyle/thyroid in a wide range of chordate taxa. We found that PfNK2.1 is expressed in both neuronal and pharyngeal structures, but its expression pattern is broken up into distinct embryonic and juvenile phases. During embryogenesis, PfNK2.1 is expressed in the apical ectoderm, with transcripts later detected in presumable neuronal structures, including the apical organ and ciliated feeding band. In the developing juvenile we detected PfNK2.1 signal throughout the pharynx, including the stomochord, and later in the hindgut. We conclude that the similar utilization of NK2.1 in apical organ development and chordate DNS is probably due to a more general role for NK2.1 in neurogenesis and that hemichordates do not possess a homologue of the chordate DNS. In addition, we conclude that P. flava most likely does not possess a true endostyle; rather during the evolution of the endostyle NK2.1 was recruited from its more general role in pharynx development. [source]

Diagnostic pitfalls in the evaluation of fine needle aspiration cytology of the thyroid: correlation with histopathology in 260 cases

CYTOPATHOLOGY, Issue 2 2009
A. N. Haberal
Objectives:, Fine needle aspiration cytology (FNAC) of the thyroid is a non-invasive, cost-effective screening procedure that is valuable for distinguishing neoplastic lesions from non-neoplastic nodules. The aim of this study was to determine the diagnostic accuracy of FNACs performed at our institution by correlating FNAC results with histopathological diagnoses. Methods:, Two hundred and seventy-one aspiration cytology specimens followed by thyroidectomy were included in the study, and the results of 260 adequate FNACs were compared with their histological diagnoses. Results:, The sensitivity and specificity of thyroid FNAC for detecting neoplasia were 92.6% and 91.6%, respectively. There were 15 (5.7%) false positives and six (2.3%) false negatives. Conclusions:, The results showed that follicular cells that exhibit some of the features of papillary carcinoma could be observed in a cytology slide of Hashimoto's thyroiditis, leading to a diagnostic pitfall. In addition, cellularity and overlapping cytological criteria in hyperplasia might lead to a false diagnosis. [source]

Fine needle aspiration cytology in the diagnosis of bone lesions

CYTOPATHOLOGY, Issue 2 2005
U. Handa
Objective:, Fine needle aspiration cytology (FNAC) in combination with radiological examination has recently gained clinical recognition for evaluating skeletal lesions. We evaluated our experience with the use of FNA in diagnosing bone lesions with emphasis on areas of difficulty and limitations. Materials and Methods:, Over a period of 5 years FNA was performed in 66 cases of bone lesions. Aspirations were done by cytopathologists using 22-gauge needle. Out of 66 cases unsatisfactory aspirate was obtained in 12 cases. Cytohistological correlation was available in 19 cases. Results:, Adequate aspirates were categorized into neoplastic (27 cases) and non-neoplastic (27 cases) lesions. Of the 27neoplastic aspirates, 20 were malignant (12 primary, 8 metastatic deposits) and 7 were benign. In the malignant group osteosarcoma was correctly diagnosed in 3 cases while other 3 were labeled as sarcoma NOS because of lack of osteoid. Metastatic deposits were sub-typed in 6 cases; from renal cell carcinoma (3 cases), proststic adenocarcinoma, follicular carcinoma thyroid, and squamous cell carcinoma. Neoplastic group comprised of 6 cases of cysts and 21 cases of chronic osteomyelitis. Thirteen cases were diagnosed as tuberculous osteomyelitis. Conclusions:, FNA is a frequent indication in metastases in the bone where distinct cytologic features can even identify an unknown primary. However, diagnosis of primary tumours of the bone is limited by precise subtyping of the tumours. FNA has emerged as a cost effective tool for initial diagnosis of both neoplastic and non-neoplastic lesions of the bone. [source]

Thyroid fine needle aspiration: the morphological features on ThinPrep® slide preparations.

CYTOPATHOLOGY, Issue 6 2003
Eighty cases with histological control
This study had several purposes: to define cytomorphological features of thyroid cells that might be modified by alcohol fixation; to optimize May-Grünwald,Giemsa (MGG) staining on ThinPrep® (TP; Cytyc Inc., Bexborough, MA, USA) slides and to compare the diagnostic accuracy of slides prepared by a liquid-based method with those obtained by conventional technique. This study included 120 cases of ultrasound-guided fine needle aspiration (FNA) of the thyroid and 55 FNAs performed on surgically resected thyroid specimens. Histological control was available in 80 cases. In the first group of 120 FNAs, a split-sample technique was used for the TP. Three screenings were performed: first, an individual screening of the conventional smears (CS) and of the TP, a second screening to compare cells observed on the TP with the histological control and a third screening to assess the previously defined diagnostic criteria. Twenty-seven TP cases (22%) were considered unsatisfactory for diagnosis compared with 10 in CS (8%). The high rate of unsatisfactory cases with TP is likely to be due to the use of the split-sample technique. The sensitivity was 94% for CS and 81% for TP. The specificity was 67% and 60% for CS and TP, respectively. Two occult papillary carcinomas were missed by both methods. As for the MGG staining, the modified technique used for TP resulted in the same quality as the standard procedure. Conversely, TP did however induce uncommon morphological features. In this study, sensitivity and specificity levels are higher for CS than for TP; the difference may be explained by the fact that the methanol fixative used for TP induces some cytological alterations, especially in oncocytic tumours and lymphocytic thyroïditis. [source]

Fine needle aspiration cytology of follicular variant of papillary carcinoma of thyroid

CYTOPATHOLOGY, Issue 4 2003
M. Powari
In this retrospective study, we tried to ascertain the fine needle aspiration cytology (FNAC) features of six histopathologically proven cases of the follicular variant of papillary carcinoma of thyroid (FVPCT). These proven cases were diagnosed from 1998,2000. May,Grunwald,Giemsa and haematoxylin & eosin stained FNAC smears were studied independently by two observers (MP and PD) for detailed cytological features. A comparison of the cytological features was undertaken with those reported in the literature. There were six cases of which only one case was diagnosed as FVPCT while the other five cases were diagnosed as follicular neoplasm (four cases) and neoplasm unclassifiable (one case) on FNAC smears. All these cases showed abundant cellularity with a prominent follicular pattern. No papillae were identified in any of the cases. Syncytial clusters (five cases), nuclear grooves (six cases), nuclear inclusions (one case) and chewing gum colloid (three cases) were noted in variable proportions. We suggest that a differential diagnosis of FVPCT should be considered if the cytology smears show abundant cellularity, syncytial clusters and follicular arrangement along with thick colloid. [source]

One of the duplicated matrix metalloproteinase-9 genes is expressed in regressing tail during anuran metamorphosis

DEVELOPMENT GROWTH & DIFFERENTIATION, Issue 4 2006
Kenta Fujimoto
The drastic morphological changes of the tadpole are induced during the climax of anuran metamorphosis, when the concentration of endogenous thyroid hormone is maximal. The tadpole tail, which is twice as long as the body, shortens rapidly and disappears completely in several days. We isolated a cDNA clone, designated as Xl MMP-9TH, similar to the previously reported Xenopus laevis MMP-9 gene, and showed that their Xenopus tropicalis counterparts are located tandemly about 9 kb apart from each other in the genome. The Xenopus MMP-9TH gene was expressed in the regressing tail and gills and the remodeling intestine and central nervous system, and induced in thyroid hormone-treated tail-derived myoblastic cultured cells, while MMP-9 mRNA was detected in embryos. Three thyroid hormone response elements in the distal promoter and the first intron were involved in the upregulation of the Xl MMP-9TH gene by thyroid hormone in transient expression assays, and their relative positions are conserved between X. laevis and X. tropicalis promoters. These data strongly suggest that the MMP-9 gene was duplicated, and differentiated into two genes, one of which was specialized in a common ancestor of X. laevis and X. tropicalis to be expressed in degenerating and remodeling organs as a response to thyroid hormone during metamorphosis. [source]

Comparative expression analysis of transcription factor genes in the endostyle of invertebrate chordates

DEVELOPMENTAL DYNAMICS, Issue 3 2005
Jin Hiruta
Abstract The endostyle of invertebrate chordates is a pharyngeal organ that is thought to be homologous with the follicular thyroid of vertebrates. Although thyroid-like features such as iodine-concentrating and peroxidase activities are located in the dorsolateral part of both ascidian and amphioxus endostyles, the structural organization and numbers of functional units are different. To estimate phylogenetic relationships of each functional zone with special reference to the evolution of the thyroid, we have investigated, in ascidian and amphioxus, the expression patterns of thyroid-related transcription factors such as TTF-2/FoxE4 and Pax2/5/8, as well as the forkhead transcription factors FoxQ1 and FoxA. Comparative gene expression analyses depicted an overall similarity between ascidians and amphioxus endostyles, while differences in expression patterns of these genes might be specifically related to the addition or elimination of a pair of glandular zones. Expressions of Ci-FoxE and BbFoxE4 suggest that the ancestral FoxE class might have been recruited for the formation of thyroid-like region in a possible common ancestor of chordates. Furthermore, coexpression of FoxE4, Pax2/5/8, and TPO in the dorsolateral part of both ascidian and amphioxus endostyles suggests that genetic basis of the thyroid function was already in place before the vertebrate lineage. Developmental Dynamics 233:1031,1037, 2005. © 2005 Wiley-Liss, Inc. [source]

Matrix metalloproteinases mediate the dismantling of mesenchymal structures in the tadpole tail during thyroid hormone-induced tail resorption

DEVELOPMENTAL DYNAMICS, Issue 3 2002
Jae-Chang Jung
Abstract It has been suggested that a family of tissue remodelling enzymes called matrix metalloproteinases (MMPs) play a causal role in the process of tail resorption during thyroid hormone-induced metamorphosis of the anuran tadpole; however, this hypothesis has never been directly substantiated. We cloned two new Xenopus MMPs, gelatinase A (MMP-2) and MT3-MMP (MMP-16), and the MMP inhibitor TIMP-2. These clones were used along with several others to perform a comprehensive expression study. We show that all MMPs and TIMP-2 are dramatically induced in the resorbing tail during spontaneous metamorphosis and are spatially coexpressed, primarily in the remodelling mesenchymal tissues. By Northern blotting, we show that all the examined MMPs/TIMP-2 are also induced by treatment of organ-cultured tails with thyroid hormone (T3). Using the organ culture model, we provide the first direct evidence that MMPs are required for T3 -induced tail resorption by showing that a synthetic inhibitor of MMP activity/expression can specifically retard the resorption process. By gelatin zymography, we also show T3 induction of a fifth MMP, preliminarily identified as gelatinase B (GelB; MMP-9). Moreover, T3 not only induces MMP/TIMP expression but also MMP activation, and we provide evidence that TIMP-2 participates in the latter process. These findings suggest that MMPs and TIMPs act in concert to effect the dismantling of mesenchymal structures during T3 -induced metamorphic tadpole tail resorption. © 2002 Wiley-Liss, Inc. [source]

Histological alterations following thyroid fine needle biopsy: A systematic review

DIAGNOSTIC CYTOPATHOLOGY, Issue 6 2009
M.Sc., Stergios A. Polyzos M.D.
Abstract Thyroid fine-needle biopsy (FNB) is a simple, reliable, inexpensive, and generally safe diagnostic procedure in the management of thyroid nodules. However, the trauma inflicted by the needle may lead to various degrees of histological alterations, observed in histological specimens, if thyroidectomy follows. Post-FNB histological alterations of the thyroid (PFHAT) can generally be divided into acute and chronic. Hemorrhage is the most common acute and fibrosis the most common chronic PFHAT. Some of the PFHAT causes problems in histological assessment, making diagnosis difficult, even leading to misdiagnosis. In this review, we tried to collect and summarize all reported PFHAT cases and studies, aiming to make involved physicians, cytologists, and pathologists aware of the spectrum of PFHAT and to provide information to help in differential diagnosis and to avoid misdiagnoses, which could lead to unnecessary radical surgery and/or adjuvant therapy. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source]

Absence of microfollicular basement membrane: A new indicator in the diagnosis of follicular carcinoma thyroid

DIAGNOSTIC CYTOPATHOLOGY, Issue 7 2008
Maheswar Sahoo M.D.
Abstract The thyroid follicles represent a biological continuum. Each follicle is closely related to the follicle that is next to it. The important feature of a follicular carcinoma is a microfollicular pattern. We report a case of follicular carcinoma in a 48-year-old female that demonstrates microfollicles which are larger in size and contain more number of follicular cells in cytologic smears (20,29 cells) in contrary to the literature definition of microfollicles containing approximately 6,12 cells. We also demonstrate absence of basement membranes in these microfollicles in histologic sections by Silver Methanamine Stain, which may be an indicator to search for vascular and capsular invasion. This case report also describes postoperative positron emission tomography scan findings. Diagn. Cytopathol. 2008;36:519,522. © 2008 Wiley-Liss, Inc. [source]

Fine-needle aspiration cytology of Hürthle cell carcinoma of the thyroid

DIAGNOSTIC CYTOPATHOLOGY, Issue 3 2008
Howard Her-Juing Wu M.D.
Abstract Specific criteria for the diagnosis of fine-needle aspiration (FNA) of Hürthle Cell Carcinoma (HCC) have rarely been discussed in the literature. A retrospective review of 35 FNA cases with the diagnosis of Hürthle cell lesion or Hürthle cell neoplasm was performed. In each case, there was a subsequent surgical excision. The FNA specimens were divided according to histologic diagnoses as HCC (12 cases), Hürthle cell adenoma (HCA) (14 cases), and benign nonneoplastic Hürthle cell lesions (BNHCL) (9 cases). Each case was examined using a semiquantitative scoring system for the following 11 features: presence or absence of colloid, lymphocytes, and transgressed blood vessels (each scored 0 or 1); the percentage of nuclear enlargement, small cell dysplasia, large cell dysplasia, nuclear crowding, and cellular dyshesion (each scored 0,3); and age, gender, and size of lesion. When diagnosed by FNA as either Hürthle cell neoplasm or Hürthle cell lesion, males were much more likely to have malignant tumors than females. Statistically significant cytologic features that favored malignant (HCC) over benign lesions (HCA and BNHCL) included small cell dysplasia, large cell dysplasia, nuclear crowding, and cellular dyshesion. The presence of colloid and lymphocytes favored a benign lesion. Nuclear enlargement and large tumor size are significantly more common in neoplasms than BNHCL. Diagn. Cytopathol. 2008;36:149,154. © 2008 Wiley-Liss, Inc. [source]

Solid/trabecular variant papillary carcinoma of the thyroid: Report of three cases with fine-needle aspiration

DIAGNOSTIC CYTOPATHOLOGY, Issue 10 2006
Gia-Khanh Nguyen M.D
No abstract is available for this article. [source]

Utility of cell blocks in the diagnosis of thyroid aspirates

DIAGNOSTIC CYTOPATHOLOGY, Issue 2 2006
Niria Sanchez M.D.
Abstract Cell blocks (CBs) are often prepared with fine-needle aspirates (FNAs) from multiple organs as an adjunct to smears in the diagnosis of aspirated lesions. However, the literature contains few reports on their utility with regard to specific organ sites. At our institution, CBs are made routinely on FNAs when there is sufficient material remaining after smear preparation, with thyroid representing the largest volume. The aim of this study was to determine the utility of CBs in the diagnosis of thyroid lesions. From January 2002 to April 2004, 546 thyroid FNAs were performed. Eighty-two (15%) cases, from 60 females and 20 males (age range, 17,88 yr; mean, 50 yr), had CBs and formed the basis of this study. Seventy-four (90%) of the cases were performed by the radiologist or the clinician and 8 (10%) by the pathologist, all of which had an immediate assessment for adequacy. One to 7 passes were performed with an average of 3/case. The needles were immediately rinsed in Hanks' Balanced Salt Solution after smear preparation. CBs were made on bloody specimens/those with tissue fragments. Cell-block slides were reviewed for the presence of cellular elements and classified into three categories: (1) contributory, (2) noncontributory, or (3) provides additional information. Of the 82 cases, 23 (28%) were neoplastic, 51 (62%) were nonneoplastic, and 8 (10%) were nondiagnostic. Fifteen of the neoplastic cases had confirmatory biopsies, 9 of which were papillary carcinoma. The overall cellularity of the CBs was low, varying from 0 to 2 follicular groups in the noncontributory CBs and 3 to 6 follicular groups or papillary formations in the contributory CBs. CBs were contributory in 25 (31%) cases: 5 neoplastic (1 follicular neoplasm, 3 papillary carcinoma, and 1 suspicious for papillary carcinoma), 18 nonneoplastic, and 2 nondiagnostic. CBs were noncontributory in 56 (68%) cases: 18 neoplastic (4 papillary carcinomas, 1 suspicious for papillary carcinoma, 4 Hürthle cell neoplasms, and 9 follicular neoplasms), 33 nonneoplastic, and 5 nondiagnostic. One case was categorized as provided additional information because the CB showed material that was not present on the slides; however, it was still nondiagnostic. In summary, CBs did not help in the majority of cases. They were contributory in only 25 (31%) of the 82 cases, and of the 23 neoplastic cases, only 5 (22%) CBs were contributory. The contribution of the CBs in the diagnosis of thyroid lesions was minimal because of the low cellularity. On-site assessment of specimen adequacy often results in fewer passes, thus contributing to the low cellularity present in cell-block preparations. Ancillary studies may require additional passes. Diagn. Cytopathol. 2006; 34:89,92. © 2006 Wiley-Liss, Inc. [source]

Morphologic predictors of papillary carcinoma on fine-needle aspiration of thyroid with ThinPrep® preparations

DIAGNOSTIC CYTOPATHOLOGY, Issue 6 2001
Yilin Zhang M.D.
Abstract Although the cytologic features of papillary carcinoma of the thyroid are well-known, none is entirely specific. We conducted this study to determine the minimal criteria necessary to achieve 100% specificity for the diagnosis of papillary carcinoma on fine-needle aspiration (FNA). Forty patients with histologically confirmed papillary carcinoma and 17 patients with other thyroid lesions who underwent preoperative FNA at Beth Israel Deaconess Medical Center during a 4-yr period were included in the study. All cytology slides were prepared with the ThinPrep® processing technique. Various architectural and nuclear features were evaluated, with a score assigned to each feature, and correlated with the histologic diagnosis of papillary carcinoma. Intranuclear inclusions, papillary and/or sheet arrangements, nuclear grooves, powdery chromatin, nuclear molding, high cellularity, and small nucleoli were significantly associated with papillary carcinoma (P < 0.05). The requirement of any intranuclear inclusions and many nuclear grooves, or a minimum of sum of scores (of the above eight features) of 10, yields 100% specificity and approximately 70% sensitivity. Cases with fewer features can be reported as suspicious or indeterminate for papillary carcinoma. A quantitative/probabilistic approach in the reporting of thyroid FNA provides a practical guide for management of patients with thyroid nodules. Diagn. Cytopathol. 24:378,383, 2001. © 2001 Wiley-Liss, Inc. [source]

Cytologic spectrum of 227 fine-needle aspiration cases of chest-wall lesions

DIAGNOSTIC CYTOPATHOLOGY, Issue 6 2001
Amit Goel M.D., D.N.B.
Abstract This study was carried out with the objective of studying the cytomorphology of the wide variety of chest-wall lesions. Two hundred twenty-seven chest-wall lesions were studied over a period of 4 yr. Routine May-Grünwald-Giemsa (MGG) and hematoxylin-eosin (H&E) slides were studied along with special stains, whenever required. The malignant lesions comprised 36.13% of all cases (81/227). Of the 126 benign lesions, the majority were inflammatory in nature (68/126), the next commonest lesion being lipoma (38/126). Rare cases of tuberculosis involving the sternum, epithelioid leiomyosarcoma, and neuroendocrine tumors involving ribs, malignant nerve sheath tumors involving the chest wall, metastatic carcinoma of the stomach and prostate, and papillary carcinoma thyroid are reported in this series. Histopathology was available in 24 cases, and hematological correlation in one case. A 100% cytohistological and cytohematological correlation was found, with no false positives or false negatives. In conclusion, fine-needle aspiration cytology is a rapid, diagnostic tool, eliciting many interesting lesions in the chest wall. It is useful not only in detecting primary and metastatic lesions, but also in follow-up of tumor recurrence. Diagn. Cytopathol. 24:384,388, 2001. © 2001 Wiley-Liss, Inc. [source]

Lithium monitoring before and after the distribution of clinical practice guidelines

ACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2000
John M. Eagles
Objective: To determine whether distribution of clinical practice guidelines improves lithium monitoring and whether standards of monitoring differed between patients in psychiatric contact and those seen only in primary care. Method: Standards of monitoring were assessed for patients on lithium in northeast Scotland throughout 1995 and/or throughout 1996. Guidelines were circulated in January 1996 to all local general practitioners and psychiatrists. Monitoring was compared between 1995 and 1996 and for patients with and without psychiatric contact. Results: Both primary care and psychiatric records were scrutinized for 422 and 403 patients prescribed lithium throughout 1995 and 1996, respectively. While monitoring was poor on several parameters during both years, frequency of measurement of both thyroid and renal function improved in 1996. Standards of monitoring were better for patients in psychiatric care. Conclusion: Standards of lithium monitoring require further improvement. Locally agreed practice guidelines are helpful but patients on lithium should be in continuing contact with an experienced psychiatrist. [source]

Tissue-specific distribution and whole-body burden estimates of persistent organic pollutants in the bottlenose dolphin (Tursiops truncatus)

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2010
Jennifer E. Yordy
Abstract Most exposure assessments for free-ranging cetaceans focus on contaminant concentrations measured in blubber, and few data are available for other tissues or the factors governing contaminant distribution among tissues. The goal of this study was to provide a detailed description of the distribution of persistent organic pollutants (POPs) within the common bottlenose dolphin (Tursiops truncatus) body and assess the role of lipid dynamics in mediating contaminant distribution. Thirteen tissues (brain, blubber, heart, liver, lung, kidney, mammary gland, melon, skeletal muscle, spleen, thyroid, thymus, and testis/uterus) were sampled during necropsy from bottlenose dolphins (n,=,4) and analyzed for lipid and 85 POPs, including polychlorinated biphenyls, organochlorine pesticides, and polybrominated diphenyl ethers. Significant correlations between tissue POP concentrations and lipid suggest that distribution of POPs is generally related to tissue lipid content. However, blubber:tissue partition coefficients ranged widely from 0.753 to 6.25, suggesting that contaminant distribution is not entirely lipid-dependent. Tissue-specific and whole-body contaminant burdens confirmed that blubber, the primary site of metabolic lipid storage, is also the primary site for POP accumulation, contributing >90% to the whole-body burdens. Observations also suggest that as lipid mobilizes from blubber, contaminants may redistribute, leading to elevated tissue concentrations. These results suggest that individuals with reduced blubber lipid may be at increased risk for exposure-related health effects. However, this study also provides evidence that the melon, a metabolically inert lipid-rich structure, may serve as an alternate depot for POPs, thus preventing the bulk of blubber contaminants from being directly available to other tissues. This unique physiological adaptation should be taken into consideration when assessing contaminant-related health effects in wild cetacean populations. Environ. Toxicol. Chem. 2010;29:1263,1273. © 2010 SETAC [source]

Interleukin-4 downregulates CD127 expression and activity on human thymocytes and mature CD8+ T cells

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2010
Angela M. Crawley
Abstract Signaling via the IL-7 receptor complex (IL-7R,/CD127 and IL-2R,/CD132) is required for T-cell development and survival. Decreased CD127 expression has been associated with persistent viral infections (e.g. HIV, HCV) and cancer. Many IL-2R,-sharing (,C) cytokines decrease CD127 expression on CD4+ and CD8+ T cells in mice (IL-2, IL-4, IL-7, IL-15) and in humans (IL-2, IL-7), suggesting a common function. IL-4 is of particular interest as it is upregulated in HIV infection and in thyroid and colon cancers. The role of IL-4 in regulating CD127 expression and IL-7 activity in human thymocytes and mature CD8+ T cells is unknown and was therefore investigated. IL-4 decreased CD127 expression on all thymocyte subsets tested and only on naïve (CD45RA+) CD8+ T cells, without altering membrane-bound CD127 mRNA expression. Pre-treatment of thymocytes or CD8+ T cells with IL-4 inhibited IL-7-mediated phosphorylation of STAT5 and decreased proliferation of CD8+ T cells. By downregulating CD127 expression and signaling on developing thymocytes and CD8+ T cells, IL-4 is a potential contributor to impaired CD8+ T-cell function in some anti-viral and anti-tumor responses. These findings are of particular consequence to diseases such as HIV, HCV, RSV, measles and cancer, in which CD127 expression is decreased, IL-7 activity is impaired and IL-4 concentrations are elevated. [source]

Nitric oxide and thyroid gland: modulation of cardiovascular function in autonomic-blocked anaesthetized rats

EXPERIMENTAL PHYSIOLOGY, Issue 3 2004
Andrea Lorena Fellet
We have previously reported that acute administration of NG -nitro- l -arginine methyl ester (l -NAME) increases the mean arterial pressure (MAP) and heart rate (HR) in autonomic-blocked (CAB) anaesthetized rats. In the present study we examined whether thyroid and adrenal glands are involved in these pressor and chronotropic responses. Sprague-Dawley rats were studied after bilateral vagotomy and ganglionic blockade with hexamethonium (10 mg kg,1), and stabilization of MAP with infusion of phenylephrine (PE) (6 ,g kg,1 min,1). The rats were divided into groups: L, CAB; PE, CAB + PE bolus (6 ,g kg,1); L-TX, thyroidectomy + CAB; L-AX, adrenalectomy + CAB; TX, only thyroidectomy; C, CAB. L, L-AX and L-TX groups received a bolus of l -NAME (7.5 mg kg,1). Triiodothyronine (T3), thyroxin (T4) and thyrotropin (TSH) levels were measured in L and L-TX rats before and after l -NAME administration. Reduced nicotamide adenine dinucleotide (NADPH) diaphorase activity was determined in heart and aorta of the TX group. The pressor response induced by l -NAME was similar in all groups. l -NAME-induced-tachycardia was associated with this rise in MAP. Adrenalectomy did not modify this chronotropic response, but it was attenuated by thyroidectomy. Thyroidectomy by itself decreased the circulating levels of T3 but it had no effect on the plasma levels of T4 and TSH. L and L-TX groups showed similar levels of circulating T4 and TSH, meanwhile the plasma level of T3 decreased in the L group. Nitric oxide synthase (NOS) activity in atria as well as in aorta was greater in the TX group compared with C. When autonomic influences are removed, the thyroid gland modulates intrinsic heart rate via a mechanism that involves, at least in part, the nitric oxide pathway. [source]

Calcium-sensing receptor mediates phenylalanine-induced cholecystokinin secretion in enteroendocrine STC-1 cells

FEBS JOURNAL, Issue 18 2008
Tohru Hira
Intraluminal l -phenylalanine (Phe) stimulates cholecystokinin (CCK) secretion in vivo and in vitro. However, the cellular mechanism by which CCK-producing enteroendocrine cells sense Phe is unknown. The calcium-sensing receptor (CaR) can sense amino acids, and is expressed in the gastrointestinal tract. In the present study, we examined whether CaR functions as a receptor for Phe in CCK-producing enteroendocrine cells. CCK secretion and intracellular Ca2+ concentration in response to Phe were measured in the murine CCK-producing enteroendocrine cell line STC-1 at various extracellular Ca2+ concentrations or after treatment with a CaR antagonist. At more than 20 mm, Phe induced dose-dependent CCK secretion and intracellular Ca2+ mobilization in STC-1 cells. In the presence of 3.0 mm extracellular Ca2+, 10 and 20 mm Phe induced significantly higher CCK secretion than under normal conditions (1.2 mm extracellular Ca2+). Intracellular Ca2+ mobilization, induced by 10 or 20 mm Phe, was also enhanced by increasing extracellular Ca2+ concentrations. In addition, intracellular Ca2+ mobilization induced by addition of extracellular Ca2+ was augmented by the presence of Phe. These results closely match the known CaR properties. Treatment with a specific CaR antagonist (NPS2143) completely inhibited Phe-induced CCK secretion and the latter phase of intracellular Ca2+ mobilization. CaR mRNA expression was demonstrated by RT-PCR in STC-1 cells, as well as in other mouse tissues including the kidney, thyroid, stomach and intestine. In conclusion, CaR functions as a receptor for Phe, stimulating CCK secretion in enteroendocrine STC-1 cells. [source]

Fas single nucleotide polymorphisms and risk of thyroid and salivary gland carcinomas: A case-control analysis,

HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 3 2008
Tang Ho MD
Abstract Background. The purpose of this study was to examine the association between 4 Fas single nucleotide polymorphisms (SNPs) and risk of differentiated thyroid carcinoma (DTC) and salivary gland carcinoma (SGC). Methods. We conducted a case-control study including 279 DTC cases, 165 benign thyroid disease (BTD) cases, 154 SGC cases, 61 benign salivary gland disease (BSGD) cases, and 510 controls. Results. The A744G SNP genotype distribution was significantly different between subjects with SGC or BSGD and controls, while that of the A18272G SNP was significantly different between subjects with DTC or SGC and controls. Risk of SGC was significantly elevated for the 22628 heterozygous CT genotype (odds ratio [OR] = 1.5, p = .050), and risk of BSGD was elevated for the 22628 homozygous TT genotype (OR = 2.9, p = .023). Conclusion. Fas C22628T SNP may be associated with risk of SGC and BSGD, but none of the investigated Fas SNPs was associated with risk of DTC. © 2007 Wiley Periodicals, Inc. Head Neck 2008 [source]

Dual thyroid ectopia with a normally located pretracheal thyroid gland: Case report and literature review

HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2007
Ting-Shuo Huang MD
Abstract Background. Only 1 case with dual thyroid ectopy and a normally located thyroid gland has been reported. Methods. We present the case of a 71-year-old woman who had 1-sided lateral neck swelling in the right submandibular space, which grew and doubled in size within 1 year. A CT scan demonstrated 2 right submandibular, lobulated, heterogeneously enhanced masses, an ectopic lingual thyroid, and bilateral thyroid goiter. A Tc-99m sodium pertechnetate thyroid scan revealed a cold area in the right lateral neck region below the submandibular gland, an ectopic lingual thyroid, and bilateral pretracheal thyroids. She underwent total thyroidectomy and en bloc excision of right neck masses. Thyroxin was prescribed following the surgery. Results. Pathological diagnoses were ectopic thyroid tissue with goitrous change and bilateral thyroid goiter. Conclusion. This report demonstrates that dual ectopic thyroid tissue accompanying a normally located thyroid gland can exist and should be differentiated from head and neck malignancies. © 2007 Wiley Periodicals, Inc. Head Neck 2007 [source]

RET rearrangements and BRAF mutation in undifferentiated thyroid carcinomas having papillary carcinoma components

HISTOPATHOLOGY, Issue 3 2010
Kunio Mochizuki
Mochizuki K, Kondo T, Nakazawa T, Iwashina M, Kawasaki T, Nakamura N, Yamane T, Murata S-i, Ito K, Kameyama K, Kobayashi M & Katoh R (2010) Histopathology,57, 444,450 RET rearrangements and BRAF mutation in undifferentiated thyroid carcinomas having papillary carcinoma components Aims:, To elucidate the genetic background of anaplastic transformation, RET rearrangements and BRAF mutation were studied in composite undifferentiated carcinomas (UCs) of the thyroid, which are UCs having papillary carcinoma (PC) components. Methods and results:, Reverse transcription,polymerase chain reaction (RT,PCR) was performed for RET rearrangements and PCR for BRAF mutation in UC and PC components that were microdissected separately from seven composite UCs. Forty-two thyroid cancers with single component histology (14 UCs and 28 PCs) were also studied in the same manner. RET/PTC1 was undetectable in both components from all seven composite UCs, and RET/PTC3 was identified in both components of one composite UC. BRAF mutation was identified in both components from three composite UCs and only in the PC components from two composite UCs. In contrast, in thyroid carcinomas with single component histology, RET/PTC1 was detected in 11% of PCs and in none of the UCs, and RET/PTC3 was not found in any of the tumours studied. BRAF mutation was identified in 82% of PCs and in 21% of UCs. Conclusions:, The high frequency of BRAF mutation and the absence of RET rearrangements in UC components from composite UCs supports the hypothesis that UCs may actually represent progressive malignant degeneration of a BRAF -mutated, well-differentiated thyroid carcinoma. [source]

Hyalinizing trabecular tumour of the thyroid,differential expression of distinct miRNAs compared with papillary thyroid carcinoma

HISTOPATHOLOGY, Issue 5 2010
Sien-Yi Sheu
Sheu S-Y, Vogel E, Worm K, Grabellus F, Schwertheim S & Schmid K W (2010) Histopathology56, 632,640 Hyalinizing trabecular tumour of the thyroid,differential expression of distinct miRNAs compared with papillary thyroid carcinoma Aims:, To compare the expression pattern of five microRNAs (miRNAs) (146b, -181b, -21, -221, -222) of papillary thyroid carcinoma (PTC) and hyalinizing trabecular tumour of the thyroid (HTT). Methods and results:, The expression pattern of five miRNAs known to be up-regulated in PTC was retrospectively analysed in 18 HTTs, adjacent normal thyroid tissue, 10 PTCs, 10 follicular adenomas and 10 non-toxic multinodular goitres (MNG) by reverse transcriptase-polymerase chain reaction using the TaqMan miRNA assay. Furthermore, the two common genetic alterations characteristic for PTC, the V600E mutation of the BRAF gene and RET/PTC 1 and 3 rearrangements, were determined in all HTTs. All miRNAs were significantly up-regulated in PTCs, whereas all miRNAs in HTT, normal thyroid tissue, adenomas, and MNGs were down-regulated. Calculating relative changes in gene expression, a 510-fold change of miRNA 146b between PTC and HTT could be observed followed by fold changes between 6.4 and 29 in the remaining miRNAs (P < 0.001). All HTTs lacked BRAF mutations and RET/PTC rearrangements. Conclusions:, Our findings do not support the concept that a high proportion of HTT represents a variant of PTC. It is suggested that HTTs lacking both a miRNA expression pattern characteristic for PTC and RET/PTC rearrangements are re-designated as ,hyalinizing trabecular adenomas'. [source]

UbcH10 expression in human lymphomas

HISTOPATHOLOGY, Issue 6 2009
Giancarlo Troncone
Aims:, The UbcH10 ubiquitin-conjugating enzyme plays a key role in regulating mitosis completion. We have previously reported that UbcH10 overexpression is associated with aggressive thyroid, ovarian and breast carcinomas. The aim of this study was to investigate UbcH10 expression in human lymphomas. Methods and results:, Cell lines and tissue samples of Hodgkin's lymphoma (HL) and of non-Hodgkin's lymphoma (NHL) were screened for UbcH10 expression at transcriptional and translational levels. UbcH10 expression was related to the grade of malignancy. In fact, it was low in indolent tumours and high in a variety of HL and NHL cell lines and in aggressive lymphomas. It was highest in Burkitt's lymphoma, as shown by quantitative real-time polymerase chain reaction and by tissue microarray immunohistochemistry. Flow cytometry of cell lines confirmed that UbcH10 expression is cell-cycle dependent, steadily increasing in S phase, peaking in G2/M phase and dramatically decreasing in G0/G1 phases. We also showed that UbcH10 plays a relevant role in lymphoid cell proliferation, since blocking of its synthesis by RNA interference inhibited cell growth. Conclusions:, Taken together, these results indicate that UbcH10 is a novel lymphoid proliferation marker encompassing the cell cycle window associated with exit from mitosis. Its overexpression in aggressive lymphomas suggests that UbcH10 could be a therapeutic target in this setting. [source]

Prognostic and predictive factors in endocrine tumours

HISTOPATHOLOGY, Issue 6 2006
T J Stephenson
This review encompasses the diagnostic features of malignancy, the routinely observable prognostic features and the prognostic and predictive features emerging from research techniques in the principal endocrine neoplasms: pancreatic and extrapancreatic endocrine cell tumours, thyroid and parathyroid neoplasia, adrenal cortical neoplasms and adrenal and extra-adrenal paragangliomas. While each endocrine tissue has its own set of diagnostic features for malignancy, and prognostic features once a diagnosis of malignancy has been established, there are a few common themes. For several endocrine neoplasms, definite recognition of malignancy can be difficult and may depend upon frank invasive or metastatic growth at presentation. Endocrine tissues are dynamic, with hyperplastic and regressive phenomena, some of which may mimic malignancy. Even when unequivocal features of malignancy are available for observation, their distribution in tissue may be very focal, necessitating thorough sampling. The accurate documentation of routinely observable histological features interpreted in the light of current literature has not been superseded by special techniques in the statement of diagnosis or prognosis in the vast majority of endocrine neoplasms. [source]

Papillary carcinoma of the thyroid: difficult yet fascinating model of oncogenesis and tumour progression

HISTOPATHOLOGY, Issue 5 2004
T J Stephenson
No abstract is available for this article. [source]

Effects of long-term exposure to ramelteon, a melatonin receptor agonist, on endocrine function in adults with chronic insomnia

HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2009
Gary Richardson
Abstract Objective To evaluate the effects of ramelteon, an MT1/MT2 melatonin receptor agonist used to treat insomnia, on endocrine function in adults with chronic insomnia. Methods This was a double-blind, placebo-controlled, trial of adults (18,45 years) with chronic insomnia. Subjects received either ramelteon 16,mg or placebo nightly for 6 months. Hormonal measures of the thyroid, reproductive, and adrenal axes were analyzed monthly and compared with baseline and placebo values. Results While isolated changes were detected at some time points, there were no consistent statistically significant differences between treatments on measures of thyroid function (total T4, free T4, TSH, and total T3), adrenal function (AM cortisol, and ACTH), or on most reproductive endocrine measures [LH, FSH, estradiol (women), total, and free testosterone (men)]. Prolactin concentrations were increased overall in women in the ramelteon group compared with placebo (p,=,0.003). No clinical effects of elevated prolactin were reported; average menstrual cycle length, duration of menses, and ovulation probability did not differ between groups. Conclusions Long-term exposure to ramelteon 16,mg, a potent melatonin receptor agonist, resulted in mild, transient increase in prolactin, in women only, that were not associated with measurable reproductive effects. There were no consistent changes in other endocrine measures. Copyright © 2008 John Wiley & Sons, Ltd. [source]