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Sample records for age-related thymic involution1

  1. [Impact of thymic function in age-related immune deterioration].

    Science.gov (United States)

    Ferrando-Martínez, Sara; de la Fuente, Mónica; Guerrero, Juan Miguel; Leal, Manuel; Muñoz-Fernández, M Ángeles

    2013-01-01

    Age-related biological deterioration also includes immune system deterioration and, in consequence, a rise in the incidence and prevalence of infections and cancers, as well as low responses to vaccination strategies. Out of all immune cell subsets, T-lymphocytes seem to be involved in most of the age-related defects. Since T-lymphocytes mature during their passage through the thymus, and the thymus shows an age-related process of atrophy, thymic regression has been proposed as the triggering event of this immune deterioration in elderly people. Historically, it has been accepted that the young thymus sets the T-lymphocyte repertoire during the childhood, whereupon atrophy begins until the elderly thymus is a non-functional evolutionary trace. However, a rising body of knowledge points toward the thymus functioning during adulthood. In the elderly, higher thymic function is associated with a younger immune system, while thymic function failure is associated with all-cause mortality. Therefore, any new strategy focused on the improvement of the elderly quality of life, especially those trying to influence the immune system, should take into account, together with peripheral homeostasis, thymus function as a key element in slowing down age-related decline. Copyright © 2012 SEGG. Published by Elsevier Espana. All rights reserved.

  2. Induction of epithelial to mesenchymal transition (EMT) and inhibition on adipogenesis: Two different sides of the same coin? Feasible roles and mechanisms of transforming growth factor β1 (TGF-β1) in age-related thymic involution.

    Science.gov (United States)

    Tan, Jianxin; Wang, Yajun; Zhang, Nannan; Zhu, Xike

    2016-08-01

    Age-related thymic involution is characterized by a loss of thymic epithelial cells (TECs) and a concomitant increase in adipocytes, but the mechanisms involved in thymic adipogenesis are still not clear. Transforming growth factor β1 (TGF-β1) is a pleiotropic cytokine that has been reported to be up-regulated with age in thymic stromal cells in both human and mouse. However, the exact role of TGF-β1 in age-related thymic involution remains to be further elucidated. On the basis of previous findings, we propose a novel hypothesis that TGF-β1 functions a dual role in age-related thymic involution. On one hand, up-regulation of TGF-β1 promotes epithelial to mesenchymal transition (EMT) process in TECs via activating forkhead box protein C2 (FoxC2). On the other hand, TGF-β1 inhibits the transdifferentiation of EMT-derived mesenchymal cells to adipocytes in the thymus. If confirmed, our hypothesis will not only provide further evidence supporting that the transdifferentiation of TECs into pre-adipocytes represents a source of thymic adiposity during age-related thymic involution, but also uncover a unique role of TGF-β1 in the transdifferentiation of TECs into pre-adipocytes. Collectively, the inhibition of TGF-β1 may serve as a strategy to hinder age-related thymic involution or even to restore thymic function in the elderly. © 2016 International Federation for Cell Biology.

  3. The effect of age on thymic function

    Directory of Open Access Journals (Sweden)

    Donald B. Palmer

    2013-10-01

    Full Text Available Age-related regression of the thymus is associated with a decline in naïve T cell output. This is thought to contribute to the reduction in T cell diversity seen in older individuals and linked with increased susceptibility to infection, autoimmune disease and cancer. Thymic involution is one of the most dramatic and ubiquitous changes seen in the ageing immune system, but the mechanisms which underlying this process are poorly understood. However, a picture is emerging, implicating the involvement of both extrinsic and intrinsic factors. In this review we assess the role of the thymic microenvironment as a potential target that regulates thymic involution, question whether thymocyte development in the aged thymus is functionally impaired and explore the kinetics of thymic involution.

  4. Significance of thymic scintigraphy

    International Nuclear Information System (INIS)

    Baba, Hiromi; Oshiumi, Yoshihiko; Nakayama, Chikashi; Morita, Kazunori; Koga, Ichinari

    1978-01-01

    Thymic scintigraphy by 67 Ga-citrate and 75 Se-methionine was done on 6 cases of thymoma, and 5 cases of myasthenia gravis. Scan was positive on 5 of 6 cases of thymoma. All patients with malignant thymoma were positive. Among the 7 cases of myasthenia gravis, scintigrams revealed 2 thymomas and 1 hyperplasia on whom no thymic mass suspected. Thymic scintigraphy is useful examination when dealing with myasthenia gravis. (auth.)

  5. Cystic thymic diseases: CT manifestations

    International Nuclear Information System (INIS)

    Song, Soon Young; Choi, Yo Won; Jeon, Eui Yong; Jeon, Seok Chol; Seo, Heung Suk; Hahm, Chang Kok

    1995-01-01

    To describe CT findings and differential points of cystic thymic lesions. We evaluated retrospectively total 19 masses with well marginated cystic lesions at thymic area on CT scans. They were 10 teratomas, 3 congenital thymic cysts, 2 multilocular thymic cysts(associated with thymoma and myasthenia gravis in each), 2 cysts Assciated with thymic Hodgkin's lymphomas an ectopic parathyroid cyst, and an infected thymic cyst. The radiological abnormalities evaluated were thickness of the wall, presence or abscene of septa, mural nodule, solid component, calcification and fat component. All three cases of congenital thymic cysts and an ectopic parathyroid cyst appeared as thin-walled unilocular cyst with homogeneous internal density and without identifiable solid component. In multilocular thymic cyst, there were thick wall and solid components(n =2), thick internal septa and calcifications(n = 1). The cysts of teratomas manifested thick walls(n = 9), internal septa(n = 4), calcifications(n = 6), fat components(n = 4), and solid components(n = 4). Cysts in Hodgkin's diseases appeared as multilocular or unilocular and had thick wall and septa without calcification. Infected thymic cyst presented with multilocular cystic mass with identifiable wall and septa, calcification, and solid components. The thymic diseases with cystic lesion include teratomas, congenital thymic cysts, multilocular thymic cysts, parathyroid cyst, and Hodgkin's disease. Congenital thymic cyst and ectopic parathyroid cyst are thin-walled unilocular cystic lesions. Cystic lesions associated with teratoma, Hodgkin's disease, and multilocular thymic cyst are thick-walled cystic lesions with or without solid component

  6. Development of Thymic Epithelial Cells

    DEFF Research Database (Denmark)

    Ulyanchenko, Svetlana; Vaidya, Harsh J.; O'Neill, Kathy E.

    2016-01-01

    The thymus is the primary lymphoid organ in which the T cell repertoire is generated. The complex cellularity of this organ is uniquely designed to facilitate T cell development: defects in thymus development or function can cause immunodeficiencies ranging from the absence of T cell-mediated imm......The thymus is the primary lymphoid organ in which the T cell repertoire is generated. The complex cellularity of this organ is uniquely designed to facilitate T cell development: defects in thymus development or function can cause immunodeficiencies ranging from the absence of T cell......-mediated immunity to broad-spectrum autoimmune disease. Peak thymus size and output occurs early in life, after which the thymus undergoes a natural process of involution. This results in the progressive loss of functional thymus tissue and correspondingly in decreased production of new naïve T cells with age...... - contributing to the diminished capacity of the aged immune system to adequately respond to new antigenic challenge. Age-related thymic involutions, together with the thymic involutions associated with cytotoxic therapies (e.g., radio- or chemotherapy), have raised interest in development of clinically useful...

  7. Cystic thymic diseases: CT manifestations

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    Song, Soon Young; Choi, Yo Won; Jeon, Eui Yong; Jeon, Seok Chol; Seo, Heung Suk; Hahm, Chang Kok [School of Medicine, Hanyang University, Seoul (Korea, Republic of)

    1995-09-15

    To describe CT findings and differential points of cystic thymic lesions. We evaluated retrospectively total 19 masses with well marginated cystic lesions at thymic area on CT scans. They were 10 teratomas, 3 congenital thymic cysts, 2 multilocular thymic cysts(associated with thymoma and myasthenia gravis in each), 2 cysts Assciated with thymic Hodgkin's lymphomas an ectopic parathyroid cyst, and an infected thymic cyst. The radiological abnormalities evaluated were thickness of the wall, presence or abscene of septa, mural nodule, solid component, calcification and fat component. All three cases of congenital thymic cysts and an ectopic parathyroid cyst appeared as thin-walled unilocular cyst with homogeneous internal density and without identifiable solid component. In multilocular thymic cyst, there were thick wall and solid components(n =2), thick internal septa and calcifications(n = 1). The cysts of teratomas manifested thick walls(n = 9), internal septa(n = 4), calcifications(n = 6), fat components(n = 4), and solid components(n = 4). Cysts in Hodgkin's diseases appeared as multilocular or unilocular and had thick wall and septa without calcification. Infected thymic cyst presented with multilocular cystic mass with identifiable wall and septa, calcification, and solid components. The thymic diseases with cystic lesion include teratomas, congenital thymic cysts, multilocular thymic cysts, parathyroid cyst, and Hodgkin's disease. Congenital thymic cyst and ectopic parathyroid cyst are thin-walled unilocular cystic lesions. Cystic lesions associated with teratoma, Hodgkin's disease, and multilocular thymic cyst are thick-walled cystic lesions with or without solid component.

  8. Computed tomography of thymic abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Schnyder, P.; Candardjis, G.

    1987-05-01

    Computed tomographic examinations of 38 patients with surgically and histologically proven diagnosis were reviewed. Twenty subjects (52%) had an invasive thymoma and 16% an hyperplastic thymus. Myasthenia gravis was present in 6 cases (16%) of thymic abnormalities, four (10,5%) with invasive thymoma and two (5%) with thymic hyperplasia. Graves' disease was also present in one case of thymic hyperplasia. We emphasize the contribution of CT to the diagnosis and the prognosis.

  9. Computed tomography of thymic abnormalities

    International Nuclear Information System (INIS)

    Schnyder, P.; Candardjis, G.

    1987-01-01

    Computed tomographic examinations of 38 patients with surgically and histologically proven diagnosis were reviewed. Twenty subjects (52%) had an invasive thymoma and 16% an hyperplastic thymus. Myasthenia gravis was present in 6 cases (16%) of thymic abnormalities, four (10,5%) with invasive thymoma and two (5%) with thymic hyperplasia. Graves' disease was also present in one case of thymic hyperplasia. We emphasize the contribution of CT to the diagnosis and the prognosis. (orig.)

  10. Expression of RAGE and HMGB1 in thymic epithelial tumors, thymic hyperplasia and regular thymic morphology.

    Science.gov (United States)

    Moser, Bernhard; Janik, Stefan; Schiefer, Ana-Iris; Müllauer, Leonhard; Bekos, Christine; Scharrer, Anke; Mildner, Michael; Rényi-Vámos, Ferenc; Klepetko, Walter; Ankersmit, Hendrik Jan

    2014-01-01

    Recently, a role of the receptor for advanced glycation endproducts (RAGE) in myasthenia gravis was described. RAGE and its ligand high mobility group box 1 (HMGB1) play key roles in autoimmunity and cancer. To test whether these molecules are involved in patients with thymic abnormalities we applied immunohistochemical analysis in 33 cases of thymic epithelial tumors, comprising 27 thymomas and 6 thymic carcinomas, and 21 nonneoplastic thymuses. Both molecules were detected in neoplastic epithelial cells: RAGE staining was most intense in WHO type B2 thymomas and thymic carcinomas (pB3>thymic carcinoma (pepithelial cells which was found in 50% of myasthenic patients. Furthermore RAGE and HMGB1 were expressed in thymocytes, macrophages, Hassall's corpuscles, thymic medulla, and germinal center cells in myasthenic patients. Immunohistochemistry results were complemented by systemic measurements (immunosorbent assay): serum levels of soluble RAGE were significantly reduced in patients with epithelial tumors (p = 0.008); and in invasive tumors (p = 0.008). Whereas RAGE was equally reduced in thymic hyperplasia and epithelial tumors (p = 0.003), HMGB1 was only elevated in malignancies (p = 0.036). Results were most pronounced in thymic carcinomas. Thus, RAGE and HMGB1 are involved in the (patho-)physiology of thymus, as evidenced by differentiated thymic and systemic expression patterns that may act as diagnostic or therapeutic targets in autoimmune disease and cancer.

  11. Expression of RAGE and HMGB1 in thymic epithelial tumors, thymic hyperplasia and regular thymic morphology.

    Directory of Open Access Journals (Sweden)

    Bernhard Moser

    Full Text Available Recently, a role of the receptor for advanced glycation endproducts (RAGE in myasthenia gravis was described. RAGE and its ligand high mobility group box 1 (HMGB1 play key roles in autoimmunity and cancer. To test whether these molecules are involved in patients with thymic abnormalities we applied immunohistochemical analysis in 33 cases of thymic epithelial tumors, comprising 27 thymomas and 6 thymic carcinomas, and 21 nonneoplastic thymuses. Both molecules were detected in neoplastic epithelial cells: RAGE staining was most intense in WHO type B2 thymomas and thymic carcinomas (pB3>thymic carcinoma (p<0.001. Conversely, HMGB1 cytoplasmic staining intensities were as follows: A and AB (none, B1 (strong, B2 (moderate, B3 and thymic carcinoma (weak; (p<0.001. Fetal thymic tissue showed a distinct expression of RAGE and HMGB1 in subcapsular cortical epithelial cells which was found in 50% of myasthenic patients. Furthermore RAGE and HMGB1 were expressed in thymocytes, macrophages, Hassall's corpuscles, thymic medulla, and germinal center cells in myasthenic patients. Immunohistochemistry results were complemented by systemic measurements (immunosorbent assay: serum levels of soluble RAGE were significantly reduced in patients with epithelial tumors (p = 0.008; and in invasive tumors (p = 0.008. Whereas RAGE was equally reduced in thymic hyperplasia and epithelial tumors (p = 0.003, HMGB1 was only elevated in malignancies (p = 0.036. Results were most pronounced in thymic carcinomas. Thus, RAGE and HMGB1 are involved in the (patho-physiology of thymus, as evidenced by differentiated thymic and systemic expression patterns that may act as diagnostic or therapeutic targets in autoimmune disease and cancer.

  12. PPARgamma Deficiency Counteracts Thymic Senescence

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    David Ernszt

    2017-11-01

    Full Text Available Thymic senescence contributes to increased incidence of infection, cancer and autoimmunity at senior ages. This process manifests as adipose involution. As with other adipose tissues, thymic adipose involution is also controlled by PPARgamma. This is supported by observations reporting that systemic PPARgamma activation accelerates thymic adipose involution. Therefore, we hypothesized that decreased PPARgamma activity could prevent thymic adipose involution, although it may trigger metabolic adverse effects. We have confirmed that both human and murine thymic sections show marked staining for PPARgamma at senior ages. We have also tested the thymic lobes of PPARgamma haplo-insufficient and null mice. Supporting our working hypothesis both adult PPARgamma haplo-insufficient and null mice show delayed thymic senescence by thymus histology, thymocyte mouse T-cell recombination excision circle qPCR and peripheral blood naive T-cell ratio by flow-cytometry. Delayed senescence showed dose–response with respect to PPARgamma deficiency. Functional immune parameters were also evaluated at senior ages in PPARgamma haplo-insufficient mice (null mice do not reach senior ages due to metabolic adverse affects. As expected, sustained and elevated T-cell production conferred oral tolerance and enhanced vaccination efficiency in senior PPARgamma haplo-insufficient, but not in senior wild-type littermates according to ELISA IgG measurements. Of note, humans also show increased oral intolerance issues and decreased protection by vaccines at senior ages. Moreover, PPARgamma haplo-insufficiency also exists in human known as a rare disease (FPLD3 causing metabolic adverse effects, similar to the mouse. When compared to age- and metabolic disorder-matched other patient samples (FPLD2 not affecting PPARgamma activity, FPLD3 patients showed increased human Trec (hTrec values by qPCR (within healthy human range suggesting delayed thymic senescence, in accordance with

  13. CT findings of thymic tumors

    International Nuclear Information System (INIS)

    Chung, Ho Son; Lee, Sang Jin; Hwang, Mi Soo; Cho, Kil Ho; Chang, Jae Chun; Park, Bok Hwan

    1991-01-01

    A CT scan can make accurate diagnoses of most thymic masses by assessing their size, shape, and internal architecture and is especially effective in detecting pleural implants, mediastinal involvement, and pulmonary parenchymal invasion in malignant thymoma. The authors analyzed the CT findings of 10 histologically-proven thymic masses from 1983 to 1990 in Yeungnam University Hospital. There were 10 cases of thymic masses in the anterior mediastinum consisting of 6 benign, 3 invasive thymomas, and one thymolipoma, while myasthenia gravis was associated with 2 cases of benign thymomas and with one case of invasive thymomas. The CT findings of the benign thymomas (6 cases) were well-defined, bordered, round-or oval-shaped masses with a well-preserved fat plane between the thymic mass and mediastinal great vessels, with no evidence of pleural implants and lung parenchymal invasion. The CT findings of the invasive thymomas (3 cases) were irregular, marginated lobular masses with obliteration of the fat plane between the thymic mass and surrounding great vessels, with evidence of local invasion such as extension to A-P window and mass effect to bronchus. Irregular pleural thickening due to pleural metastasis, multiple metastatic lung parenchymal nodules, and multiple mediastinal lymph node enlargement were also seen in the invasive thymomas. One case of thymolipoma showed an approximately 20cm-size, well-defined fat density mass containing internal septations

  14. CT findings of thymic tumors

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Ho Son; Lee, Sang Jin; Hwang, Mi Soo; Cho, Kil Ho; Chang, Jae Chun; Park, Bok Hwan [College of Medicine, Yeungnam University, Daegu (Korea, Republic of)

    1991-05-15

    A CT scan can make accurate diagnoses of most thymic masses by assessing their size, shape, and internal architecture and is especially effective in detecting pleural implants, mediastinal involvement, and pulmonary parenchymal invasion in malignant thymoma. The authors analyzed the CT findings of 10 histologically-proven thymic masses from 1983 to 1990 in Yeungnam University Hospital. There were 10 cases of thymic masses in the anterior mediastinum consisting of 6 benign, 3 invasive thymomas, and one thymolipoma, while myasthenia gravis was associated with 2 cases of benign thymomas and with one case of invasive thymomas. The CT findings of the benign thymomas (6 cases) were well-defined, bordered, round-or oval-shaped masses with a well-preserved fat plane between the thymic mass and mediastinal great vessels, with no evidence of pleural implants and lung parenchymal invasion. The CT findings of the invasive thymomas (3 cases) were irregular, marginated lobular masses with obliteration of the fat plane between the thymic mass and surrounding great vessels, with evidence of local invasion such as extension to A-P window and mass effect to bronchus. Irregular pleural thickening due to pleural metastasis, multiple metastatic lung parenchymal nodules, and multiple mediastinal lymph node enlargement were also seen in the invasive thymomas. One case of thymolipoma showed an approximately 20cm-size, well-defined fat density mass containing internal septations.

  15. Gallium 67 uptake in thymic rebound

    International Nuclear Information System (INIS)

    Hurst, R.; Sabio, H.; Teates, C.D.

    1988-01-01

    We have reported a case of localized thymic enlargement and uptake of gallium 67 in a child who had received antineoplastic chemotherapy. The enlarged thymus showed normal histology, a picture consistent with thymic rebound after nonspecific stress. This case further demonstrates the need to consider thymic rebound as a cause of gallium 67 uptake in children with neoplastic diseases

  16. Thymic hyperplasia in Graves′ disease

    Directory of Open Access Journals (Sweden)

    Narendra Kotwal

    2013-01-01

    Full Text Available Graves′ disease is an autoimmune thyroid condition characterized by the production of autoantibodies against the thyrotropin receptor. It is known to be associated with autoimmune conditions such as myasthenia gravis, Addison′s disease, type 1 diabetes mellitus, and vitiligo. We present a case of rare autoimmune association of Graves′ disease with thymic hyperplasia which regressed after treatment with antithyroid drugs. Exact pathophysiology of thymic hyperplasia in Graves′ is not well understood; it is likely to be the result of rather than the cause of Graves′ disease.

  17. Age-related hearing loss

    Science.gov (United States)

    ... grow older. Your genes and loud noise (from rock concerts or music headphones) may play a large role. The following factors contribute to age-related hearing loss: Family history (age-related hearing loss tends to run in ...

  18. Bacillus Calmette-Guérin vaccination, thymic size, and thymic output in healthy newborns

    DEFF Research Database (Denmark)

    Birk, Nina Marie; Nissen, Thomas Nørrelykke; Zingmark, Vera

    2017-01-01

    Background: The Bacillus Calmette-Guérin vaccine (BCG) has been associated with beneficial nonspecific effects on infant health. We aimed to examine the effect of BCG at birth on thymic size and the associations between thymic output, circulating lymphocytes, risk of infection, and thymic size...... with a large thymic size at birth. Conclusion: We found no effect of BCG vaccination on thymic size. The positive association between thymic output, lymphocytes, reduced risk of infections, and TI/TWI suggests that assessment of TI/TWI by ultrasound may be a predictor of the immunological capacity...... in the newborn....

  19. Detection of chemotherapy-induced thymic changes in patients with metastasised testicular tumors by computed tomography

    International Nuclear Information System (INIS)

    Hendrickx, P.; Doehring, W.

    1989-01-01

    Serial thoracic CT scans of 100 patients suffering from testicular cancer revealed that the thymus appears to atrophy temporarily during administration of cytostatic agents. About two months after cessation of chemotherapy rebound enlargement of the thymus occurs and persists for about two years followed by a slow involution. Using a semiquantitative score system, thymic CT images of these patients were compared with that of 100 patients suffering from other malignancies, 100 patients without malignant disease and 52 patients with myasthenia gravis, taking into account the age-related changes of the size of the organ. Rebound thymic enlargement should not be misinterpreted as metastatic lymph nodes. (orig.) [de

  20. Detection of chemotherapy-induced thymic changes in patients with metastasised testicular tumors by computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Hendrickx, P.; Doehring, W.

    1989-03-01

    Serial thoracic CT scans of 100 patients suffering from testicular cancer revealed that the thymus appears to atrophy temporarily during administration of cytostatic agents. About two months after cessation of chemotherapy rebound enlargement of the thymus occurs and persists for about two years followed by a slow involution. Using a semiquantitative score system, thymic CT images of these patients were compared with that of 100 patients suffering from other malignancies, 100 patients without malignant disease and 52 patients with myasthenia gravis, taking into account the age-related changes of the size of the organ. Rebound thymic enlargement should not be misinterpreted as metastatic lymph nodes.

  1. Low thymic output in the 22q11.2 deletion syndrome measured by CCR9+CD45RA+ T cell counts and T cell receptor rearrangement excision circles

    DEFF Research Database (Denmark)

    Lima, K; Abrahamsen, Gitte Meldgaard; Foelling, I

    2010-01-01

    Thymic hypoplasia is a frequent feature of the 22q11.2 deletion syndrome, but we know little about patients' age-related thymic output and long-term consequences for their immune system. We measured the expression of T cell receptor rearrangement excision circles (TREC) and used flow cytometry...

  2. Bacillus Calmette-Guérin vaccination, thymic size, and thymic output in healthy newborns

    DEFF Research Database (Denmark)

    Birk, Nina Marie; Nissen, Thomas Nørrelykke; Zingmark, Vera

    2017-01-01

    BACKGROUND: The Bacillus Calmette-Guérin vaccine (BCG) has been associated with beneficial nonspecific effects on infant health. We aimed to examine the effect of BCG at birth on thymic size and the associations between thymic output, circulating lymphocytes, risk of infection, and thymic size...... to age 3 mo were parent-reported. RESULTS: BCG vaccination did not affect thymic size at age 3 mo, measured as TI. At birth, the number of lymphocytes, CD4+ T cells, CD8+ T cells, and RTEs were positively associated with TI and TWI. Furthermore, a reduced risk of infections up to age 3 mo was associated...... with a large thymic size at birth. CONCLUSION: We found no effect of BCG vaccination on thymic size. The positive association between thymic output, lymphocytes, reduced risk of infections, and TI/TWI suggests that assessment of TI/TWI by ultrasound may be a predictor of the immunological capacity...

  3. Review of thymic pathology in 30 cats and 36 dogs.

    Science.gov (United States)

    Day, M J

    1997-09-01

    Data are presented from 30 cats and 36 dogs in which thymic disease was recognised clinically or on postmortem examination. The diagnoses included thymic lymphoma (19 cats, 12 dogs), thymoma (five cats, 18 dogs), thymic branchial cyst formation or cystic change (one cat, four dogs), thymic hyperplasia (two cats), congenital hypoplasia (one cat, one dog), thymic haemorrhage (one cat, one dog) and thymic amyloidosis (one cat). Thymic lymphoma occurred in younger dogs and cats, and was recorded equally among domestic shorthaired and purebred (especially Siamese) cats. Eight cats with thymic lymphoma were tested for feline leukaemia virus and four were positive. Thymoma occurred more frequently in older cats and dogs, and in Labradors and German shepherd dogs. Thymic tumours were associated with paraneoplastic hypercalcaemia (six dogs), megaoesophagus (two dogs) or interface dermatitis with basement membrane immune complex deposition (one cat). Non-neoplastic thymic diseases were associated with myasthenia gravis (one cat), pemphigus foliaceus (one cat) and superficial necrolytic dermatitis (one cat).

  4. Age-Related Macular Degeneration.

    Science.gov (United States)

    Mehta, Sonia

    2015-09-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Thymic epithelial cells. I. Expression of strong suppressive (veto) activity in mouse thymic epithelial cell cultures

    DEFF Research Database (Denmark)

    Claesson, Mogens Helweg; Ropke, C

    1990-01-01

    We show that thymic epithelial cells grown under serum-free conditions in a chemically defined culture medium can act as veto cells in vitro. The veto activity of thymic epithelial cells results in inactivation of specific alloreactive cytotoxic T-cell precursors at the clonal level. It is conclu......We show that thymic epithelial cells grown under serum-free conditions in a chemically defined culture medium can act as veto cells in vitro. The veto activity of thymic epithelial cells results in inactivation of specific alloreactive cytotoxic T-cell precursors at the clonal level...

  6. Thymic Carcinoma Management Patterns among International Thymic Malignancy Interest Group (ITMIG) Physicians with Consensus from the Thymic Carcinoma Working Group.

    Science.gov (United States)

    Shepherd, Annemarie; Riely, Gregory; Detterbeck, Frank; Simone, Charles B; Ahmad, Usman; Huang, James; Korst, Robert; Rajan, Arun; Rimner, Andreas

    2017-04-01

    Thymic carcinomas are rare epithelial malignancies with limited data to guide management. To identify areas of agreement and variability in current clinical practice, a 16-question electronic survey was given to members of the International Thymic Malignancy Interest Group (ITMIG). Areas of controversy were discussed with the Thymic Carcinoma Working Group and consensus was achieved, as described. A total of 100 ITMIG members responded. There was general agreement regarding the role for multimodality therapy with definitive surgical resection in physically fit patients with advanced but resectable disease. Areas of controversy included the need for histologic confirmation before surgery, the role of adjuvant therapy, the optimal first-line chemotherapy regimen, and the recommended treatment course for marginally resectable disease with invasion into the great vessels, pericardium, and lungs. The results of the questionnaire provide a description of the management of thymic carcinoma by 100 ITMIG members with a specific interest or expertise in thymic malignancies. Although there was agreement in some areas, clinical practice appears to vary significantly. There is a great need for collaborative research to identify optimal evaluation and treatment strategies. Given the need for multimodality therapy in many cases, a multidisciplinary discussion of the management of patients with thymic carcinoma is critical. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  7. Minimally Invasive Surgery in Thymic Malignances

    Directory of Open Access Journals (Sweden)

    Wentao FANG

    2018-04-01

    Full Text Available Surgery is the most important therapy for thymic malignances. The last decade has seen increasing adoption of minimally invasive surgery (MIS for thymectomy. MIS for early stage thymoma patients has been shown to yield similar oncological results while being helpful in minimize surgical trauma, improving postoperative recovery, and reduce incisional pain. Meanwhile, With the advance in surgical techniques, the patients with locally advanced thymic tumors, preoperative induction therapies or recurrent diseases, may also benefit from MIS in selected cases.

  8. Age-related oral changes.

    LENUS (Irish Health Repository)

    Mckenna, Gerald

    2010-10-01

    Age-related oral changes are seen in the oral hard and soft tissues as well as in bone, the temporomandibular joints and the oral mucosa. As older patients retain their natural teeth for longer, the clinical picture consists of normal physiological age changes in combination with pathological and iatrogenic effects. Clinical Relevance: With an ageing population retaining more of its natural teeth for longer, dental professionals should expect to observe oral age changes more frequently.

  9. Images in pediatrics: the thymic sail sign and thymic wave sign.

    Science.gov (United States)

    Alves, Nuno D; Sousa, Marta

    2013-01-01

    The authors present a radiographic image portraying the "thymic sail sign" and the "thymic wave sign," both normal findings in infant radiographs and present a short description of these signs. These are distinguished from pathologic findings such as the "spinnaker-sail sign" in pneumomediastinum.

  10. Age-related changes in the thymus gland: CT-pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Moore, A.V.; Korobkin, M.; Olanow, W.; Heaston, D.K.; Ram, P.C.; Dunnick, N.R.; Silverman, P.M.

    1983-08-01

    Recent reports suggest that computed tomography (CT) is useful for thymoma detection in patients with myasthenia gravis. However, that usefulness may be conditioned by the state of the normal thymus. To examine this concept, the CT findings in 64 consecutive patients with histologic confirmation of thymic status after thymectomy or thymic biopsy during mediastinal exploration were reviewed. The normal thymus has a bilobed, arrowhead-shaped cross section at all ages, with gradual focal or diffuse fatty infiltration of the parenchyma usually occurring between 20 and 40 years of age. A thymoma is usually a spherical or oval mass, often producing a focal, distinct bulge in the adjacent pleural reflection. The differentiation of thymoma from normal thymus should be possible in most patients if age-related changes in the normal gland are appreciated.

  11. Age-related changes in the thymus gland: CT-pathologic correlation

    International Nuclear Information System (INIS)

    Moore, A.V.; Korobkin, M.; Olanow, W.; Heaston, D.K.; Ram, P.C.; Dunnick, N.R.; Silverman, P.M.

    1983-01-01

    Recent reports suggest that computed tomography (CT) is useful for thymoma detection in patients with myasthenia gravis. However, that usefulness may be conditioned by the state of the normal thymus. To examine this concept, the CT findings in 64 consecutive patients with histologic confirmation of thymic status after thymectomy or thymic biopsy during mediastinal exploration were reviewed. The normal thymus has a bilobed, arrowhead-shaped cross section at all ages, with gradual focal or diffuse fatty infiltration of the parenchyma usually occurring between 20 and 40 years of age. A thymoma is usually a spherical or oval mass, often producing a focal, distinct bulge in the adjacent pleural reflection. The differentiation of thymoma from normal thymus should be possible in most patients if age-related changes in the normal gland are appreciated

  12. Age-related macular degeneration

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian....... Smoking is probably also a risk factor. Preventive strategies using macular laser photocoagulation are under investigation, but their efficacy in preventing visual loss is as yet unproven. There is no treatment with proven efficacy for geographic atrophy. Optimal treatment for exudative AMD requires...

  13. [Presbycusis - Age Related Hearing Loss].

    Science.gov (United States)

    Fischer, N; Weber, B; Riechelmann, H

    2016-07-01

    Presbycusis or age related hearing loss can be defined as a progressive, bilateral and symmetrical sensorineural hearing loss due to age related degeneration of inner ear structures. It can be considered a multifactorial complex disorder with environmental and genetic factors. The molecular, electrophysiological and histological damage at different levels of the inner ear cause a progressive hearing loss, which usually affects the high frequencies of hearing. The resulting poor speech recognition has a negative impact on cognitive, emotional and social function in older adults. Recent investigations revealed an association between hearing impairment and social isolation, anxiety, depression and cognitive decline in elderly. These findings emphasize the importance of diagnosis and treating hearing loss in the elderly population. Hearing aids are the most commonly used devices for treating presbycusis. The technical progress of implantable hearing devices allows an effective hearing rehabilitation even in elderly with severe hearing loss. However, most people with hearing impairments are not treated adequately. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Age-related macular degeneration.

    Science.gov (United States)

    Cheung, Lily K; Eaton, Angie

    2013-08-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, and the prevalence of the disease increases exponentially with every decade after age 50 years. It is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors. Besides smoking, hypertension, obesity, and certain dietary habits, a growing body of evidence indicates that inflammation and the immune system may play a key role in the development of the disease. AMD may progress from the early form to the intermediate form and then to the advanced form, where two subtypes exist: the nonneovascular (dry) type and the neovascular (wet) type. The results from the Age-Related Eye Disease Study have shown that for the nonneovascular type of AMD, supplementation with high-dose antioxidants (vitamin C, vitamin E, and β-carotene) and zinc is recommended for those with the intermediate form of AMD in one or both eyes or with advanced AMD or vision loss due to AMD in one eye. As for the neovascular type of the advanced AMD, the current standard of therapy is intravitreal injections of vascular endothelial growth factor inhibitors. In addition, lifestyle and dietary modifications including improved physical activity, reduced daily sodium intake, and reduced intake of solid fats, added sugars, cholesterol, and refined grain foods are recommended. To date, no study has demonstrated that AMD can be cured or effectively prevented. Clearly, more research is needed to fully understand the pathophysiology as well as to develop prevention and treatment strategies for this devastating disease. © 2013 Pharmacotherapy Publications, Inc.

  15. Thymic hyperplasia - clinical course and imaging diagnostic

    International Nuclear Information System (INIS)

    Drebov, R.; Panov, M.; Totev, M.; Deliverski, T.; Tcandev, I.; Velkovski, I.

    2006-01-01

    The real thymic hyperplasia is benign disease sometimes simulating malignant tumours. The aim of this study is to analyse the clinical symptoms of real thymic hyperplasia and the results from imaging diagnostic based on our clinical material. Clinical material include 27 children, aged from two months to 15 years, admitted in department of thoracic surgery, for a period of 20 years (1985 - 2004). We retrospectively analyze the clinical signs and results from X-ray investigation, CT (Siemens Somatom DRG and Philips Secura) and echocardiography (Acuson TX, 5 and 7 MHz). We discuss the diagnostic value of different methods as well as typical and atypical findings. (authors)

  16. Computed tomography of thymic abnormalities: review of 10 patients

    International Nuclear Information System (INIS)

    Marins, J.L.C.; Brito Pacheco, E.M. de; Cazerta, N.M.G.; Silva, M.J.G. da

    1990-01-01

    Chest radiographs and computed tomographic scans of the mediastinum were correlated with pathologic findings of the thymus following thymectomy in 10 patients with thymic disease. There were five patients with thymoma, four with thymic hiperplasia and one with benign thymic cyst. Computed tomography shoud be the imaging method of choice following plain chest radiographs when a suspect thymic abnormality requires further evaluation. Recognition of variations in the normal location, size, shape and density of the thymus prevents misinterpretation as abnormal mediastinal mass. Furthermore, knowledge of the normal computed tomography appearance has proved helpful in evaluating thymic abnormalities. (author)

  17. Thymic enlargement in patients with hyperthyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Myung, Jae Sung; Goo, Jin Mo; Im, Jung Gi [College of medicine and the Institute of Radiation Medicine, Seoul National University, Seoul (Korea, Republic of); Kim, Mi Young [Sejong General Hospital, Seoul (Korea, Republic of); Park, Yang Hee [National Police Hospital, Seoul (Korea, Republic of)

    2000-08-01

    To evaluate the radiologic findings and clinical feasibility of thymic enlargement in patients with hyperthyroidism. Seven patients with hyperthyroidism and anterior mediastinal bulging revealed by chest radiography were evaluated. The CT findings were analyzed with regard to the shape of the anterior mediastinal mass, surrounding infiltration, and enlargement of mediastinal lymph nodes. Whether or not tumor markers (alpha-fetoprotein, beta-human chorionic gonadotrophin, and chorionic embryonic antigen) showed increased levels was determined, and the size and thickness of the anterior mediastinal mass were measured and compared with previously described age-matched thymus data. In addition, changes in the thyroid gland were evaluated. In all seven patients, anterior mediastinal masses were bi-lobed, with no surrounding infiltration or enlarged mediastinal lymph node, and tumor marker levels showed no increase. The masses were therefore considered to be thymus. In six patients, the size of the thymus exceeded two upper standard deviations of mean value and in one patient, it was smaller than this. In three patients, PCNB (percutaneous needle biopsy) revealed normal thymic tissue and in two, follow-up chest PA demonstrated no interval change. CT showed that in three patients, the thyroid glands were diffusely enlarged. In patients with hyperthyroidism, an anterior mediastinal mass seen on chest radiographs was due to thymic enlargement. The recognition of CT findings of thymic enlargement in such patients may avoid unnecessary biopsy. (author)

  18. PICTORIAL ESSAY Thymic masses: A radiological review

    African Journals Online (AJOL)

    On chest X-ray, thymic abnormalities typically manifest as focal or diffuse ... Department of Radiodiagnosis and Imaging, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India. Corresponding author: B ... are considered of primary mediastinal origin if there is neither a detectable gonadal primary nor.

  19. Dietary modulation of thymic enzymes.

    Science.gov (United States)

    Susana, Feliu María; Paula, Perris; Slobodianik, Nora

    2014-01-01

    Malnutrition is a complex syndrome caused by an inadequate intake of energy, protein, minerals and vitamins which affects the immune system. Nutritional imbalances, present in children with energy-protein malnutrition and infections, make defining the specific effects of each of them on the thymus difficult. For this reason, it is necessary to design an experimental model in animals that could define a single variable. As the thymus atrophy described in humans is similar to that observed in murines, a rat experimental model makes the extrapolation to man possible. Some authors suggest that the activity of Adenosine Deaminase (ADA) and Purine Nucleoside Phosphorylase (PNP)--involved in purine metabolism--have an influence on T lymphocyte development and the immune system, due to intracellular accumulation of toxic levels of deoxynucleotides. Studies in our group, performed in an experimental model on Wistar growing rats, have demonstrated that protein deficiency or imbalance in the profile of essential amino acids in the diet, produce loss of thymus weight, reduction in the number of thymocytes, a diminished proportion of T cells presenting the W3/13 antigenic determinant and DNA content with concomitant increase in cell size, and the proportion of immature T cells and activity of ADA and PNP, without modifying the activity of 5´Nucleotidase in the thymus. It is important to point out that there were neither differences in energy intake between experimental groups and their controls, nor clinical symptoms of deficiency of other nutrients. The increase in these thymic enzyme activities was an alternative mechanism to avoid the accumulation of high levels of deoxynucleotides, which would be toxic for T lymphocytes. On the other hand, the administration of a recovery diet, with a high amount of high quality protein, was able to reverse the mentioned effects. The quick reply of Adenosine Deaminase to nutritional disorders and the following nutritional recovery, points

  20. The International Thymic Malignancy Interest Group thymic initiative: a state-of-the-art study of thymic malignancies.

    Science.gov (United States)

    Detterbeck, Frank; Korst, Robert

    2014-01-01

    Thymic malignancies are relatively rare tumors. A general lack of knowledge, misconceptions about benignancy, confusion about the definition of terms, and variability in reporting of outcomes have further hampered progress in these diseases. The International Thymic Malignancy Interest Group has emerged to counter these challenges and has brought together a worldwide multidisciplinary community determined to improve outcomes for these patients. Although the organization is young (initiated in 2010), major early accomplishments have created a foundation and infrastructure for scientific research. These include consensus definitions of terms, an unprecedented global database, development of practical clinical resources and, together with the International Association for the Study of Lung Cancer, development of proposals for the first formal stage classification of these malignant tumors. Many articles have been published or are under way, and a second phase of projects building on the early success is proceeding. The greatest accomplishment of the International Thymic Malignancy Interest Group lies in the establishment of an open culture of collaboration and the engagement of a broad group of individuals united by a common mission. It is a testament to what can be achieved, despite ongoing and inherent challenges, by determination and a collective effort. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Imaging of thymus in myasthenia gravis: From thymic hyperplasia to thymic tumor

    International Nuclear Information System (INIS)

    Priola, A.M.; Priola, S.M.

    2014-01-01

    Myasthenia gravis (MG) is an autoimmune disorder often associated with thymic abnormalities. At onset, thymic lymphoid hyperplasia (TLH) and thymoma can be found in up to 65% and 15% of patients, respectively. Diagnostic imaging is crucial in this setting in order to detect the presence and type of the thymic abnormality and in the preoperative planning, when indicated. Chest radiography has a minor role due to its low accuracy. Computed tomography is the imaging modality of choice, although the differentiation between a small thymoma and TLH that appears as a focal soft-tissue mass may be not possible. Magnetic resonance imaging (MRI) is not usually employed, but it is useful in equivocal cases, especially in differentiating focal TLH from thymoma by using chemical-shift sequences for defining the proper management. In addition, diffusion-weighted (DW)-MRI can differentiate lipid-poor normal/hyperplastic thymus from thymoma and could be useful in differentiating non-advanced from advanced thymomas. Positron emission tomography (PET)-CT is not helpful in distinguishing early from advanced thymoma but can be used to differentiate thymic carcinoma from thymoma. Hereby, we discuss the imaging features of thymic abnormalities in MG, even focusing on novel aspects of chemical-shift and DW-MRI

  2. Radiation carcinogenesis in mouse thymic lymphomas

    International Nuclear Information System (INIS)

    Kominami, Ryo; Niwa, Ohtsura

    2006-01-01

    Ionizing radiation is a well-known carcinogen for various human tissues and a complete carcinogen that is able to initiate and promote neoplastic progression. Studies of radiation-induced mouse thymic lymphomas, one of the classic models in radiation carcinogenesis, demonstrated that even the unirradiated thymus is capable of developing into full malignancy when transplanted into the kidney capsule or subcutaneous tissue of irradiated mice. This suggests that radiation targets tissues other than thymocytes to allow expansion of cells with tumorigenic potential in the thymus. The idea is regarded as the ''indirect mechanism'' for tumor development. This paper reviews the indirect mechanism and genes affecting the development of thymic lymphomas that we have analyzed. One is the Bcl11b/Rit1 tumor suppressor gene and the other is Mtf-1 gene affecting tumor susceptibility. (author)

  3. Thymic irradiation and chronic myelogenous leukemia

    International Nuclear Information System (INIS)

    Shimaoka, K.; Sokal, J.E.

    1977-01-01

    Two cases of Ph positive chronic myelogenous leukemia with a history of thymic irradiation are presented. Both patients received radiation therapy from low voltage x-ray equipment at two to three months of age. Leukemia developed 18 and 22 years later. Presentation, response to antileukemic therapy, and clinical course did not differ from that of other patients with this disease treated in our department

  4. Thymic pathology and cardiac myxomas: Coincidence or a closer relationship?

    Science.gov (United States)

    Moraitis, Sotirios D; Agrafiotis, Apostolos C; Pappas, Dimitrios; Pothitakis, Chrysovalantis; Stergianni, Maria; Koukis, Ioannis

    2018-04-30

    Myxomas are the most common benign cardiac tumors and are located more frequently in the left atrium. In the literature there are cases describing the coexistence of thymic tumors and cardiac myxomas. In the case reported herein, during the resection of a cardiac myxoma, an enlarged thymus gland was encountered and resected. The histological exam revealed a thymic hyperplasia. The aim of this case study is to assess the need of conducting further studies in order to identify a common histological pathway between thymic lesions and cardiac myxomas. The diagnosis of a cardiac myxoma could justify a further workup of the anterior mediastinum in order not to overlook a lesion of thymic origin.

  5. CT differentiation of invasive thymoma and thymic carcinoma

    International Nuclear Information System (INIS)

    Lee, Eun Jung; Jung, Gyoo Sik; Kim, Seong Min; Huh, Jin Do; Joh, Young Duk; Shin, Mi Jung; Kim, Jung Sik; Suh, Soo Jhi

    1998-01-01

    In order to determine the differential points between them, we analyzed the CT findings of invasive thymoma and thymic carcinoma. We retrospectively reviewed the CT scans of 14 patients with invasive thymoma and 15 with thymic carcinoma, confirmed by surgery(n=3D19) or percutaneous needle aspiration(n=3D10) between 1988 and 1996. CT findings were evaluated in each group for intrathoracic spread(posterior, direct posterior, and anterolateral), obliteration of the fat plane between the mass and vascular structures, vessel encasement, invasion of adjacent mediastinal structures, pleural implants, mediastinal nodes and distant metastasis. Direct posterior spread was more common in thymic carcinoma than invasive thymoma;it was seen in one case (7%) of invasive thymoma and 12(80%) of thymic carcinoma(p=3D0.00). Posterior spread was seen in six cases (43%) of in vasive thymoma and nine (60%) of thymic carcinoma. Anterolateral spread was seen only in two cases (13%) of thymic carcinoma. Obliteration of the fat plane was seen in nine cases (64%) of invasive thymoma and 14 (93%) of thymic carcinoma, while vessel encasement was seen in two cases (14%) of invasive thymoma and 13(87%) of thymic carcinoma(p=3D0.00). Invasion of adjacent structures was seen in two cases (14%) of invasive thymoma and eight (53%) of thymic carcinoma. Pleural implants were more common in invasive thymoma than thymic carcinoma, being seen in six cases (43%) of the former and one (7%) of the latter(p=3D0.04). Mediastinal lymphadenopathy was seen in three cases (21%) of invasive thymoma and ten (67%) of thymic carcinoma. Distant metastases were observed only in six cases (40%) of thymic carcinoma(p=3D0.02). Although differentiation between invasive thymoma and thymic carcinoma is difficult on the basis of CT findings, there are certain differential points. Thymic carcinomas showed a higher rate of direct posterior intrathoracic spread, vessel encasement, mediastinal nodes and distant metastases than

  6. Immune activation is associated with decreased thymic function in ...

    African Journals Online (AJOL)

    Background: Reduced thymic function causes poor immunological reconstitution in human immunodeficiency virus (HIV)-positive patients on combined antiretroviral therapy (cART). The association between immune activation and thymic function in asymptomatic HIVpositive treatment-naive individuals has thus far not been ...

  7. Massive thymic hemorrhage and hemothorax occurring in utero.

    Science.gov (United States)

    Gargano, Giancarlo; Paltrinieri, Anna Lucia; Gallo, Claudio; Di Pancrazio, Luciana; Roversi, Maria Federica; Ferrari, Fabrizio

    2015-11-14

    Thymic enlargement is a common and physiological finding in children and neonates' X-rays, but it is usually asymptomatic. Occasionally it can cause respiratory distress. In most cases the aetiology of this expansion remains unclear and it is diagnosed as a thymic hyperplasia. True thymic hyperplasia is defined as a gland expansion, both in size and weight, while maintaining normal microscopic architecture. Often it is a diagnosis of exclusion and prognosis is good. Thymic haemorrhage is an unusual condition related to high foetal and neonatal mortality. We report a case of spontaneous massive thymic haemorrhage in a newborn developing at birth acute respiratory distress associated with severe bilateral haemothorax. Thymic enlargement was evident after pleural evacuation and confirmed by radiographic, Computed Tomography (CT) images and Magnetic Resonance Imaging (MRI) sequences. The spontaneous resolution of this enlargement seen with CT scan and MRI sequences suggested a thymic haemorrhage; surgery was not necessary. Thymic haemorrhage should be considered in newborn infants with pleural effusion, mediastinal space enlargement and Respiratory Distress.

  8. Rag defects and thymic stroma: lessons from animal models

    Directory of Open Access Journals (Sweden)

    Veronica eMarrella

    2014-06-01

    Full Text Available Thymocytes and thymic epithelial cells (TECs cross-talk is essential to support T-cell development and preserve thymic architecture and maturation of TECs and Foxp3+ natural regulatory T (nTreg cells. Accordingly, disruption of thymic lymphostromal cross-talk may have major implications on the thymic mechanisms that govern T cell tolerance. Several genetic defects have been described in humans that affect early stages of T cell development (leading to Severe Combined Immune Deficiency, SCID or late stages in thymocyte maturation (resulting in combined immunodeficiency. Hypomorphic mutations in SCID-causing genes may allow for generation of a limited pool of T lymphocytes with a restricted repertoire. These conditions are often associated with infiltration of peripheral tissues by activated T cells and immune dysregulation, as best exemplified by Omenn syndrome (OS. In this review, we will discuss our recent findings on abnormalities of thymic microenvironment in OS with a special focus of defective maturation of TECs, altered distribution of thymic dendritic cells (DCs and impairment of deletional and non-deletional mechanisms of central tolerance. Here, taking advantage of mouse models of OS and atypical SCID, we will discuss how modifications in stromal compartment impact and shape lymphocyte differentiation, and vice versa how inefficient T cell signalling results in defective stromal maturation. These findings are instrumental to understand the extent to which novel therapeutic strategies should act on thymic stroma to achieve full immune reconstitution.

  9. Isolated splenic metastasis from a thymic carcinoma: A case report.

    Science.gov (United States)

    Chen, Dongmei; Meng, Xiangying; Zhao, Yaowei; Wu, Shikai

    2016-09-01

    Thymic carcinomas are rare tumors that arise in the anterior mediastinum. Most of these malignancies develop local metastases limited in the thorax. Splenic metastases from thymic carcinomas are extremely rare. Here we report a case of isolated splenic metastasis from a 38-year-old female patient with Stage IV thymic carcinoma, who was treated with chemoradiotherapy. At twenty-2 months follow-up, the patient was found to have an isolated spleen metastasis, which was treated by Cyberknife with a reduced size of the metastasis, representing a partial response. Although splenic metastasis is a rare phenomenon, physicians need to be aware of the possibility of such metastases.

  10. Thymic nurse cells and thymic repopulation after whole body sublethal irradiation in mice

    International Nuclear Information System (INIS)

    Houben-Defresne, M.P.; Varlet, A.; Boniver, J.

    1984-01-01

    Thymic Nurse Cells (TNCs) are lymphoepithelial complexes which are thought to play a role in the early stages of the intrathymic differentiation pathway. Their repopulation kinetics were analyzed in mice after sublethal whole-body irradiation. Changes of the number of TNCs per thymus were parallel with the evolution of the whole thymocyte population. Particularly, a first wave of TNCs restoration was followed by a secondary depletion and a final recovery. This suggests that TNCs restoration is related to the proliferating progeny of intrathymic radioresistant thymocytes. When normal bone marrow cells were grafted intravenously after irradiation, no secondary depletion was found. This pattern of restoration was obviously related to thymic repopulation by cells which were derived from the inoculated bone marrow. Homing studies with FITC labelled bone marrow cells showed that inoculated bone marrow cells did not penetrate TNCs early after irradiation. Later on, when immigrant cells started to proliferate, they were found preferentially within TNCs before spreading in the whole thymus. (Auth.)

  11. Age-Related White Matter Changes

    Directory of Open Access Journals (Sweden)

    Yun Yun Xiong

    2011-01-01

    Full Text Available Age-related white matter changes (WMC are considered manifestation of arteriolosclerotic small vessel disease and are related to age and vascular risk factors. Most recent studies have shown that WMC are associated with a host of poor outcomes, including cognitive impairment, dementia, urinary incontinence, gait disturbances, depression, and increased risk of stroke and death. Although the clinical relevance of WMC has been extensively studied, to date, only very few clinical trials have evaluated potential symptomatic or preventive treatments for WMC. In this paper, we reviewed the current understanding in the pathophysiology, epidemiology, clinical importance, chemical biomarkers, and treatments of age-related WMC.

  12. The period-age relation for cepheids

    International Nuclear Information System (INIS)

    Efremov, Yu.N.

    1978-01-01

    The list of 119 cepheid-members of 55 clusters and associations of the Magellanic Clouds, the Galaxy, and M31 is given. The period-age relation is found from the data on 64 cepheids in 29 clusters for which the age determinations are available, the ages of extragalactic clusters were determined mainly from their integral colours. The U-B colours are found to be of much better age parameters than the B-V ones. The composite period-age relation agrees well with the theoretical one. The observed dispersion of the period-age relation leads to an estimate of the age dispersion about 1x10 7 years in the associations. Some peculiarities of the cepheids with the shortest periods amongst others in the same clusters are probably explained if they are overtone pulsators. The period-age relation may be used for an investigation of the recent history of star formation in the galaxies. This relation allows to determine the age gradient across the spiral arm in M31 which is in agreement with the density wave theory predictions. The distribution of cepheids in our Galaxy and neighbouring galaxies is consistent with the conception of star formation lasting for some dozen million years in cells with a dimension of some hundreds of parsecs

  13. Driving and Age-Related Macular Degeneration

    OpenAIRE

    Owsley, Cynthia; McGwin, Gerald

    2008-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety, and considers directions for future research.

  14. What Is Age-Related Macular Degeneration?

    Science.gov (United States)

    ... Eye Health / Eye Health A-Z Age-Related Macular Degeneration Sections What Is Macular Degeneration? How is AMD ... What Does Macular Degeneration Look Like? What Is Macular Degeneration? Leer en Español: ¿Qué es la degeneración macular ...

  15. Thymic masses: A radiological review | Mittal | SA Journal of Radiology

    African Journals Online (AJOL)

    Abstract. Various thymic masses and their normal variations have different pathological and management consequences. Radiologists and clinicians should be aware of these entities so that appropriate and timely treatment can be given.

  16. Administration of RANKL boosts thymic regeneration upon bone marrow transplantation.

    Science.gov (United States)

    Lopes, Noella; Vachon, Hortense; Marie, Julien; Irla, Magali

    2017-06-01

    Cytoablative treatments lead to severe damages on thymic epithelial cells (TECs), which result in delayed de novo thymopoiesis and a prolonged period of T-cell immunodeficiency. Understanding the mechanisms that govern thymic regeneration is of paramount interest for the recovery of a functional immune system notably after bone marrow transplantation (BMT). Here, we show that RANK ligand (RANKL) is upregulated in CD4 + thymocytes and lymphoid tissue inducer (LTi) cells during the early phase of thymic regeneration. Importantly, whereas RANKL neutralization alters TEC recovery after irradiation, ex vivo RANKL administration during BMT boosts the regeneration of TEC subsets including thymic epithelial progenitor-enriched cells, thymus homing of lymphoid progenitors, and de novo thymopoiesis. RANKL increases specifically in LTi cells, lymphotoxin α, which is critical for thymic regeneration. RANKL treatment, dependent on lymphotoxin α, is beneficial upon BMT in young and aged individuals. This study thus indicates that RANKL may be clinically useful to improve T-cell function recovery after BMT by controlling multiple facets of thymic regeneration. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  17. Interventions for age-related diseases

    DEFF Research Database (Denmark)

    Figueira, Inês; Fernandes, Adelaide; Mladenovic Djordjevic, Aleksandra

    2016-01-01

    Over 60% of people aged over 65 are affected by multiple morbidities, which are more difficult to treat, generate increased healthcare costs and lead to poor quality of life compared to individual diseases. With the number of older people steadily increasing this presents a societal challenge. Age...... is the major risk factor for age-related diseases and recent research developments have led to the proposal that pharmacological interventions targeting common mechanisms of ageing may be able to delay the onset of multimorbidity. Here we review the state of the knowledge of multimorbidity, appraise...... the available evidence supporting the role of mechanisms of ageing in the development of the most common age-related diseases and assess potential molecules that may successfully target those key mechanisms....

  18. Prevention of age-related macular degeneration.

    Science.gov (United States)

    Wong, Ian Yat Hin; Koo, Simon Chi Yan; Chan, Clement Wai Nang

    2011-02-01

    Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review looks at current evidence on preventive measures targeted at AMD. Modalities reviewed include (1) nutritional supplements such as the Age-Related Eye Disease Study (AREDS) formula, lutein and zeaxanthin, omega-3 fatty acid, and berry extracts, (2) lifestyle modifications, including smoking and body-mass-index, and (3) filtering sunlight, i.e. sunglasses and blue-blocking intraocular lenses. In summary, the only proven effective preventive measures are stopping smoking and the AREDS formula.

  19. Immunology of age-related macular degeneration

    Science.gov (United States)

    Ambati, Jayakrishna; Atkinson, John P.; Gelfand, Bradley D.

    2014-01-01

    Age-related macular degeneration (AMD) is a leading cause of blindness in aged individuals. Recent advances have highlighted the essential role of immune processes in the development, progression and treatment of AMD. In this Review we discuss recent discoveries related to the immunological aspects of AMD pathogenesis. We outline the diverse immune cell types, inflammatory activators and pathways that are involved. Finally, we discuss the future of inflammation-directed therapeutics to treat AMD in the growing aged population. PMID:23702979

  20. Age-related hair pigment loss.

    Science.gov (United States)

    Tobin, Desmond J

    2015-01-01

    Humans are social animals that communicate disproportionately via potent genetic signals imbued in the skin and hair, including racial, ethnic, health, gender, and age status. For the vast majority of us, age-related hair pigment loss becomes the inescapable signal of our disappearing youth. The hair follicle (HF) pigmentary unit is a wonderful tissue for studying mechanisms generally regulating aging, often before this becomes evident elsewhere in the body. Given that follicular melanocytes (unlike those in the epidermis) are regulated by the hair growth cycle, this cycle is likely to impact the process of aging in the HF pigmentary unit. The formal identification of melanocyte stem cells in the mouse skin has spurred a flurry of reports on the potential involvement of melanocyte stem cell depletion in hair graying (i.e., canities). Caution is recommended, however, against simple extrapolation of murine data to humans. Regardless, hair graying in both species is likely to involve an age-related imbalance in the tissue's oxidative stress handling that will impact not only melanogenesis but also melanocyte stem cell and melanocyte homeostasis and survival. There is some emerging evidence that the HF pigmentary unit may have regenerative potential, even after it has begun to produce white hair fibers. It may therefore be feasible to develop strategies to modulate some aging-associated changes to maintain melanin production for longer. © 2015 S. Karger AG, Basel.

  1. Risk factors for age-related maculopathy.

    Science.gov (United States)

    Connell, Paul P; Keane, Pearse A; O'Neill, Evelyn C; Altaie, Rasha W; Loane, Edward; Neelam, Kumari; Nolan, John M; Beatty, Stephen

    2009-01-01

    Age-related maculopathy (ARM) is the leading cause of blindness in the elderly. Although beneficial therapeutic strategies have recently begun to emerge, much remains unclear regarding the etiopathogenesis of this disorder. Epidemiologic studies have enhanced our understanding of ARM, but the data, often conflicting, has led to difficulties with drawing firm conclusions with respect to risk for this condition. As a consequence, we saw a need to assimilate the published findings with respect to risk factors for ARM, through a review of the literature appraising results from published cross-sectional studies, prospective cohort studies, case series, and case control studies investigating risk for this condition. Our review shows that, to date, and across a spectrum of epidemiologic study designs, only age, cigarette smoking, and family history of ARM have been consistently demonstrated to represent risk for this condition. In addition, genetic studies have recently implicated many genes in the pathogenesis of age-related maculopathy, including Complement Factor H, PLEKHA 1, and LOC387715/HTRA1, demonstrating that environmental and genetic factors are important for the development of ARM suggesting that gene-environment interaction plays an important role in the pathogenesis of this condition.

  2. Risk Factors for Age-Related Maculopathy

    Directory of Open Access Journals (Sweden)

    Paul P. Connell

    2009-01-01

    Full Text Available Age-related maculopathy (ARM is the leading cause of blindness in the elderly. Although beneficial therapeutic strategies have recently begun to emerge, much remains unclear regarding the etiopathogenesis of this disorder. Epidemiologic studies have enhanced our understanding of ARM, but the data, often conflicting, has led to difficulties with drawing firm conclusions with respect to risk for this condition. As a consequence, we saw a need to assimilate the published findings with respect to risk factors for ARM, through a review of the literature appraising results from published cross-sectional studies, prospective cohort studies, case series, and case control studies investigating risk for this condition. Our review shows that, to date, and across a spectrum of epidemiologic study designs, only age, cigarette smoking, and family history of ARM have been consistently demonstrated to represent risk for this condition. In addition, genetic studies have recently implicated many genes in the pathogenesis of age-related maculopathy, including Complement Factor H, PLEKHA 1, and LOC387715/HTRA1, demonstrating that environmental and genetic factors are important for the development of ARM suggesting that gene-environment interaction plays an important role in the pathogenesis of this condition.

  3. Psychophysical function in age-related maculopathy.

    LENUS (Irish Health Repository)

    Neelam, Kumari

    2012-02-01

    Age-related macular degeneration (AMD), the late stage of age-related maculopathy (ARM), is the leading cause of blind registration in developed countries. The visual loss in AMD occurs due to dysfunction and death of photoreceptors (rods and cones) secondary to an atrophic or a neovascular event. The psychophysical tests of vision, which depend on the functional status of the photoreceptors, may detect subtle alterations in the macula before morphological fundus changes are apparent ophthalmoscopically, and before traditional measures of visual acuity exhibit deterioration, and may be a useful tool for assessing and monitoring patients with ARM. Furthermore, worsening of these visual functions over time may reflect disease progression, and some of these, alone or in combination with other parameters, may act as a prognostic indicator for identifying eyes at risk for developing neovascular AMD. Lastly, psychophysical tests often correlate with subjective and relatively undefined symptoms in patients with early ARM, and may reflect limitation of daily activities for ARM patients. However, clinical studies investigating psychophysical function have largely been cross-sectional in nature, with small sample sizes, and lack consistency in terms of the grading and classification of ARM. This article aims to comprehensively review the literature germane to psychophysical tests in ARM, and to furnish the reader with an insight into this complex area of research.

  4. Risk factors for age-related maculopathy.

    LENUS (Irish Health Repository)

    Connell, Paul P

    2012-02-01

    Age-related maculopathy (ARM) is the leading cause of blindness in the elderly. Although beneficial therapeutic strategies have recently begun to emerge, much remains unclear regarding the etiopathogenesis of this disorder. Epidemiologic studies have enhanced our understanding of ARM, but the data, often conflicting, has led to difficulties with drawing firm conclusions with respect to risk for this condition. As a consequence, we saw a need to assimilate the published findings with respect to risk factors for ARM, through a review of the literature appraising results from published cross-sectional studies, prospective cohort studies, case series, and case control studies investigating risk for this condition. Our review shows that, to date, and across a spectrum of epidemiologic study designs, only age, cigarette smoking, and family history of ARM have been consistently demonstrated to represent risk for this condition. In addition, genetic studies have recently implicated many genes in the pathogenesis of age-related maculopathy, including Complement Factor H, PLEKHA 1, and LOC387715\\/HTRA1, demonstrating that environmental and genetic factors are important for the development of ARM suggesting that gene-environment interaction plays an important role in the pathogenesis of this condition.

  5. Thymic epithelial tumours: from basic principles to individualised treatment strategies

    Directory of Open Access Journals (Sweden)

    Nicolas Girard

    2013-03-01

    Full Text Available Thymic epithelial tumours represent a wide range of anatomical, clinical, histological and molecular malignant entities that may be aggressive and difficult to treat. The histopathological classification distinguishes thymomas from thymic carcinomas. Thymomas may be associated with autoimmune disorders. The management of thymic epithelial tumours is a paradigm of co-operation between clinicians, surgeons and pathologists, from establishing the diagnosis to organising the multimodal therapeutic strategy. Surgery is the mainstay of the curative-intent treatment, as complete resection represents the most significantly favourable prognostic factor on overall survival. In case of invasion of intra-thoracic structures and/or dissemination to the pleura and the pericardium, precluding complete resection to be achieved, primary chemotherapy has been used to reduce the tumour burden, possibly allowing subsequent surgery and/or radiotherapy. Novel strategies are needed, especially for refractory, recurrent tumours and thymic carcinomas, which carry a poor prognosis. Personalised approaches are currently being developed, as potentially “druggable” molecular targets are emerging from recent integrated genomic analyses. Along with the large variety of questions relative to the treatment strategy, thymic epithelial tumours represent a model of therapeutic implementation and achievement in orphan thoracic oncology, showing how the advent of new results induces new questions, as well as diversifies further clinical research directions and international collaborative initiatives.

  6. CT findings of lymphofollicular thymic hyperplasia in adult myasthenia gravis

    International Nuclear Information System (INIS)

    Liu Fugeng; Wei Jiahu; Pan Jishu; Zhou Cheng; Chen Qihang; Yu Jingying; Wu Guogeng; Xu Xianhao

    2006-01-01

    Objective: To evaluate the CT findings of lymphofollicular thymic hyperplasia in adult myasthenia gravis (MG). Methods: The CT findings of thymus area of 134 adult patients with lymphofollicular thymic hyperplasia in MG were reviewed, all of them with surgically and histologically proven diagnosis, and compared with the CT findings of 165 normal subjects. Results: In the group of patient, CT showed enlargement of thymus in 31 patients, 5 patients had nodule or mass ( 3 cm) and 9 patients (6.7%) had normal size thymus with soft-tissue density, it can considered with thymic hyperplasia. The spotty or streak shadow showed in other patients, though it could not be certain diagnosed as thymic hyperplasia, but could not be except it. The thymus area tissue complete replacement by fatty density were not found in patient group. The CT findings of patients had marked difference when compared with group of normal subjects (P<0.01), except the spotty or streak shadows. Conclusion: CT scan is an important method in diagnosing thymic lymphofollicular hyperplasia of MG in adult. (authors)

  7. Fate of thymic radioactivity after local labeling with 125Iododeoxyuridine

    International Nuclear Information System (INIS)

    Laissue, J.A.; Chanana, A.D.; Cottier, H.; Cronkite, E.P.; Joel, D.D.

    1976-01-01

    The thymic cortex was locally labeled with 125 Iododeoxyuridine ( 125 IUdR) in young adult mice in an attempt to provide a simple quantitative assessment of the fate of cortical thymocytes. Similarly operated and nonoperated mice given 125 IUdR intravenously were used for comparison. Analogous experiments were performed in adrenalectomized animals. More than 90 percent of thymic activity present 1 day after labeling had been lost by day 8. That proportion of radioactivity contributed to a given organ by accumulation of labeled thymic migrants was estimated by comparison of values obtained after local labeling with those acquired after systemic labeling. Thymic cell accumulation was apparent in the intestine, spleen, mesenteric lymph node, and femurs of locally labeled mice; however, only a few percent of the total activity lost from the thymus was accounted for in these lymphoid organs. The pattern of fecal and urinary elimination of 125 I did not markedly differ in the various experimental groups, the bulk of the activity being recovered in the urine. The intestine could not be ruled out as a major site of thymocyte loss. Since significant radiation or pharmacologic toxicity was unlikely with the doses of 125 IUdR used, the data indicated that the vast majority of newly formed thymocytes dies after a short life and only a small fraction of thymic migrants is longer lived

  8. Age-related perspectives and emotion processing.

    Science.gov (United States)

    Lynchard, Nicholas A; Radvansky, Gabriel A

    2012-12-01

    Emotion is processed differently in younger and older adults. Older adults show a positivity effect, whereas younger adults show a negativity effect. Socioemotional selectivity theory suggests that these effects can be elicited in any age group when age-related perspectives are manipulated. To examine this, younger and older adults were oriented to actual and age-contrasting possible selves. Emotion activations were assessed using lexical decision. In line with socioemotional selectivity theory, shifts in emotion orientation varied according to perspective, with both younger and older adults showing a negativity effect when a younger adult perspective was taken and a positivity effect when an older adult perspective was taken. 2013 APA, all rights reserved

  9. Bioprocessing feasibility analysis. [thymic hormone bioassay and electrophoresis

    Science.gov (United States)

    1978-01-01

    The biology and pathophysiology of the thymus gland is discussed and a clinical procedure for thymic hormone assay is described. The separation of null lymphocytes from mice spleens and the functional characteristics of the cells after storage and transportation were investigated to develop a clinical procedure for thymic hormone assay, and to determine whether a ground-based approach will provide the desired end-product in sufficient quantities, or whether the microgravity of space should be exploited for more economical preparation of the hormone.

  10. Retinoic Acid Signaling in Thymic Epithelial Cells Regulates Thymopoiesis

    DEFF Research Database (Denmark)

    Wendland, Kerstin; Niss, Kristoffer; Kotarsky, Knut

    2018-01-01

    Despite the essential role of thymic epithelial cells (TEC) in T cell development, the signals regulating TEC differentiation and homeostasis remain incompletely understood. In this study, we show a key in vivo role for the vitamin A metabolite, retinoic acid (RA), in TEC homeostasis. In the abse......Despite the essential role of thymic epithelial cells (TEC) in T cell development, the signals regulating TEC differentiation and homeostasis remain incompletely understood. In this study, we show a key in vivo role for the vitamin A metabolite, retinoic acid (RA), in TEC homeostasis...

  11. Antiretroviral therapy increases thymic output in children with HIV

    DEFF Research Database (Denmark)

    Schou Sandgaard, Katrine; Lewis, Joanna; Adams, Stuart

    2014-01-01

    OBJECTIVE: Disease progression and response to antiretroviral therapy (ART) in HIV-infected children is different to that of adults. Immune reconstitution in adults is mainly from memory T cells, whereas in children it occurs predominantly from the naive T-cell pool. It is unclear however what...... with a recently described mathematical model to give explicit measures of thymic output. RESULTS: We found that age-adjusted thymic output is reduced in untreated children with HIV, which increases significantly with length of time on ART. CONCLUSION: Our results suggest that a highly active thymus in early...

  12. Spontaneous rupture of thymic neuroendocrine carcinoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Chan Yeong; Lee, In Jae; Min, Soo Kee [Hallym University College of Medicine, Chuncheon (Korea, Republic of)

    2015-11-15

    Thymic neuroendocrine carcinoma (NEC) is a rare neoplasm with tendencies of local invasion and metastasis. Usually, it is detected incidentally or by its symptoms caused by mass effect. Rupture of the tumor is extremely rare. In this study, we report a case of a ruptured thymic NEC that was combined with a potentially fatal hemorrhage. This lesion was manifested as a progressive bulging of the right cardiac border on serial chest radiographs, and on CT as a large anterior mediastinal mass with heterogeneous enhancement, internal necrosis, and hematoma.

  13. Sarcopenia and Age-Related Endocrine Function

    Directory of Open Access Journals (Sweden)

    Kunihiro Sakuma

    2012-01-01

    Full Text Available Sarcopenia, the age-related loss of skeletal muscle, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, and an increased risk of fall-related injuries. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, numerous targets exist for drug discovery. In this paper, we summarize the current understanding of the endocrine contribution to sarcopenia and provide an update on hormonal intervention to try to improve endocrine defects. Myostatin inhibition seems to be the most interesting strategy for attenuating sarcopenia other than resistance training with amino acid supplementation. Testosterone supplementation in large amounts and at low frequency improves muscle defects with aging but has several side effects. Although IGF-I is a potent regulator of muscle mass, its therapeutic use has not had a positive effect probably due to local IGF-I resistance. Treatment with ghrelin may ameliorate the muscle atrophy elicited by age-dependent decreases in growth hormone. Ghrelin is an interesting candidate because it is orally active, avoiding the need for injections. A more comprehensive knowledge of vitamin-D-related mechanisms is needed to utilize this nutrient to prevent sarcopenia.

  14. Age-related changes in mastication.

    Science.gov (United States)

    Peyron, M A; Woda, A; Bourdiol, P; Hennequin, M

    2017-04-01

    The paper reviews human mastication, focusing on its age-related changes. The first part describes mastication adaptation in young healthy individuals. Adaptation to obtain a food bolus ready to be swallowed relies on variations in number of cycles, muscle strength and volume of emitted saliva. As a result, the food bolus displays granulometric and rheological properties, the values of which are maintained within the adaptive range of deglutition. The second part concerns healthy ageing. Some mastication parameters are slightly modified by age, but ageing itself does not impair mastication, as the adaptation possibilities remain operant. The third part reports on very aged subjects, who display frequent systemic or local diseases. Local and/or general diseases such as tooth loss, salivary defect, or motor impairment are then indistinguishably superimposed on the effects of very old age. The resulting impaired function increases the risk of aspiration and choking. Lastly, the consequences for eating behaviour and nutrition are evoked. © 2016 John Wiley & Sons Ltd.

  15. Radiation therapy: age-related macular degeneration.

    Science.gov (United States)

    Mendez, Carlos A Medina; Ehlers, Justis P

    2013-01-01

    Age-related macular degeneration (AMD) is the leading cause of severe irreversible vision loss in patients over the age of 50 years in the developed world. Neovascular AMD (NVAMD) is responsible for 90% of the cases with severe visual loss. In the last decade, the treatment paradigm for NVAMD has been transformed by the advent of anti-vascular endothelial growth factor therapy. Despite the excellent results of anti-vascular endothelial growth factor therapy, frequent injections remain a necessity for most patients. The burden of these frequent visits as well as the cumulative risks of indefinite intravitreal injections demand continued pursuit of more enduring therapy that provides similar functional results. Radiotherapy has been studied for two decades as a potential therapy for NVAMD. Because of its antiangiogenic properties, radiation therapy remains a promising potential adjunctive resource for the treatment of choroidal neovascularization secondary to NVAMD. This review considers the past, present and future of radiation as a treatment or combination treatment of NVAMD. Copyright © 2013 S. Karger AG, Basel.

  16. Animal models of age related macular degeneration

    Science.gov (United States)

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

  17. Radiotherapy in age-related macula degeneration

    International Nuclear Information System (INIS)

    Gripp, Stephan; Stammen, Johannes; Petersen, Claudia; Hartmann, Axel; Willers, Reinhart; Althaus, Christoph

    2002-01-01

    Purpose: To ascertain the benefit from radiotherapy in age-related macula degeneration in a single-arm longitudinal study. Methods and Materials: From 1997 to 1998, 39 patients with occult and 33 patients with classic choroidal neovascularization (CNV) were irradiated with 16 Gy. Fluorescein angiography and measurements of visual acuity were performed before and 3, 6, and 12 months after irradiation. Results: Complete follow-up data for 1 year were available from 69 patients. The mean patient age was 72 years (range 49-92). Vision decreased in 43, was stable in 18, and improved in 8 cases. The mean vision deteriorated significantly (p=0.02, Wilcoxon test), particularly within the first 3 months. Patients with occult CNV did significantly better than did those with classic CNV (p=0.03). The proportion of patients retaining vision ≥0.2 fell from 65% to 42% (p <0.01), for classic and occult CNV from 50% to 23%, and for occult CNV from 77% to 56% (p<0.02), respectively. CNV size increased in 30 patients and was stable in 38. Neither age (p=0.17) nor gender (p=0.21, chi-square test) influenced prognosis. Four patients reported transitional complaints. Conclusion: Low-dose fractionated radiotherapy with 16 Gy is well tolerated. However, vision and reading ability were not preserved in most patients

  18. Age-related hearing loss or presbycusis.

    Science.gov (United States)

    Huang, Qi; Tang, Jianguo

    2010-08-01

    Aging is a natural consequence of a society developing process. Although many adults retain good hearing as they aging, hearing loss related with age-presbycusis which can vary in severity from mild to substantial is common among elderly persons. There are a number of pathophysiological processes underlying age-related changes in the auditory system as well as in the central nervous systems. Many studies have been dedicated to the illustration of risk factors accumulating presbycusis such as heritability, environment factors, medical conditions, free radical (reactive oxygen species, ROS) and damage of mitochondrial DNA. Left untreated, presbycusis can not only lead sufferers to reduced quality of life, isolation, dependence and frustration, but also affect the healthy people around. These can be partly corrected using hearing aids, but it is not enough, more and more strategies of treatment based on the findings associating with presbycusis should be added rather than using single hearing aids. We review here the pathophysiology; heritability, susceptibility genes and other risk factors including environmental, medical, especially free radical (ROS) and damage of mitochondrial DNA; and some strategies of treatment, as well as promising rehabilitations associating with presbycusis.

  19. Age related macular degeneration and visual disability.

    Science.gov (United States)

    Christoforidis, John B; Tecce, Nicola; Dell'Omo, Roberto; Mastropasqua, Rodolfo; Verolino, Marco; Costagliola, Ciro

    2011-02-01

    Age-related macular degeneration (AMD) is the leading cause of central blindness or low vision among the elderly in industrialized countries. AMD is caused by a combination of genetic and environmental factors. Among modifiable environmental risk factors, cigarette smoking has been associated with both the dry and wet forms of AMD and may increase the likelihood of worsening pre-existing AMD. Despite advances, the treatment of AMD has limitations and affected patients are often referred for low vision rehabilitation to help them cope with their remaining eyesight. The characteristic visual impairment for both forms of AMD is loss of central vision (central scotoma). This loss results in severe difficulties with reading that may be only partly compensated by magnifying glasses or screen-projection devices. The loss of central vision associated with the disease has a profound impact on patient quality of life. With progressive central visual loss, patients lose their ability to perform the more complex activities of daily living. Common vision aids include low vision filters, magnifiers, telescopes and electronic aids. Low vision rehabilitation (LVR) is a new subspecialty emerging from the traditional fields of ophthalmology, optometry, occupational therapy, and sociology, with an ever-increasing impact on the usual concepts of research, education, and services for visually impaired patients. Relatively few ophthalmologists practise LVR and fewer still routinely use prismatic image relocation (IR) in AMD patients. IR is a method of stabilizing oculomotor functions with the purpose of promoting better function of preferred retinal loci (PRLs). The aim of vision rehabilitation therapy consists in the achievement of techniques designed to improve PRL usage. The use of PRLs to compensate for diseased foveae has offered hope to these patients in regaining some function. However, in a recently published meta-analysis, prism spectacles were found to be unlikely to be of

  20. A stromal myoid cell line provokes thymic erythropoiesis between ...

    African Journals Online (AJOL)

    Background: The thymus provides an optimal cellular and humoral microenvironment for cell line committed differentiation of haematopoietic stem cells. The immigration process requires the secretion of at least one peptide called thymotaxine by cells of the reticulo-epithelial (RE) network of the thymic stromal cellular ...

  1. Thymic size at birth in preterm infants with severe respiratory ...

    African Journals Online (AJOL)

    The only maternal and postnatal factors influencing CT/T ratio were the presence of pre-eclamptic toxaemia (PET) and birth by caesarean section (CS), but these factors did not influence likelihood of survival. Factors found to be not associated with thymic size were antenatal steroid administration, maternal HIV status, ...

  2. Thymic size at birth in preterm infants with severe respiratory ...

    African Journals Online (AJOL)

    To determine whether the thymic size in preterm infants with severe respiratory distress syndrome (RDS) can be used to predict ... chorio-amnionitis is associated with a small thymus at birth.4,7. In those ..... Acta Paediatr 2000; 89: 975-978. 6.

  3. Evidence That Androgens Modulate Human Thymic T Cell Output

    Science.gov (United States)

    Olsen, Nancy J.; Kovacs, William J.

    2010-01-01

    Background The thymus has long been recognized as a target for the actions of androgenic hormones, but it has only been recently recognized that alterations in circulating levels of gonadal steroids might affect thymic output of T cells. We had the opportunity to examine parameters of thymic cellular output in several hypogonadal men undergoing androgen replacement therapy. Methods Circulating naive (CD4+CD45RA+) T cells were quantitated by flow cytometric analysis of peripheral blood mononuclear cells (PBMCs). Cells bearing T cell receptor excision circles (TRECs) were quantitated using real-time PCR amplification of DNA isolated from PBMCs from normal men and from hypogonadal men before and after testosterone replacement therapy. Results CD4+CD45+ (“naïve”) T cells comprised 10.5% of lymphocytes in normal males; this proportion was greatly increased in two hypogonadal men (35.5% and 44.4%). One man was studied sequentially during treatment with physiologic doses of testosterone. CD4+CD45RA+ cells fell from 37.36% to 20.05% after one month and to 12.51% after 7 months of normalized androgen levels. In two hypogonadal patients TREC levels fell by 83% and 78% after androgen replacement therapy. Conclusions Our observations indicate that the hypogonadal state is associated with increased thymic output of T cells and that this increase in recent thymic emigrants in peripheral blood is reversed by androgen replacement. PMID:21218609

  4. Expression of tyrosine kinase gene in mouse thymic stromal cells

    NARCIS (Netherlands)

    Rinke de Wit, T. F.; Izon, D. J.; Revilla, C.; Oosterwegel, M.; Bakker, A. Q.; van Ewijk, W.; Kruisbeek, A. M.

    1996-01-01

    Amongst the most important signal transduction molecules involved in regulating growth and differentiation are the protein tyrosine kinases (PTK). Since T cell development is a consequence of interactions between thymic stromal cells (TSC) and thymocytes, identification of the PTK in both

  5. Thymic hyperplasia in a patient with Grave's disease.

    Science.gov (United States)

    Hamzaoui, Amira A; Klii, Rim R; Salem, Randa R; Kochtali, Ines I; Golli, Mondher M; Mahjoub, Silvia S

    2012-02-09

    Hyperplastic changes of the thymus may be found in patients with Graves' disease. However, this rarely presents as an anterior mediastinal mass, particularly among adults. In this report, we describe a 46-year old woman with Graves' disease and thymic hyperplasia.

  6. Thymic hyperplasia in a patient with Grave's disease

    Directory of Open Access Journals (Sweden)

    Hamzaoui Amira A

    2012-02-01

    Full Text Available Abstract Hyperplastic changes of the thymus may be found in patients with Graves' disease. However, this rarely presents as an anterior mediastinal mass, particularly among adults. In this report, we describe a 46-year old woman with Graves' disease and thymic hyperplasia.

  7. IL-33 and Thymic Stromal Lymphopoietin in mast cell functions

    NARCIS (Netherlands)

    Saluja, Rohit; Zoltowska, Anna; Ketelaar, Maria Elizabeth; Nilsson, Gunnar

    2016-01-01

    Thymic Stromal Lymphopoietin (TSLP) and Interleukin 33 (IL-33) are two cytokines released by cells that are in proximity to our environment, e.g., keratinocytes of the skin and epithelial cells of the airways. Pathogens, allergens, chemicals and other agents induce the release of TSLP and IL-33,

  8. Sonographic measurement of thymic size in healthy Korean neonates

    International Nuclear Information System (INIS)

    Seo, Hyun Joo; Yoon, Dae Young; Han, Dae Hee; Han, Sang Wook; Kim, Ho Chul; Kim, Young Mook; Choi, Chul Soon; Bae, Sang Hoon

    2001-01-01

    To assess the variation in thymic size in healthy Korean neonates by sonography and to study the possible correlation to clinical variables. This study was made of 112 healthy Korean neonates (94 full-term and 18 preterm), at less than a week of age. The transverse diameter of the thymus was measured in a transverse scan and the largest sagittal area was assessed in a longitudinal scan. The thymic index was defined as the product of these two values. Then, this index was compared to clinical variables, such as sex, delivery method (spontaneous delivery vs cesarian section), body weight, height, body surface area, head circumference, chest circumference, gestational age, and maternal age in both full-term and preterm groups. The thymic index was 9.6 ± 3.1 (range 3.1-20.2) in full-term and 4.2 ± 2.4 (range 0.9-9.9) in preterm neonates, respectively. The thymic index was positively correlated to the body weight (R=0.550 in full-term, R=0.669 in preterm) and body surface area (R=0.540 in full-term, R=0.674 in preterm) in both full-term and preterm groups (p<0.01). There was no statistically significant correlation to sex, delivery method, height, head circumference, chest circumference, maternal age or gestational age. The thymic index in Healthy Korean neonates as measured by sonography is significantly correlated to the body weight and body surface area of the neonate.

  9. Statins for age-related macular degeneration.

    Science.gov (United States)

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2015-02-11

    Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries. Recent epidemiologic, genetic, and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. The objective of this review was to examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to June 2014), PubMed (January 1946 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 June 2014. We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. We used standard methodological procedures expected by The Cochrane Collaboration. Two authors independently evaluated the search results against the selection criteria, abstracted data, and assessed risk of bias. We did not perform meta-analysis due to heterogeneity in the interventions and outcomes among the included studies. Two RCTs with 144 total participants met the selection criteria

  10. Age-related alteration in the composition of immunocompetent blood cells in atomic bomb survivors

    International Nuclear Information System (INIS)

    Kusunoki, Yoichiro; Akiyama, Mitoshi; Kyoizumi, Seishi; Bloom, E.T.; Makinodan, Takashi; California Univ., Los Angeles

    1988-01-01

    1328 survivors of Hiroshima were studied for alterations in the number of blood lymphocytes belonging to T-cell subpopulations, CD19 antigen-positive B cells and Leu 7 and CD16 antigen-positive lymphocytes. With increasing age, significant decreasing trends in the numbers of some lymphocytes in T-cell subpopulations and of B-cells were seen. The number of blood lymphocytes positive for CD5 antigen was significantly lower in those exposed to radiation (> 1Gy) in the older age group (more than 30 years at the time of bombing) and a similar tendency for decreases in the numbers of CD4, CD8, and CD19 antigen-positive cells was observed, but differences were not significant. The results suggest aging of the T-cell related immune system is accelerated in the irradiated people of advanced age, explained by the age-related decrease in thymic function in those subjects. The number of Leu 7 or CD19 antigen-positive cells was found to be increased significantly in the older age group compared to the younger, although there was little dose dependence. (U.K.)

  11. Evaluation of thymic tumors with 18F-FDG PET-CT - A pictorial review

    International Nuclear Information System (INIS)

    Sharma, Punit; Singhal, Abhinav; Bal, Chandrasekhar; Malhotra, Arun; Kumar, Rakesh; Kumar, Arvind

    2013-01-01

    Thymic tumors represent a broad spectrum of neoplastic disorders and pose considerable diagnostic difficulties. A non-invasive imaging study to determine the nature of thymic lesions can have significant impact on management of such tumors. 18F-flurorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) has shown promising results in characterization of thymic tumors. The objective of this article is to provide an illustrative tutorial highlighting the clinical utility of 18F-FDG PET-CT imaging in patients with thymic tumors. We have pictorially depicted the 18F-FDG PET-CT salient imaging characteristics of various thymic tumors, both epithelial and non-epithelial. Also discussed is the dynamic physiology of thymus gland which is to be kept in mind when evaluating thymic pathology on 18F-FDG PET-CT, as it can lead to interpretative pitfalls

  12. LAT1 acts as a crucial transporter of amino acids in human thymic carcinoma cells

    Directory of Open Access Journals (Sweden)

    Keitaro Hayashi

    2016-11-01

    Full Text Available L-type amino acid transporter 1 (LAT1, SLC7A5 incorporates essential amino acids into cells. Recent studies have shown that LAT1 is a predominant transporter in various human cancers. However, the function of LAT1 in thymic carcinoma remains unknown. Here we demonstrate that LAT1 is a critical transporter for human thymic carcinoma cells. LAT1 was strongly expressed in human thymic carcinoma tissues. LAT1-specific inhibitor significantly suppressed leucine uptake and growth of Ty82 human thymic carcinoma cell lines, suggesting that thymic carcinoma takes advantage of LAT1 as a quality transporter and that LAT1-specific inhibitor might be clinically beneficial in therapy for thymic carcinoma.

  13. Clinical results of radiation therapy for thymic tumors

    Energy Technology Data Exchange (ETDEWEB)

    Masunaga, Shin-ichiro; Ono, Koji; Hiraoka, Masahiro; Kitakabu, Yoshizumi; Abe, Mitsuyuki (Kyoto Univ. (Japan). Faculty of Medicine); Takahashi, Masaji; Fushiki, Masato

    1991-12-01

    From August 1968 to December 1989, 58 patients with thymoma, and 3 with thymic carcinoma were treated by radiotherapy using cobalt-60 gamma ray. Eleven cases were treated by radiotherapy alone, 1 by preoperative radiotherapy, 45 by postoperative radiotherapy, and 4 in combination with intraoperative radiotherapy. In thymoma, postoperative and intraoperative radiotherapies were effective, while concerning postoperative radiotherapy, operability was the major factor influencing survival and local control, and Stage I and II tumors resected totally or subtotally as well as Stage III tumors resected totally were good indications for such therapy. Cases of thymoma complicated by myasthenia gravis had a longer survival time and better local control rate than those without it. In the treatment of thymic carcinoma, it was suggested that the tumors can be controlled using complete resection and sufficient postoperative radiotherpay. (author).

  14. Clinical results of radiation therapy for thymic tumors

    International Nuclear Information System (INIS)

    Masunaga, Shin-ichiro; Ono, Koji; Hiraoka, Masahiro; Kitakabu, Yoshizumi; Abe, Mitsuyuki; Takahashi, Masaji; Fushiki, Masato.

    1991-01-01

    From August 1968 to December 1989, 58 patients with thymoma, and 3 with thymic carcinoma were treated by radiotherapy using cobalt-60 gamma ray. Eleven cases were treated by radiotherapy alone, 1 by preoperative radiotherapy, 45 by postoperative radiotherapy, and 4 in combination with intraoperative radiotherapy. In thymoma, postoperative and intraoperative radiotherapies were effective, while concerning postoperative radiotherapy, operability was the major factor influencing survival and local control, and Stage I and II tumors resected totally or subtotally as well as Stage III tumors resected totally were good indications for such therapy. Cases of thymoma complicated by myasthenia gravis had a longer survival time and better local control rate than those without it. In the treatment of thymic carcinoma, it was suggested that the tumors can be controlled using complete resection and sufficient postoperative radiotherpay. (author)

  15. Thyroid and thymic exeresis in surgery of hyperparathyroidism.

    Science.gov (United States)

    Diaconescu, Mr; Glod, M; Costea, I; Grigorovici, M; Diaconescu, S

    2014-01-01

    Owing to close anatomical and embryological connexions between the thyroid, parathyroids and thymus,manifold coexisting pathology can be identified during the surgery of hyperparathyroidism (Hp). In this retrospective study we report the incidence, clinical forms, histology and management of thyroid and thymic synchronous lesions encountered in as eries of 82 consecutive patients with various types of Hp operated on in the last three decades. Demography, clinical records, biochemical data, imaging procedures, pathology reports and surgical protocols were revised. Between 1984-2013, 82 cases of Hp, 20 primary and 62 renal (27 secondary and 35 tertiary), 57 women and 25 males (sex ratio: 2.3 1) of 15-72 (mean 46.5) years, under went surgery in our clinic. Concomitant thyroid exereses were performed in 32 patients (2 subtotal thyroidectomies, 12 lobectomies, 8 atypical resections and 10 diagnosis biopsies), foruni- or bilateral (multi)nodular goiters or different €œminutelesions. Pathology showed 11 colloid goiters, 3 follicular adenomas,5 nodular hyperplasias and 6 thyroiditis cases, 3 papillary microcarcinomas and 4 specimens with normal thyroid tissue.Excision of the fibrofatty retromanubrial tissue in total parathyroidectomies for renal Hp (19 cases) revealed one nonmyastenicthymoma, one thymic cyst and thymic remnants in 6 patients.Morbidity in these extended operations was not significantly increased, comparing to the parathyroid exploration alone. Meticulous pre- and intraoperative evaluation in all cases of Hp enables the actual shift from bilateral neck exploration to minimally invasive surgery,increasing however the potential risk of missing thyroid or thymic coexistent significant lesions. The surgeon dedicated to this pathology must be aware of the possibility of encountering such synchronous association and make generous efforts to wards their complete cure in a single operation. Celsius.

  16. Effects of the thymic microenvironment on autoantibody production in (NZB X NZW)F1 mice

    International Nuclear Information System (INIS)

    Huston, D.P.; Smathers, P.A.; Reeves, J.P.; Steinberg, A.D.

    1983-01-01

    The effects of the thymic microenvironment on autoantibody production in (NZB X NZW)F1 mice were studied. Neonatally thymectomized male and female F1 mice reconstituted with a parental or F1-irradiated thymic lobe were compared to nonreconstituted and sham-thymectomized controls. While maleness retarded the spontaneous production of ss- and ds-DNA antibodies, thymic grafts did not suppress antibodies to ss-DNA in either sex, but did suppress the production of antibodies to ds-DNA in female mice. A unique property of NZB thymic grafts was the inability to suppress anti-RBC antibodies in male mice. Thus, (i) the gender of the F1 recipient was the most important determinant of production of antibodies to ss-DNA, (ii) either maleness or the thymic microenvironment could retard production of anti-ds-DNA antibodies, and (iii) both gender and the thymic microenvironment were important in the regulation of anti-RBC antibody production. Since the administration of thymosin did not suppress autoantibody production, the effects of the thymic grafts was not solely via thymic hormone production. These studies suggest that sex hormones and/or the thymic microenvironment can exert a suppressive effect on autoantibody production and that autoantibodies differ in their susceptibility to such suppression

  17. [Thymic carcinoma involving aortic arch; report of a case].

    Science.gov (United States)

    Noriyuki, Toshio; Hamamoto, M; Takazawa, Y; Katoh, K; Hashimoto, M; Kuranishi, F; Nakahara, M; Fukuda, T; Ishizaki, Y; Okuda, H; Akimoto, E; Yonehara, S

    2009-05-01

    Adenocarcinoma of the thymus is a very rare malignant tumor. The standard treatment for advanced thymic carcinoma has not yet been established, and the prognosis is poor. We report a case of thymic carcinoma that involving the aortic arch and the innominate vein. A 78-year-old woman was admitted to our hospital complaining of hoarseness in April 2007. The computed tomography (CT) scan showed an anterior mediastinal tumor contiguous to the aortic arch and the innominate vein with swelling lymphnodes. Microspcopic examinations of specimens obtained by CT-guided needle biopsy revealed poorly differenciated adenocarcinoma. The carcinoembryonic antigen (CEA) level of serum elevated at 54.9 ng/ml. Thymic carcinoma was diagnosed. The chemoradiotherapy [concurrent, carboplatin (CBDCA) + paclitaxel(TXL)-->vinorelbine (NVB), 60 Gy] was performed, but the effect of the therapy was limited. The resection of the tumor with a part of aortic arch and other peripheral tissues was performed in Augast 2007. The postoperative course was uneventful and the CEA level of serum lowered to the normal. She was discharged 30 days after surgery.

  18. Age-Related Maculopathy: a biochemical and immunohistochemical study

    NARCIS (Netherlands)

    M. Kliffen (Mike)

    1996-01-01

    textabstractAge-related maculopathy (ARM) is an age-related degenerative disorder of the central part of the retina, the macula lutea (yellow spot). Essentially, ARM is a clinical diagnosis based on funduscopical changes. It is customary nowadays to call the late stages of ARM, geographic atrophy

  19. Prevalence of age-related macular degeneration in elderly Caucasians

    DEFF Research Database (Denmark)

    Erke, Maja G; Bertelsen, Geir; Peto, Tunde

    2012-01-01

    To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD).......To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD)....

  20. Interaction between thymic cells and hemopoietic stem cells. Enhanced repopulation of the irradiated thymus

    International Nuclear Information System (INIS)

    Daculsi, Richard; Legrand, Elisabeth; Duplan, J.-F.

    1977-01-01

    In irradiated mice engrafted with hemopoietic cells, the thymus is repopulated more rapidly by bone marrow-derived than by spleen-derived cells. Admixing thymic cells with restorative suspension stimulates the thymic repopulation by spleen-derived cells whereas it has no effect on the repopulation by bone marrow-derived cells [fr

  1. Anti-apoptotic signature in thymic squamous cell carcinomas – functional relevance of anti-apoptotic BIRC3 expression in the thymic carcinoma cell line 1889c

    OpenAIRE

    Huang, Bei; Belharazem, Djeda; Li, Li; Kneitz, Susanne; Schnabel, Philipp A.; Rieker, Ralf J.; Körner, Daniel; Nix, Wilfried; Schalke, Berthold; Müller-Hermelink, Hans Konrad; Ott, German; Rosenwald, Andreas; Ströbel, Philipp; Marx, Alexander

    2016-01-01

    The molecular pathogenesis of thymomas and thymic carcinomas (TCs) is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and thymic carcinomas, suggesting that other oncogenic principles might ...

  2. Direct analysis of thymic function in children with Down's syndrome

    Directory of Open Access Journals (Sweden)

    Meschiari Liviana

    2005-02-01

    Full Text Available Abstract Background Down's syndrome (DS is characterized by several immunological defects, especially regarding T cell compartment. DS is considered the best example of accelerated ageing in humans. Direct observations of the thymus have shown that in DS this organ undergoes severe histological and morphological changes. However, no data on its capacity to generate T cells are present in the literature. Here, using a new technology based upon real time PCR, we have investigated the capacity of the thymus to produce and release newly generated T lymphocytes (the so called "recent thymic emigrants", RTE in children with DS. Methods We studied 8 children affected by DS, aged 2–7 years, compared with 8 age- and sex-matched healthy controls. Flow cytometry was used to determine different lymphocytes subsets. Real time PCR with the Taqman system was used to quantify the amount of RTE, i.e. peripheral blood lymphocytes that express the T cell receptor rearrangement excision circles (TREC. Results In comparison with control children, those with DS had a significant lower number of TREC+ peripheral blood cells. Moreover, in DS children but not in controls, a strong negative correlation between age and the levels of TREC+ cells was found. Conclusions The direct measure of thymic output indicates that the impairment of the organ results in a reduced production of newly generated T cells. This observation could suggest that cytokines able to modulate thymic function, such as interleukins, could be useful to improve the functionality of the organ and to treat the immunodeficiency present in DS subjects.

  3. Radiotherapy for invasive thymoma and thymic carcinoma. Clinicopathological review

    International Nuclear Information System (INIS)

    Mayer, R.; Stuecklschweiger, G.F.; Prettenhofer, U.; Stranzl, H.; Hackl, A.; Beham-Schmid, C.; Groell, R.; Smolle-Juettner, F.M.; Renner, H.; Quehenberger, F.

    1999-01-01

    All 33 patients were irradiated with a mean dose of 50 Gy after complete resection (16 patients), partial resection (9 patients) of biopsy (8 patients). Staging was done according to the Masaoka classification; there were 12 Stage II, 12 Stage III and 9 Stage IV patients. Results: In patients with invasive thymoma Stage II to IV (median follow-up 54.4 months) Kaplan-Meier estimates of overall survival (OS), disease-specific (DSS) and disease-free survival (DFS) at 5 years were 63.7% (95% confidence interval [CI], 42 to 84%), 88.3% (CI, 75 to 100%) and 77,4% (CI, 58 to 95%), respectively. Among the prognostic factors tested, such as age, myasthenia gravis, completeness of surgery and histologic subclassification, total radiation dose, and Masaoka Stage, the latter was the only significant predictor of improved survival (p=0.04). Considering local control, radiation dose was a significant prognostic factor (p=0.0006). In patients with thymic carcinoma (median follow-up 43.4 months) 5 year DSS, and DFS were 22.2% (CI, 0 to 60%) and 16.7% (CI, 0 to 46%), respectively. Thymoma as compared to thymic carcinoma had a statistically significant better DSS (p=0.007) and DFS (p=0.0007). Conclusion: Postoperative radiotherapy with sufficient doses plays an important role as adjuvant treatment in complete or incomplete resected invasive Stage II to III thymoma. In unresectable thymoma Stage III to IV as well as in thymic carcinoma a multimodality approach should be considered to improve survival. (orig.) [de

  4. Immunologic competence in adults following thymic irradiation in infancy

    International Nuclear Information System (INIS)

    Ammann, A.J.; Wara, W.M.; Wara, D.W.; Phillips, T.L.

    1977-01-01

    Removal of, or irradiation to, the thymus during the neonatal period in man has resulted in no reported adverse effects on cellular immunity, although thymectomy in neonatal experimental animals is known to produce profound immunological disturbances. Adverse effects in humans may not be recognized until several decades have passed. The immunological capabilities of 7 adults with histories of thymic irradiation as infants were evaluated; normal tests results indicated intact immune systems in all cases. The 3 women tested, however, had abnormal clinical histories, including 2 with multiple tumors and 1 with chronic mucocutaneous candidiasis

  5. Human thymic epithelial cells express functional HLA-DP molecules

    DEFF Research Database (Denmark)

    Jørgensen, A; Röpke, C; Nielsen, M

    1996-01-01

    T lymphocytes, we examined whether human thymic epithelial cells (TEC) expressed HLA-DP molecules. We present evidence that TEC obtained from short time culture express low but significant levels of HLA-DP molecules. The expression of HLA-DP molecules was comparable to or higher than the expression...... of HLA-DP allospecific primed lymphocyte typing (PLT) CD4 T cell lines. IFN-gamma treatment strongly upregulated the HLA-DP allospecific PLT responses whereas other PLT responses remained largely unchanged. In conclusion, these data indicate that human thymus epithelial cells express significant levels...

  6. Immunologic competence in adults following thymic irradiation in infancy

    Energy Technology Data Exchange (ETDEWEB)

    Ammann, A.J.; Wara, W.M.; Wara, D.W.; Phillips, T.L.

    1977-07-01

    Removal of, or irradiation to, the thymus during the neonatal period in man has resulted in no reported adverse effects on cellular immunity, although thymectomy in neonatal experimental animals is known to produce profound immunological disturbances. Adverse effects in humans may not be recognized until several decades have passed. The immunological capabilities of 7 adults with histories of thymic irradiation as infants were evaluated; normal tests results indicated intact immune systems in all cases. The 3 women tested, however, had abnormal clinical histories, including 2 with multiple tumors and 1 with chronic mucocutaneous candidiasis.

  7. The Age-Related Changes in Cartilage and Osteoarthritis

    Directory of Open Access Journals (Sweden)

    YongPing Li

    2013-01-01

    Full Text Available Osteoarthritis (OA is closely associated with aging, but its underlying mechanism is unclear. Recent publications were reviewed to elucidate the connection between aging and OA. With increasing OA incidence, more senior people are facing heavy financial and social burdens. Age-related OA pathogenesis is not well understood. Recently, it has been realized that age-related changes in other tissues besides articular cartilage may also contribute to OA development. Many factors including senescence-related secretory phenotypes, chondrocytes’ low reactivity to growth factors, mitochondrial dysfunction and oxidative stress, and abnormal accumulation of advanced glycation end products (AGEs may all play key roles in the pathogenesis of age-related OA. Lately, epigenetic regulation of gene expression was recognized for its impact on age-related OA pathogenesis. Up to now, few studies have been reported about the role of miRNA and long-noncoding RNA (lncRNA in age-related OA. Research focusing on this area may provide valuable insights into OA pathogenesis. OA-induced financial and social burdens have become an increasingly severe threat to older population. Age-related changes in noncartilage tissue should be incorporated in the understanding of OA development. Growing attention on oxidative stress and epigenetics will provide more important clues for the better understanding of the age-related OA.

  8. Impacts of age-related failures on nuclear systems

    International Nuclear Information System (INIS)

    Meale, B.M.; Satterwhite, D.G.; Krantz, E.A.; MacDonald, P.E.

    1986-01-01

    Aging-related failure data from nine light water reactor safety, support, and power conversion systems have been extracted from an operational data base. Systems and components within the systems that are most affected by aging are identified. In addition, information on aging-related root causes of component failures has been extracted for service water and Class 1E electrical power distribution systems. Engineering insights are presented, and preliminary quantification of the importance of aging-related root causes for a service water system is provided

  9. [Current concepts in pathogenesis of age-related macular degeneration].

    Science.gov (United States)

    Kubicka-Trząska, Agnieszka; Karska-Basta, Izabella; Romanowska-Dixon, Bożena

    2014-01-01

    Age-related macular degeneration is the leading cause of central blindness in elderly population of the western world. The pathogenesis of this disease, likely multifactorial, is not well known, although a number of theories have been put forward, including oxidative stress, genetic interactions, hemodynamic imbalance, immune and inflammatory processes. The understanding of age-related macular degeneration pathogenesis will give rise to new approaches in prevention and treatment of the early and late stages of both atrophic and neovascular age-related macular degeneration.

  10. Generation of Tumor Antigen-Specific iPSC-Derived Thymic Emigrants Using a 3D Thymic Culture System

    Directory of Open Access Journals (Sweden)

    Raul Vizcardo

    2018-03-01

    Full Text Available Summary: Induced pluripotent stem cell (iPSC-derived T cells may provide future therapies for cancer patients, but those generated by current methods, such as the OP9/DLL1 system, have shown abnormalities that pose major barriers for clinical translation. Our data indicate that these iPSC-derived CD8 single-positive T cells are more like CD4+CD8+ double-positive T cells than mature naive T cells because they display phenotypic markers of developmental arrest and an innate-like phenotype after stimulation. We developed a 3D thymic culture system to avoid these aberrant developmental fates, generating a homogeneous subset of CD8αβ+ antigen-specific T cells, designated iPSC-derived thymic emigrants (iTEs. iTEs exhibit phenotypic and functional similarities to naive T cells both in vitro and in vivo, including the capacity for expansion, memory formation, and tumor suppression. These data illustrate the limitations of current methods and provide a tool to develop the next generation of iPSC-based antigen-specific immunotherapies. : A barrier for clinical application of iPSC-derived CD8 T cells using OP9/DLL1 is their abnormal biology. Vizcardo et al. show that a 3D thymic culture system enables the generation of a homogeneous antigen-specific T cell subset, named iTEs, which closely mimics naive T cells and exhibits potent anti-tumor activity. Keywords: thymopoiesis, T cell differentiation, iPSC differentiation, adoptive cell transfer, naïve T cell, recent rhymic emigrants, fetal thymus organ culture, immunotherapy, 3D culture, tumor antigen specific T cell

  11. Flt3 ligand-receptor interaction is important for maintenance of early thymic progenitor numbers in steady-state thymopoiesis.

    Science.gov (United States)

    Kenins, Linda; Gill, Jason W; Holländer, Georg A; Wodnar-Filipowicz, Aleksandra

    2010-01-01

    T-cell production throughout life depends on efficient colonization and intrathymic expansion of BM-derived hematopoietic precursors. After irradiation-induced thymic damage, thymic recovery is facilitated by Flt3 ligand (FL), expressed by perivascular fibroblasts surrounding the thymic entry site of Flt3 receptor-positive progenitor cells. Whether intrathymic FL-Flt3 interactions play a role in steady-state replenishment of T cells remains unknown. Here, using competitive BM transplantation studies and fetal thymic organ cultures we demonstrated the continued numerical advantage of Flt3+ intrathymic T-cell precursors. Sub-kidney capsule thymic transplantation experiments, in which WT and FL-/- thymic lobes were grafted into FL-/- recipients, revealed that FL expression by the thymic microenvironment plays a role in steady-state thymopoiesis. The deficiency of the most immature thymic T-cell precursors correlated to upregulation of FL by thymic MTS15+ fibroblasts, suggesting that the number of Flt3+ progenitor cells may regulate the thymic expression of this cytokine. Together, these results show that FL expression by thymic stromal fibroblasts interacting with Flt3+ T-cell progenitors is important for the physiological maintenance of early T-cell development.

  12. Low Calorie Diet Affects Aging-Related Factors

    Science.gov (United States)

    ... Current Issue Past Issues Research News From NIH Low Calorie Diet Affects Aging-Related Factors Past Issues / ... to learn more about the effects of sustained low-calorie diets in humans on factors affecting aging. ...

  13. Review Article Therapeutic Potential of Statins in Age-related ...

    African Journals Online (AJOL)

    2011-08-09

    Aug 9, 2011 ... Keywords: Age-related macular, Non-invasive treatment, Pleiotropic effects, Prevention, Statins. Received 14 June ... two types: non-exudative or “dry', characterised by .... Dam Eye Study in Wisconsin, statin use at the 10-.

  14. [Depression in Patients with Age-Related Macular Degeneration].

    Science.gov (United States)

    Narváez, Yamile Reveiz; Gómez-Restrepo, Carlos

    2012-09-01

    Age-related macular degeneration is a cause for disability in the elderly since it greatly affects their quality of life and increases depression likelihood. This article discusses the negative effect depression has on patients with age-related macular degeneration and summarizes the interventions available for decreasing their depression index. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  15. Reactive thymic hyperplasia following treatment of ACTH-producing tumors

    International Nuclear Information System (INIS)

    Schmidt, S.; Klose, K.J.; Iwinska-Zelder, J.; Frank, M.; Ehlenz, K.; Kisker, O.

    1997-01-01

    Surgical or conservative treatment of ACTH-producing tumors results in acute drop of the previously excessively high cortisol levels. The following associated pathophysiological changes also occur in the organism's recovery from stress, such as trauma, operation or chemotherapy of tumors. Both cases result in a regeneration of the immune system, which might even be exalted. The corresponding radiographic feature is the 'rebound' enlargement of the thymus occuring about six months after remission of hypercortisolism. Histological examination reveals benign thymus hyperplasia. Especially in cases of still unkown primary tumor the apperance of this anterior mediastinal mass can lead to misdiagnosis. We present the cases of two patients with diffuse thymic hyperplasia following surgical and medical correction of hypercortisolism. One patient suffered from classic Cushing's disease responding to transsphenoidal resection of an ACTH-secreting pituitary microadenoma. Six monsths later CT of the chest incidentally demonstrated an anterior mediastinal mass known as thymic hyperplasia. The second patient presented with an ectopic, still unknown source of ACTH-production. (orig./AJ) [de

  16. Mutational status of EGFR and KIT in thymoma and thymic carcinoma.

    Science.gov (United States)

    Yoh, Kiyotaka; Nishiwaki, Yutaka; Ishii, Genichiro; Goto, Koichi; Kubota, Kaoru; Ohmatsu, Hironobu; Niho, Seiji; Nagai, Kanji; Saijo, Nagahiro

    2008-12-01

    This study was conducted to evaluate the prevalence of EGFR and KIT mutations in thymomas and thymic carcinomas as a means of exploring the potential for molecularly targeted therapy with tyrosine kinase inhibitors. Genomic DNA was isolated from 41 paraffin-embedded tumor samples obtained from 24 thymomas and 17 thymic carcinomas. EGFR exons 18, 19, and 21, and KIT exons 9, 11, 13, and 17, were analyzed for mutations by PCR and direct sequencing. Protein expression of EGFR and KIT was evaluated immunohistochemically. EGFR mutations were detected in 2 of 20 thymomas, but not in any of the thymic carcinomas. All of the EGFR mutations detected were missense mutations (L858R and G863D) in exon 21. EGFR protein was expressed in 71% of the thymomas and 53% of the thymic carcinomas. The mutational analysis of KIT revealed only a missense mutation (L576P) in exon 11 of one thymic carcinoma. KIT protein was expressed in 88% of the thymic carcinomas and 0% of the thymomas. The results of this study indicate that EGFR and KIT mutations in thymomas and thymic carcinomas are rare, but that many of the tumors express EGFR or KIT protein.

  17. Clinical analysis of thymic regrowth following chemotherapy in children and adolescents with malignant lymphoma

    International Nuclear Information System (INIS)

    Zhen Zijun; Sun Xiaofei; Xia Yi; Ling Jiayu; Cai Yue; Wang Juan; Guan Zhongzhen

    2010-01-01

    Thymic regrowth following chemotherapy has typical clinical and imaging manifestations that can be used to diagnose it prior to pathological diagnosis. We investigated methods for diagnosing thymic regrowth following chemotherapy with non-invasive methods. Our study included 26 children and adolescents with thymic regrowth following chemotherapy for malignant lymphoma. Computed tomography scans were routinely performed for follow-up observations. After the emergence of new mediastinal masses, patients either underwent Fluorine-18 fluorodeoxyglucose-positron emission tomography scans to identify the characteristics of the mass, or were closely followed up. Thymic regrowth occurred 1-12 months after the last chemotherapy (mean, 4 months). Computed tomography mostly revealed diffusely enlarged thymic parenchymatous tissues that maintained normal thymic morphology. Computed tomography values were 36.72±9.48 Hu and increased by 5.56±2.62 Hu in contrast enhancement. The mean volume of the mass was 19.2 cm 3 . Twenty patients underwent positron emission tomography; among them, five (25%) showed no intake of Fluorine-18 fluorodeoxyglucose in the anterior mediastinal mass, and 15 (75%) showed radioactivity distribution in the mass with a mean standardized uptake value of 2.7; the shape was regular and radioactivity distribution was uniform. The mean follow-up duration was 40 months and all patients achieved disease-free survival. In the absence of pathological diagnosis, thymic regrowth following chemotherapy can be diagnosed by clinical features combined with characteristic manifestations in computed tomography and positron emission tomography scans. (author)

  18. Risk factors of age-related macular degeneration in Argentina

    Directory of Open Access Journals (Sweden)

    María Eugenia Nano

    2013-04-01

    Full Text Available PURPOSES: To assess the risk factors of age-related macular degeneration in Argentina using a case-control study. METHODS: Surveys were used for subjects' antioxidant intake, age/gender, race, body mass index, hypertension, diabetes (and type of treatment, smoking, sunlight exposure, red meat consumption, fish consumption, presence of age-related macular degeneration and family history of age-related macular degeneration. Main effects models for logistic regression and ordinal logistic regression were used to analyze the results. RESULTS: There were 175 cases and 175 controls with a mean age of 75.4 years and 75.5 years, respectively, of whom 236 (67.4% were female. Of the cases with age-related macular degeneration, 159 (45.4% had age-related macular degeneration in their left eyes, 154 (44.0% in their right eyes, and 138 (39.4% in both eyes. Of the cases with age-related macular degeneration in their left eyes, 47.8% had the dry type, 40.3% had the wet type, and the type was unknown for 11.9%. The comparable figures for right eyes were: 51.9%, 34.4%, and 13.7%, respectively. The main effects model was dominated by higher sunlight exposure (OR [odds ratio]: 3.3 and a family history of age-related macular degeneration (OR: 4.3. Other factors included hypertension (OR: 2.1, smoking (OR: 2.2, and being of the Mestizo race, which lowered the risk of age-related macular degeneration (OR: 0.40. Red meat/fish consumption, body mass index, and iris color did not have an effect. Higher age was associated with progression to more severe age-related macular degeneration. CONCLUSION: Sunlight exposure, family history of age-related macular degeneration, and an older age were the significant risk factors. There may be other variables, as the risk was not explained very well by the existing factors. A larger sample may produce different and better results.

  19. Thymic epithelial tumors: Comparison of CT and MR imaging findings of low-risk thymomas, high-risk thymomas, and thymic carcinomas

    International Nuclear Information System (INIS)

    Sadohara, Junko; Fujimoto, Kiminori; Mueller, Nestor L.; Kato, Seiya; Takamori, Shinzo; Ohkuma, Kazuaki; Terasaki, Hiroshi; Hayabuchi, Naofumi

    2006-01-01

    Objective: To assess the CT and magnetic resonance (MR) imaging findings of thymic epithelial tumors classified according to the current World Health Organization (WHO) histologic classification and to determine useful findings in differentiating the main subtypes. Materials and methods: Sixty patients with thymic epithelial tumor who underwent both CT and MR imaging were reviewed retrospectively. All cases were classified according to the 2004 WHO classification. The following findings were assessed in each case on both CT and MRI: size of tumor, contour, perimeter of capsule; homogeneity, presence of septum, hemorrhage, necrotic or cystic component within tumor; presence of mediastinal lymphadenopathy, pleural effusion, and great vessel invasion. These imaging characteristics of 30 low-risk thymomas (4 type A, 12 type AB, and 14 type B1), 18 high-risk thymomas (11 type B2 and seven type B3), and 12 thymic carcinomas on CT and MR imaging were compared using the chi-square test. Comparison between CT and MR findings was performed by using McNemar test. Results: On both CT and MR imaging, thymic carcinomas were more likely to have irregular contours (P < .001), necrotic or cystic component (P < .05), heterogeneous contrast-enhancement (P < .05), lymphadenopathy (P < .0001), and great vessel invasion (P < .001) than low-risk and high-risk thymomas. On MR imaging, the findings of almost complete capsule, septum, and homogenous enhancement were more commonly seen in low-risk thymomas than high-risk thymomas and thymic carcinomas (P < .05). MR imaging was superior to CT in the depiction of capsule, septum, or hemorrhage within tumor (all comparison, P < .05). Conclusion: The presence of irregular contour, necrotic or cystic component, heterogeneous enhancement, lymphadenopathy, and great vessel invasion on CT or MR imaging are strongly suggestive of thymic carcinomas. On MR imaging, the findings of contour, capsule, septum, and homogenous enhancement are helpful in

  20. Intrapericardial primary thymic carcinoma in a 73-year-old man.

    Science.gov (United States)

    Calderon, Ana Maria; Merchan, Juan Andres; Rozo, Juan Carlos; Guerrero, Cesar Ivan; Treistman, Bernardo; Sulak, Laura E; Cheong, Benjamin Y C; Rodríguez, German; Mesa, Andrés

    2008-01-01

    Thymic carcinoma is a rare, highly aggressive type of tumor that typically occurs in the anterior mediastinum. We describe the case of a 73-year-old man who presented with weakness, cough, dyspnea, anorexia, and weight loss. An echocardiogram showed an intrapericardial mass that occupied the space around the lateral walls of the left ventricle and distally compressed the right ventricle. Magnetic resonance imaging and a biopsy confirmed the presence of intrapericardial primary thymic carcinoma. The patient underwent surgical excision of the tumor and died of right ventricular rupture during the procedure. This case highlights the importance of considering thymic carcinoma whenever an otherwise unexplained intrapericardial mass is encountered.

  1. Glucose and age-related changes in memory.

    Science.gov (United States)

    Gold, Paul E

    2005-12-01

    Epinephrine, released from the adrenal medulla, enhances memory in young rats and mice and apparently does so, at least in part, by increasing blood glucose levels. Like epinephrine, administration of glucose enhances cognitive functions in humans and rodents, including reversing age-related impairments in learning and memory. Epinephrine responses to training are increased in aged rats but the subsequent increase in blood glucose levels is severely blunted. The absence of increases in blood glucose levels during training might contribute to age-related deficits in learning and memory. Also, extracellular glucose levels in the hippocampus are depleted during spontaneous alternation testing to a far greater extent in aged than in young rats. Importantly, systemic injections of glucose block the depletion in the hippocampus and also enhance performance on the alternation task. Thus, the extensive depletion of extracellular glucose during training in aged rats may be associated with age-related memory impairments, an effect that might be related to - or may exacerbate - the effects on learning and memory of an absence of the increases in blood glucose levels to training as seen in young rats. Together, these findings suggest that age-related changes in both peripheral and central glucose physiology contribute to age-related impairments in memory.

  2. Age-related synthesis of glucocorticoids in thymocytes

    International Nuclear Information System (INIS)

    Qiao Shengjun; Chen Liying; Okret, Sam; Jondal, Mikael

    2008-01-01

    Glucocorticoids (GCs) are primarily synthesized in the adrenal glands but an ectopic production has also been reported in the brain, the gastrointestinal tract and in thymic epithelial cells (TEC). Here we show that thymocytes express genes encoding for all enzymes required for de novo GC synthesis and produce the hormone as demonstrated by both a GC specific reporter assay and a corticosterone specific ELISA assay. Interestingly, GC synthesis is detectable in cells from young mice (4 weeks) and thereafter increases during aging (14-22 weeks) together with an increased gene expression of the rate-limiting enzymes StAR and CYP11A1. Hormone production occurred at a thymocyte differentiation stage characterized by being double positive for the CD4 and CD8 surface markers but was found to be unrelated to CD69 expression, a marker for thymocytes undergoing positive selection. No GC synthesis was found in resting or anti-CD3 activated CD4 and CD8 positive T cells isolated from the spleen. Thymocyte-derived GC had an anti-proliferative effect on a GR-transfected cell line and induced apoptosis in thymocytes. The age- and differentiation stage-related GC synthesis in thymocytes may play a role in the involution process that the thymus gland undergoes

  3. CREB Overexpression Ameliorates Age-related Behavioral and Biophysical Deficits

    Science.gov (United States)

    Yu, Xiao-Wen

    Age-related cognitive deficits are observed in both humans and animals. Yet, the molecular mechanisms underlying these deficits are not yet fully elucidated. In aged animals, a decrease in intrinsic excitability of pyramidal neurons from the CA1 sub-region of hippocampus is believed to contribute to age-related cognitive impairments, but the molecular mechanism(s) that modulate both these factors has yet to be identified. Increasing activity of the transcription factor cAMP response element-binding protein (CREB) in young adult rodents has been shown to facilitate cognition, and increase intrinsic excitability of their neurons. However, how CREB changes with age, and how that impacts cognition in aged animals, is not clear. Therefore, we first systematically characterized age- and training-related changes in CREB levels in dorsal hippocampus. At a remote time point after undergoing behavioral training, levels of total CREB and activated CREB (phosphorylated at S133, pCREB) were measured in both young and aged rats. We found that pCREB, but not total CREB was significantly reduced in dorsal CA1 of aged rats. Importantly, levels of pCREB were found to be positively correlated with short-term spatial memory in both young and aged rats i.e. higher pCREB in dorsal CA1 was associated with better spatial memory. These findings indicate that an age-related deficit in CREB activity may contribute to the development of age-related cognitive deficits. However, it was still unclear if increasing CREB activity would be sufficient to ameliorate age-related cognitive, and biophysical deficits. To address this question, we virally overexpressed CREB in CA1, where we found the age-related deficit. Young and aged rats received control or CREB virus, and underwent water maze training. While control aged animals exhibited deficits in long-term spatial memory, aged animals with CREB overexpression performed at levels comparable to young animals. Concurrently, aged neurons

  4. T-lymphocyte subsets, thymic size and breastfeeding in infancy

    DEFF Research Database (Denmark)

    Jeppesen, Dorthe Lisbeth; Hasselbalch, Helle; Lisse, Ida M

    2004-01-01

    We followed the changes in concentration of T-lymphocyte subsets (CD4+ and CD8+ cells) in peripheral blood and thymus size during infancy. Previous studies have found increased thymus size in breastfed infants. The present study analyzed the association between breastfeeding and the number of CD4......+ and CD8+ cells. Two different populations of infants between birth and 1 year of age were examined. Study Group I: infants with a variable duration of breastfeeding. Study Group II: long-term breastfed infants. In both groups a correlation was found between CD8+ cells and the thymic index at 10 months...... to 10 months of age; and a positive correlation between the number of breastfeedings per day at 8 months of age, and an increase in CD4+ cells from 8 to 10 months of age (p Breastfeeding might have both a current and long...

  5. The diagnosis of thymoma and thymic atrophy in patients with myasthenia gravis

    International Nuclear Information System (INIS)

    Sund, K.K.; Skeie, G.O.; Gilhus, N.E.; Aarli, J.A.; Varhaug, J.E.

    1997-01-01

    The authors have compared clinical, immunological and radiological data in 20 patients with myasthenia gravis and thymoma and in 21 patients with myasthenia gravis and thymic atrophy. The median age at onset was 54 years in the thymoma group and 63 years in the thymic atrophy group. The severity of the disease was similar in the two groups, and there was no significant difference in the concentration of acetylcholine receptor antibodies. CA antibodies were demonstrated in 17/20 thymoma patients and in 6/21 with thymic atrophy, while 19/20 thymoma patients had antibodies to titin, compared with 9/21 among those with thymic atrophy. The diagnosis and treatment of patients with myasthenia gravis is based upon an evaluation of clinical, immunological and radiological data. 28 refs., 2 tabs

  6. Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration

    Science.gov (United States)

    Wertheimer, Tobias; Velardi, Enrico; Tsai, Jennifer; Cooper, Kirsten; Xiao, Shiyun; Kloss, Christopher C.; Ottmüller, Katja J.; Mokhtari, Zeinab; Brede, Christian; deRoos, Paul; Kinsella, Sinéad; Palikuqi, Brisa; Ginsberg, Michael; Young, Lauren F.; Kreines, Fabiana; Lieberman, Sophia R.; Lazrak, Amina; Guo, Peipei; Malard, Florent; Smith, Odette M.; Shono, Yusuke; Jenq, Robert R.; Hanash, Alan M.; Nolan, Daniel J.; Butler, Jason M.; Beilhack, Andreas; Manley, Nancy R.; Rafii, Shahin; Dudakov, Jarrod A; van den Brink, Marcel RM

    2018-01-01

    The thymus is extremely sensitive to damage but also has a remarkable ability to repair itself. However, the mechanisms underlying this endogenous regeneration remain poorly understood and this capacity diminishes considerably with age. Here we show that thymic endothelial cells (ECs) comprise a critical pathway of regeneration, via their production of BMP4. ECs increased their production of BMP4 after thymic damage, and abrogating BMP4 signalling or production by either pharmacologic or genetic inhibition impaired thymic repair. EC-derived BMP4 acted on thymic epithelial cells (TECs) to increase their expression of Foxn1, a key transcription factor involved in TEC development, maintenance and regeneration; and its downstream targets such as Dll4, itself a key mediator of thymocyte development and regeneration. These studies demonstrate the importance of the BMP4 pathway in endogenous tissue regeneration and offer a potential clinical approach to enhance T cell immunity. PMID:29330161

  7. Implantation of cultured thymic fragments in patients with acquired immunodeficiency syndrome

    NARCIS (Netherlands)

    Danner, S. A.; Schuurman, H. J.; Lange, J. M.; Gmelig Meyling, F. H.; Schellekens, P. T.; Huber, J.; Kater, L.

    1986-01-01

    Cultured thymic fragments were implanted in one patient with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) and in eight AIDS patients with opportunistic infections (OIs, four patients), Kaposi's sarcoma (KS, two patients), or both (two patients). Thereafter, objective clinical

  8. A rear case of multilocular thymic cyst with follicular lymphoid hyperplasia; Radiologic and histopathologic features

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Suk; Cha, Eun Jung [Konyang University Hospital, Daejeon (Korea, Republic of)

    2016-06-15

    Multilocular thymic cysts are rare and acquired lesions induced by an inflammatory arising within the thymus. We report a rare case of multilocular thymic cyst with follicular lymphoid hyperplasia in a 59-year-old female. Chest CT and MRI revealed a large multilocular cystic mass, which contains thick septa and nodules in the thymus. F-18 FDG PET/CT showed almost no FDG uptake of the multilocular cystic mass but moderate FDG uptake of the solid nodules. Extended total thymectomy was performed. Histopathological findings revealed follicular lymphoid hyperplasia of thymic tissue but no neoplastic lesion. Based on these findings, diagnosis of multilocular thymic cyst with follicular lymphoid hyperplasia was made. This is a rare case that preoperatively was difficult to diagnose.

  9. Genetic analysis of radiation-induced mouse thymic lymphomas

    International Nuclear Information System (INIS)

    Kominami, R.; Wakabayashi, Y.; Niwa, O.

    2003-01-01

    Mouse thymic lymphomas are one of the classic models of radiation-induced malignancies, and the model has been used for the study of genes involved in carcinogenesis. ras oncogenes are the first isolate which undergoes mutations in 10 to 30 % of lymphomas, and p16INK4a and p19ARF in the INK4a-ARF locus are also frequently inactivated. In our previous study, the inactivation of Ikaros, a key regurator of lymphoid system, was found in those lymphomas, and it was suggested that there are other responsible genes yet to be discovered. On the other hand, genetic predisposition to radiation-induced lymphoma often differs in different strains, and this reflects the presence of low penetrance genes that can modify the impact of a given mutation. Little study of such modifiers or susceptibility genes has been performed, either. Recent availability of databases on mouse genome information and the power of mouse genetic system underline usefulness of the lymphoma model in search for novel genes involved, which may provide clues to molecular mechanisms of development of the radiogenic lymphoma and also genes involved in human lymphomas and other malignancies. Accordingly, we have carried out positional cloning for the two different types of tumor-related genes. In this symposium, our current progress is presented that includes genetic mapping of susceptibility/ resistance loci on mouse chromosomes 4, 5 and 19, and also functional analysis of a novel tumor suppressor gene, Rit1/Bcl11b, that has been isolated from allelic loss (LOH) mapping and sequence analysis for γ -ray induced mouse thymic lymphomas

  10. Radiation-induced quantitative alterations in prenatal thymic development in the beagle dog

    International Nuclear Information System (INIS)

    Miller, G.K.; Benjamin, S.A.

    1985-01-01

    Quantitative morphology of the canine fetal thymus was studied to evaluate the age-dependent radiosensitivity of the developing immune system. Pregnant beagle dams received abdominal 60 Co gamma exposures (200 R) or were sham irradiated at one of three ages in gestation, 30, 40, or 45 days. The mean calculated dose to each fetus was 1.5 Gray. One-half of the fetuses in each litter were harvested by hysterotomy at 5 days and one-half at 10 days post-irradiation (PI). The volumes of the thymic lobules and lobular cortices were significantly reduced at 5 and 10 days PI when compared with age-matched controls. Thymic cortical volumes in irradiated fetuses were reduced between 13 and 29% from control volumes by 5 days PI and 8 and 13% by 10 day PI. Thymic medullary volumes in irradiated fetuses were reduced 18 to 23% by 5 days PI and 27 to 54% by 10 days PI. The reductions in medullary volumes in fetuses irradiated at 35, 40, and 45 days of gestation and evaluated at 10 days PI were 54, 38, and 27%, respectively. Although injury to both thymic cortices and medullas was greater following exposures earlier in gestation, damage to medullas was relatively more severe than in cortices following exposure at any one age. The degree of reduction of medullary volume reflects thymic epithelial injury and is surprising since thymic epithelium is considered to be radioresistant in the adult. Such injury may have serious consequences postnatally as normal differentiation of T cell subpopulations is dependent upon the integrity of the thymic microenvironment. Damage to the thymic microenvironment could result in defects in immunologic regulation and in immune deficiencies

  11. Optimal surgical approach to thymic malignancies: New trends challenging old dogmas.

    Science.gov (United States)

    Ruffini, Enrico; Filosso, Pier Luigi; Guerrera, Francesco; Lausi, Paolo; Lyberis, Paraskevas; Oliaro, Alberto

    2018-04-01

    Until recently, the surgical approach to thymic tumors has remained basically unchanged. The collaborative effort led by ITMIG with the collaboration of regional and society-based interest groups (ESTS, JART) produced an enthusiastic surge of interest in testing the new technological advances in thoracic surgery and many historical dogmas in thymic surgery have been questioned and challenged. The present review addresses the new trends in the optimal surgical management of thymic tumors based on the review of the current literature. 1. Minimally-invasive techniques (MIT) including video-assisted thoracic surgery (VATS) and robotic-assisted thoracic Surgery (RATS) are now to be considered the standard of care in early-stage thymic tumors. MIT are no inferior to open approaches in terms of postoperative complications, loco-regional recurrence rates and survival. MIT are associated with a shorter length of stay, reduced intraoperative blood loss and better cosmetic results. 2. The adoption of the ITMIG/IASLC TNM staging system for thymic tumors requires a paradigm shift among thoracic surgeons to include regional lymphadenectomy according to the IASLC/ITMIG nodal map in the surgical management of thymic tumors. 3. A limited thymectomy instead of total thymectomy along with the removal of the thymic tumor in nonmyasthenic Stage I-II tumors has been proposed by some authors, although the results are not uniform. Until more mature data is available, adherence to the current guidelines recommending total thymectomy in addition to thymomectomy is always indicated. 4. In locally-advanced Stage IVa patients with pleural involvement, major pleural resections, including pleurectomy/decortication or extrapleural pneumonectomy are indicated, provided a complete resection of the pleural deposits is anticipated, usually in a multidisciplinary setting, with excellent long-term results. The incorporation of these new concepts and techniques in the surgical armamentarium of the

  12. Effect of allogenic thymic cells on radioleukaemogenesis in AKR-T1ALD mice

    International Nuclear Information System (INIS)

    Legrand, E.; Sankar-Mistry, P.; Kressmann, M.C.

    1975-01-01

    When AKR mice are irradiated with a sub-lethal dose (4 times 175 R), thymic lymphosarcomas (L.S.) occur earlier than in controls. This accelerated leukaemogenesis is not inhibited by syngenic restoration with bone marrows cells (BM). Using the AKR/T1ALD substrain which bears 38 chromosomes with 1 metacentric markers, it has been shown that AKR radio-chimaeras restored by T1ALD BM developed two kinds of L.S.: early (radiation-induced) L.S. originating mainly from host cells surviving irradiation and late L.S. from donor cells. The experiments were to investigate the potential influence of normal allogenic thymic cells, with or without syngenic B.M., on the incidence, latency and origin of LS appearing in irradiated AKR recipients. Adding C3H allogenic thymic cells to syngenic B.M. increases the percentage of early L.S. whose latencies are unchanged. Besides, when C3H thymic cells are injected to irradiated controls without syngenic B.M. cells, L.S. are seen to occur significantly earlier than in just the irradiated animals alone. In radio-chimaeras restored by allogenic thymic cells and syngenic B.M., except in one case, all the L.S. were seen to originate from B.M. cells. The interpretation of these results depends on the possible role of allogenic thymic cells on host cells surviving the irradiation, or the exogeneous B.M. In the first case, allogenic thymocytes could induce a graft versus host reaction increasing the post-irradiation depletion of lymphoid system and hastening thymic endoregeneration which is supposed to be the first step towards leukaemogenesis. The second hypothesis, which seems the most likely, would be that C1H thymic cells could selectively act on host cells surviving irradiation and enhance the differenciation of haemopoietic precursors at the expense of the lymphoid cells [fr

  13. Genetics Home Reference: age-related hearing loss

    Science.gov (United States)

    ... quality of life. Because affected individuals have trouble understanding speech, the condition affects their ability to communicate. It can contribute to social isolation, depression, and loss of self-esteem. Age-related hearing loss also causes safety issues if individuals become ...

  14. Age-Related Differences in Idiom Production in Adulthood

    Science.gov (United States)

    Conner, Peggy S.; Hyun, Jungmoon; O'Connor Wells, Barbara; Anema, Inge; Goral, Mira; Monereau-Merry, Marie-Michelle; Rubino, Daniel; Kuckuk, Raija; Obler, Loraine K.

    2011-01-01

    To investigate whether idiom production was vulnerable to age-related difficulties, we asked 40 younger (ages 18-30) and 40 older healthy adults (ages 60-85) to produce idiomatic expressions in a story-completion task. Younger adults produced significantly more correct idiom responses (73%) than did older adults (60%). When older adults generated…

  15. Age-related maculopathy: A genetic and epidemiological approach

    NARCIS (Netherlands)

    J.J.M. Willemse-Assink (Jacqueline)

    2000-01-01

    textabstractIn the 19th century, age-related maculopathy (ARM) was described for the first time as an agerelated abnormality of the macula lutea. ARM consists of a variety of clinical signs, from the early stages with soft distinct drusen, indistinct drusen and pigment alterations up to the late

  16. Prevalence of Age-Related Macular Degeneration in Europe

    NARCIS (Netherlands)

    Colijn, Johanna M.; Buitendijk, Gabriëlle H. S.; Prokofyeva, Elena; Alves, Dalila; Cachulo, Maria L.; Khawaja, Anthony P.; Cougnard-Gregoire, Audrey; Merle, Bénédicte M. J.; Korb, Christina; Erke, Maja G.; Bron, Alain; Anastasopoulos, Eleftherios; Meester-Smoor, Magda A.; Segato, Tatiana; Piermarocchi, Stefano; de Jong, Paulus T. V. M.; Vingerling, Johannes R.; Topouzis, Fotis; Creuzot-Garcher, Catherine; Bertelsen, Geir; Pfeiffer, Norbert; Fletcher, Astrid E.; Foster, Paul J.; Silva, Rufino; Korobelnik, Jean-François; Delcourt, Cécile; Klaver, Caroline C. W.; Ajana, Soufiane; Arango-Gonzalez, Blanca; Arndt, Verena; Bhatia, Vaibhav; Bhattacharya, Shomi S.; Biarnés, Marc; Borrell, Anna; Bühren, Sebastian; Calado, Sofia M.; Cougnard-Grégoire, Audrey; Dammeier, Sascha; de Jong, Eiko K.; de la Cerda, Berta; den Hollander, Anneke I.; Diaz-Corrales, Francisco J.; Diether, Sigrid; Emri, Eszter; Endermann, Tanja; Ferraro, Lucia L.; Garcia, Míriam; Heesterbeek, Thomas J.; Honisch, Sabina; Bergen, Arthur

    2017-01-01

    Purpose: Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in

  17. Age-Related Changes in Binaural Interaction at Brainstem Level

    NARCIS (Netherlands)

    Yper, L.N. Van; Vermeire, K.; Vel, E.F. De; Beynon, A.J.; Dhooge, I.J.

    2016-01-01

    OBJECTIVES: Age-related hearing loss hampers the ability to understand speech in adverse listening conditions. This is attributed to a complex interaction of changes in the peripheral and central auditory system. One aspect that may deteriorate across the lifespan is binaural interaction. The

  18. Extrinsic Mechanisms Involved in Age-Related Defective Bone Formation

    DEFF Research Database (Denmark)

    Trinquier, Anne Marie-Pierre Emilie; Kassem, Moustapha

    2011-01-01

    Context: Age-related bone loss is associated with progressive changes in bone remodeling characterized by decreased bone formation relative to bone resorption. Both trabecular and periosteal bone formation decline with age in both sexes, which contributes to bone fragility and increased risk of f...

  19. Pathophysiology of Age-Related Hearing Loss (Peripheral and Central)

    OpenAIRE

    Lee, Kyu-Yup

    2013-01-01

    Age-related hearing loss (presbycusis) refers to bilaterally symmetrical hearing loss resulting from aging process. Presbycusis is a complex phenomenon characterized by audiometric threshold shift, deterioration in speech-understanding and speech-perception difficulties in noisy environments. Factors contributing to presbycusis include mitochondria DNA mutation, genetic disorders including Ahl, hypertension, diabetes, metabolic disease and other systemic diseases in the intrinsic aspects. Ext...

  20. Age-related differences in muscular capacity among workers

    NARCIS (Netherlands)

    Hamberg-van Reenen, H.H.; Beek, A.J. van der; Blatter, B.M.

    2009-01-01

    Purpose: To quantify the age-related changes in muscular capacity in a working population, and to investigate whether these changes are dependent on sports participation. Methods: Data were used from the longitudinal study on musculoskeletal disorders, absenteeism, stress and health (n = 1,800). At

  1. Nutritional influences on epigenetics and age-related disease

    Science.gov (United States)

    Nutritional epigenetics has emerged as a novel mechanism underlying gene–diet interactions, further elucidating the modulatory role of nutrition in aging and age-related disease development. Epigenetics is defined as a heritable modification to the DNA that regulates chromosome architecture and modu...

  2. Age-related macular degeneration in Onitsha, Nigeria | Nwosu ...

    African Journals Online (AJOL)

    Objectives: To determine the incidence, pattern and ocular morbidity associated with age-related macular degeneration (AMD) at the Guinness Eye Center Onitsha Nigeria. Materials and Methods: The case files of all new patients aged 50 years and above seen between January 1997 and December 2004 were reviewed.

  3. Age-related decrements in cycling and running performance ...

    African Journals Online (AJOL)

    South African Journal of Sports Medicine ... This study examined age-related decrements in athletic performance during running and cycling activities. ... These findings establish a trend that there is 'accelerated' aging during running which can perhaps be attributed to the increased weight-bearing stress on the muscles ...

  4. Age Related Variations in The Architecture of Caprine Haemal Nodes

    African Journals Online (AJOL)

    Age related variations in the architecture of caprine haemal nodes were studied in West African dwarf goats aged between 1-24 months. Variations were observed in the thickness of the capsule, the content and organization of the cortical and medullary parenchyma as well as the stroma. In young goats age between 1-4 ...

  5. Gene-diet interactions in age-related macular degeneration

    Science.gov (United States)

    Age-related macular degeneration (AMD) is a prevalent blinding disease, accounting for roughly 50% of blindness in developed nations. Very significant advances have been made in terms of discovering genetic susceptibilities to AMD as well as dietary risk factors. To date, nutritional supplementation...

  6. Prevalence of Age-Related Macular Degeneration in Europe

    DEFF Research Database (Denmark)

    Colijn, Johanna M; Buitendijk, Gabriëlle H S; Prokofyeva, Elena

    2017-01-01

    PURPOSE: Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD...

  7. Ranibizumab vs. aflibercept for wet age-related macular degeneration

    DEFF Research Database (Denmark)

    Szabo, Shelagh M; Hedegaard, Morten; Chan, Keith

    2015-01-01

    OBJECTIVE: Although a reduced aflibercept (2.0 mg) injection frequency relative to the approved dosing posology is included in national treatment guidelines for wet age-related macular degeneration (AMD), there is limited evidence of its comparative efficacy. The objective was to compare...

  8. Awareness, Knowledge, and Concern about Age-Related Macular Degeneration

    Science.gov (United States)

    Cimarolli, Verena R.; Laban-Baker, Allie; Hamilton, Wanda S.; Stuen, Cynthia

    2012-01-01

    Age-related macular degeneration (AMD)--a common eye disease causing vision loss--can be detected early through regular eye-health examinations, and measures can be taken to prevent visual decline. Getting eye examinations requires certain levels of awareness, knowledge, and concern related to AMD. However, little is known about AMD-related…

  9. Nutritional modulation of age-related macular degeneration

    Science.gov (United States)

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30-50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated wi...

  10. Thymic B cell development is controlled by the B potential of progenitors via both hematopoietic-intrinsic and thymic microenvironment-intrinsic regulatory mechanisms.

    Directory of Open Access Journals (Sweden)

    Shiyun Xiao

    Full Text Available Hematopoietic stem cells (HSCs derived from birth through adult possess differing differentiation potential for T or B cell fate in the thymus; neonatal bone marrow (BM cells also have a higher potential for B cell production in BM compared to adult HSCs. We hypothesized that this hematopoietic-intrinsic B potential might also regulate B cell development in the thymus during ontogeny.Foxn1lacZ mutant mice are a model in which down regulation of a thymic epithelial cell (TEC specific transcription factor beginning one week postnatal causes a dramatic reduction of thymocytes production. In this study, we found that while T cells were decreased, the frequency of thymic B cells was greatly increased in these mutants in the perinatal period. We used this model to characterize the mechanisms in the thymus controlling B cell development.Foxn1lacZ mutants, T cell committed intrathymic progenitors (DN1a,b were progressively reduced beginning one week after birth, while thymic B cells peaked at 3-4 weeks with pre-B-II progenitor phenotype, and originated in the thymus. Heterochronic chimeras showed that the capacity for thymic B cell production was due to a combination of higher B potential of neonatal HSCs, combined with a thymic microenvironment deficiency including reduction of DL4 and increase of IL-7 that promoted B cell fate.Our findings indicate that the capacity and time course for thymic B-cell production are primarily controlled by the hematopoietic-intrinsic potential for B cells themselves during ontogeny, but that signals from TECs microenvironment also influence the frequency and differentiation potential of B cell development in the thymus.

  11. In vitro analysis of age-related changes in the developmental potential of bone marrow thymocyte progenitors.

    Science.gov (United States)

    Sharp, A; Kukulansky, T; Globerson, A

    1990-12-01

    Mechanisms underlying the age-related decrease in the developmental capacity of thymocyte progenitors from the bone marrow (BM) were analyzed, focussing on interaction of these cells with the thymic microenvironment. We employed the experimental model in which mixtures of young and old mouse BM cells, congenic for the Thy-1 marker, were seeded onto fetal thymus (FT) explains depleted of self lymphocytes and the levels of Thy-1+ cells developing from each of the two donor types were measured. When cells from young and old BM donors were seeded simultaneously, in saturating quantities, a higher level of T cells developed from the young donors. To find out whether there were originally more thymocyte progenitors in the young BM, we carried out the competitive colonization under limiting dilution conditions and found that the advantage of the young had diminished under these conditions, thus suggesting that the age-related changes could not be related solely to quantitative differences. We then incubated the FT sequentially with old donor cells for 24 h, followed by young for an additional 48 h and found that the advantage of the young progenitors was eliminated. We thus established that the initial stage of colonization of the FT was important in determining the outcome of the subsequent development. The kinetics of simultaneous competition within the FT, however, revealed that the advantage of the young BM-derived cells became significant only from day 7 in organ culture, thus suggesting that sequential divisions of these cells were at a higher level than those of the old. Recolonization of FT explants by young or old BM-derived thymocytes obtained from the first colonization of the FT stroma showed a reduced, but still significant advantage for the young BM-derived cells over the old. Thus, we concluded that the old BM thymocyte progenitors manifested a qualitative disadvantage which became apparent during competitive colonization of the FT.

  12. Dietary compound score and risk of age-related macular degeneration in the Age-Related Eye Disease Study

    Science.gov (United States)

    Purpose: Because foods provide many nutrients, which may interact with each other to modify risk for multifactorial diseases such as age-related macular degeneration (AMD), we sought to develop a composite scoring system to summarize the combined effect of multiple dietary nutrients on AMD risk. Th...

  13. Lipids, lipid genes, and incident age-related macular degeneration: the three continent age-related macular degeneration consortium

    NARCIS (Netherlands)

    Klein, Ronald; Myers, Chelsea E.; Buitendijk, Gabriëlle H. S.; Rochtchina, Elena; Gao, Xiaoyi; de Jong, Paulus T. V. M.; Sivakumaran, Theru A.; Burlutsky, George; McKean-Cowdin, Roberta; Hofman, Albert; Iyengar, Sudha K.; Lee, Kristine E.; Stricker, Bruno H.; Vingerling, Johannes R.; Mitchell, Paul; Klein, Barbara E. K.; Klaver, Caroline C. W.; Wang, Jie Jin

    2014-01-01

    To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). Meta-analysis. setting: Three population-based cohorts. population: A total of 6950 participants from the Beaver Dam Eye Study (BDES), Blue Mountains Eye Study (BMES),

  14. A data mining approach for classifying DNA repair genes into ageing-related or non-ageing-related

    Directory of Open Access Journals (Sweden)

    Vasieva Olga

    2011-01-01

    Full Text Available Abstract Background The ageing of the worldwide population means there is a growing need for research on the biology of ageing. DNA damage is likely a key contributor to the ageing process and elucidating the role of different DNA repair systems in ageing is of great interest. In this paper we propose a data mining approach, based on classification methods (decision trees and Naive Bayes, for analysing data about human DNA repair genes. The goal is to build classification models that allow us to discriminate between ageing-related and non-ageing-related DNA repair genes, in order to better understand their different properties. Results The main patterns discovered by the classification methods are as follows: (a the number of protein-protein interactions was a predictor of DNA repair proteins being ageing-related; (b the use of predictor attributes based on protein-protein interactions considerably increased predictive accuracy of attributes based on Gene Ontology (GO annotations; (c GO terms related to "response to stimulus" seem reasonably good predictors of ageing-relatedness for DNA repair genes; (d interaction with the XRCC5 (Ku80 protein is a strong predictor of ageing-relatedness for DNA repair genes; and (e DNA repair genes with a high expression in T lymphocytes are more likely to be ageing-related. Conclusions The above patterns are broadly integrated in an analysis discussing relations between Ku, the non-homologous end joining DNA repair pathway, ageing and lymphocyte development. These patterns and their analysis support non-homologous end joining double strand break repair as central to the ageing-relatedness of DNA repair genes. Our work also showcases the use of protein interaction partners to improve accuracy in data mining methods and our approach could be applied to other ageing-related pathways.

  15. CT features of the subtypes of thymic epithelial tumors on the basis of the world health organization classification

    International Nuclear Information System (INIS)

    Guo Xiaoyu; Yu Hong; Xiao Xiangsheng

    2013-01-01

    Thymic epithelial tumors including thymomas and thymic carcinomas have well-known heterogeneous oncologic behaviors and variable histologic features. They show variable and unpredictable evolutions ranging from an indolent non-invasive feature to a highly infiltrative and metastasising one. Currently, CT is a common and efficient imaging method for assessing thymic epithelial tumors. CT evaluation is the main reference for preoperative clinic staging and histological classification. CT features of subtypes of thymic epithelial tumors on the basis of the World Health Organization classification provide the foundation for the diagnosis and predicting prognosis. (authors)

  16. Age-Related Neurodegeneration and Memory Loss in Down Syndrome

    Directory of Open Access Journals (Sweden)

    Jason P. Lockrow

    2012-01-01

    Full Text Available Down syndrome (DS is a condition where a complete or segmental chromosome 21 trisomy causes variable intellectual disability, and progressive memory loss and neurodegeneration with age. Many research groups have examined development of the brain in DS individuals, but studies on age-related changes should also be considered, with the increased lifespan observed in DS. DS leads to pathological hallmarks of Alzheimer's disease (AD by 40 or 50 years of age. Progressive age-related memory deficits occurring in both AD and in DS have been connected to degeneration of several neuronal populations, but mechanisms are not fully elucidated. Inflammation and oxidative stress are early events in DS pathology, and focusing on these pathways may lead to development of successful intervention strategies for AD associated with DS. Here we discuss recent findings and potential treatment avenues regarding development of AD neuropathology and memory loss in DS.

  17. Idiom understanding in adulthood: examining age-related differences.

    Science.gov (United States)

    Hung, Pei-Fang; Nippold, Marilyn A

    2014-03-01

    Idioms are figurative expressions such as hold your horses, kick the bucket, and lend me a hand, which commonly occur in everyday spoken and written language. Hence, the understanding of these expressions is essential for daily communication. In this study, we examined idiom understanding in healthy adults in their 20s, 40s, 60s and 80s (n=30 per group) to determine if performance would show an age-related decline. Participants judged their own familiarity with a set of 20 idioms, explained the meaning of each, described a situation in which the idiom could be used, and selected the appropriate interpretation from a set of choices. There was no evidence of an age-related decline on any tasks. Rather, the 60s group reported greater familiarity and offered better explanations than did the 20s group. Moreover, greater familiarity with idioms was associated with better understanding in adults.

  18. Age-related changes of monoaminooxidases in rat cerebellar cortex

    Directory of Open Access Journals (Sweden)

    FM Tranquilli Leali

    2009-06-01

    Full Text Available Age-related changes of the monoaminoxidases, evaluated by enzymatic staining, quantitative analysis of images, biochemical assay and statistical analysis of data were studied in cerebellar cortex of young (3-month-old and aged (26- month-old male Sprague-Dawley rats. The enzymatic staining shows the presence of monoamino-oxidases within the molecular and granular layers as well as within the Purkinje neurons of the cerebellum of young and aged animals. In molecular layer, and in Purkinje neurons the levels of monoaminooxidases were strongly increased in old rats. The granular layer showed, on the contrary, an age-dependent loss of enzymatic staining. These morphological findings were confirmed by biochemical results. The possibility that age-related changes in monoaminooxidase levels may be due to impaired energy production mechanisms and/or represent the consequence of reduced energetic needs is discussed.

  19. Reviewing fluid systems for age-related degradation

    International Nuclear Information System (INIS)

    Smith, Stan

    1991-01-01

    Yankee Atomic Electric Company has developed the component degradation assessment tool (CoDAT), an expert system, that aids in handling and evaluating the large amounts of data required to support the license renewal process for nuclear power station fluid systems. In 1990, CoDAT evaluated the Yankee Nuclear Power Station fluid systems for age-related degradation. Its results are now being used to help focus the plant's maintenance programs and manage the expected degradation. CoDAT uses 'If-Then' rules, developed from industry codes, standards and publications, to determine the potential for 19 age-related degradation mechanisms. Other nuclear utilities pursuing the license renewal option also could use CoDAT. (author)

  20. The age-related performance decline in ultraendurance mountain biking.

    Science.gov (United States)

    Haupt, Samuel; Knechtle, Beat; Knechtle, Patrizia; Rüst, Christoph Alexander; Rosemann, Thomas; Lepers, Romuald

    2013-01-01

    The age-related changes in ultraendurance performance have been previously examined for running and triathlon but not mountain biking. The aims of this study were (i) to describe the performance trends and (ii) to analyze the age-related performance decline in ultraendurance mountain biking in a 120-km ultraendurance mountain bike race the "Swiss Bike Masters" from 1995 to 2009 in 9,325 male athletes. The mean (±SD) race time decreased from 590 ± 80 min to 529 ± 88 min for overall finishers and from 415 ± 8 min to 359 ± 16 min for the top 10 finishers, respectively. The mean (±SD) age of all finishers significantly (P Bike Masters" appears to start earlier compared with other ultraendurance sports.

  1. Hot Topics in Pharmacogenetics of Age-Related Macular Degeneration.

    Science.gov (United States)

    Schwartz, Stephen G; Brantley, Milam A; Kovach, Jaclyn L; Grzybowski, Andrzej

    2017-01-01

    Age-related macular degeneration (AMD) is a leading cause of irreversible visual loss and is primarily treated with nutritional supplementation as well as with anti-vascular endothelial growth factor (VEGF) agents for certain patients with neovascular disease. AMD is a complex disease with both genetic and environmental risk factors. In addition, treatment outcomes from nutritional supplementation and anti-VEGF agents vary considerably. Therefore, it is reasonable to suspect that there may be pharmacogenetic influences on these treatments. Many series have reported individual associations with variants in complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2), and other loci. However, at this time there are no validated associations. With respect to AMD, pharmacogenetics remains an intriguing area of research but is not helpful for routine clinical management. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Heart Failure as an Aging-Related Phenotype.

    Science.gov (United States)

    Morita, Hiroyuki; Komuro, Issei

    2018-01-27

    The molecular pathophysiology of heart failure, which is one of the leading causes of mortality, is not yet fully understood. Heart failure can be regarded as a systemic syndrome of aging-related phenotypes. Wnt/β-catenin signaling and the p53 pathway, both of which are key regulators of aging, have been demonstrated to play a critical role in the pathogenesis of heart failure. Circulating C1q was identified as a novel activator of Wnt/β-catenin signaling, promoting systemic aging-related phenotypes including sarcopenia and heart failure. On the other hand, p53 induces the apoptosis of cardiomyocytes in the failing heart. In these molecular mechanisms, the cross-talk between cardiomyocytes and non-cardiomyocytes (e,g,. endothelial cells, fibroblasts, smooth muscle cells, macrophages) deserves mentioning. In this review, we summarize recent advances in the understanding of the molecular pathophysiology underlying heart failure, focusing on Wnt/β-catenin signaling and the p53 pathway.

  3. Age-related percutaneous penetration part 1: skin factors.

    Science.gov (United States)

    Konda, S; Meier-Davis, S R; Cayme, B; Shudo, J; Maibach, H I

    2012-05-01

    Changes in the skin that occur in the elderly may put them at increased risk for altered percutaneous penetration from pharmacotherapy along with potential adverse effects. Skin factors that may have a role in age-related percutaneous penetration include blood flow, pH, skin thickness, hair and pore density, and the content and structure of proteins, glycosaminoglycans (GAGs), water, and lipids. Each factor is examined as a function of increasing age along with its potential impact on percutaneous penetration. Additionally, topical drugs that successfully overcome the barrier function of the skin can still fall victim to cutaneous metabolism, thereby producing metabolites that may have increased or decreased activity. This overview discusses the current data and highlights the importance of further studies to evaluate the impact of skin factors in age-related percutaneous penetration.

  4. Expertise and age-related changes in components of intelligence.

    Science.gov (United States)

    Masunaga, H; Horn, J

    2001-06-01

    In a sample of 263 male GO players at 48 levels of expertise and ranging from 18 to 78 years of age, it was found that factors of expertise deductive reasoning (EDR) and expertise working memory (EWM) were independent of factors of fluid reasoning (Gf) and short-term working memory (STWM) that, along with cognitive speed (Gs), have been found to characterize decline of intelligence in adulthood. The main effects of analyses of cross-sectional age differences indicated age-related decline in EDR and EWM as well as in Gf, STWM, and Gs. However, interaction and partialing analyses indicated that decline in EDR and EWM decreased to no decline with increase in level of expertise. The results thus suggest that with increase in factors known to raise the level of expertise--particularly, intensive, well-designed practice--there may be no age-related decline in the intelligence that is measured in the abilities of expertise.

  5. Radiation treatment for age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Taniguchi, Tomoko; Mandai, Michiko; Honjo, Megumi; Matsuda, Naoko; Miyamoto, Hideki; Takahashi, Masayo; Ogura, Yuichiro; Sasai, Keisuke [Kyoto Univ. (Japan). Faculty of Medicine

    1996-11-01

    Fifteen eyes of age-related macular degeneration were treated by low-dose radiation. All the affected eyes had subfoveal neovascular membrane. Seventeen nontreated eyes with similar macular lesion served as control. Radiation was performed using photon beam at 6MV. Each eye received daily dose of 2 Gy for 5 consecutive days. When evaluated 9 to 12 months after treatment, the size of neovascular membrane had decreased in 47% of treated eyes and 7% of control eyes. The visual acuity improved by 2 lines or more in 13% of treated eyes and in none of control eyes. When the initial neovascular membrane was less than 1.5 disc diameter in size, the visual acuity had improved or remained stationary in 90% of treated eyes and in 36% of control eyes. The findings show the potential beneficial effect of radiation for age-related macular degeneration. (author)

  6. Age-Related Differences in Multiple Task Monitoring

    OpenAIRE

    Todorov, Ivo; Del Missier, Fabio; Mäntylä, Timo

    2014-01-01

    Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men excee...

  7. eNOS-uncoupling in age-related erectile dysfunction

    OpenAIRE

    Johnson, JM; Bivalacqua, TJ; Lagoda, GA; Burnett, AL; Musicki, B

    2011-01-01

    Aging is associated with ED. Although age-related ED is attributed largely to increased oxidative stress and endothelial dysfunction in the penis, the molecular mechanisms underlying this effect are not fully defined. We evaluated whether endothelial nitric oxide synthase (eNOS) uncoupling in the aged rat penis is a contributing mechanism. Correlatively, we evaluated the effect of replacement with eNOS cofactor tetrahydrobiopterin (BH4) on erectile function in the aged rats. Male Fischer 344 ...

  8. Complement pathway biomarkers and age-related macular degeneration

    Science.gov (United States)

    Gemenetzi, M; Lotery, A J

    2016-01-01

    In the age-related macular degeneration (AMD) ‘inflammation model', local inflammation plus complement activation contributes to the pathogenesis and progression of the disease. Multiple genetic associations have now been established correlating the risk of development or progression of AMD. Stratifying patients by their AMD genetic profile may facilitate future AMD therapeutic trials resulting in meaningful clinical trial end points with smaller sample sizes and study duration. PMID:26493033

  9. Radiotherapy for invasive thymoma and thymic carcinoma. Clinicopathological review

    Energy Technology Data Exchange (ETDEWEB)

    Mayer, R.; Stuecklschweiger, G.F.; Prettenhofer, U.; Stranzl, H.; Hackl, A. [Univ. Graz (Austria). Dept. of Radiotherapy; Beham-Schmid, C. [Univ. Graz (Austria). Dept. of Pathology; Groell, R. [Univ. Graz (Austria). Dept. of Radiology; Smolle-Juettner, F.M.; Renner, H. [Univ. Graz (Austria). Dept. of Thoracic and Hyperbaric Surgery; Quehenberger, F. [Univ. Graz (Austria). Dept. of Medical Informatics, Statistics and Documentation

    1999-06-01

    All 33 patients were irradiated with a mean dose of 50 Gy after complete resection (16 patients), partial resection (9 patients) of biopsy (8 patients). Staging was done according to the Masaoka classification; there were 12 Stage II, 12 Stage III and 9 Stage IV patients. Results: In patients with invasive thymoma Stage II to IV (median follow-up 54.4 months) Kaplan-Meier estimates of overall survival (OS), disease-specific (DSS) and disease-free survival (DFS) at 5 years were 63.7% (95% confidence interval [CI], 42 to 84%), 88.3% (CI, 75 to 100%) and 77,4% (CI, 58 to 95%), respectively. Among the prognostic factors tested, such as age, myasthenia gravis, completeness of surgery and histologic subclassification, total radiation dose, and Masaoka Stage, the latter was the only significant predictor of improved survival (p=0.04). Considering local control, radiation dose was a significant prognostic factor (p=0.0006). In patients with thymic carcinoma (median follow-up 43.4 months) 5 year DSS, and DFS were 22.2% (CI, 0 to 60%) and 16.7% (CI, 0 to 46%), respectively. Thymoma as compared to thymic carcinoma had a statistically significant better DSS (p=0.007) and DFS (p=0.0007). Conclusion: Postoperative radiotherapy with sufficient doses plays an important role as adjuvant treatment in complete or incomplete resected invasive Stage II to III thymoma. In unresectable thymoma Stage III to IV as well as in thymic carcinoma a multimodality approach should be considered to improve survival. (orig.) [Deutsch] Alle 33 Patienten wurden nach kompletter Resektion (n=16), Teilresektion (n=9) oder Biopsie (n=8) mit einer mittleren Dosis von 50 Gy (30 bis 60 Gy) bestrahlt. Die Stadieneinteilung nach Masaoka ergab jeweils zwoelf Patienten in Stadium II und III sowie neun Patienten im Stadium IV. Ergebnisse: Patienten mit einem invasivem Thymom Masaoka-Stadium II bis IV (mediane Nachsorgezeit 54,4 Monate) hatten ein Fuenf-Jahres-Gesamtueberleben, krankheitsspezifisches und

  10. Age-related differences in working memory updating components.

    Science.gov (United States)

    Linares, Rocío; Bajo, M Teresa; Pelegrina, Santiago

    2016-07-01

    The aim of this study was to investigate possible age-related changes throughout childhood and adolescence in different component processes of working memory updating (WMU): retrieval, transformation, and substitution. A set of numerical WMU tasks was administered to four age groups (8-, 11-, 14-, and 21-year-olds). To isolate the effect of each of the WMU components, participants performed different versions of a task that included different combinations of the WMU components. The results showed an expected overall decrease in response times and an increase in accuracy performance with age. Most important, specific age-related changes in the retrieval component were found, demonstrating that the effect of retrieval on accuracy was larger in children than in adolescents or young adults. These findings indicate that the availability of representations from outside the focus of attention may change with age. Thus, the retrieval component of updating could contribute to the age-related changes observed in the performance of many updating tasks. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Age-Related Changes in Trabecular and Cortical Bone Microstructure

    Directory of Open Access Journals (Sweden)

    Huayue Chen

    2013-01-01

    Full Text Available The elderly population has substantially increased worldwide. Aging is a complex process, and the effects of aging are myriad and insidious, leading to progressive deterioration of various organs, including the skeleton. Age-related bone loss and resultant osteoporosis in the elderly population increase the risk for fractures and morbidity. Osteoporosis is one of the most common conditions associated with aging, and age is an independent risk factor for osteoporotic fractures. With the development of noninvasive imaging techniques such as computed tomography (CT, micro-CT, and high resolution peripheral quantitative CT (HR-pQCT, imaging of the bone architecture provides important information about age-related changes in bone microstructure and estimates of bone strength. In the past two decades, studies of human specimens using imaging techniques have revealed decreased bone strength in older adults compared with younger adults. The present paper addresses recently studied age-related changes in trabecular and cortical bone microstructure based primarily on HR-pQCT and micro-CT. We specifically focus on the three-dimensional microstructure of the vertebrae, femoral neck, and distal radius, which are common osteoporotic fracture sites.

  12. Age-related changes in trabecular and cortical bone microstructure.

    Science.gov (United States)

    Chen, Huayue; Zhou, Xiangrong; Fujita, Hiroshi; Onozuka, Minoru; Kubo, Kin-Ya

    2013-01-01

    The elderly population has substantially increased worldwide. Aging is a complex process, and the effects of aging are myriad and insidious, leading to progressive deterioration of various organs, including the skeleton. Age-related bone loss and resultant osteoporosis in the elderly population increase the risk for fractures and morbidity. Osteoporosis is one of the most common conditions associated with aging, and age is an independent risk factor for osteoporotic fractures. With the development of noninvasive imaging techniques such as computed tomography (CT), micro-CT, and high resolution peripheral quantitative CT (HR-pQCT), imaging of the bone architecture provides important information about age-related changes in bone microstructure and estimates of bone strength. In the past two decades, studies of human specimens using imaging techniques have revealed decreased bone strength in older adults compared with younger adults. The present paper addresses recently studied age-related changes in trabecular and cortical bone microstructure based primarily on HR-pQCT and micro-CT. We specifically focus on the three-dimensional microstructure of the vertebrae, femoral neck, and distal radius, which are common osteoporotic fracture sites.

  13. Accident sequence precursor events with age-related contributors

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, G.A.; Kohn, W.E.

    1995-12-31

    The Accident Sequence Precursor (ASP) Program at ORNL analyzed about 14.000 Licensee Event Reports (LERs) filed by US nuclear power plants 1987--1993. There were 193 events identified as precursors to potential severe core accident sequences. These are reported in G/CR-4674. Volumes 7 through 20. Under the NRC Nuclear Plant Aging Research program, the authors evaluated these events to determine the extent to which component aging played a role. Events were selected that involved age-related equipment degradation that initiated an event or contributed to an event sequence. For the 7-year period, ORNL identified 36 events that involved aging degradation as a contributor to an ASP event. Except for 1992, the percentage of age-related events within the total number of ASP events over the 7-year period ({approximately}19%) appears fairly consistent up to 1991. No correlation between plant ape and number of precursor events was found. A summary list of the age-related events is presented in the report.

  14. Identification of Age-Related Macular Degeneration Using OCT Images

    Science.gov (United States)

    Arabi, Punal M., Dr; Krishna, Nanditha; Ashwini, V.; Prathibha, H. M.

    2018-02-01

    Age-related Macular Degeneration is the most leading retinal disease in the recent years. Macular degeneration occurs when the central portion of the retina, called macula deteriorates. As the deterioration occurs with the age, it is commonly referred as Age-related Macular Degeneration. This disease can be visualized by several imaging modalities such as Fundus imaging technique, Optical Coherence Tomography (OCT) technique and many other. Optical Coherence Tomography is the widely used technique for screening the Age-related Macular Degeneration disease, because it has an ability to detect the very minute changes in the retina. The Healthy and AMD affected OCT images are classified by extracting the Retinal Pigmented Epithelium (RPE) layer of the images using the image processing technique. The extracted layer is sampled, the no. of white pixels in each of the sample is counted and the mean value of the no. of pixels is calculated. The average mean value is calculated for both the Healthy and the AMD affected images and a threshold value is fixed and a decision rule is framed to classify the images of interest. The proposed method showed an accuracy of 75%.

  15. Adjuvant Therapy for Thymic Carcinoma--A Decade of Experience in a Taiwan National Teaching Hospital.

    Directory of Open Access Journals (Sweden)

    Yen-Han Tseng

    Full Text Available Thymic carcinomas are rare tumors for which surgical resection is the first treatment of choice. The role of adjuvant treatment after surgery is unknown because of limited available data. The present study evaluated the efficacy of post-surgery adjuvant chemotherapy or radiotherapy in patients with thymic carcinoma.To evaluate the role of adjuvant therapy in patients with thymic carcinoma, we retrospectively reviewed the records of patients with thymic carcinoma who were diagnosed and treated between 2004 and 2014.Among 78 patients with thymic carcinoma, 30 patients received surgical resection. Progression-free survival (PFS and overall survival (OS were significantly longer among these patients than among patients who received other treatments (PFS: 88.4 months vs 9.1 months, p<0.001; OS: 134.9 months vs 60.9 months; p = 0.003. Patients with stage III thymic carcinoma who received surgery had a longer OS than patients who did not receive surgery (70.1 months vs 23.9 months; p = 0.017, n = 11. Among 47 patients with stage IV carcinoma, 12 patients who received an extended thymothymectomy had a longer PFS than 35 patients who did not receive surgery (18.9 months vs 8.7 months; p = 0.029. Among 30 patients (with stage I- IV carcinoma who received primary lesion surgery, 19 patients received an R0 resection and 9 patients of the 19 patients received adjuvant radiotherapy. These patients had longer PFS (50.3 months than 2 patients who received adjuvant chemotherapy (5.9 months or 4 patients who received concurrent chemoradiotherapy (7.5 months after surgery (p = 0.003.Surgical resection should be considered for patients with thymic carcinoma, even for patients with locally advanced or stage IV carcinoma. Adjuvant radiotherapy resulted in a better PFS after R0 resection.

  16. Lymphocyte depletion in thymic nurse cells: a tool to identify in situ lympho-epithelial complexes having thymic nurse cell characteristics

    NARCIS (Netherlands)

    Leene, W.; de Waal Malefijt, R.; Roholl, P. J.; Hoeben, K. A.

    1988-01-01

    In situ pre-existing complexes of epithelial cells and thymocytes having thymic nurse cell characteristics were visualized in the murine thymus cortex using dexamethasone as a potent killer of cortisone-sensitive thymocytes. The degradation and subsequent depletion of cortisone-sensitive thymocytes

  17. Polyhexamethyleneguanidine phosphate induces severe lung inflammation, fibrosis, and thymic atrophy.

    Science.gov (United States)

    Song, Jeong Ah; Park, Hyun-Ju; Yang, Mi-Jin; Jung, Kyung Jin; Yang, Hyo-Seon; Song, Chang-Woo; Lee, Kyuhong

    2014-07-01

    Polyhexamethyleneguanidine phosphate (PHMG-P) has been widely used as a disinfectant because of its strong bactericidal activity and low toxicity. However, in 2011, the Korea Centers for Disease Control and Prevention and the Ministry of Health and Welfare reported that a suspicious outbreak of pulmonary disease might have originated from humidifier disinfectants. The purpose of this study was to assess the toxicity of PHMG-P following direct exposure to the lung. PHMG-P (0.3, 0.9, or 1.5 mg/kg) was instilled into the lungs of mice. The levels of proinflammatory markers and fibrotic markers were quantified in lung tissues and flow cytometry was used to evaluate T cell distribution in the thymus. Administration of PHMG-P induced proinflammatory cytokines elevation and infiltration of immune cells into the lungs. Histopathological analysis revealed a dose-dependent exacerbation of both inflammation and pulmonary fibrosis on day 14. PHMG-P also decreased the total cell number and the CD4(+)/CD8(+) cell ratio in the thymus, with the histopathological examination indicating severe reduction of cortex and medulla. The mRNA levels of biomarkers associated with T cell development also decreased markedly. These findings suggest that exposure of lung tissue to PHMG-P leads to pulmonary inflammation and fibrosis as well as thymic atrophy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Appearance of thymic nurse cells after gamma irradiation

    International Nuclear Information System (INIS)

    Mulder, A.H.; Bekkum, D.W. van

    1983-01-01

    Since prothymocytes home from the bone marrow to the thymus, it was tested in the mouse whether prothymocytes could be recaptured from thymic nurse cells (TNC). Bone marrow cells were labelled with the red fluorescing anthracycline daunomycin and varying numbers (up to 25 x 10 6 nucleated bone marrow cells) were injected into lethally irradiated recipients. At several time intervals after transplantation (up to 24 hours), thymuses were removed and the TNCs were isolated. No specific red fluorescence was found within the TNCs. These experiments were repeated with supravital compounds at concentrations which have been shown not to affect viability, homing pattern and function. Again, no specific fluoresence was found in the TNC after transplantation of labelled bone marrow into irradiated mice. The relationship between the dose of total body gamma irradiation and the time after irradiation was investigated. Maximal numbers of TNCs were found at 6 hours after irradiation with 4 Gy. Eight to 12 hours after irradiation, the number of TNCs isolated decreased and had returned to preirradiation levels at 24 hours. The relation between TBI dose and the number of TNCs per thymus is shown. The number determined at 3 hours increased with the dose to reach a maximum at 4 Gy. The authors later studied the morphology of the TNCs isolated at 4 to 6 hours after irradiation. On electron microscopic examination, signs of degeneration and death of the enclosed thymocytes was detected. (Auth.)

  19. Therapeutic implications of thymic uptake of radioiodine in thyroid carcinoma

    International Nuclear Information System (INIS)

    Wilson, L.M.; Barrington, S.F.; Kettle, A.G.; O'Doherty, M.J.; Coakley, A.J.; Morrison, I.D.

    1998-01-01

    The management of 38 consecutive patients with differentiated thyroid carcinoma in the period 1991-1996, who each received at least one therapy dose of iodine-131, was reviewed, looking in particular at those in whom anterior mediastinal uptake was demonstrated on scans taken 3 and 7 days post-therapy. Such activity was noted in ten patients. On the basis of clinical follow-up, thyroglobulin measurement and radiological and other scintigraphic imaging, in nine of the ten patients the anterior mediastinal activity was attributed to physiological thymic uptake. Of those nine, all were under 50 years of age; seven were considered disease free, one had residual disease in the neck and one had distant metastases. Physiological uptake by the thymus was more prominent on the 7-day scans and in patients with low tumour volumes. For appropriate patient management it is essential to recognise that physiological uptake of 131 I by the thymus in patients under 50 years of age is a potential cause of false-positive therapy scans. (orig.)

  20. Preoperative CT prediction for Masaoka staging of thymic epithelial tumor

    International Nuclear Information System (INIS)

    Feng Zhan; Huang Zhen; Zhang Liang

    2013-01-01

    Objective: To discuss the value of CT prognosis on the Masaoka staging system of thymic epithelial tumors (TET) before surgical resection. Methods: The CT images of 102 patients with TET proved by surgery and pathology were reviewed retrospectively. The TET were reclassified according to Masaoka stage system. The size, homogeneity, sharp, contour, infiltration of surrounding tissue, and metastasis on CT were analyzed with Logistic analysis. The diagnostic value was also evaluated with a ROC curve. Results: Masaoka pathologic stages were stage Ⅰ for 36 (35.3 %), stage Ⅱ for 27 (26.5 %), stage Ⅲ for 30 (29.4 %), and stage Ⅳ for 9 (8.8 %). A multivariable Logistic regression model showed that TET with larger size of tumor (20/35, P = 0.0371, OR = 4.539), irregular or lobulated tumor contour (26/42, P = 0.0230, OR = 4.870), heterogeneous (21/33, P = 0.0154, OR = 6.020), infiltration of surrounding fat (25/32, P = 0.0019, OR = 14.005), and pleural seeding (11/11, P = 0.0032, OR = 36.153) were more likely to have stage Ⅲ or Ⅳ disease. The area under ROC curve was 0.940. Conclusions: The tumor CT imaging features can differentiate between stage Ⅰ, Ⅱ and stage Ⅲ, Ⅳ disease. This helps identified patients more likely to benefit from neoadjuvant therapy. (authors)

  1. Signal transduction around thymic stromal lymphopoietin (TSLP in atopic asthma

    Directory of Open Access Journals (Sweden)

    Kuepper Michael

    2008-08-01

    Full Text Available Abstract Thymic stromal lymphopoietin (TSLP, a novel interleukin-7-like cytokine, triggers dendritic cell-mediated inflammatory responses ultimately executed by T helper cells of the Th2 subtype. TSLP emerged as a central player in the development of allergic symptoms, especially in the airways, and is a prime regulatory cytokine at the interface of virus- or antigen-exposed epithelial cells and dendritic cells (DCs. DCs activated by epithelium-derived TSLP can promote naïve CD4+ T cells to adopt a Th2 phenotype, which in turn recruite eosinophilic and basophilic granulocytes as well as mast cells into the airway mucosa. These different cells secrete inflammatory cytokines and chemokines operative in inducing an allergic inflammation and atopic asthma. TSLP is, thus, involved in the control of both an innate and an adaptive immune response. Since TSLP links contact of allergen with the airway epithelium to the onset and maintainance of the asthmatic syndrome, defining the signal transduction underlying TSLP expression and function is of profound interest for a better understandimg of the disease and for the development of new therapeutics.

  2. Pathogenesis of age-related bone loss in humans.

    Science.gov (United States)

    Khosla, Sundeep

    2013-10-01

    Although data from rodent systems are extremely useful in providing insights into possible mechanisms of age-related bone loss, concepts evolving from animal models need to ultimately be tested in humans. This review provides an update on mechanisms of age-related bone loss in humans based on the author's knowledge of the field and focused literature reviews. Novel imaging, experimental models, biomarkers, and analytic techniques applied directly to human studies are providing new insights into the patterns of bone mass acquisition and loss as well as the role of sex steroids, in particular estrogen, on bone metabolism and bone loss with aging in women and men. These studies have identified the onset of trabecular bone loss at multiple sites that begins in young adulthood and remains unexplained, at least based on current paradigms of the mechanisms of bone loss. In addition, estrogen appears to be a major regulator of bone metabolism not only in women but also in men. Studies assessing mechanisms of estrogen action on bone in humans have identified effects of estrogen on RANKL expression by several different cell types in the bone microenvironment, a role for TNF-α and IL-1β in mediating effects of estrogen deficiency on bone, and possible regulation of the Wnt inhibitor, sclerostin, by estrogen. There have been considerable advances in our understanding of age-related bone loss in humans. However, there are also significant gaps in knowledge, particularly in defining cell autonomous changes in bone in human studies to test or validate concepts emerging from studies in rodents. Decision Editor: Luigi Ferrucci, MD, PhD.

  3. Age-related deterioration of rod vision in mice.

    Science.gov (United States)

    Kolesnikov, Alexander V; Fan, Jie; Crouch, Rosalie K; Kefalov, Vladimir J

    2010-08-18

    Even in healthy individuals, aging leads to deterioration in visual acuity, contrast sensitivity, visual field, and dark adaptation. Little is known about the neural mechanisms that drive the age-related changes of the retina and, more specifically, photoreceptors. According to one hypothesis, the age-related deterioration in rod function is due to the limited availability of 11-cis-retinal for rod pigment formation. To determine how aging affects rod photoreceptors and to test the retinoid-deficiency hypothesis, we compared the morphological and functional properties of rods of adult and aged B6D2F1/J mice. We found that the number of rods and the length of their outer segments were significantly reduced in 2.5-year-old mice compared with 4-month-old animals. Aging also resulted in a twofold reduction in the total level of opsin in the retina. Behavioral tests revealed that scotopic visual acuity and contrast sensitivity were decreased by twofold in aged mice, and rod ERG recordings demonstrated reduced amplitudes of both a- and b-waves. Sensitivity of aged rods determined from single-cell recordings was also decreased by 1.5-fold, corresponding to not more than 1% free opsin in these photoreceptors, and kinetic parameters of dim flash response were not altered. Notably, the rate of rod dark adaptation was unaffected by age. Thus, our results argue against age-related deficiency of 11-cis-retinal in the B6D2F1/J mouse rod visual cycle. Surprisingly, the level of cellular dark noise was increased in aged rods, providing an alternative mechanism for their desensitization.

  4. Age-related degradation of Westinghouse 480-volt circuit breakers

    International Nuclear Information System (INIS)

    Subudhi, M.; Shier, W.; MacDougall, E.

    1990-07-01

    An aging assessment of Westinghouse DS-series low-voltage air circuit breakers was performed as part of the Nuclear Plant Aging Research (NPAR) program. The objectives of this study are to characterize age-related degradation within the breaker assembly and to identify maintenance practices to mitigate their effect. Since this study has been promulgated by the failures of the reactor trip breakers at the McGuire Nuclear Station in July 1987, results relating to the welds in the breaker pole lever welds are also discussed. The design and operation of DS-206 and DS-416 breakers were reviewed. Failure data from various national data bases were analyzed to identify the predominant failure modes, causes, and mechanisms. Additional operating experiences from one nuclear station and two industrial breaker-service companies were obtained to develop aging trends of various subcomponents. The responses of the utilities to the NRC Bulletin 88-01, which discusses the center pole lever welds, were analyzed to assess the final resolution of failures of welds in the reactor trips. Maintenance recommendations, made by the manufacturer to mitigate age-related degradation were reviewed, and recommendations for improving the monitoring of age-related degradation are discussed. As described in Volume 2 of this NUREG, the results from a test program to assess degradation in breaker parts through mechanical cycling are also included. The testing has characterized the cracking of center-pole lever welds, identified monitoring techniques to determine aging in breakers, and provided information to augment existing maintenance programs. Recommendations to improve breaker reliability using effective maintenance, testing, and inspection programs are suggested. 13 refs., 21 figs., 8 tabs

  5. Ectopic Thymic Cyst of the Subglottis: Considerations for Diagnosis and Management.

    Science.gov (United States)

    Ahmad, Iram; Kirby, Patricia; Liming, Bryan

    2018-03-01

    To share the diagnostic and management challenges created by an extremely rare airway lesion-the subglottic ectopic thymic cyst. Case report and literature review. We review the presentation, management, and clinical course of an infant who presented with a subglottic mass that was histologically confirmed as a thymic cyst. A brief literature review supplements the case presentation Results: We present the third described case of an ectopic thymic cyst presenting as a subglottic mass. The differential diagnosis of subglottic masses in neonates consists primarily of subglottic hemangioma and mucous retention cysts. Otolaryngologists must be prepared for unexpected findings when dealing with critical airways. We compare the presentation and management of our patient with the 2 previously described cases. We propose an embryologic theory for the origin of these rare lesions. An ectopic thymic cyst is a rare and unexpected cause of neonatal stridor. Management of pediatric airway lesions must allow for unexpected findings at the time of diagnostic and therapeutic endoscopy. The appropriate management of subglottic thymic cysts is poorly defined, but close surveillance for recurrence is mandatory.

  6. Utility of Electrocardiography (ECG)-Gated Computed Tomography (CT) for Preoperative Evaluations of Thymic Epithelial Tumors.

    Science.gov (United States)

    Ozawa, Yoshiyuki; Hara, Masaki; Nakagawa, Motoo; Shibamoto, Yuta

    2016-01-01

    Preoperative evaluation of invasion to the adjacent organs is important for the thymic epithelial tumors on CT. The purpose of our study was to evaluate the utility of electrocardiography (ECG)-gated CT for assessing thymic epithelial tumors with regard to the motion artifacts produced and the preoperative diagnostic accuracy of the technique. Forty thymic epithelial tumors (36 thymomas and 4 thymic carcinomas) were examined with ECG-gated contrast-enhanced CT using a dual source scanner. The scan delay after the contrast media injection was 30 s for the non-ECG-gated CT and 100 s for the ECG-gated CT. Two radiologists blindly evaluated both the non-ECG-gated and ECG-gated CT images for motion artifacts and determined whether the tumors had invaded adjacent structures (mediastinal fat, superior vena cava, brachiocephalic veins, aorta, pulmonary artery, pericardium, or lungs) on each image. Motion artifacts were evaluated using a 3-grade scale. Surgical and pathological findings were used as a reference standard for tumor invasion. Motion artifacts were significantly reduced for all structures by ECG gating ( p =0.0089 for the lungs and p ECG-gated CT and ECG-gated CT demonstrated 79% and 95% accuracy, respectively, during assessments of pericardial invasion ( p =0.03). ECG-gated CT reduced the severity of motion artifacts and might be useful for preoperative assessment whether thymic epithelial tumors have invaded adjacent structures.

  7. Application values of 99mTc-methoxyisobutylisonitrile imaging for differentiating benign and malignant thymic masses.

    Science.gov (United States)

    Lu, Chenghui; Wang, Xufu; Liu, Bin; Liu, Xinfeng; Wang, Guoming; Zhang, Qin

    2017-08-01

    The aim of the present study was to investigate the application value of 99m Tc-methoxyisobutylisonitrile (MIBI) imaging to differentiate between benign and malignant thymic masses. A total of 32 patients with space-occupying mediastinal masses were enrolled and early and delayed-phase images were collected following injection with the imaging agent. The tumor to background ratio (T/N) values at the different phases were also recorded. The sensitivity of the qualitative analysis to distinguish between benign and malignant thymic masses was 95.24%, with specificity as 90.91%. The T/N values in the early and delayed phases were not significantly different in the group with benign thymic masses, but demonstrated statistical significant differences in the groups with low- and intermediate-grade malignant thymic masses. The T/N values at the above early and delayed phase were significantly different between the benign and low-grade malignancy groups, as well as between low- and moderate-grade malignancy groups. Those between the benign and moderate-grade malignancy groups demonstrated no significant difference. 99m Tc-MIBI imaging was able to differentiate between benign and malignant thymic masses, and the simultaneous semi-quantitative analysis of the T/N values of the tumors may be able to initially determine the degree of malignancy of thymoma.

  8. Acute respiratory failure revealing a multilocular thymic cyst in an infant: a case report.

    Science.gov (United States)

    Asma, Bouziri; Ammar, Khaldi; Khaled, Menif; Najoua, Guandoura; Nejla, Ben Jaballah

    2009-11-30

    Multilocular thymic cysts are rare benign lesions of the neck and mediastinum that can occur at any age. In children, multilocular thymic cysts are usually symptomatic after the age of 2 years and produce few symptoms. We present an unusual case of a multilocular thymic cyst diagnosed in a 3-month-old girl and causing severe respiratory failure. A 3 month-old-girl, with a medical history of dyspnea and wheezing since the age of 20 days, presented in our pediatric intensive care unit for acute respiratory failure requiring mechanical ventilation. The chest radiograph showed thoracic distension without any other abnormalities. The diagnosis of severe asthma was initially suspected and the patient was treated by intravenous corticosteroids and continuous perfusion of salbutamol without any improvement. A chest tomography scan was performed and demonstrated an anterior mediastinal multiseptated cystic mass extending from the inferior face of the thyroid gland to the left cardiophrenic angle. Sternotomy and excision biopsy were planned urgently. The cystic mass was excised completely. The histopathological examination confirmed the diagnosis of a multilocular thymic cyst. The particularities of our observation are the occurrence of a multilocular thymic cyst in a young infant and its presentation by a severe acute respiratory failure mimicking asthma.

  9. Platinum-based chemotherapy with or without thoracic radiation therapy in patients with unresectable thymic carcinoma

    International Nuclear Information System (INIS)

    Nakamura, Yoichi; Kunitoh, Hideo; Kubota, Kaoru

    2000-01-01

    Thymic carcinoma is a rare mediastinal neoplasm with poor prognosis. Although the clinical benefit of chemotherapy for thymic carcinoma is controversial, cisplatin-based chemotherapy with or without radiation therapy is ordinarily adopted in advanced cases. We evaluated the clinical outcome of platinum-based chemotherapy with or without radiation therapy in unresectable thymic carcinoma patients. Ten patients with unresectable thymic carcinoma were treated with platinum-based chemotherapy with or without radiation therapy in the National Cancer Center Hospital between 1989 and 1998. We reviewed the histological type, treatment, response and survival of these patients. Four of the 10 patients responded to chemotherapy and both the median progression-free survival period and the median response duration were 6.0 months. The median survival time was 11.0 months. There was no relationship between histological classification and prognosis. Platinum-based chemotherapy with or without thoracic radiation is, regardless of tumor histology, marginally effective in advanced thymic carcinoma patients, giving only a modest tumor response rate and short response duration and survival. (author)

  10. Age-Related Macular Degeneration: Advances in Management and Diagnosis

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    Yoshihiro Yonekawa

    2015-02-01

    Full Text Available Age-related macular degeneration (AMD is the most common cause of irreversible visual impairment in older populations in industrialized nations. AMD is a late-onset deterioration of photoreceptors and retinal pigment epithelium in the central retina caused by various environmental and genetic factors. Great strides in our understanding of AMD pathogenesis have been made in the past several decades, which have translated into revolutionary therapeutic agents in recent years. In this review, we describe the clinical and pathologic features of AMD and present an overview of current diagnosis and treatment strategies.

  11. Figure ground discrimination in age-related macular degeneration.

    Science.gov (United States)

    Tran, Thi Ha Chau; Guyader, Nathalie; Guerin, Anne; Despretz, Pascal; Boucart, Muriel

    2011-03-01

    To investigate impairment in discriminating a figure from its background and to study its relation to visual acuity and lesion size in patients with neovascular age-related macular degeneration (AMD). Seventeen patients with neovascular AMD and visual acuity Figure/ground segregation is impaired in patients with AMD. A white space surrounding an object is sufficient to improve the object's detection and to facilitate figure/ground segregation. These results may have practical applications to the rehabilitation of the environment in patients with AMD.

  12. Age related macular degeneration - modern diagnostic and therapeutic preventive approach

    OpenAIRE

    Gogelová, Blanka

    2009-01-01

    Age-related macular degeneration (AMD) is a disease associated with aging that gradually destroys sharp, central vision. Central vision is needed for seeing objects clearly and for common daily tasks such as reading and driving. AMD affects the macula, the part of the eye that alows seeing of fine details. AMD occurs in two form: dry and wet. In dry AMD, the light sensitive cells in the macula slowly break down. As fewer cells in the macula are able to function, people will see details less c...

  13. New developments in age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Lyndon da Cruz

    2008-09-01

    Full Text Available The World Health Organization (WHO estimates that over 3 million people (9% of global blindness are blinded by age-related macular degeneration (AMD. AMD affects people over the age of 55. There are two main types of AMD, dry and wet. In dry AMD, patients slowly lose vision through progressive atrophy of the macular tissue. Wet, or exudative, AMD, is associated with new blood vessels called subretinal neovascular membranes (or SRNVM and affected patients lose vision more rapidly due to fluid leakage and haemorrhage at the macula.

  14. Counteracting age-related loss of skeletal muscle mass

    DEFF Research Database (Denmark)

    Bechshøft, Rasmus; Reitelseder, Søren; Højfeldt, Grith

    2016-01-01

    Background Aging is associated with decreased muscle mass and functional capacity, which in turn decrease quality of life. The number of citizens over the age of 65 years in the Western world will increase by 50 % over the next four decades, and this demographic shift brings forth new challenges...... at both societal and individual levels. Only a few longitudinal studies have been reported, but whey protein supplementation seems to improve muscle mass and function, and its combination with heavy strength training appears even more effective. However, heavy resistance training may reduce adherence...... Intervention Study will generate scientific evidence and recommendations to counteract age-related loss of skeletal muscle mass in elderly individuals....

  15. Age-related macular degeneration: epidemiology and optimal treatment

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian....... Smoking is probably also a risk factor. Preventive strategies using macular laser photocoagulation are under investigation, but their efficacy in preventing visual loss is as yet unproven. There is no treatment with proven efficacy for geographic atrophy. Optimal treatment for exudative AMD requires...

  16. Research status of conbercept treating age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Hai-Yan He

    2015-08-01

    Full Text Available Age-related macular degeneration(AMDis one of the major reasons of blindness among the elderly in the developed countries. As AMD patients are increasing year by year, AMD has become one of the important topics of ophthalmic research to prevent blindness. Its pathogenesis is not fully understood, but many studies have shown that vascular endothelial growth factor(VEGFplays an important role in the pathogenesis. With the development and application of anti-VEGF drugs, there are a variety of drugs applied to the disease. This article introduces conbercept for the treatment of AMD.

  17. Age-related changes in crowding and reading speed

    OpenAIRE

    Liu, Rong; Patel, Bhavika N.; Kwon, MiYoung

    2017-01-01

    Crowding, the inability to recognize objects in clutter, is known to play a role in developmental changes in reading speed. Here, we investigated whether crowding also plays a role in age-related changes in reading speed. We recruited 18 young (mean age: 22.6???3.5; range: 18~31) and 21 older adults (mean age: 58.2???7.0; range: 50~73) with normal vision. Reading speed was measured with short blocks of text. The degree of crowding was determined by measuring crowding zone (the distance betwee...

  18. Effect of Bcl11b genotypes and γ-radiation on the development of mouse thymic lymphomas

    International Nuclear Information System (INIS)

    Yoshikai, Yoshihiro; Sato, Toshihiro; Morita, Shinichi; Kohara, Yuki; Takagi, Ritsuo; Mishima, Yukio; Kominami, Ryo

    2008-01-01

    Bcl11b is a haploinsufficient tumor suppressor gene and expressed in many tissues such as thymus, brain and skin. Irradiated Bcl11b +/- heterozygous mice mostly develop thymic lymphomas, but the preference of Bcl11b inactivation for thymic lymphomas remains to be addressed. We produced Bcl11b +/- heterozygous and Bcl11b wild-type mice of p53 +/- background and compared their incidence of γ-ray induced thymic lymphomas. Majority of the tumors in p53 +/- mice were skin tumors, and only 5 (36%) of the 14 tumors were thymic lymphomas. In contrast, Bcl11b +/- p53 +/- doubly heterozygous mice developed thymic lymphomas at the frequency of 27 (79%) of the 34 tumors developed (P = 0.008). This indicates the preference of Bcl11b impairment for thymic lymphoma development. We also analyzed loss of the wild-type alleles in the 27 lymphomas, a predicted consequence given by γ-irradiation. However, the loss frequency was low, only six (22%) for Bcl11b and five (19%) for p53. The frequencies did not differ from those of spontaneously developed thymic lymphomas in the doubly heterozygous mice, though the latency of lymphoma development markedly differed between them. This suggests that the main contribution of irradiation at least in those mice is not for the tumor initiation by inducing allelic losses but probably for the promotion of thymic lymphoma development

  19. Age-related retinopathy in NRF2-deficient mice.

    Directory of Open Access Journals (Sweden)

    Zhenyang Zhao

    2011-04-01

    Full Text Available Cumulative oxidative damage is implicated in the pathogenesis of age-related macular degeneration (AMD. Nuclear factor erythroid 2-related factor 2 (NRF2 is a transcription factor that plays key roles in retinal antioxidant and detoxification responses. The purposes of this study were to determine whether NRF2-deficient mice would develop AMD-like retinal pathology with aging and to explore the underlying mechanisms.Eyes of both wild type and Nrf2(-/- mice were examined in vivo by fundus photography and electroretinography (ERG. Structural changes of the outer retina in aged animals were examined by light and electron microscopy, and immunofluorescence labeling. Our results showed that Nrf2(-/- mice developed age-dependent degenerative pathology in the retinal pigment epithelium (RPE. Drusen-like deposits, accumulation of lipofuscin, spontaneous choroidal neovascularization (CNV and sub-RPE deposition of inflammatory proteins were present in Nrf2(-/- mice after 12 months. Accumulation of autophagy-related vacuoles and multivesicular bodies was identified by electron microscopy both within the RPE and in Bruch's membrane of aged Nrf2(-/- mice.Our data suggest that disruption of Nfe2l2 gene increased the vulnerability of outer retina to age-related degeneration. NRF2-deficient mice developed ocular pathology similar to cardinal features of human AMD and deregulated autophagy is likely a mechanistic link between oxidative injury and inflammation. The Nrf2(-/- mice can provide a novel model for mechanistic and translational research on AMD.

  20. KCNQ channels regulate age-related memory impairment.

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    Sonia Cavaliere

    Full Text Available In humans KCNQ2/3 heteromeric channels form an M-current that acts as a brake on neuronal excitability, with mutations causing a form of epilepsy. The M-current has been shown to be a key regulator of neuronal plasticity underlying associative memory and ethanol response in mammals. Previous work has shown that many of the molecules and plasticity mechanisms underlying changes in alcohol behaviour and addiction are shared with those of memory. We show that the single KCNQ channel in Drosophila (dKCNQ when mutated show decrements in associative short- and long-term memory, with KCNQ function in the mushroom body α/βneurons being required for short-term memory. Ethanol disrupts memory in wildtype flies, but not in a KCNQ null mutant background suggesting KCNQ maybe a direct target of ethanol, the blockade of which interferes with the plasticity machinery required for memory formation. We show that as in humans, Drosophila display age-related memory impairment with the KCNQ mutant memory defect mimicking the effect of age on memory. Expression of KCNQ normally decreases in aging brains and KCNQ overexpression in the mushroom body neurons of KCNQ mutants restores age-related memory impairment. Therefore KCNQ is a central plasticity molecule that regulates age dependent memory impairment.

  1. Age Related Changes in Hematological Values of Myanmar Local Puppies

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    Thandar Oo

    2017-10-01

    Full Text Available The hematological parameters were used to monitor the health status and its components also changed according to the ages. However, there were no reports for this issues in Myanmar local dogs. Thus, this study was carried out to investigate the age-related changes on the hematological parameters of local puppies in Myanmar. Ten local puppies with the age of 2-3 month old were used in this experiment, which was lasted for 8 weeks.The daily clinical examinations were conducted throughout the entire experimental period for general health check-up. Haematological parameters (Total WBC count and its differential counts, and RBC, HCT, MCV, HGB, MCH, MCHC and platelets were measured bi-weekly with Abacus Vet-5 automate haematology analyser. According to the results, the total WBC and eosinophil counts were not significantly different (P>0.05, while lymphocytes, monocytes, neutrophils and basophils were significantly different (P0.05 throughout the experimental periods. Thus, the age-related changes were observed on cell counts of lymphocytes, monocytes, neutrophils, basophils in Myanmar local puppies.

  2. Splicing regulatory factors, ageing and age-related disease.

    Science.gov (United States)

    Latorre, Eva; Harries, Lorna W

    2017-07-01

    Alternative splicing is a co-transcriptional process, which allows for the production of multiple transcripts from a single gene and is emerging as an important control point for gene expression. Alternatively expressed isoforms often have antagonistic function and differential temporal or spatial expression patterns, yielding enormous plasticity and adaptability to cells and increasing their ability to respond to environmental challenge. The regulation of alternative splicing is critical for numerous cellular functions in both pathological and physiological conditions, and deregulated alternative splicing is a key feature of common chronic diseases. Isoform choice is controlled by a battery of splicing regulatory proteins, which include the serine arginine rich (SRSF) proteins and the heterogeneous ribonucleoprotein (hnRNP) classes of genes. These important splicing regulators have been implicated in age-related disease, and in the ageing process itself. This review will outline the important contribution of splicing regulator proteins to ageing and age-related disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Gender effects on age-related changes in brain structure.

    Science.gov (United States)

    Xu, J; Kobayashi, S; Yamaguchi, S; Iijima, K; Okada, K; Yamashita, K

    2000-01-01

    Previous reports have suggested that brain atrophy is associated with aging and that there are gender differences in brain atrophy with aging. These reports, however, neither exclude silent brain lesions in "healthy subjects" nor divide the brain into subregions. The aim of this study is to clarify the effect of gender on age-related changes in brain subregions by MR imaging. A computer-assisted system was used to calculate the brain matter area index (BMAI) of various regions of the brain from MR imaging of 331 subjects without brain lesions. There was significantly more brain atrophy with aging in the posterior parts of the right frontal lobe in male subjects than there was in female subjects. Age-related atrophy in the middle part of the right temporal lobe, the left basal ganglia, the parietal lobe, and the cerebellum also was found in male subjects, but not in female subjects. In the temporal lobe, thalamus, parieto-occipital lobe, and cerebellum, brain volume in the left hemisphere is significantly smaller than in the right hemisphere; sex and age did not affect the hemisphere differences of brain volume in these regions. The effect of gender on brain atrophy with aging varied in different subregions of the brain. There was more brain atrophy with aging in male subjects than in female subjects.

  4. MORPHOLOGICAL STUDY OF THE AGE RELATED CHANGES OF THE CERVIX

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    Monjushree Chakravarty

    2016-07-01

    Full Text Available BACKGROUND Disease of the cervix is a common clinical condition in females, worldwide and especially in a developing country like India. The study was undertaken in Guwahati Medical College to see the age related changes in the morphology of the cervix. AIM The study was done to observe the age related changes in the cervix and compare the same with the different studies done by the previous workers around the world so as to help clinicians to diagnose the pathologies of this part of the female reproductive system better. MATERIALS AND METHOD The specimens were divided into three groups viz. pre-reproductive, reproductive and post-menopausal. Twenty specimens were collected of each group. The results were statistically analysed and ‘t’ test was employed to find out the significant difference between the mean value. SUMMARY A study of the 60 specimens collected were done to find the morphological parameters of each group viz. pre-reproductive, reproductive and post-menopausal and the findings of each group were compared to one another and were related to the finding of previous workers. CONCLUSION The study showed that there were certain differences in the morphology of the three groups and these differences tallied with that of the previous workers.

  5. Radiation therapy for neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Robert Petrarca

    2011-01-01

    Full Text Available Robert Petrarca, Timothy L JacksonDepartment of Ophthalmology, King’s College Hospital NHS Foundation Trust, London, UKAbstract: Antivascular endothelial growth factor (anti-VEGF therapies represent the standard of care for most patients presenting with neovascular (wet age-related macular degeneration (neovascular AMD. Anti-VEGF drugs require repeated injections and impose a considerable burden of care, and not all patients respond. Radiation targets the proliferating cells that cause neovascular AMD, including fibroblastic, inflammatory, and endothelial cells. Two new neovascular AMD radiation treatments are being investigated: epimacular brachytherapy and stereotactic radiosurgery. Epimacular brachytherapy uses beta radiation, delivered to the lesion via a pars plana vitrectomy. Stereotactic radiosurgery uses low voltage X-rays in overlapping beams, directed onto the lesion. Feasibility data for epimacular brachytherapy show a greatly reduced need for anti-VEGF therapy, with a mean vision gain of 8.9 ETDRS letters at 12 months. Pivotal trials are underway (MERLOT, CABERNET. Preliminary stereotactic radiosurgery data suggest a mean vision gain of 8 to 10 ETDRS letters at 12 months. A large randomized sham controlled stereotactic radiosurgery feasibility study is underway (CLH002, with pivotal trials to follow. While it is too early to conclude on the safety and efficacy of epimacular brachytherapy and stereotactic radiosurgery, preliminary results are positive, and these suggest that radiation offers a more durable therapeutic effect than intraocular injections.Keywords: wet age-related macular degeneration, neovascular, radiation therapy, epimacular brachytherapy, stereotactic radiosurgery, anti-VEGF

  6. Age-related motor unit remodeling in the Tibialis Anterior.

    Science.gov (United States)

    Siddiqi, Ariba; Kumar, Dinesh; Arjunan, Sridhar

    2015-01-01

    Limited studies exist on the use of surface electromyogram (EMG) signal features to detect age-related motor unit remodeling in the Tibialis Anterior. Motor unit remodeling leads to declined muscle strength and force steadiness during submaximal contractions which are factors for risk of falls in the elderly. This study investigated the remodeling phenomena in the Tibialis Anterior using sample entropy and higher order statistics. Eighteen young (26.1 ± 2.9 years) and twelve elderly (68.7 ± 9.0 years) participants performed isometric dorsiflexion of the ankle at 20% maximal voluntary contraction (MVC) and their Tibialis Anterior (TA) EMG was recorded. Sample entropy, Gaussianity and Linearity Test statistics were calculated from the recorded EMG for each MVC. Shapiro-Wilk test was used to determine normality, and either a two-tail student t-test or Wilcoxon rank sum test was performed to determine significant difference in the EMG features between the young and old cohorts. Results show age-related motor unit remodeling to be depicted by decreased sample entropy (p <; 0.1), increased non-Gaussianity (p <; 0.05) and lesser degree of linearity in the elderly. This is due to the increased sparsity of the MUAPs as a result of the denervation-reinnervation process, and the decrease in total number of motor units.

  7. Parainflammation, chronic inflammation and age-related macular degeneration

    Science.gov (United States)

    Chen, Mei; Xu, Heping

    2016-01-01

    Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune privileged tissue due to its unique anatomical and physiological properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate immune system, particularly microglia and the complement system, undergo low levels of activation (para-inflammation). In many cases, this para-inflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration (AMD), this para-inflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal para-inflammation include genetic predisposition, environmental risk factors and old age. Dysregulated para-inflammation (chronic inflammation) in AMD damages the blood retina barrier (BRB), resulting in the breach of retinal immune privilege leading to the development of retinal lesions. This review discusses the basic principles of retinal innate immune responses to endogenous chronic insults in normal aging and in AMD, and explores the difference between beneficial para-inflammation and the detrimental chronic inflammation in the context of AMD. PMID:26292978

  8. Radiation therapy for age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Takagi, Chikako; Mori, Hideo; Akuta, Keizou [Otsu Red Cross Hospital, Shiga (Japan); Yoshimura, Nagahisa

    1998-04-01

    We evaluated the effect of low-dose radiation on age-related macular degeneration in 8 affected eyes. Radiation was applied using photons at 4 MV. Each eye received 10 fractions of 2 Gy per day over 2 weeks. At 6 months after treatment, funduscopic or angiographic findings had either improved or remained unchanged in all the eyes. The visual acuity improved by 2 lines or more in 2 eyes (25%), remained unchanged in 5 eyes (63%) and deteriorated in 1 eye (13%). At the last examination, fundus findings had improved in 2 eyes (25%), remained unchanged in 1 eye (13%) and deteriorated in 5 eyes (63%). The visual acuity had improved or unchanged in 2 eyes each (25%) and deteriorated in 4 eyes (50%). There has been no negative side effects of radiation. Above findings show that low-dose radiation is potentially beneficial for subfoveal or juxtafoveal choroidal neovascularizations in age-related macular degeneration on a short term basis. (author)

  9. Auditory white noise reduces age-related fluctuations in balance.

    Science.gov (United States)

    Ross, J M; Will, O J; McGann, Z; Balasubramaniam, R

    2016-09-06

    Fall prevention technologies have the potential to improve the lives of older adults. Because of the multisensory nature of human balance control, sensory therapies, including some involving tactile and auditory noise, are being explored that might reduce increased balance variability due to typical age-related sensory declines. Auditory white noise has previously been shown to reduce postural sway variability in healthy young adults. In the present experiment, we examined this treatment in young adults and typically aging older adults. We measured postural sway of healthy young adults and adults over the age of 65 years during silence and auditory white noise, with and without vision. Our results show reduced postural sway variability in young and older adults with auditory noise, even in the absence of vision. We show that vision and noise can reduce sway variability for both feedback-based and exploratory balance processes. In addition, we show changes with auditory noise in nonlinear patterns of sway in older adults that reflect what is more typical of young adults, and these changes did not interfere with the typical random walk behavior of sway. Our results suggest that auditory noise might be valuable for therapeutic and rehabilitative purposes in older adults with typical age-related balance variability. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Modification of radiation-induced murine thymic lymphoma incidence by curcumin

    International Nuclear Information System (INIS)

    Dange, P.S.; Yadav, H.D.; Kumar, Vimalesh; Bhilwade, H.N.; Pandey, B.N.; Sarma, H.D.

    2017-01-01

    Curcumin is a known antioxidant, preventing radiation damage including carcinogenesis. However, concentration and feeding schedule of curcumin in modification of radiation induced thymic lymphoma incidence in vivo model has not been studied. We report here modification of incidence of γ-radiation-induced thymic lymphoma in mice fed with different doses of curcumin (0.05 to 1 %) in diet. Results: Female Swiss mice (6-8 weeks) fed with normal diet and exposed to 3 Gy whole body "6"0Co γ-irradiation (WBI) showed 85 % incidence of thymic lymphoma (TL) at 120 days post-irradiation. A concentration of 1 % curcumin was found the most effective in TL incidence prevention than other fed concentrations. The TL incidence was remarkably reduced when curcumin was fed to the mice before than after the radiation exposure. These results suggest modification of TL incidence by curcumin in irradiated mice involving DNA damage and apoptotic death mechanisms

  11. Alteration of T cell function in healthy persons with a history of thymic x irradiation

    International Nuclear Information System (INIS)

    Rieger, C.H.L.; Kraft, S.C.; Rothberg, R.M.

    1975-01-01

    The possible late effects of x irradiation to the infantile thymus were investigated by studying immune functions in 12 healthy persons with a history of thymic x irradiation and healthy control subjects. No differences were found in serum immunoglobulin values, humoral antibody levels, lymphocyte counts, and lymphocyte reactivity to phytohemagglutinin, vaccinia virus, purified protein derivative (PPD), and allogeneic cells. The irradiation group exhibited cellular hyperresponsiveness to streptokinase-streptodornase (SK-SD). In contrast, mean skin and in vitro lymphocyte responses to Candida albicans were depressed in the patients with thymic irradiation. A dissociation of these two Candida responses was found in only 1 of 14 healthy control subjects but in 7 of 12 irradiated individuals. While thymic irradiation did not result in impaired immunologic defenses leading to clinical disease, it caused alterations in T cell responses similar to those reported in patients with chronic mucocutaneous candidiasis

  12. Alteration of T cell function in healthy persons with a history of thymic x irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Rieger, C.H.L.; Kraft, S.C.; Rothberg, R.M.

    1975-10-01

    The possible late effects of x irradiation to the infantile thymus were investigated by studying immune functions in 12 healthy persons with a history of thymic x irradiation and healthy control subjects. No differences were found in serum immunoglobulin values, humoral antibody levels, lymphocyte counts, and lymphocyte reactivity to phytohemagglutinin, vaccinia virus, purified protein derivative (PPD), and allogeneic cells. The irradiation group exhibited cellular hyperresponsiveness to streptokinase-streptodornase (SK-SD). In contrast, mean skin and in vitro lymphocyte responses to Candida albicans were depressed in the patients with thymic irradiation. A dissociation of these two Candida responses was found in only 1 of 14 healthy control subjects but in 7 of 12 irradiated individuals. While thymic irradiation did not result in impaired immunologic defenses leading to clinical disease, it caused alterations in T cell responses similar to those reported in patients with chronic mucocutaneous candidiasis.

  13. Rapid development of thymic neuroendocrine carcinoma despite transcervical thymectomy in a patient with multiple endocrine neoplasia type 1

    Directory of Open Access Journals (Sweden)

    Dhalapathy Sadacharan

    2013-01-01

    Full Text Available Thymic neuroendocrine (NE tumors are a rare manifestation of multiple endocrine neoplasia syndrome type 1 (MEN-1. They are malignant and aggressive tumors and form a major cause of mortality in MEN-1. Transcervical thymectomy (TCT at the time of parathyroid surgery for primary hyperparathyroidism (PHPT in MEN-1 usually prevents thymic NE tumors. We report a 56-year-old nonsmoker male with sporadic MEN-1 who presented with thymic NE carcinoma developing rapidly within a span of 8 months after subtotal parathyroidectomy and TCT for PHPT. We present a brief review of literature on this rare NE malignancy, focusing on its occurrence despite TCT. This case highlights the fact that thymic NE carcinoma may develop even after TCT in MEN-1. Regular surveillance for these aggressive thymic NE tumors is mandatory even after TCT in MEN-1 setting.

  14. Transplantation of retinal pigment epithelial cells - a possible future treatment for age-related macular degeneration

    DEFF Research Database (Denmark)

    Wiencke, Anne Katrine

    2001-01-01

    ophthalmology, age-related macular degeneration, transplantation, retinal pigment epithelial cells, treatment......ophthalmology, age-related macular degeneration, transplantation, retinal pigment epithelial cells, treatment...

  15. Transplantation of retinal pigment epithelial cells - a possible future treatment for age-related macular degeneration

    DEFF Research Database (Denmark)

    Wiencke, Anne Katrine

    2001-01-01

    ophthalmology, age-related macular degeneration, retinal pigment epithelial cells, transplantation, treatment......ophthalmology, age-related macular degeneration, retinal pigment epithelial cells, transplantation, treatment...

  16. Frequent silencing of RASSF1A by DNA methylation in thymic neuroendocrine tumours.

    Science.gov (United States)

    Kajiura, Koichiro; Takizawa, Hiromitsu; Morimoto, Yuki; Masuda, Kiyoshi; Tsuboi, Mitsuhiro; Kishibuchi, Reina; Wusiman, Nuliamina; Sawada, Toru; Kawakita, Naoya; Toba, Hiroaki; Yoshida, Mitsuteru; Kawakami, Yukikiyo; Naruto, Takuya; Imoto, Issei; Tangoku, Akira; Kondo, Kazuya

    2017-09-01

    Aberrant methylation of promoter CpG islands (CGIs) of tumour suppressor genes is a common epigenetic mechanism underlying cancer pathogenesis. The methylation patterns of thymic tumours have not been studied in detail since such tumours are rare. Herein, we sought to identify genes that could serve as epigenetic targets for thymic neuroendocrine tumour (NET) therapy. Genome-wide screening for aberrantly methylated CGIs was performed in three NET samples, seven thymic carcinoma (TC) samples, and eight type-B3 thymoma samples. The methylation status of thymic epithelial tumours (TETs) samples was validated by pyrosequencing in a larger cohort. The expression status was analysed by quantitative polymerase chain reaction (PCR) and immunohistochemistry. We identified a CGI on a novel gene, RASSF1A, which was strongly hypermethylated in NET, but not in thymic carcinoma or B3 thymoma. RASSF1A was identified as a candidate gene statistically and bibliographically, as it showed frequent CGI hypermethylation in NET by genome-wide screening. Pyrosequencing confirmed significant hypermethylation of a RASSF1A CGI in NET. Low-grade NET tissue was more strongly methylated than high-grade NET. Quantitative PCR and immunohistochemical staining revealed that RASSF1A mRNA and protein expression levels were negatively regulated by DNA methylation. RASSF1A is a tumour suppressor gene epigenetically dysregulated in NET. Aberrant methylation of RASSF1A has been reported in various tumours, but this is the first report of RASSF1A hypermethylation in TETs. RASSF1A may represent an epigenetic therapeutic target in thymic NET. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Phenotypic characterization of thymic prelymphoma cells of B10 mice treated with split-dose irradiation

    International Nuclear Information System (INIS)

    Muto, M.; Kubo, E.; Kamisaku, H.; Sado, T.

    1990-01-01

    Using an intrathymic injection assay on B10 Thy-1 congenic mice, it was demonstrated that thymic prelymphoma cells first developed within the thymuses from 4 to 8 days after split-dose irradiation and were detected in more than 63% of the test donor thymuses when examined at 21 and 31 days after irradiation. Moreover, some mice (25%) at 2 mo after split-dose irradiation had already developed thymic lymphomas in their thymuses. To characterize these thymic prelymphoma cells, the thymocytes from B10 Thy-1.1 mice 1 mo after irradiation were stained with anti-CD4 and anti-CD8 mAb and were sorted into four subpopulations. These fractionated cells were injected into the recipient thymuses to examine which subpopulation contained thymic prelymphoma cells. The results indicated that thymic prelymphoma cells existed mainly in CD4- CD8- and CD4- CD8+ thymocyte subpopulations and also in CD4+ CD8+ subpopulation. T cell lymphomas derived from CD4- CD8- prelymphoma cells had mainly CD4- CD8- or CD4- CD8+ phenotypes. T cell lymphomas developed from CD4- CD8+ prelymphoma cells mainly expressed CD4- CD8+ or CD4+ CD8+ phenotype. T cell lymphomas originating from CD4+ CD8+ prelymphoma cells were mainly CD4+ CD8+ but some CD4- CD8+ or CD4+ CD8- cells were also present. These thymic prelymphoma cells were further characterized phenotypically in relation to their expression of the marker defined by the mAb against J11d marker and TL-2 (thymus-leukemia) Ag, which is not expressed on normal thymocytes of B10.Thy-1.2 or B10.Thy-1.1 strain, but appears on the thymocytes of lymphomagenic irradiated mice. The results indicated that the prelymphoma cells existed in J11d+, TL-2+ cells

  18. Studies on radiation-induced thymic lymphomagenesis in B10 strain mice

    International Nuclear Information System (INIS)

    Muto, Masahiro

    1989-01-01

    Using B10.Thy 1 congenic strain mice, we reexamined the earlier results by Kaplan and others that lymphomas could develop from lymphocytes present in the nonirradiated parental thymuses grafted into thymectomized, fractionally irradiated H-2 semiincompatible recipient mice. The results indicated that 37 out of 91 thymectomized and irradiated B10.Thy 1.2 mice developed lymphomas of which 75 % were shown to have originated from grafted thymuses. The evidence was not obtained that supported the involvement of endogenous MuLV or some kind of transmissible agents during thymic lymphomagenesis. We found, with intrathymic injection assay, that 'preneoplastic' cells that will eventually develop into thymic lymphomas under the influence of thymic microenvironment first appeared in the thymuses about 4-8 days after irradiation. These thymic prelymphoma cells 'thymus-dependent' preneoplastic cells were detected in 26.1 % of the test donor thymuses when examined at 14 days and in more than 63 % 21 and 31 days after irradiation. It was found that lymphomagenic irradiation resulted in the anomalous appearance of CD4 + and/or CD8 + thymocytes bearing IL-2 receptor (IL-2R) which were different from normal thymocyte subpopulations. Thymic prelymphoma cells existed mainly in CD4 - CD8 - and CD4 - CD8 + thymocyted subpopulations and also in CD4 + CD8 + subpopulation. T cell lymphomas derived from CD4 - CD8 - prelymphoma cells had mainly CD4 - CD8 - or CD4 - CD8 + phenotypes. T cell lymphomas developed from CD4 - CD8 + prelymphoma cells mainly expressed CD4 - CD8 + or CD4 + CD8 + phenotype. T cell lymphomas originated from CD4 + CD8 + prelymphoma cells were mainly CD4 + CD8 + but some CD4 - CD8 + or CD4 + CD8 - cells were also present. These T cell lymphomas expressed IL-2R on various levels. The development of thymic prelymphoma cells is discussed in view of thymocyte differentiation. (J.P.N)

  19. Prevalence of age-related maculopathy and age-related macular degeneration among the inuit in Greenland. The Greenland Inuit Eye Study

    DEFF Research Database (Denmark)

    Andersen, Mads Varis Nis; Rosenberg, Thomas; la Cour, Morten

    2008-01-01

    To examine the age- and gender-specific prevalence and describe the common phenotype of early age-related maculopathy (ARM) and late-stage age-related macular degeneration (AMD) among the Inuit in Greenland.......To examine the age- and gender-specific prevalence and describe the common phenotype of early age-related maculopathy (ARM) and late-stage age-related macular degeneration (AMD) among the Inuit in Greenland....

  20. Adipocyte and leptin accumulation in tumor-induced thymic involution.

    Science.gov (United States)

    Lamas, Alejandro; Lopez, Elena; Carrio, Roberto; Lopez, Diana M

    2016-01-01

    Cell-mediated immunity is an important defense mechanism against pathogens and developing tumor cells. The thymus is the main lymphoid organ involved in the formation of the cell-mediated immune response by the maturation and differentiation of lymphocytes that travel from the bone marrow, through the lymphatic ducts, to become T lymphocytes. Thymic involution has been associated with aging; however, other factors such as obesity, viral infection and tumor development have been shown to increase the rate of shrinkage of this organ. The heavy infiltration of adipocyte fat cells has been reported in the involuted thymuses of aged mice. In the present study, the possible accumulation of such cells in the thymus during tumorigenesis was examined by immunohistochemistry. A significant number of adipocytes around and infiltrating the thymuses of tumor-bearing mice was observed. Leptin is a pro-inflammatory adipocytokine that enhances thymopoiesis and modulates T cell immune responses. The levels of leptin and adiponectin, another adipocytokine that has anti-inflammatory properties, were examined by western blot analysis. While no changes were observed in the amounts of adiponectin present in the thymuses of the normal and tumor-bearing mice, significantly higher levels of leptin were detected in the thymocytes of the tumor-bearing mice. This correlated with an increase in the expression of certain cytokines, such as interleukin (IL)-2, interferon (IFN)-γ and granulocyte-macrophage colony-stimulating factor (GM-CSF). The co-culture of thymocytes isolated from normal mice with ex vivo isolated adipocytes from tumor-bearing mice yielded similar results. Our findings suggest that the infiltration and accumulation of adipocytes in the thymuses of tumor-bearing mice play an important role in their altered morphology and functions.

  1. The molecular biology of radiation-induced carcinogenesis: thymic lymphoma, myeloid leukaemia and osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Janowski, M [Centre d' Etude de l' Energie Nucleaire, Mol (Belgium); Cox, R [Medical Research Council, Harwell (UK). Radiobiological Research Unit; Strauss, P G [GSF, Neuherberg (Germany, F.R.). Abt. fuer Molekulare Zellpathologie

    1990-04-01

    In mice, external X- or {gamma}-irradiation may induce thymic lymphomas or myeloid leukaemias, while bone-seeking {alpha}-emitters may induce osteosarcomas, and to a lesser extent acute myeloid leukaemia. The paper reviews briefly some experimental data in respect to molecular mechanisms underlying these radio-carcinogenic processes. Thymic lymphomagenesis proceeds by an indirect mechanism in which recombinant proviruses could be involved. Myeloid leukaemogenesis is characterized by a very early putative initiating event, consisting of non-random rearrangements and/or deletions of chromosome 2. Osteosarcomagenesis in mice is often associated with the expression of proviruses, and the tumors often contain somatically acquired proviruses. (UK).

  2. A pediatric case of life-threatening airway obstruction caused by a cervicomediastinal thymic cyst

    Energy Technology Data Exchange (ETDEWEB)

    Komura, Makoto; Kanamori, Yutaka; Sugiyama, Masahiko; Iwanaka, Tadashi [University of Tokyo Hospital, Department of Pediatric Surgery, Tokyo (Japan); Fukushima, Noriyoshi [University of Tokyo Hospital, Department of Pathology, Tokyo (Japan)

    2010-09-15

    Most patients with thymic cysts complain of a slowly enlarging, asymptomatic cervical mass. Only 6-10% suffer dysphagia, dyspnoea, stridor, cervical pain or vocal paralysis. In some rare cases sudden onset of severe dyspnoea or asphyxia is the first symptom, especially in neonates and small infants. We report a unique case of a 20-month-old child, who required emergency tracheal intubation due to asphyxia. Cervicomediastinal thymic cyst might need to be included in causes of life-threatening airway obstruction in young children. (orig.)

  3. Age-related differences in multiple task monitoring.

    Science.gov (United States)

    Todorov, Ivo; Del Missier, Fabio; Mäntylä, Timo

    2014-01-01

    Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men exceeded women in multitasking, measured as monitoring accuracy. Individual differences in executive functioning and spatial ability were independent predictors of young adults' monitoring accuracy, but only spatial ability was related to sex differences. For older adults, age and executive functioning, but not spatial ability, predicted multitasking performance. These results suggest that executive functions contribute to multiple task performance across the adult life span and that reliance on spatial skills for coordinating deadlines is modulated by age.

  4. Age-related effects in the neocortical organization of chimpanzees

    DEFF Research Database (Denmark)

    Autrey, Michelle M; Reamer, Lisa A; Mareno, Mary Catherine

    2014-01-01

    chimpanzees. We used the BrainVisa software to measure total brain volume, gray and white matter volumes, gray matter thickness, and gyrification index in a cross-sectional sample of 219 captive chimpanzees (8-53 years old), with 38 subjects being 40 or more years of age. Mean depth and cortical fold opening...... of 11 major sulci of the chimpanzee brains were also measured. We found that chimpanzees showed increased gyrification with age and a cubic relationship between age and white matter volume. For the association between age and sulcus depth and width, the results were mostly non......Among primates, humans exhibit the most profound degree of age-related brain volumetric decline in particular regions, such as the hippocampus and the frontal lobe. Recent studies have shown that our closest living relatives, the chimpanzees, experience little to no volumetric decline in gray...

  5. Vitamin D and Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Alfredo Garcia Layana

    2017-10-01

    Full Text Available In recent years, the relationship between vitamin D and health has received growing attention from the scientific and medical communities. Vitamin D deficiencies have been repeatedly associated with various acute and chronic diseases, including age-related macular degeneration (AMD. Its active metabolite, 1α,25-dihydoxy vitamin D, acts as a modulator of cell proliferation, differentiation and apoptosis, and cumulative data from experimental and observational studies suggest that relatively a lower vitamin D status could be a potential risk factor for the development of early and/or late AMD. Herein, we made a narrative review of the mechanisms linking a potential role of vitamin D with the current concepts of AMD pathophysiology.

  6. Stem cells: Potential therapy for age-related diseases

    DEFF Research Database (Denmark)

    Kassem, Moustapha

    2006-01-01

    Aging is associated with a progressive failing of tissues and organs of the human body leading to a large number of age-related diseases. Regenerative medicine is an emerging clinical discipline that aims to employ cellular medicines (normal cells, ex vivo expanded cells, or tissue......-engineered organs) to restore the functions of damaged or defective tissues and organs and thus to "rejuvenate" the failing aging body. One of the most important sources for cellular medicine is embryonic and adult (somatic) stem cells (SSCs). One example of SCCs with enormous clinical potential is the mesenchymal...... and organs in tissue-engineering protocols. However, several challenges confront the use of these cells in the clinic, ranging from biological challenges (e.g., how to isolate a homogenous populations of the cells with specific criteria from the bone marrow and how to expand them ex vivo without affecting...

  7. Age-related decline in global form suppression

    DEFF Research Database (Denmark)

    Wiegand, Iris Michaela; Finke, Kathrin; Töllner, Thomas

    2015-01-01

    . Selective attention, i.e., the ability to focus on relevant and ignore irrelevant information, declines with increasing age; however, how this deficit affects selection of global vs. local configurations remains unknown. On this background, the present study examined for age-related differences in a global...... differences in the subsequent (250–500 ms) posterior contralateral negativity (PCN) indicated that attentional resources were allocated faster to Kanisza, as compared to non-Kanisza, targets in both age groups, while the allocation of spatial attention seemed to be generally delayed in older relative...... to younger age. Our results suggest that the enhanced global-local asymmetry in the older age group originated from less effective suppression of global distracter forms on early processing stages – indicative of older observers having difficulties with disengaging from a global default selection mode...

  8. Imaging geographic atrophy in age-related macular degeneration.

    Science.gov (United States)

    Göbel, Arno P; Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Brinkmann, Christian K; Holz, Frank G

    2011-01-01

    Advances in retinal imaging technology have largely contributed to the understanding of the natural history, prognostic markers and disease mechanisms of geographic atrophy (GA) due to age-related macular degeneration. There is still no therapy available to halt or slow the disease process. In order to evaluate potential therapeutic effects in interventional trials, there is a need for precise quantification of the GA progression rate. Fundus autofluorescence imaging allows for accurate identification and segmentation of atrophic areas and currently represents the gold standard for evaluating progressive GA enlargement. By means of high-resolution spectral-domain optical coherence tomography, distinct microstructural alterations related to GA can be visualized. Copyright © 2011 S. Karger AG, Basel.

  9. Age-related associative deficits and the isolation effect.

    Science.gov (United States)

    Badham, Stephen P; Maylor, Elizabeth A

    2013-01-01

    If all but one of the items in a list are similar (e.g., all black except one red), memory for the different item is enhanced (the isolation effect). Older adults generally show similar or smaller isolation effects compared to young adults, which has been attributed to age-related deficits in associative memory whereby older adults are less able to associate an isolated stimulus to its isolating feature. Experiment 1 examined the isolation effect for isolation based on spatial position, modality and color; in Experiment 2, the criterion for isolation was the associative relation between stimuli. The results consistently showed no differences between young and older participants in the magnitude of the isolation effect. Whilst age deficits in associative memory may act to reduce the isolation effect in older adults, age deficits in self-initiated processing and inhibitory functionality may counteract this reduction by enhancing the isolation effect in older adults.

  10. Transcriptome changes in age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Whitmore S Scott

    2012-02-01

    Full Text Available Abstract Age-related macular degeneration (AMD is a debilitating, common cause of visual impairment. While the last decade has seen great progress in understanding the pathophysiology of AMD, the molecular changes that occur in eyes with AMD are still poorly understood. In the current issue of Genome Medicine, Newman and colleagues present the first systematic transcriptional profile analysis of AMD-affected tissues, providing a comprehensive set of expression data for different regions (macula versus periphery, tissues (retina versus retinal pigment epithelium (RPE/choroid, and disease state (control versus early or advanced AMD. Their findings will serve as a foundation for additional systems-level research into the pathogenesis of this blinding disease. Please see related article: http://genomemedicine.com/content/4/2/16

  11. Age-related differences in the attention network test (ANT).

    Science.gov (United States)

    Gamboz, Nadia; Zamarian, Stefania; Cavallero, Corrado

    2010-07-01

    This study investigates the effect of aging on alerting, orienting, and conflict resolution by assessing younger (mean age = 25.8) and older (mean age = 67.9) adults' performance in the Attention Network Test that combines, in a single experimental paradigm, a flanker task with alerting and orienting cues. The analyses of response times indicated equivalent orienting and conflict resolution effects in younger and older adults. By contrast, alerting was found to be significantly reduced in the elderly. This result is only marginally in accordance with recent studies addressing the issues of age-related differences in alerting, which provide mixed results. The possible role of methodological differences across studies in accounting for the controversial results concerning the aging affect on alerting is discussed.

  12. Vitamin D and Age-Related Macular Degeneration.

    Science.gov (United States)

    Layana, Alfredo Garcia; Minnella, Angelo Maria; Garhöfer, Gerhard; Aslam, Tariq; Holz, Frank G; Leys, Anita; Silva, Rufino; Delcourt, Cécile; Souied, Eric; Seddon, Johanna M

    2017-10-13

    In recent years, the relationship between vitamin D and health has received growing attention from the scientific and medical communities. Vitamin D deficiencies have been repeatedly associated with various acute and chronic diseases, including age-related macular degeneration (AMD). Its active metabolite, 1α,25-dihydoxy vitamin D, acts as a modulator of cell proliferation, differentiation and apoptosis, and cumulative data from experimental and observational studies suggest that relatively a lower vitamin D status could be a potential risk factor for the development of early and/or late AMD. Herein, we made a narrative review of the mechanisms linking a potential role of vitamin D with the current concepts of AMD pathophysiology.

  13. Age-related Deterioration of Hematopoietic Stem Cells.

    Science.gov (United States)

    Kim, Mi Jung; Kim, Min Hwan; Kim, Seung Ah; Chang, Jae Suk

    2008-11-01

    Aging is the process of system deterioration over time in the whole body. Stem cells are self-renewing and therefore have been considered exempt from the aging process. Earlier studies by Hayflick showed that there is an intrinsic limit to the number of divisions that mammalian somatic cells can undergo, and cycling kinetics and ontogeny-related studies strongly suggest that even the most primitive stem cell functions exhibit a certain degree of aging. Despite these findings, studies on the effects of aging on stem cell functions are inconclusive. Here we review the age-related properties of hematopoietic stem cells in terms of intrinsic and extrinsic alterations, proliferative potential, signaling molecules, telomere and telomerase, senescence and cancer issues, regenerative potential and other indications of stem cell aging are discussed in detail.

  14. Age-related differences in multiple task monitoring.

    Directory of Open Access Journals (Sweden)

    Ivo Todorov

    Full Text Available Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men exceeded women in multitasking, measured as monitoring accuracy. Individual differences in executive functioning and spatial ability were independent predictors of young adults' monitoring accuracy, but only spatial ability was related to sex differences. For older adults, age and executive functioning, but not spatial ability, predicted multitasking performance. These results suggest that executive functions contribute to multiple task performance across the adult life span and that reliance on spatial skills for coordinating deadlines is modulated by age.

  15. Age-Related Macular Degeneration: Insights into Inflammatory Genes

    Directory of Open Access Journals (Sweden)

    Raffaella Cascella

    2014-01-01

    Full Text Available Age-related macular degeneration (AMD is a progressive neurodegenerative disease that affects approximately 8.7% of elderly people worldwide (>55 years old. AMD is characterized by a multifactorial aetiology that involves several genetic and environmental risk factors (genes, ageing, smoking, family history, dietary habits, oxidative stress, and hypertension. In particular, ageing and cigarette smoking (including oxidative compounds and reactive oxygen species have been shown to significantly increase susceptibility to the disease. Furthermore, different genes (CFH, CFI, C2, C3, IL-6, IL-8, and ARMS2 that play a crucial role in the inflammatory pathway have been associated with AMD risk. Several genetic and molecular studies have indicated the participation of inflammatory molecules (cytokines and chemokines, immune cells (macrophages, and complement proteins in the development and progression of the disease. Taking into consideration the genetic and molecular background, this review highlights the genetic role of inflammatory genes involved in AMD pathogenesis and progression.

  16. Female age-related fertility decline. Committee Opinion No. 589.

    Science.gov (United States)

    2014-03-01

    The fecundity of women decreases gradually but significantly beginning approximately at age 32 years and decreases more rapidly after age 37 years. Education and enhanced awareness of the effect of age on fertility are essential in counseling the patient who desires pregnancy. Given the anticipated age-related decline in fertility, the increased incidence of disorders that impair fertility, and the higher risk of pregnancy loss, women older than 35 years should receive an expedited evaluation and undergo treatment after 6 months of failed attempts to conceive or earlier, if clinically indicated. In women older than 40 years, more immediate evaluation and treatment are warranted. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  17. Risk Factors and Biomarkers of Age-Related Macular Degeneration

    Science.gov (United States)

    Lambert, Nathan G.; Singh, Malkit K.; ElShelmani, Hanan; Mansergh, Fiona C.; Wride, Michael A.; Padilla, Maximilian; Keegan, David; Hogg, Ruth E.; Ambati, Balamurali K.

    2016-01-01

    A biomarker can be a substance or structure measured in body parts, fluids or products that can affect or predict disease incidence. As age-related macular degeneration (AMD) is the leading cause of blindness in the developed world, much research and effort has been invested in the identification of different biomarkers to predict disease incidence, identify at risk individuals, elucidate causative pathophysiological etiologies, guide screening, monitoring and treatment parameters, and predict disease outcomes. To date, a host of genetic, environmental, proteomic, and cellular targets have been identified as both risk factors and potential biomarkers for AMD. Despite this, their use has been confined to research settings and has not yet crossed into the clinical arena. A greater understanding of these factors and their use as potential biomarkers for AMD can guide future research and clinical practice. This article will discuss known risk factors and novel, potential biomarkers of AMD in addition to their application in both academic and clinical settings. PMID:27156982

  18. Radiation Therapy for Neovascular Age-related Macular Degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Kishan, Amar U. [Harvard Medical School, Boston, Massachusetts (United States); Modjtahedi, Bobeck S.; Morse, Lawrence S. [Department of Ophthalmology and Vision Sciences, University of California, Davis, Sacramento, California (United States); Lee, Percy, E-mail: percylee@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States)

    2013-03-01

    In the enormity of the public health burden imposed by age-related macular degeneration (ARMD), much effort has been directed toward identifying effective and efficient treatments. Currently, anti-vascular endothelial growth factor (VEGF) injections have demonstrated considerably efficacy in treating neovascular ARMD, but patients require frequent treatment to fully benefit. Here, we review the rationale and evidence for radiation therapy of ARMD. The results of early photon external beam radiation therapy are included to provide a framework for the sequential discussion of evidence for the usage of stereotactic radiation therapy, proton therapy, and brachytherapy. The evidence suggests that these 3 modern modalities can provide a dose-dependent benefit in the treatment of ARMD. Most importantly, preliminary data suggest that all 3 can be used in conjunction with anti-VEGF therapeutics, thereby reducing the frequency of anti-VEGF injections required to maintain visual acuity.

  19. Nutritional supplements in age-related macular degeneration.

    Science.gov (United States)

    Schmidl, Doreen; Garhöfer, Gerhard; Schmetterer, Leopold

    2015-03-01

    Age-related macular degeneration (AMD) is the most frequent cause of blindness in the Western World. While with new therapies that are directed towards vascular endothelial growth factor (VEGF), a potentially efficient treatment option for the wet form of the disease has been introduced, a therapeutic regimen for dry AMD is still lacking. There is evidence from several studies that oral intake of supplements is beneficial in preventing progression of the disease. Several formulations of micronutrients are currently available. The present review focuses on the role of supplements in the treatment and prevention of AMD and sums up the current knowledge about the most frequently used micronutrients. In addition, regulatory issues are discussed, and future directions for the role of supplementation in AMD are highlighted. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  20. Age-related degradation of boiling water reactor vessel internals

    International Nuclear Information System (INIS)

    Ware, A.G.; Shah, V.N.

    1992-01-01

    Researchers at the Idaho National Engineering Laboratory performed an assessment of the aging of the reactor internals in boiling water reactors (BWRs), and identified the unresolved technical issues related to the degradation of these components. The overall life-limiting mechanism is intergranular stress corrosion cracking (IGSCC). Irradiation-assisted stress corrosion cracking, fatigue, and thermal aging embrittlement are other potential degradation mechanisms. Several failures in BWR internals have been caused by a combination of factors such as environment, high residual or preload stresses, and flow-induced vibration. The ASME Code Section XI in-service inspection requirements are insufficient for detecting aging-related degradation at many locations in reactor internals. Many of the potential locations for IGSCC or fatigue are not accessible for inspection. (orig.)

  1. Age-related degradation of Westinghouse 480-volt circuit breakers

    International Nuclear Information System (INIS)

    Subudhi, M.; MacDougall, E.; Kochis, S.; Wilhelm, W.; Lee, B.S.

    1990-11-01

    After the McGuire event in 1987 relating to failure of the center pole weld in one of its reactor trip breakers, activities were initiated by the NRC to investigate the probable causes. A review of operating experience suggested that the burning of coils, jamming of the operating mechanism, and deterioration of the contacts dominated the breakers failures. Although failures of the pole shaft weld were not included as one of the generic problems, the NRC augmented inspection team had suspected that these welds were substandard which led them to crack prematurely. A DS-416 low voltage air circuit breaker manufactured by Westinghouse was mechanically cycled to identify age-related degradations. This accelerated aging test was conducted for over 36,000 cycles during nine months. Three separate pole shafts, one with a 60 degree weld, one with a 120 degree and one with a 180 degree were used to characterize the cracking in the pole level welds. In addition, three different operating mechanisms and several other parts were replaced as they became inoperable. The testing yielded many useful results. The burning of the closing coils was found to be the effect of binding in the linkages that are connected to this device. Among the seven welds on the pole shaft, number-sign 1 and number-sign 3 were the critical ones which cracked first to cause misalignment of the pole levers, which, in turn, had led to many problems with the operating mechanism including the burning of coils, excessive wear in certain parts, and overstressed linkages. Based on these findings, a maintenance program is suggested to alleviate the age-related degradations that occur due to mechanical cycling of this type of breaker. 3 refs., 39 figs., 7 tabs

  2. Age-related changes in the retinal pigment epithelium (RPE.

    Directory of Open Access Journals (Sweden)

    Xiaorong Gu

    Full Text Available Age-related changes in the retina are often accompanied by visual impairment but their mechanistic details remain poorly understood.Proteomic studies were pursued toward a better molecular understanding of retinal pigment epithelium (RPE aging mechanisms. RPE cells were isolated from young adults (3-4 month-old and old (24-25 month-old F344BN rats, and separated into subcellular fractions containing apical microvilli (MV and RPE cell bodies (CB lacking their apical microvilli. Proteins were extracted in detergent, separated by SDS-PAGE, digested in situ with trypsin and analyzed by LC MS/MS. Select proteins detected in young and old rat RPE were further studied using immunofluorescence and Western blot analysis.A total of 356 proteins were identified in RPE MV from young and 378 in RPE MV from old rats, 48% of which were common to each age group. A total of 897 proteins were identified in RPE CB from young rats and 675 in old CB, 56% of which were common to each age group. Several of the identified proteins, including proteins involved in response to oxidative stress, displayed both quantitative and qualitative changes in overall abundance during RPE aging. Numerous proteins were identified for the first time in the RPE. One such protein, collectrin, was localized to the apical membrane of apical brush border of proximal tubules where it likely regulates several amino acid transporters. Elsewhere, collectrin is involved in pancreatic β cell proliferation and insulin secretion. In the RPE, collectrin expression was significantly modulated during RPE aging. Another age-regulated, newly described protein was DJ-1, a protein extensively studied in brain where oxidative stress-related functions have been described.The data presented here reveals specific changes in the RPE during aging, providing the first protein database of RPE aging, which will facilitate future studies of age-related retinal diseases.

  3. Serum 25-hydroxyvitamin D and Age-Related Cataract.

    Science.gov (United States)

    Park, Sangshin; Choi, Nam-Kyong

    2017-10-01

    Cataract and insufficient vitamin D intake are both increasing worldwide concerns, yet little is known about the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and age-related cataract. We performed this study to determine the association between serum 25(OH)D levels and age-related cataract in adults. Study participants comprised 16,086 adults aged 40 years or older who had never been diagnosed with or undergone surgery for cataract using Korean National Health and Nutrition Examination Survey data from 2008 to 2012. Participants were assessed to have cataract when diagnosed with cortical, nuclear, anterior subcapsular, posterior subcapsular, or mixed cataract. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the magnitude and significance of the association between serum 25(OH)D levels and cataract in multivariable logistic regression models. The OR for nuclear cataract with the highest quintile of serum 25(OH)D levels was 0.86 (95% CI 0.75-0.99) compared to the lowest quintile. A linear trend across quintiles was significant. Natural log-transformed serum 25(OH)D levels were also significantly associated with nuclear cataract (OR 0.84, 95% CI 0.75-0.95). The opulation-attributable fraction of nuclear cataract due to serum 25(OH)D insufficiency (D levels were inversely associated with the risk of nuclear cataract. Prospective studies investigating the effects of serum 25(OH)D levels on the development of nuclear cataract are needed to confirm our findings.

  4. Age-Related Neurochemical Changes in the Vestibular Nuclei

    Directory of Open Access Journals (Sweden)

    Paul eSmith

    2016-03-01

    Full Text Available There is evidence that the normal aging process is associated with impaired vestibulo-ocular (VOR and vestibulo-spinal reflexes, causing reduced visual acuity and postural instability. Nonetheless, the available evidence is not entirely consistent, especially with respect to the VOR. Some recent studies have reported that VOR gain can be intact even above 80 years of age. Similarly, although there is evidence for age-related hair cell loss and neuronal loss in Scarpa’s ganglion and the vestibular nucleus complex (VNC, it is not entirely consistent. Whatever structural and functional changes occur in the VNC as a result of aging, either to cause vestibular impairment or to compensate for it, neurochemical changes must underlie them. However, the neurochemical changes that occur in the VNC with aging are poorly understood because the available literature is very limited. This review summarises and critically evaluates the available evidence relating to the noradrenaline, serotonin, dopamine, glutamate, GABA, glycine, and nitric oxide neurotransmitter systems in the aging VNC. It is concluded that, at present, it is difficult, if not impossible, to relate the neurochemical changes observed to the function of specific VNC neurons and whether the observed changes are the cause of a functional deficit in the VNC or an effect of it. A better understanding of the neurochemical changes that occur during aging may be important for the development of potential drug treatments for age-related vestibular disorders. However, this will require the use of more sophisticated methodology such as in vivo microdialysis with single neuron recording and perhaps new technologies such as optogenetics.

  5. Age-Related Neurochemical Changes in the Vestibular Nuclei.

    Science.gov (United States)

    Smith, Paul F

    2016-01-01

    There is evidence that the normal aging process is associated with impaired vestibulo-ocular reflexes (VOR) and vestibulo-spinal reflexes, causing reduced visual acuity and postural instability. Nonetheless, the available evidence is not entirely consistent, especially with respect to the VOR. Some recent studies have reported that VOR gain can be intact even above 80 years of age. Similarly, although there is evidence for age-related hair cell loss and neuronal loss in Scarpa's ganglion and the vestibular nucleus complex (VNC), it is not entirely consistent. Whatever structural and functional changes occur in the VNC as a result of aging, either to cause vestibular impairment or to compensate for it, neurochemical changes must underlie them. However, the neurochemical changes that occur in the VNC with aging are poorly understood because the available literature is very limited. This review summarizes and critically evaluates the available evidence relating to the noradrenaline, serotonin, dopamine, glutamate, GABA, glycine, and nitric oxide neurotransmitter systems in the aging VNC. It is concluded that, at present, it is difficult, if not impossible, to relate the neurochemical changes observed to the function of specific VNC neurons and whether the observed changes are the cause of a functional deficit in the VNC or an effect of it. A better understanding of the neurochemical changes that occur during aging may be important for the development of potential drug treatments for age-related vestibular disorders. However, this will require the use of more sophisticated methodology such as in vivo microdialysis with single neuron recording and perhaps new technologies such as optogenetics.

  6. Age-related changes in contextual associative learning.

    Science.gov (United States)

    Luu, Trinh T; Pirogovsky, Eva; Gilbert, Paul E

    2008-01-01

    The hippocampus plays a critical role in processing contextual information. Although age-related changes in the hippocampus are well documented in humans, nonhuman primates, and rodents, few studies have examined contextual learning deficits in old rats. The present study investigated age-related differences in contextual associative learning in young (6 mo) and old (24 mo) rats using olfactory stimuli. Stimuli consisted of common odors mixed in sand and placed in clear plastic cups. Testing was conducted in two boxes that represented two different contexts (Context 1 and Context 2). The contexts varied based on environmental features of the box such as color (black vs. white), visual cues on the walls of the box, and flooring texture. Each rat was simultaneously presented with two cups, one filled with Odor A and one filled with Odor B in each context. In Context 1, the rat received a food reward for digging in the cup containing Odor A, but did not receive a food reward for digging in the cup containing Odor B. In Context 2, the rat was rewarded for digging in the cup containing Odor B, but did receive a reward for digging in the cup containing Odor A. Therefore, the rat learned to associate Context 1 with Odor A and Context 2 with Odor B. The rat was tested for eight days using the same odor problem throughout all days of testing. The results showed no significant difference between young and old rats on the first two days of testing; however, young rats significantly outperformed old rats on Day 3. Young rats continued to maintain superior performance compared to old rats on Days 4-8. The results suggest that aging results in functional impairments in brain regions that support memory for associations between specific cues and their respective context.

  7. Nutritional Modulation of Age-Related Macular Degeneration

    Science.gov (United States)

    Weikel, Karen A; Taylor, Allen

    2012-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30–50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated with AMD are in excess of $340 billion US (American-Health-Assistance-Foundation, 2012). The majority of AMD patients in the United States are not eligible for clinical treatments (Biarnes et al., 2011; Klein et al., 2011). Preventive interventions through dietary modulation are attractive strategies because many studies suggest a benefit of micro and macronutrients with respect to AMD, as well as other age-related debilities, and with few, if any, adverse effects (Chiu, 2011). Preservation of vision would enhance quality of life for millions of elderly people, and alleviate the personal and public health financial burden of AMD (Frick et al., 2007; Wood et al., 2011). Observational studies indicate that maintaining adequate levels of omega-3 fatty acids (i.e. with 2 servings/wk of fish) or a low glycemic index diet may be particularly beneficial for early AMD and that higher levels of carotenoids may be protective, most probably, against neovascular AMD. Intervention trials are needed to better understand the full effect of these nutrients and/or combinations of nutrients on retinal health. Analyses that describe effects of a nutrient on onset and/or progress of AMD are valuable because they indicate the value of a nutrient to arrest AMD at the early stages. This comprehensive summary provides essential information about the value of nutrients with regard to diminishing risk for onset or progress of AMD and can serve as a guide until data from ongoing intervention trials are available. PMID:22503690

  8. Anti-apoptotic signature in thymic squamous cell carcinomas - functional relevance of anti-apoptotic BIRC3 expression in the thymic carcinoma cell line 1889c

    Directory of Open Access Journals (Sweden)

    Bei eHuang

    2013-12-01

    Full Text Available The molecular pathogenesis of thymomas and thymic carcinomas (TCs is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and thymic carcinomas, suggesting that other oncogenic principles might be important. This made us re-analyze historic expression data obtained in a spectrum of thymomas and thymic squamous cell carcinomas (TSCC with a custom made cDNA microarray. By cluster analysis, different anti-apoptotic signatures were detected in type B3 thymoma and TSCC, including overexpression of BIRC3 in TSCCs. This was confirmed by qRT-PCR in the original and an independent validation set of tumors. In contrast to several other cancer cell lines, the BIRC3-positive TSCC cell line, 1889c showed spontaneous apoptosis after BIRC3 knock-down. Targeting apoptosis genes is worth testing as therapeutic principle in TSCC.

  9. Thymic function in the regulation of T cells, and molecular mechanisms underlying the modulation of cytokines and stress signaling (Review).

    Science.gov (United States)

    Yan, Fenggen; Mo, Xiumei; Liu, Junfeng; Ye, Siqi; Zeng, Xing; Chen, Dacan

    2017-11-01

    The thymus is critical in establishing and maintaining the appropriate microenvironment for promoting the development and selection of T cells. The function and structure of the thymus gland has been extensively studied, particularly as the thymus serves an important physiological role in the lymphatic system. Numerous studies have investigated the morphological features of thymic involution. Recently, research attention has increasingly been focused on thymic proteins as targets for drug intervention. Omics approaches have yielded novel insights into the thymus and possible drug targets. The present review addresses the signaling and transcriptional functions of the thymus, including the molecular mechanisms underlying the regulatory functions of T cells and their role in the immune system. In addition, the levels of cytokines secreted in the thymus have a significant effect on thymic functions, including thymocyte migration and development, thymic atrophy and thymic recovery. Furthermore, the regulation and molecular mechanisms of stress‑mediated thymic atrophy and involution were investigated, with particular emphasis on thymic function as a potential target for drug development and discovery using proteomics.

  10. Genetic Regulation of Development of Thymic Lymphomas Induced by N‐Propyl‐N‐nitrosourea in the Rat

    Science.gov (United States)

    Fukami, Hiroko; Nishimura, Mayumi; Matsuyama, Mutsushi

    1995-01-01

    To clarify the linkage between Hbb and Tls‐1 (thymic lymphoma susceptible‐1) loci and to investigate other loci concerned in thymic lymphomagenesis, the BUF/Mna rat, which is highly sensitive to the lymphomagenic activity of N‐propyl‐N‐nitrosourea (PNU), the WKY/NCrj rat, reported to be resistant, and their cross offspring were subjected to genetic analysis. F1 hybrid and backcross generations were raised from the 2 strains, and 6 genetic markers including Hbb were analyzed in individuals of the backcross generation. However, no linkage between Hbb and Tls‐1 loci could be demonstrated since WKY rats also developed a high incidence of thymic lymphomas in response to PNU. Nevertheless, thymic lymphomas developed more rapidly and reached a larger size in the BUF rats. F1 rats expressed a rather rapid and large tumor growth phenotype, while the [(WKY × BUF) × WKY] backcross generation consisted of rats with either rapidly growing or slowly growing tumors. It was thus concluded that rapid development of thymic lymphomas is determined by a gene, provisionally designated Tls‐3. Analysis of the relationship between 6 genetic markers and development of thymic lymphoma in the backcross generation demonstrated that the Tls‐3 locus is loosely linked to the Gc locus, suggesting a possible location on rat chromosome 14. Tls‐3 may not be identical with Tls‐1 and other genes known to be relevant to thymic tumors, but its relationship with Tls‐2 remains obscure. PMID:7559080

  11. Imaging Polarimetry in Age-Related Macular Degeneration

    Science.gov (United States)

    Miura, Masahiro; Yamanari, Masahiro; Iwasaki, Takuya; Elsner, Ann E.; Makita, Shuichi; Yatagai, Toyohiko; Yasuno, Yoshiaki

    2010-01-01

    PURPOSE To evaluate the birefringence properties of eyes with age-related macular degeneration (AMD). To compare the information from two techniques—scanning laser polarimetry (GDx) and polarization-sensitive spectral-domain optical coherence tomography (OCT)—and investigate how they complement each other. METHODS The authors prospectively examined the eyes of two healthy subjects and 13 patients with exudative AMD. Using scanning laser polarimetry, they computed phase-retardation maps, average reflectance images, and depolarized light images. To obtain polarimetry information with improved axial resolution, they developed a fiber-based, polarization-sensitive, spectral-domain OCT system and measured the phase retardation associated with birefringence in the same eyes. RESULTS Both GDx and polarization-sensitive spectral-domain optical coherence tomography detected abnormal birefringence at the locus of exudative lesions. Polarization-sensitive, spectral-domain OCT showed that in the old lesions with fibrosis, phase-retardation values were significantly larger than in the new lesions (P = 0.020). Increased scattered light and altered polarization scramble were associated with portions of the lesions. CONCLUSIONS GDx and polarization-sensitive spectral-domain OCT are complementary in probing birefringence properties in exudative AMD. Polarimetry findings in exudative AMD emphasized different features and were related to the progression of the disease, potentially providing a noninvasive tool for microstructure in exudative AMD. PMID:18515594

  12. Mechanism of Inflammation in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Francesco Parmeggiani

    2012-01-01

    Full Text Available Age-related macular degeneration (AMD is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease.

  13. Age related changes in steroid receptors on cultured lung fibroblasts

    International Nuclear Information System (INIS)

    Barile, F.A.; Bienkowski, R.S.

    1986-01-01

    The number of high affinity glucocorticoid receptors (Ro) on human fetal lung fibroblasts decreases as the cells age in vitro, and it has been suggested that these cell systems may be useful models of age-related changes in vivo. They examined the relation between change in Ro with in vitro aging and donor age. Confluent monolayers of lung fibroblasts at various population doubling levels (PDL), were incubated with ( 3 H)-dexamethasone (( 3 H)Dex) either alone or with excess (.01 mM) Dex. Specific binding was calculated as the difference between radioactivity in cells incubated with and without unlabeled Dex; Scatchard plots were used to analyze the data. Ro, measured as fmol ( 3 H)Dex/10 6 cells, for two lines of human fetal cells (HFL-1 and MRC-5) decreased with increasing age in vitro. However, human newborn (CRL-1485) and adult (CCL-201) cells and fetal rabbit cells (FAB-290), showed increases in Ro with continuous passage. For each cell line, the affinity constant (K/sub d/) did not change significantly with passage. They conclude that the direction of changes in steroid receptor levels on cells aging in vitro is influenced by donor age and species. Caution should be used in applying results obtained from model systems to aging organisms

  14. Age-related cerebral white matter changes on computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, Hitoshi; Kobayashi, Shotai; Koide, Hiromi; Yamaguchi, Shuhei; Okada, Kazunori; Shimote, Kouichi; Tsunematsu, Tokugoro

    1989-01-01

    Changes of cerebral white matter on computed cranial tomography related to aging were studied in 70 subjects aged 30 to 94 years. The subjects had no histories of cerebrovascular accidents and no abnormalities in the central nervous system were shown by physical examinations and CT scans. We measured the average attenuation values (CT numbers) of each elliptical region (165 pixels, 0.39cm/sup 2/) in the bilateral thalamus and twelve areas of deep white matter. Multiple regression analysis was used to assess the effects of age, cranial size and cranial bone CT numbers on the brain CT numbers. We also studied the association between brain CT numbers and brain atrophy, hypertension, diabetes mellitus. CT numbers of frontal white matter surrounding anterior horns decreased with aging in 70 subjects aged 30 to 94 years. No significant correlation between age and brain CT numbers was found in any other region by multivariate analysis, because of the prominent effect of cranial bone CT numbers on brain CT numbers. Although no age-related changes of white matter CT numbers was found in 41 subjects aged 30 to 65 years, there were significant negative correlations between age and white matter CT numbers at all regions in 29 subjects aged 66 to 94 years. Brain atrophy was associated with brain CT numbers. No association was found for hypertension or diabetes mellitus. Brain CT numbers decreased with aging even in neurologically healthy persons in older age. Brain CT numbers also decreased as cerebral atrophy advanced. (author).

  15. Bioactive Nutrients and Nutrigenomics in Age-Related Diseases

    Directory of Open Access Journals (Sweden)

    Tania Rescigno

    2017-01-01

    Full Text Available The increased life expectancy and the expansion of the elderly population are stimulating research into aging. Aging may be viewed as a multifactorial process that results from the interaction of genetic and environmental factors, which include lifestyle. Human molecular processes are influenced by physiological pathways as well as exogenous factors, which include the diet. Dietary components have substantive effects on metabolic health; for instance, bioactive molecules capable of selectively modulating specific metabolic pathways affect the development/progression of cardiovascular and neoplastic disease. As bioactive nutrients are increasingly identified, their clinical and molecular chemopreventive effects are being characterized and systematic analyses encompassing the “omics” technologies (transcriptomics, proteomics and metabolomics are being conducted to explore their action. The evolving field of molecular pathological epidemiology has unique strength to investigate the effects of dietary and lifestyle exposure on clinical outcomes. The mounting body of knowledge regarding diet-related health status and disease risk is expected to lead in the near future to the development of improved diagnostic procedures and therapeutic strategies targeting processes relevant to nutrition. The state of the art of aging and nutrigenomics research and the molecular mechanisms underlying the beneficial effects of bioactive nutrients on the main aging-related disorders are reviewed herein.

  16. Age-related cerebral white matter changes on computed tomography

    International Nuclear Information System (INIS)

    Fukuda, Hitoshi; Kobayashi, Shotai; Koide, Hiromi; Yamaguchi, Shuhei; Okada, Kazunori; Shimote, Kouichi; Tsunematsu, Tokugoro

    1989-01-01

    Changes of cerebral white matter on computed cranial tomography related to aging were studied in 70 subjects aged 30 to 94 years. The subjects had no histories of cerebrovascular accidents and no abnormalities in the central nervous system were shown by physical examinations and CT scans. We measured the average attenuation values (CT numbers) of each elliptical region (165 pixels, 0.39cm 2 ) in the bilateral thalamus and twelve areas of deep white matter. Multiple regression analysis was used to assess the effects of age, cranial size and cranial bone CT numbers on the brain CT numbers. We also studied the association between brain CT numbers and brain atrophy, hypertension, diabetes mellitus. CT numbers of frontal white matter surrounding anterior horns decreased with aging in 70 subjects aged 30 to 94 years. No significant correlation between age and brain CT numbers was found in any other region by multivariate analysis, because of the prominent effect of cranial bone CT numbers on brain CT numbers. Although no age-related changes of white matter CT numbers was found in 41 subjects aged 30 to 65 years, there were significant negative correlations between age and white matter CT numbers at all regions in 29 subjects aged 66 to 94 years. Brain atrophy was associated with brain CT numbers. No association was found for hypertension or diabetes mellitus. Brain CT numbers decreased with aging even in neurologically healthy persons in older age. Brain CT numbers also decreased as cerebral atrophy advanced. (author)

  17. Targeting Mitochondria to Counteract Age-Related Cellular Dysfunction

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    Corina T. Madreiter-Sokolowski

    2018-03-01

    Full Text Available Senescence is related to the loss of cellular homeostasis and functions, which leads to a progressive decline in physiological ability and to aging-associated diseases. Since mitochondria are essential to energy supply, cell differentiation, cell cycle control, intracellular signaling and Ca2+ sequestration, fine-tuning mitochondrial activity appropriately, is a tightrope walk during aging. For instance, the mitochondrial oxidative phosphorylation (OXPHOS ensures a supply of adenosine triphosphate (ATP, but is also the main source of potentially harmful levels of reactive oxygen species (ROS. Moreover, mitochondrial function is strongly linked to mitochondrial Ca2+ homeostasis and mitochondrial shape, which undergo various alterations during aging. Since mitochondria play such a critical role in an organism’s process of aging, they also offer promising targets for manipulation of senescent cellular functions. Accordingly, interventions delaying the onset of age-associated disorders involve the manipulation of mitochondrial function, including caloric restriction (CR or exercise, as well as drugs, such as metformin, aspirin, and polyphenols. In this review, we discuss mitochondria’s role in and impact on cellular aging and their potential to serve as a target for therapeutic interventions against age-related cellular dysfunction.

  18. Effect of NCAM on aged-related deterioration in vision.

    Science.gov (United States)

    Luke, Margaret Po-Shan; LeVatte, Terry L; O'Reilly, Amanda M; Smith, Benjamin J; Tremblay, François; Brown, Richard E; Clarke, David B

    2016-05-01

    The neural cell adhesion molecule (NCAM) is involved in developmental processes and age-associated cognitive decline; however, little is known concerning the effects of NCAM in the visual system during aging. Using anatomical, electrophysiological, and behavioral assays, we analyzed age-related changes in visual function of NCAM deficient (-/-) and wild-type mice. Anatomical analyses indicated that aging NCAM -/- mice had fewer retinal ganglion cells, thinner retinas, and fewer photoreceptor cell layers than age-matched controls. Electroretinogram testing of retinal function in young adult NCAM -/- mice showed a 2-fold increase in a- and b-wave amplitude compared with wild-type mice, but the retinal activity dropped dramatically to control levels when the animals reached 10 months. In behavioral tasks, NCAM -/- mice had no visual pattern discrimination ability and showed premature loss of vision as they aged. Together, these findings demonstrate that NCAM plays significant roles in the adult visual system in establishing normal retinal anatomy, physiology and function, and in maintaining vision during aging. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Cellular models and therapies for age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    David L. Forest

    2015-05-01

    Full Text Available Age-related macular degeneration (AMD is a complex neurodegenerative visual disorder that causes profound physical and psychosocial effects. Visual impairment in AMD is caused by the loss of retinal pigmented epithelium (RPE cells and the light-sensitive photoreceptor cells that they support. There is currently no effective treatment for the most common form of this disease (dry AMD. A new approach to treating AMD involves the transplantation of RPE cells derived from either human embryonic or induced pluripotent stem cells. Multiple clinical trials are being initiated using a variety of cell therapies. Although many animal models are available for AMD research, most do not recapitulate all aspects of the disease, hampering progress. However, the use of cultured RPE cells in AMD research is well established and, indeed, some of the more recently described RPE-based models show promise for investigating the molecular mechanisms of AMD and for screening drug candidates. Here, we discuss innovative cell-culture models of AMD and emerging stem-cell-based therapies for the treatment of this vision-robbing disease.

  20. MR imaging of proximal femur: age-related changes

    International Nuclear Information System (INIS)

    Kim, Ju Heon; Jeon, Woo Jin; Sohn, Cheol Ho; Park, Mi Ok; Lee, Seong Mun; Joo, Yang Gu; Suh, Soo Jhi; Pyun, Young Sik

    1995-01-01

    The purpose of this study is to illustrate MR patterns of signal intensity of proximal femur in normal subjects according to the age distribution. T1-weighted MR images of the proximal femur in 125 subjects, aged 13 days to 25 years, were retrospectively analyzed. Age distribution was classified to 4 groups; below 4 months, 5 months to 4 years, 5 years to 14 years, and 15 years to 25 years. By the age of 4 months, the non-ossified femoral epiphysis was seen as intermediate-signal-intensity cartilage. At 5 months-4 years, the ossified femoral capital epiphysis was seen within intermediate-signal-intensity cartilage and appeared as decreased or increased signal-intensity red or yellow marrow surrounded by a rim of low-signal-intensity cortical bone. At 5-14 years, the ossified femoral capital and greater trochanteric epiphysis were seen within the intermediate-signal-intensity cartilage and appeared as decreased or increased signal-intensity red or yellow marrow. At 15-25 years, the proximal metaphyseal marrow showed increased signal intensity. Four patterns of the metaphyseal marrow were recognized by Ricci et al. The frequency of pattern 1 a progressively decreased with age. Pattern 2 and 3 were visible in the 15-25 years age group. An understanding of the spectrum of normal age-related change of the proximal femoral cartilage and marrow patterns serves as the foundation for interpretation of proximal femur pathologies

  1. Age-Related Changes in Binaural Interaction at Brainstem Level.

    Science.gov (United States)

    Van Yper, Lindsey N; Vermeire, Katrien; De Vel, Eddy F J; Beynon, Andy J; Dhooge, Ingeborg J M

    2016-01-01

    Age-related hearing loss hampers the ability to understand speech in adverse listening conditions. This is attributed to a complex interaction of changes in the peripheral and central auditory system. One aspect that may deteriorate across the lifespan is binaural interaction. The present study investigates binaural interaction at the level of the auditory brainstem. It is hypothesized that brainstem binaural interaction deteriorates with advancing age. Forty-two subjects of various age participated in the study. Auditory brainstem responses (ABRs) were recorded using clicks and 500 Hz tone-bursts. ABRs were elicited by monaural right, monaural left, and binaural stimulation. Binaural interaction was investigated in two ways. First, grand averages of the binaural interaction component were computed for each age group. Second, wave V characteristics of the binaural ABR were compared with those of the summed left and right ABRs. Binaural interaction in the click ABR was demonstrated by shorter latencies and smaller amplitudes in the binaural compared with the summed monaural responses. For 500 Hz tone-burst ABR, no latency differences were found. However, amplitudes were significantly smaller in the binaural than summed monaural condition. An age-effect was found for 500 Hz tone-burst, but not for click ABR. Brainstem binaural interaction seems to decline with age. Interestingly, these changes seem to be stimulus-dependent.

  2. The Hayflick Limit and Age-Related Adaptive Immune Deficiency.

    Science.gov (United States)

    Gill, Zoe; Nieuwoudt, Martin; Ndifon, Wilfred

    2018-01-01

    The adaptive immune system (AIS) acquires significant deficiency during chronological ageing, making older individuals more susceptible to infections and less responsive to vaccines compared to younger individuals. At the cellular level, one of the most striking features of this ageing-related immune deficiency is the dramatic loss of T-cell diversity that occurs in elderly humans. After the age of 70 years, there is a sharp decline in the diversity of naïve T cells, including a >10-fold decrease in the CD4+ compartment and a >100-fold decrease in the CD8+ compartment. Such changes are detrimental because the AIS relies on a diverse naïve T-cell pool to respond to novel pathogens. Recent work suggests that this collapse of naïve T-cell diversity results from T cells reaching the Hayflick limit and being eliminated through both antigen-dependent and -independent pathways. The progressive attrition of telomeres is the molecular mechanism that underlies this Hayflick limit. Therefore, we propose that by measuring the telomere lengths of T cells with high resolution, it is possible to develop a unique biomarker of immune deficiency, potentially much better correlated with individual susceptibility to diseases compared to chronological age alone. © 2017 S. Karger AG, Basel.

  3. The theory behind the age-related positivity effect

    Directory of Open Access Journals (Sweden)

    Andrew E Reed

    2012-09-01

    Full Text Available The positivity effect refers to an age-related trend that favors positive over negative stimuli in cognitive processing. Relative to their younger counterparts, older people attend to and remember more positive than negative information. Since the effect was initially identified and the conceptual basis articulated (Mather & Carstensen, 2005 scores of independent replications and related findings have appeared in the literature. Over the same period, a number of investigations have failed to observe age differences in the cognitive processing of emotional material. When findings are considered in theoretical context, a reliable pattern of evidence emerges that helps to refine conceptual tenets. In this article we articulate the operational definition and theoretical foundations of the positivity effect and review the empirical evidence based on studies of visual attention, memory, decision-making, and neural activation. We conclude with a discussion of future research directions with emphasis on the conditions where a focus on positive information may benefit and/or impair cognitive performance in older people.

  4. Radiation therapy for age-related macular degeneration

    International Nuclear Information System (INIS)

    Yoshida, Ayako; Honda, Kaoru; Ishibashi, Tatsuro; Shioyama, Yoshiyuki

    1998-01-01

    We evaluated the effects of low-dose radiation on choroidal neovascular membrane (CNV) in age-related macular degeneration (AMD). Since Chakravarthy reported the benefits from administration of low-dose external-beam irradiation for CNV, many studies have demonstrated that irradiation could have a beneficial treatment effect, whereas several reports have not. In our hospital, 12 eyes with AMD received 10 Gy of 4 MV photons and the other 9 eyes received 20 Gy. Another 4 eyes were untreated as control. After 6 months of treatment, visual acuity was maintained in 11 eyes, improved in 5 eyes, and deteriorated in 5 eyes of treated patients. In control group, visual acuity was maintained in 1 eye and deteriorated in 3 eyes. The size of CNV regressed in 10 eyes, remained stationary in 2 eyes and progressed in 2 eyes of treated patients, while in control group CNV regressed in 2 eyes and remained stationary in 1 eye. After 12 months some CNV progressed. Although the present result seems to be better than those in previous reports, whether or not the treatment is beneficial has to be awaited. (author)

  5. Mechanism of Inflammation in Age-Related Macular Degeneration

    Science.gov (United States)

    Parmeggiani, Francesco; Romano, Mario R.; Costagliola, Ciro; Semeraro, Francesco; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Palma, Paolo; De Nadai, Katia; Sebastiani, Adolfo

    2012-01-01

    Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease. PMID:23209345

  6. Ocular Surface Temperature in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Andrea Sodi

    2014-01-01

    Full Text Available Background. The aim of this study is to investigate the ocular thermographic profiles in age-related macular degeneration (AMD eyes and age-matched controls to detect possible hemodynamic abnormalities, which could be involved in the pathogenesis of the disease. Methods. 32 eyes with early AMD, 37 eyes with atrophic AMD, 30 eyes affected by untreated neovascular AMD, and 43 eyes with fibrotic AMD were included. The control group consisted of 44 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, diabetes mellitus, and a body temperature higher than 37.5°C. A total of 186 eyes without pupil dilation were investigated by infrared thermography (FLIR A320. The ocular surface temperature (OST of three ocular points was calculated by means of an image processing technique from the infrared images. Two-sample t-test and one-way analysis of variance (ANOVA test were used for statistical analyses. Results. ANOVA analyses showed no significant differences among AMD groups (P value >0.272. OST in AMD patients was significantly lower than in controls (P>0.05. Conclusions. Considering the possible relationship between ocular blood flow and OST, these findings might support the central role of ischemia in the pathogenesis of AMD.

  7. Automatic age-related macular degeneration detection and staging

    Science.gov (United States)

    van Grinsven, Mark J. J. P.; Lechanteur, Yara T. E.; van de Ven, Johannes P. H.; van Ginneken, Bram; Theelen, Thomas; Sánchez, Clara I.

    2013-03-01

    Age-related macular degeneration (AMD) is a degenerative disorder of the central part of the retina, which mainly affects older people and leads to permanent loss of vision in advanced stages of the disease. AMD grading of non-advanced AMD patients allows risk assessment for the development of advanced AMD and enables timely treatment of patients, to prevent vision loss. AMD grading is currently performed manually on color fundus images, which is time consuming and expensive. In this paper, we propose a supervised classification method to distinguish patients at high risk to develop advanced AMD from low risk patients and provide an exact AMD stage determination. The method is based on the analysis of the number and size of drusen on color fundus images, as drusen are the early characteristics of AMD. An automatic drusen detection algorithm is used to detect all drusen. A weighted histogram of the detected drusen is constructed to summarize the drusen extension and size and fed into a random forest classifier in order to separate low risk from high risk patients and to allow exact AMD stage determination. Experiments showed that the proposed method achieved similar performance as human observers in distinguishing low risk from high risk AMD patients, obtaining areas under the Receiver Operating Characteristic curve of 0.929 and 0.934. A weighted kappa agreement of 0.641 and 0.622 versus two observers were obtained for AMD stage evaluation. Our method allows for quick and reliable AMD staging at low costs.

  8. Radiation therapy for age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Ayako; Honda, Kaoru; Ishibashi, Tatsuro; Shioyama, Yoshiyuki [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1998-11-01

    We evaluated the effects of low-dose radiation on choroidal neovascular membrane (CNV) in age-related macular degeneration (AMD). Since Chakravarthy reported the benefits from administration of low-dose external-beam irradiation for CNV, many studies have demonstrated that irradiation could have a beneficial treatment effect, whereas several reports have not. In our hospital, 12 eyes with AMD received 10 Gy of 4 MV photons and the other 9 eyes received 20 Gy. Another 4 eyes were untreated as control. After 6 months of treatment, visual acuity was maintained in 11 eyes, improved in 5 eyes, and deteriorated in 5 eyes of treated patients. In control group, visual acuity was maintained in 1 eye and deteriorated in 3 eyes. The size of CNV regressed in 10 eyes, remained stationary in 2 eyes and progressed in 2 eyes of treated patients, while in control group CNV regressed in 2 eyes and remained stationary in 1 eye. After 12 months some CNV progressed. Although the present result seems to be better than those in previous reports, whether or not the treatment is beneficial has to be awaited. (author)

  9. Recent developments in age-related macular degeneration: a review

    Science.gov (United States)

    Al-Zamil, Waseem M; Yassin, Sanaa A

    2017-01-01

    Background Visual impairment in elderly people is a considerable health problem that significantly affects quality of life of millions worldwide. The magnitude of this issue is becoming more evident with an aging population and an increasing number of older individuals. Objective The objective of this article was to review the clinical and pathological aspects of age-related macular degeneration (AMD), diagnostic tools, and therapeutic modalities presently available or underway for both atrophic and wet forms of the disease. Methods An online review of the PubMed database was performed, searching for the key words. The search was limited to articles published since 1980 to date. Results Several risk factors have been linked to AMD, such as age (>60 years), lifestyle (smoking and diet), and family history. Although the pathogenesis of AMD remains unclear, genetic factors have been implicated in the condition. Treatment for atrophic AMD is mainly close observation, coupled with nutritional supplements such as zinc and antioxidants, whereas treatment of wet AMD is based on targeting choroidal neovascular membranes. Conclusion Identification of modifiable risk factors would improve the possibilities of preventing the progression of AMD. The role of anti-vascular endothelial growth factor (anti-VEGF) agents has transformed the therapeutic approach of the potentially blinding disease “wet AMD” into a more favorable outcome. PMID:28860733

  10. Chlorinative stress in age-related diseases: a literature review.

    Science.gov (United States)

    Casciaro, Marco; Di Salvo, Eleonora; Pace, Elisabetta; Ventura-Spagnolo, Elvira; Navarra, Michele; Gangemi, Sebastiano

    2017-01-01

    Aging is an agglomerate of biological long-lasting processes that result being inevitable. Main actors in this scenario are both long-term inflammation and oxidative stress. It has been proved that oxidative stress induce alteration in proteins and this fact itself is critically important in the pathophysiological mechanisms leading to diseases typical of aging. Among reactive species, chlorine ones such as hypochlorous acid (HOCl) are cytotoxic oxidants produced by activated neutrophils during chronic inflammation processes. HOCl can also cause damages by reacting with biological molecules. HOCl is generated by myeloperoxidase (MPO) and augmented serum levels of MPO have been described in acute and chronic inflammatory conditions in cardiovascular patients and has been implicated in many inflammatory diseases such as atherosclerosis, neurodegenerative conditions, and some cancers. Due to these data, we decided to conduct an up-to-date review evaluating chlorinative stress effects on every age-related disease linked; potential anti-oxidant countermeasures were also assessed. Results obtained associated HOCl generation to the aging processes and confirmed its connection with diseases like neurodegenerative and cardiovascular pathologies, atherosclerosis and cancer; chlorination was mainly linked to diseases where molecular (protein) alteration constitute the major suspected cause: i.e. inflammation, tissue lesions, DNA damages, apoptosis and oxidative stress itself. According data collected, a healthy lifestyle together with some dietary suggestion and/or the administration of nutracetical antioxidant integrators could balance the effects of chlorinative stress and, in some cases, slow down or prevent the onset of age-releated diseases.

  11. Thymic stromal lymphopoietin as a novel mediator amplifying immunopathology in rheumatic disease

    NARCIS (Netherlands)

    Hillen, Maarten R.; Radstake, Timothy R. D. J.; Hack, Cornelis E.; van Roon, Joel A. G.

    2015-01-01

    Thymic stromal lymphopoietin (TSLP) is an IL-7-related cytokine that has been studied extensively in atopic diseases and more recently in various rheumatic disorders. It is involved in T cell development in the thymus and promotes homeostatic T cell expansion by classical dendritic cells. However,

  12. Primary thymic extranodal marginal zone B cell lymphoma as an incidental finding in a Caucasian woman

    DEFF Research Database (Denmark)

    Krogh Petersen, Jeanette; Larsen, Thomas Stauffer; Møller, Michael Boe

    2015-01-01

    Primary thymic extranodal marginal zone B cell lymphoma (TML) is an extremely rare lymphoma strongly associated with autoimmune disease. We report an exceedingly rare case of TML found in a non-Asian population. TML was found incidentally in a 60-year-old Caucasian woman with a short history...

  13. Case Report: CT diagnosis of thymic remnant cyst/thymopharyngeal duct cyst

    International Nuclear Information System (INIS)

    Daga, Bipin V; Chaudhary, VA; Dhamangaokar, VB

    2009-01-01

    A 4-year-old boy presented with history of left anterolateral neck swelling since birth. He was clinically diagnosed to have a branchial cleft cyst. A CT scan revealed findings suggestive of a thymic remnant cyst. The lesion was excised and the diagnosis was confirmed by histopathology

  14. The effect of early measles vaccination on thymic size. A randomized study from Guinea-Bissau

    DEFF Research Database (Denmark)

    Christensen, Lone Damkjær; Eriksen, Helle Brander; Biering-Sørensen, Sofie

    2014-01-01

    In low-income countries early measles vaccine (MV) is associated with reduced child mortality which cannot be explained by prevention of measles. A large thymus gland in infancy is also associated with reduced mortality. We hypothesized that early MV is associated with increased thymic size. Within...

  15. Spleen and thymic sonography as estimator of the immune response in children with repeated infections

    International Nuclear Information System (INIS)

    Rabaza, Jesus; Fundora, Hermes; Rodriguez, Alexis; Hernandez, Maria de los Angeles

    2010-01-01

    The spleen is a secondary lymphoid organ. The spleen has many functions: IgM class antibody production and phagocytosis of encapsulated bacteria. We propose to measure the dimensions of the spleen in children with repeated infections, in order to describe them as a diagnosis marker and to explore the probable correlation between the thymic characteristics and the dimensions of the spleen. We study 81 patients that attended the consultation of Immunology from Aballi hospital with repeated infections and they were from 8 months to 9 years old. Children with nutritional value up to the third percentile and those taking steroids 45 days before the study were excluded. We measured the thymic and splenic areas by mediastinal and abdominal echography. The length, the splenic index and the weight are less in patients with repeated infections. These data were significant in 12 to 23 month of age group. The length and the splenic index were less in patients with depletion of thymic area. The sonographic evaluation of the spleen is very important in patients from 1 to 2 years old and in patients with thymic depletion, because they are on the age of vaccine administration according to the Cuban schedule and having affected a main organ for immune response might be a reason for them to show a deficient response and need special schedules

  16. Elevation of oleate-activated phospholipase D activity during thymic atrophy

    Science.gov (United States)

    Lee, Youngkyun; Song, Soo-Mee; Park, Heung Soon; Kim, Sungyeol; Koh, Eun-Hee; Choi, Myung Sun; Choi, Myung-Un

    2002-01-01

    Various phospholipases are thought to be associated with the in vitro apoptosis of thymocytes. In the present study, the in vivo phospholipase D (PLD) activity of rat thymus was studied after whole-body X-irradiation or injection of dexamethasone (DEX). Using exogenous [14C]dipalmitoyl phosphatidylcholine (PC) as the substrate, an elevation of oleate-activated PLD activity was observed during thymic atrophy. The activity increases were sevenfold at 48 hr after 5-Gy irradiation and fourfold at 72 hr after injection of 5 mg/kg DEX. The elevation of PLD activity appeared to parallel extensive thymus shrinkage. An increased level of thymic phosphatidic acid (PA), the presumed physiological product of PLD action on PC, was also detected. By comparing the acyl chains of PA with those of other phospholipids, PA appeared to originate from PC. To assess the role of PLD during thymic atrophy, thymocytes and stromal cells were isolated. Although thymocytes themselves exhibited significant PLD activation, the major elevation in PLD activity (greater than fourfold) was found in isolated stromal cells. PLD was also activated during in vitro phagocytosis of apoptotic thymocytes by the macrophage-like cell line P388D1. This in vitro phagocytosis was significantly inhibited by PLD action blockers, such as 2,3-diphosphoglycerate and 1-butanol. These observations strongly suggest that the alteration of oleate-activated PLD activity is part of an in vivo event in the progression of thymic atrophy, including phagocytic clearance of apoptotic thymocytes. PMID:12460188

  17. Doubling time of thymic epithelial tumours on CT: correlation with histological subtype

    Energy Technology Data Exchange (ETDEWEB)

    Choe, Jooae; Lee, Sang Min; Kim, Namkug; Do, Kyung-Hyun; Seo, Joon Beom [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Songpa-gu, Seoul (Korea, Republic of); Lim, Soyeoun [Ulsan University Hospital, Department of Radiology, University of Ulsan College of Medicine, Ulsan (Korea, Republic of); Choi, Se Hoon [University of Ulsan College of Medicine, Department of Thoracic and Cardiovascular Surgery, Seoul (Korea, Republic of)

    2017-10-15

    We retrospectively evaluated the doubling time (DT) of thymic epithelial tumours (TET) according to the histological subtype on CT. From January 2005 to June 2016, we enrolled 53 patients who had pathologically confirmed TET and at least two CT scans. Tumour size was measured using a two-dimensional method, and the DT was calculated. DTs were compared among histological subtypes, and factors associated with rapid tumour growth (DT <180 days) were assessed. In 42 of the 53 patients (79.2%) the tumours showed interval growth (>2 mm) during follow-up. The median DT for all tumours was 400 days (range 48-1,964 days). There were no significant differences in DT in relation to histological subtype (p = 0.177). When TETs were recategorized into three groups, i.e. low-risk thymomas (types A, AB, B1), high-risk thymomas (types B2, B3), and thymic carcinoma, DT was significantly different among the groups (median DT 436, 381 and 189 days, respectively; p = 0.031). Histological subtype (type B3 and thymic carcinoma) was the single independent predictor of rapid tumour growth. The majority of TETs grew during follow-up with variable and relatively slow growth rates. Histological features of aggressive behaviour significantly correlated with a decreased DT and rapid growth. circle The majority of thymic epithelial tumours grew during follow-up (79.2%, 42/53). (orig.)

  18. Deregulation of mTOR signaling is involved in thymic lymphoma development in Atm-/- mice

    International Nuclear Information System (INIS)

    Kuang, Xianghong; Shen, Jianjun; Wong, Paul K.Y.; Yan, Mingshan

    2009-01-01

    Abnormal thymocyte development with thymic lymphomagenesis inevitably occurs in Atm-/- mice, indicating that ATM plays a pivotal role in regulating postnatal thymocyte development and preventing thymic lymphomagenesis. The mechanism for ATM controls these processes is unclear. We have shown previously that c-Myc, an oncoprotein regulated by the mammalian target of rapamycin (mTOR), is overexpressed in Atm-/- thymocytes. Here, we show that inhibition of mTOR signaling with its specific inhibitor, rapamycin, suppresses normal thymocyte DNA synthesis by downregulating 4EBP1, but not S6K, and that 4EBP1 phosphorylation and cyclin D1 expression are coordinately increased in Atm-/- thymocytes. Administration of rapamycin to Atm-/- mice attenuates elevated phospho-4EBP1, c-Myc and cyclin D1 in their thymocytes, and delays thymic lymphoma development. These results indicate that mTOR downstream effector 4EBP1 is essential for normal thymocyte proliferation, but deregulation of 4EBP1 in Atm deficiency is a major factor driving thymic lymphomagenesis in the animals.

  19. Micronodular thymic neoplasms: case series and literature review with emphasis on the spectrum of differentiation.

    Science.gov (United States)

    Mneimneh, Wadad S; Gökmen-Polar, Yesim; Kesler, Kenneth A; Loehrer, Patrick J; Badve, Sunil

    2015-11-01

    We report nine cases of micronodular thymoma with lymphoid B-cell hyperplasia and one case of micronodular thymic carcinoma with lymphoid hyperplasia from our institution. For a better understanding of these rare tumors, clinical records, and histological features of these cases were reviewed, with detailed review of additional 64 literature cases of micronodular thymic neoplasms. The joint analysis identified 64 cases of micronodular thymoma with lymphoid B-cell hyperplasia and 9 cases of micronodular thymic carcinoma with lymphoid hyperplasia. Both groups revealed slight male predilection, with male:female ratio of 1.3:1 and 5:4, and occurred at >40 years of age, with a mean of 64 (41-83) and 62 (42-78) years, respectively. Myasthenia gravis was noted in 3/64 (5%) and 1/9 (11%) patients, respectively. Other systemic, disimmune, or hematologic disorders were noted in 6/64 (9%) and 1/9 (11%) patients, respectively. Components of conventional thymoma were reported in 11/64 (17%) micronodular thymomas with lymphoid B-cell hyperplasia, with transitional morphology between the two components in most of them. Cellular morphology was predominantly spindle in micronodular thymoma with lymphoid B-cell hyperplasia when specified (30/43), and epithelioid in micronodular thymic carcinoma with lymphoid hyperplasia (6/9), and cytological atypia was more encountered in the latter. Dedifferentiation/transformation from micronodular thymoma with lymphoid B-cell hyperplasia to micronodular thymic carcinoma with lymphoid hyperplasia seems to occur in a small subset of cases. Three cases of micronodular thymomas with lymphoid B-cell hyperplasia were described with co-existent low-grade B-cell lymphomas. Follow-up data were available for 30 micronodular thymomas with lymphoid B-cell hyperplasia and 6 micronodular thymic carcinomas with lymphoid hyperplasia, with a mean of 47 (0.2-180) months and 23 (3-39) months, respectively. Patients were alive without disease, except for five

  20. A case of congenital Langerhans cell histiocytosis with skin and thymic lesions: Exploring the prognostic value of thymus involvement

    Directory of Open Access Journals (Sweden)

    M.M. Escudero-Góngora

    2016-10-01

    Full Text Available Thymus evaluation is not included in the guidelines of the Histiocyte Society, so its prevalence, management and prognosis are not well established. We present a newborn with self-healing cutaneous LCH and thymic involvement that was evaluated with a thoracic ultrasound. With the current evidence we are unable to predict the prognosis of the thymus association in neonatal LCH. We suggest that performing thymic ultrasound study, which is a non-invasive technique, would allow us to know the incidence of thymic involvement and its role on prognosis.

  1. Chest roentgenographic findings of thymic size and shape in respiratory distress syndrome

    International Nuclear Information System (INIS)

    Oh, Young Ho; Yoon, Sung Do; Sung, Ki Yeal; Park, Seog Hee; Kim, Jong Woo; Bahk, Yong Whee

    1984-01-01

    Thymic size can be affected by both exogenous and endogenous glucocorticoids. Development of the respiratory distress syndrome (RDS) is influenced by adrenal cortical function. Thus, thymic size in RDS is considered to be enlarged due to decreased adrenal cortical function. To find whether the presence of RDS correlates with the thymus, the size and shape of the thymus were evaluated in the radiographs of premature infants with RDS, without RDS (control prematurity) and normal infants. The subjects were consisted of chest films of Korean premature infants, 120 with RDS, 60 without RDS, and 60 of normal infants taken at the Department of Radiology, Our Lady of Mercy Hospital during the period of 62 months since January 1978. Relative size of the thymus was determine by cardiothymic/thoracic ratio (CT /T ratio). Grading and location of the thymic prominence as well as incidence of the shape were examined. And all the relations among the radiographs of RDS, control prematurity and normal infants were analyzed. The results were as follows: 1. The CT/T ratio of premature infants with RDS was significantly greater than that of control prematurity and normal infants (P< 0.01). 2. The incidence of bilateral thymic prominence was more frequent in premature infant with RDS than in control prematurity and normal infants (P<0.05). 3. The frequency of thymic prominence was greater in the right than left side in all the three groups (P<0.05). 4. As in the shape of the thymus, a rounded type was most frequent, and a triangular type was least frequent in all three groups. 5. Incident of RDS was very low (9.8%) when the CT/T ratio is below 0.3 and it was very high (90.9%) when the CT/T ratio is above 0.49.

  2. Age-related distance esotropia: Clinical features and therapeutic outcomes.

    Science.gov (United States)

    Gómez de Liaño Sánchez, P; Olavarri González, G; Merino Sanz, P; Escribano Villafruela, J C

    2016-12-01

    To describe the clinical characteristics and surgical outcomes of a group of patients with age-related distance esotropia (ARDE). A retrospective study was conducted on a consecutive case series of 16 adult patients diagnosed with ARDE between 2008 and 2015. The clinical features evaluated included mean age and gender, primary position deviations at distance and near, measured in prism dioptres (pd), treatment offered in each case, and post-surgical deviations. Ductions and versions were full, with no evidence of lateral rectus paresis. None of these patients had any obvious underlying neurological disorder, such as, high myopia or thyroid disease. A good result is considered to be the disappearance of diplopia in all positions of gaze. A total of 16 patients (11 females [68.8%]) were identified. The mean age at diagnosis was 78.19±6.77 years. The mean initial esodeviation was 2.25±3.08 pd at near (-4 to +8 pd) and 9.5±4.18 pd at distance (2 to 18 pd). Treatment was not necessary in 5 cases because the symptoms were intermittent or well-tolerated. Of the 11 patients with symptoms, one was corrected with an external base therapeutic prism. Botulinum toxin was administered in another patient, without satisfactory results. Unilateral medial rectus muscle recession was performed on one patient, and unilateral lateral rectus plication on 7 patients, indicating prisms before surgery. One patient refused surgery despite continuous diplopia in far vision. After a mean follow-up of 16.5 months, all operated patients were asymptomatic. Not all patients with ARDE require treatment, as the tolerance to diplopia varies from one subject to another. Both medial rectus weakening and lateral rectus strengthening provides excellent results. Crown Copyright © 2016. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Age-related changes in factor VII proteolysis in vivo.

    Science.gov (United States)

    Ofosu, F A; Craven, S; Dewar, L; Anvari, N; Andrew, M; Blajchman, M A

    1996-08-01

    Previous studies have reported that pre-operative plasmas of patients over the age of 40 years who developed post-operative deep vein thrombosis (DVT) had approximately twice the amount of proteolysed factor VII found in plasmas of patients in whom prophylaxis with heparin or low M(r) heparin was successful. These and other studies also reported higher concentrations of thrombin-antithrombin III in pre- and post-operative plasmas of patients who developed post-operative thrombosis than in plasmas of patients in whom prophylaxis was successful. Whether the extent of factor VII proteolysis seen in the patients who developed post-operative DVT is related to the severity of their disease or age is not known. This report investigated age-related changes in the concentrations of total factor VII protein, factor VII zymogen, factor VIIa, tissue factor pathway inhibitor, thrombin-antithrombin III, and prothrombin fragment 1 + 2 in normal plasmas and the relationships between these parameters. With the exception of thrombin-antithrombin III, statistically significant increases in the concentrations of these parameters with age were found. Additionally, the differences between the concentrations of total factor VII protein and factor VII zymogen, an index factor VII proteolysis in vivo, were statistically significant only for individuals over age 40. Using linear regression analysis, a significant correlation was found to exist between the concentrations of plasma factor VIIa and prothrombin fragment 1 + 2. Since factor VIIa-tissue factor probably initiates coagulation in vivo, we hypothesize that the elevated plasma factor VIIa (reflecting a less tightly regulated tissue factor activity and therefore increased thrombin production in vivo) accounts for the high risk for post-operative thrombosis seen in individuals over the age of 40.

  4. Age-Related Difference in Functional Brain Connectivity of Mastication

    Science.gov (United States)

    Lin, Chia-shu; Wu, Ching-yi; Wu, Shih-yun; Lin, Hsiao-Han; Cheng, Dong-hui; Lo, Wen-liang

    2017-01-01

    The age-related decline in motor function is associated with changes in intrinsic brain signatures. Here, we investigated the functional connectivity (FC) associated with masticatory performance, a clinical index evaluating general masticatory function. Twenty-six older adults (OA) and 26 younger (YA) healthy adults were recruited and assessed using the masticatory performance index (MPI) and resting-state functional magnetic resonance imaging (rs-fMRI). We analyzed the rs-fMRI FC network related to mastication, which was constructed based on 12 bilateral mastication-related brain regions according to the literature. For the OA and the YA group, we identified the mastication-related hubs, i.e., the nodes for which the degree centrality (DC) was positively correlated with the MPI. For each pair of nodes, we identified the inter-nodal link for which the FC was positively correlated with the MPI. The network analysis revealed that, in the YA group, the FC between the sensorimotor cortex, the thalamus (THA) and the cerebellum was positively correlated with the MPI. Consistently, the cerebellum nodes were defined as the mastication-related hubs. In contrast, in the OA group, we found a sparser connection within the sensorimotor regions and cerebellum and a denser connection across distributed regions, including the FC between the superior parietal lobe (SPL), the anterior insula (aINS) and the dorsal anterior cingulate cortex (dACC). Compared to the YA group, the network of the OA group also comprised more mastication-related hubs, which were spatially distributed outside the sensorimotor regions, including the right SPL, the right aINS, and the bilateral dACC. In general, the findings supported the hypothesis that in OA, higher masticatory performance is associated with a widespread pattern of mastication-related hubs. Such a widespread engagement of multiple brain regions associated with the MPI may reflect an increased demand in sensorimotor integration, attentional

  5. Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy

    Science.gov (United States)

    Ferrer, Isidro; Grinberg, Lea T.; Alafuzoff, Irina; Attems, Johannes; Budka, Herbert; Cairns, Nigel J.; Crary, John F.; Duyckaerts, Charles; Ghetti, Bernardino; Halliday, Glenda M.; Ironside, James W.; Love, Seth; Mackenzie, Ian R.; Munoz, David G.; Murray, Melissa E.; Nelson, Peter T.; Takahashi, Hitoshi; Trojanowski, John Q.; Ansorge, Olaf; Arzberger, Thomas; Baborie, Atik; Beach, Thomas G.; Bieniek, Kevin F.; Bigio, Eileen H.; Bodi, Istvan; Dugger, Brittany N.; Feany, Mel; Gelpi, Ellen; Gentleman, Stephen M.; Giaccone, Giorgio; Hatanpaa, Kimmo J.; Heale, Richard; Hof, Patrick R.; Hofer, Monika; Hortobágyi, Tibor; Jellinger, Kurt; Jicha, Gregory A.; Ince, Paul; Kofler, Julia; Kövari, Enikö; Kril, Jillian J.; Mann, David M.; Matej, Radoslav; McKee, Ann C.; McLean, Catriona; Milenkovic, Ivan; Montine, Thomas J.; Murayama, Shigeo; Lee, Edward B.; Rahimi, Jasmin; Rodriguez, Roberta D.; Rozemüller, Annemieke; Schneider, Julie A.; Schultz, Christian; Seeley, William; Seilhean, Danielle; Smith, Colin; Tagliavini, Fabrizio; Takao, Masaki; Thal, Dietmar Rudolf; Toledo, Jon B.; Tolnay, Markus; Troncoso, Juan C.; Vinters, Harry V.; Weis, Serge; Wharton, Stephen B.; White, Charles L.; Wisniewski, Thomas; Woulfe, John M.; Yamada, Masahito

    2016-01-01

    Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of

  6. Individual and age-related variation in chromatic contrast adaptation

    Science.gov (United States)

    Elliott, Sarah L.; Werner, John S.; Webster, Michael A.

    2012-01-01

    Precortical color channels are tuned primarily to the LvsM (stimulation of L and M cones varied, but S cone stimulation held constant) or SvsLM (stimulation of S cones varied, but L and M cone stimulation held constant) cone-opponent (cardinal) axes, but appear elaborated in the cortex to form higher-order mechanisms tuned to both cardinal and intermediate directions. One source of evidence for these higher-order mechanisms has been the selectivity of color contrast adaptation for noncardinal directions, yet the degree of this selectivity has varied widely across the small sample of observers tested in previous studies. This study explored the possible bases for this variation, and in particular tested whether it reflected age-related changes in the distribution or tuning of color mechanisms. Observers included 15 younger (18–22 years of age) and 15 older individuals (66–82), who adapted to temporal modulations along one of four chromatic axes (two cardinal and two intermediate axes) and then matched the hue and contrast of test stimuli lying along eight different directions in the equiluminant plane. All observers exhibited aftereffects that were selective for both the cardinal and intermediate directions, although selectivity was weaker for the intermediate axes. The degree of selectivity increased with the magnitude of adaptation for all axes, and thus adaptation strength alone may account for much of the variance in selectivity among observers. Older observers showed a stronger magnitude of adaptation thus, surprisingly, more conspicuous evidence for higher-order mechanisms. For both age groups the aftereffects were well predicted by response changes in chromatic channels with linear spectral sensitivities, and there was no evidence for weakened channel tuning with aging. The results suggest that higher-order mechanisms may become more exposed in observers or conditions in which the strength of adaptation is greater, and that both chromatic contrast

  7. Age-related changes in oscillatory power affect motor action.

    Directory of Open Access Journals (Sweden)

    Liqing Liu

    Full Text Available With increasing age cognitive performance slows down. This includes cognitive processes essential for motor performance. Additionally, performance of motor tasks becomes less accurate. The objective of the present study was to identify general neural correlates underlying age-related behavioral slowing and the reduction in motor task accuracy. To this end, we continuously recorded EEG activity from 18 younger and 24 older right-handed healthy participants while they were performing a simple finger tapping task. We analyzed the EEG records with respect to local changes in amplitude (power spectrum as well as phase locking between the two age groups. We found differences between younger and older subjects in the amplitude of post-movement synchronization in the β band of the sensory-motor and medial prefrontal cortex (mPFC. This post-movement β amplitude was significantly reduced in older subjects. Moreover, it positively correlated with the accuracy with which subjects performed the motor task at the electrode FCz, which detects activity of the mPFC and the supplementary motor area. In contrast, we found no correlation between the accurate timing of local neural activity, i.e. phase locking in the δ-θ frequency band, with the reaction and movement time or the accuracy with which the motor task was performed. Our results show that only post-movement β amplitude and not δ-θ phase locking is involved in the control of movement accuracy. The decreased post-movement β amplitude in the mPFC of older subjects hints at an impaired deactivation of this area, which may affect the cognitive control of stimulus-induced motor tasks and thereby motor output.

  8. Systemic complement activation in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Hendrik P N Scholl

    Full Text Available Dysregulation of the alternative pathway (AP of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD, the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112 and controls (n = 67. Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH, factor B-C2 (BF-C2 and complement C3 (C3 genes which were previously found to be associated with AMD. All activation products, especially markers of chronic complement activation Ba and C3d (p<0.001, were significantly elevated in AMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with CFH haplotypes.This study is the first to show systemic complement activation in AMD patients. This suggests that AMD is a systemic disease with local disease manifestation at the ageing macula. Furthermore, the data provide evidence for an association of systemic activation of the alternative complement pathway with genetic variants of CFH that were previously linked to AMD susceptibility.

  9. Tremor in the Elderly: Essential and Aging-Related Tremor

    Science.gov (United States)

    Deuschl, Günthe; Petersen, Inge; Lorenz, Delia; Christensen, Kaare

    2016-01-01

    Isolated tremor in the elderly is commonly diagnosed as essential tremor (ET). The prevalence of tremor increases steeply with increasing age, whereas hereditary tremor is becoming less common. Moreover, late-manifesting tremor seems to be associated with dementia and earlier mortality. We hypothesize that different entities underlie tremor in the elderly. Two thousand four hundred forty-eight subjects from the Longitudinal Study of Aging Danish Twins older than 70 y answered screening questions for ET in 2001. Two thousan fifty-six (84%) participants drew Archimedes spirals to measure their tremor severity, and classical aging phenotypes were assessed. A subgroup of 276 individuals fulfilling either screening criteria for ET or being controls were personally assessed. Medications and mortality data are available. The spiral score increased with age. The spiral score correlated with tremor severity. For the whole cohort, mortality was significantly correlated with the spiral score, and higher spiral scores were associated with lower physical and cognitive functioning. Multivariate analysis identified higher spiral scores as an independent risk factor for mortality. In contrast, the ET patients did not show an increased but rather a lower mortality rate although it was not statistically significant. Consistent with a slower than normal aging, they were also physically and cognitively better functioning than controls. Because incident tremors beyond 70 y of age show worse aging parameters and mortality than controls and ET, we propose to label it ‘aging-related tremor’ (ART). This tremor starts later in life and is accompanied by subtle signs of aging both cognitively and physically. More detailed clinical features and pathogenesis warrant further assessment. PMID:26095699

  10. Tear film proteome in age-related macular degeneration.

    Science.gov (United States)

    Winiarczyk, Mateusz; Kaarniranta, Kai; Winiarczyk, Stanisław; Adaszek, Łukasz; Winiarczyk, Dagmara; Mackiewicz, Jerzy

    2018-06-01

    Age-related macular degeneration (AMD) is the main reason for blindness in elderly people in the developed countries. Current screening protocols have limitations in detecting the early signs of retinal degeneration. Therefore, it would be desirable to find novel biomarkers for early detection of AMD. Development of novel biomarkers would help in the prevention, diagnostics, and treatment of AMD. Proteomic analysis of tear film has shown promise in this research area. If an optimal set of biomarkers could be obtained from accessible body fluids, it would represent a reliable way to monitor disease progression and response to novel therapies. Tear films were collected on Schirmer strips from a total of 22 patients (8 with wet AMD, 6 with dry AMD, and 8 control individuals). 2D electrophoresis was used to separate tear film proteins prior to their identification with matrix-assisted laser desorption/ionization time of flight spectrometer (MALDI-TOF/TOF) and matching with functional databases. A total of 342 proteins were identified. Most of them were previously described in various proteomic studies concerning AMD. Shootin-1, histatin-3, fidgetin-like protein 1, SRC kinase signaling inhibitor, Graves disease carrier protein, actin cytoplasmic 1, prolactin-inducible protein 1, and protein S100-A7A were upregulated in the tear film samples isolated from AMD patients and were not previously linked with this disease in any proteomic analysis. The upregulated proteins supplement our current knowledge of AMD pathogenesis, providing evidence that certain specific proteins are expressed into the tear film in AMD. As far we are aware, this is the first study to have undertaken a comprehensive in-depth analysis of the human tear film proteome in AMD patients.

  11. Modelling the genetic risk in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Felix Grassmann

    Full Text Available Late-stage age-related macular degeneration (AMD is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69-2.05 than patients aged 75 and above (1.45, 95% CI: 1.36-1.54. Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11-1131.96 for individuals in the highest category (GRS 3.44-5.18, 0.5% of the general population compared to subjects with the most common genetic background (GRS -0.05-1.70, 40.2% of general population. The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available.

  12. DNA damage and repair in age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Szaflik, Jacek P. [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Janik-Papis, Katarzyna; Synowiec, Ewelina; Ksiazek, Dominika [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Zaras, Magdalena [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Wozniak, Katarzyna [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Szaflik, Jerzy [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Blasiak, Janusz, E-mail: januszb@biol.uni.lodz.pl [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland)

    2009-10-02

    Age-related macular degeneration (AMD) is a retinal degenerative disease that is the main cause of vision loss in individuals over the age of 55 in the Western world. Clinically relevant AMD results from damage to the retinal pigment epithelial (RPE) cells thought to be mainly caused by oxidative stress. The stress also affects the DNA of RPE cells, which promotes genome instability in these cells. These effects may coincide with the decrease in the efficacy of DNA repair with age. Therefore individuals with DNA repair impaired more than average for a given age may be more susceptible to AMD if oxidative stress affects their RPE cells. This may be helpful in AMD risk assessment. In the present work we determined the level of basal (measured in the alkaline comet assay) endogenous and endogenous oxidative DNA damage, the susceptibility to exogenous mutagens and the efficacy of DNA repair in lymphocytes of 100 AMD patients and 110 age-matched individuals without visual disturbances. The cells taken from AMD patients displayed a higher extent of basal endogenous DNA damage without differences between patients of dry and wet forms of the disease. DNA double-strand breaks did not contribute to the observed DNA damage as checked by the neutral comet assay and pulsed field gel electrophoresis. The extent of oxidative modification to DNA bases was grater in AMD patients than in the controls, as probed by DNA repair enzymes NTH1 and Fpg. Lymphocytes from AMD patients displayed a higher sensitivity to hydrogen peroxide and UV radiation and repaired lesions induced by these factors less effectively than the cells from the control individuals. We postulate that the impaired efficacy of DNA repair may combine with enhanced sensitivity of RPE cells to blue and UV lights, contributing to the pathogenesis of AMD.

  13. Age-related macular degeneration: prevention and treatment. A review

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2014-07-01

    Full Text Available Age-related macular degeneration (AMD is a multifactorial disease. Age, light exposure, smoking, melanin levels and low-antioxidant diet are contributed to AMD development and progression. Cardiovascular disorders are of considerable importance as well. In macula, photoreceptor outer segments that are rich in polyunsaturated fatty acids (FA, particularly, docosahexaenoic acid (DHA, are susceptible to free radicals damage. High blood flow velocity and oxygen partial pressure as well as direct sunlight exposure induce oxidative processes. The source of free radicals in photoreceptor cells and retinal pigment epithelium (RPE is an extensive mitochondrial metabolism, photoreceptor outer segments phagocytosis, lipofuscin phototoxic activity and hemoglobin or protoporphyrin precursors photosensitization. Oxidative stress is considered as an universal component of cell depth in necrosis, apoptosis and toxic damage. Antioxidant protective system consists of enzymes (superoxide dismutase, glutathione peroxidase and catalase and non-enzymatic factors (ascorbic acid, alpha tocopherol, retinol, carotenoids. Specific antioxidant food supplement containing ascorbic acid (500 mg, vitamin E (400 IU and beta carotene (15 mg coupled with zinc (80 mg of zinc oxide and copper (2 mg of copper oxide results in 25 % decrease in late-stage AMD development rate. Amongst the agents that can protect retina from oxidative stress and AMD development, carotenoids are of special importance. Lutein and zeaxanthin containing in retina and lens screen blue light from central area of the retina. They also absorb blue light and inhibit free radicals generation thus preventing polyunsaturated FA light destruction. Association between lutein and zeaxanthin intake and late-stage AMD risk was revealed. Amongst the most important factors which deficiency favors macular degeneration are omega-3 FAs, i.e., DHA. DHA is the key component of visual pigment rhodopsin transformation. It

  14. Age-related macular degeneration: prevention and treatment. A review

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2014-01-01

    Full Text Available Age-related macular degeneration (AMD is a multifactorial disease. Age, light exposure, smoking, melanin levels and low-antioxidant diet are contributed to AMD development and progression. Cardiovascular disorders are of considerable importance as well. In macula, photoreceptor outer segments that are rich in polyunsaturated fatty acids (FA, particularly, docosahexaenoic acid (DHA, are susceptible to free radicals damage. High blood flow velocity and oxygen partial pressure as well as direct sunlight exposure induce oxidative processes. The source of free radicals in photoreceptor cells and retinal pigment epithelium (RPE is an extensive mitochondrial metabolism, photoreceptor outer segments phagocytosis, lipofuscin phototoxic activity and hemoglobin or protoporphyrin precursors photosensitization. Oxidative stress is considered as an universal component of cell depth in necrosis, apoptosis and toxic damage. Antioxidant protective system consists of enzymes (superoxide dismutase, glutathione peroxidase and catalase and non-enzymatic factors (ascorbic acid, alpha tocopherol, retinol, carotenoids. Specific antioxidant food supplement containing ascorbic acid (500 mg, vitamin E (400 IU and beta carotene (15 mg coupled with zinc (80 mg of zinc oxide and copper (2 mg of copper oxide results in 25 % decrease in late-stage AMD development rate. Amongst the agents that can protect retina from oxidative stress and AMD development, carotenoids are of special importance. Lutein and zeaxanthin containing in retina and lens screen blue light from central area of the retina. They also absorb blue light and inhibit free radicals generation thus preventing polyunsaturated FA light destruction. Association between lutein and zeaxanthin intake and late-stage AMD risk was revealed. Amongst the most important factors which deficiency favors macular degeneration are omega-3 FAs, i.e., DHA. DHA is the key component of visual pigment rhodopsin transformation. It

  15. Age-related distribution of vertebral bone-marrow diffusivity

    Energy Technology Data Exchange (ETDEWEB)

    Herrmann, Jochen, E-mail: j.herrmann@uke.de [Department of Diagnostic and Interventional Radiology, Martinistraße 52, D-20246 Hamburg (Germany); Department of Pediatric Radiology, Martinistraße 52, D-20246 Hamburg (Germany); Krstin, Nina, E-mail: ninakrstin@web.de [Department of Diagnostic and Interventional Radiology, Martinistraße 52, D-20246 Hamburg (Germany); Schoennagel, Bjoern P., E-mail: b.schoennagel@uke.de [Department of Diagnostic and Interventional Radiology, Martinistraße 52, D-20246 Hamburg (Germany); Sornsakrin, Marjike, E-mail: m.sornsakrin@uke.de [Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Martinistraße 52, D-20246 Hamburg (Germany); Derlin, Thorsten, E-mail: t.derlin@uke.de [Department of Diagnostic and Interventional Radiology, Martinistraße 52, D-20246 Hamburg (Germany); Busch, Jasmin D., E-mail: jd.busch@uke.de [Department of Diagnostic and Interventional Radiology, Martinistraße 52, D-20246 Hamburg (Germany); Petersen, Kay Uwe, E-mail: Kay.Petersen@med.uni-tuebingen.de [Department of Psychiatry, University Clinic Tübingen, Calwerstraße 14 Tübingen 72076 (Germany); Graessner, Joachim, E-mail: joachim.graessner@siemens.com [Siemens AG Healthcare, Lindenplatz 2, 20099 Hamburg (Germany); Adam, Gerhard, E-mail: g.adam@uke.de [Department of Diagnostic and Interventional Radiology, Martinistraße 52, D-20246 Hamburg (Germany); Habermann, Christian R., E-mail: c.habermann@uke.de [Department of Diagnostic and Interventional Radiology, Martinistraße 52, D-20246 Hamburg (Germany)

    2012-12-15

    Purpose: To determine age-related diffusivity changes of the lumbar bone marrow by measurement of apparent diffusion coefficient (ADC) values. Materials and methods: The local ethics committee approved this study and written informed consent was obtained. The study group comprised 88 individuals including 75 healthy volunteers and 13 patients (48 female, 40 male; mean age 36 years, range 0–84 years). The pediatric cases were recruited from patients. Echo-planar diffusion weighted imaging (DWI) was performed with b-values of 50, 400 and 800 s/mm{sup 2}. ADC-values were calculated and measured in the 1st and 2nd vertebral body of the lumbar spine. Correlation between age and ADC-values was analyzed with Spearman's rho test. Results: The ADC values of the vertebral bone marrow of the lumbar spine showed a significant negative correlation with age (rho = −0.398, p = 0.001). The mean ADC values (×10{sup −3} mm{sup 2}/s) in the age groups 0–29 years (mean age 18.0 years, n = 42) and 30–88 years (mean age 51.6 years, n = 46) were 0.54 ± 0.07 and 0.47 ± 0.08, respectively (p < 0.001, T-test). No significant differences were found between children and young adults. Conclusion: Bone marrow ADC values of the lumbar spine show a linear decrease with growing age and thereby reflect the gradual changes of cell composition occurring during marrow conversion.

  16. Alzheimer's disease and age-related memory decline (preclinical).

    Science.gov (United States)

    Terry, Alvin V; Callahan, Patrick M; Hall, Brandon; Webster, Scott J

    2011-08-01

    An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer's disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as "Mild Cognitive Impairment" (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD and MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy and adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory

  17. DNA damage and repair in age-related macular degeneration

    International Nuclear Information System (INIS)

    Szaflik, Jacek P.; Janik-Papis, Katarzyna; Synowiec, Ewelina; Ksiazek, Dominika; Zaras, Magdalena; Wozniak, Katarzyna; Szaflik, Jerzy; Blasiak, Janusz

    2009-01-01

    Age-related macular degeneration (AMD) is a retinal degenerative disease that is the main cause of vision loss in individuals over the age of 55 in the Western world. Clinically relevant AMD results from damage to the retinal pigment epithelial (RPE) cells thought to be mainly caused by oxidative stress. The stress also affects the DNA of RPE cells, which promotes genome instability in these cells. These effects may coincide with the decrease in the efficacy of DNA repair with age. Therefore individuals with DNA repair impaired more than average for a given age may be more susceptible to AMD if oxidative stress affects their RPE cells. This may be helpful in AMD risk assessment. In the present work we determined the level of basal (measured in the alkaline comet assay) endogenous and endogenous oxidative DNA damage, the susceptibility to exogenous mutagens and the efficacy of DNA repair in lymphocytes of 100 AMD patients and 110 age-matched individuals without visual disturbances. The cells taken from AMD patients displayed a higher extent of basal endogenous DNA damage without differences between patients of dry and wet forms of the disease. DNA double-strand breaks did not contribute to the observed DNA damage as checked by the neutral comet assay and pulsed field gel electrophoresis. The extent of oxidative modification to DNA bases was grater in AMD patients than in the controls, as probed by DNA repair enzymes NTH1 and Fpg. Lymphocytes from AMD patients displayed a higher sensitivity to hydrogen peroxide and UV radiation and repaired lesions induced by these factors less effectively than the cells from the control individuals. We postulate that the impaired efficacy of DNA repair may combine with enhanced sensitivity of RPE cells to blue and UV lights, contributing to the pathogenesis of AMD.

  18. Diastolic pressure underestimates age-related hemodynamic impairment.

    Science.gov (United States)

    Galarza, C R; Alfie, J; Waisman, G D; Mayorga, L M; Cámera, L A; del Río, M; Vasvari, F; Limansky, R; Farías, J; Tessler, J; Cámera, M I

    1997-10-01

    It has been hypothesized that as large arteries become more rigid with age, the pattern of hypertension changes from diastolic to systolic. Thus, diastolic blood pressure (DBP) may lose its ability to reflect the increase in vascular resistance with age. To assess this, we studied the age-related changes in blood pressure pattern and its steady-state and pulsatile determinants. We performed an epidemiological analysis based on a national survey of 10,462 subjects from Argentina. A hemodynamic analysis (impedance cardiography) was then carried out in 636 consecutive hypertensive patients (age, 25 to 74 years). Whereas the rate of increment in the prevalence of mild to moderate hypertension (MMH) reached a plateau after the sixth decade, isolated and borderline systolic forms of hypertension began a steep and sustained rise. Among patients with MMH, DBP remained stable from the third to the seventh decade, whereas SBP maintained a sustained increase. Despite similar DBP, the systemic vascular resistance index increased 47% (P<.01) and the cardiac index decreased 27% (P<.01), whereas the ratio of stroke volume to pulse pressure, an index of arterial compliance, decreased 45% (P<.01). However, there were no significant differences between older patients with MMH and those with isolated systolic hypertension in the level of SBP, vascular resistance, stroke volume, and cardiac index. Compared with age-matched normotensive control subjects, the ratio of stroke volume to pulse pressure was much more reduced in isolated systolic hypertension (48%) than in MMH (30%). In summary, the present study, carried out in a large sample of hypertensive subjects with a wide age range, showed a simultaneous impairment in vascular resistance and arterial compliance associated with aging in different patterns of hypertension. The magnitude of these changes, with opposite effects on DBP but additive effects on SBP, suggests that a hemodynamic mechanism could determine the transition in the

  19. Interleukin-13 and age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Bo Fu

    2017-04-01

    Full Text Available AIM: To identify the effects of interleukin (IL-13 on retinal pigment epithelial (RPE cells and the IL-13 level in aqueous humor of age-related macular degeneration (AMD patients. METHODS: IL-13 levels in aqueous humor specimens from AMD patients were detected with enzyme-linked immunosorbent assay (ELISA. ARPE-19 cells were treated with 10 ng/mL IL-13 for 12, 24, and 48h. The cell proliferaton was evaluated by the MTS method. The mRNA and protein levels of α-SMA and ZO-1 were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR and Western blot respectively. The expression of tumor necrosis factor-α (TNF-α, transforming growth factor-β (TGF-β and vascular endothelial growth factor (VEGF were assessed by ELISA. RESULTS: IL-13 levels in the aqueous humor of patients with AMD were significantly higher than those in the control (167.33±17.64 vs 27.12±5.65 pg/mL; P<0.01. In vitro, IL-13 of high concentrations (10, 15, and 20 ng/mL inhibited ARPE-19 cell proliferation. α-SMA mRNA in ARPE-19 cell were increased (1.017±0.112 vs 1.476±0.168; P<0.001 and ZO-1 decreased (1.051±0.136 vs 0.702±0.069; P<0.001 after treated with 10 ng/mL IL-13 for 48h. The protein expression of α-SMA and ZO-1 also showed the same tendency (α-SMA: P=0.038; ZO-1: P=0.008. IL-13 significantly reduced the level of TNF-α (44.70±1.67 vs 31.79±3.53 pg/mL; P=0.005 at 48h, but the level of TGF-β2 was significantly increased from 34.44±2.92 to 57.61±6.31 pg/mL at 24h (P=0.004 and from 61.26±1.11 to 86.91±3.59 pg/mL at 48h (P<0.001. While expressions of VEGF didn’t change after IL-13 treatment. CONCLUSION: IL-13 in vitro inhibit ARPE-19 cell proliferation and expression in the aqueous may be associated with AMD.

  20. Oxidative stress, innate immunity, and age-related macular degeneration

    Science.gov (United States)

    Shaw, Peter X.; Stiles, Travis; Douglas, Christopher; Ho, Daisy; Fan, Wei; Du, Hongjun; Xiao, Xu

    2016-01-01

    Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE). These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD). Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs) have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM) remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer’s disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory molecules, we have

  1. Complement inhibitors for age-related macular degeneration.

    Science.gov (United States)

    Williams, Michael A; McKay, Gareth J; Chakravarthy, Usha

    2014-01-15

    Given the relatively high prevalence of age-related macular degeneration (AMD) and the increased incidence of AMD as populations age, the results of trials of novel treatments are awaited with much anticipation. The complement cascade describes a series of proteolytic reactions occurring throughout the body that generate proteins with a variety of roles including the initiation and promotion of immune reactions against foreign materials or micro-organisms. The complement cascade is normally tightly regulated, but much evidence implicates complement overactivity in AMD and so it is a logical therapeutic target in the treatment of AMD. To assess the effects and safety of complement inhibitors in the prevention or treatment of advanced AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 11), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2013), EMBASE (January 1980 to November 2013), Allied and Complementary Medicine Database (AMED) (January 1985 to November 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to November 2013), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), Web of Science Conference Proceedings Citation Index - Science (CPCI-S) (January 1990 to November 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 21 November 2013. We also performed handsearching of proceedings, from 2012 onwards, of meetings and conferences of specific professional organisations. We planned to include randomised controlled trials (RCTs) with

  2. Bilateral cervical ectopic thymic nodules with accessory thyroid tissue and an ectopic parathyroid in the neck region

    Directory of Open Access Journals (Sweden)

    Wea-Lung Lin

    2011-03-01

    Full Text Available Some remnants of thymic tissue may be deposited along the pathway of the descent of the neck during embryologic development of the thymus. Ectopic thymic tissue is usually deposited along the pathway from the mandibular angle to the manubrium of the sternum. Most reported cases of an ectopic thymus occurred in children, and cases are less common in adults. We report a 26-year-old woman, who was incidentally found to have 2 neck nodules on the posterior side of the bilateral upper pole of the thyroid gland while undergoing a subtotal thyroidectomy. The left-side neck nodule showed accessory thyroid follicles intermixed with ectopic thymic tissue, and the right-side neck nodule was ectopic parathyroid tissue together with ectopic thymic tissue.

  3. Can a Proper T-Cell Development Occur in an Altered Thymic Epithelium? Lessons From EphB-Deficient Thymi

    Directory of Open Access Journals (Sweden)

    Juan José Muñoz

    2018-04-01

    Full Text Available For a long time, the effects of distinct Eph tyrosine kinase receptors and their ligands, ephrins on the structure, immunophenotype, and development of thymus and their main cell components, thymocytes (T and thymic epithelial cells (TECs, have been studied. In recent years, the thymic phenotype of mutant mice deficient in several Ephs and ephrins B has been determined. Remarkably, thymic stroma in these animals exhibits important defects that appear early in ontogeny but little alterations in the proportions of distinct lymphoid cell populations. In the present manuscript, we summarize and extend these results discussing possible mechanisms governing phenotypical and functional thymocyte maturation in an absence of the critical T–TEC interactions, concluding that some signaling mediated by key molecules, such as MHCII, CD80, β5t, Aire, etc. could be sufficient to enable a proper maturation of thymocytes, independently of morphological alterations affecting thymic epithelium.

  4. Fate of thymic lymphocytes. [/sup 125/IudR and /sup 3/HTdR tracer studies in mice

    Energy Technology Data Exchange (ETDEWEB)

    Laissue, J A; Chanana, A D; Cronkite, E P; Joel, D D

    1976-01-01

    Data are summarized from a number of studies on the fate of thymic lymphocytes. Results are reported from studies in mice in which /sup 125/IudR and /sup 3/HTdR were used as tracers to study the production, maturation, migration, and life span of thymic lymphocytes. It is pointed out that thymus-derived cells constitute the majority of recirculating lymphocytes and that peripheral, differentiated thymus-derived lymphocytes exhibit a number of immunological functions. 114 references.

  5. Risk factors for age-related maculopathy in a 14-year follow-up study

    DEFF Research Database (Denmark)

    Buch, Helena; Vinding, Troels; la Cour, Morten

    2005-01-01

    To examine the association between potential risk factors and the 14-year incidence of age-related maculopathy (ARM).......To examine the association between potential risk factors and the 14-year incidence of age-related maculopathy (ARM)....

  6. Age-Related Racial Disparity in Suicide Rates Among U.S. Youth

    Science.gov (United States)

    ... May 30, 2018 Age-Related Racial Disparity in Youth Suicide Rates May 21, 2018 News by Year 2018 ... May 30, 2018 Age-Related Racial Disparity in Youth Suicide Rates May 21, 2018 News by Year 2018 ...

  7. Three Studies Point to Same Risk Gene for Age-Related Macular Degeneration

    Science.gov (United States)

    ... point to same risk gene for age-related macular degeneration NIH-funded research helps unravel the biology of ... rare, but powerful risk factor for age-related macular degeneration (AMD), a common cause of vision loss in ...

  8. Does eating particular diets alter risk of age-related macular degeneration in users of the Age-Related Eye Disease Study supplements?

    Science.gov (United States)

    Background: Recent information suggests that the Age-Related Eye Disease Study (AREDS) supplement, enhanced intake of omega-3 fatty acids, and diminishing dietary glycemic index (dGI) are protective against advanced age-related macular degeneration (AMD). Methods: Dietary information was collected a...

  9. The Association between Plasma 25-Hydroxyvitamin D and Subgroups in Age-Related Macular Degeneration

    DEFF Research Database (Denmark)

    Singh, Amardeep; Falk, Mads Krüger; Subhi, Yousif

    2013-01-01

    To evaluate potential differences in plasma 25-hydroxyvitamin in subtypes of age-related macular degeneration (AMD), and in patients in Clinical Age-Related Maculopathy Staging (CARMS) group 5 with or without subretinal fibrosis.......To evaluate potential differences in plasma 25-hydroxyvitamin in subtypes of age-related macular degeneration (AMD), and in patients in Clinical Age-Related Maculopathy Staging (CARMS) group 5 with or without subretinal fibrosis....

  10. Photoperiodic modulation of local melatonin synthesis and its role in regulation of thymic homeostasis in Funambulus pennanti.

    Science.gov (United States)

    Gupta, Sameer; Haldar, Chandana

    2016-12-01

    The effect of photo-neuroendocrine system on the thymic (immune) functions is mediated by gonadal steroid and the pineal hormone melatonin. The present study explored the effect of photoperiod on the thymic melatonergic system and its role in protection of thymic T-cells from the testosterone induced seasonal oxidative stress and apoptosis. Exposure to long day-length (LD) was noted to decrease local (thymic) melatonin content and induce oxidative stress and apoptosis in the thymus. Increased peripheral level of testosterone upregulated the androgen receptor expression and, consequently reduced proliferation response of the thymocytes. Short day conditions (SD) however, reversed the effect of LD on the thymic physiology. Low level of testosterone was concomitant with diminished nitro-oxidative stress and decreased expression of redox sensitive factors (NF-κB, p53 and Bax/Bcl-2 ratio) in the thymus. SD retarded activation of caspase-3 resulting in procaspase-3 accumulation. Further, in vitro treatment of thymocytes with AR antagonist flutamide impaired the sensitivity of thymocytes to androgen and reversed the deleterious effects of testosterone on the proliferative and apoptotic responses of thymocytes. Therefore, it can be suggested that thymus derived melatonin protects thymic T-cells from testosterone induced seasonal oxidative stress, apoptosis and also acts as a potent paracrine factor for maintenance of redox status to ensure thymocyte survival. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Volume-based quantification using dual-energy computed tomography in the differentiation of thymic epithelial tumours: an initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Suyon; Hur, Jin; Im, Dong Jin; Suh, Young Joo; Hong, Yoo Jin; Lee, Hye-Jeong; Kim, Young Jin; Choi, Byoung Wook [Yonsei University College of Medicine, Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Seoul (Korea, Republic of); Han, Kyunghwa [Yonsei University College of Medicine, Yonsei Biomedical Research Institute, Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Seoul (Korea, Republic of); Kim, Dae Joon; Lee, Chang Young [Yonsei University College of Medicine, Department of Thoracic and Cardiovascular Surgery, Seoul (Korea, Republic of); Shin, Ha Young [Yonsei University College of Medicine, Department of Neurology, Seoul (Korea, Republic of)

    2017-05-15

    To investigate the diagnostic value of dual-energy computed tomography (DECT) in differentiating between low- and high-risk thymomas and thymic carcinomas. Our institutional review board approved this study, and patients provided informed consent. We prospectively enrolled 37 patients (20 males, mean age: 55.6 years) with thymic epithelial tumour. All patients underwent DECT. For quantitative analysis, two reviewers measured the following tumour parameters: CT attenuation value in contrast Hounsfield units (CHU), iodine-related HU and iodine concentration (mg/ml). Pathological results confirmed the final diagnosis. Of the 37 thymic tumours, 23 (62.2 %) were low-risk thymomas, five (13.5 %) were high-risk thymomas and nine (24.3 %) were thymic carcinomas. According to quantitative analysis, iodine-related HU and iodine concentration were significantly different among low-risk thymomas, high-risk thymomas and thymic carcinomas (median: 29.78 HU vs. 14.55 HU vs. 19.95 HU, p = 0.001 and 1.92 mg/ml vs. 0.99 mg/ml vs. 1.18 mg/ml, p < 0.001, respectively). DECT using a quantitative analytical method based on iodine concentration measurement can be used to differentiate among thymic epithelial tumours using single-phase scanning. (orig.)

  12. Age-Related Differences in Quality of Standing Balance Using a Composite Score

    NARCIS (Netherlands)

    Pasma, J.H.; Bijlsma, A.Y.; van der Bij, M.D.W.; Arendzen, J.H.; Meskers, C.G.M.; Maier, A.B.

    2014-01-01

    Background: Age-related differences in standing balance are not detected by testing the ability to maintain balance. Quality of standing balance might be more sensitive to detect age-related differences. Objective: To study age-related differences in quality of standing balance, center of pressure

  13. Immune recovery in acute and chronic HIV infection and the impact of thymic stromal lymphopoietin

    DEFF Research Database (Denmark)

    Gelpi, Marco; Hartling, Hans J; Thorsteinsson, Kristina

    2016-01-01

    was comparable in all groups, and no differences in immune homeostasis were found between primary HIV infection and early presenters, whereas differences in absolute counts and proportions of CD4+ T cell subpopulations were found between primary HIV infection and late presenters. TSLP was elevated in primary HIV...... thymic output, but not with immune recovery. These findings indicate a possible role of TSLP in immune homeostasis in HIV infection but do not support TSLP to affect immune recovery in primary HIV infection.......BACKGROUND: Symptomatic primary HIV infection is associated with an adverse prognosis, and immediate initiation of combination antiretroviral therapy (cART) is recommended. However, little is known about immunological predictors of immune recovery. Thymic Stromal Lymphopoietin (TSLP) is a cytokine...

  14. Models of Aire-dependent gene regulation for thymic negative selection

    Directory of Open Access Journals (Sweden)

    Dina eDanso-Abeam

    2011-05-01

    Full Text Available Mutations in the Autoimmune Regulator (AIRE gene lead to Autoimmune Polyendocrinopathy Syndrome type 1 (APS1, characterized by the development of multi-organ autoimmune damage. The mechanism by which defects in AIRE result in autoimmunity has been the subject of intense scrutiny. At the cellular level, the working model explains most of the clinical and immunological characteristics of APS1, with AIRE driving the expression of tissue restricted antigens (TRAs in the epithelial cells of the thymic medulla. This TRA expression results in effective negative selection of TRA-reactive thymocytes, preventing autoimmune disease. At the molecular level, the mechanism by which AIRE initiates TRA expression in the thymic medulla remains unclear. Multiple different models for the molecular mechanism have been proposed, ranging from classical transcriptional activity, to random induction of gene expression, to epigenetic tag recognition effect, to altered cell biology. In this review, we evaluate each of these models and discuss their relative strengths and weaknesses.

  15. Factors associated with thymic size at birth among low and normal birth-weight infants

    DEFF Research Database (Denmark)

    Eriksen, Helle Brander; Biering-Sørensen, Sofie; Lund, Najaaraq

    2014-01-01

    treatment at the time of labor (0.84 [0.70-1.00]), number of pregnancy consultations (1.03 [1.00-1.05]), maternal age (0.91 [0.84-0.98]), Apgar score (1.06 [1.03-1.10]), and infant convulsions (0.44 [0.29-0.65]) were all independent determinants of thymic index but not all were determinants of thymus....../weight index. Pathologic amniotic fluid and cesarean delivery were associated with thymus/weight index among LBW infants (0.85 [0.75-0.95] and 0.80 [0.67-0.96]) but were only borderline significant for thymic index. CONCLUSION: Exposures mainly related to stress and infections were associated with a smaller...

  16. Cellular and biochemical actions of adrenal glucocorticoid hormones on rat thymic lymphocytes.

    OpenAIRE

    Young, D A; Voris, B P; Nicholson, M L

    1981-01-01

    The molecular, biochemical, and cellular effects of adrenal glucocorticoid hormones on thymic lymphocytes are reviewed, with emphasis on their relationship to the growth suppressive and lethal actions that occur in lymphoid tissues when glucocorticoids are administered to the whole animal. The data support the hypothesis that the hormonal inhibition of growth and development is a consequence of its ability to suppress cellular energy production, causing the cells to behave as though they were...

  17. Generation of Functional Thymic Epithelium from Human Embryonic Stem Cells that Supports Host T Cell Development

    OpenAIRE

    Parent, Audrey V.; Russ, Holger A.; Khan, Imran S.; LaFlam, Taylor N.; Metzger, Todd C.; Anderson, Mark S.; Hebrok, Matthias

    2013-01-01

    Inducing immune tolerance to prevent rejection is a key step toward successful engraftment of stem-cell-derived tissue in a clinical setting. Using human pluripotent stem cells to generate thymic epithelial cells (TECs) capable of supporting T cell development represents a promising approach to reach this goal; however, progress toward generating functional TECs has been limited. Here, we describe a robust in vitro method to direct differentiation of human embryonic stem cells (hESCs) into th...

  18. Inferior Vena Cava and Renal Vein Thrombosis Associated with Thymic Carcinoma

    Directory of Open Access Journals (Sweden)

    Vlad Teodor Berbecar

    2017-01-01

    Full Text Available Thymic tumors are rare mediastinal tumors that can present with a wide variety of symptoms. They can cause distant manifestations and are frequently associated with paraneoplastic syndromes. In our case, we describe the evolution of a 68-year-old male whose first manifestation was thrombosis of the inferior vena cava and renal veins. Thrombosis of large abdominal veins is rare, especially without being associated with any other comorbidity or risk factors.

  19. Three distinct subsets of thymic epithelial cells in rats and mice defined by novel antibodies.

    Directory of Open Access Journals (Sweden)

    Yasushi Sawanobori

    Full Text Available Thymic epithelial cells (TECs are thought to play an essential role in T cell development and have been detected mainly in mice using lectin binding and antibodies to keratins. Our aim in the present study was to create a precise map of rat TECs using antibodies to putative markers and novel monoclonal antibodies (i.e., ED 18/19/21 and anti-CD205 antibodies and compare it with a map from mouse counterparts and that of rat thymic dendritic cells.Rat TECs were subdivided on the basis of phenotype into three subsets; ED18+ED19+/-keratin 5 (K5+K8+CD205+ class II MHC (MHCII+ cortical TECs (cTECs, ED18+ED21-K5-K8+Ulex europaeus lectin 1 (UEA-1+CD205- medullary TECs (mTEC1s, and ED18+ED21+K5+K8dullUEA-1-CD205- medullary TECs (mTEC2s. Thymic nurse cells were defined in cytosmears as an ED18+ED19+/-K5+K8+ subset of cTECs. mTEC1s preferentially expressed MHCII, claudin-3, claudin-4, and autoimmune regulator (AIRE. Use of ED18 and ED21 antibodies revealed three subsets of TECs in mice as well. We also detected two distinct TEC-free areas in the subcapsular cortex and in the medulla. Rat dendritic cells in the cortex were MHCII+CD103+ but negative for TEC markers, including CD205. Those in the medulla were MHCII+CD103+ and CD205+ cells were found only in the TEC-free area.Both rats and mice have three TEC subsets with similar phenotypes that can be identified using known markers and new monoclonal antibodies. These findings will facilitate further analysis of TEC subsets and DCs and help to define their roles in thymic selection and in pathological states such as autoimmune disorders.

  20. The Wnt Signaling Antagonist Kremen1 is Required for Development of Thymic Architecture

    Directory of Open Access Journals (Sweden)

    Masako Osada

    2006-01-01

    Full Text Available Wnt signaling has been reported to regulate thymocyte proliferation and selection at several stages during T cell ontogeny, as well as the expression of FoxN1 in thymic epithelial cells (TECs. Kremen1 (Krm1 is a negative regulator of the canonical Wnt signaling pathway, and functions together with the secreted Wnt inhibitor Dickkopf (Dkk by competing for the lipoprotein receptor-related protein (LRP-6 co-receptor for Wnts. Here krm1 knockout mice were used to examine krm1 expression in the thymus and its function in thymocyte and TEC development. krm1 expression was detected in both cortical and medullary TEC subsets, as well as in immature thymocyte subsets, beginning at the CD25+CD44+ (DN2 stage and continuing until the CD4+CD8+(DP stage. Neonatal mice show elevated expression of krm1 in all TEC subsets. krm1− / − mice exhibit a severe defect in thymic cortical architecture, including large epithelial free regions. Much of the epithelial component remains at an immature Keratin 5+ (K5 Keratin 8+(K8 stage, with a loss of defined cortical and medullary regions. A TOPFlash assay revealed a 2-fold increase in canonical Wnt signaling in TEC lines derived from krm1− / − mice, when compared with krm1+ / + derived TEC lines. Fluorescence activated cell sorting (FACS analysis of dissociated thymus revealed a reduced frequency of both cortical (BP1+EpCAM+ and medullary (UEA-1+ EpCAMhi epithelial subsets, within the krm1− / − thymus. Surprisingly, no change in thymus size, total thymocyte number or the frequency of thymocyte subsets was detected in krm1− / − mice. However, our data suggest that a loss of Krm1 leads to a severe defect in thymic architecture. Taken together, this study revealed a new role for Krm1 in proper development of thymic epithelium.

  1. FOXN1: a master regulator gene of thymic epithelial development programme

    Directory of Open Access Journals (Sweden)

    Rosa eRomano

    2013-07-01

    Full Text Available T cell ontogeny is a sophisticated process, which takes place within the thymus through a series of well-defined discrete stages. The process requires a proper lympho-stromal interaction. In particular, cortical and medullary thymic epithelial cells (cTECs, mTECs drive T cell differentiation, education and selection processes, while the thymocyte-dependent signals allow TECs to maturate and provide an appropriate thymic microenvironment. Alterations in genes implicated in thymus organogenesis, including Tbx1, Pax1, Pax3, Pax9, Hoxa3, Eya1 and Six1, affect this well-orchestrated process, leading to disruption of thymic architecture. Of note, in both human and mice, the primordial TECs are yet unable to fully support T cell development and only after the transcriptional activation of the Forkhead-box n1 (FOXN1 gene in the thymic epithelium this essential function is acquired. FOXN1 is a master regulator in the TEC lineage specification in that it down-stream promotes transcription of genes, which, in turn, regulate TECs differentiation. In particular, FOXN1 mainly regulates TEC patterning in the fetal stage and TEC homeostasis in the postnatal thymus. An inborn null mutation in FOXN1 leads to Nude/SCID phenotype in mouse, rat and humans. In Foxn1-/- nude animals, initial formation of the primordial organ is arrested and the primordium is not colonized by hematopoietic precursors, causing a severe primary T cell immunodeficiency. In humans, the Nude/SCID phenotype is characterized by congenital alopecia of the scalp, eyebrows, and eyelashes, nail dystrophy and a severe T cell immunodeficiency, inherited as an autosomal recessive disorder. Aim of this review is to summarize all the scientific information so far available to better characterize the pivotal role of the master regulator FOXN1 transcription factor in the TEC lineage specifications and functionality.

  2. Changes in protein expression in p53 deleted spontaneous thymic lymphomas

    DEFF Research Database (Denmark)

    Honoré, Bent; Vorum, Henrik; Pedersen, Anders Elm

    2004-01-01

    with the protein expression in p53+/+ and p53-/- thymocytes. Only a minority (13 proteins) of the quantitatively changed proteins were common for the two thymic lymphoma cell lines, suggesting that the p53 deficiency mainly results in genetic dysfunctions which are individual for a given tumor. Two of the detected...... structure containing motifs of the glyoxalase-bleomycin resistance protein family (MDR) as deduced from the cDNA....

  3. Apoptosis-promoted tumorigenesis: γ-irradiation-induced thymic lymphomagenesis requires Puma-driven leukocyte death

    OpenAIRE

    Michalak, Ewa M.; Vandenberg, Cassandra J.; Delbridge, Alex R.D.; Wu, Li; Scott, Clare L.; Adams, Jerry M.; Strasser, Andreas

    2010-01-01

    Although tumor development requires impaired apoptosis, we describe a novel paradigm of apoptosis-dependent tumorigenesis. Because DNA damage triggers apoptosis through p53-mediated induction of BH3-only proteins Puma and Noxa, we explored their roles in γ-radiation-induced thymic lymphomagenesis. Surprisingly, whereas Noxa loss accelerated it, Puma loss ablated tumorigenesis. Tumor suppression by Puma deficiency reflected its protection of leukocytes from γ-irradiation-induced death, because...

  4. Effects of neonatal thymic exposure to high doses of X-irradiation

    International Nuclear Information System (INIS)

    Bains, G.S.; Sundaram, K.

    1979-01-01

    The thymic region of neonatal Swiss mice was exposed to doses varying from 1000 R to 2000 R of X-irradiation. The animals did not show any signs of wasting syndrome up to 6 months after irradiation. At this time hyperplasia of the thymus with an associated lymphocytosis was evident in irradiated animals. Antibody production to sheep red blood cells (SRBC) was not affected. However, at 12 months post-irradiation the animals showed signs of wasting disease with a progressive increase in their numbers at 18 and 24 months of age. The percentage incidence of animals with wasting disease was dose dependent. At this stage in the majority of the animals with the disease the thymus showed varying degrees of atrophy along with splenomegaly. There were no significant differences in the number of lymphocytes but the number of granulocytes showed a substantial increase. This was more evident in animals exposed to 2000 R to the thymic region. Though one observed a lowered ability to form antibodies to bovine serum albumin (BSA) with advancing age, the thymic irradiation did not affect the immune response to BSA even in animals manifesting wasting disease. An interesting observation has been the development of a severe loss of muscle power and tone in the hind limbs in a large majority of animals. (author)

  5. Mesothelioma and thymic tumors: Treatment challenges in (outside) a network setting.

    Science.gov (United States)

    Imbimbo, Martina; Maury, Jean-Michel; Garassino, Marina; Girard, Nicolas

    2018-02-02

    The management of patients with mesothelioma and thymic malignancy requires continuous multidisciplinary expertise at any step of the disease. A dramatic improvement in our knowledge has occurred in the last few years, through the development of databases, translational research programs, and clinical trials. Access to innovative strategies represents a major challenge, as there is a lack of funding for clinical research in rare cancers and their rarity precludes the design of robust clinical trials that could lead to specific approval of drugs. In this context, patient-centered initiatives, such as the establishment of dedicated networks, are warranted. International societies, such as IMIG (International Mesothelioma Interest Group) and ITMIG (International Thymic Malignancy Interest Group) provide infrastructure for global collaboration, and there are many advantages to having strong regional groups working on the same issues. There may be regional differences in risk factors, susceptibility, management and outcomes. The ability to address questions both regionally as well as globally is ideal to develop a full understanding of mesothelioma and thymic malignancies. In Europe, through the integration of national networks with EURACAN, the collaboration with academic societies and international groups, the development of networks in thoracic oncology provides multiplex integration of clinical care and research, ultimately ensuring equal access to high quality care to all patients, with the opportunity of conducting high level clinical and translational research projects. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  6. nab-Paclitaxel in Combination with Carboplatin for a Previously Treated Thymic Carcinoma

    Directory of Open Access Journals (Sweden)

    Go Makimoto

    2014-01-01

    Full Text Available We present the case of a 40-year-old man with previously treated thymic carcinoma, complaining of gradually worsening back pain. Computed tomography scans of the chest showed multiple pleural disseminated nodules with a pleural effusion in the right thorax. The patient was treated with carboplatin on day 1 plus nab-paclitaxel on day 1 and 8 in cycles repeated every 4 weeks. Objective tumor shrinkage was observed after 4 cycles of this regimen. In addition, the elevated serum cytokeratin 19 fragment level decreased, and the patient's back pain was relieved without any analgesics. Although he experienced grade 4 neutropenia and granulocyte colony-stimulating factor (G-CSF injection, the severity of thrombocytopenia and nonhematological toxicities such as reversible neuropathy did not exceed grade 1 during the treatment. To our knowledge, this is the first report to demonstrate the efficacy of combination chemotherapy consisting of carboplatin and nab-paclitaxel against thymic carcinoma. This case report suggests that nab-paclitaxel in combination with carboplatin can be a favorable chemotherapy regimen for advanced thymic carcinoma.

  7. HTLV-1-infected thymic epithelial cells convey the virus to CD4+ T lymphocytes.

    Science.gov (United States)

    Carvalho Barros, Luciana Rodrigues; Linhares-Lacerda, Leandra; Moreira-Ramos, Klaysa; Ribeiro-Alves, Marcelo; Machado Motta, Maria Cristina; Bou-Habib, Dumith Chequer; Savino, Wilson

    2017-12-01

    The human T-lymphotropic virus type-1 (HTLV-1) is the causative agent of adult T cell leukemia/lymphoma (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD4 + T cells are the main target of HTLV-1, but other cell types are known to be infected, including immature lymphocytes. Developing T cells undergo differentiation in the thymus, through migration and interaction with the thymic microenvironment, in particular with thymic epithelial cells (TEC) the major component of this three dimensional meshwork of non-lymphoid cells. Herein, we show that TEC express the receptors for HTLV-1 and can be infected by this virus through cell-cell contact and by cell-free virus suspensions. The expression of anti-apoptosis, chemokine and adhesion molecules genes are altered in HTLV-1-infected TEC, although gene expression of antigen presentation molecules remained unchanged. Furthermore, HTLV-1-infected TEC transmitted the virus to a CD4 + T cell line and to CD4 + T cells from healthy donors, during in vitro cellular co-cultures. Altogether, our data point to the possibility that the human thymic epithelial cells play a role in the establishment and progression of HTLV-1 infection, functioning as a reservoir and transmitting the virus to maturing CD4 + T lymphocytes, which in turn will cause disease in the periphery. Copyright © 2017. Published by Elsevier GmbH.

  8. Association between thymic function and allogeneic hematopoietic stem cell transplantation outcome: results of a pediatric study.

    Science.gov (United States)

    Saglio, Francesco; Cena, Silvia; Berger, Massimo; Quarello, Paola; Boccasavia, Viola; Ferrando, Federica; Pittana, Laura; Bruno, Benedetto; Fagioli, Franca

    2015-06-01

    Robust T cell function recovery has been shown to be crucial in determining allogeneic hematopoietic stem cell transplantation (HSCT) outcome, and there is growing evidence that the thymus plays a central role in regulating this process. We performed a long-term analysis of the role of thymic activity recovery in a population of pediatric patients undergoing allogeneic HSCT by signal joint T cell receptor excision circle (sjTREC) quantification. In this study, characterized by a long-term follow-up (median, 72 months), we found patients with higher levels of sjTRECs before transplantation had a statistically significant reduced risk of death compared with patients with lower values (relative risk, .31; 95% confidence interval, .30 to .32; P = .02), showing this different outcome was mainly related to a reduction of relapse incidence (14% versus 43%, P = .02). Unlike previous reports, we observed no correlation between sjTREC levels and lymphocyte recovery. Moreover, we confirmed that only graft-versus-host disease influenced thymic activity after transplantation. In conclusion, our results suggest an association between pretransplantation thymic activity and the long-term outcome of pediatric patients undergoing HSCT, mainly through a reduction of relapse opportunities. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  9. Anti-Apoptotic Signature in Thymic Squamous Cell Carcinomas - Functional Relevance of Anti-Apoptotic BIRC3 Expression in the Thymic Carcinoma Cell Line 1889c.

    Science.gov (United States)

    Huang, Bei; Belharazem, Djeda; Li, Li; Kneitz, Susanne; Schnabel, Philipp A; Rieker, Ralf J; Körner, Daniel; Nix, Wilfred; Schalke, Berthold; Müller-Hermelink, Hans Konrad; Ott, German; Rosenwald, Andreas; Ströbel, Philipp; Marx, Alexander

    2013-01-01

    The molecular pathogenesis of thymomas and thymic carcinomas (TCs) is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and TCs, suggesting that other oncogenic principles might be important. This made us re-analyze historic expression data obtained in a spectrum of thymomas and thymic squamous cell carcinomas (TSCCs) with a custom-made cDNA microarray. By cluster analysis, different anti-apoptotic signatures were detected in type B3 thymoma and TSCC, including overexpression of BIRC3 in TSCCs. This was confirmed by qRT-PCR in the original and an independent validation set of tumors. In contrast to several other cancer cell lines, the BIRC3-positive TSCC cell line, 1889c showed spontaneous apoptosis after BIRC3 knock-down. Targeting apoptosis genes is worth testing as therapeutic principle in TSCC.

  10. Anti-Apoptotic Signature in Thymic Squamous Cell Carcinomas – Functional Relevance of Anti-Apoptotic BIRC3 Expression in the Thymic Carcinoma Cell Line 1889c

    Science.gov (United States)

    Huang, Bei; Belharazem, Djeda; Li, Li; Kneitz, Susanne; Schnabel, Philipp A.; Rieker, Ralf J.; Körner, Daniel; Nix, Wilfred; Schalke, Berthold; Müller-Hermelink, Hans Konrad; Ott, German; Rosenwald, Andreas; Ströbel, Philipp; Marx, Alexander

    2013-01-01

    The molecular pathogenesis of thymomas and thymic carcinomas (TCs) is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and TCs, suggesting that other oncogenic principles might be important. This made us re-analyze historic expression data obtained in a spectrum of thymomas and thymic squamous cell carcinomas (TSCCs) with a custom-made cDNA microarray. By cluster analysis, different anti-apoptotic signatures were detected in type B3 thymoma and TSCC, including overexpression of BIRC3 in TSCCs. This was confirmed by qRT-PCR in the original and an independent validation set of tumors. In contrast to several other cancer cell lines, the BIRC3-positive TSCC cell line, 1889c showed spontaneous apoptosis after BIRC3 knock-down. Targeting apoptosis genes is worth testing as therapeutic principle in TSCC. PMID:24427739

  11. DKK1 mediated inhibition of Wnt signaling in postnatal mice leads to loss of TEC progenitors and thymic degeneration.

    Directory of Open Access Journals (Sweden)

    Masako Osada

    2010-02-01

    Full Text Available Thymic epithelial cell (TEC microenvironments are essential for the recruitment of T cell precursors from the bone marrow, as well as the subsequent expansion and selection of thymocytes resulting in a mature self-tolerant T cell repertoire. The molecular mechanisms, which control both the initial development and subsequent maintenance of these critical microenvironments, are poorly defined. Wnt signaling has been shown to be important to the development of several epithelial tissues and organs. Regulation of Wnt signaling has also been shown to impact both early thymocyte and thymic epithelial development. However, early blocks in thymic organogenesis or death of the mice have prevented analysis of a role of canonical Wnt signaling in the maintenance of TECs in the postnatal thymus.Here we demonstrate that tetracycline-regulated expression of the canonical Wnt inhibitor DKK1 in TECs localized in both the cortex and medulla of adult mice, results in rapid thymic degeneration characterized by a loss of DeltaNP63(+ Foxn1(+ and Aire(+ TECs, loss of K5K8DP TECs thought to represent or contain an immature TEC progenitor, decreased TEC proliferation and the development of cystic structures, similar to an aged thymus. Removal of DKK1 from DKK1-involuted mice results in full recovery, suggesting that canonical Wnt signaling is required for the differentiation or proliferation of TEC populations needed for maintenance of properly organized adult thymic epithelial microenvironments.Taken together, the results of this study demonstrate that canonical Wnt signaling within TECs is required for the maintenance of epithelial microenvironments in the postnatal thymus, possibly through effects on TEC progenitor/stem cell populations. Downstream targets of Wnt signaling, which are responsible for maintenance of these TEC progenitors may provide useful targets for therapies aimed at counteracting age associated thymic involution or the premature thymic

  12. Age-related changes in the macula. A histopathological study of fifty Indian donor eyes

    OpenAIRE

    Biswas Jyotirmay; Raman Rajiv

    2002-01-01

    PURPOSE: Age-related macular degeneration (ARMD) is clinically less common in India compared to the West. Therefore, clinicians are unfamiliar with histopathologic evidence of age-related macular changes in the Indian population. METHODS: Fifty consecutive human donor eyes removed for corneal grafting were studied for gross, microscopic and histochemical features of age-related changes in the macula in the Indian population. A horizontal block was cut from the globe including the optic disc, ...

  13. A Whole-Tumor Histogram Analysis of Apparent Diffusion Coefficient Maps for Differentiating Thymic Carcinoma from Lymphoma.

    Science.gov (United States)

    Zhang, Wei; Zhou, Yue; Xu, Xiao-Quan; Kong, Ling-Yan; Xu, Hai; Yu, Tong-Fu; Shi, Hai-Bin; Feng, Qing

    2018-01-01

    To assess the performance of a whole-tumor histogram analysis of apparent diffusion coefficient (ADC) maps in differentiating thymic carcinoma from lymphoma, and compare it with that of a commonly used hot-spot region-of-interest (ROI)-based ADC measurement. Diffusion weighted imaging data of 15 patients with thymic carcinoma and 13 patients with lymphoma were retrospectively collected and processed with a mono-exponential model. ADC measurements were performed by using a histogram-based and hot-spot-ROI-based approach. In the histogram-based approach, the following parameters were generated: mean ADC (ADC mean ), median ADC (ADC median ), 10th and 90th percentile of ADC (ADC 10 and ADC 90 ), kurtosis, and skewness. The difference in ADCs between thymic carcinoma and lymphoma was compared using a t test. Receiver operating characteristic analyses were conducted to determine and compare the differentiating performance of ADCs. Lymphoma demonstrated significantly lower ADC mean , ADC median , ADC 10 , ADC 90 , and hot-spot-ROI-based mean ADC than those found in thymic carcinoma (all p values histogram analysis of ADC maps can improve the differentiating performance between thymic carcinoma and lymphoma.

  14. Abnormalities of thymic stroma may contribute to immune dysregulation in murine models of leaky severe combined immunodeficiency

    Directory of Open Access Journals (Sweden)

    Francesca eRucci

    2011-05-01

    Full Text Available Lymphostromal cross-talk in the thymus is essential to allow generation of a diversified repertoire of T lymphocytes and to prevent autoimmunity by self-reactive T cells. Hypomorphic mutations in genes that control T cell development have been associated with immunodeficiency and immune dysregulation both in humans and in mice. We have studied T cell development and thymic stroma architecture and maturation in two mouse models of leaky SCID, carrying hypomorphic mutations in Rag1 and Lig4 genes. Defective T cell development was associated with abnormalities of thymic architecture that predominantly affect the thymic medulla, with reduction of the pool of mature medullary thymic epithelial cells (mTECs. While the ability of mTECs to express Aire is preserved in mutant mice, the frequency of mature mTECs expressing Aire and tissue-specific antigens (TSAs is severely reduced. Similarly, the ability of CD4+ T cells to differentiate into Foxp3+ natural regulatory T cells is preserved in Rag1 and Lig4 mutant mice, but their number is greatly reduced. These data indicate that hypomorphic defects in T cell development may cause defective lymphostromal cross-talk and impinge on thymic stromal cells maturation, and thus favor immune dysregulation.

  15. Association of murine lupus and thymic full-length endogenous retroviral expression maps to a bone marrow stem cell

    International Nuclear Information System (INIS)

    Krieg, A.M.; Gourley, M.F.; Steinberg, A.D.

    1991-01-01

    Recent studies of thymic gene expression in murine lupus have demonstrated 8.4-kb (full-length size) modified polytropic (Mpmv) endogenous retroviral RNA. In contrast, normal control mouse strains do not produce detectable amounts of such RNA in their thymuses. Prior studies have attributed a defect in experimental tolerance in murine lupus to a bone marrow stem cell rather than to the thymic epithelium; in contrast, infectious retroviral expression has been associated with the thymic epithelium, rather than with the bone marrow stem cell. The present study was designed to determine whether the abnormal Mpmv expression associated with murine lupus mapped to thymic epithelium or to a marrow precursor. Lethally irradiated control and lupus-prone mice were reconstituted with T cell depleted bone marrow; one month later their thymuses were studied for endogenous retroviral RNA and protein expression. Recipients of bone marrow from nonautoimmune donors expressed neither 8.4-kb Mpmv RNA nor surface MCF gp70 in their thymuses. In contrast, recipients of bone marrow from autoimmune NZB or BXSB donors expressed thymic 8.4-kb Mpmv RNA and mink cell focus-forming gp70. These studies demonstrate that lupus-associated 8.4-kb Mpmv endogenous retroviral expression is determined by bone marrow stem cells

  16. Age-related synaptic loss of the medial olivocochlear efferent innervation

    Directory of Open Access Journals (Sweden)

    Schrader Angela

    2010-11-01

    Full Text Available Abstract Age-related functional decline of the nervous system is consistently observed, though cellular and molecular events responsible for this decline remain largely unknown. One of the most prevalent age-related functional declines is age-related hearing loss (presbycusis, a major cause of which is the loss of outer hair cells (OHCs and spiral ganglion neurons. Previous studies have also identified an age-related functional decline in the medial olivocochlear (MOC efferent system prior to age-related loss of OHCs. The present study evaluated the hypothesis that this functional decline of the MOC efferent system is due to age-related synaptic loss of the efferent innervation of the OHCs. To this end, we used a recently-identified transgenic mouse line in which the expression of yellow fluorescent protein (YFP, under the control of neuron-specific elements from the thy1 gene, permits the visualization of the synaptic connections between MOC efferent fibers and OHCs. In this model, there was a dramatic synaptic loss between the MOC efferent fibers and the OHCs in older mice. However, age-related loss of efferent synapses was independent of OHC status. These data demonstrate for the first time that age-related loss of efferent synapses may contribute to the functional decline of the MOC efferent system and that this synaptic loss is not necessary for age-related loss of OHCs.

  17. Increased cell division but not thymic dysfunction rapidly affects the T-cell receptor excision circle content of the naive T cell population in HIV-1 infection

    NARCIS (Netherlands)

    Hazenberg, Mette D.; Borleffs, J.C.C.; Otto, S.A.; Cohen Stuart, J.W.T. (James Willem Theodoor); Verschuren, M.C.M. (Martie); Boucher, C.A.B.; Coutinho, R.A.; Lange, Joep M.A.; Rinke de Wit, T.F. (Tobias); Tsegaye, A. (Aster); Dongen, J.J.M. (Jaques) van; Hamann, D. (Dörte); Boer, R.J. de; Miedema, F.

    2000-01-01

    Recent thymic emigrants can be identified by T cell receptor excision circles (TRECs) formed during T-cell receptor rearrangement. Decreasing numbers of TRECs have been observed with aging and in human immunodeficiency virus (HIV)-1 infected individuals, suggesting for thymic impairment. Here,

  18. [Physical activity diminishes aging-related decline of physical and cognitive performance].

    Science.gov (United States)

    Apor, Péter; Babai, László

    2014-05-25

    Aging-related decline of muscle force, walking speed, locomotor coordination, aerobic capacity and endurance exert prognostic impact on life expectancy. Proper use of training may diminish the aging process and it may improve the quality of life of elderly persons. This paper provides a brief summary on the impact of training on aging-related decline of physical and cognitive functions.

  19. Incidence and progression rates of age-related maculopathy: the Rotterdam Study

    NARCIS (Netherlands)

    J.J.M. Willemse-Assink (Jacqueline); R. van Leeuwen (Redmer); R.C.W. Wolfs (Roger); J.R. Vingerling (Hans); Th. Stijnen (Theo); P.T.V.M. de Jong (Paulus); C.C.W. Klaver (Caroline); A. Hofman (Albert)

    2001-01-01

    textabstractPURPOSE: To describe the incidence rate of age-related macular degeneration (AMD) and the progression rates of early stages of age-related maculopathy (ARM), and to study the hierarchy of fundus features that determine progression. METHODS: A group of 4953 subjects

  20. Development of age-related maculopathy: a histochemical and molecular approach

    NARCIS (Netherlands)

    A.C. Lambooij (Antoinette)

    2002-01-01

    textabstractAge-related maculopathy (ARM) is a severe threat to the visual ability of people over 65 years of age. In the late stages of ARM, called age-related macular degeneration (AMD), photoreceptor cells gradually disappear. New vessels growing beneath the retina may complicateb the disease;

  1. Age-related attitudes: the influence on relationships and performance at work

    NARCIS (Netherlands)

    Dr. Franz Josef Gellert; R. Schalk

    2012-01-01

    Purpose: – This paper aims to examine the influence of age and age-related attitudes on relationship factors. In addition, it seeks to assess how both factors affect care service work performance. Design/methodology/approach: – The paper explores the influence of age and age-related attitudes on the

  2. Experience-Based Mitigation of Age-Related Performance Declines: Evidence from Air Traffic Control

    Science.gov (United States)

    Nunes, Ashley; Kramer, Arthur F.

    2009-01-01

    Previous research has found age-related deficits in a variety of cognitive processes. However, some studies have demonstrated age-related sparing on tasks where individuals have substantial experience, often attained over many decades. Here, the authors examined whether decades of experience in a fast-paced demanding profession, air traffic…

  3. Induced Pluripotent Stem Cell Derived Mesenchymal Stem Cells for Attenuating Age-Related Bone Loss

    Science.gov (United States)

    2012-07-01

    Mesenchymal stem cell (MSC) differentiation towards the bone forming osteoblastic lineage decreases as a function of age and may contribute to age-related...problem of age-related reduced availability of MSC we propose to examine the bone anabolic potential of induced pluripotent stem cell (iPS) derived MSC

  4. Subfoveal fibrosis in eyes with neovascular age-related macular degeneration treated with intravitreal ranibizumab

    DEFF Research Database (Denmark)

    Bloch, Sara Brandi; Lund-Andersen, Henrik; Sander, Birgit

    2013-01-01

    To assess baseline and follow-up characteristics of choroidal neovascularization (CNV) lesions in age-related macular degeneration in relation to the development of subfoveal subretinal fibrosis.......To assess baseline and follow-up characteristics of choroidal neovascularization (CNV) lesions in age-related macular degeneration in relation to the development of subfoveal subretinal fibrosis....

  5. The relationship of major American dietary patterns to age-related macular degeneration

    Science.gov (United States)

    We hypothesized that major American dietary patterns are associated with age-related macular degeneration (AMD) risk. This was a cross-sectional study with 8,103 eyes from 4,088 eligible participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into control (n=2,739), early ...

  6. Verteporfin plus ranibizumab for choroidal neovascularization in age-related macular degeneration

    DEFF Research Database (Denmark)

    Larsen, Michael; Schmidt-Erfurth, Ursula; Lanzetta, Paolo

    2012-01-01

    To compare the efficacy and safety of same-day verteporfin photodynamic therapy (PDT) and intravitreal ranibizumab combination treatment versus ranibizumab monotherapy in neovascular age-related macular degeneration.......To compare the efficacy and safety of same-day verteporfin photodynamic therapy (PDT) and intravitreal ranibizumab combination treatment versus ranibizumab monotherapy in neovascular age-related macular degeneration....

  7. How nonuniform contact profiles of T cell receptors modulate thymic selection outcomes

    Science.gov (United States)

    Chen, Hanrong; Chakraborty, Arup K.; Kardar, Mehran

    2018-03-01

    T cell receptors (TCRs) bind foreign or self-peptides attached to major histocompatibility complex (MHC) molecules, and the strength of this interaction determines T cell activation. Optimizing the ability of T cells to recognize a diversity of foreign peptides yet be tolerant of self-peptides is crucial for the adaptive immune system to properly function. This is achieved by selection of T cells in the thymus, where immature T cells expressing unique, stochastically generated TCRs interact with a large number of self-peptide-MHC; if a TCR does not bind strongly enough to any self-peptide-MHC, or too strongly with at least one self-peptide-MHC, the T cell dies. Past theoretical work cast thymic selection as an extreme value problem and characterized the statistical enrichment or depletion of amino acids in the postselection TCR repertoire, showing how T cells are selected to be able to specifically recognize peptides derived from diverse pathogens yet have limited self-reactivity. Here, we investigate how the diversity of the postselection TCR repertoire is modified when TCRs make nonuniform contacts with peptide-MHC. Specifically, we were motivated by recent experiments showing that amino acids at certain positions of a TCR sequence have large effects on thymic selection outcomes, and crystal structure data that reveal a nonuniform contact profile between a TCR and its peptide-MHC ligand. Using a representative TCR contact profile as an illustration, we show via simulations that the statistical enrichment or depletion of amino acids now varies by position according to the contact profile, and, importantly, it depends on the implementation of nonuniform contacts during thymic selection. We explain these nontrivial results analytically. Our study has implications for understanding the selection forces that shape the functionality of the postselection TCR repertoire.

  8. Treatment Results and Prognostic Indicators in Thymic Epithelial Tumors: A Clinicopathological Analysis of 45 Patients

    Directory of Open Access Journals (Sweden)

    Mansour Ansari

    2014-07-01

    Full Text Available Background: Thymomas are rare epithelial tumors arising from thymus gland. This study aims at investigating the clinical presentation, prognostic factors and treatment outcome of forty five patients with thymoma and thymic carcinoma. Methods: Forty-five patients being histologically diagnosed with thymoma or thymic carcinoma that were treated and followed-up at a tertiary academic hospital during January 1987 and December 2008 were selected for the present study. Twelve patients were solely treated with surgery, 14 with surgery followed by adjuvant radiotherapy, 12 with sequential combined treatment of surgery, radiotherapy and/or chemotherapy and 7 with non-surgical approach including radiotherapy and/or chemotherapy. Tumors were classified based on the new World Health Organization (WHO histological classification. Results: There were 18 women and 27 men with a median age of 43 years. Twelve patients (26.7% had stage I, 7 (17.8% had stage II, 23 (51% had stage III and 2 (4.5% had stage IV disease. Tumors types were categorized as type A (n=4, type AB (n=10, type B1 (n=9, type B2 (n=10, type B3 (n=5 and type C (n=7. In univariate analysis for overall survival, disease stage (P=0.001, tumor size (P=0.017 and the extent of surgical resection (P<0.001 were prognostic factors. Regarding the multivariate analysis, only the extent of the surgical resection (P<0.001 was the independent prognostic factor and non-surgical treatment had a negative influence on the survival. The 5-year and 10-year overall survival rates were 70.8% and 62.9%, respectively. Conclusion: Complete surgical resection is the most important prognostic factor in patients with thymic epithelial tumors.

  9. Treatment results and prognostic indicators in thymic epithelial tumors: a clinicopathological analysis of 45 patients.

    Science.gov (United States)

    Ansari, Mansour; Dehsara, Farzin; Mohammadianpanah, Mohammad; Mosalaei, Ahmad; Omidvari, Shapour; Ahmadloo, Niloofar

    2014-07-01

    Thymomas are rare epithelial tumors arising from thymus gland. This study aims at investigating the clinical presentation, prognostic factors and treatment outcome of forty five patients with thymoma and thymic carcinoma. Forty-five patients being histologically diagnosed with thymoma or thymic carcinoma that were treated and followed-up at a tertiary academic hospital during January 1987 and December 2008 were selected for the present study. Twelve patients were solely treated with surgery, 14 with surgery followed by adjuvant radiotherapy, 12 with sequential combined treatment of surgery, radiotherapy and/or chemotherapy and 7 with non-surgical approach including radiotherapy and/or chemotherapy.  Tumors were classified based on the new World Health Organization (WHO) histological classification. There were 18 women and 27 men with a median age of 43 years. Twelve patients (26.7%) had stage I, 7 (17.8%) had stage II, 23 (51%) had stage III and 2 (4.5%) had stage IV disease. Tumors types were categorized as type A (n=4), type AB (n=10), type B1 (n=9), type B2 (n=10), type B3 (n=5) and type C (n=7). In univariate analysis for overall survival, disease stage (P=0.001), tumor size (P=0.017) and the extent of surgical resection (P<0.001) were prognostic factors. Regarding the multivariate analysis, only the extent of the surgical resection (P<0.001) was the independent prognostic factor and non-surgical treatment had a negative influence on the survival. The 5-year and 10-year overall survival rates were 70.8% and 62.9%, respectively. Complete surgical resection is the most important prognostic factor in patients with thymic epithelial tumors.

  10. Plxnd1 expression in thymocytes regulates their intrathymic migration while that in thymic endothelium impacts medullary topology

    Directory of Open Access Journals (Sweden)

    Young Il Choi

    2013-11-01

    Full Text Available An important role for plexinD1 in thymic development is inferred from studies of germline Plxnd1 knockout (KO mice where mislocalized CD69+ thymocytes as well as ectopic thymic subcapsular medullary structures were observed. Given embryonic lethality of the Plxnd1-/- genotype, fetal liver transplantation was employed in these prior analyses. Such embryonic hematopoietic reconstitution may have transferred Plxnd1 KO endothelial and/or epithelial stem cells in addition to Plxnd1 KO lymphoid progenitors, thereby contributing to that phenotype. Here we use Plxnd1flox/flox mice crossed to pLck-Cre, pKeratin14-Cre or pTek-Cre transgenic animals to create cell-type specific conditional knockout (CKO lines involving thymocytes (D1ThyCKO, thymic epithelium (D1EpCKO and thymic endothelium (D1EnCKO, respectively. These CKOs allowed us to directly assess the role of plexinD1 in each lineage. Loss of plexinD1 expression on double positive (DP thymocytes leads to their aberrant migration and cortical retention after TCR-mediated positive selection. In contrast, ectopic medulla formation is a consequence of loss of plexinD1 expression on endothelial cells, in turn linked to dysregulation of thymic angiogenesis. D1EpCKO thymi manifest neither abnormality. Collectively, our findings underscore the non-redundant roles for plexinD1 on thymocytes and endothelium, including the dynamic nature of medulla formation resulting from crosstalk between these thymic cellular components.

  11. A thymic neuroendocrine tumour in a young female: a rare cause of relapsing and remitting Cushing's syndrome.

    Science.gov (United States)

    Trott, M J; Farah, G; Stokes, V J; Wang, L M; Grossman, A B

    2016-01-01

    We present a case of a young female patient with a rare cause of relapsing and remitting Cushing's syndrome due to ectopic ACTH secretion from a thymic neuroendocrine tumour. A 34-year-old female presented with a constellation of symptoms of Cushing's syndrome, including facial swelling, muscle weakness and cognitive impairment. We use the terms 'relapsing and remitting' in this case report, given the unpredictable time course of symptoms, which led to a delay of 2 years before the correct diagnosis of hypercortisolaemia. Diagnostic workup confirmed ectopic ACTH secretion, and a thymic mass was seen on mediastinal imaging. The patient subsequently underwent thymectomy with complete resolution of her symptoms. Several case series have documented the association of Cushing's syndrome with thymic neuroendocrine tumours (NETs), although to our knowledge there are a few published cases of patients with relapsing and remitting symptoms. This case is also notable for the absence of features of the MEN-1 syndrome, along with the female gender of our patient and her history of non-smoking. Ectopic corticotrophin (ACTH) secretion should always be considered in the diagnostic workup of young patients with Cushing's syndromeThere is a small but growing body of literature describing the correlation between ectopic ACTH secretion and thymic neuroendocrine tumours (NETs)The possibility of a MEN-1 syndrome should be considered in all patients with thymic NETs, and we note the observational association with male gender and cigarette smoking in this cohortAn exception to these associations is the finding of relatively high incidence of thymic NETs among female non-smoking MEN-1 patients in the Japanese compared with Western populationsThe relapsing and remitting course of our patient's symptoms is noteworthy, given the paucity of this finding among other published cases.

  12. S1P lyase in thymic perivascular spaces promotes egress of mature thymocytes via up-regulation of S1P receptor 1.

    Science.gov (United States)

    Maeda, Yasuhiro; Yagi, Hideki; Takemoto, Kana; Utsumi, Hiroyuki; Fukunari, Atsushi; Sugahara, Kunio; Masuko, Takashi; Chiba, Kenji

    2014-05-01

    Sphingosine 1-phosphate (S1P) and S1P receptor 1 (S1P1) play an important role in the egress of mature CD4 or CD8 single-positive (SP) thymocytes from the thymus. Fingolimod hydrochloride (FTY720), an S1P1 functional antagonist, induced significant accumulation of CD62L(high)CD69(low) mature SP thymocytes in the thymic medulla. Immunohistochemical staining using anti-S1P1 antibody revealed that S1P1 is predominantly expressed on thymocytes in the thymic medulla and is strongly down-regulated even at 3h after FTY720 administration. 2-Acetyl-4-tetrahydroxybutylimidazole (THI), an S1P lyase inhibitor, also induced accumulation of mature SP thymocytes in the thymic medulla with an enlargement of the perivascular spaces (PVS). At 6h after THI administration, S1P1-expressing thymocytes reduced partially as if to form clusters and hardly existed in the proximity of CD31-expressing blood vessels in the thymic medulla, suggesting S1P lyase expression in the cells constructing thymic medullary PVS. To determine the cells expressing S1P lyase in the thymus, we newly established a mAb (YK19-2) specific for mouse S1P lyase. Immunohistochemical staining with YK19-2 revealed that S1P lyase is predominantly expressed in non-lymphoid thymic stromal cells in the thymic medulla. In the thymic medullary PVS, S1P lyase was expressed in ER-TR7-positive cells (reticular fibroblasts and pericytes) and CD31-positive vascular endothelial cells. Our findings suggest that S1P lyase expressed in the thymic medullary PVS keeps the tissue S1P concentration low around the vessels and promotes thymic egress via up-regulation of S1P1.

  13. PATTERNS OF FUNDUS AUTOFLUORESCENCE DEFECTS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION SUBTYPES.

    Science.gov (United States)

    Ozkok, Ahmet; Sigford, Douglas K; Tezel, Tongalp H

    2016-11-01

    To test define characteristic fundus autofluorescence patterns of different exudative age-related macular degeneration subtypes. Cross-sectional study. Fifty-two patients with choroidal neovascularization because of three different neovascular age-related macular degeneration subtypes were included in the study. Macular and peripheral fundus autofluorescence patterns of study subjects were compared in a masked fashion. Fundus autofluorescence patterns of all three neovascular age-related macular degeneration subtypes revealed similar patterns. However, peripapillary hypo-autofluorescence was more common among patients with polypoidal choroidal vasculopathy (88.2%) compared with patients with retinal angiomatous proliferation (12.5%) and patients without retinal angiomatous proliferation and polypoidal choroidal vasculopathy (21.1%) (P autofluorescence defects in neovascular age-related macular degeneration maybe suggestive of polypoidal choroidal vasculopathy as a variant of neovascular age-related macular degeneration.

  14. Age-related changes in strategic variations during arithmetic problem solving: The role of executive control.

    Science.gov (United States)

    Hinault, T; Lemaire, P

    2016-01-01

    In this review, we provide an overview of how age-related changes in executive control influence aging effects in arithmetic processing. More specifically, we consider the role of executive control in strategic variations with age during arithmetic problem solving. Previous studies found that age-related differences in arithmetic performance are associated with strategic variations. That is, when they accomplish arithmetic problem-solving tasks, older adults use fewer strategies than young adults, use strategies in different proportions, and select and execute strategies less efficiently. Here, we review recent evidence, suggesting that age-related changes in inhibition, cognitive flexibility, and working memory processes underlie age-related changes in strategic variations during arithmetic problem solving. We discuss both behavioral and neural mechanisms underlying age-related changes in these executive control processes. © 2016 Elsevier B.V. All rights reserved.

  15. Thymic involvement in immune recovery during antiretroviral treatment of HIV infection in adults; comparison of CT and sonographic findings

    DEFF Research Database (Denmark)

    Kolte, Lilian; Strandberg, Charlotte; Dreves, Anne-Mette

    2002-01-01

    In adult HIV-infected patients, thymic size evaluated from CT scans seems to be important to the degree of immune reconstitution obtainable during treatment with highly active antiretroviral therapy (HAART). To examine whether ultrasound is as reliable as CT for estimating thymic size...... and predicting immune recovery, CT and ultrasound scans were performed in 25 adult HIV-infected patients and 10 controls. CD4 counts and naive CD4 counts were measured in order to determine immune reconstitution. Furthermore, the CD4+ T-cell receptor excision circle (TREC) frequency and T-cell receptor (TCR...

  16. Effect of granulocyte colony-stimulating factor on murine thymic emigration and subsets reconstitution after a sublethal dose of irradiation

    International Nuclear Information System (INIS)

    Zhao Hongxia; Guo Mei; Sun Xuedong; Ai Huisheng

    2011-01-01

    Objective: To investigate the effects of recombinant human granulocyte colony stimulating factor (G-CSF) on murine thymic emigration and subsets reconstitution after a sublethal dose of irradiation. Methods: Female BALB/c mice were irradiated with a 6.0 Gy of γ-ray total-body irradiation and then randomly divided into GCSF group and control group. For mice in the GCSF group, recombinant human G-CSF 100 μg · kg -1 · d -1 was injected subcutaneously once daily for 14 continuous days and mice in the control group were given the same volume of phosphate buffered solution (PBS). At 7, 14, 21 and 28 days later, mice were killed and thymus mononuclear cell suspension were analyzed by flow cytometry for the percentage of the four stages of thymic CD4 - CD8 - double negative cells (DN1-4) and the CD4 + CD8 + double positive ( CD4 + CD8 + DP), CD4 + CD8 - single positive (CD4 + SP), CD4 - CD8 + single positive cells (CD8 + SP).Real-time PCR was used for detection and quantitation of murine T cell receptor rearrangement excision circles (sjTRECs) of the thymic cells of 30 and 60 d after irradiation. Results: The percentage of thymic DN1 cells in GCSF group was significantly higher than that of the control group 7 d after irradiation (t=9.59, P<0.05). 21 d later, the proportion of thymic DN3 and DN4 cells were higher than those of the control group (t=16.37, 7.6, P<0.05). The percentage of thymic CD4 + CD8 + DP cells decreased 7 d after irradiation,increased at 14 d, decreased again at 21 days,and then got a permanent recover. The percentage of thymic CD4 + CD8 + DP cells in the GCSF group recovered to normal and was significantly higher than that of the control group 28 days after irradiation (t=12.22, P<0.05). The percentage of thymic CD8 + SP cells of the GCSF group was significantly higher than that of the control group 21 d after irradiation (t=3.77, P<0.05), while G-CSF had no obvious influence on the percentage of the thymic CD4 + SP cells. The sjTRECs copies in the

  17. Age-related variations of visuo-motor adaptation beyond explicit knowledge

    Directory of Open Access Journals (Sweden)

    Herbert eHeuer

    2014-07-01

    Full Text Available Visuo-motor adaptation suffers at older working age. The age-related decline of behavioural adjustments is accompanied by reduced explicit knowledge of the visuo-motor transformation. It disappears when explicit knowledge is kept constant across the age range, except for particularly high levels of explicit knowledge. According to these findings, at older adult age both the acquisition of explicit knowledge and its application for strategic corrections become poorer. Recently it has been posited that visuo-motor adaptation can involve model-free reinforcement mechanisms of learning in addition to model-based mechanisms. We tested whether age-related declines of reinforcement learning can also contribute to the age-related changes of visuo-motor adaptation. Therefore we enhanced the contribution of reinforcement learning to visuo-motor adaptation by way of introducing salient markers of success and failure during practice. With such modified practice conditions, there were residual age-related variations of behavioural adjustments at all levels of explicit knowledge, even when explicit knowledge was absent. The residual age-related variations were observed for practiced target directions only, but not for new target directions. These findings are consistent with an age-related decline of model-free reinforcement learning as a third factor in the age-related decline of visuo-motor adaptation. Under practice conditions, which spur model-free reward-based learning, this factor adds to the decrements of the acquisition of explicit knowledge and its use for strategic corrections.

  18. Association of HTRA1 rs11200638 with age-related macular degeneration (AMD) in Brazilian patients.

    Science.gov (United States)

    Lana, Tamires Prates; da Silva Costa, Sueli Matilde; Ananina, Galina; Hirata, Fábio Endo; Rim, Priscila Hae Hyun; Medina, Flávio MacCord; de Vasconcellos, José Paulo Cabral; de Melo, Mônica Barbosa

    2018-01-01

    Age-related macular degeneration is a multifactorial disease that can lead to vision impairment in older individuals. Although the etiology of age-related macular degeneration remains unknown, risk factors include age, ethnicity, smoking, hypertension, obesity, and genetic factors. Two main loci have been identified through genome-wide association studies, on chromosomes 1 and 10. Among the variants located at the 10q26 region, rs11200638, located at the HTRA1 gene promoter, has been associated with age-related macular degeneration in several populations and is considered the main polymorphism. We conducted a replication case-control study to analyze the frequency and participation of rs11200638 in the etiology of age-related macular degeneration in a sample of patients and controls from the State of São Paulo, Brazil, through polymerase chain reaction and enzymatic digestion. The frequency of the A allele was 57.60% in patients with age-related macular degeneration and 36.45% in controls (p value age-related macular degeneration group compared to the control group (p = 1.21 e-07 and 0.0357, respectively). No statistically significant results were observed after stratification in dry versus wet types or advanced versus non-advanced forms. To our knowledge, this is the first time the association between rs11200638 and overall age-related macular degeneration has been reported in South America.

  19. Thymic lesions and myasthenia gravis. Diagnosis based on mediastinal imaging and pathological findings

    International Nuclear Information System (INIS)

    Pirronti, T.; Rinaldi, P.; Marano, P.; Batocchi, A.P.; Evoli, A.; Di Schino, C.

    2002-01-01

    Purpose: To achieve a better understanding of the role of CT and MR imaging in the study of the mediastinum in patients with myasthenia gravis (MG). Material and Methods: Mediastinal CT and MR findings were correlated with the histopathological results in 104 thymectomized MG patients. Results: CT was performed in 104 patients; in 11 of them, MR was also carried out. 44 patients had hyperplasia at histology. On CT, thymic hyperplasia was confirmed in 16 cases, thymoma was diagnosed in 10 and a normal thymus in 18 (sensitivity 36%, specificity 95%). Of 52 patients with thymoma at histology, CT showed thymoma in 46, hyperplasia in 1, and normal thymus in 5. CT showed 88.5% sensitivity and 77% specificity for thymoma. In 10 patients with invasive thymoma, CT was indiscriminate, while invasiveness was detected in 7 cases at MR (70% sensitivity) and at CT in 1 case. Both CT and MR detected tumor recurrence in 5 cases, but the exact localization and degree of invasion were best defined by MR. Conclusion: In MG patients CT is a sensitive, specific and efficient modality for detecting thymoma, but is less so for detecting thymic hyperplasia. MR was shown to be accurate in detecting invasive thymoma both preoperatively and in postoperative follow-up

  20. Complicated biallelic inactivation of Pten in radiation-induced mouse thymic lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, Yu [Department of Biology, Graduate School of Science, Chiba University, Yayoicho, Inage-ku, Chiba 263-8522 (Japan); Experimental Radiobiology for Children' s Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan); Takabatake, Takashi; Kakinuma, Shizuko; Amasaki, Yoshiko; Nishimura, Mayumi; Imaoka, Tatsuhiko; Yamauchi, Kazumi; Shang, Yi [Experimental Radiobiology for Children' s Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan); Miyoshi-Imamura, Tomoko [Experimental Radiobiology for Children' s Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan); Genetic Counseling Program, Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyou-ku, Tokyo 112-8610 (Japan); Nogawa, Hiroyuki [Department of Biology, Graduate School of Science, Chiba University, Yayoicho, Inage-ku, Chiba 263-8522 (Japan); Kobayashi, Yoshiro [Department of Biomolecular Science, Faculty of Science, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510 (Japan); Shimada, Yoshiya, E-mail: y_shimad@nirsgo.jp [Experimental Radiobiology for Children' s Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2010-04-01

    Inactivation of the phosphatase and tensin homolog gene (Pten) occurs via multiple tissue-dependent mechanisms including epigenetic silencing, point mutations, insertions, and deletions. Although frequent loss of heterozygosity around the Pten locus and plausible involvement of epigenetic silencing have been reported in radiation-induced thymic lymphomas, the proportion of lymphomas with inactivated Pten and the spectrum of causal aberrations have not been extensively characterized. Here, we assessed the mode of Pten inactivation by comprehensive analysis of the expression and alteration of Pten in 23 radiation-induced thymic lymphomas developed in B6C3F1 mice. We found no evidence for methylation-associated silencing of Pten; rather, complex structural abnormalities comprised of missense and nonsense mutations, 1- and 3-bp insertions, and focal deletions were identified in 8 of 23 lymphomas (35%). Sequencing of deletion breakpoints suggested that aberrant V(D)J recombination and microhomology-mediated rearrangement were responsible for the focal deletions. Seven of the 8 lymphomas had biallelic alterations, and 4 of them did not express Pten protein. These Pten aberrations coincided with downstream Akt phosphorylation. In conclusion, we demonstrate that Pten inactivation is frequently biallelic and is caused by a variety of structural abnormalities (rather than by epigenetic silencing) and is involved in radiation-induced lymphomagenesis.

  1. Postoperative Radiation Therapy for Non-Small Cell Lung Cancer and Thymic Malignancies

    International Nuclear Information System (INIS)

    Gomez, Daniel R.; Komaki, Ritsuko

    2012-01-01

    For many thoracic malignancies, surgery, when feasible, is the preferred upfront modality for local control. However, adjuvant radiation plays an important role in minimizing the risk of locoregional recurrence. Tumors in the thoracic category include certain subgroups of non-small cell lung cancer (NSCLC) as well as thymic malignancies. The indications, radiation doses, and treatment fields vary amongst subtypes of thoracic tumors, as does the level of data supporting the use of radiation. For example, in the setting of NSCLC, postoperative radiation is typically reserved for close/positive margins or N2/N3 disease, although such diseases as superior sulcus tumors present unique cases in which the role of neoadjuvant vs. adjuvant treatment is still being elucidated. In contrast, for thymic malignancies, postoperative radiation therapy is often used for initially resected Masaoka stage III or higher disease, with its use for stage II disease remaining controversial. This review provides an overview of postoperative radiation therapy for thoracic tumors, with a separate focus on superior sulcus tumors and thymoma, including a discussion of acceptable radiation approaches and an assessment of the current controversies involved in its use

  2. Homeostatic properties and phenotypic maturation of murine CD4+ pre-thymic emigrants in the thymus.

    Directory of Open Access Journals (Sweden)

    Jie Dong

    Full Text Available After a tightly regulated developmental program in the thymus, "mature" single positive (SP thymocytes leave the thymus and enter the periphery. These newly arrived recent thymic emigrants (RTEs are phenotypically and functionally immature, and will complete a dynamic maturation in the peripheral lymphoid organs before being licensed to be resident naïve T cells. To study the early events occurring in the RTE maturation process, we identified the phenotype of CD4(+ pre-RTEs, a population of CD4(+ SP thymocytes that have acquired the thymus egress capability. Compared to peripheral naïve T cells, CD4(+ pre-RTEs displayed superior survival capability in lymphoreplete mice and faster proliferation under lymphopenic condition. The differences in Bcl2/Bim expression and/or heightened IL-7 signaling pathway may account for the pre-RTEs' better responsiveness to homeostatic signals. Qa2, the expression of which indicates the phenotypic maturation of SPs and RTEs, was found to be upregulated in CD4(+ pre-RTEs in thymic perivascular space. Migratory dendritic cells that surround this region contribute to Qa2 expression in pre-RTEs. The dendritic cell-driven Qa2 induction of CD4(+ pre-RTEs is independent of MHC class II and Aire molecules.

  3. Synergistic action of radiation and chemical carcinogen in induction of thymic lymphoma in mice

    International Nuclear Information System (INIS)

    Kajitani, Takashi; Kamiya, Kenji; Seyama, Toshio; Ito, Takaaki; Yokoro, Kenjiro

    1980-01-01

    Young adult C57BL/6 female mice were used to study the induction of leukemia by a combined treatment of x-rays and N-nitrosoethylurea (NEU). Administration of NEU after x-ray irradiation induced the leukemia in 100% with shortening latent period, which indicated that the combined treatment enhanced the leukemia induction. Thymic localized X-irradiation decreased the leukemia induction ratio from 100 to 55% and prolonged the latent period from 86 days to 128 days, compared with the whole body irradiation. For whole body irradiation, thymus weights, cell counts, rates of DNA-synthesizing cells, and rates, of mitotic index were decreased markedly after irradiation. For thymus weights and cell counts minimum values were observed after 3 days, and recovered by 10 days. DNA-synthesizing cells and the rates of mitotic index began to increase from the minimum value at the first day to the maximum value at the 5th day after irradiation. By thymic localized irradiation, no marked damage nor recovering process could be followed. It was suggested that the administration of NEU after irradiation, especially, to the young recovering cells with high potential for proliferation derived the high induction rate of leukemia. (Nakanishi, T.)

  4. Hematological alterations and thymic function in newborns of HIV-infected mothers receiving antiretroviral drugs.

    Science.gov (United States)

    Wongnoi, Rotjanee; Penvieng, Nawaporn; Singboottra, Panthong; Kingkeow, Doungnapa; Oberdorfer, Peninnah; Sirivatanapa, Pannee; Pornprasert, Sakorn

    2013-06-08

    To investigate the effects of antiretroviral (ARV) drugs on hematological parameters and thymic function in HIV-uninfected newborns of HIV-infected mothers. Cross sectional study. Chiang-Mai University Hospital, Chiang-Mai, Thailand. 49 HIV-uninfected and 26 HIV-infected pregnancies. Cord blood samples of newborns from HIV-uninfected and HIV-infected mothers were collected. Hematological parameters were measured using automatic blood cell count. T-cell receptor excision circles (TRECs) levels in cord blood mononuclear cells (CBMCs), CD4+ and CD8+ T-cells were quantified using real-time PCR.. Hemotological parameters and thymic function. Newborn of HIV-infected mother tended to have lower mean levels of hemoglobin than those of HIV-uninfected mother (137 ±22 vs 146 ±17 g/L, P = 0.05). Furthermore, mean of red blood cell (RBC) counts and hematocrit and median of TRECs in CD4+ T-cells in the newborns of the former were significantly lower than those of the latter [3.6 ±0.7 vs 4.8 ±0.6 x 1012 cells/L, P cells) in HIV-uninfected newborns of HIV-infected mothers.

  5. S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling

    Science.gov (United States)

    Kumar, Ashok; Zamora-Pineda, Jesus; Degagné, Emilie

    2017-01-01

    Sphingosine-1-phosphate (S1P) is a potent lipid signaling molecule that regulates pleiotropic biological functions including cell migration, survival, angiogenesis, immune cell trafficking, inflammation, and carcinogenesis. It acts as a ligand for a family of cell surface receptors. S1P concentrations are high in blood and lymph but low in tissues, especially the thymus and lymphoid organs. S1P chemotactic gradients are essential for lymphocyte egress and other aspects of physiological cell trafficking. S1P is irreversibly degraded by S1P lyase (SPL). SPL regulates lymphocyte trafficking, inflammation and other physiological and pathological processes. For example, SPL located in thymic dendritic cells acts as a metabolic gatekeeper that controls the normal egress of mature T lymphocytes from the thymus into the circulation, whereas SPL deficiency in gut epithelial cells promotes colitis and colitis-associated carcinogenesis (CAC). Recently, we identified a complex syndrome comprised of nephrosis, adrenal insufficiency, and immunological defects caused by inherited mutations in human SGPL1, the gene encoding SPL. In the present article, we review current evidence supporting the role of SPL in thymic egress, inflammation, and cancer. Lastly, we summarize recent progress in understanding other SPL functions, its role in inherited disease, and SPL targeting for therapeutic purposes. PMID:29333002

  6. Thymic lesions and myasthenia gravis. Diagnosis based on mediastinal imaging and pathological findings

    Energy Technology Data Exchange (ETDEWEB)

    Pirronti, T.; Rinaldi, P.; Marano, P. [Univ. Cattolica del S. Cuore, Roma (Italy). Inst. of Radiology; Batocchi, A.P.; Evoli, A.; Di Schino, C. [Univ. Cattolica del S. Cuore, Roma (Italy). Inst. of Neurology

    2002-07-01

    Purpose: To achieve a better understanding of the role of CT and MR imaging in the study of the mediastinum in patients with myasthenia gravis (MG). Material and Methods: Mediastinal CT and MR findings were correlated with the histopathological results in 104 thymectomized MG patients. Results: CT was performed in 104 patients; in 11 of them, MR was also carried out. 44 patients had hyperplasia at histology. On CT, thymic hyperplasia was confirmed in 16 cases, thymoma was diagnosed in 10 and a normal thymus in 18 (sensitivity 36%, specificity 95%). Of 52 patients with thymoma at histology, CT showed thymoma in 46, hyperplasia in 1, and normal thymus in 5. CT showed 88.5% sensitivity and 77% specificity for thymoma. In 10 patients with invasive thymoma, CT was indiscriminate, while invasiveness was detected in 7 cases at MR (70% sensitivity) and at CT in 1 case. Both CT and MR detected tumor recurrence in 5 cases, but the exact localization and degree of invasion were best defined by MR. Conclusion: In MG patients CT is a sensitive, specific and efficient modality for detecting thymoma, but is less so for detecting thymic hyperplasia. MR was shown to be accurate in detecting invasive thymoma both preoperatively and in postoperative follow-up.

  7. S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling

    Directory of Open Access Journals (Sweden)

    Ashok Kumar

    2017-01-01

    Full Text Available Sphingosine-1-phosphate (S1P is a potent lipid signaling molecule that regulates pleiotropic biological functions including cell migration, survival, angiogenesis, immune cell trafficking, inflammation, and carcinogenesis. It acts as a ligand for a family of cell surface receptors. S1P concentrations are high in blood and lymph but low in tissues, especially the thymus and lymphoid organs. S1P chemotactic gradients are essential for lymphocyte egress and other aspects of physiological cell trafficking. S1P is irreversibly degraded by S1P lyase (SPL. SPL regulates lymphocyte trafficking, inflammation and other physiological and pathological processes. For example, SPL located in thymic dendritic cells acts as a metabolic gatekeeper that controls the normal egress of mature T lymphocytes from the thymus into the circulation, whereas SPL deficiency in gut epithelial cells promotes colitis and colitis-associated carcinogenesis (CAC. Recently, we identified a complex syndrome comprised of nephrosis, adrenal insufficiency, and immunological defects caused by inherited mutations in human SGPL1, the gene encoding SPL. In the present article, we review current evidence supporting the role of SPL in thymic egress, inflammation, and cancer. Lastly, we summarize recent progress in understanding other SPL functions, its role in inherited disease, and SPL targeting for therapeutic purposes.

  8. Protective role of the apolipoprotein E2 allele in age-related disease traits and survival

    DEFF Research Database (Denmark)

    Kulminski, Alexander M; Raghavachari, Nalini; Arbeev, Konstantin G

    2016-01-01

    , which can link this allele with age-related phenotypes. We focused on age-related macular degeneration, bronchitis, asthma, pneumonia, stroke, creatinine, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, diseases of heart (HD), cancer, and survival. Our analysis......-related mechanism is also sensitive to gender. The LDL-C-related mechanism appears to be independent of these factors. Insights into mechanisms linking ε2 allele with age-related phenotypes given biodemographic structure of the population studied may benefit translation of genetic discoveries to health care...

  9. Histogram analysis of apparent diffusion coefficient maps for assessing thymic epithelial tumours: correlation with world health organization classification and clinical staging.

    Science.gov (United States)

    Kong, Ling-Yan; Zhang, Wei; Zhou, Yue; Xu, Hai; Shi, Hai-Bin; Feng, Qing; Xu, Xiao-Quan; Yu, Tong-Fu

    2018-04-01

    To investigate the value of apparent diffusion coefficients (ADCs) histogram analysis for assessing World Health Organization (WHO) pathological classification and Masaoka clinical stages of thymic epithelial tumours. 37 patients with histologically confirmed thymic epithelial tumours were enrolled. ADC measurements were performed using hot-spot ROI (ADC HS-ROI ) and histogram-based approach. ADC histogram parameters included mean ADC (ADC mean ), median ADC (ADC median ), 10 and 90 percentile of ADC (ADC 10 and ADC 90 ), kurtosis and skewness. One-way ANOVA, independent-sample t-test, and receiver operating characteristic were used for statistical analyses. There were significant differences in ADC mean , ADC median , ADC 10 , ADC 90 and ADC HS-ROI among low-risk thymoma (type A, AB, B1; n = 14), high-risk thymoma (type B2, B3; n = 9) and thymic carcinoma (type C, n = 14) groups (all p-values histogram analysis may assist in assessing the WHO pathological classification and Masaoka clinical stages of thymic epithelial tumours. Advances in knowledge: 1. ADC histogram analysis could help to assess WHO pathological classification of thymic epithelial tumours. 2. ADC histogram analysis could help to evaluate Masaoka clinical stages of thymic epithelial tumours. 3. ADC 10 might be a promising imaging biomarker for assessing and characterizing thymic epithelial tumours.

  10. Effects of marrow grafting on preleukemia cells and thymic nurse cells in C57BL/Ka mice after a leukemogenic split-dose irradiation

    International Nuclear Information System (INIS)

    Defresne, M.P.; Greimers, R.; Lenaerts, P.; Boniver, J.

    1986-01-01

    A split-dose regimen of whole-body irradiation (4 X 175 rad at weekly intervals) induced thymic lymphomas in C57BL/Ka mice after a latent period of 3-9 months. Meanwhile, preleukemia cells arose in the thymus and bone marrow and persisted until the onset of lymphomas. Simultaneously, thymic lymphopoiesis was impaired; thymocyte numbers were subnormal and thymic nurse cells disappeared in a progressive but irreversible fashion. The depletion of these lymphoepithelial complexes, which are normally involved in the early steps of thymic lymphopoiesis, was related to altered prothymocyte activity in bone marrow and to damaged thymic microenvironment, perhaps as a consequence of the presence of preleukemia cells. The grafting of normal bone marrow cells after irradiation prevented the development of lymphomas. However, marrow reconstitution did not inhibit the induction of preleukemia cells. They disappeared from the thymus during the second part of the latent period. At the same time, thymic lymphopoiesis was restored; thymocytes and nurse cell numbers returned to normal as a consequence of the proliferation of grafted marrow-derived cells within the thymus. The results thus demonstrated an intimate relationship between preleukemia cells and an alteration of thymic lymphopoiesis, which particularly involved the nurse cell microenvironment. Some preleukemia cells in marrow-reconstituted, irradiated mice derived from the unirradiated marrow inoculate. Thus these cells acquired neoplastic potential through a factor present in the irradiated tissues. The nature of this indirect mechanism was briefly discussed

  11. Age-Associated Decline in Thymic B Cell Expression of Aire and Aire-Dependent Self-Antigens

    Directory of Open Access Journals (Sweden)

    Sergio Cepeda

    2018-01-01

    Full Text Available Although autoimmune disorders are a significant source of morbidity and mortality in older individuals, the mechanisms governing age-associated increases in susceptibility remain incompletely understood. Central T cell tolerance is mediated through presentation of self-antigens by cells constituting the thymic microenvironment, including epithelial cells, dendritic cells, and B cells. Medullary thymic epithelial cells (mTECs and B cells express distinct cohorts of self-antigens, including tissue-restricted self-antigens (TRAs, such that developing T cells are tolerized to antigens from peripheral tissues. We find that expression of the TRA transcriptional regulator Aire, as well as Aire-dependent genes, declines with age in thymic B cells in mice and humans and that cell-intrinsic and cell-extrinsic mechanisms contribute to the diminished capacity of peripheral B cells to express Aire within the thymus. Our findings indicate that aging may diminish the ability of thymic B cells to tolerize T cells, revealing a potential mechanistic link between aging and autoimmunity.

  12. Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic and conventional splenic NK cells

    Science.gov (United States)

    Sojka, Dorothy K; Plougastel-Douglas, Beatrice; Yang, Liping; Pak-Wittel, Melissa A; Artyomov, Maxim N; Ivanova, Yulia; Zhong, Chao; Chase, Julie M; Rothman, Paul B; Yu, Jenny; Riley, Joan K; Zhu, Jinfang; Tian, Zhigang; Yokoyama, Wayne M

    2014-01-01

    Natural killer (NK) cells belong to the innate immune system; they can control virus infections and developing tumors by cytotoxicity and producing inflammatory cytokines. Most studies of mouse NK cells, however, have focused on conventional NK (cNK) cells in the spleen. Recently, we described two populations of liver NK cells, tissue-resident NK (trNK) cells and those resembling splenic cNK cells. However, their lineage relationship was unclear; trNK cells could be developing cNK cells, related to thymic NK cells, or a lineage distinct from both cNK and thymic NK cells. Herein we used detailed transcriptomic, flow cytometric, and functional analysis and transcription factor-deficient mice to determine that liver trNK cells form a distinct lineage from cNK and thymic NK cells. Taken together with analysis of trNK cells in other tissues, there are at least four distinct lineages of NK cells: cNK, thymic, liver (and skin) trNK, and uterine trNK cells. DOI: http://dx.doi.org/10.7554/eLife.01659.001 PMID:24714492

  13. Osseous oligometastases from thymic carcinoma: a case report suggesting the effectiveness of palliative-intent radiotherapy treatment

    Directory of Open Access Journals (Sweden)

    Kashima J

    2016-02-01

    Full Text Available Jumpei Kashima,1 Hirotoshi Horio,1 Yusuke Okuma,1,2 Yukio Hosomi,1 Tsunekazu Hishima3 1Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan; 2Division of Oncology, Research Center for Medical Sciences, Jikei University School of Medicine, Tokyo, Japan; 3Department of Pathology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan Background: Oligometastasis, a recently proposed concept, is defined as an intermediate state of cancer, between localized and systemic disease, that may be well controlled by local ablative treatment. Thymic carcinoma is a rare cancer with a poor prognosis. A definitive management approach has yet to be confirmed by a high level of evidence.Case presentation: We present the case of a 41-year-old female who underwent curative-intent surgery for a stage III squamous cell carcinoma of the thymus. Bone metastases were detected 1 year later by magnetic resonance imaging. These were treated with palliative-intent radiotherapy. Disease progression has not been observed in more than 15 years since the achievement of complete radiological remission.Conclusion: The treatment outcomes in this and other reported cases suggest that some patients with oligometastatic thymic carcinoma may achieve prolonged survival or even cure with low-dose radiotherapy delivered to the metastases. Keywords: oligometastasis, thymic carcinoma, thymic epithelial tumor, bone metastasis

  14. Intrathymic radioresistant stem cells follow an IL-2/IL-2R pathway during thymic regeneration after sublethal irradiation

    International Nuclear Information System (INIS)

    Zuniga-Pfluecker, J.C.K.; Kruisbeek, A.M.

    1990-01-01

    Sublethally irradiated mice undergo thymic regeneration which follows a phenotypic pattern of events similar to that observed during normal fetal development. Thymic regeneration after irradiation is the product of a limited pool of intrathymic radioresistant stem cells undergoing simultaneous differentiation. We show that in this model of T cell development, thymic regeneration follows a pathway in which the IL-2R is transiently expressed on CD4-/CD8- cells. IL-2R expression occurred during the exponential growth period of thymic regeneration, and IL-2R blocking prevented this explosive growth. Flow cytometry analysis revealed that the IL-2R blockade affected primarily the development of the immature CD3-/CD4-/CD8- (triple negative) cells and their ability to generate CD3+/CD4+/CD8+ or CD3+/CD4+/CD8- and CD3+/CD4-/CD8+ thymocytes. Thus, our findings demonstrate that blocking of the IL-2R resulted in an arrest in proliferation and differentiation by intrathymic radioresistant stem cells, indicating that the IL-2/IL-2R pathway is necessary for the expansion of immature triple negative T cells

  15. In vitro evidence for participation of DEC-205 expressed by thymic cortical epithelial cells in clearance of apoptotic thymocytes.

    NARCIS (Netherlands)

    Small, M; Kraal, G.

    2003-01-01

    Binding of apoptotic cells was compared after incubation of thymocytes with two clones of murine thymic stromal cells to which CD4(+)/CD8(+) thymocytes attach. With the BA/10, but not the BA/2, clone, thymocytes with apoptotic morphology were bound irreversibly. These tightly bound thymocytes were

  16. A False Positive I-131 Metastatic Survey Caused by Radioactive Iodine Uptake by a Benign Thymic Cyst

    Directory of Open Access Journals (Sweden)

    Avneet K. Singh

    2017-01-01

    Full Text Available Thyroid carcinoma is the most common endocrine malignancy in the United States with increasing incidence and diagnosis but stable mortality. Differentiated thyroid cancer rarely presents with distant metastases and is associated with a low risk of morbidity and mortality. Despite this, current protocols recommend remnant ablation with radioactive iodine and evaluation for local and distant metastasis in some patients with higher risk disease. There are several case reports of false positive results of metastatic surveys that are either normal physiologic variants or other pathological findings. Most false positive findings are associated with tissue that has physiologic increased uptake of I-131, such as breast tissue or lung tissue; pathological findings such as thymic cysts are also known to have increased uptake. Our case describes a rare finding of a thymic cyst found on a false positive I-131 metastatic survey. The patient was taken for surgical excision and the final pathology was a benign thymic cyst. Given that pulmonary metastases of differentiated thyroid cancer are rare, thymic cysts, though also rare, must be part of the differential diagnosis for false positive findings on an I-131 survey.

  17. Examining Age-Related Differences in Auditory Attention Control Using a Task-Switching Procedure

    OpenAIRE

    Vera Lawo; Iring Koch

    2014-01-01

    Objectives. Using a novel task-switching variant of dichotic selective listening, we examined age-related differences in the ability to intentionally switch auditory attention between 2 speakers defined by their sex.

  18. Cataract surgery in patients with neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Kessel, Line; Theil, Pernille Koefoed; Sørensen, Torben Lykke

    2016-01-01

    Purpose To examine the outcome after cataract surgery in patients with neovascular age-related macular degeneration (AMD) treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections in routine clinical practice. Methods We extracted information about patients recorded...

  19. Public opinion on age-related degradation in nuclear power plants

    International Nuclear Information System (INIS)

    Matsuda, Toshihiro

    2005-01-01

    The first objective of this study is to shed light on the public opinion on age-related degradation at nuclear power plants, namely, on how the general public recognizes or views age-related degradation, which is a safety-related issue and one of the factors contributing to accidents and failures which occur at nuclear power plants. The second objective is to look into the impacts of the accident at Mihama Unit 3, which was caused by a failure to check on the piping wall thickness, on the public opinion on age-related degradation. The first survey was conducted in August 2003, followed by the second survey in October 2004, two months after the accident. The surveys found that the age-related degradation is being perceived by people as one of the risk factors that affect the safety of nuclear power plants. The characteristics of the citizens' perceptions toward age-related degradation in the form of piping cracks are that: (a) many respondents feel uneasy but a relatively few people consider that nuclear operators are technologically capable of coping with this problem; (b) many people believe that radioactivity may be released; and (c) numerous respondents consider that signs of cracks must be thoroughly detected through inspections, while on the other hand, a large percentage of the respondents attribute the accident to improper inspections/maintenance. Based on these results, the government and nuclear operators are expected to give most illuminating explanation on the current situation of and remedial measures against age-related degradation at nuclear power plants. As for the effects of the Mihama-3 accident on the public opinion on age-related degradation, it was revealed that the accident has not so significantly affected the general view for the safety of nuclear power plants, but has newly or strongly aroused people's consciousness of two of the risk factors - improper inspections/maintenance and the age-related degradation of piping. (author)

  20. Self-reported optometric practise patterns in age-related macular degeneration.

    Science.gov (United States)

    Ly, Angelica; Nivison-Smith, Lisa; Zangerl, Barbara; Assaad, Nagi; Kalloniatis, Michael

    2017-11-01

    The use of advanced imaging in clinical practice is emerging and the use of this technology by optometrists in assessing patients with age-related macular degeneration is of interest. Therefore, this study explored contemporary, self-reported patterns of practice regarding age-related macular degeneration diagnosis and management using a cross-sectional survey of optometrists in Australia and New Zealand. Practising optometrists were surveyed on four key areas, namely, demographics, clinical skills and experience, assessment and management of age-related macular degeneration. Questions pertaining to self-rated competency, knowledge and attitudes used a five-point Likert scale. Completed responses were received from 127 and 87 practising optometrists in Australia and New Zealand, respectively. Advanced imaging showed greater variation in service delivery than traditional techniques (such as slitlamp funduscopy) and trended toward optical coherence tomography, which was routinely performed in age-related macular degeneration by 49 per cent of respondents. Optical coherence tomography was also associated with higher self-rated competency, knowledge and perceived relevance to practice than other modalities. Most respondents (93 per cent) indicated that they regularly applied patient symptoms, case history, visual function results and signs from traditional testing, when queried about their management of patients with age-related macular degeneration. Over half (63 per cent) also considered advanced imaging, while 31 per cent additionally considered all of these as well as the disease stage and clinical guidelines. Contrary to the evidence base, 68 and 34 per cent rated nutritional supplements as highly relevant or relevant in early age-related macular degeneration and normal aging changes, respectively. These results highlight the emergence of multimodal and advanced imaging (especially optical coherence tomography) in the assessment of age-related macular degeneration

  1. Incidence of legal blindness from age-related macular degeneration in denmark: year 2000 to 2010

    DEFF Research Database (Denmark)

    Bloch, Sara Brandi; Larsen, Michael; Munch, Inger Christine

    2012-01-01

    To report incidence rates of legal blindness from age-related macular degeneration (AMD) and other causes in Denmark from years 2000 to 2010 in the age group at risk of AMD aged 50 years and older.......To report incidence rates of legal blindness from age-related macular degeneration (AMD) and other causes in Denmark from years 2000 to 2010 in the age group at risk of AMD aged 50 years and older....

  2. Multiple Brain Markers are Linked to Age-Related Variation in Cognition

    Science.gov (United States)

    Hedden, Trey; Schultz, Aaron P.; Rieckmann, Anna; Mormino, Elizabeth C.; Johnson, Keith A.; Sperling, Reisa A.; Buckner, Randy L.

    2016-01-01

    Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65–90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70–80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health. PMID:25316342

  3. The Digital Ageing Atlas: integrating the diversity of age-related changes into a unified resource.

    Science.gov (United States)

    Craig, Thomas; Smelick, Chris; Tacutu, Robi; Wuttke, Daniel; Wood, Shona H; Stanley, Henry; Janssens, Georges; Savitskaya, Ekaterina; Moskalev, Alexey; Arking, Robert; de Magalhães, João Pedro

    2015-01-01

    Multiple studies characterizing the human ageing phenotype have been conducted for decades. However, there is no centralized resource in which data on multiple age-related changes are collated. Currently, researchers must consult several sources, including primary publications, in order to obtain age-related data at various levels. To address this and facilitate integrative, system-level studies of ageing we developed the Digital Ageing Atlas (DAA). The DAA is a one-stop collection of human age-related data covering different biological levels (molecular, cellular, physiological, psychological and pathological) that is freely available online (http://ageing-map.org/). Each of the >3000 age-related changes is associated with a specific tissue and has its own page displaying a variety of information, including at least one reference. Age-related changes can also be linked to each other in hierarchical trees to represent different types of relationships. In addition, we developed an intuitive and user-friendly interface that allows searching, browsing and retrieving information in an integrated and interactive fashion. Overall, the DAA offers a new approach to systemizing ageing resources, providing a manually-curated and readily accessible source of age-related changes. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. Age-related changes in the macula. A histopathological study of fifty Indian donor eyes.

    Science.gov (United States)

    Biswas, Jyotirmay; Raman, Rajiv

    2002-09-01

    Age-related macular degeneration (ARMD) is clinically less common in India compared to the West. Therefore, clinicians are unfamiliar with histopathologic evidence of age-related macular changes in the Indian population. Fifty consecutive human donor eyes removed for corneal grafting were studied for gross, microscopic and histochemical features of age-related changes in the macula in the Indian population. A horizontal block was cut from the globe including the optic disc, and the macula. Six sections, 6 microns thick, were cut from three levels in the macula at a distance of 140 microns. These were stained with haemotoxylin-eosin, periodic acid-Schiff, Mallory, Masson trichrome, alcian blue and von Kossa stains. The presence of basal laminar deposits, drusen and thickening and calcification of Bruch's membrane in the macula were assessed at 400 x magnification using a modified version of Sark's classification. Twenty-four donor eyes (48%) had some form of age-related macular change. These included basal laminar deposits, hard drusen, soft drusen, extensive retinal pigment epithelium atrophy of the macula, and disciform degeneration of macula. A combination of changes was often seen. Age-related changes were more common in the seventh and eighth decade. Our study shows that histological changes characteristic of the early stages of age-related macular degeneration are fairly common in the Indian population. However, advanced macular changes are significantly rare.

  5. Age-related changes in the macula. A histopathological study of fifty Indian donor eyes

    Directory of Open Access Journals (Sweden)

    Biswas Jyotirmay

    2002-01-01

    Full Text Available PURPOSE: Age-related macular degeneration (ARMD is clinically less common in India compared to the West. Therefore, clinicians are unfamiliar with histopathologic evidence of age-related macular changes in the Indian population. METHODS: Fifty consecutive human donor eyes removed for corneal grafting were studied for gross, microscopic and histochemical features of age-related changes in the macula in the Indian population. A horizontal block was cut from the globe including the optic disc, and the macula. Six sections, 6 microns thick, were cut from three levels in the macula at a distance of 140 microns. These were stained with haemotoxylin-eosin, periodic acid-Schiff, Mallory, Masson trichrome, alcian blue and von Kossa stains. The presence of basal laminar deposits, drusen and thickening and calcification of Bruch′s membrane in the macula were assessed at 400 x magnification using a modified version of Sark′s classification. RESULTS: Twenty-four donor eyes (48% had some form of age-related macular change. These included basal laminar deposits, hard drusen, soft drusen, extensive retinal pigment epithelium atrophy of the macula, and disciform degeneration of macula. A combination of changes was often seen. Age-related changes were more common in the seventh and eighth decade. CONCLUSION: Our study shows that histological changes characteristic of the early stages of age-related macular degeneration are fairly common in the Indian population. However, advanced macular changes are significantly rare.

  6. Association of age-related macular degeneration and reticular macular disease with cardiovascular disease.

    Science.gov (United States)

    Rastogi, Neelesh; Smith, R Theodore

    2016-01-01

    Age-related macular degeneration is the leading cause of adult blindness in the developed world. Thus, major endeavors to understand the risk factors and pathogenesis of this disease have been undertaken. Reticular macular disease is a proposed subtype of age-related macular degeneration correlating histologically with subretinal drusenoid deposits located between the retinal pigment epithelium and the inner segment ellipsoid zone. Reticular lesions are more prevalent in females and in older age groups and are associated with a higher mortality rate. Risk factors for developing age-related macular degeneration include hypertension, smoking, and angina. Several genes related to increased risk for age-related macular degeneration and reticular macular disease are also associated with cardiovascular disease. Better understanding of the clinical and genetic risk factors for age-related macular degeneration and reticular macular disease has led to the hypothesis that these eye diseases are systemic. A systemic origin may help to explain why reticular disease is diagnosed more frequently in females as males suffer cardiovascular mortality at an earlier age, before the age of diagnosis of reticular macular disease and age-related macular degeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. [Age-related macular degeneration as a local manifestation of atherosclerosis - a novel insight into pathogenesis].

    Science.gov (United States)

    Machalińska, Anna

    2013-01-01

    Age-related macular degeneration is the leading cause of irreversible visual impairment and disability among the elderly in developed countries. There is compelling evidence that atherosclerosis and age-related macular degeneration share a similar pathogenic process. The association between atherosclerosis and age-related macular degeneration has been inferred from histological, biochemical and epidemiological studies. Many published data indicate that drusen are similar in molecular composition to plaques in atherosclerosis. Furthermore, a great body of evidence has emerged over the past decade that implicates the chronic inflammatory processes in the pathogenesis and progression of both disorders. We speculate that vascular atherosclerosis and age-related macular degeneration may represent different manifestations of the same disease induced by a pathologic tissue response to the damage caused by oxidative stress and local ischemia. In this review, we characterise in detail a strong association between age-related macular degeneration and atherosclerosis development, and we postulate the hypothesis that age-related macular degeneration is a local manifestation of a systemic disease. This provides a new approach for understanding the aspects of pathogenesis and might improve the prevention and treatment of both diseases which both result from ageing of the human body.

  8. Antagonistic pleiotropy and mutation accumulation contribute to age-related decline in stress response.

    Science.gov (United States)

    Everman, Elizabeth R; Morgan, Theodore J

    2018-02-01

    As organisms age, the effectiveness of natural selection weakens, leading to age-related decline in fitness-related traits. The evolution of age-related changes associated with senescence is likely influenced by mutation accumulation (MA) and antagonistic pleiotropy (AP). MA predicts that age-related decline in fitness components is driven by age-specific sets of alleles, nonnegative genetic correlations within trait across age, and an increase in the coefficient of genetic variance. AP predicts that age-related decline in a trait is driven by alleles with positive effects on fitness in young individuals and negative effects in old individuals, and is expected to lead to negative genetic correlations within traits across age. We build on these predictions using an association mapping approach to investigate the change in additive effects of SNPs across age and among traits for multiple stress-response fitness-related traits, including cold stress with and without acclimation and starvation resistance. We found support for both MA and AP theories of aging in the age-related decline in stress tolerance. Our study demonstrates that the evolution of age-related decline in stress tolerance is driven by a combination of alleles that have age-specific additive effects, consistent with MA, as well as nonindependent and antagonistic genetic architectures characteristic of AP. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  9. Different mechanisms for the resistance of C3H and STS strain mice to the development of thymic lymphomas following fractionated whole-body irradiation

    International Nuclear Information System (INIS)

    Aizawa, Shiro; Kamisaku, Hitoko

    1999-01-01

    B10 strain mice are extremely susceptible for induction of thymic lymphomas by fractionated whole-body irradiation (FI), whereas C3H and STS mice are fairly resistant. In the present study, we constructed radiation bone marrow chimeras in the reciprocal donor-host combinations of susceptible and resistant mice with use of Thy1 markers that allow to determine genetic origins of donor- and host-type thymocytes, and then to analyze the influence of host/thymic environment on the strain-dependent susceptibility to thymic lymphomagenesis. B10.Thy1.1→C3H, B10.Thy1.1→STS as well as B10.Thy1.1→B10 bone marrow chimeras manifested a high incidence of thymic lymphomas after FI-treatment, whereas C3H. Thy1.1→B10 and STS→B10 as well as C3H→C3H and STS→STS chimeras manifested a low incidence of thymic lymphoma. Furthermore, FI-treatment of [B10.Thy1.1+C3H]→B10 mixed chimeras resulted in the generation of similar numbers of thymic lymphomas of B10 and C3H origins, whereas FI-treatment of [B10.Thy1.1+STS]→B10 mixed chimeras preferentially induced thymic lymphomas of B10 origin. These results indicated that host environments of C3H and STS resistant mice are not inhibitory for the development of thymic lymphomas, genetic factors responsible for the strain-dependent susceptibility and/or resistance to FI-induced lymphomagenesis exert their effects entirely on bone-marrow derived cells, and the resistance of STS mice to FI-induced thymic lymphomagenesis is an intrinsic property of thymocytes as the targets of thymic lymphoma induction, whereas bone marrow-derived thymic stroma cells seem to play a significant role in the resistance of C3H mice for the induction of thymic lymphomas. (author)

  10. HLA-B*39:06 Efficiently Mediates Type 1 Diabetes in a Mouse Model Incorporating Reduced Thymic Insulin Expression.

    Science.gov (United States)

    Schloss, Jennifer; Ali, Riyasat; Racine, Jeremy J; Chapman, Harold D; Serreze, David V; DiLorenzo, Teresa P

    2018-04-09

    Type 1 diabetes (T1D) is characterized by T cell-mediated destruction of the insulin-producing β cells of the pancreatic islets. Among the loci associated with T1D risk, those most predisposing are found in the MHC region. HLA-B*39:06 is the most predisposing class I MHC allele and is associated with an early age of onset. To establish an NOD mouse model for the study of HLA-B*39:06, we expressed it in the absence of murine class I MHC. HLA-B*39:06 was able to mediate the development of CD8 T cells, support lymphocytic infiltration of the islets, and confer T1D susceptibility. Because reduced thymic insulin expression is associated with impaired immunological tolerance to insulin and increased T1D risk in patients, we incorporated this in our model as well, finding that HLA-B*39:06-transgenic NOD mice with reduced thymic insulin expression have an earlier age of disease onset and a higher overall prevalence as compared with littermates with typical thymic insulin expression. This was despite virtually indistinguishable blood insulin levels, T cell subset percentages, and TCR Vβ family usage, confirming that reduced thymic insulin expression does not impact T cell development on a global scale. Rather, it will facilitate the thymic escape of insulin-reactive HLA-B*39:06-restricted T cells, which participate in β cell destruction. We also found that in mice expressing either HLA-B*39:06 or HLA-A*02:01 in the absence of murine class I MHC, HLA transgene identity alters TCR Vβ usage by CD8 T cells, demonstrating that some TCR Vβ families have a preference for particular class I MHC alleles. Copyright © 2018 by The American Association of Immunologists, Inc.

  11. Thymic lymphocytes. III. Cooperative phenomenon in the proliferation of thymocytes under Con A stimulation.

    Science.gov (United States)

    Papiernik, M; Jacobson, J B

    1986-01-01

    In the present paper, the response of thymocytes to Con A is analyzed in terms of a cooperative phenomenon between medullary thymocytes, cortical thymocytes, thymic accessory cells, and interleukin 2. Medullary thymocytes respond spontaneously to Con A and produce IL-2. The addition of exogenously produced IL-2 enhances their proliferation. Small numbers of cortical (PNA+) thymocytes do not respond to Con A, even in the presence of IL-2-containing supernatant. By increasing the number of PNA+ cells per well, sensitivity to Con A and IL-2 appears. This response may be linked either to the increase in a minor PNA+-responding population and/or to the enhanced contamination by medullary thymocytes and macrophages in non-responding PNA+ thymocyte population. In this hypothesis, either the contaminating cells respond by themselves and/or cooperate with PNA+ cells to induce their proliferation. Coculture of non-responding low numbers of PNA+ thymocytes with Con A- and IL-2-containing supernatant in the presence of PNA- cells containing thymic medullary thymocytes and macrophages always produces a higher response than that of each individual population. These results show that a cooperative phenomenon occurs in the cocultures of PNA+ and PNA- thymic cells. We can show using PNA+ and PNA- thymocytes with different Thy 1 alleles, that indeed both PNA+ and populations participate PNA-thymocytes with different Thy 1 alleles, that indeed both PNA+ and PNA- populations participate in the generation of proliferating cells. We can demonstrate, by lysis experiments with monoclonal antibodies and complement that at the end of coculture, most of the proliferating cells are Lyt 1+, and part are Lyt 2+ or L3T4+. We discuss the fact that the phenotype of the cells after activation does not allow us to deduce the phenotype of their precursors. Lysis of Ia+ cells prior to coculture, reduces the level of the proliferative response but does not modify the percentage of cooperation produced

  12. Different alpha crystallin expression in human age-related and congenital cataract lens epithelium.

    Science.gov (United States)

    Yang, Jing; Zhou, Sheng; Guo, Minfei; Li, Yuting; Gu, Jianjun

    2016-05-28

    The purpose of this study was to investigate the different expressions of αA-crystallin and αB-crystallin in human lens epithelium of age-related and congenital cataracts. The central part of the human anterior lens capsule approximately 5 mm in diameter together with the adhering epithelial cells, were harvested and processed within 6 hours after cataract surgery from age-related and congenital cataract patients or from normal eyes of fresh cadavers. The mRNA and soluble protein levels of αA-crystallin and αB-crystallin in the human lens epithelium were detected by real-time PCR and western blots, respectively. The mRNA and soluble protein expressions of αA-crystallin and αB-crystallin in the lens epithelium were both reduced in age-related and congenital cataract groups when compared with the normal control group. However, the degree of α-crystallin loss in the lens epithelium was highly correlated with different cataract types. The α-crystallin expression of the lens epithelium was greatly reduced in the congenital cataract group but only moderately decreased in the age-related cataract group. The reduction of αA-crystallin soluble protein levels in the congenital cataract group was approximately 2.4 fold decrease compared with that of the age-related cataract group, while an mRNA fold change of 1.67 decrease was observed for the age-related cataract group. Similarly, the reduction of soluble protein levels of αB-crystallin in the congenital cataract group was approximately a 1.57 fold change compared with that of the age-related cataract group. A 1.75 fold change for mRNA levels compared with that of the age-related cataract group was observed. The results suggest that the differential loss of α-crystallin in the human lens epithelium could be associated with the different mechanisms of cataractogenesis in age-related versus congenital cataracts, subsequently resulting in different clinical presentations.

  13. [Pharmacological therapy of age-related macular degeneration based on etiopathogenesis].

    Science.gov (United States)

    Fischer, Tamás

    2015-11-15

    It is of great therapeutic significance that disordered function of the vascular endothelium which supply the affected ocular structures plays a major role in the pathogenesis and development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfunction, and age-related macular degeneration is accompanied by a general inflammatory response. According to current concept, age-related macular degeneration is a local manifestation of systemic vascular disease. This recognition could have therapeutic implications because restoration of endothelial dysfunction can restabilize the condition of chronic vascular disease including age-related macular degeneration as well. Restoration of endothelial dysfunction by pharmaacological or non pharmacological interventions may prevent the development or improve endothelial dysfunction, which result in prevention or improvement of age related macular degeneration as well. Medicines including inhibitors of the renin-angiotensin system (converting enzyme inhibitors, angiotensin-receptor blockers and renin inhibitors), statins, acetylsalicylic acid, trimetazidin, third generation beta-blockers, peroxisome proliferator-activated receptor gamma agonists, folate, vitamin D, melatonin, advanced glycation end-product crosslink breaker alagebrium, endothelin-receptor antagonist bosentan, coenzyme Q10; "causal" antioxidant vitamins, N-acetyl-cysteine, resveratrol, L-arginine, serotonin receptor agonists, tumor necrosis factor-alpha blockers, specific inhibitor of the complement alternative pathway, curcumin and doxycyclin all have beneficial effects on endothelial dysfunction. Restoration of endothelial dysfunction can restabilize chronic vascular disease including age-related macular degeneration as well. Considering that the human vascular system is consubstantial, medicines listed above should be given to patients (1) who have no macular degeneration but have risk factors

  14. Unique loss of heterozygosity of murine thymic lymphomas as a candidate of radiation signature

    Energy Technology Data Exchange (ETDEWEB)

    Shimada, Yoshiya; Nishimura, Mayumi; Kakinuma, Shizuko [National Inst. of Radiological Sciences, Chiba (Japan); Wakana, Shigeharu; Okumoto, Masaaki

    1999-06-01

    Signature(s) of prior exposure to carcinogens have immediate application to the identification of environmental risk factors. Such signatures have been sought to aid in developing policies for the protection from risks of environmental carcinogens. Although ionizing radiation is a potent carcinogenic agent, little is known about possible radiation signatures. This is because radiation induces a broad spectrum of DNA lesions. Here we describe a diversity of K-ras mutations and a unique locus with frequent loss of heterozygisity (LOH) on chromosome 11 of radiation induced thymic lymphomas. The latter locus has never been observed to be similarly altered in either ethylnitrosourea-induced or spontaneously developed lymphomas. These results describe, to our knowledge for the first time, a molecular basis for radiation signature. (author)

  15. Gender Differences in Age-Related Striatal Dopamine Depletion in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Jae Jung Lee

    2015-09-01

    Full Text Available Objective Gender differences are a well-known clinical characteristic of Parkinson’s disease (PD. In-vivo imaging studies demonstrated that women have greater striatal dopamine transporter (DAT activity than do men, both in the normal population and in PD patients. We hypothesize that women exhibit more rapid aging-related striatal DAT reduction than do men, as the potential neuroprotective effect of estrogen wanes with age. Methods This study included 307 de novo PD patients (152 men and 155 women who underwent DAT scans for an initial diagnostic work-up. Gender differences in age-related DAT decline were assessed in striatal sub-regions using linear regression analysis. Results Female patients exhibited greater DAT activity compared with male patients in all striatal sub-regions. The linear regression analysis revealed that age-related DAT decline was greater in the anterior and posterior caudate, and the anterior putamen in women compared with men; we did not observe this difference in other sub-regions. Conclusions This study demonstrated the presence of gender differences in age-related DAT decline in striatal sub-regions, particularly in the antero-dorsal striatum, in patients with PD, presumably due to aging-related decrease in estrogen. Because this difference was not observed in the sensorimotor striatum, this finding also suggests that women may not have a greater capacity to tolerate PD pathogenesis than do men.

  16. The epigenetic landscape of age-related diseases: the geroscience perspective.

    Science.gov (United States)

    Gensous, Noémie; Bacalini, Maria Giulia; Pirazzini, Chiara; Marasco, Elena; Giuliani, Cristina; Ravaioli, Francesco; Mengozzi, Giacomo; Bertarelli, Claudia; Palmas, Maria Giustina; Franceschi, Claudio; Garagnani, Paolo

    2017-08-01

    In this review, we summarize current knowledge regarding the epigenetics of age-related diseases, focusing on those studies that have described DNA methylation landscape in cardio-vascular diseases, musculoskeletal function and frailty. We stress the importance of adopting the conceptual framework of "geroscience", which starts from the observation that advanced age is the major risk factor for several of these pathologies and aims at identifying the mechanistic links between aging and age-related diseases. DNA methylation undergoes a profound remodeling during aging, which includes global hypomethylation of the genome, hypermethylation at specific loci and an increase in inter-individual variation and in stochastic changes of DNA methylation values. These epigenetic modifications can be an important contributor to the development of age-related diseases, but our understanding on the complex relationship between the epigenetic signatures of aging and age-related disease is still poor. The most relevant results in this field come from the use of the so called "epigenetics clocks" in cohorts of subjects affected by age-related diseases. We report these studies in final section of this review.

  17. A Systematic Investigation into Aging Related Genes in Brain and Their Relationship with Alzheimer's Disease.

    Science.gov (United States)

    Meng, Guofeng; Zhong, Xiaoyan; Mei, Hongkang

    2016-01-01

    Aging, as a complex biological process, is accompanied by the accumulation of functional loses at different levels, which makes age to be the biggest risk factor to many neurological diseases. Even following decades of investigation, the process of aging is still far from being fully understood, especially at a systematic level. In this study, we identified aging related genes in brain by collecting the ones with sustained and consistent gene expression or DNA methylation changes in the aging process. Functional analysis with Gene Ontology to these genes suggested transcriptional regulators to be the most affected genes in the aging process. Transcription regulation analysis found some transcription factors, especially Specificity Protein 1 (SP1), to play important roles in regulating aging related gene expression. Module-based functional analysis indicated these genes to be associated with many well-known aging related pathways, supporting the validity of our approach to select aging related genes. Finally, we investigated the roles of aging related genes on Alzheimer's Disease (AD). We found that aging and AD related genes both involved some common pathways, which provided a possible explanation why aging made the brain more vulnerable to Alzheimer's Disease.

  18. [Vitreomacular adhesion in HD-OCT images in the age-related macular degeneration].

    Science.gov (United States)

    Latalska, Małgorzata; Swiech-Zubilewicz, Anna; Mackiewicz, Jerzy

    2013-01-01

    The aim of this study was to evaluate an incidence of the vitreomacular adhesion in patients with age-related macular degeneration. We examined 472 eyes in 241 patients (136 W/ 105 M) in age of 54-92 years (mean 62.6 years +/- 8.5) with dry or wet age-related macular degeneration using Cirrus HD-OCT (Zeiss) macular cube 512x128 program or 5-line pro-gram. Vitreomacular adhesion was observed in 139 eyes with dry age-related macular degeneration (29.4%, p=0.000*), in 101 eyes with drusen (21.4%, p=0.000*), in 38 eyes with retinal pigment epithelium alterations (8%, p=0.202), in 278 eyes with wet age-related macular degeneration (58.9%, p=0.001*), in 21 eyes with pigment epithelial detachment (4.4%, p=0.303), in 161 eyes with choroidal neovascularzation (34. 1%, p=0.031*/ and in 96 eyes with scar (20.4%, p=0.040*). Probably, vitreomacular adhesion alone is not able to induce age-related macular degeneration, but it may be associated with choroidal neovascularization development, it can contribute to exudate formation and choroidal neovascularization, it may induces or sustains a chronic low-grade inflammation in the macula region.

  19. New approaches and potential treatments for dry age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Francisco Max Damico

    2012-02-01

    Full Text Available Emerging treatments for dry age-related macular degeneration (AMD and geographi c atrophy focus on two strategies that target components involved in physiopathological pathways: prevention of photoreceptors and retinal pigment epithelium loss (neuroprotection induction, oxidative damage prevention, and visual cycle modification and suppression of inflammation. Neuroprotective drugs, such as ciliary neurotrophic factor, brimonidine tartrate, tandospirone, and anti-amyloid β antibodies, aim to prevent apoptosis of retinal cells. Oxidative stress and depletion of essential micronutrients are targeted by the Age-Related Eye Disease Study (AREDS formulation. Visual cycle modulators reduce the activity of the photoreceptors and retinal accumulation of toxic fluorophores and lipofuscin. Eyes with dry age-related macular degeneration present chronic inflammation and potential treatments include corticosteroid and complement inhibition. We review the current concepts and rationale of dry age-related macular degeneration treatment that will most likely include a combination of drugs targeting different pathways involved in the development and progression of age-related macular degeneration.

  20. Exploring the link between innate immune activation and thymic function by measuring sCD14 and TRECs in HIV patients living in Belgium.

    Directory of Open Access Journals (Sweden)

    Adrien De Voeght

    Full Text Available Microbial translocation is now viewed as a central event in the pathogenesis of chronic inflammation during HIV infection. Thymic function failure is another crucial factor involved in HIV disease progression. The goal of this study was to explore the hypothesis of potential links between microbial translocation and thymic function in HIV-1 patients living in Belgium. The extent of microbial translocation was assessed through the measurement of soluble CD14 (sCD14. T-cell receptor excision circles (sjTRECs and dβTRECs were used as a measure of thymic function. Data were collected from 75 HIV-infected patients. Simple and complex linear regressions were done to analyze the link between these two processes. We found a statistically relevant negative correlation between thymopoiesis (sjTREC and sCD14 level (p = 0.004. These results suggest a link between thymic function failure, microbial translocation and innate immune activation.

  1. The diagnosis of thymoma and thymic atrophy in patients with myasthenia gravis; Dignostikk av tymom og thymusatrofi hos pasienter med myasthenia gravis

    Energy Technology Data Exchange (ETDEWEB)

    Sund, K.K.; Skeie, G.O.; Gilhus, N.E.; Aarli, J.A.; Varhaug, J.E. [Haukeland Sykehus, Bergen (Norway)

    1997-11-01

    The authors have compared clinical, immunological and radiological data in 20 patients with myasthenia gravis and thymoma and in 21 patients with myasthenia gravis and thymic atrophy. The median age at onset was 54 years in the thymoma group and 63 years in the thymic atrophy group. The severity of the disease was similar in the two groups, and there was no significant difference in the concentration of acetylcholine receptor antibodies. CA antibodies were demonstrated in 17/20 thymoma patients and in 6/21 with thymic atrophy, while 19/20 thymoma patients had antibodies to titin, compared with 9/21 among those with thymic atrophy. The diagnosis and treatment of patients with myasthenia gravis is based upon an evaluation of clinical, immunological and radiological data. 28 refs., 2 tabs.

  2. Influence of age on the proliferation and peripheralization of thymic T cells

    International Nuclear Information System (INIS)

    Hirokawa, K.; Utsuyama, M.; Katsura, Y.; Sado, T.

    1988-01-01

    Bone marrow cells obtained from B10.Thy-1.1 mice (H-2b, Thy-1.1) were injected directly into the thymus of C57BL/6 mice (H-2b,Thy 1.2) of various ages. Thymocyte precursors in the injected donor-bone marrow cells could proliferate in the thymic microenvironment in the following manner: first, preferentially proliferating into the subcapsular cortex; and second, spreading to the whole layer of the cortex, a portion of them gradually moving into the medulla. The proliferation of donor-type thymocytes was most pronounced when intrathymic injection of bone marrow cells (ITB) was performed in newborn mice and especially prominent in week-old mice; it took approximately ten weeks for donor-type thymocytes to finish the whole course of proliferation, differentiation, and emigration to the periphery. When ITB was performed in mice 4 weeks of age and older, the proliferation of donor-type thymocytes was retarded at onset, less pronounced in magnitude, and disappeared earlier. Emigration of donor-type T cells from the thymus to the peripheral lymphoid tissues occurred most rapidly when ITB was performed in newborn mice, and these T cells continued to reside thereafter in the peripheral lymphoid tissues. However, when ITB was performed in mice 4 weeks of age and older, the number of emigrated T cells in the spleen decreased (about a tenth of that in newborn mice) and, moreover, these T cells resided only transiently in the spleen. It was suggested that T cells emigrating from the thymus of mice from newborn to 2 weeks of age are long-lived, whereas those from the thymus in mice 4 weeks of age and older are short-lived. However, when 4-week-old young adult mice were treated by irradiation or hydrocortisone, the thymic capacity was enhanced in terms of proliferation and peripheralization of thymocytes, and emigrated T cells became long-lived

  3. Origins and Properties of Dental, Thymic, and Bone Marrow Mesenchymal Cells and Their Stem Cells

    Science.gov (United States)

    Komada, Yukiya; Yamane, Toshiyuki; Kadota, Daiji; Isono, Kana; Takakura, Nobuyuki; Hayashi, Shin-Ichi; Yamazaki, Hidetoshi

    2012-01-01

    Mesenchymal cells arise from the neural crest (NC) or mesoderm. However, it is difficult to distinguish NC-derived cells from mesoderm-derived cells. Using double-transgenic mouse systems encoding P0-Cre, Wnt1-Cre, Mesp1-Cre, and Rosa26EYFP, which enabled us to trace NC-derived or mesoderm-derived cells as YFP-expressing cells, we demonstrated for the first time that both NC-derived (P0- or Wnt1-labeled) and mesoderm-derived (Mesp1-labeled) cells contribute to the development of dental, thymic, and bone marrow (BM) mesenchyme from the fetal stage to the adult stage. Irrespective of the tissues involved, NC-derived and mesoderm-derived cells contributed mainly to perivascular cells and endothelial cells, respectively. Dental and thymic mesenchyme were composed of either NC-derived or mesoderm-derived cells, whereas half of the BM mesenchyme was composed of cells that were not derived from the NC or mesoderm. However, a colony-forming unit-fibroblast (CFU-F) assay indicated that CFU-Fs in the dental pulp, thymus, and BM were composed of NC-derived and mesoderm-derived cells. Secondary CFU-F assays were used to estimate the self-renewal potential, which showed that CFU-Fs in the teeth, thymus, and BM were entirely NC-derived cells, entirely mesoderm-derived cells, and mostly NC-derived cells, respectively. Colony formation was inhibited drastically by the addition of anti-platelet–derived growth factor receptor-β antibody, regardless of the tissue and its origin. Furthermore, dental mesenchyme expressed genes encoding critical hematopoietic factors, such as interleukin-7, stem cell factor, and cysteine-X-cysteine (CXC) chemokine ligand 12, which supports the differentiation of B lymphocytes and osteoclasts. Therefore, the mesenchymal stem cells found in these tissues had different origins, but similar properties in each organ. PMID:23185234

  4. Mediastinal neoplasms in patients with Graves disease: a possible link between sustained hyperthyroidism and thymic neoplasia?

    Directory of Open Access Journals (Sweden)

    Boyd Jonathan D

    2012-07-01

    Full Text Available Abstract Background Anterior mediastinal masses are a rare but well documented finding in Graves disease. The vast majority of these lesions represents benign thymic hypertrophy and regress after treatment of the hyperthyroidism. A small percentage of these cases however represent neoplastic/malignant diseases which require further treatment. Cases 12 year old boy with one year history of refractory Graves disease was found to have an anterior mediastinal mass and underwent curative thyroidectomy for sustained hyperthyroidism. Cervical lymphadenopathy was detected during the procedure and biopsy was obtained. A 23 year old woman who presented with a one month history of hyperthyroid symptoms, was diagnosed with Graves disease and also was found to have an anterior mediastinal mass on imaging. Biopsy of the anterior mediastinal mass was obtained and subsequently the patient underwent robotic thymectomy. Histologic examination and immunophenotyping of the cervical lymph node in a 12 year old boy revealed neoplastic proliferation of T lymphoblasts diagnostic of T lymphoblastic leukemia/lymphoma. Examination of the anterior mediastinal mass biopsy in the 23 year old woman revealed type B1 thymoma which was confirmed after examination of the subsequent robotic thymectomy specimen. Conclusion This is the first reported case of T cell lymphoblastic lymphoma and the third reported case of thymoma associated with sustained hyperthyroidism due to Graves disease. These cases indicate that an anterior mediastinal mass in a patient with active Graves disease may be due to a neoplastic cause, which may require definitive treatment. Caution should be exercised when dismissing a mediastinal mass as benign thymic hyperplasia in patients with active Graves disease.

  5. Selective lymphoid irradiation. V. Synergism with pretransplant thymectomy or thymic irradiation in cardiac transplantation in rats

    International Nuclear Information System (INIS)

    Iga, C.; Fawwaz, R.; Nowygrod, R.; Reemtsma, K.; Hardy, M.A.

    1985-01-01

    Selective lymphoid irradiation (SLI) using palladium-109-hematoporphyrin (Pd-H), given four days prior to transplantation, combined with two doses of antilymphocyte globulin (ALG) (10 mg, days -2 and -1), was evaluated as a method of induction of permanent heterotopic cardiac allograft survival in the highly histoincompatible rat strain combination of ACI (RT1(1))-to-Lewis (RT1a). Both Pd-H and ALG localize poorly in the thymus, so this study evaluated whether thymic irradiation (TI) or thymectomy (TX) of the adult recipient results in indefinite allograft survival. Immunosuppression with Pd-H or ALG alone gave a mean survival time (MST) of 6.7 +/- 0.6 days, but the combination of the two agents led to an MST of 17.6 +/- 3.4 days. When TI was combined with Pd-H and ALG, cardiac allograft survival was prolonged to 50.2 +/- 13.9 days, but TI alone showed an MST of 10.3 +/- 1.8 days. Permanent cardiac allograft survival (greater than 250 days) was achieved in all thymectomized recipients treated with the combination of Pd-H and a brief course of ALG. These animals also accepted second-set skin grafts and rejected third-party skin grafts following more than 150 days of ACI cardiac allograft survival. Thymic irradiation, although effective in acting synergistically with SLI and ALG, led to prolonged, but limited allograft survival, although thymectomy with SLI and ALG is synergistic in prolonging allograft survival permanently without chronic immunosuppression

  6. Analysis of early initiating event(s) in radiation-induced thymic lymphomagenesis

    International Nuclear Information System (INIS)

    Muto, Masahiro; Ying Chen; Kubo, Eiko; Mita, Kazuei

    1996-01-01

    Since the T cell receptor rearrangement is a sequential process and unique to the progeny of each clone, we investigated the early initiating events in radiation-induced thymic lymphomagenesis by comparing the oncogenic alterations with the pattern of γ T cell receptor (TCR) rearrangements. We reported previously that after leukemogenic irradiation, preneoplastic cells developed, albeit infrequently, from thymic leukemia antigen-2 + (TL-2 + ) thymocytes. Limited numbers of TL-2 + cells from individual irradiated B10.Thy-1.1 mice were injected into B10.Thy-1.2 mice intrathymically, and the common genetic changes among the donor-type T cell lymphomas were investigated with regard to p53 gene and chromosome aberrations. The results indicated that some mutations in the p53 gene had taken place in these lymphomas, but there was no common mutation among the donor-type lymphomas from individual irradiated mice, suggesting that these mutations were late-occurring events in the process of oncogenesis. On the other hand, there were common chromosome aberrations or translocations such as trisomy 15, t(7F; 10C), t(1A; 13D) or t(6A; XB) among the donor-type lymphomas derived from half of the individual irradiated mice. This indicated that the aberrations/translocations, which occurred in single progenitor cells at the early T cell differentiation either just before or after γ T cell receptor rearrangements, might be important candidates for initiating events. In the donor-type lymphomas from the other half of the individual irradiated mice, microgenetic changes were suggested to be initial events and also might take place in single progenitor cells just before or right after γ TCR rearrangements. (author)

  7. Implications of Age-Related Changes in Anatomy for Geriatric-Focused Difficult Airways

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    Shih-Yi Lee

    2017-09-01

    Full Text Available The structure and function surrounding the airway change by the age, which may ultimately result in having anatomic features of difficult airways in the elderly. Hence, we reviewed the literature focusing on the age-related anatomic changes and accordingly to compare the characteristics of difficult airways. With age, teeth wear and loss, protein and collagen synthesis reduction, and bone loss and muscle atrophy results in aged face (chin protrusion, cheek retraction and drooping, jaw restriction (temporo-madibular joint disc displacement and osteoarthritis, neck and back stiffness, and kyphotic deformities (degeneration of spinal articular cartilage, intervertebral discs, and spinal osteoporosis. These age-related changes in anatomy are compatible with the predictors of a difficult airway. We hope that these age-related anatomic approaches will prospectively allow a detailed understanding of the hallmarks resulting in geriatric-focused difficult airways in the future studies.

  8.  Age-related changes of skeletal muscles: physiology, pathology and regeneration

    Directory of Open Access Journals (Sweden)

    Aleksandra Ławniczak

    2012-06-01

    Full Text Available  This review provides a short presentation of the aging-related changes of human skeletal muscles. The aging process is associated with the loss of skeletal muscle mass (sarcopenia and strength. This results from fibre atrophy and apoptosis, decreased regeneration capacity, mitochondrial dysfunction, gradual reduction of the number of spinal cord motor neurons, and local and systemic metabolic and hormonal alterations. The latter involve age-related decrease of the expression and activity of some mitochondrial and cytoplasmic enzymes, triacylglycerols and lipofuscin accumulation inside muscle fibres, increased proteolytic activity, insulin resistance and decreased serum growth hormone and IGF-1 concentrations. Aging of the skeletal muscles is also associated with a decreased number of satellite cells and their proliferative activity. The age-related reduction of skeletal muscle mass and function may be partially prevented by dietary restriction and systematic physical exercises.

  9. Oxidative stress participates in age-related changes in rat lumbar intervertebral discs.

    Science.gov (United States)

    Hou, Gang; Lu, Huading; Chen, Mingjuan; Yao, Hui; Zhao, Huiqing

    2014-01-01

    Aging is a major factor associated with lumber intervertebral disc degeneration, and oxidative stress is known to play an essential role in the pathogenesis of many age-related diseases. In this study, we investigated oxidative stress in intervertebral discs of Wistar rats in three different age groups: youth, adult, and geriatric. Age-related intervertebral disc changes were examined by histological analysis. In addition, oxidative stress was evaluated by assessing nitric oxide (NO), superoxide dismutase (SOD), malondialdehyde (MDA), and advanced oxidation protein products (AOPPs). Intervertebral disc, but not serum, NO concentrations significantly differed between the three groups. Serum and intervertebral disc SOD activity gradually decreased with age. Furthermore, both serum and intervertebral disc MDA and AOPP levels gradually increased with age. Our studies suggest that oxidative stress is associated with age-related intervertebral disc changes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Unusual Thymic Hyperplasia Mimicking Lipomatous Tumor in an Eight-Year-Old Boy with Concomitant Pericardial Lipomatosis and Right Facial Hemihypertrophy

    International Nuclear Information System (INIS)

    Kim, Yoo Jin; Kim Woo Sun; Cheon, Jung Eun; Lim, Yun Jung; Kim, In One; Yeon, Kyung Mo; Jung, Kyeong Cheon; Byun, Sun Ju

    2011-01-01

    We report a case of thymic hyperplasia accompanied by pericardial lipomatosis and right facial hemihypertrophy in an 8-year-old boy. On imaging studies, the hyperplastic thymus had prominent curvilinear and nodular fatty areas simulating a fat-containing anterior mediastinal mass, which is an unusual finding in children. To our knowledge, this is the first report on a child with a combination of thymic hyperplasia, pericardial lipomatosis, and right facial hemihypertrophy. The radiologic findings are presented with a brief discussion.

  11. Dizziness and Imbalance in the Elderly: Age-related Decline in the Vestibular System

    Science.gov (United States)

    Iwasaki, Shinichi; Yamasoba, Tatsuya

    2015-01-01

    Dizziness and imbalance are amongst the most common complaints in older people, and are a growing public health concern since they put older people at a significantly higher risk of falling. Although the causes of dizziness in older people are multifactorial, peripheral vestibular dysfunction is one of the most frequent causes. Benign paroxysmal positional vertigo is the most frequent form of vestibular dysfunction in the elderly, followed by Meniere’s disease. Every factor associated with the maintenance of postural stability deteriorates during aging. Age-related deterioration of peripheral vestibular function has been demonstrated through quantitative measurements of the vestibulo-ocular reflex with rotational testing and of the vestibulo-collic reflex with testing of vestibular evoked myogenic potentials. Age-related decline of vestibular function has been shown to correlate with the age-related decrease in the number of vestibular hair cells and neurons. The mechanism of age-related cellular loss in the vestibular endorgan is unclear, but it is thought that genetic predisposition and cumulative effect of oxidative stress may both play an important role. Since the causes of dizziness in older people are multi-factorial, management of this disease should be customized according to the etiologies of each individual. Vestibular rehabilitation is found to be effective in treating both unilateral and bilateral vestibular dysfunction. Various prosthetic devices have also been developed to improve postural balance in older people. Although there have been no medical treatments improving age-related vestibular dysfunction, new medical treatments such as mitochondrial antioxidants or caloric restriction, which have been effective in preventing age-related hearing loss, should be ienvestigated in the future. PMID:25657851

  12. Age-related X-ray feature of the spine in patients with achondroplasia

    International Nuclear Information System (INIS)

    Shevtsov, V.I.; D'yachkova, G.V.; Novikova, O.S.

    1999-01-01

    Age-related X-ray features of the spine in patients with achondroplasia are studied. It gives the time course of changes in the shape of vertebrae, the specific features of apophyseal ossification, provides a quantitative account of the shorter caudal lumbar vertebral arch root distance symptom. The time course of changes in the size of the lumbosacral angle was examined. The findings suggest that there are not only considerable static changes in the spine of patients with achondroplasia, but also significant age-related features of vertebral tissue growth and differentiation [ru

  13. Age-related inequalities in health and healthcare: the life stages approach.

    Science.gov (United States)

    Jecker, Nancy S

    2017-05-16

    How should healthcare systems prepare to care for growing numbers and proportions of older people? Older people generally suffer worse health than younger people do. Should societies take steps to reduce age-related health inequalities? Some express concern that doing so would increase age-related inequalities in healthcare. This paper addresses this debate by (1) presenting an argument in support of three principles for distributing scarce resources between age groups; (2) framing these principles of age group justice in terms of life stages; and (3) indicating policy implications that merit further attention in light of rapidly aging societies. © 2017 John Wiley & Sons Ltd.

  14. Improved word recognition for observers with age-related maculopathies using compensation filters

    Science.gov (United States)

    Lawton, Teri B.

    1988-01-01

    A method for improving word recognition for people with age-related maculopathies, which cause a loss of central vision, is discussed. It is found that the use of individualized compensation filters based on an person's normalized contrast sensitivity function can improve word recognition for people with age-related maculopathies. It is shown that 27-70 pct more magnification is needed for unfiltered words compared to filtered words. The improvement in word recognition is positively correlated with the severity of vision loss.

  15. Radiation therapy for subfoveal chroidal neovascularization complicating age-related macular degeneration

    International Nuclear Information System (INIS)

    Kawabata, Yuko; Ohara, Masae; Ishii, Kentaro

    2004-01-01

    We evaluated the effect of low-dose external beam irradiation on the visual function of 14 eyes with subfoveal chroidal neovascularization complicating age-related macular degeneration. Patient received external beam irradiation at a dose of 20 Gy in 10 fraction of 2 Gy. After treatment the visual function improved in 2 eyes, remained stable in 8 eyes and deteriorated in 4 eyes. At the last examination visual function improved in 1 eyes, remained stable in 2 eyes and deteriorated in 5 eyes. The low-dose irradiation is potentially beneficial for subfoveal chroidal neovascularization complicating age-related macular degeneration. (author)

  16. Fatty old hearts: role of cardiac lipotoxicity in age-related cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Konstantinos Drosatos

    2016-08-01

    Full Text Available Age-related cardiomyopathy accounts for a significant part of heart failure cases. Imbalance of the energetic equilibrium of the heart along with mitochondrial dysfunction and impaired β-adrenergic receptor signaling contributes in the aggravation of cardiac function in the elderly. In this review article, studies that correlate cardiac aging with lipotoxicity are summarized. The involvement of inhibition of peroxisome proliferator-activated receptor-α, β-adrenergic receptor desensitization, and mitochondrial dysfunction as underlying mechanisms for the lipid-driven age-related cardiomyopathy are presented with the aim to indicate potential therapeutic targets for cardiac aging.

  17. The Potential of Chitosan and Its Derivatives in Prevention and Treatment of Age-Related Diseases

    Science.gov (United States)

    Kerch, Garry

    2015-01-01

    Age-related, diet-related and protein conformational diseases, such as atherosclerosis, diabetes mellitus, cancer, hypercholesterolemia, cardiovascular and neurodegenerative diseases are common in the elderly population. The potential of chitosan, chitooligosaccharides and their derivatives in prevention and treatment of age-related dysfunctions is reviewed and discussed in this paper. The influence of oxidative stress, low density lipoprotein oxidation, increase of tissue stiffness, protein conformational changes, aging-associated chronic inflammation and their pathobiological significance have been considered. The chitosan-based functional food also has been reviewed. PMID:25871293

  18. Age-related changes in the transmission properties of the human lens and their relevance to circadian entrainment

    DEFF Research Database (Denmark)

    Kessel, Line; Lundeman, Jesper Holm; Herbst, Kristina

    2010-01-01

    To characterize age-related changes in the transmission of light through noncataractous human lenses.......To characterize age-related changes in the transmission of light through noncataractous human lenses....

  19. European survey on the opinion and use of micronutrition in age-related macular degeneration: 10 years on from the Age-Related Eye Disease Study

    Directory of Open Access Journals (Sweden)

    Aslam T

    2014-10-01

    Full Text Available Tariq Aslam,1 Cécile Delcourt,2 Frank Holz,3 Alfredo García-Layana,4 Anita Leys,5 Rufino M Silva,6 Eric Souied7 1Manchester Royal Eye Hospital, Manchester, UK; 2University of Bordeaux, Bordeaux, France; 3University of Bonn, Bonn, Germany; 4Clínica Universidad de Navarra, Pamplona, Spain; 5University Hospitals, Leuven, Belgium; 6University of Coimbra, Coimbra, Portugal; 7Université Paris Est Créteil, Créteil, FrancePurpose: To evaluate ophthalmologists’ opinion of, and use of, micronutritional dietary supplements 10 years after publication of the first Age-Related Eye Disease Study (AREDS study.Methods: Participation was solicited from 4,000 European ophthalmologists. Responding physicians were screened, and those treating at least 40 patients with age-related macular degeneration (AMD per month and prescribing nutrition supplements at least 4 times per month were admitted and completed a 40-item questionnaire.Results: The surveyed sample included 112 general ophthalmologists and 104 retinal specialists. Most nutritional supplements (46% were initiated when early/intermediate AMD was confirmed, although 18% were initiated on confirmation of neovascular AMD. Clinical studies were well known: 90% were aware of AREDS, with 88% aware of AREDS1 and 36% aware of the, as-yet-unpublished, AREDS2 studies. Respondents considered lutein, zeaxanthin, zinc, omega-3, and vitamins to be the most important components of nutritional supplements, with the results of AREDS2 already having been taken into consideration by many. Ophthalmologists anticipate more scientific studies as well as improved product quality but identify cost as a barrier to wider uptake.Conclusion: Micronutrition is now part of the routine management of AMD for many ophthalmologists. Ophthalmologists choosing to use nutritional supplements are well-informed regarding current scientific studies. Keywords: age-related macular degeneration, micronutrition, nutritional

  20. The Association of Statin Use with Age-Related Macular Degeneration Progression: The Age-Related Eye Disease Study 2 Report Number 9.

    Science.gov (United States)

    Al-Holou, Shaza N; Tucker, William R; Agrón, Elvira; Clemons, Traci E; Cukras, Catherine; Ferris, Frederick L; Chew, Emily Y

    2015-12-01

    To evaluate the association of statin use with progression of age-related macular degeneration (AMD). Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50 to 85 years. Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke-all known to be associated with statin use-were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses adjusting for the competing risk of death were also performed. Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.83-1.41; P = 0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant (HR, 0.81; 95% CI, 0.55-1.20; P = 0.29). Furthermore, subgroup analyses of persons with or without late AMD at baseline and the various components of late AMD (neovascular AMD, central GA, or any GA) also showed no statistically significant association of statin use with progression to AMD. Statin use was not statistically significantly associated with progression to late AMD in the AREDS2 participants, and these findings are consistent with findings in the

  1. The Association of Statin Use with Age-Related Macular Degeneration Progression The Age-Related Eye Disease Study 2 Report Number 9

    Science.gov (United States)

    Al-Holou, Shaza N.; Tucker, William R.; Agrón, Elvira; Clemons, Traci E.; Cukras, Catherine; Ferris, Frederick L.; Chew, Emily Y.

    2015-01-01

    Objective/purpose To evaluate the association of statin use with progression of age-related macular degeneration (AMD). Design Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. Subjects Age-Related Eye Disease Study 2 participants, aged 50 to 85 years. Methods Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke, all known to be associated with statin use, were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses were also performed adjusting for the competing risk of death. Main Outcome Measures Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). Results Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratios [HR] of 1.08, 95% confidence intervals [CI] of 0.83–1.41, P=0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant with HR: 0.81, 95% CI: 0.55–1.20, P=0.29. Further subgroup analyses of persons with or without late AMD at baseline to the various components of late AMD (neovascular, central geographic atrophy, or any geographic atrophy) also showed no statistically significant association of statin use with progression to AMD. Conclusions Statin use was not statistically significantly associated with the

  2. AVE0991, a nonpeptide analogue of Ang-(1-7), attenuates aging-related neuroinflammation.

    Science.gov (United States)

    Jiang, Teng; Xue, Liu-Jun; Yang, Yang; Wang, Qing-Guang; Xue, Xiao; Ou, Zhou; Gao, Qing; Shi, Jian-Quan; Wu, Liang; Zhang, Ying-Dong

    2018-04-17

    During the aging process, chronic neuroinflammation induced by microglia is detrimental for the brain and contributes to the etiology of several aging-related neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. As a newly identified axis of renin-angiotensin system, ACE2/Ang-(1-7)/MAS1 axis plays a crucial role in modulating inflammatory responses under various pathological conditions. However, its relationship with aging-related neuroinflammation is less studied so far. In this study, by using SAMP8 mice, an animal model of accelerated aging, we revealed that the neuroinflammation in the aged brain might be attributed to a decreased level of Ang-(1-7). More importantly, we provided evidence that AVE0991, a nonpeptide analogue of Ang-(1-7), attenuated the aging-related neuroinflammation via suppression of microglial-mediated inflammatory response through a MAS1 receptor-dependent manner. Meanwhile, this protective effect might be ascribed to the M2 activation of microglia induced by AVE0991. Taken together, these findings reveal the association of Ang-(1-7) with the inflammatory response in the aged brain and uncover the potential of its nonpeptide analogue AVE0991 in attenuation of aging-related neuroinflammation.

  3. Alcohol consumption, smoking and development of visible age-related signs: a prospective cohort study.

    Science.gov (United States)

    Schou, Anne L; Mølbak, Marie-Louise; Schnor, Peter; Grønbæk, Morten; Tolstrup, Janne S

    2017-12-01

    Visible age-related signs indicate biological age, as individuals that appear old for their age are more likely to be at poor health, compared with people that appear their actual age. The aim of this study was to investigate whether alcohol and smoking are associated with four visible age-related signs (arcus corneae, xanthelasmata, earlobe crease and male pattern baldness). We used information from 11 613 individuals in the Copenhagen City Heart Study (1976-2003). Alcohol intake, smoking habits and other lifestyle factors were assessed prospectively and visible age-related signs were inspected during subsequent examinations. The risk of developing arcus corneae, earlobe crease and xanthelasmata increased stepwise with increased smoking as measured by pack-years. For alcohol consumption, a high intake was associated with the risk of developing arcus corneae and earlobe crease, but not xanthelasmata. High alcohol consumption and smoking predict development of visible age-related signs. This is the first prospective study to show that heavy alcohol use and smoking are associated with generally looking older than one's actual age. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Perceptions of oocyte banking from women intending to circumvent age-related fertility decline

    NARCIS (Netherlands)

    de Groot, Marije; Dancet, Eline; Repping, Sjoerd; Goddijn, Mariette; Stoop, Dominic; van der Veen, Fulco; Gerrits, Trudie

    2016-01-01

    Women can now opt to bank their oocytes with the intention of increasing their chances of achieving a pregnancy after their fertility has declined. This exploratory study aimed to gain insight into how women, considering oocyte banking to circumvent age-related fertility decline, perceive this

  5. Wandering stars: age-related habitat use and dispersal of Javan Hawk-eagles (Spizaetus bartelsi)

    NARCIS (Netherlands)

    Nijman, V.; Balen, van S.

    2003-01-01

    Natal dispersal and philopatry have rarely been studied in tropical forest raptors. Especially with respect to endangered species with fragmented distributions more knowledge of dispersal and age-related habitat preferences is needed for proper management. We conducted an island-wide study on

  6. GRM7 variants confer susceptibility to age-related hearing impairment

    DEFF Research Database (Denmark)

    Friedman, Rick A; Van Laer, Lut; Huentelman, Matthew J

    2009-01-01

    Age-related hearing impairment (ARHI), or presbycusis, is the most prevalent sensory impairment in the elderly. ARHI is a complex disease caused by an interaction between environmental and genetic factors. Here we describe the results of the first whole genome association study for ARHI. The stud...

  7. Age-related changes of structures in cerebellar cortex of cat

    Indian Academy of Sciences (India)

    We studied the structures of the cerebellar cortex of young adult and old cats for age-related changes, which were statistically analysed. Nissl staining was used to visualize the cortical neurons. The immunohistochemical method was used to display glial fibrillary acidic protein (GFAP)-immunoreactive (IR) astrocytes and ...

  8. Ability of university-level education to prevent age-related decline in emotional intelligence

    Science.gov (United States)

    Cabello, Rosario; Navarro Bravo, Beatriz; Latorre, José Miguel; Fernández-Berrocal, Pablo

    2014-01-01

    Numerous studies have suggested that educational history, as a proxy measure of active cognitive reserve, protects against age-related cognitive decline and risk of dementia. Whether educational history also protects against age-related decline in emotional intelligence (EI) is unclear. The present study examined ability EI in 310 healthy adults ranging in age from 18 to 76 years using the Mayer–Salovey–Caruso Emotional Intelligence Test (MSCEIT). We found that older people had lower scores than younger people for total EI and for the EI branches of perceiving, facilitating, and understanding emotions, whereas age was not associated with the EI branch of managing emotions. We also found that educational history protects against this age-related EI decline by mediating the relationship between age and EI. In particular, the EI scores of older adults with a university education were higher than those of older adults with primary or secondary education, and similar to those of younger adults of any education level. These findings suggest that the cognitive reserve hypothesis, which states that individual differences in cognitive processes as a function of lifetime intellectual activities explain differential susceptibility to functional impairment in the presence of age-related changes and brain pathology, applies also to EI, and that education can help preserve cognitive-emotional structures during aging. PMID:24653697

  9. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease.

    Science.gov (United States)

    Potter, Paul K; Bowl, Michael R; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E; Simon, Michelle M; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V; Law, Gemma; MacLaren, Robert E; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H; Foster, Russell G; Jackson, Ian J; Peirson, Stuart N; Thakker, Rajesh V; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D M

    2016-08-18

    Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss.

  10. Audiovisual Temporal Perception in Aging: The Role of Multisensory Integration and Age-Related Sensory Loss.

    Science.gov (United States)

    Brooks, Cassandra J; Chan, Yu Man; Anderson, Andrew J; McKendrick, Allison M

    2018-01-01

    Within each sensory modality, age-related deficits in temporal perception contribute to the difficulties older adults experience when performing everyday tasks. Since perceptual experience is inherently multisensory, older adults also face the added challenge of appropriately integrating or segregating the auditory and visual cues present in our dynamic environment into coherent representations of distinct objects. As such, many studies have investigated how older adults perform when integrating temporal information across audition and vision. This review covers both direct judgments about temporal information (the sound-induced flash illusion, temporal order, perceived synchrony, and temporal rate discrimination) and judgments regarding stimuli containing temporal information (the audiovisual bounce effect and speech perception). Although an age-related increase in integration has been demonstrated on a variety of tasks, research specifically investigating the ability of older adults to integrate temporal auditory and visual cues has produced disparate results. In this short review, we explore what factors could underlie these divergent findings. We conclude that both task-specific differences and age-related sensory loss play a role in the reported disparity in age-related effects on the integration of auditory and visual temporal information.

  11. Risk factors for age-related macular degeneration: Pooled findings from three continents

    NARCIS (Netherlands)

    Smith, W.; Assink, J.; Klein, R.; Mitchell, P.; Klaver, C. C.; Klein, B. E.; Hofman, A.; Jensen, S.; Wang, J. J.; de Jong, P. T.

    2001-01-01

    To assess the prevalence and potential risk factors for late age-related macular degeneration (AMD) in three racially similar populations from North America, Europe, and AUSTRALIA: Combined analysis of population-based eye disease prevalence data. There were 14,752 participants with gradable

  12. Adaptation to Low Vision Caused by Age-Related Macular Degeneration: A Case Study

    Science.gov (United States)

    Smith, Theresa Marie

    2008-01-01

    One in eight Americans aged 65 and older has an eye disease resulting in low vision, and more women than men are visually impaired, mainly because women live longer. Age-related visual impairments are an indicator of a decline in activities of daily living and self-help skills. The top eye conditions that affect older adults are macular…

  13. Association of gait and balance disorders with age-related white matter changes

    NARCIS (Netherlands)

    Baezner, H.; Blahak, C.; Poggesi, A.; Pantoni, L.; Inzitari, D.; Chabriat, H.; Erkinjuntti, T.; Fazekas, F.; Ferro, J.M.; Langhorne, P.; O'Brien, J.; Scheltens, P.; Visser, M.C.; Wahlund, L.O.; Waldemar, G.; Wallin, A.; Hennerici, M.G.

    2008-01-01

    OBJECTIVE: In the Leukoaraiosis and Disability (LADIS) Study, 11 European centers are evaluating the role of age-related white matter changes (ARWMC) as an independent determinant of the transition to disability in the elderly (65 to 84 years). We aimed at determining the influence of ARWMC on

  14. Age-related differences in cognition across the adult lifespan in autism spectrum disorder

    NARCIS (Netherlands)

    Lever, A.G.; Geurts, H.M.

    It is largely unknown how age impacts cognition in autism spectrum disorder (ASD). We investigated whether age-related cognitive differences are similar, reduced or increased across the adult lifespan, examined cognitive strengths and weaknesses, and explored whether objective test performance is

  15. Age-related adaptations of brain function during a memory task are also present at rest

    NARCIS (Netherlands)

    Filippini, N.; Nickerson, L.D.; Beckmann, Christian; Ebmeier, K.P.; Frisoni, G.B.; Matthews, P.M.; Smith, S.M.; Mackay, C.E.

    2012-01-01

    Several studies have demonstrated age-related regional differences in the magnitude of the BOLD signal using task-based fMRI. It has been suggested that functional changes reflect either compensatory or de-differentiation mechanisms, both of which assume response to a specific stimulus. Here, we

  16. The Prevalence of Age-Related Eye Diseases and Visual Impairment in Aging: Current Estimates

    Science.gov (United States)

    Klein, Ronald; Klein, Barbara E. K.

    2013-01-01

    Purpose. To examine prevalence of five age-related eye conditions (age-related cataract, AMD, open-angle glaucoma, diabetic retinopathy [DR], and visual impairment) in the United States. Methods. Review of published scientific articles and unpublished research findings. Results. Cataract, AMD, open-angle glaucoma, DR, and visual impairment prevalences are high in four different studies of these conditions, especially in people over 75 years of age. There are disparities among racial/ethnic groups with higher age-specific prevalence of DR, open-angle glaucoma, and visual impairment in Hispanics and blacks compared with whites, higher prevalence of age-related cataract in whites compared with blacks, and higher prevalence of late AMD in whites compared with Hispanics and blacks. The estimates are based on old data and do not reflect recent changes in the distribution of age and race/ethnicity in the United States population. There are no epidemiologic estimates of prevalence for many visually-impairing conditions. Conclusions. Ongoing prevalence surveys designed to provide reliable estimates of visual impairment, AMD, age-related cataract, open-angle glaucoma, and DR are needed. It is important to collect objective data on these and other conditions that affect vision and quality of life in order to plan for health care needs and identify areas for further research. PMID:24335069

  17. Significance of categorization and the modeling of age related factors for radiation protection

    International Nuclear Information System (INIS)

    Matsuoka, Osamu

    1987-01-01

    It is proposed that the categorization and modelling are necessary with regard to age related factors of radionuclide metabolism for the radiation protection of the public. In order to utilize the age related information as a model for life time risk estimate of public, it is necessary to generalize and simplify it according to the categorized model patterns. Since the patterns of age related changes in various parameters of radionuclide metabolism seem to be rather simple, it is possible to categorize them into eleven types of model patterns. Among these models, five are selected as positively significant models to be considered. Examples are shown as to the fitting of representative parameters of both physiological and metabolic parameter of radionuclides into the proposed model. The range of deviation from adult standard value is also analyzed for each model. The fitting of each parameter to categorized models, and its comparative consideration provide the effective information as to the physiological basis of radionuclide metabolism. Discussions are made on the problems encountered in the application of available age related information to radiation protection of the public, i.e. distribution of categorized parameter, period of life covered, range of deviation from adult value, implication to other dosimetric and pathological models and to the final estimation. 5 refs.; 3 figs.; 4 tabs

  18. Masking Period Patterns & Forward Masking for Speech-Shaped Noise: Age-related effects

    Science.gov (United States)

    Grose, John H.; Menezes, Denise C.; Porter, Heather L.; Griz, Silvana

    2015-01-01

    Objective The purpose of this study was to assess age-related changes in temporal resolution in listeners with relatively normal audiograms. The hypothesis was that increased susceptibility to non-simultaneous masking contributes to the hearing difficulties experienced by older listeners in complex fluctuating backgrounds. Design Participants included younger (n = 11), middle-aged (n = 12), and older (n = 11) listeners with relatively normal audiograms. The first phase of the study measured masking period patterns for speech-shaped noise maskers and signals. From these data, temporal window shapes were derived. The second phase measured forward-masking functions, and assessed how well the temporal window fits accounted for these data. Results The masking period patterns demonstrated increased susceptibility to backward masking in the older listeners, compatible with a more symmetric temporal window in this group. The forward-masking functions exhibited an age-related decline in recovery to baseline thresholds, and there was also an increase in the variability of the temporal window fits to these data. Conclusions This study demonstrated an age-related increase in susceptibility to non-simultaneous masking, supporting the hypothesis that exacerbated non-simultaneous masking contributes to age-related difficulties understanding speech in fluctuating noise. Further support for this hypothesis comes from limited speech-in-noise data suggesting an association between susceptibility to forward masking and speech understanding in modulated noise. PMID:26230495

  19. Masking Period Patterns and Forward Masking for Speech-Shaped Noise: Age-Related Effects.

    Science.gov (United States)

    Grose, John H; Menezes, Denise C; Porter, Heather L; Griz, Silvana

    2016-01-01

    The purpose of this study was to assess age-related changes in temporal resolution in listeners with relatively normal audiograms. The hypothesis was that increased susceptibility to nonsimultaneous masking contributes to the hearing difficulties experienced by older listeners in complex fluctuating backgrounds. Participants included younger (n = 11), middle-age (n = 12), and older (n = 11) listeners with relatively normal audiograms. The first phase of the study measured masking period patterns for speech-shaped noise maskers and signals. From these data, temporal window shapes were derived. The second phase measured forward-masking functions and assessed how well the temporal window fits accounted for these data. The masking period patterns demonstrated increased susceptibility to backward masking in the older listeners, compatible with a more symmetric temporal window in this group. The forward-masking functions exhibited an age-related decline in recovery to baseline thresholds, and there was also an increase in the variability of the temporal window fits to these data. This study demonstrated an age-related increase in susceptibility to nonsimultaneous masking, supporting the hypothesis that exacerbated nonsimultaneous masking contributes to age-related difficulties understanding speech in fluctuating noise. Further support for this hypothesis comes from limited speech-in-noise data, suggesting an association between susceptibility to forward masking and speech understanding in modulated noise.

  20. A Longitudinal Study of Age-Related Differences in Reactions to Psychological Contract Breach

    NARCIS (Netherlands)

    Bal, P.M.; Lange, A.H. de; Jansen, P.G.W.; Velde, M.E.G. van der

    2013-01-01

    The current paper investigated age-related differences in the relations of psychological contract breach with work outcomes over time. Based on affective events theory, we expected job satisfaction to mediate the longitudinal relationship of contract breach with changes in job performance. Moreover,

  1. A longitudinal study of age-related differences in reactions to psychological contract breach

    NARCIS (Netherlands)

    Bal, P.M.; de Lange, A.H.; Jansen, P.G.W.; van der Velde, E.G.

    2013-01-01

    The current paper investigated age-related differences in the relations of psychological contract breach with work outcomes over time. Based on affective events theory, we expected job satisfaction to mediate the longitudinal relationship of contract breach with changes in job performance. Moreover,

  2. Cognitive Abilities Explaining Age-Related Changes in Time Perception of Short and Long Durations

    Science.gov (United States)

    Zelanti, Pierre S.; Droit-Volet, Sylvie

    2011-01-01

    The current study investigated how the development of cognitive abilities explains the age-related changes in temporal judgment over short and long duration ranges from 0.5 to 30 s. Children (5- and 9-year-olds) as well as adults were given a temporal bisection task with four different duration ranges: a duration range shorter than 1 s, two…

  3. A novel radial water tread maze tracks age-related cognitive decline in mice

    Directory of Open Access Journals (Sweden)

    Christina Pettan-Brewer

    2013-10-01

    Full Text Available There is currently no treatment and cure for age-related dementia and cognitive impairment in humans. Mice suffer from age-related cognitive decline just as people do, but assessment is challenging because of cumbersome and at times stressful performance tasks. We developed a novel radial water tread (RWT maze and tested male C57BL/6 (B6 and C57BL/6 x Balb/c F1 (CB6F1 mice at ages 4, 12, 20, and 28 months. B6 mice showed a consistent learning experience and memory retention that gradually decreased with age. CB6F1 mice showed a moderate learning experience in the 4 and 12 month groups, which was not evident in the 20 and 28 month groups. In conclusion, CB6F1 mice showed more severe age-related cognitive impairment compared to B6 mice and might be a suitable model for intervention studies. In addition, the RWT maze has a number of operational advantages compared to currently accepted tasks and can be used to assess age-related cognition impairment in B6 and CB6F1 mice as early as 12 months of age.

  4. Myelin Breakdown Mediates Age-Related Slowing in Cognitive Processing Speed in Healthy Elderly Men

    Science.gov (United States)

    Lu, Po H.; Lee, Grace J.; Tishler, Todd A.; Meghpara, Michael; Thompson, Paul M.; Bartzokis, George

    2013-01-01

    Background: To assess the hypothesis that in a sample of very healthy elderly men selected to minimize risk for Alzheimer's disease (AD) and cerebrovascular disease, myelin breakdown in late-myelinating regions mediates age-related slowing in cognitive processing speed (CPS). Materials and methods: The prefrontal lobe white matter and the genu of…

  5. Psychosocial Intervention for Age-Related Macular Degeneration: A Pilot Project

    Science.gov (United States)

    Wahl, Hans-Werner; Kammerer, Annette; Holz, Frank; Miller, Daniel; Becker, Stefanie; Kaspar, Roman; Himmelsbach, Ines

    2006-01-01

    This study evaluated an emotion-focused and a problem-focused intervention designed for patients with age-related macular degeneration. It found a limited decrease in depression in the emotion-focused group and an increase in active problem orientation and in adaptation to vision loss in the problem-focused group.

  6. Age and muscle strength mediate the age-related biomechanical plasticity of gait

    NARCIS (Netherlands)

    Hortobagyi, Tibor; Rider, Patrick; Gruber, Allison H.; DeVita, Paul

    Old compared with young adults walk with reduced ankle and increased hip mechanical output. We examined the idea that age, leg strength, or both are related to the age-related changes in mechanical output during gait. Healthy young (n = 32, age 21.5 years) and old adults (n = 32, age 76.8 years)

  7. Mediterranean Diet Score and Its Association with Age-Related Macular Degeneration : The European Eye Study

    NARCIS (Netherlands)

    Hogg, Ruth E; Woodside, Jayne V; McGrath, Alanna; Young, Ian S; Vioque, Jesus L; Chakravarthy, Usha; de Jong, Paulus T; Rahu, Mati; Seland, Johan; Soubrane, Gisele; Tomazzoli, Laura; Topouzis, Fotis; Fletcher, Astrid E

    2017-01-01

    PURPOSE: To examine associations between adherence to a Mediterranean diet and prevalence of age-related macular degeneration (AMD) in countries ranging from Southern to Northern Europe. DESIGN: Cross-sectional, population-based epidemiologic study. PARTICIPANTS: Of 5060 randomly sampled people aged

  8. HISTORY OF SUNLIGHT EXPOSURE IS A RISK FACTOR FOR AGE-RELATED MACULAR DEGENERATION

    NARCIS (Netherlands)

    Schick, T.; Ersoy, L.; Lechanteur, Y.T.; Saksens, N.T.; Hoyng, C.B.; Hollander, A.I. den; Kirchhof, B.; Fauser, S.

    2016-01-01

    PURPOSE: To evaluate effects of current and past sunlight exposure and iris color on early and late age-related macular degeneration (AMD). METHODS: Of 3,701 individuals from the EUGENDA database, 752 (20.3%) showed early AMD, 1,179 (31.9%) late AMD, and 1,770 (47.8%) were controls. Information

  9. Multiple gait parameters derived from iPod accelerometry predict age-related gait changes

    NARCIS (Netherlands)

    Kosse, Nienke; Vuillerme, Nicolas; Hortobagyi, Tibor; Lamoth, Claude

    Introduction Normative data of how natural aging affects gait can serve as a frame of reference for changes in gait dynamics due to pathologies. Therefore, the present study aims (1) to identify gait variables sensitive to age-related changes in gait over the adult life span using the iPod and (2)

  10. Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages

    NARCIS (Netherlands)

    Schick, T.; Altay, L.; Viehweger, E.; Hoyng, C.B.; Hollander, A.I. den; Felsch, M.; Fauser, S.

    2016-01-01

    BACKGROUND: Age-related macular degeneration (AMD) is a common disease causing visual impairment and blindness. Various gene variants are strongly associated with late stage AMD, but little is known about the genetics of early forms of the disease. This study evaluated associations of genetic

  11. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans.

    NARCIS (Netherlands)

    Rahimi, M.; Vinciguerra, M.; Daghighi, M.; Ozcan, B.; Akbarkhanzadeh, V.; Sheedfar, F.; Amini, M.; Mazza, T.; Pazienza, V.; Motazacker, M.M.; Mahmoudi, M.; Rooij, F.W. De; Sijbrands, E.; Peppelenbosch, M.P.; Rezaee, F.

    2015-01-01

    Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and

  12. Role of growth factors and the wound healing response in age-related macular degeneration

    NARCIS (Netherlands)

    Schlingemann, Reinier O.

    2004-01-01

    Growth factors (GF) are important in several stages of the pathogenesis of age-related macular disease (AMD). In choroidal neovascularization (CNV) in exudative AMD, the GF involved are similar to those involved in wound healing of the skin. Like granulation tissue of skin, CNV is characterized by

  13. Fruits, Nuts, and Brain Aging: Nutritional Interventions Targeting Age-Related Neuronal and Behavioral Deficits

    Science.gov (United States)

    By the year 2050, 30% of the total population of the US will be over 65 years of age. As the aged population expands, the economic burden of care and treatment of those with age-related health disorders also increases, necessitating the immediate implementation of therapeutics to prevent or even rev...

  14. Repetition Priming in Adults with Williams Syndrome: Age-Related Dissociation between Implicit and Explicit Memory

    Science.gov (United States)

    Krinsky-McHale, Sharon J.; Kittler, Phyllis; Brown, W. Ted; Jenkins, Edmund C.; Devenny, Darlynne A.

    2005-01-01

    We examined implicit and explicit memory in adults with Williams syndrome. An age-related dissociation was found; repetition priming (reflecting implicit memory) did not show change with age, but free recall (reflecting explicit memory) was markedly reduced. We also compared the performance of adults with Williams syndrome to adults with Down…

  15. Increased expression of angiogenic growth factors in age-related maculopathy

    NARCIS (Netherlands)

    M. Kliffen (Mike); H.S. Sharma (Hari); C.M. Mooy (Cornelia); S. Kerkvliet (Sonja); P.T.V.M. de Jong (Paulus)

    1997-01-01

    textabstractAIMS/BACKGROUND: The late stages of age-related maculopathy (ARM), especially neovascular macular degeneration (ARMD), can severely affect central vision and are the main cause of blindness in the elderly in the Western world. It has been shown that

  16. Age-related macular disease : studies on incidence, risk factors, and prognosis

    NARCIS (Netherlands)

    R. van Leeuwen (Redmer)

    2003-01-01

    textabstractAge-related macular disease (AMD) is a new name, recently coined by Bird,25 for a progressive and degenerative disease in elderly persons affecting the macula lutea. Dysfunction of this part of the retina, and especially its centre, the fovea, results in the inability to read,

  17. Genetic association of apolipoprotein E with age-related macular degeneration

    NARCIS (Netherlands)

    M. Kliffen (Mike); C.M. van Duijn (Cornelia); M. Cruts (Marc); D.E. Grobbee (Diederick); P.T.V.M. de Jong (Paulus); C.C.W. Klaver (Caroline); C. van Broeckhoven (Christine); A. Hofman (Albert)

    1998-01-01

    textabstractAge-related macular degeneration (AMD) is the most common geriatric eye disorder leading to blindness and is characterized by degeneration of the neuroepithelium in the macular area of the eye. Apolipoprotein E (apoE), the major apolipoprotein of the CNS and an

  18. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans

    NARCIS (Netherlands)

    Rahimi, Mehran; Vinciguerra, Manlio; Daghighi, Mojtaba; Oezcan, Behiye; Akbarkhanzadeh, Vishtaseb; Sheedfar, Fareeba; Amini, Marzyeh; Mazza, Tommaso; Pazienza, Valerio; Motazacker, Mahdi M.; Mahmoudi, Morteza; De Rooij, Felix W. M.; Sijbrands, Eric; Peppelenbosch, Maikel P.; Rezaee, Farhad

    2015-01-01

    Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and

  19. Mechanisms of Age-Related Decline in Memory Search across the Adult Life Span

    Science.gov (United States)

    Hills, Thomas T.; Mata, Rui; Wilke, Andreas; Samanez-Larkin, Gregory R.

    2013-01-01

    Three alternative mechanisms for age-related decline in memory search have been proposed, which result from either reduced processing speed (global slowing hypothesis), overpersistence on categories (cluster-switching hypothesis), or the inability to maintain focus on local cues related to a decline in working memory (cue-maintenance hypothesis).…

  20. Aging of marrow stromal (skeletal) stem cells and their contribution to age-related bone loss

    DEFF Research Database (Denmark)

    Bellantuono, Ilaria; Aldahmash, Abdullah; Kassem, Moustapha

    2009-01-01

    Marrow stromal cells (MSC) are thought to be stem cells with osteogenic potential and therefore responsible for the repair and maintenance of the skeleton. Age related bone loss is one of the most prevalent diseases in the elder population. It is controversial whether MSC undergo a process of agi...

  1. Age-Related Hearing Loss: Quality of Care for Quality of Life

    Science.gov (United States)

    Li-Korotky, Ha-Sheng

    2012-01-01

    Age-related hearing loss (ARHL), known as presbycusis, is characterized by progressive deterioration of auditory sensitivity, loss of the auditory sensory cells, and central processing functions associated with the aging process. ARHL is the third most prevalent chronic condition in older Americans, after hypertension and arthritis, and is a…

  2. Audiovisual Temporal Perception in Aging: The Role of Multisensory Integration and Age-Related Sensory Loss

    Science.gov (United States)

    Brooks, Cassandra J.; Chan, Yu Man; Anderson, Andrew J.; McKendrick, Allison M.

    2018-01-01

    Within each sensory modality, age-related deficits in temporal perception contribute to the difficulties older adults experience when performing everyday tasks. Since perceptual experience is inherently multisensory, older adults also face the added challenge of appropriately integrating or segregating the auditory and visual cues present in our dynamic environment into coherent representations of distinct objects. As such, many studies have investigated how older adults perform when integrating temporal information across audition and vision. This review covers both direct judgments about temporal information (the sound-induced flash illusion, temporal order, perceived synchrony, and temporal rate discrimination) and judgments regarding stimuli containing temporal information (the audiovisual bounce effect and speech perception). Although an age-related increase in integration has been demonstrated on a variety of tasks, research specifically investigating the ability of older adults to integrate temporal auditory and visual cues has produced disparate results. In this short review, we explore what factors could underlie these divergent findings. We conclude that both task-specific differences and age-related sensory loss play a role in the reported disparity in age-related effects on the integration of auditory and visual temporal information. PMID:29867415

  3. Distinct age-related differences in temporal discounting and risk taking in adolescents and young adults

    NARCIS (Netherlands)

    Water, E. de; Cillessen, A.H.N.; Scheres, A.P.J.

    2014-01-01

    Age-related differences in temporal discounting (TD) and risk taking, and their association, were examined in adolescents and young adults (n=337) aged 12-27years. Since monetary rewards are typically used in TD and risk-taking tasks, the association between monetary reward valuation and age and

  4. Vitamin K’s role in age-related bone loss: A critical review

    Science.gov (United States)

    The protective role of vitamin K in age-related bone loss continues to be controversial. The results of observational analyses are inconsistent with respect to associations between vitamin K status and bone, which arguably may be related to the limitations of observational study designs and analyt...

  5. Age-Related Decline in Controlled Retrieval: The Role of the PFC and Sleep

    Directory of Open Access Journals (Sweden)

    Kristine A. Wilckens

    2012-01-01

    Full Text Available Age-related cognitive impairments often include difficulty retrieving memories, particularly those that rely on executive control. In this paper we discuss the influence of the prefrontal cortex on memory retrieval, and the specific memory processes associated with the prefrontal cortex that decline in late adulthood. We conclude that preretrieval processes associated with preparation to make a memory judgment are impaired, leading to greater reliance on postretrieval processes. This is consistent with the view that impairments in executive control significantly contribute to deficits in controlled retrieval. Finally, we discuss age-related changes in sleep as a potential mechanism that contributes to deficiencies in executive control that are important for efficient retrieval. The sleep literature points to the importance of slow-wave sleep in restoration of prefrontal cortex function. Given that slow-wave sleep significantly declines with age, we hypothesize that age-related changes in slow-wave sleep could mediate age-related decline in executive control, manifesting a robust deficit in controlled memory retrieval processes. Interventions, like physical activity, that improve sleep could be effective methods to enhance controlled memory processes in late life.

  6. Obesity and Age-Related Changes in Markers of Oxidative Stress and Inflammation Across Four Generations

    NARCIS (Netherlands)

    Hulsegge, Gerben; Herber-Gast, Gerrie-Cor M; Spijkerman, Annemieke M W; Picavet, H. Susan J; van der Schouw, Yvonne T; Bakker, Stephan J L; Gansevoort, Ron T; Dollé, Martijn E T; Smit, Henriette A; Monique Verschuren, W M

    OBJECTIVE: The prevalence of obesity increases with age and is higher in each younger generation (unfavorable generation shift). This may influence patterns of oxidative stress and inflammation. Age-related changes and generation shifts in markers of oxidative stress and inflammation were

  7. Obesity and Age-Related Changes in Markers of Oxidative Stress and Inflammation Across Four Generations

    NARCIS (Netherlands)

    Hulsegge, Gerben; Herber-Gast, Gerrie-Cor M; Spijkerman, Annemieke M W; Susan, H; Picavet, J; van der Schouw, Yvonne T; Bakker, Stephan J L; Gansevoort, Ron T; Dollé, Martijn E T; Smit, Henriette A; Monique Verschuren, W M

    ObjectiveThe prevalence of obesity increases with age and is higher in each younger generation (unfavorable generation shift). This may influence patterns of oxidative stress and inflammation. Age-related changes and generation shifts in markers of oxidative stress and inflammation were

  8. Aging-Related Systemic Manifestations in COPD Patients and Cigarette Smokers

    Science.gov (United States)

    Boyer, Laurent; Marcos, Elisabeth; Margarit, Laurent; Le Corvoisier, Philippe; Vervoitte, Laetitia; Hamidou, Leila; Frih, Lamia; Audureau, Etienne; Covali-Noroc, Ala; Andujar, Pascal; Saakashvili, Zakaria; Lino, Anne; Ghaleh, Bijan; Hue, Sophie; Derumeaux, Geneviève; Housset, Bruno; Dubois-Randé, Jean-Luc; Boczkowski, Jorge; Maitre, Bernard; Adnot, Serge

    2015-01-01

    Rationale Chronic obstructive pulmonary disease (COPD) is often associated with age-related systemic abnormalities that adversely affect the prognosis. Whether these manifestations are linked to the lung alterations or are independent complications of smoking remains unclear. Objectives To look for aging-related systemic manifestations and telomere shortening in COPD patients and smokers with minor lung destruction responsible for a decline in the diffusing capacity for carbon monoxide (DLCO) corrected for alveolar volume (KCO). Methods Cross-sectional study in 301 individuals (100 with COPD, 100 smokers without COPD, and 101 nonsmokers without COPD). Measurements and Main Results Compared to control smokers, patients with COPD had higher aortic pulse-wave velocity (PWV), lower bone mineral density (BMD) and appendicular skeletal muscle mass index (ASMMI), and shorter telomere length (TL). Insulin resistance (HOMA-IR) and glomerular filtration rate (GFR) were similar between control smokers and COPD patients. Smokers did not differ from nonsmokers for any of these parameters. However, smokers with normal spirometry but low KCO had lower ASMMI values compared to those with normal KCO. Moreover, female smokers with low KCO, had lower BMD and shorter TL compared to those with normal KCO. Conclusions Aging-related abnormalities in patients with COPD are also found in smokers with minor lung dysfunction manifesting as a KCO decrease. Decreased KCO might be useful, particularly among women, for identifying smokers at high risk for aging-related systemic manifestations and telomere shortening. PMID:25785739

  9. Improvement in age-related cognitive functions and life expectancy by ketogenic diets

    DEFF Research Database (Denmark)

    Astrup, Arne; Hjorth, Mads Fiil

    2017-01-01

    Rodent studies have indicated that low-carbohydrate diets prevent age-related cognitive decline and extend lifespan due to increased circulating levels of ketone bodies. A possible physiological mechanism for how ketone bodies exert this effect might be by improving central nervous system insulin...

  10. Prediction and characterization of human ageing-related proteins by using machine learning.

    Science.gov (United States)

    Kerepesi, Csaba; Daróczy, Bálint; Sturm, Ádám; Vellai, Tibor; Benczúr, András

    2018-03-06

    Ageing has a huge impact on human health and economy, but its molecular basis - regulation and mechanism - is still poorly understood. By today, more than three hundred genes (almost all of them function as protein-coding genes) have been related to human ageing. Although individual ageing-related genes or some small subsets of these genes have been intensively studied, their analysis as a whole has been highly limited. To fill this gap, for each human protein we extracted 21000 protein features from various databases, and using these data as an input to state-of-the-art machine learning methods, we classified human proteins as ageing-related or non-ageing-related. We found a simple classification model based on only 36 protein features, such as the "number of ageing-related interaction partners", "response to oxidative stress", "damaged DNA binding", "rhythmic process" and "extracellular region". Predicted values of the model quantify the relevance of a given protein in the regulation or mechanisms of the human ageing process. Furthermore, we identified new candidate proteins having strong computational evidence of their important role in ageing. Some of them, like Cytochrome b-245 light chain (CY24A) and Endoribonuclease ZC3H12A (ZC12A) have no previous ageing-associated annotations.

  11. Automatic Drusen Quantification and Risk Assessment of Age-related Macular Degeneration on Color Fundus Images

    NARCIS (Netherlands)

    Grinsven, M.J.J.P. van; Lechanteur, Y.T.E.; Ven, J.P.H. van de; Ginneken, B. van; Hoyng, C.B.; Theelen, T.; Sanchez, C.I.

    2013-01-01

    PURPOSE: To evaluate a machine learning algorithm that allows for computer aided diagnosis (CAD) of non-advanced age-related macular degeneration (AMD) by providing an accurate detection and quantification of drusen location, area and size. METHODS: Color fundus photographs of 407 eyes without AMD

  12. Risk factors for visually disabling age-related cataracts in Ibadan ...

    African Journals Online (AJOL)

    Objective: To assess the risk factors for visually disabling age related cataracts. Methods: A hospital based case-control study carried out at the university College Hospital Ibadan between May 1996 and March 1997. Three hundred and eighty three cases were matched for age and sex with five hundred and ninety nine ...

  13. The posterior parahippocampal gyrus is preferentially affected in age-related memory decline.

    NARCIS (Netherlands)

    Burgmans, S.; van Boxtel, M.P.J.; van den Berg, K.E.M.; Gronenschild, E.H.B.M.; Jacobs, H.I.L.; Jolles, J.; Uylings, H.B.M.

    2011-01-01

    Atrophy in the medial temporal lobe is generally considered to be highly associated with age-related memory decline. Volume loss in the hippocampus and entorhinal cortex has extensively been investigated, but the posterior parts of the parahippocampal gyrus have received little attention. The

  14. The posterior parahippocampal gyrus is preferentially affected in age-related memory decline

    NARCIS (Netherlands)

    Burgmans, S.; van Boxtel, M.P.J.; van den Berg, K.E.M.; Gronenschild, E.H.; Jacobs, H.I.L.; Jolles, J.; Uylings, H.B.M.

    2009-01-01

    Atrophy in the medial temporal lobe is generally considered to be highly associated with age-related memory decline. Volume loss in the hippocampus and entorhinal cortex has extensively been investigated, but the posterior parts of the parahippocampal gyrus have received little attention. The

  15. Assessing Age-Related Etiologic Heterogeneity in the Onset of Islet Autoimmunity

    Directory of Open Access Journals (Sweden)

    Brittni N. Frederiksen

    2015-01-01

    Full Text Available Type 1 diabetes (T1D, a chronic autoimmune disease, is often preceded by a preclinical phase of islet autoimmunity (IA where the insulin-producing beta cells of the pancreas are destroyed and circulating autoantibodies can be detected. The goal of this study was to demonstrate methods for identifying exposures that differentially influence the disease process at certain ages by assessing age-related heterogeneity. The Diabetes Autoimmunity Study in the Young (DAISY has followed 2,547 children at increased genetic risk for T1D from birth since 1993 in Denver, Colorado, 188 of whom developed IA. Using the DAISY population, we evaluated putative determinants of IA, including non-Hispanic white (NHW ethnicity, maternal age at birth, and erythrocyte membrane n-3 fatty acid (FA levels, for age-related heterogeneity. A supremum test, weighted Schoenfeld residuals, and restricted cubic splines were used to assess nonproportional hazards, that is, an age-related association of the exposure with IA risk. NHW ethnicity, maternal age, and erythrocyte membrane n-3 FA levels demonstrated a significant age-related association with IA risk. Assessing heterogeneity in disease etiology enables researchers to identify associations that may lead to better understanding of complex chronic diseases.

  16. Side effects after radiotherapy of age-related macular degeneration with the Nijmegen technique.

    NARCIS (Netherlands)

    Hoyng, C.B.; Tromp, A.I.; Meulendijks, C.F.M.; Leys, A.; Maazen, R.W.M. van der; Deutman, A.F.; Vingerling, J.R.

    2002-01-01

    BACKGROUND: In a randomized trial concerning radiotherapy for age-related macular degeneration, fluorescein angiograms were taken of controls and patients. In this study the frequency of side effects in eyes receiving radiotherapy with the Nijmegen technique is compared with the findings in the eyes

  17. Immunological Factors in the Pathogenesis and Treatment of Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Kijlstra, A.; Heij, La E.C.; Hendrikse, F.

    2005-01-01

    Recent findings indicate that immunological factors are involved not only in the pathogenesis of age-related macular degeneration (AMD), but also in its treatment. Earlier data showing the presence of inflammatory cells in affected areas of AMD retinas support this statement. Although a possible

  18. Risk assessment model for development of advanced age-related macular degeneration.

    Science.gov (United States)

    Klein, Michael L; Francis, Peter J; Ferris, Frederick L; Hamon, Sara C; Clemons, Traci E

    2011-12-01

    To design a risk assessment model for development of advanced age-related macular degeneration (AMD) incorporating phenotypic, demographic, environmental, and genetic risk factors. We evaluated longitudinal data from 2846 participants in the Age-Related Eye Disease Study. At baseline, these individuals had all levels of AMD, ranging from none to unilateral advanced AMD (neovascular or geographic atrophy). Follow-up averaged 9.3 years. We performed a Cox proportional hazards analysis with demographic, environmental, phenotypic, and genetic covariates and constructed a risk assessment model for development of advanced AMD. Performance of the model was evaluated using the C statistic and the Brier score and externally validated in participants in the Complications of Age-Related Macular Degeneration Prevention Trial. The final model included the following independent variables: age, smoking history, family history of AMD (first-degree member), phenotype based on a modified Age-Related Eye Disease Study simple scale score, and genetic variants CFH Y402H and ARMS2 A69S. The model did well on performance measures, with very good discrimination (C statistic = 0.872) and excellent calibration and overall performance (Brier score at 5 years = 0.08). Successful external validation was performed, and a risk assessment tool was designed for use with or without the genetic component. We constructed a risk assessment model for development of advanced AMD. The model performed well on measures of discrimination, calibration, and overall performance and was successfully externally validated. This risk assessment tool is available for online use.

  19. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans

    NARCIS (Netherlands)

    M. Rahimi (Mehran); M. Vinciguerra (Manlio); M. Daghighi (Mojtaba); B. Özcan (Behiye); V. Akbarkhanzadeh (Vishtaseb); F. Sheedfar (Fareeba); M. Amini (Marzyeh); T. Mazza (Tommaso); V. Pazienza (Valerio); M.M. Motazacker (Mohammad); T. Mahmoudi (Tokameh); F.W.M. de Rooij (Felix); E.J.G. Sijbrands (Eric); M.P. Peppelenbosch (Maikel); F. Rezaee (Farhad)

    2015-01-01

    textabstractDespite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue

  20. Aging-related systemic manifestations in COPD patients and cigarette smokers.

    Directory of Open Access Journals (Sweden)

    Laurent Boyer

    Full Text Available Chronic obstructive pulmonary disease (COPD is often associated with age-related systemic abnormalities that adversely affect the prognosis. Whether these manifestations are linked to the lung alterations or are independent complications of smoking remains unclear.To look for aging-related systemic manifestations and telomere shortening in COPD patients and smokers with minor lung destruction responsible for a decline in the diffusing capacity for carbon monoxide (DLCO corrected for alveolar volume (KCO.Cross-sectional study in 301 individuals (100 with COPD, 100 smokers without COPD, and 101 nonsmokers without COPD.Compared to control smokers, patients with COPD had higher aortic pulse-wave velocity (PWV, lower bone mineral density (BMD and appendicular skeletal muscle mass index (ASMMI, and shorter telomere length (TL. Insulin resistance (HOMA-IR and glomerular filtration rate (GFR were similar between control smokers and COPD patients. Smokers did not differ from nonsmokers for any of these parameters. However, smokers with normal spirometry but low KCO had lower ASMMI values compared to those with normal KCO. Moreover, female smokers with low KCO, had lower BMD and shorter TL compared to those with normal KCO.Aging-related abnormalities in patients with COPD are also found in smokers with minor lung dysfunction manifesting as a KCO decrease. Decreased KCO might be useful, particularly among women, for identifying smokers at high risk for aging-related systemic manifestations and telomere shortening.

  1. Single-Chain Antibody Fragment VEGF Inhibitor RTH258 for Neovascular Age-Related Macular Degeneration

    DEFF Research Database (Denmark)

    Holz, Frank G; Dugel, Pravin U.; Weissgerber, Georges

    2016-01-01

    Purpose To assess the safety and efficacy of different doses of RTH258 applied as single intravitreal administration compared with ranibizumab 0.5 mg in patients with neovascular age-related macular degeneration (AMD). Design Six-month, phase 1/2, prospective, multicenter, double-masked, randomized...

  2. VITRECTOMY FOR INTERMEDIATE AGE-RELATED MACULAR DEGENERATION ASSOCIATED WITH TANGENTIAL VITREOMACULAR TRACTION: A CLINICOPATHOLOGIC CORRELATION.

    Science.gov (United States)

    Ziada, Jean; Hagenau, Felix; Compera, Denise; Wolf, Armin; Scheler, Renate; Schaumberger, Markus M; Priglinger, Siegfried G; Schumann, Ricarda G

    2018-03-01

    To describe the morphologic characteristics of the vitreomacular interface in intermediate age-related macular degeneration associated with tangential traction due to premacular membrane formation and to correlate with optical coherence tomography (OCT) findings and clinical data. Premacular membrane specimens were removed sequentially with the internal limiting membrane from 27 eyes of 26 patients with intermediate age-related macular degeneration during standard vitrectomy. Specimens were processed for immunocytochemical staining of epiretinal cells and extracellular matrix components. Ultrastructural analysis was performed using transmission electron microscopy. Spectral domain optical coherence tomography images and patient charts were evaluated in retrospect. Immunocytochemistry revealed hyalocytes and myofibroblasts as predominant cell types. Ultrastructural analysis demonstrated evidence of vitreoschisis in all eyes. Myofibroblasts with contractile properties were observed to span between folds of the internal limiting membrane and vitreous cortex collagen. Retinal pigment epithelial cells or inflammatory cells were not detected. Mean visual acuity (Snellen) showed significant improvement from 20/72 ± 20/36 to 20/41 ± 20/32 (P age-related macular degeneration predominantly consists of vitreous collagen, hyalocytes, and myofibroblasts with contractile properties. Vitreoschisis and vitreous-derived cells appear to play an important role in traction formation of this subgroup of eyes. In patients with intermediate age-related macular degeneration and contractile premacular membrane, release of traction by vitrectomy with internal limiting membrane peeling results in significantly functional and anatomical improvement.

  3. Physical activity patterns in patients with early and late age-related macular degeneration

    DEFF Research Database (Denmark)

    Subhi, Yousif; Sørensen, Torben Lykke

    2016-01-01

    INTRODUCTION: Age-related macular degeneration (AMD) leads to visual impairment that affects visual functioning and thereby the ability to be physically active. We investigated physical activity patterns in patients with AMD. METHODS: Patients with early and late AMD and elderly controls were...

  4. Visual outcomes in relation to time to treatment in neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Rasmussen, Annette; Bloch, Sara Brandi; Fuchs, Josefine

    2015-01-01

    PURPOSE: To study the relation between the interval from diagnosis to initiation of intravitreal injection therapy and visual outcome in neovascular age-related macular degeneration (nAMD) and to report changes over time in fellow-eye status. METHODS: Retrospective chart review. The study included...

  5. The association between Neovascular Age-related Macular Degeneration and Regulatory T cells in peripheral blood

    DEFF Research Database (Denmark)

    Madelung, Christopher Fugl; Falk, Mads; Sørensen, Torben Lykke

    2015-01-01

    PURPOSE: To investigate regulatory T cells (Tregs) and subsets of the Treg population in patients with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: Twenty-one neovascular AMD cases and 12 age-matched controls without retinal pathology were selected. Patients were...

  6. Cataract surgery and age-related macular degeneration. An evidence-based update

    DEFF Research Database (Denmark)

    Kessel, Line; Erngaard, Ditte; Flesner, Per

    2015-01-01

    PURPOSE: Age-related macular degeneration (AMD) and cataract often coexist in patients and concerns that cataract surgery is associated with an increased risk of incidence or progression of existing AMD has been raised. This systematic review and meta-analysis is focused on presenting the evidence...

  7. Cardiovascular risk factors associated with age-related macular degeneration: the Tromso Study

    DEFF Research Database (Denmark)

    Erke, M. G.; Bertelsen, G.; Peto, T.

    2014-01-01

    PurposeTo examine associations between cardiovascular risk factors and age-related macular degeneration (AMD). MethodsA population-based, cross-sectional study of Caucasians aged 65-87years was conducted in Norway in 2007/2008. Retinal photographs were graded for AMD. Multivariable logistic...

  8. RISK FACTORS AND CLINICAL SIGNIFICANCE OF PRECHOROIDAL CLEFT IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

    Science.gov (United States)

    Kim, Jong Min; Kang, Se Woong; Son, Dae Yong; Bae, Kunho

    2017-11-01

    To investigate the risk factors associated with prechoroidal cleft occurrence after treatment for neovascular age-related macular degeneration (nAMD) and to elucidate its clinical significance. Two hundred thirty-four subjects who were treated for neovascular age-related macular degeneration were assessed to identify prechoroidal cleft on optical coherence tomography. Clinical variables were compared between patients manifesting a cleft (cleft group) and patients who did not (control group). Prechoroidal cleft was detected in 29 of 234 patients (8.1%). Although the baseline visual acuity was not different between the 2 groups, logMAR visual acuity at final visit was 0.89 ± 0.74 (with approximate Snellen equivalent of 20/160) in the cleft group and 0.65 ± 0.69 (with approximate Snellen equivalent of 20/100) in controls (P age-related macular degeneration (P age-related macular degeneration, and a submacular hemorrhage treated by pneumatic displacement were the independent risk factors for development of prechoroidal cleft. Eyes with a cleft, especially clefts that develop early, generally had worse prognoses than eyes without clefts.

  9. A systematic review on zinc for the prevention and treatment of age-related macular degeneration

    Science.gov (United States)

    Zinc is a potential candidate for the prevention and treatment of age-related macular degeneration (AMD) due to its high concentration in the retina and role as a cofactor for antioxidant enzymes. The objective of this work was to conduct a systematic review of studies that investigated dietary inta...

  10. Visualization of dietary patterns and their associations with age-related macular degeneration

    Science.gov (United States)

    PURPOSE: We aimed to visualize the relationship of predominant dietary patterns and their associations with AMD. METHODS: A total of 8103 eyes from 4088 participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into three groups: control (n=2739), early AMD (n=4599), and adv...

  11. ESTIMATION OF INTRINSIC AND EXTRINSIC ENVIRONMENT FACTORS OF AGE-RELATED TOOTH COLOUR CHANGES

    Czech Academy of Sciences Publication Activity Database

    Hyšpler, P.; Jezbera, D.; Fürst, T.; Mikšík, Ivan; Waclawek, M.

    2010-01-01

    Roč. 17, č. 4 (2010), s. 515-525 ISSN 1898-6196 Institutional research plan: CEZ:AV0Z50110509 Keywords : age-related colour changes of teeth * intrinsic and extrinsic factors * 3D mathematical regression models * estimation of real age Subject RIV: ED - Physiology Impact factor: 0.294, year: 2010

  12. Circadian and age-related modulation of thermoception and temperature regulation: mechanisms and functional implications.

    NARCIS (Netherlands)

    van Someren, E.J.W.; Raymann, RJEM; Scherder, E.J.A.; Daanen, H.A.M.; Swaab, D.F.

    2002-01-01

    At older ages, the circadian rhythm of body temperature shows a decreased amplitude, an advanced phase, and decreased stability. The present review evaluates to what extent these changes may result from age-related deficiencies at several levels of the thermoregulatory system, including

  13. Circadian and age-related modulation of thermoreception and temperature regulation: mechanisms and functional implications

    NARCIS (Netherlands)

    van Someren, Eus J. W.; Raymann, Roy J. E. M.; Scherder, Erik J. A.; Daanen, Hein A. M.; Swaab, Dick F.

    2002-01-01

    At older ages, the circadian rhythm of body temperature shows a decreased amplitude, an advanced phase, and decreased stability. The present review evaluates to what extent these changes may result from age-related deficiencies at several levels of the thermoregulatory system, including

  14. Osseous oligometastases from thymic carcinoma: a case report suggesting the effectiveness of palliative-intent radiotherapy treatment.

    Science.gov (United States)

    Kashima, Jumpei; Horio, Hirotoshi; Okuma, Yusuke; Hosomi, Yukio; Hishima, Tsunekazu

    2016-01-01

    Oligometastasis, a recently proposed concept, is defined as an intermediate state of cancer, between localized and systemic disease, that may be well controlled by local ablative treatment. Thymic carcinoma is a rare cancer with a poor prognosis. A definitive management approach has yet to be confirmed by a high level of evidence. We present the case of a 41-year-old female who underwent curative-intent surgery for a stage III squamous cell carcinoma of the thymus. Bone metastases were detected 1 year later by magnetic resonance imaging. These were treated with palliative-intent radiotherapy. Disease progression has not been observed in more than 15 years since the achievement of complete radiological remission. The treatment outcomes in this and other reported cases suggest that some patients with oligometastatic thymic carcinoma may achieve prolonged survival or even cure with low-dose radiotherapy delivered to the metastases.

  15. Thymic involvement in immune recovery during antiretroviral treatment of HIV infection in adults; comparison of CT and sonographic findings

    DEFF Research Database (Denmark)

    Kolte, Lilian; Strandberg, Charlotte; Dreves, Anne-Mette

    2002-01-01

    ) repertoire were determined. The study demonstrated no correlation between the 2 scanning methods (r = 0.201, p = 0.358 in patients and r = 0.457, p = 0.184 in controls). Among the patients, no association was found between the sonographically estimated thymic size and immunological parameters such as CD4...... count (r = 0.083, p = 0.706), naive CD4 count (r = 0.067, p = 0.762), CD4 + TREC frequency (r = 0.028, p = 0.900) and CD4 + TCR repertoire (r = -0.057, p = 0.828). These findings show that CT remains superior for assessing thymic size in adults and is preferable to ultrasound when evaluating...

  16. Diagnostic value of plain chest roentgenogram and CT scan findings in four cases of massive thymic hyperplasia

    International Nuclear Information System (INIS)

    Kobayashi, T.; Hirabayashi, Y.; Kobayashi, Y.

    1986-01-01

    Massive thymic hyperplasia (MTH) is rare in the pediatric age group, especially in infants. However, because of a wide variation in size and weight of the thymus, an enlarged gland is often resected because of suspicion of a neoplasm or a cyst. Some cases of thymoma resembling pulmonary acute infection occur less frequently than MTH, but if respiratory problems are accompanied by a large thymus immediate diagnosis is often necessary to differentiate between these two conditions. Four infants (14 days to 4 months of age) with MTH were recently studied, all having an acute onset an of severe respiratory distress. The infants were referred to our center with a tentative diagnosis of thymic or other intrathoracic tumors. The following case reports illustrate our diagnostic approach to evaluate patients with symptoms suggesting MTH and the response to the ''steroid test''. (orig.)

  17. Identification of differentially expressed proteins in spontaneous thymic lymphomas from knockout mice with deletion of p53

    DEFF Research Database (Denmark)

    Honoré, Bent; Buus, Søren; Claësson, Mogens H

    2008-01-01

    ABSTRACT: BACKGROUND: Knockout mice with a deletion of p53 spontaneously develop thymic lymphomas. Two cell lines (SM5 and SM7), established from two independent tumours, exhibited about fifty to seventy two-fold differentially expressed proteins compared to wild type thymocytes by two-dimensiona......ABSTRACT: BACKGROUND: Knockout mice with a deletion of p53 spontaneously develop thymic lymphomas. Two cell lines (SM5 and SM7), established from two independent tumours, exhibited about fifty to seventy two-fold differentially expressed proteins compared to wild type thymocytes by two...... alpha type 3, transforming acidic coiled-coil containing protein 3, mitochondrial ornithine aminotransferase and epidermal fatty acid binding protein and down-regulation of adenylosuccinate synthetase, tubulin beta-3 chain, a 25 kDa actin fragment, proteasome subunit beta type 9, cofilin-1 and glia...

  18. B and T lymphocytes in man. I. Effect of infant thymic irradiation on the circulating B and T lymphocytes

    International Nuclear Information System (INIS)

    Reddy, M.M.; Goh, K.; Hempelmann, L.H.

    1976-01-01

    B and T lymphocytes were studied in a group of adults whose thymic glands were irradiated in infancy for alleged thymic enlargement. Two independent methods were used to determine the B and T lymphocytes from each peripheral blood specimen: (1) the relative proportion of cells with surface immunoglobulins (B lymphocytes) and cells forming rosettes with sheep erythrocytes (T lymphocytes); and (2) the relative mitogenic response to phytohemagglutinin (T lymphocytes) and to pokeweed mitogen (B lymphocytes). All specimens were coded. The results obtained indicate: (1) a reduction of B and T lymphocytes; and (2) a decreased mitogenic response of lymphocytes to phytohemagglutinin and pokeweed mitogen in this group of patients as compared with the controls. These observations suggest that (1) the effect of irradiation to the thymus gland on lymphocytes is long lasting and (2) both B and T lymphocytes are affected by irradiation to the thymus gland

  19. Long-term persistence of functional thymic epithelial progenitor cells in vivo under conditions of low FOXN1 expression

    DEFF Research Database (Denmark)

    Jin, Xin; Nowell, Craig S; Ulyanchenko, Svetlana

    2014-01-01

    does not require FOXN1. Here, we have used a revertible severely hypomorphic allele of Foxn1, Foxn1R, to test the stability of the common TEPC in vivo. By reactivating Foxn1 expression postnatally in Foxn1R/- mice we demonstrate that functional TEPCs can persist in the thymic rudiment until at least 6...... months of age, and retain the potential to give rise to both cortical and medullary thymic epithelial cells (cTECs and mTECs). These data demonstrate that the TEPC-state is remarkably stable in vivo under conditions of low Foxn1 expression, suggesting that manipulation of FOXN1 activity may prove...... a valuable method for long term maintenance of TEPC in vitro....

  20. Age-Related Reversals in Neural Recruitment across Memory Retrieval Phases.

    Science.gov (United States)

    Ford, Jaclyn H; Kensinger, Elizabeth A

    2017-05-17

    Over the last several decades, neuroimaging research has identified age-related neural changes that occur during cognitive tasks. These changes are used to help researchers identify functional changes that contribute to age-related impairments in cognitive performance. One commonly reported example of such a change is an age-related decrease in the recruitment of posterior sensory regions coupled with an increased recruitment of prefrontal regions across multiple cognitive tasks. This shift is often described as a compensatory recruitment of prefrontal regions due to age-related sensory-processing deficits in posterior regions. However, age is not only associated with spatial shifts in recruitment, but also with temporal shifts, in which younger and older adults recruit the same neural region at different points in a task trial. The current study examines the possible contribution of temporal modifications in the often-reported posterior-anterior shift. Participants, ages 19-85, took part in a memory retrieval task with a protracted retrieval trial consisting of an initial memory search phase and a subsequent detail elaboration phase. Age-related neural patterns during search replicated prior reports of age-related decreases in posterior recruitment and increases in prefrontal recruitment. However, during the later elaboration phase, the same posterior regions were associated with age-related increases in activation. Further, ROI and functional connectivity results suggest that these posterior regions function similarly during search and elaboration. These results suggest that the often-reported posterior-anterior shift may not reflect the inability of older adults to engage in sensory processing, but rather a change in when they recruit this processing. SIGNIFICANCE STATEMENT The current study provides evidence that the often-reported posterior-anterior shift in aging may not reflect a global sensory-processing deficit, as has often been reported, but rather a