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Sample records for age-related thymic involution

  1. Declining expression of a single epithelial cell-autonomous gene accelerates age-related thymic involution

    PubMed Central

    Sun, Liguang; Guo, Jianfei; Brown, Robert; Amagai, Takashi; Zhao, Yong; Su, Dong-Ming

    2010-01-01

    SUMMARY Age-related thymic involution may be triggered by gene expression changes in lymphohematopoietic and/or non-hematopoietic thymic epithelial cells (TECs). The role of epithelial cell-autonomous gene FoxN1 may be involved in the process, but it is still a puzzle due to shortage of evidence from gradual loss-of-function and exogenous gain-of-function studies. Using our recently generated loxP-floxed-FoxN1(fx) mouse carrying the ubiquitous CreERT (uCreERT) transgene with a low dose of spontaneous activation, which causes gradual FoxN1 deletion with age, we found that the uCreERT-fx/fx mice showed an accelerated age-related thymic involution due to progressive loss of FoxN1+ TECs. The thymic aging phenotypes were clearly observable as early as at 3–6 months of age, resembling the naturally aged (18–22-month-old) murine thymus. By intrathymically supplying aged wild-type mice with exogenous FoxN1-cDNA, thymic involution and defective peripheral CD4+ T-cell function could be partially rescued. The results support the notion that decline of a single epithelial cell-autonomous gene FoxN1 levels with age causes primary deterioration in TECs followed by impairment of the total postnatal thymic microenvironment, and potentially triggers age-related thymic involution in mice. PMID:20156205

  2. Prolongevity hormone FGF21 protects against immune senescence by delaying age-related thymic involution.

    PubMed

    Youm, Yun-Hee; Horvath, Tamas L; Mangelsdorf, David J; Kliewer, Steven A; Dixit, Vishwa Deep

    2016-01-26

    Age-related thymic degeneration is associated with loss of naïve T cells, restriction of peripheral T-cell diversity, and reduced healthspan due to lower immune competence. The mechanistic basis of age-related thymic demise is unclear, but prior evidence suggests that caloric restriction (CR) can slow thymic aging by maintaining thymic epithelial cell integrity and reducing the generation of intrathymic lipid. Here we show that the prolongevity ketogenic hormone fibroblast growth factor 21 (FGF21), a member of the endocrine FGF subfamily, is expressed in thymic stromal cells along with FGF receptors and its obligate coreceptor, βKlotho. We found that FGF21 expression in thymus declines with age and is induced by CR. Genetic gain of FGF21 function in mice protects against age-related thymic involution with an increase in earliest thymocyte progenitors and cortical thymic epithelial cells. Importantly, FGF21 overexpression reduced intrathymic lipid, increased perithymic brown adipose tissue, and elevated thymic T-cell export and naïve T-cell frequencies in old mice. Conversely, loss of FGF21 function in middle-aged mice accelerated thymic aging, increased lethality, and delayed T-cell reconstitution postirradiation and hematopoietic stem cell transplantation (HSCT). Collectively, FGF21 integrates metabolic and immune systems to prevent thymic injury and may aid in the reestablishment of a diverse T-cell repertoire in cancer patients following HSCT. PMID:26755598

  3. Global transcriptional profiling reveals distinct functions of thymic stromal subsets and age-related changes during thymic involution

    PubMed Central

    Ki, Sanghee; Park, Daechan; Selden, Hilary J.; Seita, Jun; Chung, Haewon; Kim, Jonghwan; Iyer, Vishwanath R.; Ehrlich, Lauren I. R.

    2014-01-01

    Summary Age-associated thymic involution results in diminished T cell output and function in aged individuals. However, molecular mediators contributing to the decline in thymic function during early thymic involution remain largely unknown. Here we present transcriptional profiling of purified thymic stromal subsets from mice 1, 3, and 6 months of age, spanning early thymic involution. The data implicate novel biological functions for a subset of thymic epithelial cells. The predominant transcriptional signature of early thymic involution is decreased expression of cell cycle associated genes and E2F3 transcriptional targets in thymic epithelial subsets. Also, expression of pro-inflammatory genes increases with age in thymic dendritic cells. Many genes previously implicated in late involution are already deregulated by 3 to 6 months of age. We provide these thymic stromal datasets, along with thymocyte datasets, in a readily searchable web-based platform, as a resource for investigations into thymocyte: stromal interactions and mechanisms of thymic involution. PMID:25284794

  4. Trade off situation between thymus and growth hormone: age-related decline of growth hormone is a cause of thymic involution but favorable for elongation of lifespan.

    PubMed

    Hirokawa, Katsuiku; Utsuyama, Masanori; Kikuchi, Yuko

    2016-02-01

    High level of growth hormone (GH) is necessary for the activation of thymic function to promote T cell differentiation in the early stage of animal life. In the later stage of the life, administration of GH promotes the development of immune system and rejuvenates declined immune function of elderly people. By contraries, GH deficiency is favorable for the longer lifespan, as hypo-pituitary dwarf mice such as Ames and Snell dwarf mice exhibit longer lifespan than control. Furthermore over-expression of heterologous or homologous GH in transgenic mice shortens the lifespan. Ecuadorians carrying mutations of GH receptor gene are short in height, but exhibited low frequency of malignancy and no cases of diabetes. These data indicate that GH is necessary for the development of thymus dependent immune system but GH deficiency is favorable for long life span and decreases occurrence of cancer and DM. This situation is a kind of trade off situation between the immune system and GH. Thus the early decline of high level of GH occurring shortly after the birth is a cause of early decline of thymic functions, but favorable for longer lifespan. This situation could be a kind of trade off situation between thymus and GH.

  5. Foxn1 Is Dynamically Regulated in Thymic Epithelial Cells during Embryogenesis and at the Onset of Thymic Involution.

    PubMed

    O'Neill, Kathy E; Bredenkamp, Nicholas; Tischner, Christin; Vaidya, Harsh J; Stenhouse, Frances H; Peddie, C Diana; Nowell, Craig S; Gaskell, Terri; Blackburn, C Clare

    2016-01-01

    Thymus function requires extensive cross-talk between developing T-cells and the thymic epithelium, which consists of cortical and medullary TEC. The transcription factor FOXN1 is the master regulator of TEC differentiation and function, and declining Foxn1 expression with age results in stereotypical thymic involution. Understanding of the dynamics of Foxn1 expression is, however, limited by a lack of single cell resolution data. We have generated a novel reporter of Foxn1 expression, Foxn1G, to monitor changes in Foxn1 expression during embryogenesis and involution. Our data reveal that early differentiation and maturation of cortical and medullary TEC coincides with precise sub-lineage-specific regulation of Foxn1 expression levels. We further show that initiation of thymic involution is associated with reduced cTEC functionality, and proportional expansion of FOXN1-negative TEC in both cortical and medullary sub-lineages. Cortex-specific down-regulation of Foxn1 between 1 and 3 months of age may therefore be a key driver of the early stages of age-related thymic involution. PMID:26983083

  6. Foxn1 Is Dynamically Regulated in Thymic Epithelial Cells during Embryogenesis and at the Onset of Thymic Involution

    PubMed Central

    O’Neill, Kathy E.; Bredenkamp, Nicholas; Tischner, Christin; Vaidya, Harsh J.; Stenhouse, Frances H.; Peddie, C. Diana; Nowell, Craig S.; Gaskell, Terri; Blackburn, C. Clare

    2016-01-01

    Thymus function requires extensive cross-talk between developing T-cells and the thymic epithelium, which consists of cortical and medullary TEC. The transcription factor FOXN1 is the master regulator of TEC differentiation and function, and declining Foxn1 expression with age results in stereotypical thymic involution. Understanding of the dynamics of Foxn1 expression is, however, limited by a lack of single cell resolution data. We have generated a novel reporter of Foxn1 expression, Foxn1G, to monitor changes in Foxn1 expression during embryogenesis and involution. Our data reveal that early differentiation and maturation of cortical and medullary TEC coincides with precise sub-lineage-specific regulation of Foxn1 expression levels. We further show that initiation of thymic involution is associated with reduced cTEC functionality, and proportional expansion of FOXN1-negative TEC in both cortical and medullary sub-lineages. Cortex-specific down-regulation of Foxn1 between 1 and 3 months of age may therefore be a key driver of the early stages of age-related thymic involution. PMID:26983083

  7. Thymic Involution in Ontogenesis: Role in Aging Program.

    PubMed

    Shilovsky, G A; Feniouk, B A; Skulachev, V P

    2015-12-01

    In most mammals, involution of the thymus occurs with aging. In this issue of Biochemistry (Moscow) devoted to phenoptosis, A. V. Khalyavkin considered involution of a thymus as an example of the program of development and further--of proliferation control and prevention of tumor growth. However, in animals devoid of a thymus (e.g. naked mice), stimulation of carcinogenesis, but not its prevention was observed. In this report, we focus on the involution of the thymus as a manifestation of the aging program (slow phenoptosis). We also consider methods of reversal/arrest of this program at different levels of organization of life (cell, tissue, and organism) including surgical manipulations, hormonal effects, genetic techniques, as well as the use of conventional and mitochondria-targeted antioxidants. We conclude that programmed aging (at least on the model of age-dependent thymic atrophy) can be inhibited. PMID:26638690

  8. Thymic involution in the suspended rat - Adrenal hypertrophy and glucocorticoid receptor content

    NASA Technical Reports Server (NTRS)

    Steffen, J. M.; Musacchia, X. J.

    1986-01-01

    The relationship between thymic involution and adrenal hypertrophy is studied. The thymus, adrenal glands, and tissue water content are evaluated in male Sprague rats suspended in antiorthostatic (AO) or orthostatic (O) positions. A 50 percent decrease in the wet weight of the thymus and hypertrophy of the adrenal glands are observed during the seven days of AO suspension. After seven days of recovery the thymus weight is increased to control level; however, the hypertrophy of the adrenal glands remains unchanged. Thymic and renal responses in O postioned rats are similar to AO reactions. Thymic glucocorticoid (GC) receptor concentrations in the rats are analyzed; a 20 percent decrease in GC receptor site concentration, which is related to thymic involution, is detected in both AO and O rats. It is concluded that there is a temporal correlation between thymic involution and adrenal hypertrophy, which is not affected by AO positioning, and thymic involution is not associated with an increased sensitivity to GC.

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

    PubMed

    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.

  10. Expression of nerve growth factor is upregulated in the rat thymic epithelial cells during thymus regeneration following acute thymic involution.

    PubMed

    Lee, Hee-Woo; Kim, Sung-Min; Shim, Na-Ri; Bae, Soo-Kyung; Jung, Il-Gun; Kwak, Jong-Young; Kim, Bong-Seon; Kim, Jae-Bong; Moon, Jeon-Ok; Chung, Joo-Seop; Yoon, Sik

    2007-06-01

    Neuroimmune networks in the thymic microenvironment are thought to be involved in the regulation of T cell development. Nerve growth factor (NGF) is increasingly recognized as a potent immunomodulator, promoting "cross-talk" between various types of immune system cells. The present study describes the expression of NGF during thymus regeneration following acute involution induced by cyclophosphamide in the rat. Immunohistochemical stain demonstrated not only the presence of NGF but also its upregulated expression mainly in the subcapsular, paraseptal, and perivascular epithelial cells, and medullary epithelial cells including Hassall's corpuscles in both the normal and regenerating thymus. Biochemical data obtained using Western blot and RT-PCR supported these results and showed that thymic extracts contain NGF protein and mRNA, at higher levels during thymus regeneration. Thus, our results suggest that NGF expressed in these thymic epithelial cells plays a role in the T lymphopoiesis associated with thymus regeneration during recovery from acute thymic involution.

  11. Thymic involution in the suspended rat model for weightlessness - Decreased glucocorticoid receptor concentration

    NASA Technical Reports Server (NTRS)

    Steffen, J. M.; Musacchia, X. J.

    1984-01-01

    Hindlimb muscle atrophy, thymic involution and adrenal hypertrophy in rats during spaceflight can be simulated using suspension models. Skeletal muscle and thymus are sensitive to gluco-corticoids (GC), and previous studies have demonstrated that muscle atrophy in suspended rats is associated with increased GC receptor concentration. The objectives were to confirm thymic involution during suspension, and determine if involution correlated with increased GC receptor concentration. Seven days of antiorthostatic (AO) suspension of rats produced a significant (P less than 0.001) reduction in thymic wet weight not associated with an alteration of percent water content. GC receptor concentration (pmol/mg protein) decreased 20 percent (P less than 0.025) in thymus glands from 7 day AO suspended rats. Suspension, therefore, is associated with involution of the thymus, but this is not dependent upon AO positioning. Thymus GC receptor concentrations were depressed in 7-day suspended rats, in contrast with previous observations on skeletal muscle, suggesting that different mechanisms may underlie these responses.

  12. Digital histologic analysis reveals morphometric patterns of age-related involution in breast epithelium and stroma.

    PubMed

    Sandhu, Rupninder; Chollet-Hinton, Lynn; Kirk, Erin L; Midkiff, Bentley; Troester, Melissa A

    2016-02-01

    Complete age-related regression of mammary epithelium, often termed postmenopausal involution, is associated with decreased breast cancer risk. However, most studies have qualitatively assessed involution. We quantitatively analyzed epithelium, stroma, and adipose tissue from histologically normal breast tissue of 454 patients in the Normal Breast Study. High-resolution digital images of normal breast hematoxylin and eosin-stained slides were partitioned into epithelium, adipose tissue, and nonfatty stroma. Percentage area and nuclei per unit area (nuclear density) were calculated for each component. Quantitative data were evaluated in association with age using linear regression and cubic spline models. Stromal area decreased (P = 0.0002), and adipose tissue area increased (P < 0.0001), with an approximate 0.7% change in area for each component, until age 55 years when these area measures reached a steady state. Although epithelial area did not show linear changes with age, epithelial nuclear density decreased linearly beginning in the third decade of life. No significant age-related trends were observed for stromal or adipose nuclear density. Digital image analysis offers a high-throughput method for quantitatively measuring tissue morphometry and for objectively assessing age-related changes in adipose tissue, stroma, and epithelium. Epithelial nuclear density is a quantitative measure of age-related breast involution that begins to decline in the early premenopausal period.

  13. Natural history of age-related lobular involution and impact on breast cancer risk.

    PubMed

    Radisky, Derek C; Visscher, Daniel W; Frank, Ryan D; Vierkant, Robert A; Winham, Stacey; Stallings-Mann, Melody; Hoskin, Tanya L; Nassar, Aziza; Vachon, Celine M; Denison, Lori A; Hartmann, Lynn C; Frost, Marlene H; Degnim, Amy C

    2016-02-01

    Age-related lobular involution (LI) is a physiological process in which the terminal duct lobular units of the breast regress as a woman ages. Analyses of breast biopsies from women with benign breast disease (BBD) have found that extent of LI is negatively associated with subsequent breast cancer development. Here we assess the natural course of LI within individual women, and the impact of progressive LI on breast cancer risk. The Mayo Clinic BBD cohort consists of 13,455 women with BBD from 1967 to 2001. The BBD cohort includes 1115 women who had multiple benign biopsies, 106 of whom had developed breast cancer. Within this multiple biopsy cohort, the progression of the LI process was examined by age at initial biopsy and time between biopsies. The relationship between LI progression and breast cancer risk was assessed using standardized incidence ratios and by Cox proportional hazards analysis. Women who had multiple biopsies were younger age and had a slightly higher family history of breast cancer as compared with the overall BBD cohort. Extent of LI at subsequent biopsy was greater with increasing time between biopsies and for women age 55 + at initial biopsy. Among women with multiple biopsies, there was a significant association of higher breast cancer risk among those with involution stasis (lack of progression, HR 1.63) as compared with those with involution progression, p = 0.036. The multiple biopsy BBD cohort allows for a longitudinal study of the natural progression of LI. The majority of women in the multiple biopsy cohort showed progression of LI status between benign biopsies, and extent of progression was highest for women who were in the perimenopausal age range at initial biopsy. Progression of LI status between initial and subsequent biopsy was associated with decreased breast cancer risk. PMID:26846985

  14. The NLRP3 Inflammasome Promotes Age-related Thymic Demise and Immunosenescence

    PubMed Central

    Youm, Yun-Hee; Kanneganti, Thirumala-Devi; Vandanmagsar, Bolormaa; Zhu, Xuewei; Ravussin, Anthony; Adijiang, Ayinuer; Owen, John S.; Thomas, Michael J.; Francis, Joseph; Parks, John S.; Dixit, Vishwa Deep

    2013-01-01

    The collapse of thymic stromal cell microenvironment with age and resultant inability of the thymus to produce naïve T cells contributes to lower immune-surveillance in the elderly. Here we show that age-related increase in ‘lipotoxic danger signals’ such as free cholesterol (FC) and ceramides, leads to thymic caspase-1 activation via the Nlrp3 inflammasome. Elimination of Nlrp3 and Asc, a critical adaptor required for inflammasome assembly, reduces age-related thymic atrophy and results in an increase in cortical thymic epithelial cells, T cell progenitors and maintenance of T cell repertoire diversity. Using a mouse model of irradiation and hematopoietic stem cell transplantation (HSCT), we show that deletion of the Nlrp3 inflammasome accelerates T cell reconstitution and immune recovery in middle-aged animals. Collectively, these data demonstrate that lowering inflammasome-dependent caspase-1 activation increases thymic lymphopoiesis and suggest that Nlrp3 inflammasome inhibitors may aid the reestablishment of a diverse T cell repertoire in middle-aged or elderly patients undergoing HSCT. PMID:22832107

  15. Age-Related Disruption of Steady-State Thymic Medulla Provokes Autoimmune Phenotype via Perturbing Negative Selection.

    PubMed

    Xia, Jiangyan; Wang, Hongjun; Guo, Jianfei; Zhang, Zhijie; Coder, Brandon; Su, Dong-Ming

    2012-06-01

    The hymic medulla plays an essential role in the generation of central tolerance by eliminating self-reactive T-cell clones through thymic negative selection and developing natural regulatory T cells. Age-related FoxN1 decline induces disruption of medullary thymic epithelial cells (mTECs). However, it is unknown whether this perturbs central tolerance to increase autoimmune predisposition in the elderly. Using a loxP-floxed-FoxN1 (FoxN1(flox)) mouse model, which exhibits a spontaneous ubiquitous deletion of FoxN1 with age to accelerate thymic aging, we investigated whether disruption of steady-state thymic medulla results in an increase of autoimmune-prone associated with age. We demonstrated age-associated ubiquitous loss of FoxN1(flox)-formed two-dimensional thymic epithelial cysts were primarily located in the medulla. This resulted in disruption of thymic medullary steady state, with evidence of perturbed negative selection, including reduced expression of the autoimmune regulator (Aire) gene and disrupted accumulation of thymic dendritic cells in the medulla, which are required for negative selection. These provoke autoimmune phenotypes, including increased inflammatory cell infiltration in multiple organs in these mice. This finding in an animal model provides a mechanistic explanation of increased susceptibility to autoimmunity in aged humans, although they may not show clinic manifestations without induction.

  16. Young, proliferative thymic epithelial cells engraft and function in aging thymuses

    PubMed Central

    Kim, Mi-Jeong; Miller, Christine M.; Shadrach, Jennifer L.; Wagers, Amy J.; Serwold, Thomas

    2015-01-01

    The thymus reaches its maximum size early in life and then begins to shrink, producing fewer T cells with increasing age. This thymic decline is thought to contribute to age-related T cell lymphopenias and hinder T cell recovery following bone marrow transplantation. While several cellular and molecular processes have been implicated in age-related thymic involution, their relative contributions are not known. Using heterochronic parabiosis, we observe that young circulating factors are not sufficient to drive regeneration of the aged thymus. In contrast, we find that resupplying young, engraftable thymic epithelial cells to a middle-aged or defective thymus leads to thymic growth and increased T cell production. Intrathymic transplantation and in vitro colony forming assays reveal that the engraftment and proliferative capacities of thymic epithelial cells diminish early in life, whereas the receptivity of the thymus to thymic epithelial cell engraftment remains relatively constant with age. These results support a model in which thymic growth and subsequent involution are driven by cell intrinsic changes in the proliferative capacity of thymic epithelial cells, and further show that young thymic epithelial cells can engraft and directly drive the growth of involuted thymuses. PMID:25870244

  17. Thymic endocrinology.

    PubMed

    Hadden, J W

    1998-05-01

    The thymus involutes relatively early in life; cellular immune deficiencies of aging correspond to decline in function of the hypothalamic-pituitary-endocrine axis. Recent studies point to important roles for the pituitary, the pineal, and the autonomic nervous system as well as the thyroid, gonads and adrenals in the thymus integrity and function. Thymic function at the local level requires complex cellular interactions among thymic stromal cells and developing thymocytes involving paracrine and autocrine mediators including interleukins (ILs) 1, 2, 6, 7, 8, colony-stimulating factors (CSFs), interferon-gamma, thymosin alpha 1, and zinc-thymulin. An important endocrine function of the thymus is to package zinc in zinc-thymulin for delivery to the periphery. Thymic involution has been treated with interleukins, thymic hormones, growth hormone, prolactin, melatonin, zinc, and others. Our work to reverse thymic involution in hydrocortisone-treated, aged mice with interleukins, thymosin alpha 1, and zinc will be reviewed. Recent efforts to treat successfully immune deficiency in aged and cancer-bearing humans will be presented.

  18. Thymic Rejuvenation and Aging

    PubMed Central

    Ventevogel, Melissa S.; Sempowski, Gregory D.

    2013-01-01

    The thymus is a vital organ for homeostatic maintenance of the peripheral immune system. It is within this mediastinal tissue that T cells develop and are extensively educated and exported to the periphery for establishment of a functional and effective immune system. A striking paradoxical feature of this critical lymphoid tissue is that it undergoes profound age– associated involution. Thymic decline is of minimal consequence to healthy individuals, but the reduced efficacy of the immune system with age has direct aetiological linkages with an increase in diseases including opportunistic infections, autoimmunity, and incidence / burden of cancer. Furthermore the inability of adults to restore immune function following insult induced by chemotherapy, ionizing radiation exposure or therapy, and infections (e.g. HIV-1) leads to increased morbidity and often mortality in the elderly. For these reasons, it is important that investigators strive to translate their understanding of mechanisms that drive thymic involution, and develop safe and effective strategies to rejuvenate the thymus in settings of clinical need. In this review, we present a discussion of the current status of thymic rejuvenation efforts associated with: sex steroid ablation, cytokines, growth factors, and hormones. PMID:23831111

  19. High prevalence of thymic tissue in adults with human immunodeficiency virus-1 infection.

    PubMed Central

    McCune, J M; Loftus, R; Schmidt, D K; Carroll, P; Webster, D; Swor-Yim, L B; Francis, I R; Gross, B H; Grant, R M

    1998-01-01

    The thymus in adults infected with the HIV-1 is generally thought to be inactive, both because of age-related involution and viral destruction. We have revisited the question of thymic function in adults, using chest-computed tomography (CT) to measure thymic tissue in HIV-1-seropositive (n = 99) or HIV-1-seronegative (n = 32) subjects, and correlating these results with the level of circulating CD4(+) and CD8(+) T cells that are phenotypically described as naive thymic emigrants. Abundant thymic tissue was detectable in many (47/99) HIV-1-seropositive adults, aged 20-59. Independent of age, radiographic demonstration of thymic tissue was significantly associated with both a higher CD4(+) T cell count (P = 0.02) and a higher percentage and absolute number of circulating naive (CD45RA+CD62L+) CD4(+) T cells (P < 0.04). The prevalence of an abundant thymus was especially high in younger HIV-1-seropositive adults ( 40 yr) regardless of CD4 count (P = 0.03). These studies suggest that the thymus is functional in some but not all adults with HIV-1 disease. PMID:9616201

  20. Rapidly involuting congenital hemangioma with fetal involution.

    PubMed

    Maguiness, Sheilagh; Uihlein, Lily Changchien; Liang, Marilyn G; Kozakewich, Harry; Mulliken, John B

    2015-01-01

    Uncommon congenital hemangiomas differ from common infantile hemangiomas in their appearance, postnatal behavior, histopathology, and immunohistologic staining. Two types are well described in the literature: noninvoluting congenital hemangioma (NICH) and rapidly involuting congenital hemangioma (RICH). We report a series of infants with another presentation of congenital hemangioma that arises prenatally and is nearly regressed at birth. This was a retrospective case series. We describe six infants with unusual congenital vascular tumors. Each lesion presented at birth as a violaceous, atrophic plaque with a surrounding pale halo. The lesions involuted in infancy, fading in color and becoming atrophic, with prominent central veins, similar to RICH in the final stage of regression. The distinctive morphology and behavior suggests that these tumors undergo a life cycle of proliferation and involution during fetal life. We describe a new variant of congenital hemangioma that we refer to as rapidly involuting congenital hemangioma with fetal involution.

  1. [Thymic carcinomas].

    PubMed

    Ströbel, P; Weis, C-A; Marx, A

    2016-09-01

    Thymic carcinomas (TC) are approximately 10 times less prevalent than thymomas but of high clinical relevance because they are more aggressive, less frequently resectable than thymomas and usually refractory to classical and targeted long-term treatment approaches. Furthermore, in children and adolescents TC are more frequent than thymomas and particularly in this age group, germ cell tumors need to be a differential diagnostic consideration. In diagnostic terms pathologists face two challenges: a), the distinction between thymic carcinomas and thymomas with a similar appearance and b), the distinction between TC and histologically similar metastases and tumor extensions from other primary tumors. Overcoming these diagnostic challenges is the focus of the new WHO classification of thymic epithelial tumors. The objectives of this review are to highlight novel aspects of the WHO classification of thymic carcinomas and to address therapeutically relevant diagnostic pitfalls. PMID:27538748

  2. Age related microsatellite instability in T cells from healthy individuals.

    PubMed

    Krichevsky, Svetlana; Pawelec, Graham; Gural, Alexander; Effros, Rita B; Globerson, Amiela; Yehuda, Dina Ben; Yehuda, Arie Ben

    2004-04-01

    Many immune functions decline with age and may jeopardize the elderly, as illustrated, for example by the significantly higher mortality rate from influenza in old age. Although innate and humoral immunity are affected by aging, it is the T cell compartment, which manifests most alterations. The mechanisms behind these alterations are still unclear, and several explanations have been offered including thymic involution and Telomere attrition leading to cell senescence. Age related accumulation of mutations has been documented and could serve as an additional mechanism of T cell dysfunction. One effective repair mechanism capable of rectifying errors in DNA replications is the mismatch repair (MMR) system. We previously reported a comparative examination of individual DNA samples from blood cells obtained at 10 year intervals from young and old subjects. We showed significantly higher rates of microsatellite instability (MSI), an indicator of MMR dysfunction in older subjects, compared to young. In the present study we confirm this result, using direct automated sequencing and in addition, we demonstrate that as CD8 lymphocytes from aged individuals, undergo repeated population doublings (PDs) in culture, they develop MSI. CD4 clones that also undergo repeated PDs in culture develop significant MSI as well. Elucidation of this previously unexplored facet of lymphocyte dynamics in relation to aging may help identify novel mechanisms of immunosenescence and pathways that could serve as targets for interventions to restore immune function.

  3. Mitochondria-targeted antioxidant SkQ1 inhibits age-dependent involution of the thymus in normal and senescence-prone rats

    PubMed Central

    Obukhova, Lidia A.; Skulachev, Vladimir P.; Kolosova, Natalia G.

    2009-01-01

    One of the most striking changes during mammal aging is a progressive involution of the thymus, associated with an increase in susceptibility to infections, autoimmune diseases and cancer. In order to delay age-related processes, we have developed mitochondria-targeted antioxidant plastoquinonyl decyltriphenyl phosphonium (SkQ1). Here we report that, at low doses, SkQ1 (250 nmol/kg per day) inhibited age-dependent involution of the thymus in normal (Wistar) and senescence-prone (OXYS) rats. SkQ1 preserved total weight and volume of the organ, the volume of thymic cortex and medulla, the thymic cellularity, and the number of CD3+, CD4+, and CD8+ cells in the thymus. Moreover, SkQ1 was especially effective in senescence-prone rats.   Thus SkQ1 slows down age-linked decline of the immune system, explaining prevention by this compound of infection-caused death in rodents, previously described in our group. PMID:20195490

  4. Age-related deregulation of Aire and peripheral tissue antigen genes in the thymic stroma of non-obese diabetic (NOD) mice is associated with autoimmune type 1 diabetes mellitus (DM-1).

    PubMed

    Fornari, Thaís A; Donate, Paula B; Macedo, Claudia; Marques, Márcia M C; Magalhães, Danielle A; Passos, Geraldo A S

    2010-09-01

    Gene expression of peripheral tissue antigens (PTAs) in stromal medullary thymic epithelial cells (mTECs) is a key process to the negative selection of autoreactive thymocytes. This phenomenon was termed "promiscuous gene expression" (PGE), which is partially controlled by the Aire gene. Nevertheless, reasons for the correlation of Aire and PTAs with the emergence of autoimmune diseases are largely unknown, though it may be a result of a chronological effect. Although the effect of Aire mutations in pathogenic autoimmunity is well know, it could not be a unique cause for autoimmunity. Independently of mutations, temporal deregulation of Aire expression may imbalance Aire-dependent PTAs and/or wide PGE. This deregulation may be an early warning sign for autoimmune diseases as it guarantees autoantigen representation in the thymus. To assess this hypothesis, we studied the expression levels of Aire, Aire-dependent (Ins2) and Aire-independent (Gad67 and Col2a1) PTAs using real-time-PCR of the thymic stromal cells of NOD mice during the development of autoimmune type 1 diabetes mellitus (DM-1). Wide PGE was studied by microarrays in which the PTA genes were identified through parallel CD80(+) mTEC 3.10 cell line expression profiling. The results show that Aire gene was down-regulated in young pre-autoimmune (pre-diabetic) NOD mice. PGE and specific PTA genes were down-regulated in adult autoimmune diabetic animals. These findings represent evidence indicating that chronological deregulation of genes important to negative selection may be associated with the development of an autoimmune disease (DM-1) in mice.

  5. Apoptosis and the thymic microenvironment in murine lupus.

    PubMed

    Takeoka, Y; Taguchi, N; Shultz, L; Boyd, R L; Naiki, M; Ansari, A A; Gershwin, M E

    1999-11-01

    The thymus of New Zealand black (NZB) mice undergoes premature involution. In addition, cultured thymic epithelial cells from NZB mice undergo accelerated preprogrammed degeneration. NZB mice also have distinctive and well-defined abnormalities of thymic architecture involving stromal cells, defined by staining with monoclonal antibodies specific for the thymic microenvironment. We took advantage of these findings, as well as our large panel of monoclonal antibodies which recognize thymic stroma, to study the induction of apoptosis in the thymus of murine lupus and including changes of epithelial architecture. We studied NZB, MRL/lpr, BXSB/Yaa, C3H/gld mice and BALB/c and C57BL/6 as control mice. Apoptosis was studied both at basal levels and following induction with either dexamethasone or lipopolysaccharide (LPS). The apoptotic cells were primarily found in the thymic cortex, and the frequency of apoptosis in murine lupus was less than 20% of controls. Moreover, all strains of murine lupus had severe abnormalities of the cortical network. These changes were not accentuated by dexamethasone treatment in cultured thymocytes. However, the thymus in murine lupus was less susceptible to LPS-induced apoptosis than control mice. Finally we note that the number of thymic nurse cells (TNC) was lowest in NZB mice. Our findings demonstrate significant abnormalities in the induction of apoptosis and the formation of TNC-like epithelial cells in SLE mice, and suggest that the abnormalities of the thymic microenvironment have an important role in the pathogenesis of murine lupus.

  6. Regenerative capacity of adult cortical thymic epithelial cells.

    PubMed

    Rode, Immanuel; Boehm, Thomas

    2012-02-28

    Involution of the thymus is accompanied by a decline in the number of thymic epithelial cells (TECs) and a severely restricted peripheral repertoire of T-cell specificities. TECs are essential for T-cell differentiation; they originate from a bipotent progenitor that gives rise to cells of cortical (cTEC) and medullary (mTEC) phenotypes, via compartment-specific progenitors. Upon acute selective near-total ablation during embryogenesis, regeneration of TECs fails, suggesting that losses from the pool of TEC progenitors are not compensated. However, it is unclear whether this is also true for the compartment-specific progenitors. The decline of cTECs is a prominent feature of thymic involution. Because cTECs support early stages of T-cell development and hence determine the overall lymphopoietic capacity of the thymus, it is possible that the lack of sustained regenerative capacity of cTEC progenitor cells underlies the process of thymic involution. Here, we examine this hypothesis by cell-type-specific conditional ablation of cTECs. Expression of the human diphtheria toxin receptor (hDTR) gene under the regulatory influence of the chemokine receptor Ccx-ckr1 gene renders cTECs sensitive to the cytotoxic effects of diphtheria toxin (DT). As expected, DT treatment of preadolescent and adult mice led to a dramatic loss of cTECs, accompanied by a rapid demise of immature thymocytes. Unexpectedly, however, the cTEC compartment regenerated after cessation of treatment, accompanied by the restoration of T-cell development. These findings provide the basis for the development of targeted interventions unlocking the latent regenerative potential of cTECs to counter thymic involution.

  7. Hydraulic involute cam actuator

    DOEpatents

    Love, Lonnie J.; Lind, Randall F.

    2011-11-01

    Mechanical joints are provided in which the angle between a first coupled member and a second coupled member may be varied by mechanical actuators. In some embodiments the angle may be varied around a pivot axis in one plane and in some embodiments the angle may be varied around two pivot axes in two orthogonal planes. The joints typically utilize a cam assembly having two lobes with an involute surface. Actuators are configured to push against the lobes to vary the rotation angle between the first and second coupled member.

  8. Thymus involution in the acquired immunodeficiency syndrome.

    PubMed

    Grody, W W; Fligiel, S; Naeim, F

    1985-07-01

    Acquired immunodeficiency syndrome (AIDS) is a severe disorder of unknown etiology and pathogenesis, predominantly affecting homosexual males and other high-risk groups and characterized by profound alterations in T-lymphocyte function. The authors have examined thymus tissue from 14 patients who died of AIDS and compared the results with findings in five control groups: healthy age-matched controls, elderly individuals, patients with chronic or debilitating illnesses other than AIDS, infants with conditions causing "stress atrophy," and patients with myasthenia gravis. The AIDS group included 11 homosexual males, 1 Haitian, 1 homosexual who was also a drug abuser, and a 10-month-old infant believed to have contracted AIDS following blood transfusion. All the AIDS cases showed marked thymus involution with severe depletion of both lymphocytes and epithelial elements. The latter component consisted primarily of thin cords and nests of primitive-appearing epithelial cells that could be defined by positive immunohistochemical staining for keratin. Many cases showed a variable plasma cell infiltration, and the majority exhibited distinct vascular changes in the form of hyalinization and/or onion-skin patterns, primarily in the adventitia. Most striking of all was the marked paucity of Hassall's corpuscles; four patients had none at all, while in the other ten patients all the Hassall's corpuscles were calcified. These changes were far more extensive than those seen in any of the control groups, which retained most of their complement of Hassall's corpuscles even in the face of marked overall involution. The physiologic function of Hassall's corpuscles is not known, but recent immunohistochemical studies have implicated them in the synthesis of "facteur thymique serique" (FTS, thymulin) and other thymic hormones known to play a role in regulating T-helper and suppressor cell activity. It is conceivable that the extensive destruction of Hassall's corpuscles observed in

  9. Thymic generation and regeneration.

    PubMed

    Gill, Jason; Malin, Mark; Sutherland, Jayne; Gray, Daniel; Hollander, George; Boyd, Richard

    2003-10-01

    The thymus is a complex epithelial organ in which thymocyte development is dependent upon the sequential contribution of morphologically and phenotypically distinct stromal cell compartments. It is these microenvironments that provide the unique combination of cellular interactions, cytokines, and chemokines to induce thymocyte precursors to undergo a differentiation program that leads to the generation of functional T cells. Despite the indispensable role of thymic epithelium in the generation of T cells, the mediators of this process and the differentiation pathway undertaken by the primordial thymic epithelial cells are not well defined. There is a lack of lineage-specific cell-surface-associated markers, which are needed to characterize putative thymic epithelial stem cell populations. This review explores the role of thymic stromal cells in T-cell development and thymic organogenesis, as well as the molecular signals that contribute to the growth and expansion of primordial thymic epithelial cells. It highlights recent advances in these areas, which have allowed for a lineage relationship amongst thymic epithelial cell subsets to be proposed. While many fundamental questions remain to be addressed, collectively these works have broadened our understanding of how the thymic epithelium becomes specialized in the ability to support thymocyte differentiation. They should also facilitate the development of novel, rationally based therapeutic strategies for the regeneration and manipulation of thymic function in the treatment of many clinical conditions in which defective T cells have an important etiological role.

  10. Giant thymic carcinoid.

    PubMed

    John, L C; Hornick, P; Lang, S; Wallis, J; Edmondson, S J

    1991-05-01

    Thymic carcinoid is a rare tumour. It may present with ectopic endocrine secretion or with symptoms of compression as a result of its size. A case is reported which presented with symptoms of compression where the size of the tumour was uniquely large such as to warrant the term giant thymic carcinoid. The typical histological features are described, together with its possible origin and its likely prognosis.

  11. Gonadotropin-releasing hormone agonist selectively augments thymopoiesis and prevents cell apoptosis in LPS induced thymic atrophy model independent of gonadal steroids.

    PubMed

    Ullewar, Meenal P; Umathe, Sudhir N

    2014-11-01

    Lipopolysaccharide (LPS) causes acute thymic atrophy, a phenomenon that has been linked to immune dysfunction and poor survival during sepsis. The systemic response to LPS involves a rise in glucocorticoids and proinflammatory cytokines which contribute greatly to thymic involution and apoptosis. Gonadotropin-releasing hormone (GnRH) analog exerts thymopoietic regulatory effects and possesses immunostimulant properties. We determined whether leuprolide, a GnRH analog can be useful in LPS induced thymic involution and apoptosis. Mice injected with 100 μg of LPS intraperitoneally led to involution of thymus, to decrease of CD4(+)8(+) thymocyte subset, and to fragmentation of thymic DNA. Leuprolide (100 μg/mouse, s.c.) pretreatment significantly attenuated LPS induced thymic atrophy, and also reduced LPS induced systemic rise in corticosterone levels. The observed effect of leuprolide remained unaffected in castrated and ovariectomized mice. Collectively, leuprolide has protective action independent of gonadal steroids, which was mediated by blunting of the systemic corticosteroid response in LPS induced thymic atrophy model.

  12. Arachidonic acid accumulates in the stromal macrophages during thymus involution in diabetes.

    PubMed

    Gruia, Alexandra T; Barbu-Tudoran, Lucian; Mic, Ani A; Ordodi, Valentin L; Paunescu, Virgil; Mic, Felix A

    2011-07-01

    Diabetes is a debilitating disease with chronic evolution that affects many tissues and organs over its course. Thymus is an organ that is affected early after the onset of diabetes, gradually involuting until it loses most of its thymocyte populations. We show evidence of accumulating free fatty acids with generation of eicosanoids in the diabetic thymus and we present a possible mechanism for the involution of the organ during the disease. Young rats were injected with streptozotocin and their thymuses examined for cell death by flow cytometry and TUNEL reaction. Accumulation of lipids in the diabetic thymus was investigated by histology and electron microscopy. The identity and quantitation of accumulating lipids was done with gas chromatography-mass spectrometry and liquid chromatography. The expression and dynamics of the enzymes were monitored via immunohistochemistry. Diabetes causes thymus involution by elevating the thymocyte apoptosis. Exposure of thymocytes to elevated concentration of glucose causes apoptosis. After the onset of diabetes, there is a gradual accumulation of free fatty acids in the stromal macrophages including arachidonic acid, the substrate for eicosanoids. The eicosanoids do not cause thymocyte apoptosis but administration of a cyclooxygenase inhibitor reduces the staining for ED1, a macrophage marker whose intensity correlates with phagocytic activity. Diabetes causes thymus involution that is accompanied by accumulation of free fatty acids in the thymic macrophages. Excess glucose is able to induce thymocyte apoptosis but eicosanoids are involved in the chemoattraction of macrophage to remove the dead thymocytes.

  13. Thymic necrosis following oral inoculation of mouse thymic virus.

    PubMed

    Morse, S S

    1989-11-01

    Mouse thymic virus (MTLV;ICTV designation murid herpesvirus 3) infects developing T lymphocytes of neonatal mice, causing thymic necrosis and acute immunosuppression. Infected animals shed virus indefinitely. However, although transmission in nature is presumably by contact and is likely to involve the oral-nasal route, virtually all experimental studies with MTLV have used systemic (intraperitoneal) inoculation. In order to determine whether systemic inoculation causes artifacts in pathogenesis of the infection, effects of intraperitoneal and oral-nasal inoculation were compared in newborn mice. Thymic necrosis occurred with either route of inoculation, although rate of infection was lower with oral inoculation, varying from about 20% to 67%. There were no gross differences in pathogenesis. Orally infected animals seroconverted and shed virus. These data indicate that the apparent lymphotropism of thymic virus, and induction of thymic necrosis, are not dependent on route of inoculation.

  14. Early Thymus Involution--Manifestation of an Aging Program or a Program of Development?

    PubMed

    Khalyavkin, A V; Krut'ko, V N

    2015-12-01

    "I see no physical reason why it should not have been possible for life to construct ageless individuals", said Carl von Weizsacker in 1979 at the Conference on DNA. An obvious biological reason for senescence may be the action of a built-in aging program. Many gerontologists believe that early thymic involution is an argument in favor of the existence of such a program. On the other hand, this involution may be a result of the program of development rather than aging. According to the concepts of noninfectious immunology, the immune system of vertebrates is also designed for immune surveillance over initial tumor development and for tissue-specific regulation of cell proliferation both in ontogenesis and during physiological and reparative regeneration of organs and tissues. Natural anti-tissue autoantibodies are the main effectors of such regulation. Therefore, the number of inherited genes of the variable part of immunoglobulin (V-genes) is not less than the number of all proliferative-competent cell types (~100). For the same reason, the maximal rate of growth, which is usually observed in the prepubertal period, coincides with the maximal thymus index and the maximal number of immunoglobulin-secreting cells as well as the minimal force of mortality during ontogeny. Thus, the circa-pubertal beginning of thymic involution is probably caused by the programmed deceleration of the growth rate in ontogeny, and not by the early manifestation of an aging program. This approach allows us to understand the mechanism of the well-known antitumor effect of the regeneration process of the organ homologous to the tumor, and hence we can try to use it in practical oncology. PMID:26638688

  15. mTORC1 in Thymic Epithelial Cells Is Critical for Thymopoiesis, T-Cell Generation, and Temporal Control of γδT17 Development and TCRγ/δ Recombination.

    PubMed

    Wang, Hong-Xia; Shin, Jinwook; Wang, Shang; Gorentla, Balachandra; Lin, Xingguang; Gao, Jimin; Qiu, Yu-Rong; Zhong, Xiao-Ping

    2016-02-01

    Thymus is crucial for generation of a diverse repertoire of T cells essential for adaptive immunity. Although thymic epithelial cells (TECs) are crucial for thymopoiesis and T cell generation, how TEC development and function are controlled is poorly understood. We report here that mTOR complex 1 (mTORC1) in TECs plays critical roles in thymopoiesis and thymus function. Acute deletion of mTORC1 in adult mice caused severe thymic involution. TEC-specific deficiency of mTORC1 (mTORC1KO) impaired TEC maturation and function such as decreased expression of thymotropic chemokines, decreased medullary TEC to cortical TEC ratios, and altered thymic architecture, leading to severe thymic atrophy, reduced recruitment of early thymic progenitors, and impaired development of virtually all T-cell lineages. Strikingly, temporal control of IL-17-producing γδT (γδT17) cell differentiation and TCRVγ/δ recombination in fetal thymus is lost in mTORC1KO thymus, leading to elevated γδT17 differentiation and rearranging of fetal specific TCRVγ/δ in adulthood. Thus, mTORC1 is central for TEC development/function and establishment of thymic environment for proper T cell development, and modulating mTORC1 activity can be a strategy for preventing thymic involution/atrophy. PMID:26889835

  16. mTORC1 in Thymic Epithelial Cells Is Critical for Thymopoiesis, T-Cell Generation, and Temporal Control of γδT17 Development and TCRγ/δ Recombination

    PubMed Central

    Wang, Hong-Xia; Shin, Jinwook; Wang, Shang; Gorentla, Balachandra; Lin, Xingguang; Gao, Jimin; Qiu, Yu-Rong; Zhong, Xiao-Ping

    2016-01-01

    Thymus is crucial for generation of a diverse repertoire of T cells essential for adaptive immunity. Although thymic epithelial cells (TECs) are crucial for thymopoiesis and T cell generation, how TEC development and function are controlled is poorly understood. We report here that mTOR complex 1 (mTORC1) in TECs plays critical roles in thymopoiesis and thymus function. Acute deletion of mTORC1 in adult mice caused severe thymic involution. TEC-specific deficiency of mTORC1 (mTORC1KO) impaired TEC maturation and function such as decreased expression of thymotropic chemokines, decreased medullary TEC to cortical TEC ratios, and altered thymic architecture, leading to severe thymic atrophy, reduced recruitment of early thymic progenitors, and impaired development of virtually all T-cell lineages. Strikingly, temporal control of IL-17-producing γδT (γδT17) cell differentiation and TCRVγ/δ recombination in fetal thymus is lost in mTORC1KO thymus, leading to elevated γδT17 differentiation and rearranging of fetal specific TCRVγ/δ in adulthood. Thus, mTORC1 is central for TEC development/function and establishment of thymic environment for proper T cell development, and modulating mTORC1 activity can be a strategy for preventing thymic involution/atrophy. PMID:26889835

  17. Age-related synthesis of glucocorticoids in thymocytes

    SciTech Connect

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

    2008-10-01

    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.

  18. Rac1 deletion causes thymic atrophy.

    PubMed

    Hunziker, Lukas; Benitah, Salvador Aznar; Aznar Benitah, Salvador; Braun, Kristin M; Jensen, Kim; McNulty, Katrina; Butler, Colin; Potton, Elspeth; Nye, Emma; Boyd, Richard; Laurent, Geoff; Glogauer, Michael; Wright, Nick A; Watt, Fiona M; Janes, Sam M

    2011-04-29

    The thymic stroma supports T lymphocyte development and consists of an epithelium maintained by thymic epithelial progenitors. The molecular pathways that govern epithelial homeostasis are poorly understood. Here we demonstrate that deletion of Rac1 in Keratin 5/Keratin 14 expressing embryonic and adult thymic epithelial cells leads to loss of the thymic epithelial compartment. Rac1 deletion led to an increase in c-Myc expression and a generalized increase in apoptosis associated with a decrease in thymic epithelial proliferation. Our results suggest Rac1 maintains the epithelial population, and equilibrium between Rac1 and c-Myc may control proliferation, apoptosis and maturation of the thymic epithelial compartment. Understanding thymic epithelial maintenance is a step toward the dual goals of in vitro thymic epithelial cell culture and T cell differentiation, and the clinical repair of thymic damage from graft-versus-host-disease, chemotherapy or irradiation.

  19. The descrease of the in vitro proliferative response of zinc-treated stressed mice's thymic lymphocytes.

    PubMed

    García-Tamayo, F; Malpica López, N; Aguirre, M; Terrazas-Valdés, L I

    1999-01-01

    Prolonged stimulation of newborn mice by intraperitoneal injections with inactivated staphylococci induces a chronic neonatal inflammatory reaction and an associated oxidative-stress response. The chronically stimulated animals exhibit anorexy. show a reduction in their body weight and undergo a depression in both antibody synthesis andin vitro proliferativc response of Con A-stimulated splenic T-lymphocytes. These stressed animals also develop adrenal hyperplasia, hypozincamia and thymic hypoplasia. Despite this stress-mediated thymic involution, Con-A stimulated T-lymphocytes from thymus displayed increased theirin vitro proliferative response. Results of the present work show that intramuscular injections of zinc acetate in stressed mice, one single dose (5 microg) every other day for two weeks, reduce both the zinc concentration in the thymus gland and thein vitro proliferative response of their Con A-stimulated T-lymphocytes. The results suggest that prophylactic administration of zinc can have benefical consequences on the immunity of chronically stressed mice.

  20. Meis1 Is Required for the Maintenance of Postnatal Thymic Epithelial Cells

    PubMed Central

    Hirayama, Takehiro; Asano, Yusuke; Iida, Hajime; Watanabe, Takeshi; Nakamura, Takuro; Goitsuka, Ryo

    2014-01-01

    Most epithelial tissues retain stem/progenitor cells to maintain homeostasis of the adult tissues; however, the existence of a thymic epithelial cell (TEC) progenitor capable of maintaining homeostasis of the postnatal thymus remains unclear. Here, we show that a cell population expressing high levels of Meis1, a homeodomain transcription factor, is enriched in TECs with an immature cellular phenotype. These TECs selectively express genes involved in embryonic thymic organogenesis and epithelial stem cell maintenance, and also have the potential to proliferate and differentiate into mature TEC populations. Furthermore, postnatal inactivation of Meis1 in TECs caused disorganization of the thymic architecture, which ultimately leads to premature disappearance of the thymus. There was an age-associated reduction in the proportion of the TEC population expressing high levels of Meis1, which may also be related to thymic involution. These findings indicate that Meis1 is potentially involved in the maintenance of postnatal TECs with progenitor activity that is required for homeostasis of the postnatal thymus. PMID:24594519

  1. Age-Related Macular Degeneration.

    PubMed

    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.

  2. Treatment Options for Thymoma and Thymic Carcinoma

    MedlinePlus

    ... symptoms of thymoma and thymic carcinoma include a cough and chest pain. Thymoma and thymic carcinoma may ... if you have any of the following: A cough that doesn't go away. Chest pain. Trouble ...

  3. Stages of Thymoma and Thymic Carcinoma

    MedlinePlus

    ... symptoms of thymoma and thymic carcinoma include a cough and chest pain. Thymoma and thymic carcinoma may ... if you have any of the following: A cough that doesn't go away. Chest pain. Trouble ...

  4. General Information about Thymoma and Thymic Carcinoma

    MedlinePlus

    ... and Thymic Carcinoma Treatment (PDQ®)–Patient Version General Information About Thymoma and Thymic Carcinoma Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  5. Computer programs for generating involute gears

    SciTech Connect

    Emery, J.D.; Wolf, M.L.

    1992-02-01

    Methods and computer programs are given for computing the shapes of involute gears. A proof is given of conditions under which uniform angular velocity is maintained for a pair of interacting cams. A program is given for the animation of gear motion. It runs on an APOLLO 4500 computer. The other programs are general and are written in FORTRAN and C.

  6. [Presbycusis - Age Related Hearing Loss].

    PubMed

    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. PMID:27392191

  7. Differential Expression of microRNAs in Thymic Epithelial Cells from Trypanosoma cruzi Acutely Infected Mice: Putative Role in Thymic Atrophy

    PubMed Central

    Linhares-Lacerda, Leandra; Palu, Cintia Cristina; Ribeiro-Alves, Marcelo; Paredes, Bruno Diaz; Morrot, Alexandre; Garcia-Silva, Maria Rosa; Cayota, Alfonso; Savino, Wilson

    2015-01-01

    A common feature seen in acute infections is a severe atrophy of the thymus. This occurs in the murine model of acute Chagas disease. Moreover, in thymuses from Trypanosoma cruzi acutely infected mice, thymocytes exhibit an increase in the density of fibronectin and laminin integrin-type receptors, with an increase in migratory response ex vivo. Thymic epithelial cells (TEC) play a major role in the intrathymic T cell differentiation. To date, the consequences of molecular changes promoted by parasite infection upon thymus have not been elucidated. Considering the importance of microRNA for gene expression regulation, 85 microRNAs (mRNAs) were analyzed in TEC from T. cruzi acutely infected mice. The infection significantly modulated 29 miRNAs and modulation of 9 was also dependent whether TEC sorted out from the thymus exhibited cortical or medullary phenotype. In silico analysis revealed that these miRNAs may control target mRNAs known to be responsible for chemotaxis, cell adhesion, and cell death. Considering that we sorted TEC in the initial phase of thymocyte loss, it is conceivable that changes in TEC miRNA expression profile are functionally related to thymic atrophy, providing new clues to better understanding the mechanisms of the thymic involution seen in experimental Chagas disease. PMID:26347748

  8. [Age-related macular degeneration].

    PubMed

    Garcia Layana, A

    1998-01-01

    Age-related macular degeneration (ARMD) is the leading cause of blindness in the occidental world. Patients suffering this process have an important reduction on their quality of life being handicapped to read, to write, to recognise faces of their friends, or even to watch the television. One of the main problems of that disease is the absence of an effective treatment able to revert the process. Laser treatment is only useful in a limited number of patients, and even in these cases recurrent lesions are frequent. These facts and the progressive ageing of our society establish the ARMD as one of the biggest aim of medical investigations for the next century, and currently is focus of attention in the most industrialised countries. One of the most promising pieces of research is focused in the investigation of the risk factors associated with the age-related macular degeneration, in order to achieve a prophylactic treatment avoiding its appearance. Diet elements such as fat ingestion or reduced antioxidant intakes are being investigated as some of these factors, what open a new possibility for a prophylactic treatment. Finally, research is looking for new therapeutic modalities such as selective radiotherapy in order to improve or maintain the vision of these patients.

  9. Thymic pathologies in myasthenia gravis: a preoperative assessment of CAT scan and nuclear based imaging.

    PubMed

    Jordan, Berit; Kellner, Juliane; Jordan, Karin; Bähre, Manfred; Behrmann, Curd; Zierz, Stephan

    2016-04-01

    Precise diagnostic work up of a suspected thymic pathology in patients with myasthenia gravis (MG) is very important for potential surgical implications and further disease course. In this study the diagnostic value of combined preoperative radiological (CAT scan) and nuclear based imaging (octreotide and thallium scintigraphy) in patients with MG was evaluated. Twenty four patients were included. Histopathology revealed thymoma in nine patients, thymic carcinoma (TC) in one patient, lymphofollicular hyperplasia in seven patients, and involuted thymus in another seven patients. Diagnostic sensitivity for detecting thymoma/TC was 80 % in CAT scan as well as in somatostatin scintigraphy; the combination of both procedures reached 90 %. However, the diagnostic specifity to exclude thymoma in CAT scan was 100 % and in octreotide scintigraphy 85.7 %. Semiquantitative octreotide uptake significantly correlated with histological grading of thymoma/TC (r = 0.764) and histological proliferation rate Ki67 (r = 0.894). Thallium scintigraphy was positive only in one out of four thymoma cases. In this study, somatostatin scintigraphy has been shown to be a useful additional diagnostic technique in detecting thymic malignancies in patients with MG. These results might be especially helpful in patients with late onset MG as these patients are in general no candidates for thymectomy. PMID:26810725

  10. Thymic pathologies in myasthenia gravis: a preoperative assessment of CAT scan and nuclear based imaging.

    PubMed

    Jordan, Berit; Kellner, Juliane; Jordan, Karin; Bähre, Manfred; Behrmann, Curd; Zierz, Stephan

    2016-04-01

    Precise diagnostic work up of a suspected thymic pathology in patients with myasthenia gravis (MG) is very important for potential surgical implications and further disease course. In this study the diagnostic value of combined preoperative radiological (CAT scan) and nuclear based imaging (octreotide and thallium scintigraphy) in patients with MG was evaluated. Twenty four patients were included. Histopathology revealed thymoma in nine patients, thymic carcinoma (TC) in one patient, lymphofollicular hyperplasia in seven patients, and involuted thymus in another seven patients. Diagnostic sensitivity for detecting thymoma/TC was 80 % in CAT scan as well as in somatostatin scintigraphy; the combination of both procedures reached 90 %. However, the diagnostic specifity to exclude thymoma in CAT scan was 100 % and in octreotide scintigraphy 85.7 %. Semiquantitative octreotide uptake significantly correlated with histological grading of thymoma/TC (r = 0.764) and histological proliferation rate Ki67 (r = 0.894). Thallium scintigraphy was positive only in one out of four thymoma cases. In this study, somatostatin scintigraphy has been shown to be a useful additional diagnostic technique in detecting thymic malignancies in patients with MG. These results might be especially helpful in patients with late onset MG as these patients are in general no candidates for thymectomy.

  11. Age-related changes in the morphology and protein expression of the thymus of healthy yaks (Bos grunniens).

    PubMed

    Zhang, Qian; Yang, Kun; Yangyang, Pan; He, Junfeng; Yu, Sijiu; Cui, Yan

    2016-06-01

    OBJECTIVE To evaluate age-related changes in the morphology and expression of cluster of differentiation 3 (CD3), S100 β, and caspase-3 of the thymus of healthy yaks (Bos grunniens). ANIMALS 15 healthy male yaks of various ages from highland plateaus. PROCEDURES Yaks were allocated to 3 groups on the basis of age (newborn [1 to 7 days old; n = 5], juvenile [5 to 7 months old, 5], and adult [3 to 4 years old; 5]) and euthanized. The thymus was harvested from each yak within 10 minutes after euthanasia. Morphological characteristics were assessed by histologic examination and transmission electron microscopy. Expression of CD3, S100 β, and caspase-3 mRNA and protein was measured by quantitative real-time PCR assay, Western blot analysis, and immunohistochemical staining. RESULTS As age increased, functional thymic tissue was replaced with adipose and connective tissues and the thymic capsule thickened. Expression of CD3 and S100 β mRNA and protein decreased with age, whereas expression of caspase-3 mRNA and protein increased with age. Immunohistochemical staining revealed that CD3-positive thymocytes were located within both the thymic cortex and medulla, S100 β-positive thymic dendritic cells were located in the corticomedullary junction and medulla, and caspase-3-positive thymocytes were diffusely scattered throughout the cortex and medulla. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that age-related thymic changes in yaks that live on highland plateaus were similar to those observed in humans and other mammals. Thus, yaks might serve as a model to study thymic immune system adaptations to high elevations. PMID:27227493

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

    SciTech Connect

    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.

  13. [Clinical evaluation of thymic function].

    PubMed

    Castermans, E; Morrhaye, G; Marchand, S; Martens, H; Moutschen, M; Baron, F; Beguin, Y; Geenen, V

    2007-11-01

    The essential role of the thymus is to install an extremely diverse repertoire of T lymphocytes that are self-tolerant and competent against non-self, as well as to generate self-antigen specific regulatory T cells (Treg) able to inactivate in periphery self-reactive T cells having escaped the thymic censorship. Although indirect, techniques of medical imaging and phenotyping of peripheral T cells may help in the investigation of thymic function. Nowadays however, thymopoiesis is better evaluated through quantification by PCR of T-cell receptor excision circles (TREC) generated by intrathymic random recombination of the gene segments coding for the variable parts of the T-cell receptor for antigen (TCR). The TREC methodology is very valuable in the circumstances not associated with intense proliferation or apoptosis of peripheral T lymphocytes. PMID:18217644

  14. Age-related atrial fibrosis.

    PubMed

    Gramley, Felix; Lorenzen, Johann; Knackstedt, Christian; Rana, Obaida R; Saygili, Erol; Frechen, Dirk; Stanzel, Sven; Pezzella, Francesco; Koellensperger, Eva; Weiss, Christian; Münzel, Thomas; Schauerte, Patrick

    2009-03-01

    Many age-related diseases are associated with, and may be promoted by, cardiac fibrosis. Transforming growth factor (TGF)-beta, hypoxia-induced factor (HIF), and the matrix metalloproteinase (MMP) system have been implicated in fibrogenesis. Thus, we investigated whether age is related to these systems and to atrial fibrosis. Right atrial appendages (RAA) obtained during heart surgery (n = 115) were grouped according to patients' age (<50 years, 51-60 years, 61-70 years, or >70 years). Echocardiographic ejection fractions (EF) and fibrosis using Sirius-red-stained histological sections were determined. TGF-beta was determined by quantitative RT-PCR and hypoxia-related factors [HIF1 alpha, the vascular endothelial growth factor (VEGF)-receptor, CD34 (a surrogate marker for microvessel density), the factor inhibiting HIF (FIH), and prolyl hydroxylase 3 (PHD 3)] were detected by immunostaining. MMP-2 and -9 activity were determined zymographically, and mRNA levels of their common tissue inhibitor TIMP-1 were determined by RT-PCR. Younger patients (<50 years) had significantly less fibrosis (10.1% +/- 4.4% vs 16.6% +/- 8.3%) than older individuals (>70 years). While HIF1 alpha, FIH, the VEGF-receptor, and CD34 were significantly elevated in the young, TGF-beta and PHD3 were suppressed in these patients. MMP-2 and -9 activity was found to be higher while TIMP-1 levels were lower in older patients. Statistical analysis proved age to be the only factor influencing fibrogenesis. With increasing age, RAAs develop significantly more fibrosis. An increase of fibrotic and decrease of hypoxic signalling and microvessel density, coupled with differential expression of MMPs and TIMP-1 favouring fibrosis may have helped promote atrial fibrogenesis. PMID:19234766

  15. Microfabricated Segmented-Involute-Foil Regenerator for Stirling Engines

    NASA Technical Reports Server (NTRS)

    Ibrahim, Mounir; Danila, Daniel; Simon, Terrence; Mantell, Susan; Sun, Liyong; Gedeon, David; Qiu, Songgang; Wood, Gary; Kelly, Kevin; McLean, Jeffrey

    2010-01-01

    An involute-foil regenerator was designed, microfabricated, and tested in an oscillating-flow test rig. The concept consists of stacked involute-foil nickel disks (see figure) microfabricated via a lithographic process. Test results yielded a performance of about twice that of the 90-percent random-fiber currently used in small Stirling converters. The segmented nature of the involute- foil in both the axial and radial directions increases the strength of the structure relative to wrapped foils. In addition, relative to random-fiber regenerators, the involute-foil has a reduced pressure drop, and is expected to be less susceptible to the release of metal fragments into the working space, thus increasing reliability. The prototype nickel involute-foil regenerator was adequate for testing in an engine with a 650 C hot-end temperature. This is lower than that required by larger engines, and high-temperature alloys are not suited for the lithographic microfabrication approach.

  16. Macrophage-induced thymic lymphocyte maturation.

    PubMed Central

    Van den Tweel, J G; Walker, W S

    1977-01-01

    Guinea-pig peritoneal macrophages were found to influence the functional maturation of thymic lymphocytes. Autologous thymic lymphocytes obtained from macrophage co-cultures responded to three different mitogens and were reduced in their ability to reassociate spontaneously with macrophages. Neither of these properties were found in thymic lymphocytes that had not been cultured with macrophages. These functional changes appeared to be specific for macrophages since thymic lymphocytes incubated with skin fibroblasts failed to respond to the test mitogens. Furthermore, they were not the result of either the inactivation, by macrophages, of a putative suppressor thymocyte or a soluble macrophage product. In addition to influencing the functional maturation of thymic lymphocytes, macrophages also appeared to play a direct role in inducing the mitogen response of functionally mature cells. PMID:304037

  17. SHP1-ing thymic selection.

    PubMed

    Gascoigne, Nicholas R J; Brzostek, Joanna; Mehta, Monika; Acuto, Oreste

    2016-09-01

    Thymocyte development and maintenance of peripheral T-cell numbers and functions are critically dependent on T-cell receptor (TCR) signal strength. SHP1 (Src homology region 2 domain-containing phosphatase-1), a tyrosine phosphatase, acts as a negative regulator of TCR signal strength. Moreover, germline SHP1 knockout mice have shown impaired thymic development. However, this has been recently questioned by an analysis of SHP1 conditional knockout mice, which reported normal thymic development of SHP1 deficient thymocytes. Using this SHP1 conditional knockout mice, in this issue of the European Journal of Immunology, Martinez et al. [Eur. J. Immunol. 2016. 46: 2103-2110] show that SHP1 indeed does have a role in the negative regulation of TCR signal strength in positively selected thymocytes, and in the final maturation of single positive thymocytes. They report that thymocyte development in such mice shows loss of mature, post-selection cells. This is due to increased TCR signal transduction in thymocytes immediately post positive-selection, and increased cell death in response to weak TCR ligands. Thus, SHP1-deficiency shows strong similarities to deficiency in the T-cell specific SHP1-associated protein Themis. PMID:27600672

  18. BDNF and its receptors in human myasthenic thymus: implications for cell fate in thymic pathology.

    PubMed

    Berzi, Angela; Ayata, C Korcan; Cavalcante, Paola; Falcone, Chiara; Candiago, Elisabetta; Motta, Teresio; Bernasconi, Pia; Hohlfeld, Reinhard; Mantegazza, Renato; Meinl, Edgar; Farina, Cinthia

    2008-07-15

    Here we show that in myasthenic thymus several cell types, including thymic epithelial cells (TEC) and immune cells, were the source and the target of the neurotrophic factor brain-derived growth factor (BDNF). Interestingly, many actively proliferating medullary thymocytes expressed the receptor TrkB in vivo in involuted thymus, while this population was lost in hyperplastic or neoplastic thymuses. Furthermore, in hyperplastic thymuses the robust coordinated expression of BDNF in the germinal centers together with the receptor p75NTR on all proliferating B cells strongly suggests that this factor regulates germinal center reaction. Finally, all TEC dying of apoptosis expressed BDNF receptors, indicating that this neurotrophin is involved in TEC turnover. In thymomas both BDNF production and receptor expression in TEC were strongly hindered. This may represent an attempt of tumour escape from cell death.

  19. Nutrition and age-related eye diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vision loss among the elderly is an important health problem. Approximately one person in three has some form of vision-reducing eye disease by the age of 65 [1]. Age-related cataract, age-related macular degeneration (AMD), diabetic retinopathy and glaucoma are the major diseases resulting in visu...

  20. X-82 to Treat Age-related Macular Degeneration

    ClinicalTrials.gov

    2016-08-16

    Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

  1. Phenotypic Characterization of Chicken Thymic Stromal Elements

    PubMed Central

    Wilson, Trevor J.; Bean, Andrew G.; Ward, Harry A.; Gershwin, M. Eric

    1992-01-01

    Phenotypic profiles of the thymic stromal components provide an excellent approach to elucidating the nature of the microenvironment of this organ. To address this issue in chickens, we have produced an extensive panel of 18 mAb to the thymic stroma. These mAb have been extensively characterized with respect to their phenotypic specificities and reveal that the stromal cells are equally as complex as the T cells whose maturation they direct. They further demonstrate that, in comparison to the mammalian thymus, there is a remarkable degree of conservation in thymic architecture between phylogenetically diverse species. Eleven mAb reacted with thymic epithelial cells: MUI-73 was panepithelium, MUI-54 stained all cortical and medullary epithelium but only a minority of the subcapsule, MUI-52 was specific for isolated stellate cortical epithelial cells, MUI-62, -69, and -71 were specific for the medulla (including Hassall’s corpusclelike structures), MUI-51, -53, -70, and -75 reacted only with the type-I epithelium, or discrete regions therein, lining the subcapsular and perivascular regions and MUI-58 demonstrated the antigenic similarity between the subcapsule and the medulla. Seven other mAb identified distinct isolated stromal cells throughout the cortex and medulla. Large thymocyte-rich regions, which often spanned from the outer cortex to medulla, lacked epithelial cells. These mAb should prove invaluable for determining the functional significance of thymic stromal-cell subsets to thymopoiesis. PMID:1387829

  2. Preparation and Applications of Organotypic Thymic Slice Cultures.

    PubMed

    Sood, Aditi; Dong, Mengqi; Melichar, Heather J

    2016-01-01

    Thymic selection proceeds in a unique and highly organized thymic microenvironment resulting in the generation of a functional, self-tolerant T cell repertoire. In vitro models to study T lineage commitment and development have provided valuable insights into this process. However, these systems lack the complete three-dimensional thymic milieu necessary for T cell development and, therefore, are incomplete approximations of in vivo thymic selection. Some of the challenges related to modeling T cell development can be overcome by using in situ models that provide an intact thymic microenvironment that fully supports thymic selection of developing T cells. Thymic slice organotypic cultures complement existing in situ techniques. Thymic slices preserve the integrity of the thymic cortical and medullary regions and provide a platform to study development of overlaid thymocytes of a defined developmental stage or of endogenous T cells within a mature thymic microenvironment. Given the ability to generate ~20 slices per mouse, thymic slices present a unique advantage in terms of scalability for high throughput experiments. Further, the relative ease in generating thymic slices and potential to overlay different thymic subsets or other cell populations from diverse genetic backgrounds enhances the versatility of this method. Here we describe a protocol for the preparation of thymic slices, isolation and overlay of thymocytes, and dissociation of thymic slices for flow cytometric analysis. This system can also be adapted to study non-conventional T cell development as well as visualize thymocyte migration, thymocyte-stromal cell interactions, and TCR signals associated with thymic selection by two-photon microscopy. PMID:27585240

  3. Involute composite design evaluation using global design sensitivity derivatives

    NASA Technical Reports Server (NTRS)

    Hart, J. K.; Stanton, E. L.

    1989-01-01

    An optimization capability for involute structures has been developed. Its key feature is the use of global material geometry variables which are so chosen that all combinations of design variables within a set of lower and upper bounds correspond to manufacturable designs. A further advantage of global variables is that their number does not increase with increasing mesh density. The accuracy of the sensitivity derivatives has been verified both through finite difference tests and through the successful use of the derivatives by an optimizer. The state of the art in composite design today is still marked by point design algorithms linked together using ad hoc methods not directly related to a manufacturing procedure. The global design sensitivity approach presented here for involutes can be applied to filament wound shells and other composite constructions using material form features peculiar to each construction. The present involute optimization technology is being applied to the Space Shuttle SRM nozzle boot ring redesigns by PDA Engineering.

  4. Non-convex entropies for conservation laws with involutions.

    PubMed

    Dafermos, Constantine M

    2013-12-28

    The paper discusses systems of conservation laws endowed with involutions and contingent entropies. Under the assumption that the contingent entropy function is convex merely in the direction of a cone in state space, associated with the involution, it is shown that the Cauchy problem is locally well posed in the class of classical solutions, and that classical solutions are unique and stable even within the broader class of weak solutions that satisfy an entropy inequality. This is on a par with the classical theory of solutions to hyperbolic systems of conservation laws endowed with a convex entropy. The equations of elastodynamics provide the prototypical example for the above setting.

  5. Depression in Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Casten, Robin; Rovner, Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling…

  6. Driving and Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Owsley, Cynthia; McGwin, Gerald, Jr.

    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,…

  7. Age Related Changes in Preventive Health Behavior.

    ERIC Educational Resources Information Center

    Leventhal, Elaine A.; And Others

    Health behavior may be influenced by age, beliefs, and symptomatology. To examine age-related health beliefs and behaviors with respect to six diseases (the common cold, colon-rectal cancer, lung cancer, heart attack, high blood pressure, and senility), 396 adults (196 males, 200 females) divided into three age groups completed a questionnaire…

  8. A Microfabricated Involute-Foil Regenerator for Stirling Engines

    NASA Technical Reports Server (NTRS)

    Tew, Roy; Ibrahim, Mounir; Danila, Daniel; Simon, Terrence; Mantell, Susan; Sun, Liyong; Gedeon, David; Kelly, Kevin; McLean, Jeffrey; Qiu, Songgang

    2007-01-01

    A segmented involute-foil regenerator has been designed, microfabricated and tested in an oscillating-flow rig with excellent results. During the Phase I effort, several approximations of parallel-plate regenerator geometry were chosen as potential candidates for a new microfabrication concept. Potential manufacturers and processes were surveyed. The selected concept consisted of stacked segmented-involute-foil disks (or annular portions of disks), originally to be microfabricated from stainless-steel via the LiGA (lithography, electroplating, and molding) process and EDM. During Phase II, re-planning of the effort led to test plans based on nickel disks, microfabricated via the LiGA process, only. A stack of nickel segmented-involute-foil disks was tested in an oscillating-flow test rig. These test results yielded a performance figure of merit (roughly the ratio of heat transfer to pressure drop) of about twice that of the 90 percent random fiber currently used in small approx.100 W Stirling space-power convertors-in the Reynolds Number range of interest (50 to 100). A Phase III effort is now underway to fabricate and test a segmented-involute-foil regenerator in a Stirling convertor. Though funding limitations prevent optimization of the Stirling engine geometry for use with this regenerator, the Sage computer code will be used to help evaluate the engine test results. Previous Sage Stirling model projections have indicated that a segmented-involute-foil regenerator is capable of improving the performance of an optimized involute-foil engine by 6 to 9 percent; it is also anticipated that such involute-foil geometries will be more reliable and easier to manufacture with tight-tolerance characteristics, than random-fiber or wire-screen regenerators. Beyond the near-term Phase III regenerator fabrication and engine testing, other goals are (1) fabrication from a material suitable for high temperature Stirling operation (up to 850 C for current engines; up to 1200 C

  9. A Microfabricated Involute-Foil Regenerator for Stirling Engines

    NASA Technical Reports Server (NTRS)

    Tew, Roy; Ibrahim, Mounir; Danila, Daniel; Simon, Terry; Mantell, Susan; Sun, Liyong; Gedeon, David; Kelly, Kevin; McLean, Jeffrey; Wood, Gary; Qiu, Songgang

    2007-01-01

    A segmented involute-foil regenerator has been designed, microfabricated and tested in an oscillating-flow rig with excellent results. During the Phase I effort, several approximations of parallel-plate regenerator geometry were chosen as potential candidates for a new microfabrication concept. Potential manufacturers and processes were surveyed. The selected concept consisted of stacked segmented-involute-foil disks (or annular portions of disks), originally to be microfabricated from stainless-steel via the LiGA (lithography, electroplating, and molding) process and EDM (electric discharge machining). During Phase II, re-planning of the effort led to test plans based on nickel disks, microfabricated via the LiGA process, only. A stack of nickel segmented-involute-foil disks was tested in an oscillating-flow test rig. These test results yielded a performance figure of merit (roughly the ratio of heat transfer to pressure drop) of about twice that of the 90% random fiber currently used in small 100 W Stirling space-power convertors in the Reynolds Number range of interest (50-100). A Phase III effort is now underway to fabricate and test a segmented-involute-foil regenerator in a Stirling convertor. Though funding limitations prevent optimization of the Stirling engine geometry for use with this regenerator, the Sage computer code will be used to help evaluate the engine test results. Previous Sage Stirling model projections have indicated that a segmented-involute-foil regenerator is capable of improving the performance of an optimized involute-foil engine by 6-9%; it is also anticipated that such involute-foil geometries will be more reliable and easier to manufacture with tight-tolerance characteristics, than random-fiber or wire-screen regenerators. Beyond the near-term Phase III regenerator fabrication and engine testing, other goals are (1) fabrication from a material suitable for high temperature Stirling operation (up to 850 C for current engines; up to

  10. Surface family with a common involute asymptotic curve

    NASA Astrophysics Data System (ADS)

    Bayram, Ergi˙n; Bi˙li˙ci˙, Mustafa

    2016-03-01

    We construct a surface family possessing an involute of a given curve as an asymptotic curve. We express necessary and sufficient conditions for that curve with the above property. We also present natural results for such ruled surfaces. Finally, we illustrate the method with some examples, e.g. circles and helices as given curves.

  11. Distribution of age-related thymulin titres in normal subjects through the course of life

    PubMed Central

    Consolini, R; Legitimo, A; Calleri, A; Milani, M

    2000-01-01

    The thymus has a dominant immunological role in utero and in early childhood, being a primary source of T lymphopoiesis, and its investigation may be particularly relevant for the immunological study of paediatric patients. Thymulin, a nonapeptide secreted by the thymus, is an essential hormone for T lymphocyte differentiation and function. As thymulin values in the normal population have not been well documented, especially for children under the age of 1 year, we detail thymic endocrine function by presenting age-related plasma thymulin levels in a large series (n = 93) of healthy individuals, ranging from birth to old age. We demonstrate that thymulin is already detectable at birth; it then gradually increases with age, reaching the highest level in children aged 5–10 years. Starting at adolescence, thymulin titres gradually start to fall, reaching the lowest value at 36 years of age and remaining steady until 80 years (the oldest person tested). PMID:10971509

  12. Immunology of age-related macular degeneration

    PubMed Central

    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

  13. [Epidemiology of age related macular degeneration].

    PubMed

    Leveziel, N; Delcourt, C; Zerbib, J; Dollfus, H; Kaplan, J; Benlian, P; Coscas, G; Souied, E H; Soubrane, G

    2009-06-01

    Age-related macular degeneration (ARMD) is a multifactorial and polygenic disease and is the main cause of vision loss in developed countries. The environmental factors of ARMD can modify prevalence and incidence of this disease. This article is a review of the main environmental factors currently recognized as at risk or protective factor for ARMD. Modification of these factors is of crucial importance because it could delay the onset of exudative or atrophic forms of the disease. PMID:19515460

  14. Vanadium toxicity in the thymic development

    PubMed Central

    Cui, Hengmin

    2015-01-01

    The purpose of this study was to define the toxic effects of vanadium on thymic development in broilers fed on diets supplemented with 0, 5, 15, 30, 45 and 60 mg/kg of vanadium for 42 days. We examined the changes of relative weight, cell cycle phase, apoptotic cells, and protein expression of Bcl-2, Bax, and caspase-3 in the thymus by the methods of flow cytometry, TUNEL (terminal-deoxynucleotidyl transferase mediated nick end labeling) and immunohistochemistry. The results showed that dietary high vanadium (30mg/kg, 45mg/kg and 60mg/kg) caused the toxic effects on thymic development, which was characterized by decreasing relative weight, increasing G0/G1 phase (a prolonged nondividing state), reducing S phase (DNA replication) and proliferating index (PI), and increasing percentages of apoptotic thymocytes. Concurrently, the protein expression levels of Bax and caspase-3 were increased, and protein expression levels of Bcl-2 were decreased. The thymic development suppression caused by dietary high vanadium further leads to inhibitive effects on T lymphocyte maturity and activity, and cellular immune function. The above-mentioned results provide new evidences for further understanding the vanadium immunotoxicity. In contrast, dietary 5 mg/kg vanadium promoted the thymic development by increasing relative weight, decreasing G0/G1 phase, increasing S phase and PI, and reducing percentages of apoptotic thymocytes when compared to the control group and high vanadium groups. PMID:26416460

  15. Ontogeny of rat thymic dendritic cells.

    PubMed Central

    Vicente, A; Varas, A; Alonso, L; Gómez de Moral, M; Zapata, A G

    1994-01-01

    In the present study we have combined various in vivo and in vitro approaches to analyse the appearance and development throughout ontogeny and postnatal life of the dendritic cell (DC) populations of rat thymus. The in situ ultrastructural study demonstrated immature interdigitating cells (IDC)/DC in the thymus of 17-day-old embryonic rats, but thymic stromal cell cultures from 16-day-old fetal rats seemed to contain DC precursors which, after several days in culture, produced strongly class II major histocompatibility complex (MHC)-positive, mature DC. According to morphology and class II MHC expression we also defined three different DC populations in the late embryonic rat thymus; two of them, which remained in the adult rat thymus, could represent distinct developmental stages within the IDC/DC lineage. The third cell subset might be involved in a massive process of negative selection, presumably occurring at the end of fetal life in the rat thymus. In supporting the existence of thymic DC subpopulations, we also demonstrated a differential expression of various cell markers, including CD4, CD8, CD25, adhesion molecules and the antigen recognized by OX44 monoclonal antibody (mAb), on thymic DC during both embryonic and adult life. Their possible significance for the attributed functions to thymic DC are discussed extensively. Images Figure 1 Figures 3-5 Figures 6-9 PMID:7913915

  16. NUT midline carcinomas in the thymic region.

    PubMed

    Gökmen-Polar, Yesim; Cano, Oscar D; Kesler, Kenneth A; Loehrer, Patrick J; Badve, Sunil

    2014-12-01

    NUT midline carcinomas (NMCs) are rare tumors described predominantly in the pediatric age group. We recently reported two cases of these tumors occurring in the thymic region. In order to establish the true incidence of these tumors, we examined a large series of thymic carcinomas for morphological features of NUT tumor and further assessed the expression of NUTM1 (also known as NUT) protein by immunohistochemistry. The histological review of slides from 110 cases of thymic carcinoma was undertaken to identify carcinomas with mixed undifferentiated and squamous features that are typically associated with NUT carcinomas. The presenting symptoms, morphological spectrum of tumors and outcome data of patients with these histologies are presented. Immunohistochemistry for NUTM1 was performed on 35 cases of thymic carcinoma with available blocks (3 with these histological features and 32 without these features) to exclude the possibility of midline carcinoma. Tumors from 10 patients had features of mixed small cell undifferentiated squamous cell carcinoma (M:F, 1.5:1; age range, 22-79). These patients predominantly presented with advanced disease and had respiratory-related symptoms or chest pain; four had paraneoplastic syndromes. The squamous component in all cases was well differentiated with little or no atypia. The undifferentiated component varied in cell size and lacked characteristic features of small cell carcinoma. All but one patients developed metastases or died within 3 years of diagnosis. NUTM1 expression was seen in two of three tumors with these histological features and in none of the 32 cases without. Mixed small cell undifferentiated carcinomas share histological and immunohistochemical similarity with NMCs and have aggressive clinical course. These tumors are not uncommon and should be considered in the differential diagnosis of carcinomas in the thymic region as novel therapies might be available.

  17. Dietary modulation of thymic enzymes.

    PubMed

    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

  18. Thymic function in HIV-infection.

    PubMed

    Kolte, Lilian

    2013-04-01

    This thesis is based on seven previously published articles. The work was performed during my employment at The Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, as a scholarship student from 2000-2001 and as a research assistant in the period 2004-2010. HIV-infection is characterized by CD4+ cell depletion. The differences between patients in the degree of CD4+ cell recovery upon treatment with highly active antiretroviral therapy (HAART) may in part be due to differences in the supply of naïve CD4+ cells from the thymus. The thymus atrophies with increasing age for which reason the adult thymus was previously assumed to be without function. The aim of these investigations was to examine the role of the thymus in different aspects of HIV-infection: In adult HIV-infected patients, during HIV-positive pregnancy, and in HIV-exposed uninfected (HIV-EU) children born to HIV-infected mothers. Thymic size and output were determined in 25 adult HIV-infected patients receiving HAART and in 10 controls. Larger thymic size was associated with higher CD4 counts and higher thymic output. Furthermore, patients with abundant thymic tissue seemed to have broader immunological repertoires, compared with patients with minimal thymic tissue. The study supports the mounting evidence of a contribution by the adult thymus to immune reconstitution in HIV-infection. In a follow-up study conducted till 5 years of HAART, the importance of the thymus to the rate of cellular restoration was found to primarily lie within the first two years of HAART. The effect of recombinant human growth hormone (rhGH) was then investigated in a randomized, double-blinded placebo controlled trial in 46 adult HIV-infected patients on HAART. Daily treatment with a low dose of rhGH of 0.7mg for 40 weeks stimulated thymopoiesis as expressed by thymic size, density, and output strongly supporting the assumption that rhGH possesses the potential to stimulate the ageing thymus, holding

  19. Age-related hair pigment loss.

    PubMed

    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. PMID:26370651

  20. [Age-related changes of the brain].

    PubMed

    Paltsyn, A A; Komissarova, S V

    2015-01-01

    The first morphological signs of aging of the brain are found in the white matter already at a young age (20-40 years), and later (40-50 years) in a gray matter. After the 40-50 years appear and in subsequently are becoming more pronounced functional manifestations of morphological changes: the weakening of sensory-motor and cognitive abilities. While in principle this dynamic of age-related changes is inevitable, the rate of their development to a large extent determined by the genetic characteristics and lifestyle of the individual. According to modem concepts age-related changes in the number of nerve cells are different in different parts of the brain. However, these changes are not large and are not the main cause of senile decline brain. The main processes that contribute to the degradation of the brain develop as in the bodies of neurons and in neuropil. In the bodies of neurons--it is a damage (usually decrease) of the level of expression of many genes, and especially of the genes determining cell communication. In neuropil: reduction in the number of synapses and the strength of synaptic connections, reduction in the number of dendritic spines and axonal buttons, reduction in the number and thickness of the dendritic branches, demyelination of axons. As the result of these events, it becomes a violation of the rate of formation and rebuilding neuronal circuits. It is deplete associative ability, brain plasticity, and memory. PMID:27116888

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

    PubMed

    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.

  2. Separation distance and static transmission error of involute spur gears

    NASA Technical Reports Server (NTRS)

    Tse, David K.; Lin, Hsiang H.

    1992-01-01

    The effects of separation distance and deflection of gear teeth on the static transmission error of involute spur gears are investigated. In this paper, only low-contact-ratio gears with true involute profile are studied. Gear ratio and tooth addendum are varied to examine their effects on the separation distance and static transmission error. Results obtained from the investigation shows that the contact ratio and static transmission error are affected significantly if considering the separation distance. In general, the magnitude of contact ratio has been increased and the variation of static transmission error has been smoothed. The most significant change occurs for a gear pair with a theoretical contact ratio close to 1.95.

  3. Spontaneous Involution of Congenital Melanocytic Nevus With Halo Phenomenon.

    PubMed

    Lee, Noo Ri; Chung, Hee-Chul; Hong, Hannah; Lee, Jin Wook; Ahn, Sung Ku

    2015-12-01

    Congenital melanocytic nevus (CMN) is a neural crest-derived hamartoma, which appear at or soon after birth. CMN has a dynamic course and may show variable changes over time, including spontaneous involution. Spontaneous involution of CMN is a rare phenomenon and is often reported in association with halo phenomenon or vitiligo. The mechanism of halo phenomenon is yet to be investigated but is suggested to be a destruction of melanocytes by immune responses of cytotoxic T cells or IgM autoantibodies. Here, the authors report an interesting case of spontaneously regressed medium-sized CMN with halo phenomenon and without vitiligo, which provides evidence that cytotoxic T cells account for the halo formation and pigmentary regression of CMN.

  4. Reduced thymic output in elite athletes.

    PubMed

    Prieto-Hinojosa, Adria; Knight, Andrea; Compton, Claude; Gleeson, Michael; Travers, Paul J

    2014-07-01

    Athletes undergoing intensive training schedules have chronic exposure to stress-induced hormones such as cortisol that can depress immune function. We compared the circulating levels of T cell receptor excision circles (TREC), a marker of recent thymic emigrants, as well as the levels of naïve and memory subsets in a group of elite endurance athletes and in controls. The athletes showed a reduction in absolute numbers of naïve T cells, particularly in CD4 T cells. In contrast, memory cells were increased. TREC levels in the athletes were significantly reduced compared to age-matched controls. Such changes resemble premature ageing of the T cell component of the immune system. Since thymic production of T cells naturally decline with age, these results raise the concern that prolonging high intensity exercise into the 4th decade of life may have deleterious consequences for athletes' health.

  5. Functional anatomy of the thymic microenvironment.

    PubMed Central

    Kendall, M D

    1991-01-01

    This paper presents a review of our current understanding of the nature of the thymic microenvironment, after briefly considering the major role of the gland. The epithelial cells and their products are of fundamental importance, and other cells of the macrophage series are implicated in most functional events. The embryological origin of the epithelium is still not clear, although disease conditions would suggest a single origin. Immigration and emigration of thymocytes is considered, and also the passage of antigens into the gland. The events within the thymus are under the control of the CNS acting through the innervation or via hormonal pathways. Both of these areas are considered in detail, especially thymic hormone origins, functions and interactions. Images Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 11 PMID:1769884

  6. Analysis of hydraulic instability of ANS involute fuel plates

    SciTech Connect

    Sartory, W.K.

    1991-11-01

    Curved shell equations for the involute Advanced Neutron Source (ANS) fuel plates are coupled to two-dimensional hydraulic channel flow equations that include fluid friction. A complete set of fluid and plate boundary conditions is applied at the entrance and exit and along the sides of the plate and the channel. The coupled system is linearized and solved to assess the hydraulic instability of the plates.

  7. Heisenberg Groups and their Automorphisms over Algebras with Central Involution

    NASA Astrophysics Data System (ADS)

    Johnson, Robert W.

    2015-08-01

    Heisenberg groups over algebras with central involution and their automorphism groups are constructed. The complex quaternion group algebra over a prime field is used as an example. Its subspaces provide finite models for each of the real and complex quadratic spaces with dimension 4 or less. A model for the representations of these Heisenberg groups and automorphism groups is constructed. A pseudo-differential operator enables a parallel treatment of spaces defined over finite and real fields.

  8. [Treatment options for age-related infertility].

    PubMed

    Belaisch-Allart, Joëlle

    2010-06-20

    There has been a consistent trend towards delayed childbearing in most Western countries. Treatment options for age-related infertility includes controlled ovarian hyperstimulation with intrauterine insemination and in vitro fertilization (IVF). A sharp decline in pregnancy rate with advancing female age is noted with assisted reproductive technologies (ART) including IVF. Evaluation and treatment of infertility should not be delayed in women 35 years and older. No treatment other than oocyte donation has been shown to be effective for women over 40 and for those with compromised ovarian reserve, but its pratice is not easy in France hence the procreative tourism. As an increasing number of couples choose to postpone childbearing, they should be informed that maternal age is an important risk factor for failure to conceive. PMID:20623902

  9. [Epidemiology of age-related macular degeneration].

    PubMed

    Brandl, C; Stark, K J; Wintergerst, M; Heinemann, M; Heid, I M; Finger, R P

    2016-09-01

    Age-related macular degeneration (AMD) is the main cause of blindness in industrialized societies. Population-based epidemiological investigations generate important data on prevalence, incidence, risk factors, and future trends. This review summarizes the most important epidemiological studies on AMD with a focus on their transferability to Germany including existing evidence for the main risk factors for AMD development and progression. Future tasks, such as the standardization of grading systems and the use of recent retinal imaging technology in epidemiological studies are discussed. In Germany, epidemiological data on AMD are scarce. However, the need for epidemiological research in ophthalmology is currently being addressed by several recently started population-based studies. PMID:27541733

  10. Inflammation in age-related macular degeneration.

    PubMed

    Ozaki, Ema; Campbell, Matthew; Kiang, Anna-Sophia; Humphries, Marian; Doyle, Sarah L; Humphries, Peter

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of legal blindness in elderly individuals in the developed world, affecting 30-50 million people worldwide. AMD primarily affects the macular region of the retina that is responsible for the majority of central, color and daytime vision. The presence of drusen, extracellular protein aggregates that accumulate under the retinal pigment epithelium (RPE), is a major pathological hallmark in the early stages of the disease. The end stage 'dry' and 'wet' forms of the disease culminate in vision loss and are characterized by focal degeneration of the RPE and cone photoreceptors, and choroidal neovascularization (CNV), respectively. Being a multifactorial and genetically heterogeneous disease, the pathophysiology of AMD remains unclear, yet, there is ample evidence supporting immunological and inflammatory processes. Here, we review the recent literature implicating some of these immune processes in human AMD and in animal models. PMID:24664703

  11. Consequences of Age-Related Cognitive Declines

    PubMed Central

    Salthouse, Timothy

    2013-01-01

    Adult age differences in a variety of cognitive abilities are well documented, and many of those abilities have been found to be related to success in the workplace and in everyday life. However, increased age is seldom associated with lower levels of real-world functioning, and the reasons for this lab-life discrepancy are not well understood. This article briefly reviews research concerned with relations of age to cognition, relations of cognition to successful functioning outside the laboratory, and relations of age to measures of work performance and achievement. The final section discusses several possible explanations for why there are often little or no consequences of age-related cognitive declines in everyday functioning. PMID:21740223

  12. Medical bioremediation of age-related diseases

    PubMed Central

    Mathieu, Jacques M; Schloendorn, John; Rittmann, Bruce E; Alvarez, Pedro JJ

    2009-01-01

    Catabolic insufficiency in humans leads to the gradual accumulation of a number of pathogenic compounds associated with age-related diseases, including atherosclerosis, Alzheimer's disease, and macular degeneration. Removal of these compounds is a widely researched therapeutic option, but the use of antibodies and endogenous human enzymes has failed to produce effective treatments, and may pose risks to cellular homeostasis. Another alternative is "medical bioremediation," the use of microbial enzymes to augment missing catabolic functions. The microbial genetic diversity in most natural environments provides a resource that can be mined for enzymes capable of degrading just about any energy-rich organic compound. This review discusses targets for biodegradation, the identification of candidate microbial enzymes, and enzyme-delivery methods. PMID:19358742

  13. Age-related macular degeneration: current treatments

    PubMed Central

    Hubschman, Jean Pierre; Reddy, Shantan; Schwartz, Steven D

    2009-01-01

    Purpose: Although important progress has been made in understanding age-related macular degeneration (AMD), management of the disease continues to be a challenge. AMD research has led to a widening of available treatment options and improved prognostic perspectives. This essay reviews these treatment options. Design: Interpretative essay. Methods: Literature review and interpretation. Results: Current treatments to preserve vision in patients with non-exudative AMD include antioxidant vitamins and mineral supplementations. Exudative AMD is currently most often treated monthly with anti-VEGF intravitreal injections. However, investigators are beginning to experiment with combination therapy and surgical approaches in an attempt to limit the number of treatment and reduce the financial burden on the health care system. Conclusion: By better understanding the basis and pathogenesis of AMD, newer therapies will continue to be developed that target specific pathways in patients with AMD, with the hoped for outcome of better management of the disease and improved visual acuity. PMID:19668560

  14. [The involutional age from the viewpoint of the gynecologist].

    PubMed

    Ledermair, O

    1985-01-01

    Besides the normal aging processes, which affect all human beings, regardless of their gender the involutional years of women have a number of special characteristics. These are based on the fact, that one group of organs-the reproductive system - hold their function earlier than the others. Because of this fact the involution of women ist basically different from that of men. During these years she often require therapeutic help by a physician not only for drug therapy but also psychologically. The drug-therapy seems to be relatively simple: balance of the oestrogen deficit. But today the oestrogen therapy became more difficult and has to be adjusted individually. The decision has to be made in regard to the type of hormone, the dose, the time sequence, the question of the gestagen component, the risk for malignancy, the effect on clothing and vessels etc. Old and new types of therapy including diet, tea, climate and bathing cures, tranquilizers, drugs for the autonomic nervous system, homeopathic therapy, acupuncture etc. also have their place. We will discuss these questions in the afternoon session extensively since the involutional years of women from the view of the gynaecologists are a very interesting and important field of medicine still for therapy and research.

  15. On classifying the divisor involutions in Calabi-Yau threefolds

    NASA Astrophysics Data System (ADS)

    Gao, Xin; Shukla, Pramod

    2013-11-01

    In order to support the odd moduli in models of (type IIB) string compactification, we classify the Calabi-Yau threefolds with h 1,1 ≤ 4 which exhibit pairs of identical divisors, with different line-bundle charges, mapping to each other under possible divisor exchange involutions. For this purpose, the divisors of interest are identified as completely rigid surface, Wilson surface, K3 surface and some other deformation surfaces. Subsequently, various possible exchange involutions are examined under the symmetry of Stanley-Reisner Ideal. In addition, we search for the Calabi-Yau theefolds which contain a divisor with several disjoint components. Under certain reflection involution, such spaces also have nontrivial odd components in (1,1)-cohomology class. String compactifications on such Calabi-Yau orientifolds with non-zero could be promising for concrete model building in both particle physics and cosmology. In the spirit of using such Calabi-Yau orientifolds in the context of LARGE volume scenario, we also present some concrete examples of (strong/weak) swiss-cheese type volume form.

  16. Graves' Patient with Thymic Expression of Thyrotropin Receptors and Dynamic Changes in Thymic Hyperplasia Proportional to Graves' Disease Activity

    PubMed Central

    Song, Young Shin; Won, Jae-Kyung; Kim, Mi Jeong; Lee, Ji Hyun; Kim, Dong-Wan; Chung, June-Key; Park, Do Joon

    2016-01-01

    Thymic hyperplasia is frequently observed in Graves' disease. However, detectable massive enlargement of the thymus is rare, and the mechanism of its formation has remained elusive. This case showed dynamic changes in thymic hyperplasia on serial computed tomography images consistent with changes in serum thyrotropin receptor (TSH-R) antibodies and thyroid hormone levels. Furthermore, the patient's thymic tissues underwent immunohistochemical staining for TSH-R, which demonstrated the presence of thymic TSH-R. The correlation between serum TSH-R antibody levels and thymic hyperplasia sizes and the presence of TSH-R in her thymus suggest that TSH-R antibodies could have a pathogenic role in thymic hyperplasia. PMID:26996584

  17. Animal models of age related macular degeneration

    PubMed Central

    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

  18. Aging, frailty and age-related diseases.

    PubMed

    Fulop, T; Larbi, A; Witkowski, J M; McElhaney, J; Loeb, M; Mitnitski, A; Pawelec, G

    2010-10-01

    The concept of frailty as a medically distinct syndrome has evolved based on the clinical experience of geriatricians and is clinically well recognizable. Frailty is a nonspecific state of vulnerability, which reflects multisystem physiological change. These changes underlying frailty do not always achieve disease status, so some people, usually very elderly, are frail without a specific life threatening illness. Current thinking is that not only physical but also psychological, cognitive and social factors contribute to this syndrome and need to be taken into account in its definition and treatment. Together, these signs and symptoms seem to reflect a reduced functional reserve and consequent decrease in adaptation (resilience) to any sort of stressor and perhaps even in the absence of extrinsic stressors. The overall consequence is that frail elderly are at higher risk for accelerated physical and cognitive decline, disability and death. All these characteristics associated with frailty can easily be applied to the definition and characterization of the aging process per se and there is little consensus in the literature concerning the physiological/biological pathways associated with or determining frailty. It is probably true to say that a consensus view would implicate heightened chronic systemic inflammation as a major contributor to frailty. This review will focus on the relationship between aging, frailty and age-related diseases, and will highlight possible interventions to reduce the occurrence and effects of frailty in elderly people. PMID:20559726

  19. Physics of Age Related Macular Degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon

    2009-11-01

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer's disease, and Parkinson's disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. In this talk I will discuss a model of non-equilibrium cluster growth that we have developed for studying the formation and growth of lipofuscin in AMD [K.I. Mazzitello, C.M. Arizmendi, Fereydoon Family, H. E. Grossniklaus, Physical Review E (2009)]. I will also present an overview of our theoretical and computational efforts in modeling some other aspects of the physics of AMD, including CNV and the breakdown of Bruch's membrane [Ongoing collaboration with Abbas Shirinifard and James A. Glazier, Biocomplexity Institute and Department of Physics, Indiana University, Y. Jiang, Los Alamos, and Hans E. Grossniklaus, Department of Ophthalmology, Emory University].

  20. Mechanisms of age-related macular degeneration

    PubMed Central

    Ambati, Jayakrishna; Fowler, Benjamin J.

    2012-01-01

    Age-related macular degeneration (AMD), a progressive condition that is untreatable in up to 90% of patients, is a leading cause of blindness in the elderly worldwide. The two forms of AMD, wet and dry, are classified based on the presence or absence of blood vessels that have disruptively invaded the retina, respectively. A detailed understanding of the molecular mechanisms underlying wet AMD has led to several robust FDA-approved therapies. In contrast, there are not any approved treatments for dry AMD. In this review, we provide insight into the critical effector pathways that mediate each form of disease. The interplay of immune and vascular systems for wet AMD, and the proliferating interest in hunting for gene variants to explain AMD pathogenesis, are placed in the context of the latest clinical and experimental data. Emerging models of dry AMD pathogenesis are presented, with a focus on DICER1 deficit and the toxic accumulation of retinal debris. A recurring theme that spans most aspects of AMD pathogenesis is defective immune modulation in the classically immune-privileged ocular haven. Interestingly, the latest advances in AMD research highlight common molecular disease pathways with other common neurodegenerations. Finally, the therapeutic potential of intervening at known mechanisms of AMD pathogenesis is discussed. PMID:22794258

  1. Age related degradation in operating nuclear plants

    SciTech Connect

    Hermann, R.A.; Davis, J.A.; Banic, M.J.

    1995-12-01

    The aging issues being addressed for today`s operating commercial nuclear power plants encompass a wide spectrum of components, complexities, and reasons for concern. Issues include such things as the intergranular stress corrosion cracking (IGSCC) of boiling water reactor (BWR) internals, the degradation of pressurized water reactor (PWR) Alloy 600 components by primary water stress corrosion cracking (PWSCC) to those associated with significant portions of piping systems, such as service water systems. a discussion of the regulatory activity and action associated with the above issues is provided. Proactive NRC/Industry programs for inspection and repair or replacement of affected components are essential for continued operation of these nuclear reactors. These programs are also essential as licensees consider license extensions for their facilities. These plants are licensed for 40 years and can be granted an extension for an additional 20 years of operation if all of the NRC rules and regulations are met. Proper handling of potential age related problems will be a key consideration in the granting of a license extension.

  2. Statistical physics of age related macular degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon; Mazzitello, K. I.; Arizmendi, C. M.; Grossniklaus, H. E.

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer disease and Parkinson disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. We introduce a model of non-equilibrium cluster growth and aggregation that we have developed for studying the formation and growth of lipofuscin in the aging RPE. Our results agree with a linear growth of the number of lipofuscin granules with age. We apply the dynamic scaling approach to our model and find excellent data collapse for the cluster size distribution. An unusual feature of our model is that while small particles are removed from the RPE the larger ones become fixed and grow by aggregation.

  3. GENETICS OF HUMAN AGE RELATED DISORDERS.

    PubMed

    Srivastava, I; Thukral, N; Hasija, Y

    2015-01-01

    Aging is an inevitable biological phenomenon. The incidence of age related disorders (ARDs) such as cardiovascular diseases, cancer, arthritis, dementia, osteoporosis, diabetes, neurodegenerative diseases increase rapidly with aging. ARDs are becoming a key social and economic trouble for the world's elderly population (above 60 years), which is expected to reach 2 billion by 2050. Advancement in understanding of genetic associations, particularly through genome wide association studies (GWAS), has revealed a substantial contribution of genes to human aging and ARDs. In this review, we have focused on the recent understanding of the extent to which genetic predisposition may influence the aging process. Further analysis of the genetic association studies through pathway analysis several genes associated with multiple ARDs have been highlighted such as apolipoprotein E (APOE), brain-derived neurotrophic factor (BDNF), cadherin 13 (CDH13), CDK5 regulatory subunit associated protein 1 (CDKAL-1), methylenetetrahydrofolate reductase (MTHFR), disrupted in schizophrenia 1 (DISC1), nitric oxide synthase 3 (NOS3), paraoxonase 1 (PON1), indicating that these genes could play a pivotal role in ARD causation. These genes were found to be significantly enriched in Jak-STAT signalling pathway, asthma and allograft rejection. Further, interleukin-6 (IL-6), insulin (INS), vascular endothelial growth factor A (VEGFA), estrogen receptor1 (ESR1), transforming growth factor, beta 1(TGFB1) and calmodulin 1 (CALM1) were found to be highly interconnected in network analysis. We believe that extensive research on the presence of common genetic variants among various ARDs may facilitate scientists to understand the biology behind ARDs causation. PMID:26856084

  4. Nut consumption and age-related disease.

    PubMed

    Grosso, G; Estruch, R

    2016-02-01

    Current knowledge on the effects of nut consumption on human health has rapidly increased in recent years and it now appears that nuts may play a role in the prevention of chronic age-related diseases. Frequent nut consumption has been associated with better metabolic status, decreased body weight as well as lower body weight gain over time and thus reduce the risk of obesity. The effect of nuts on glucose metabolism, blood lipids, and blood pressure is still controversial. However, significant decreased cardiovascular risk has been reported in a number of observational and clinical intervention studies. Thus, findings from cohort studies show that increased nut consumption is associated with a reduced risk of cardiovascular disease and mortality (especially that due to cardiovascular-related causes). Similarly, nut consumption has been also associated with reduced risk of certain cancers, such as colorectal, endometrial, and pancreatic neoplasms. Evidence regarding nut consumption and neurological or psychiatric disorders is scarce, but a number of studies suggest significant protective effects against depression, mild cognitive disorders and Alzheimer's disease. The underlying mechanisms appear to include antioxidant and anti-inflammatory actions, particularly related to their mono- and polyunsaturated fatty acids (MUFA and PUFA, as well as vitamin and polyphenol content). MUFA have been demonstrated to improve pancreatic beta-cell function and regulation of postprandial glycemia and insulin sensitivity. PUFA may act on the central nervous system protecting neuronal and cell-signaling function and maintenance. The fiber and mineral content of nuts may also confer health benefits. Nuts therefore show promise as useful adjuvants to prevent, delay or ameliorate a number of chronic conditions in older people. Their association with decreased mortality suggests a potential in reducing disease burden, including cardiovascular disease, cancer, and cognitive impairments

  5. Nut consumption and age-related disease.

    PubMed

    Grosso, G; Estruch, R

    2016-02-01

    Current knowledge on the effects of nut consumption on human health has rapidly increased in recent years and it now appears that nuts may play a role in the prevention of chronic age-related diseases. Frequent nut consumption has been associated with better metabolic status, decreased body weight as well as lower body weight gain over time and thus reduce the risk of obesity. The effect of nuts on glucose metabolism, blood lipids, and blood pressure is still controversial. However, significant decreased cardiovascular risk has been reported in a number of observational and clinical intervention studies. Thus, findings from cohort studies show that increased nut consumption is associated with a reduced risk of cardiovascular disease and mortality (especially that due to cardiovascular-related causes). Similarly, nut consumption has been also associated with reduced risk of certain cancers, such as colorectal, endometrial, and pancreatic neoplasms. Evidence regarding nut consumption and neurological or psychiatric disorders is scarce, but a number of studies suggest significant protective effects against depression, mild cognitive disorders and Alzheimer's disease. The underlying mechanisms appear to include antioxidant and anti-inflammatory actions, particularly related to their mono- and polyunsaturated fatty acids (MUFA and PUFA, as well as vitamin and polyphenol content). MUFA have been demonstrated to improve pancreatic beta-cell function and regulation of postprandial glycemia and insulin sensitivity. PUFA may act on the central nervous system protecting neuronal and cell-signaling function and maintenance. The fiber and mineral content of nuts may also confer health benefits. Nuts therefore show promise as useful adjuvants to prevent, delay or ameliorate a number of chronic conditions in older people. Their association with decreased mortality suggests a potential in reducing disease burden, including cardiovascular disease, cancer, and cognitive impairments.

  6. Association of Age Related Macular Degeneration and Age Related Hearing Impairment

    PubMed Central

    Ghasemi, Hassan; Pourakbari, Malihe Shahidi; Entezari, Morteza; Yarmohammadi, Mohammad Ebrahim

    2016-01-01

    Purpose: To evaluate the association between age-related macular degeneration (ARMD) and sensory neural hearing impairment (SHI). Methods: In this case-control study, hearing status of 46 consecutive patients with ARMD were compared with 46 age-matched cases without clinical ARMD as a control group. In all patients, retinal involvements were confirmed by clinical examination, fluorescein angiography (FA) and optical coherence tomography (OCT). All participants were examined with an otoscope and underwent audiological tests including pure tone audiometry (PTA), speech reception threshold (SRT), speech discrimination score (SDS), tympanometry, reflex tests and auditory brainstem response (ABR). Results: A significant (P = 0.009) association was present between ARMD, especially with exudative and choroidal neovascularization (CNV) components, and age-related hearing impairment primarily involving high frequencies. Patients had higher SRT and lower SDS against anticipated presbycusis than control subjects. Similar results were detected in exudative, CNV and scar patterns supporting an association between late ARMD with SRT and SDS abnormalities. ABR showed significantly prolonged wave I and IV latency times in ARMD (P = 0.034 and 0.022, respectively). Average latency periods for wave I in geographic atrophy (GA) and CNV, and that for wave IV in drusen patterns of ARMD were significantly higher than controls (P = 0.030, 0.007 and 0.050, respectively). Conclusion: The association between ARMD and age-related SHI may be attributed to common anatomical components such as melanin in these two sensory organs. PMID:27195086

  7. Age-Related Changes in the Misinformation Effect.

    ERIC Educational Resources Information Center

    Sutherland, Rachel; Hayne, Harlene

    2001-01-01

    Two experiments examined relation between age-related changes in retention and age-related changes in the misinformation effect. Found large age-related retention differences when participants were interviewed immediately and after 1 day, but after 6 weeks, differences were minimal. Exposure to misleading information increased commission errors.…

  8. Statins for age-related macular degeneration

    PubMed Central

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2016-01-01

    Background 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. Objectives 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. Search methods 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. Selection criteria 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. Data collection and analysis 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

  9. Statins for age-related macular degeneration

    PubMed Central

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2016-01-01

    Background 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. Objectives 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. Search methods 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. Selection criteria 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. Data collection and analysis 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

  10. Acute intestinal obstruction due to a non-involuted uterus after cesarean section: case report.

    PubMed

    Karaman, K; Ercan, M; Demir, H; Yener Uzunoglu, M; Bostanci, S

    2016-01-01

    The involution of the uterus is influenced by a number of factors such as advanced childbearing age, electrolyte disturbances, multiparity, repeated cesarean sections, and vaginal infections. The authors report the management of a clinical case of a 41-year-old female who presented with acute intestinal obstruction due to a non-involuted uterus after cesarean section.

  11. Modified Involute Helical Gears: Computerized Design, Simulation of Meshing, and Stress Analysis

    NASA Technical Reports Server (NTRS)

    Handschuh, Robert (Technical Monitor); Litvin, Faydor L.; Gonzalez-Perez, Ignacio; Carnevali, Luca; Kawasaki, Kazumasa; Fuentes-Aznar, Alfonso

    2003-01-01

    The computerized design, methods for generation, simulation of meshing, and enhanced stress analysis of modified involute helical gears is presented. The approaches proposed for modification of conventional involute helical gears are based on conjugation of double-crowned pinion with a conventional helical involute gear. Double-crowning of the pinion means deviation of cross-profile from an involute one and deviation in longitudinal direction from a helicoid surface. Using the method developed, the pinion-gear tooth surfaces are in point-contact, the bearing contact is localized and oriented longitudinally, and edge contact is avoided. Also, the influence of errors of aligment on the shift of bearing contact, vibration, and noise are reduced substantially. The theory developed is illustrated with numerical examples that confirm the advantages of the gear drives of the modified geometry in comparison with conventional helical involute gears.

  12. Modified Involute Helical Gears: Computerized Design, Simulation of Meshing and Stress Analysis

    NASA Technical Reports Server (NTRS)

    2003-01-01

    The computerized design, methods for generation, simulation of meshing, and enhanced stress analysis of modified involute helical gears is presented. The approaches proposed for modification of conventional involute helical gears are based on conjugation of double-crowned pinion with a conventional helical involute gear. Double-crowning of the pinion means deviation of cross-profile from an involute one and deviation in longitudinal direction from a helicoid surface. Using the method developed, the pinion-gear tooth surfaces are in point-contact, the bearing contact is localized and oriented longitudinally, and edge contact is avoided. Also, the influence of errors of alignment on the shift of bearing contact, vibration, and noise are reduced substantially. The theory developed is illustrated with numerical examples that confirm the advantages of the gear drives of the modified geometry in comparison with conventional helical involute gears.

  13. Involution and Difference Schemes for the Navier-Stokes Equations

    NASA Astrophysics Data System (ADS)

    Gerdt, Vladimir P.; Blinkov, Yuri A.

    In the present paper we consider the Navier-Stokes equations for the two-dimensional viscous incompressible fluid flows and apply to these equations our earlier designed general algorithmic approach to generation of finite-difference schemes. In doing so, we complete first the Navier-Stokes equations to involution by computing their Janet basis and discretize this basis by its conversion into the integral conservation law form. Then we again complete the obtained difference system to involution with eliminating the partial derivatives and extracting the minimal Gröbner basis from the Janet basis. The elements in the obtained difference Gröbner basis that do not contain partial derivatives of the dependent variables compose a conservative difference scheme. By exploiting arbitrariness in the numerical integration approximation we derive two finite-difference schemes that are similar to the classical scheme by Harlow and Welch. Each of the two schemes is characterized by a 5×5 stencil on an orthogonal and uniform grid. We also demonstrate how an inconsistent difference scheme with a 3×3 stencil is generated by an inappropriate numerical approximation of the underlying integrals.

  14. Loss of Pten Disrupts the Thymic Epithelium and Alters Thymic Function.

    PubMed

    Garfin, Phillip M; Nguyen, Thuyen; Sage, Julien

    2016-01-01

    The thymus is the site of T cell development and selection. In addition to lymphocytes, the thymus is composed of several types of stromal cells that are exquisitely organized to create the appropriate environment and microenvironment to support the development and selection of maturing T cells. Thymic epithelial cells (TECs) are one of the more important cell types in the thymic stroma, and they play a critical role in selecting functional T cell clones and supporting their development. In this study, we used a mouse genetics approach to investigate the consequences of deleting the Pten tumor suppressor gene in the TEC compartment of the developing thymus. We found that PTEN deficiency in TECs results in a smaller thymus with significantly disordered architecture and histology. Accordingly, loss of PTEN function also results in decreased T cells with a shift in the distribution of T cell subtypes towards CD8+ T cells. These experiments demonstrate that PTEN is critically required for the development of a functional thymic epithelium in mice. This work may help better understand the effects that certain medical conditions or clinical interventions have upon the thymus and immune function.

  15. Loss of Pten Disrupts the Thymic Epithelium and Alters Thymic Function.

    PubMed

    Garfin, Phillip M; Nguyen, Thuyen; Sage, Julien

    2016-01-01

    The thymus is the site of T cell development and selection. In addition to lymphocytes, the thymus is composed of several types of stromal cells that are exquisitely organized to create the appropriate environment and microenvironment to support the development and selection of maturing T cells. Thymic epithelial cells (TECs) are one of the more important cell types in the thymic stroma, and they play a critical role in selecting functional T cell clones and supporting their development. In this study, we used a mouse genetics approach to investigate the consequences of deleting the Pten tumor suppressor gene in the TEC compartment of the developing thymus. We found that PTEN deficiency in TECs results in a smaller thymus with significantly disordered architecture and histology. Accordingly, loss of PTEN function also results in decreased T cells with a shift in the distribution of T cell subtypes towards CD8+ T cells. These experiments demonstrate that PTEN is critically required for the development of a functional thymic epithelium in mice. This work may help better understand the effects that certain medical conditions or clinical interventions have upon the thymus and immune function. PMID:26914657

  16. Sonic Hedgehog regulates thymic epithelial cell differentiation

    PubMed Central

    Saldaña, José Ignacio; Solanki, Anisha; Lau, Ching-In; Sahni, Hemant; Ross, Susan; Furmanski, Anna L.; Ono, Masahiro; Holländer, Georg; Crompton, Tessa

    2016-01-01

    Sonic Hedgehog (Shh) is expressed in the thymus, where it regulates T cell development. Here we investigated the influence of Shh on thymic epithelial cell (TEC) development. Components of the Hedgehog (Hh) signalling pathway were expressed by TEC, and use of a Gli Binding Site-green fluorescence protein (GFP) transgenic reporter mouse demonstrated active Hh-dependent transcription in TEC in the foetal and adult thymus. Analysis of Shh-deficient foetal thymus organ cultures (FTOC) showed that Shh is required for normal TEC differentiation. Shh-deficient foetal thymus contained fewer TEC than wild type (WT), the proportion of medullary TEC was reduced relative to cortical TEC, and cell surface expression of MHC Class II molecules was increased on both cortical and medullary TEC populations. In contrast, the Gli3-deficient thymus, which shows increased Hh-dependent transcription in thymic stroma, had increased numbers of TEC, but decreased cell surface expression of MHC Class II molecules on both cortical and medullary TEC. Neutralisation of endogenous Hh proteins in WT FTOC led to a reduction in TEC numbers, and in the proportion of mature Aire-expressing medullary TEC, but an increase in cell surface expression of MHC Class II molecules on medullary TEC. Likewise, conditional deletion of Shh from TEC in the adult thymus resulted in alterations in TEC differentiation and consequent changes in T cell development. TEC numbers, and the proportion of mature Aire-expressing medullary TEC were reduced, and cell surface expression of MHC Class II molecules on medullary TEC was increased. Differentiation of mature CD4 and CD8 single positive thymocytes was increased, demonstrating the regulatory role of Shh production by TEC on T cell development. Treatment of human thymus explants with recombinant Shh or neutralising anti-Shh antibody indicated that the Hedgehog pathway is also involved in regulation of differentiation from DP to mature SP T cells in the human thymus. PMID

  17. Handbook on Face Gear Drives with a Spur Involute Pinion

    NASA Technical Reports Server (NTRS)

    Litvin, F. L.; Egelja, A.; Tan, J.; Chen, D. Y.-D.; Heath, G.

    2000-01-01

    The use of face gears in power transmission and drive systems has a significant number of benefits. Face gears allow a variety of new transmission arrangements as well as high reduction ratio capability. This leads to drive system weight reduction and improvements in performance. In this work, basic information about the design and analysis of face gear drives is presented. The work considers face gears in mesh with spur involute pinions for both intersecting axes and offset drives. Tooth geometry, kinematics, generation of face gears with localized bearing contact by cutting and grinding, avoidance of tooth undercutting, avoidance of tooth pointing, tooth contact analysis, and algorithms for the simulation of meshing and contact arc all topics which are discussed. In addition, applications of face gear drives are presented. Included are design uses in aerospace applications such as helicopter transmissions, split-torque face gear arrangements, comparisons of face gears with bevel gears, and general design considerations.

  18. Comparative Analysis of the Extracellular Matrix Composition in Proliferating and Involuted Infantile Hemangiomas

    PubMed Central

    Park, Hyochun; Park, Hannara; O, Teresa M; Waner, Milton

    2015-01-01

    Background Changes in the composition of the extracellular matrix (ECM) occur between the proliferating and involuted phases of infantile hemangiomas (IH), and are associated with angiogenic growth. We examined the composition of the ECM in proliferating and involuted IHs and assessed correlations between the composition of the ECM and whether the IH was in the proliferating or the involuted phase. Methods We evaluated IH samples from a cohort of patients who had five proliferating IHs and five involuted IHs. The following ECM molecules were analyzed using enzyme-linked immunosorbent assays and immunohistochemistry: laminin, fibronectin, collagen type I, collagen type II, and collagen type III. Results The involuted IHs had higher levels of deposition of collagen type III than the proliferating IHs. The median values (interquartile ranges) were 1.135 (0.946-1.486) and 1.008 (0.780-1.166) (P=0.019), respectively. The level of laminin was higher in involuted IHs than in proliferating IHs, with median values (interquartile ranges) of 3.191 (2.945-3.191) and 2.479 (1.699-3.284) (P=0.047), respectively. Abundant collagen type III staining was found in involuted IHs. Laminin α4 chain staining was clearly present within the basement membrane adjacent to the blood vessels, and was significantly more intense in involuted IHs than in proliferative IHs. Conclusions Involuted hemangiomas showed extensive deposition of collagen III and laminin, suggesting that differences in the composition of the ECM reflect stages of the development of IHs. This pattern may be due to the rapid senescence of IHs. PMID:26430624

  19. Evaluation of a histogenetic classification for thymic epithelial tumours.

    PubMed

    Ho, F C; Fu, K H; Lam, S Y; Chiu, S W; Chan, A C; Müller-Hermelink, H K

    1994-07-01

    We reviewed 87 thymic epithelial tumours from Chinese patients and typed them according to the Marino and Müller-Hermelink classification as updated by Kirschner and Müller-Hermelink in 1989. Related categories were grouped for statistical analyses: group 1, medullary thymoma and mixed thymoma; group 2, cortical predominant thymoma; group 3, cortical thymoma and well-differentiated thymic carcinoma; group 4, other thymic carcinomas; and group 5, unclassified. Group 3 tumours were more frequently associated with the myasthenia gravis syndrome compared with group 1 tumours (P = 0.001). They also presented at a more advanced stage. Groups 1 and 2 showed an excellent prognosis (100% survival at 10 years). The 10-year survival for groups 3 and 4 patients was 40% and 30% respectively. Pure medullary thymoma made up a higher proportion of our cases (10.3%) than those of a similar Caucasian study (5.3%). The eight thymic carcinomas (group 4) included two thymic lymphoepitheliomas. We conclude that the histogenetic classification evaluated shows a clear correlation with prognosis and clinical features, even when tested on separate geographic groups, where pathogenetic factors may be different. A common approach to classification of thymic epithelial tumours would greatly facilitate future studies on these possible differences.

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

    PubMed

    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. PMID:26572116

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

    PubMed

    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.

  2. Slowing Down: Age-Related Neurobiological Predictors of Processing Speed

    PubMed Central

    Eckert, Mark A.

    2011-01-01

    Processing speed, or the rate at which tasks can be performed, is a robust predictor of age-related cognitive decline and an indicator of independence among older adults. This review examines evidence for neurobiological predictors of age-related changes in processing speed, which is guided in part by our source based morphometry findings that unique patterns of frontal and cerebellar gray matter predict age-related variation in processing speed. These results, together with the extant literature on morphological predictors of age-related changes in processing speed, suggest that specific neural systems undergo declines and as a result slow processing speed. Future studies of processing speed – dependent neural systems will be important for identifying the etiologies for processing speed change and the development of interventions that mitigate gradual age-related declines in cognitive functioning and enhance healthy cognitive aging. PMID:21441995

  3. Expression of LIF in transgenic mice results in altered thymic epithelium and apparent interconversion of thymic and lymph node morphologies.

    PubMed Central

    Shen, M M; Skoda, R C; Cardiff, R D; Campos-Torres, J; Leder, P; Ornitz, D M

    1994-01-01

    Leukemia inhibitory factor (LIF) is a cytokine involved in embryonic and hematopoietic development. To investigate the effects of LIF on the lymphoid system, we generated a line of transgenic mice that expresses diffusible LIF protein specifically in T cells. These mice display two categories of phenotype that were not previously attributed to LIF overexpression. First, they display B cell hyperplasia, polyclonal hypergammaglobulinemia and mesangial proliferative glomerulonephritis, defects similar to those described for transgenic mice overexpressing the functionally related cytokine, interleukin-6. Secondly, the LIF transgenic mice display novel thymic and lymph node abnormalities. In the thymus, cortical CD4+CD8+ lymphocytes are lost, while numerous B cell follicles develop. Peripheral lymph nodes contain a vastly expanded CD4+CD8+ lymphocyte population. Furthermore, the thymic epithelium is profoundly disorganized, suggesting that disruption of stroma-lymphocyte interactions is responsible for many observed defects. Transplantation of transgenic bone marrow into wild type recipients transfers both the thymic and lymph node defects. However, transplantation of wild type marrow into transgenic recipients rescues the lymph node abnormality, but not the thymic defect, indicating the thymic epithelium is irreversibly altered. Our observations are consistent with a role for LIF in maintaining a functional thymic epithelium that will support proper T cell maturation. Images PMID:8137821

  4. On a class of fractional elliptic problems with an involution perturbation

    NASA Astrophysics Data System (ADS)

    Turmetov, Batirkhan Kh.; Torebek, Berikbol T.

    2016-08-01

    In this paper, we study some boundary value problems for fractional analogue of Helmholtz equation with an involution perturbation in a rectangular domain. Theorems on existence and uniqueness of a solution of the considered problems are proved by spectral method.

  5. The relevance of aging-related changes in brain function to rehabilitation in aging-related disease

    PubMed Central

    Crosson, Bruce; McGregor, Keith M.; Nocera, Joe R.; Drucker, Jonathan H.; Tran, Stella M.; Butler, Andrew J.

    2015-01-01

    The effects of aging on rehabilitation of aging-related diseases are rarely a design consideration in rehabilitation research. In this brief review we present strong coincidental evidence from these two fields suggesting that deficits in aging-related disease or injury are compounded by the interaction between aging-related brain changes and disease-related brain changes. Specifically, we hypothesize that some aphasia, motor, and neglect treatments using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in stroke patients may address the aging side of this interaction. The importance of testing this hypothesis and addressing the larger aging by aging-related disease interaction is discussed. Underlying mechanisms in aging that most likely are relevant to rehabilitation of aging-related diseases also are covered. PMID:26074807

  6. Wound healing-like immune program facilitates postpartum mammary gland involution and tumor progression

    PubMed Central

    Martinson, Holly A.; Jindal, Sonali; Durand-Rougely, Clarissa; Borges, Virginia F.; Schedin, Pepper

    2014-01-01

    Women diagnosed with breast cancer within 5 years postpartum have poor survival rates. The process of postpartum mammary gland involution, whereby the lactating gland remodels to its pre-pregnant state, promotes breast cancer progression in xenograft models. Macrophage influx occurs during mammary gland involution, implicating immune modulation in the promotion of postpartum breast cancer. Herein, we characterize the postpartum murine mammary gland and find an orchestrated influx of immune cells similar to that which occurs during wound healing. Further, the normal involuting gland may be in an immunosuppressed state as discerned by the transient presence of Foxp3+ regulatory T cells and IL-10+ macrophages with T cell suppressive function. To determine the influence of the postpartum immune microenvironment on mammary tumor promotion, we developed an immune-competent model. In this model, mammary tumors in the involution group are six-fold larger than nulliparous group tumors, have decreased CD4+ and CD8+ T cell infiltrates and contain a greater number of macrophages with the ability to inhibit T cell activation. Targeting involution with a neutralizing antibody against the immunosuppressive cytokine IL-10 reduces tumor growth in involution group mice but not in nulliparous mice, implicating the involution microenvironment as the primary target of αIL-10 treatment. Relevance to women is implicated, as we find post-lactational human breast tissue has transient high IL-10+ and Foxp3+ immune cell infiltrate. These data show an immune modulated microenvironment within the normal involuting mammary gland suggestive of immunosuppression, that when targeted reduces tumor promotion, revealing possible immune-based strategies for postpartum breast cancer. PMID:25187059

  7. Wound healing-like immune program facilitates postpartum mammary gland involution and tumor progression.

    PubMed

    Martinson, Holly A; Jindal, Sonali; Durand-Rougely, Clarissa; Borges, Virginia F; Schedin, Pepper

    2015-04-15

    Women diagnosed with breast cancer within 5 years postpartum have poor survival rates. The process of postpartum mammary gland involution, whereby the lactating gland remodels to its prepregnant state, promotes breast cancer progression in xenograft models. Macrophage influx occurs during mammary gland involution, implicating immune modulation in the promotion of postpartum breast cancer. Herein, we characterize the postpartum murine mammary gland and find an orchestrated influx of immune cells similar to that which occurs during wound healing. Further, the normal involuting gland may be in an immunosuppressed state as discerned by the transient presence of Foxp3(+) regulatory T cells and IL-10(+) macrophages with T cell suppressive function. To determine the influence of the postpartum immune microenvironment on mammary tumor promotion, we developed an immune-competent model. In this model, mammary tumors in the involution group are sixfold larger than nulliparous group tumors, have decreased CD4(+) and CD8(+) T cell infiltrates and contain a greater number of macrophages with the ability to inhibit T cell activation. Targeting involution with a neutralizing antibody against the immunosuppressive cytokine IL-10 reduces tumor growth in involution group mice but not in nulliparous mice, implicating the involution microenvironment as the primary target of αIL-10 treatment. Relevance to women is implicated, as we find postlactational human breast tissue has transient high IL-10(+) and Foxp3(+) immune cell infiltrate. These data show an immune modulated microenvironment within the normal involuting mammary gland suggestive of immunosuppression, that when targeted reduces tumor promotion, revealing possible immune-based strategies for postpartum breast cancer.

  8. Mammary gland involution as an immunotherapeutic target for postpartum breast cancer.

    PubMed

    Fornetti, Jaime; Martinson, Holly A; Betts, Courtney B; Lyons, Traci R; Jindal, Sonali; Guo, Qiuchen; Coussens, Lisa M; Borges, Virginia F; Schedin, Pepper

    2014-07-01

    Postpartum mammary gland involution has been identified as tumor-promotional and is proposed to contribute to the increased rates of metastasis and poor survival observed in postpartum breast cancer patients. In rodent models, the involuting mammary gland microenvironment is sufficient to induce enhanced tumor cell growth, local invasion, and metastasis. Postpartum involution shares many attributes with wound healing, including upregulation of genes involved in immune responsiveness and infiltration of tissue by immune cells. In rodent models, treatment with non-steroidal anti-inflammatory drugs (NSAIDs) ameliorates the tumor-promotional effects of involution, consistent with the immune milieu of the involuting gland contributing to tumor promotion. Currently, immunotherapy is being investigated as a means of breast cancer treatment with the purpose of identifying ways to enhance anti-tumor immune responses. Here we review evidence for postpartum mammary gland involution being a uniquely defined 'hot-spot' of pro-tumorigenic immune cell infiltration, and propose that immunotherapy should be explored for prevention and treatment of breast cancers that arise in this environment.

  9. Low Calorie Diet Affects Aging-Related Factors

    MedlinePlus

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

  10. New Clues to Age-Related Hearing Loss

    MedlinePlus

    ... gov/news/fullstory_161359.html New Clues to Age-Related Hearing Loss Older people's brains have a ... the brain's ability to process speech declines with age. For the study, Alessandro Presacco and colleagues divided ...

  11. The evolution of thymic lymphomas in p53 knockout mice

    PubMed Central

    Dudgeon, Crissy; Chan, Chang; Kang, Wenfeng; Sun, Yvonne; Emerson, Ryan; Robins, Harlan

    2014-01-01

    Germline deletion of the p53 gene in mice gives rise to spontaneous thymic (T-cell) lymphomas. In this study, the p53 knockout mouse was employed as a model to study the mutational evolution of tumorigenesis. The clonality of the T-cell repertoire from p53 knockout and wild-type thymic cells was analyzed at various ages employing TCRβ sequencing. These data demonstrate that p53 knockout thymic lymphomas arose in an oligoclonal fashion, with tumors evolving dominant clones over time. Exon sequencing of tumor DNA revealed that all of the independently derived oligoclonal mouse tumors had a deletion in the Pten gene prior to the formation of the TCRβ rearrangement, produced early in development. This was followed in each independent clone of the thymic lymphoma by the amplification or overexpression of cyclin Ds and Cdk6. Alterations in the expression of Ikaros were common and blocked further development of CD-4/CD-8 T cells. While the frequency of point mutations in the genome of these lymphomas was one per megabase, there were a tremendous number of copy number variations producing the tumors’ driver mutations. The initial inherited loss of p53 functions appeared to delineate an order of genetic alterations selected for during the evolution of these thymic lymphomas. PMID:25452272

  12. Thymic malignancies: Moving forward with new systemic treatments.

    PubMed

    Remon, J; Lindsay, C R; Bluthgen, M V; Besse, B

    2016-05-01

    Thymic neoplasms are rare malignant tumours, for which the mainstay of treatment is surgical resection. Platinum-based chemotherapy remains the principal treatment in metastatic tumours, with no standard second-line option. Many genes implicated in tumour onset, growth and metastases have been demonstrated to be therapeutic targets in thymic malignancies. Other current efforts to improve outcomes are based on a better understanding of the stromal compartment and tumour microenvironment, facilitating novel therapeutic approaches such as angiogenesis inhibition and immunotherapy. This review seeks to explore the present cutting edge for systemic treatment of advanced thymic neoplasms, examining novel agents under clinical investigation such as cytotoxic therapies, targeted therapies and immunotherapy. Based on the literature review we have selected potential treatment schemes, which could be used in daily clinical practice as second-line treatment. PMID:27057658

  13. Invasive atypical thymic carcinoid: three case reports and literature review

    PubMed Central

    Zhu, Shan; Wang, Zhong-Tang; Liu, Wen-Zhi; Zong, Shi-Xiang; Li, Bao-Sheng

    2016-01-01

    Atypical thymic carcinoid is an extremely rare thymic neuroendocrine tumor derived from the neuroendocrine system. The aims of this paper were to investigate the clinical features of atypical thymic carcinoid and collate information and experience to improve the diagnosis and treatment of this disease. We describe three cases of atypical carcinoid of the thymus; clinical features, pathological data, treatment modalities, and short-term patient outcomes were summarized and analyzed. The initial clinical symptoms and signs of all three patients were nonspecific and an anterior mediastinal mass was found in each patient on chest computed tomography scan. All three patients underwent surgical resection (total thymectomy and complete excision of the tumor), followed by postoperative radiotherapy, with or without chemotherapy. The diagnoses of three patients were confirmed by pathological and immunohistochemical evaluation. We also present a review of the literature to collate as much information as possible and provide a reference for proper diagnosis and treatment of atypical thyroid carcinoid. PMID:27785065

  14. Ataxia induced by a thymic neuroblastoma in the elderly patient.

    PubMed

    Wiesel, Ory; Bhattacharyya, Shamik; Vaitkevicius, Henrikas; Prasad, Sashank; McNamee, Ciaran

    2015-05-12

    Thymic neuroblastoma is a rare tumor with only few reports in modern literature. Whereas most data is taken from childhood neuroblastoma, little is known about the characteristics of the disease in the adult and elderly population. There are significant differences between adult and childhood neuroblastoma which are reviewed below. We report a case of a 62-year-old male who presented with neurological symptoms of ataxia and opsoclonus and an anterior mediastinal mass. Ultimately, the patient underwent a resection of the mass and pathologic review identified a thymic neuroblastoma. This is the first case of thymic neuroblastoma associated with symptomatic central nervous system disease; it is presented with an up-to-date review of the previous cases in the field as well with a review of the literature of post adolescent neuroblastoma.

  15. Transcriptome analysis of the mammary gland from GH transgenic goats during involution.

    PubMed

    Lin, Jian; Bao, Ze Kun; Zhang, Qiang; Hu, Wei Wei; Yu, Qing Hua; Yang, Qian

    2015-07-10

    Mammary glands are organs for milk production in female mammals. Growth hormone (GH) is known to affect the growth and development of the mammary gland, as well as to increase milk production in dairy goats. This study performed a comprehensive expression profiling of genes expressed in the mammary gland of early involution GH transgenic (n=4) and non-transgenic goats (n=4) by RNA sequencing. RNA was extracted from mammary gland tissues collected at day 3 of involution. Gene expression analysis was conducted by Illumina RNA sequencing and sequence reads were assembled and analyzed using TopHat. FPKM (fragments per kilobase of exon per million) values were analyzed for differentially expressed genes using the Cufflinks package. Gene ontology analysis of differentially expressed genes was categorized using agriGO, while KEGG pathway analysis was performed with the online KEGG automatic annotation server. Our results revealed that 75% of NCBI goat annotated genes were expressed during early involution. A total of 18,323 genes were expressed during early involution in GH transgenic goats, compared with 18,196 expressed genes during early involution of non-transgenic goats. In these expressed genes, the majority (17,589) were ubiquitously expressed in GH transgenic and non-transgenic goats. However, there were 745 differentially expressed genes, 421 of which were upregulated and 324 were downregulated in GH transgenic goats. GO and KEGG pathway analysis showed that these genes were involved in mammary gland physiology, including cell adhesion molecules, ECM-receptor interaction, Jak-STAT signaling pathway, and fat metabolism. Our results demonstrated that the GH receptor was strongly affected in GH transgenic goats, which may activate the IGF-1/Stat3 signaling pathway. Overall, our study provided a global view of the transcriptome during involution of GH transgenic and non-transgenic goats, which increases our understanding of the biology of involution in the goat.

  16. Natural and abrupt involution of the mammary gland affects differently the metabolic and health consequences of weaning.

    PubMed

    Silanikove, Nissim

    2014-04-25

    In most mammals under natural conditions weaning is gradual. Weaning occurs after the mammary gland naturally produces much less milk than it did at peak and established lactation. Involution occurs following the cessation of milk evacuation from the mammary glands. The abrupt termination of the evacuation of milk from the mammary gland at peak and established lactation induces abrupt involution. Evidence on mice has shown that during abrupt involution, mammary gland utilizes some of the same tissue remodeling programs that are activated during wound healing. These results led to the proposition of the "involution hypothesis". According to the involution hypothesis, involution is associated with increased risk for developing breast cancer. However, the involution hypothesis is challenged by the metabolic and immunological events that characterize the involution process that follows gradual weaning. It has been shown that gradual weaning is associated with pre-adaption to the forthcoming break between dam and offspring and is followed by an orderly reprogramming of the mammary gland tissue. As discussed herein, such response may actually protect the mammary glands against the development of breast cancer and thus, may explain the protective effect of extended breastfeeding. On the other hand, the termination of breastfeeding during the first 6 months of lactation is likely associated with an abrupt involution and thus with an increased risk for developing breast cancer. Review of the literature on the epidemiology of breast cancer principally supports those conclusions.

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

    NASA Technical Reports Server (NTRS)

    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.

  18. Thymus organogenesis and development of the thymic stroma.

    PubMed

    Nowell, Craig S; Farley, Alison M; Blackburn, C Clare

    2007-01-01

    T-cell development occurs principally in the thymus. Here, immature progenitor cells are guided through the differentiation and selection steps required to generate a complex T-cell repertoire that is both self-tolerant and has propensity to bind self major histocompatibility complex. These processes depend on an array of functionally distinct epithelial cell types within the thymic stroma, which have a common developmental origin in the pharyngeal endoderm. Here, we describe the structural and phenotypic attributes of the thymic stroma, and review current cellular and molecular understanding of thymus organogenesis.

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

    PubMed

    Chen, Mei; Xu, Heping

    2015-11-01

    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 as a result of its unique anatomic and physiologic 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, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, 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 age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration.

  20. Two distinct phases of apoptosis in mammary gland involution: proteinase-independent and -dependent pathways

    SciTech Connect

    Lund, Leif R; Romer, John; Thomasset, Nicole; Solberg, Helene; Pyke, Charles; Bissell, Mina J; Dano, Keld; Werb, Zena

    1996-01-01

    Postlactational involution of the mammary gland is characterized by two distinct physiological events: apoptosis of the secretory, epithelial cells undergoing programmed cell death, and proteolytic degradation of the mammary gland basement membrane. We examined the spatial and temporal patterns of apoptotic cells in relation to those of proteinases during involution of the BALB/c mouse mammary gland. Apoptosis was almost absent during lactation but became evident at day 2 of involution, when {beta}-casein gene expression was still high. Apoptotic cells were then seen at least up to day 8 of involution, when {beta}-casein gene expression was being extinguished. Expression of sulfated glycoprotein-2 (SGP-2), interleukin-1{beta} converting enzyme (ICE) and tissue inhibitor of metalloproteinases-1 was upregulated at day 2, when apoptotic cells were seen initially. Expression of the matrix metalloproteinases gelatinase A and stromelysin-1 and the serine proteinase urokinase-type plasminogen activator, which was low during lactation, was strongly upregulated in parallel starting at day 4 after weaning, coinciding with start of the collapse of the lobulo-alveolar structures and the intensive tissue remodeling in involution. The major sites of mRNA synthesis for these proteinases were fibroblast-like cells in the periductal stroma and stromal cells surrounding the collapsed alveoli, suggesting that the degradative phase of involution is due to a specialized mesenchymal-epithelial interaction. To elucidate the functional role of these proteinases during involution, at the onset of weaning we treated mice systemically with the glucocorticoid hydrocortisone, which is known to inhibit mammary gland involution. Although the initial wave of apoptotic cells appeared in the lumina of the gland, the dramatic regression and tissue remodeling usually evident by day 5 was substantially inhibited by systemic treatment with hydrocortisone. mRNA and protein for gelatinase A, stromelysin

  1. Pathophysiology of ageing, longevity and age related diseases

    PubMed Central

    Bürkle, Alexander; Caselli, Graziella; Franceschi, Claudio; Mariani, Erminia; Sansoni, Paolo; Santoni, Angela; Vecchio, Giancarlo; Witkowski, Jacek M; Caruso, Calogero

    2007-01-01

    On April 18, 2007 an international meeting on Pathophysiology of Ageing, Longevity and Age-Related Diseases was held in Palermo, Italy. Several interesting topics on Cancer, Immunosenescence, Age-related inflammatory diseases and longevity were discussed. In this report we summarize the most important issues. However, ageing must be considered an unavoidable end point of the life history of each individual, nevertheless the increasing knowledge on ageing mechanisms, allows envisaging many different strategies to cope with, and delay it. So, a better understanding of pathophysiology of ageing and age-related disease is essential for giving everybody a reasonable chance for living a long and enjoyable final part of the life. PMID:17683521

  2. Mouse models of age-related mitochondrial neurosensory hearing loss.

    PubMed

    Han, Chul; Someya, Shinichi

    2013-07-01

    Hearing loss is the most common sensory disorder in the elderly population. Overall, 10% of the population has a hearing loss in the US, and this age-related hearing disorder is projected to afflict more than 28 million Americans by 2030. Age-related hearing loss is associated with loss of sensory hair cells (sensory hearing loss) and/or spiral ganglion neurons (neuronal hearing loss) in the cochlea of the inner ear. Many lines of evidence indicate that oxidative stress and associated mitochondrial dysfunction play a central role in age-related neurodegenerative diseases and are a cause of age-related neurosensory hearing loss. Yet, the molecular mechanisms of how oxidative stress and/or mitochondrial dysfunction lead to hearing loss during aging remain unclear, and currently there is no treatment for this age-dependent disorder. Several mouse models of aging and age-related diseases have been linked to age-related mitochondrial neurosensory hearing loss. Evaluation of these animal models has offered basic knowledge of the mechanism underlying hearing loss associated with oxidative stress, mitochondrial dysfunction, and aging. Here we review the evidence that specific mutations in the mitochondrial DNA or nuclear DNA that affect mitochondrial function result in increased oxidative damage and associated loss of sensory hair cells and/or spiral ganglion neurons in the cochlea during aging, thereby causing hearing loss in these mouse models. Future studies comparing these models will provide further insight into fundamental knowledge about the disordered process of hearing and treatments to improve the lives of individuals with communication disorders. This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'.

  3. Age-related differences in human skin proteoglycans

    PubMed Central

    Carrino, David A; Calabro, Anthony; Darr, Aniq B; Dours-Zimmermann, Maria T; Sandy, John D; Zimmermann, Dieter R; Sorrell, J Michael; Hascall, Vincent C; Caplan, Arnold I

    2011-01-01

    Previous work has shown that versican, decorin and a catabolic fragment of decorin, termed decorunt, are the most abundant proteoglycans in human skin. Further analysis of versican indicates that four major core protein species are present in human skin at all ages examined from fetal to adult. Two of these are identified as the V0 and V1 isoforms, with the latter predominating. The other two species are catabolic fragments of V0 and V1, which have the amino acid sequence DPEAAE as their carboxyl terminus. Although the core proteins of human skin versican show no major age-related differences, the glycosaminoglycans (GAGs) of adult skin versican are smaller in size and show differences in their sulfation pattern relative to those in fetal skin versican. In contrast to human skin versican, human skin decorin shows minimal age-related differences in its sulfation pattern, although, like versican, the GAGs of adult skin decorin are smaller than those of fetal skin decorin. Analysis of the catabolic fragments of decorin from adult skin reveals the presence of other fragments in addition to decorunt, although the core proteins of these additional decorin catabolic fragments have not been identified. Thus, versican and decorin of human skin show age-related differences, versican primarily in the size and the sulfation pattern of its GAGs and decorin in the size of its GAGs. The catabolic fragments of versican are detected at all ages examined, but appear to be in lower abundance in adult skin compared with fetal skin. In contrast, the catabolic fragments of decorin are present in adult skin, but are virtually absent from fetal skin. Taken together, these data suggest that there are age-related differences in the catabolism of proteoglycans in human skin. These age-related differences in proteoglycan patterns and catabolism may play a role in the age-related changes in the physical properties and injury response of human skin. PMID:20947661

  4. Role of pigment epithelium-derived factor in the involution of hemangioma: Autocrine growth inhibition of hemangioma-derived endothelial cells

    SciTech Connect

    Kim, Kyung-Jin; Yun, Jang-Hyuk; Heo, Jong-Ik; Lee, Eun Hui; Min, Hye Sook; Choi, Tae Hyun; Cho, Chung-Hyun

    2014-11-14

    Highlights: • PEDF was expressed and induced during the involuting phase of IH. • PEDF inhibited the cell growth of the involuting HemECs in an autocrine manner. • PEDF suppression restored the impaired cell growth of the involuting HemECs. - Abstract: Hemangioma is a benign tumor derived from abnormal blood vessel growth. Unlike other vascular tumor counterparts, a hemangioma is known to proliferate during its early stage but it is followed by a stage of involution where regression of the tumor occurs. The critical onset leading to the involution of hemangioma is currently not well understood. This study focused on the molecular identities of the involution of hemangioma. We demonstrated that a soluble factor released from the involuting phase of hemangioma-derived endothelial cells (HemECs) and identified pigment epithelium-derived factor (PEDF) as an anti-angiogenic factor that was associated with the growth inhibition of the involuting HemECs. The growth inhibition of the involuting HemECs was reversed by suppression of PEDF in the involuting HemECs. Furthermore, we found that PEDF was more up-regulated in the involuting phase of hemangioma tissues than in the proliferating or the involuted. Taken together, we propose that PEDF accelerates the involution of hemangioma by growth inhibition of HemECs in an autocrine manner. The regulatory mechanism of PEDF expression could be a potential therapeutic target to treat hemangiomas.

  5. Age-related decline in emotional prosody discrimination: acoustic correlates.

    PubMed

    Mitchell, Rachel L C; Kingston, Rachel A

    2014-01-01

    It is now accepted that older adults have difficulty recognizing prosodic emotion cues, but it is not clear at what processing stage this ability breaks down. We manipulated the acoustic characteristics of tones in pitch, amplitude, and duration discrimination tasks to assess whether impaired basic auditory perception coexisted with our previously demonstrated age-related prosodic emotion perception impairment. It was found that pitch perception was particularly impaired in older adults, and that it displayed the strongest correlation with prosodic emotion discrimination. We conclude that an important cause of age-related impairment in prosodic emotion comprehension exists at the fundamental sensory level of processing.

  6. Glutamatergic treatment strategies for age-related memory disorders.

    PubMed

    Müller, W E; Scheuer, K; Stoll, S

    1994-01-01

    Age-related changes of N-methyl-D-aspartate (NMDA) receptors have been found in cortical areas and in the hippocampus of many species. On the basis of a variety of experimental observations it has been suggested that the decrease of NMDA receptor density might be one of the causative factors of the cognitive decline with aging. Based on these findings several strategies have been developed to improve cognition by compensating the NMDA receptor deficits in aging. The most promising approaches are the indirect activation of glutamatergic neurotransmission by agonists of the glycine site or the restoration of the age-related deficit of receptor density by several nootropics. PMID:7997073

  7. Comparison of Patterns of Relapse in Thymic Carcinoma and Thymoma

    PubMed Central

    Huang, James; Rizk, Nabil P.; Travis, William D.; Riely, Gregory J.; Park, Bernard J.; Bains, Manjit S.; Dycoco, Joseph; Flores, Raja M.; Downey, Robert J.; Rusch, Valerie W.

    2014-01-01

    Objective Thymic carcinomas (TC) are considered to be more aggressive than thymomas and carry a worse prognosis. We reviewed our recent experience with the surgical management of thymic tumors and compared the outcomes and patterns of relapse between TC and thymoma. Methods Single institution retrospective cohort study. Data included patient demographics, stage, treatment, pathologic findings, and postoperative outcomes. Results During the period 1995–2006, 120 patients with thymic tumors underwent surgery, including 23 patients with TC and 97 patients with thymoma by the WHO 2004 histologic classification. The overall 5 year survival was significantly different between TC and thymoma (TC 53%, thymoma 89%, p=0.01). Data on relapse was available for 112 patients. The progression-free 5 year survival was also significantly different between TC and thymoma (TC 36%, thymoma 75%, p<0.01). By multivariate analysis, thymic carcinoma and incomplete resection were found to be independent predictors of progression-free survival. Relapses in TC tended to occur earlier, and occurred signficantly more frequently at distant sites than in thymoma (60% vs. 13%, p=0.01). Conclusions Patterns of relapse differ significantly between TC and thymoma with lower progression-free survival, earlier onset and more distant relapses in TC. Given the greater propensity for distant failures, the inclusion of systemic therapy in the treatment of TC may take on greater importance. Despite significantly higher rates of distant relapse, good overall survival in TC can be achieved. PMID:19577051

  8. Low Thymic Activity and Dendritic Cell Numbers Are Associated with the Immune Response to Primary Viral Infection in Elderly Humans.

    PubMed

    Schulz, Axel Ronald; Mälzer, Julia Nora; Domingo, Cristina; Jürchott, Karsten; Grützkau, Andreas; Babel, Nina; Nienen, Mikalai; Jelinek, Tomas; Niedrig, Matthias; Thiel, Andreas

    2015-11-15

    Immunological competence declines progressively with age, resulting in increased susceptibility of the elderly to infection and impaired responses to vaccines. Underlying mechanisms remain largely obscure as they have been related to complex, individual systemic immune properties that are challenging to investigate. In this study, we explored age-related changes in human immunity during a primary virus infection experimentally induced by immunization with live-attenuated yellow fever (YF) vaccine. Applying detailed serology, advanced FACS analysis, and systems biology, we discovered that aged subjects developed fewer neutralizing Abs, mounted diminished YF-specific CD8(+) T cell responses, and showed quantitatively and qualitatively altered YF-specific CD4(+) T cell immunity. Among numerous immune signatures, low in vivo numbers of naive CD4(+) recent thymic emigrants and peripheral dendritic cells correlated well with reduced acute responsiveness and altered long-term persistence of human cellular immunity to YF vaccination. Hence, we reveal in this article that essential elements of immune responses such as recent thymic emigrants and dendritic cells strongly relate to productive immunity in the elderly, providing a conceivable explanation for diminished responsiveness to vaccination with neoantigens and infection with de novo pathogens in the aged population. PMID:26459351

  9. Improving Efficiency of Gear Shaping of Wheels with Internal Non-involute Gears

    NASA Astrophysics Data System (ADS)

    Tarapanov, A.; Anisimov, R.; Kanatnikov, N.; Pilipenko, A.

    2016-04-01

    In the article questions of improving efficiency of gear shaping of wheels with internal non-involute profile gears. The technique of the analysis of kinematics parameters of gear shaping process is presented. Researches devoted to the influence of root profile form of processed wheel with interna. In the article questions of improving efficiency of gear shaping of wheels with internal non-involute profile gears. The technique of the analysis of kinematics parameters of gear shaping process is presented. Researches devoted to the influence of root profile form of processed wheel with internal non-involute gears on the thickness of the cutting-off metal layer, size of components of cutting forces and a roughness of the processed surface are given.

  10. PPARα agonist, fenofibrate, ameliorates age-related renal injury.

    PubMed

    Kim, Eun Nim; Lim, Ji Hee; Kim, Min Young; Kim, Hyung Wook; Park, Cheol Whee; Chang, Yoon Sik; Choi, Bum Soon

    2016-08-01

    The kidney ages quickly compared with other organs. Expression of senescence markers reflects changes in the energy metabolism in the kidney. Two important issues in aging are mitochondrial dysfunction and oxidative stress. Peroxisome proliferator-activated receptor α (PPARα) is a member of the ligand-activated nuclear receptor superfamily. PPARα plays a major role as a transcription factor that regulates the expression of genes involved in various processes. In this study, 18-month-old male C57BL/6 mice were divided into two groups, the control group (n=7) and the fenofibrate-treated group (n=7) was fed the normal chow plus fenofibrate for 6months. The PPARα agonist, fenofibrate, improved renal function, proteinuria, histological change (glomerulosclerosis and tubular interstitial fibrosis), inflammation, and apoptosis in aging mice. This protective effect against age-related renal injury occurred through the activation of AMPK and SIRT1 signaling. The activation of AMPK and SIRT1 allowed for the concurrent deacetylation and phosphorylation of their target molecules and decreased the kidney's susceptibility to age-related changes. Activation of the AMPK-FOXO3a and AMPK-PGC-1α signaling pathways ameliorated oxidative stress and mitochondrial dysfunction. Our results suggest that activation of PPARα and AMPK-SIRT1 signaling may have protective effects against age-related renal injury. Pharmacological targeting of PPARα and AMPK-SIRT1 signaling molecules may prevent or attenuate age-related pathological changes in the kidney. PMID:27130813

  11. Nutritional antioxidants and age-related cataract and maculopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Loss of vision is the second greatest, next to death, fear among the elderly. Age-related cataract (ARC) and maculopathy (ARM) are two major causes of blindness worldwide. There are several important reasons to study relationships between risk for ARC/ARM and nutrition: (1) because it is likely that...

  12. Age-Related Differences in Idiom Production in Adulthood

    ERIC Educational Resources Information Center

    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…

  13. Age-Related Factors in Second Language Acquisition.

    ERIC Educational Resources Information Center

    Twyford, Charles William

    The convergence of several lines of psycholinguistic and sociolinguistic research suggests possible explanations for age-related influences on language acquisition. These factors, which include cognitive development, sociocultural context, affective factors, and language input, can be helpful to language educators. By being alert to the cognitive…

  14. A Context for Teaching Aging-Related Public Policy.

    ERIC Educational Resources Information Center

    Brown, David K.

    1999-01-01

    Describes two points of view regarding age-related public programs (Medicaid, Medicare, Social Security): that of devolutionists who would curtail them and safety netters who maintain the government's role is indispensable. Uses Relative Deprivation theory as a framework for teaching public policy about aging. (SK)

  15. Age-Related Differences in the Production of Textual Descriptions

    ERIC Educational Resources Information Center

    Marini, Andrea; Boewe, Anke; Caltagirone, Carlo; Carlomagno, Sergio

    2005-01-01

    Narratives produced by 69 healthy Italian adults were analyzed for age-related changes of microlinguistic, macrolinguistic and informative aspects. The participants were divided into five age groups (20-24, 25-39, 40-59, 60-74, 75-84). One single-picture stimulus and two cartoon sequences were used to elicit three stories per subject. Age-related…

  16. Managed care implications of age-related ocular conditions.

    PubMed

    Cardarelli, William J; Smith, Roderick A

    2013-05-01

    The economic costs of age-related ocular diseases and vision loss are increasing rapidly as our society ages. In addition to the direct costs of treating age-related eye diseases, elderly persons with vision loss are at significantly increased risk for falls and fractures, experiencing social isolation, and suffering from an array of comorbid medical conditions compared with individuals with normal vision. Recent studies estimate the total economic burden (direct and indirect costs) of adult vision impairment in the United States at $51.4 billion. This figure is expected to increase as the baby boomer generation continues to age. While a number of highly effective new therapies have caused a paradigm shift in the management of several major age-related ocular diseases in recent years, these treatments come at a substantial cost. This article reviews the economic burdens and treatment-related costs of 4 major ocular diseases of aging-glaucoma, age-related macular degeneration, diabetic retinopathy, and dry eye disease-and the implications for managed care.

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

    ERIC Educational Resources Information Center

    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…

  18. The Experience of Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Wong, Elaine Y. H.; Guymer, Robyn H.; Hassell, Jennifer B.; Keeffe, Jill E.

    2004-01-01

    This qualitative article describes the impact of age-related macular degeneration (ARMD) among 15 participants: how a person makes sense of ARMD, the effect of ARMD on the person's quality of life, the psychological disturbances associated with the limitations of ARMD, and the influence of ARMD on social interactions. Such in-depth appreciation of…

  19. Nutritional influences on epigenetics and age-related disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  20. Age-Related Differences in Moral Identity across Adulthood

    ERIC Educational Resources Information Center

    Krettenauer, Tobias; Murua, Lourdes Andrea; Jia, Fanli

    2016-01-01

    In this study, age-related differences in adults' moral identity were investigated. Moral identity was conceptualized a context-dependent self-structure that becomes differentiated and (re)integrated in the course of development and that involves a broad range of value-orientations. Based on a cross-sectional sample of 252 participants aged 14 to…

  1. Neuroanatomical Substrates of Age-Related Cognitive Decline

    ERIC Educational Resources Information Center

    Salthouse, Timothy A.

    2011-01-01

    There are many reports of relations between age and cognitive variables and of relations between age and variables representing different aspects of brain structure and a few reports of relations between brain structure variables and cognitive variables. These findings have sometimes led to inferences that the age-related brain changes cause the…

  2. Nutritional modulation of age-related macular degeneration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  3. Age-Related Health Stereotypes and Illusory Correlation

    ERIC Educational Resources Information Center

    Madey, Scott F.; Chasteen, Alison L.

    2004-01-01

    This experiment investigated how age-related health stereotypes affect people's judgments of younger and older patients' medical compliance. Previous research has shown that stereotypes of young adults include healthy components, but stereotypes of older adults include both healthy and unhealthy components (Hummert, 1990). We predicted that…

  4. Age-Related Changes in 1/f Neural Electrophysiological Noise

    PubMed Central

    Kramer, Mark A.; Case, John; Lepage, Kyle Q.; Tempesta, Zechari R.; Knight, Robert T.; Gazzaley, Adam

    2015-01-01

    Aging is associated with performance decrements across multiple cognitive domains. The neural noise hypothesis, a dominant view of the basis of this decline, posits that aging is accompanied by an increase in spontaneous, noisy baseline neural activity. Here we analyze data from two different groups of human subjects: intracranial electrocorticography from 15 participants over a 38 year age range (15–53 years) and scalp EEG data from healthy younger (20–30 years) and older (60–70 years) adults to test the neural noise hypothesis from a 1/f noise perspective. Many natural phenomena, including electrophysiology, are characterized by 1/f noise. The defining characteristic of 1/f is that the power of the signal frequency content decreases rapidly as a function of the frequency (f) itself. The slope of this decay, the noise exponent (χ), is often <−1 for electrophysiological data and has been shown to approach white noise (defined as χ = 0) with increasing task difficulty. We observed, in both electrophysiological datasets, that aging is associated with a flatter (more noisy) 1/f power spectral density, even at rest, and that visual cortical 1/f noise statistically mediates age-related impairments in visual working memory. These results provide electrophysiological support for the neural noise hypothesis of aging. SIGNIFICANCE STATEMENT Understanding the neurobiological origins of age-related cognitive decline is of critical scientific, medical, and public health importance, especially considering the rapid aging of the world's population. We find, in two separate human studies, that 1/f electrophysiological noise increases with aging. In addition, we observe that this age-related 1/f noise statistically mediates age-related working memory decline. These results significantly add to this understanding and contextualize a long-standing problem in cognition by encapsulating age-related cognitive decline within a neurocomputational model of 1/f noise

  5. Age-Related Changes in 1/f Neural Electrophysiological Noise.

    PubMed

    Voytek, Bradley; Kramer, Mark A; Case, John; Lepage, Kyle Q; Tempesta, Zechari R; Knight, Robert T; Gazzaley, Adam

    2015-09-23

    Aging is associated with performance decrements across multiple cognitive domains. The neural noise hypothesis, a dominant view of the basis of this decline, posits that aging is accompanied by an increase in spontaneous, noisy baseline neural activity. Here we analyze data from two different groups of human subjects: intracranial electrocorticography from 15 participants over a 38 year age range (15-53 years) and scalp EEG data from healthy younger (20-30 years) and older (60-70 years) adults to test the neural noise hypothesis from a 1/f noise perspective. Many natural phenomena, including electrophysiology, are characterized by 1/f noise. The defining characteristic of 1/f is that the power of the signal frequency content decreases rapidly as a function of the frequency (f) itself. The slope of this decay, the noise exponent (χ), is often <-1 for electrophysiological data and has been shown to approach white noise (defined as χ = 0) with increasing task difficulty. We observed, in both electrophysiological datasets, that aging is associated with a flatter (more noisy) 1/f power spectral density, even at rest, and that visual cortical 1/f noise statistically mediates age-related impairments in visual working memory. These results provide electrophysiological support for the neural noise hypothesis of aging. Significance statement: Understanding the neurobiological origins of age-related cognitive decline is of critical scientific, medical, and public health importance, especially considering the rapid aging of the world's population. We find, in two separate human studies, that 1/f electrophysiological noise increases with aging. In addition, we observe that this age-related 1/f noise statistically mediates age-related working memory decline. These results significantly add to this understanding and contextualize a long-standing problem in cognition by encapsulating age-related cognitive decline within a neurocomputational model of 1/f noise-induced deficits in

  6. Stem cell transplantation improves aging-related diseases

    PubMed Central

    Ikehara, Susumu; Li, Ming

    2014-01-01

    Aging is a complex process of damage accumulation, and has been viewed as experimentally and medically intractable. The number of patients with age-associated diseases such as type 2 diabetes mellitus (T2DM), osteoporosis, Alzheimer's disease (AD), Parkinson's disease, atherosclerosis, and cancer has increased recently. Aging-related diseases are related to a deficiency of the immune system, which results from an aged thymus and bone marrow cells. Intra bone marrow-bone marrow transplantation (IBM-BMT) is a useful method to treat intractable diseases. This review summarizes findings that IBM-BMT can improve and treat aging-related diseases, including T2DM, osteoporosis and AD, in animal models. PMID:25364723

  7. Veterans have less age-related cognitive decline.

    PubMed

    McLay, R N; Lyketsos, C G

    2000-08-01

    Military service involves exposure to a number of stresses, both psychological and physical. On the other hand, military personnel generally maintain excellent fitness, and veterans have increased access to education and health care. The overall effect on age-related cognitive decline, whether for good or ill, of having served in the armed forces has not been investigated previously. In this study, we examined a diverse population of 208 veterans and 1,216 civilians followed as part of the Epidemiologic Catchment Area Study in 1981, 1982, and 1993 to 1996. We examined change in Mini-Mental State Examination (MMSE) score after a median of 11.5 years. Veterans were found to have significantly less decrease in MMSE scores at follow-up even after sex, race, and education were taken into account. These results suggest an overall positive effect of military service on the rate of age-related cognitive decline. PMID:10957857

  8. Age-related cochlear hair cell loss in the chinchilla.

    PubMed

    Bhattacharyya, T K; Dayal, V S

    1985-01-01

    The spiral organ of the chinchilla was studied by the surface-preparation technique in four different age groups: 1 month, 6 months, 1 year, and 4 years, to assess age-related hair cell loss. Decrease in hair cell population is linearly related to age, and damage rate of outer hair cells is greater than that of inner hair cells. The mean percentage of damaged total outer hair cells was 0.60%, 1.16%, 1.71%, and 7.07% in animals in 1 month, 6 months, 1 year, and 4 years of age, respectively. Outer hair cell loss was greatest in the apex of the cochlea and, of these cells, the outermost row was the most affected. Damage to inner hair cells also increases with age. Age-related apical cochlear cell loss in the chinchilla is comparable to that observed in other laboratory animals. PMID:3970507

  9. The suprachiasmatic nucleus: age-related decline in biological rhythms.

    PubMed

    Nakamura, Takahiro J; Takasu, Nana N; Nakamura, Wataru

    2016-09-01

    Aging is associated with changes in sleep duration and quality, as well as increased rates of pathologic/disordered sleep. While several factors contribute to these changes, emerging research suggests that age-related changes in the mammalian central circadian clock within the suprachiasmatic nucleus (SCN) may be a key factor. Prior work from our group suggests that circadian output from the SCN declines because of aging. Furthermore, we have previously observed age-related infertility in female mice, caused by a mismatch between environmental light-dark cycles and the intrinsic, internal biological clocks. In this review, we address regulatory mechanisms underlying circadian rhythms in mammals and summarize recent literature describing the effects of aging on the circadian system.

  10. Ageism, age relations, and garment industry work in Montreal.

    PubMed

    McMullin, J A; Marshall, V W

    2001-02-01

    This study examined the complexities of age relations at work. Garment workers believed that their fate was linked to ageism and that their work experience was discounted by management. Managers wanted to be rid of older workers because they commanded higher wages than younger workers. The issue was cost reduction, and age was implicated unintendedly. Still, managers seemed to use stereotypical images to discourage older workers and they did not organize work routines to facilitate the adaptation of them. Instead, they subcontracted the easy jobs, relying on the experience of the older employees for difficult work while not adapting the workplace. Theoretically, the authors argue that ageism and age discrimination can best be understood through a recognition of the importance of structured age relations and human agency.

  11. Smoking and Age-Related Macular Degeneration: Review and Update

    PubMed Central

    Velilla, Sara; García-Medina, José Javier; García-Layana, Alfredo; Pons-Vázquez, Sheila; Pinazo-Durán, M. Dolores; Gómez-Ulla, Francisco; Arévalo, J. Fernando; Díaz-Llopis, Manuel; Gallego-Pinazo, Roberto

    2013-01-01

    Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health. PMID:24368940

  12. Age-related changes in ultra-triathlon performances

    PubMed Central

    2012-01-01

    Background The age-related decline in performance has been investigated in swimmers, runners and triathletes. No study has investigated the age-related performance decline in ultra-triathletes. The purpose of this study was to analyse the age-related declines in swimming, cycling, running and overall race time for both Triple Iron ultra-triathlon (11.4-km swimming, 540-km cycling and 126.6-km running) and Deca Iron ultra-triathlon (38-km swimming, 1,800-km cycling and 420-km running). Methods The age and performances of 423 male Triple Iron ultra-triathletes and 119 male Deca Iron ultra-triathletes were analysed from 1992 to 2010 using regression analyses and ANOVA. Results The mean age of the finishers was significantly higher for Deca Iron ultra-triathletes (41.3 ± 3.1 years) compared to a Triple Iron ultra-triathletes (38.5 ± 3.3 years) (P < 0.05). For both ultra-distances, the fastest overall race times were achieved between the ages of 25 and 44 years. Deca Iron ultra-triathletes achieved the same level of performance in swimming and cycling between 25 and 54 years of age. Conclusions The magnitudes of age-related declines in performance in the three disciplines of ultra-triathlon differ slightly between Triple and Deca Iron ultra-triathlon. Although the ages of Triple Iron ultra-triathletes were on average younger compared to Deca Iron ultra-triathletes, the fastest race times were achieved between 25 and 44 years for both distances. Further studies should investigate the motivation and training of ultra-triathletes to gain better insights in ultra-triathlon performance. PMID:23849327

  13. Age-Related Hyperkyphosis: Its Causes, Consequences, and Management

    PubMed Central

    Katzman, Wendy B.; Wanek, Linda; Shepherd, John A.; Sellmeyer, Deborah E.

    2010-01-01

    Age-related postural hyperkyphosis is an exaggerated anterior curvature of the thoracic spine, sometimes referred to as Dowager’s hump or gibbous deformity. This condition impairs mobility,2,31 and increases the risk of falls33 and fractures.26 The natural history of hyperkyphosis is not firmly established. Hyperkyphosis may develop from either muscle weakness and degenerative disc disease, leading to vertebral fractures and worsening hyperkyphosis, or from initial vertebral fractures that precipitate its development. PMID:20511692

  14. Hhip haploinsufficiency sensitizes mice to age-related emphysema.

    PubMed

    Lao, Taotao; Jiang, Zhiqiang; Yun, Jeong; Qiu, Weiliang; Guo, Feng; Huang, Chunfang; Mancini, John Dominic; Gupta, Kushagra; Laucho-Contreras, Maria E; Naing, Zun Zar Chi; Zhang, Li; Perrella, Mark A; Owen, Caroline A; Silverman, Edwin K; Zhou, Xiaobo

    2016-08-01

    Genetic variants in Hedgehog interacting protein (HHIP) have consistently been associated with the susceptibility to develop chronic obstructive pulmonary disease and pulmonary function levels, including the forced expiratory volume in 1 s (FEV1), in general population samples by genome-wide association studies. However, in vivo evidence connecting Hhip to age-related FEV1 decline and emphysema development is lacking. Herein, using Hhip heterozygous mice (Hhip(+/-)), we observed increased lung compliance and spontaneous emphysema in Hhip(+/-) mice starting at 10 mo of age. This increase was preceded by increases in oxidative stress levels in the lungs of Hhip(+/-) vs. Hhip(+/+) mice. To our knowledge, these results provide the first line of evidence that HHIP is involved in maintaining normal lung function and alveolar structures. Interestingly, antioxidant N-acetyl cysteine treatment in mice starting at age of 5 mo improved lung function and prevented emphysema development in Hhip(+/-) mice, suggesting that N-acetyl cysteine treatment limits the progression of age-related emphysema in Hhip(+/-) mice. Therefore, reduced lung function and age-related spontaneous emphysema development in Hhip(+/-) mice may be caused by increased oxidative stress levels in murine lungs as a result of haploinsufficiency of Hhip. PMID:27444019

  15. Later developments: molecular keys to age-related memory impairment.

    PubMed

    Barad, Mark

    2003-01-01

    Age-related memory impairment, a cognitive decline not clearly related to any gross pathology, is progressive and widespread in the population, although not universal. While the mechanisms of learning and memory remain incompletely understood, the study of their molecular mechanisms is already yielding promising approaches toward therapy for such "normal" declines in the efficiency of learning. This review presents the rationale and results for two such approaches. One approach, partial inhibition of the type IV cAMP specific phosphodiesterase, appears to act indirectly. Although little evidence supports an age-related decline in this system, considerable evidence indicates that this approach can facilitate the transition from short-term to long-term memory and thus counterbalance defects in long-term memory, which may be due to other causes. A second approach, inhibition of l-type voltage gated calcium channels (LVGCCs) may be a specific corrective for a molecular pathology of aging, as substantial evidence indicates that an ongoing increase occurs throughout the lifespan in the density of these channels in hippocampal pyramidal cells, with a concomitant reduction in cellular excitability. Because LVGCCs are also crucial to extinction, a paradigm of inhibitory learning, age-related memory impairment may be an unfortunate side effect of a developmental process necessary to the maturation of the ability to suppress inappropriate behavior, an interpretation consistent with the antagonistic pleiotropy theory of aging.

  16. Age related alterations of adrenoreceptor activity in erythrocyte membrane.

    PubMed

    Lomsadze, G; Khetsuriani, R; Arabuli, M; Intskirveli, N; Sanikidze, T

    2011-06-01

    The aim of the study was the investigation of age-related functional alterations of adrenoreceptors and the effect of agonist and antagonist drugs on age related adrenoreceptor activity in erythrocyte membrane. The impact of isopropanol and propanol on functional activity β- adrenergic receptors in red blood cell membrane were studied in 50 practically healthy men--volunteers. (I group--75-89 years old, II group--22-30 years old). The EPR signals S1 and S2 were registered in red blood cell membrane samples after incubation with isopropanol and propanol respectively. It was found that decreasing sensitivity (functional activity) of red blood cells membrane adrenoreceptors comes with aging (S1oldage-related hypertension, heart failure, type II diabetes and other diseases, The findings suggests that the erythrocyte could be a new therapeutic marker in the treatment different diseases.

  17. Telomere length variations in aging and age-related diseases.

    PubMed

    Rizvi, Saliha; Raza, Syed Tasleem; Mahdi, Farzana

    2014-01-01

    Telomeres are gene sequences present at chromosomal ends and are responsible for maintaining genome integrity. Telomere length is maximum at birth and decreases progressively with advancing age and thus is considered as a biomarker of chronological aging. This age associated decrease in the length of telomere is linked to various ageing associated diseases like diabetes, hypertension, Alzheimer's disease, cancer etc. and their associated complications. Telomere length is a result of combined effect of oxidative stress, inflammation and repeated cell replication on it, and thus forming an association between telomere length and chronological aging and related diseases. Thus, decrease in telomere length was found to be important in determining both, the variations in longevity and age-related diseases in an individual. Ongoing and progressive research in the field of telomere length dynamics has proved that aging and age-related diseases apart from having a synergistic effect on telomere length were also found to effect telomere length independently also. Here a short description about telomere length variations and its association with human aging and age-related diseases is reviewed.

  18. Adverse environmental conditions influence age-related innate immune responsiveness

    PubMed Central

    May, Linda; van den Biggelaar, Anita HJ; van Bodegom, David; Meij, Hans J; de Craen, Anton JM; Amankwa, Joseph; Frölich, Marijke; Kuningas, Maris; Westendorp, Rudi GJ

    2009-01-01

    Background- The innate immune system plays an important role in the recognition and induction of protective responses against infectious pathogens, whilst there is increasing evidence for a role in mediating chronic inflammatory diseases at older age. Despite indications that environmental conditions can influence the senescence process of the adaptive immune system, it is not known whether the same holds true for the innate immune system. Therefore we studied whether age-related innate immune responses are similar or differ between populations living under very diverse environmental conditions. Methods- We compared cross-sectional age-related changes in ex vivo innate cytokine responses in a population living under affluent conditions in the Netherlands (age 20–68 years old, n = 304) and a population living under adverse environmental conditions in Ghana (age 23–95 years old, n = 562). Results- We found a significant decrease in LPS-induced Interleukin (IL)-10 and Tumor Necrosis Factor (TNF) production with age in the Dutch population. In Ghana a similar age-related decline in IL-10 responses to LPS, as well as to zymosan, or LPS plus zymosan, was observed. TNF production, however, did not show an age-associated decline, but increased significantly with age in response to co-stimulation with LPS and zymosan. Conclusion- We conclude that the decline in innate cytokine responses is an intrinsic ageing phenomenon, while pathogen exposure and/or selective survival drive pro-inflammatory responses under adverse living conditions. PMID:19480711

  19. Soybean β-Conglycinin Prevents Age-Related Hearing Impairment.

    PubMed

    Tanigawa, Tohru; Shibata, Rei; Kondo, Kazuhisa; Katahira, Nobuyuki; Kambara, Takahiro; Inoue, Yoko; Nonoyama, Hiroshi; Horibe, Yuichiro; Ueda, Hiromi; Murohara, Toyoaki

    2015-01-01

    Obesity-related complications are associated with the development of age-related hearing impairment. β-Conglycinin (β-CG), one of the main storage proteins in soy, offers multiple health benefits, including anti-obesity and anti-atherosclerotic effects. Here, to elucidate the potential therapeutic application of β-CG, we investigated the effect of β-CG on age-related hearing impairment. Male wild-type mice (age 6 months) were randomly divided into β-CG-fed and control groups. Six months later, the body weight was significantly lower in β-CG-fed mice than in the controls. Consumption of β-CG rescued the hearing impairment observed in control mice. Cochlear blood flow also increased in β-CG-fed mice, as did the expression of eNOS in the stria vascularis (SV), which protects vasculature. β-CG consumption also ameliorated oxidative status as assessed by 4-HNE staining. In the SV, lipofuscin granules of marginal cells and vacuolar degeneration of microvascular pericytes were decreased in β-CG-fed mice, as shown by transmission electron microscopy. β-CG consumption prevented loss of spiral ganglion cells and reduced the frequencies of lipofuscin granules, nuclear invaginations, and myelin vacuolation. Our observations indicate that β-CG ameliorates age-related hearing impairment by preserving cochlear blood flow and suppressing oxidative stress.

  20. Computerized Simulation of Meshing of Conventional Helical Involute Gears and Modification of Geometry

    NASA Technical Reports Server (NTRS)

    Litvin, F. L.; Lu, J.; Townsend, D. P.; Hawkins, M.

    1997-01-01

    An approach is proposed for computerized simulation of meshing of aligned and misaligned involute helical gears. Algorithms for TCA (Tooth Contact Analysis) computer programs were developed. Influence of misalignment on the shift of the bearing contact and transmission errors has been investigated. Numerical examples that illustrate the developed theory are provided.

  1. Thymic hyperplasia after chemotherapy in adults with mature B cell lymphoma and its influence on thymic output and CD4(+) T cells repopulation.

    PubMed

    Sun, Dao-Ping; Jin, Hui; Ding, Chong-Yang; Liang, Jin-Hua; Wang, Li; Fan, Lei; Wu, Yu-Jie; Xu, Wei; Li, Jian-Yong

    2016-05-01

    To investigate the thymic regenerative potential in adults accepting chemotherapy for lymphoma. The dynamics of thymic activity in 54 adults from baseline to 12 mo post-chemotherapy was analyzed by assessing thymic structural changes with serial computed tomography (CT) scans, and correlating these with measurements of thymic output by concurrent analysis of single-joint (sj) T-cell receptor excision circles (sjTREC) and CD31(+) recent thymic emigrants (RTE) in peripheral blood. Furthermore, the consequence of thymic renewal on peripheral CD4(+) T cell recovery after chemotherapy was evaluated. Time-dependent changes of thymic size and thymic output assessed by both sjTREC levels and CD31(+) RTE counts in peripheral blood were observed during and after chemotherapy. Enlargement of thymus over baseline following chemotherapy regarded as rebound thymic hyperplasia (TH) was identified in 20 patients aged 18-53 y (median 33 y). By general linear models repeated measure analysis, it was found that, patients with TH (n = 20) had a faster recovery of sjTREC levels and CD31(+) RTE counts after chemotherapy than patients with comparable age, gender, diagnosis, disease stage, thymic volume and output function at baseline but without TH (n = 18) (p = 0.035, 0.047); besides, patients with TH had a faster repopulation of both naïve CD4(+) T cell and natural regulatory CD4(+) T cell subsets than those without TH (p = 0.042, 0.038). These data suggested that adult thymus retains the capacity of regeneration after chemotherapy, especially in young adults. The presence of TH could contribute to the renewal of thymopoiesis and the replenishment of peripheral CD4(+) T cell pool following chemotherapy in adults. PMID:27467956

  2. Thymic carcinoids in multiple endocrine neoplasia type 1.

    PubMed Central

    Teh, B T; Zedenius, J; Kytölä, S; Skogseid, B; Trotter, J; Choplin, H; Twigg, S; Farnebo, F; Giraud, S; Cameron, D; Robinson, B; Calender, A; Larsson, C; Salmela, P

    1998-01-01

    OBJECTIVE: To study the clinical, pathologic, and genetic features of thymic carcinoids in the setting of multiple endocrine neoplasia type 1 (MEN1) and to study means for detection and prevention of this tumor in patients with MEN1. SUMMARY BACKGROUND DATA: Thymic carcinoid is a rare malignancy, with approximately 150 cases reported to date. It may be associated with MEN1 and carries a poor prognosis, with no effective treatment. Its underlying etiology is unknown. METHODS: Ten patients with MEN1 from eight families with anterior mediastinal tumors were included in a case series study at tertiary referring hospitals. Clinicopathologic studies were done on these patients, with a review of the literature. Mutation analysis was performed on the MEN1 gene in families with clusterings of the tumor to look for genotype-phenotype correlation. Loss of heterozygosity was studied in seven cases to look for genetic abnormalities. RESULTS: Histologic studies of all tumors were consistent with the diagnosis of thymic carcinoid. Clustering of this tumor was found in some of the families-three pairs of brothers and three families with first- or second-degree relatives who had thymic carcinoid. All patients described here were men, with a mean age at detection of 44 years (range 31 to 66). Most of the patients had chest pain or were asymptomatic; none had Cushing's or carcinoid syndrome. All tumors were detected by computed tomography (CT) or magnetic resonance imaging (MRI) of the chest. The results of octreoscans performed in three patients were all positive. Histopathologic studies were consistent with the diagnosis of thymic carcinoid and did not stain for ACTH. Mutation analysis of the families with clustering revealed mutations in different exons/introns of the MEN1 gene. Loss of heterozygosity (LOH) studies of seven tumors did not show LOH in the MEN1 region, but two tumors showed LOH in the 1p region. CONCLUSIONS: MEN1-related thymic carcinoids constitute approximately 25

  3. Reduced gonadotropins in athymic mice: prevention by thymic transplantation.

    PubMed

    Rebar, R W; Morandini, I C; Benirschke, K; Petze, J E

    1980-12-01

    The reduction in pituitary concentrations of gonadotropins observed in 20-day old congenitally athymic nude mice in comparison to their normal heterozygous littermates was completely prevented in females and partially prevented in males by thymic transplantation on the first day of life. Those athymic mice receiving transplants but in which no thymic tissue could be found at sacrifice had reduced pituitary gonadotropin concentrations equivalent to sham-operated athymic animals. From these data we infer that the reduced concentrations of gonadotropins seen in the athymic animals are causally related to the absence of the thymus and suggest that the thymus, directly or indirectly, is necessary for development of normal function of the hypothalamic-pituitary-gonadal axis in mice.

  4. Intercellular Protein Transfer from Thymocytes to Thymic Epithelial Cells.

    PubMed

    Wang, Hong-Xia; Qiu, Yu-Rong; Zhong, Xiao-Ping

    2016-01-01

    Promiscuous expression of tissue restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs) is crucial for negative selection of self-reactive T cells to establish central tolerance. Intercellular transfer of self-peptide-MHC complexes from mTECs to thymic dendritic cells (DCs) allows DCs to acquire TRAs, which in turn contributes to negative selection and regulatory T cell generation. However, mTECs are unlikely to express all TRAs, such as immunoglobulins generated only in B cells after somatic recombination, hyper-mutation, or class-switches. We report here that both mTECs and cortical TECs can efficiently acquire not only cell surface but also intracellular proteins from thymocytes. This reveals a previously unappreciated intercellular sharing of molecules from thymocytes to TECs, which may broaden the TRA inventory in mTECs for establishing a full spectrum of central tolerance. PMID:27022746

  5. Intercellular Protein Transfer from Thymocytes to Thymic Epithelial Cells

    PubMed Central

    Wang, Hong-Xia; Qiu, Yu-Rong; Zhong, Xiao-Ping

    2016-01-01

    Promiscuous expression of tissue restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs) is crucial for negative selection of self-reactive T cells to establish central tolerance. Intercellular transfer of self-peptide-MHC complexes from mTECs to thymic dendritic cells (DCs) allows DCs to acquire TRAs, which in turn contributes to negative selection and regulatory T cell generation. However, mTECs are unlikely to express all TRAs, such as immunoglobulins generated only in B cells after somatic recombination, hyper-mutation, or class-switches. We report here that both mTECs and cortical TECs can efficiently acquire not only cell surface but also intracellular proteins from thymocytes. This reveals a previously unappreciated intercellular sharing of molecules from thymocytes to TECs, which may broaden the TRA inventory in mTECs for establishing a full spectrum of central tolerance. PMID:27022746

  6. A tour of the thymus: a review of thymic lesions with radiologic and pathologic correlation.

    PubMed

    Goldstein, Alan J; Oliva, Isabel; Honarpisheh, Hedieh; Rubinowitz, Ami

    2015-02-01

    The thymus is routinely encountered on cross-sectional imaging studies of the chest. It has a variable appearance, undergoes dynamic changes during periods of stress, and demonstrates numerous different pathologic lesions. Understanding the imaging characteristics of these different lesions facilitates accurate radiographic diagnosis and can prevent unnecessary follow-up imaging and intervention. This article will review normal thymic anatomy and development, thymic hyperplasia and associated medical conditions, and the imaging and pathologic features of various benign and malignant thymic lesions.

  7. RETINOPATHY OF PREMATURITY: INVOLUTION, FACTORS PREDISPOSING TO RETINAL DETACHMENT, AND EXPECTED UTILITY OF PREEMPTIVE SURGICAL REINTERVENTION

    PubMed Central

    Coats, David K

    2005-01-01

    Purpose To characterize involution of retinopathy of prematurity (ROP) following treatment at threshold, to identify findings during involution that portend development of retinal detachment, and to assess the potential utility of preemptive vitrectomy for eyes with high-risk features. Methods The probability of ROP involution and of retinal detachment evolution over time was analyzed in 262 treated eyes of 138 infants in a retrospective observational non–case controlled series. Expected utility of preemptive reintervention in eyes with high-risk features was evaluated using decision analysis. Modifications were devised to enhance classification of advanced ROP. Results ROP fully involuted in approximately 80% of eyes within 28 days of treatment. Vitreous organization meeting the study’s clinically important definition was associated with a 31-fold (5.37 to 183.63; P < .0001) and a 13-fold (2.97 to 58.59; P < .0001) increase in the odds for retinal detachment for right and left eyes, respectively. Vitreous hemorrhage defined as clinically important was associated with a 38-fold (2.69 to 551.19; P = .007) and a 15-fold (1.65 to 144.12; P = .02) increase in the odds for retinal detachment for right and left eyes, respectively. As modeled, an expected utility of 0.85 was calculated for preemptive vitrectomy compared with 0.79 for deferred vitrectomy for eyes with clinically important vitreous organization. Conclusions Acute-phase ROP involuted quickly in most eyes. Vitreous organization and vitreous hemorrhage were predictive of eyes that developed a retinal detachment. Decision analysis suggests that preemptive vitrectomy for eyes with vitreous organization meeting specific criteria is not likely to be worse than deferred vitrectomy, and it could be advantageous in some scenarios. PMID:17057808

  8. Uterine involution and progesterone level during the postpartum period in Barbary ewes in north Libya.

    PubMed

    Medan, M S; El-Daek, T

    2015-01-01

    The objectives of the present study were to determine the time of uterine involution and ovarian activity using ultrasound examination and progesterone assay. Weekly progesterone levels were measured starting one week postpartum until two weeks after the 1(st) postpartum estrus in Barbary ewes lambed during winter in AL-Bayda city, north of Libya. A total of 15 Barbary ewes were used in the present study distributed in three groups according to the month of lambing as group 1 (lambed in January), group 2 (lambed in February) and group 3 (lambed in March). Ewes were examined weekly by trans-rectal ultrasound to check involution of the uterus starting one week after lambing until complete uterine involution. Blood samples were collected from the jugular vein, and serum was separated and stored at -20 °C until measuring progesterone using ELISA. Results showed that uterine involution completed at day 35 postpartum in groups 1 and 2, while it occurred at day 28 in group 3. The mean progesterone level was basal (less than 1 ng/ml) for a long period and started to increase at days 119, 99 and 77 postpartum in group 1, 2 and 3, respectively. One ewe did not show estrus at all during the period of study in group 2 and there were no growing follicles on their ovaries. The obtained results indicate that, uterine involution as determined by ultrasound completed earlier in ewes lambed in March than those lambed in February or January. Also, progesterone level and ultrasound examination showed that there was no ovarian activity for a longtime after parturition indicating that reproduction in Barbary ewes tends to be seasonal in AL-Bayda city, north Libya.

  9. Uterine involution and progesterone level during the postpartum period in Barbary ewes in north Libya

    PubMed Central

    Medan, M.S.; EL-Daek, T.

    2015-01-01

    The objectives of the present study were to determine the time of uterine involution and ovarian activity using ultrasound examination and progesterone assay. Weekly progesterone levels were measured starting one week postpartum until two weeks after the 1st postpartum estrus in Barbary ewes lambed during winter in AL-Bayda city, north of Libya. A total of 15 Barbary ewes were used in the present study distributed in three groups according to the month of lambing as group 1 (lambed in January), group 2 (lambed in February) and group 3 (lambed in March). Ewes were examined weekly by trans-rectal ultrasound to check involution of the uterus starting one week after lambing until complete uterine involution. Blood samples were collected from the jugular vein, and serum was separated and stored at -20 °C until measuring progesterone using ELISA. Results showed that uterine involution completed at day 35 postpartum in groups 1 and 2, while it occurred at day 28 in group 3. The mean progesterone level was basal (less than 1 ng/ml) for a long period and started to increase at days 119, 99 and 77 postpartum in group 1, 2 and 3, respectively. One ewe did not show estrus at all during the period of study in group 2 and there were no growing follicles on their ovaries. The obtained results indicate that, uterine involution as determined by ultrasound completed earlier in ewes lambed in March than those lambed in February or January. Also, progesterone level and ultrasound examination showed that there was no ovarian activity for a longtime after parturition indicating that reproduction in Barbary ewes tends to be seasonal in AL-Bayda city, north Libya. PMID:26623357

  10. Thymic Atrophy and Apoptosis of CD4+CD8+ Thymocytes in the Cuprizone Model of Multiple Sclerosis

    PubMed Central

    Talaber, Gergely; Veto, Sara; Acs, Peter; Gallyas, Ferenc; Illes, Zsolt; Fekete, Katalin; Zalan, Petra; Szanto, Arpad; Bognar, Zita

    2015-01-01

    Previous studies on the degenerative animal model of multiple sclerosis suggested that the copper-chelator cuprizone might directly suppress T-cell functions. Peripheral T-cell function in the cuprizone model has already been explored; therefore, in the present study, we investigated, for the first time, how cuprizone feeding affects the thymus, the organ of T-cell maturation and selection. We found that even one week of cuprizone treatment induced significant thymic atrophy, affecting the cortex over the medulla. Fluorescent microscopy and flow-cytometric analyses of thymi from cuprizone- and vehicle-treated mice indicated that eradication of the cluster of the differentiation-4 (CD4)-CD8 double-positive T-cell subset was behind the substantial cell loss. This result was confirmed with CD3-CD4-CD8 triple-staining experiments. Ultrastructurally, we observed degraded as well as enlarged mitochondria, myelin-bodies, large lipid droplets, and large lysosomes in the thymi of cuprizone-treated mice. Some of these features were similar to those in physiological and steroid-induced accelerated aging. According to our results, apoptosis was mainly of mitochondrial origin mediated by both caspase-3- and apoptosis inducing factor-mediated mechanisms. Additionally, mitogen activated protein kinase activation and increased pro-apoptotic B cell lymphoma-2 family protein expression were the major underlying processes. Our results do not indicate a functional relationship between cuprizone-induced thymus involution and the absence of inflammatory responses or the selective demyelination observed in the cuprizone model. On the other hand, due to the reversible nature of cuprizone’s deleterious effects, the cuprizone model could be valuable in studying thymus regeneration as well as remyelination processes. PMID:26053248

  11. Thymic stromal cell subsets for T cell development.

    PubMed

    Nitta, Takeshi; Suzuki, Harumi

    2016-03-01

    The thymus provides a specialized microenvironment in which a variety of stromal cells of both hematopoietic and non-hematopoietic origin regulate development and repertoire selection of T cells. Recent studies have been unraveling the inter- and intracellular signals and transcriptional networks for spatiotemporal regulation of development of thymic stromal cells, mainly thymic epithelial cells (TECs), and the molecular mechanisms of how different TEC subsets control T cell development and selection. TECs are classified into two functionally different subsets: cortical TECs (cTECs) and medullary TECs (mTECs). cTECs induce positive selection of diverse and functionally distinct T cells by virtue of unique antigen-processing systems, while mTECs are essential for establishing T cell tolerance via ectopic expression of peripheral tissue-restricted antigens and cooperation with dendritic cells. In addition to reviewing the role of the thymic stroma in conventional T cell development, we will discuss recently discovered novel functions of TECs in the development of unconventional T cells, such as natural killer T cells and γδT cells. PMID:26825337

  12. Thymic proliferative response during different physiological states: a comparative study

    PubMed Central

    Habbal, O A; McLean, I M; Abu-Hijleh, M F

    2000-01-01

    Objective To study the thymic proliferative response during different physiological states to distinguish those changes due to alterations in steroid hormone secretion from those resulting from the presence of spermatozoa and/or early conceptual products in the female reproductive tract. Method Using mature female rats of an inbred AO(RT1u) strain, observations on the thymus were made at 24 hour intervals during the oestrous cycle, early pseudopregnancy and early syngeneic pregnancy. Each daily group contained a minimum of 6 animals. Results During the oestrous cycle, a significant mid-cycle increase of thymocyte proliferation occurred during dioestrus which peaked on day 2, and as a repetitive response may be a preparation for a coital challenge. This response may be oestrogen-dependent since oestrogen levels begin to increase during early dioestrus. The induction of pseudopregnancy generates a comparable but delayed increase in thymic proliferative activity. Since thymocyte proliferation and oestrogen secretion both peak on day 3 of pseudopregnancy, such a response may indeed also be oestrogen-dependent. After syngeneic mating, there was a significant depression in thymic proliferative activity on day 3 followed by a significant increase on day 5 compared with the same days of pseudopregnancy. Conclusion This initial depression of proliferative activity may be induced by the immunosuppressive action of seminal plasma, to safeguard the preimplantation conceptus while the day 5 increase in cellular proliferation suggests a response to implantation. PMID:24019701

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

    SciTech Connect

    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.

  14. Age-related changes in the meibomian gland.

    PubMed

    Nien, Chyong Jy; Paugh, Jerry R; Massei, Salina; Wahlert, Andrew J; Kao, Winston W; Jester, James V

    2009-12-01

    The purpose of this study was to characterize the age-related changes of the mouse meibomian gland. Eyelids from adult C57Bl/6 mice at 2, 6, 12 and 24 months of age were stained with specific antibodies against peroxisome proliferator activated receptor gamma (PPARgamma) to identify differentiating meibocytes, Oil Red O (ORO) to identify lipid, Ki67 nuclear antigen to identify cycling cells, B-lymphocyte-induced maturation protein-1 (Blimp1) to identify potential stem cells and CD45 to identify immune cells. Meibomian glands from younger mice (2 and 6 months) showed cytoplasmic and perinuclear staining with anti-PPARgamma antibodies with abundant ORO staining of small, intracellular lipid droplets. Meibomian glands from older mice (12 and 24 months) showed only nuclear PPARgamma localization with less ORO staining and significantly reduced acinar tissue (p < 0.04). Acini of older mice also showed significantly reduced (p < 0.004) numbers of Ki67 stained nuclei. While Blimp1 appeared to diffusely stain the superficial ductal epithelium, isolated cells were occasionally stained within the meibomian gland duct and acini of older mice that also stained with CD45 antibodies, suggesting the presence of infiltrating plasmacytoid cells. These findings suggest that there is altered PPARgamma receptor signaling in older mice that may underlie changes in cell cycle entry/proliferation, lipid synthesis and gland atrophy during aging. These results are consistent with the hypothesis that mouse meibomian glands undergo age-related changes similar to those identified in humans and may be used as a model for age-related meibomian gland dysfunction.

  15. Age-Related Deterioration of Rod Vision in Mice

    PubMed Central

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

    2010-01-01

    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 of 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 to 4 month-old animals. Aging also resulted in a 2-fold reduction in the total level of opsin in the retina. Behavioral tests revealed that scotopic visual acuity and contrast sensitivity were decreased by 2-fold 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. PMID:20720130

  16. Age-related differences in updating working memory.

    PubMed

    Van der Linden, M; Brédart, S; Beerten, A

    1994-02-01

    Age-related differences in updating working memory were investigated in two experiments using a running memory task. In the first experiment, the task of the young and elderly subjects was to watch strings of four to 10 consonants and then to recall serially the four most recent items. Results revealed no age effect. A second experiment was then carried out using a memory load that was close to memory span: lists of six to 12 consonants were presented and subjects had to recall the last six items. Age interacted with list length but not with serial position. This dissociation is discussed in terms of Baddeley's (1986) model.

  17. [Diagnostic Criteria for Atrophic Age-related Macular Degeneration].

    PubMed

    Takahashi, Kanji; Shiraga, Fumio; Ishida, Susumu; Kamei, Motohiro; Yanagi, Yasuo; Yoshimura, Nagahisa

    2015-10-01

    Diagnostic criteria for dry age-related macular degeneration is described. Criteria include visual acuity, fundscopic findings, diagnostic image findings, exclusion criteria and classification of severity grades. Essential findings to make diagnosis as "geographic atrophy" are, 1) at least 250 μm in diameter, 2) round/oval/cluster-like or geographic in shape, 3) sharp delineation, 4) hypopigmentation or depigmentation in retinal pigment epithelium, 5) choroidal vessels are more visible than in surrounding area. Severity grades were classified as mild, medium and severe by relation of geographic atrophy to the fovea and attendant findings. PMID:26571627

  18. Effects of Vitreomacular Adhesion on Age-Related Macular Degeneration

    PubMed Central

    Kang, Eui Chun; Koh, Hyoung Jun

    2015-01-01

    Herein, we review the association between vitreomacular adhesion (VMA) and neovascular age-related macular degeneration (AMD). Meta-analyses have shown that eyes with neovascular AMD are twice as likely to have VMA as normal eyes. VMA in neovascular AMD may induce inflammation, macular traction, decrease in oxygenation, sequestering of vascular endothelial growth factor (VEGF), and other cytokines or may directly stimulate VEGF production. VMA may also interfere with the treatment effects of anti-VEGF therapy, which is the standard treatment for neovascular AMD, and releasing VMA can improve the treatment response to anti-VEGF treatment in neovascular AMD. We also reviewed currently available methods of relieving VMA. PMID:26425354

  19. [Glaucoma and age-related macular degeneration intricacy].

    PubMed

    Valtot, F

    2008-07-01

    Age-related macular degeneration (AMD) is the leading cause of legal blindness among the elderly in Western nations. Age is also a well-known and well-evidenced risk factor for glaucoma. With increasing longevity and the rising prevalence of older people around the world, more and more patients will have glaucoma and AMD. Clinical evaluation of these patients still poses problems for clinicians. It is very important to order the right tests at the right time to distinguish glaucomatous defects from those caused by retinal lesions, because appropriate therapy has a beneficial effect on slowing or halting damage. PMID:18957915

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

    PubMed Central

    Yonekawa, Yoshihiro; Miller, Joan W.; Kim, Ivana K.

    2015-01-01

    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. PMID:26239130

  1. Squalamine lactate for exudative age-related macular degeneration.

    PubMed

    Connolly, Brian; Desai, Avinash; Garcia, Charles A; Thomas, Edgar; Gast, Michael J

    2006-09-01

    Squalamine lactate inhibits angiogenesis by a long-lived, intracellular mechanism of action. The drug is taken up into activated endothelial cells through caveolae, small invaginations in the cellular membrane. Subsequently, the drug binds to and "chaperones" calmodulin to an intracellular membrane compartment and blocks angiogenesis at several levels. A series of basic investigations, preclinical studies, and human clinical trials have begun to establish the proof of concept, efficacy, and safety parameters for use of squalamine lactate as a therapeutic agent for exudative age-related macular degeneration and several types of malignancies. PMID:16935213

  2. Thymic progenitor homing and lymphocyte homeostasis are linked via S1P-controlled expression of thymic P-selectin/CCL25

    PubMed Central

    Gossens, Klaus; Naus, Silvia; Corbel, Stephane Y.; Lin, Shujun; Rossi, Fabio M.V.; Kast, Jürgen

    2009-01-01

    Thymic T cell progenitor (TCP) importation is a periodic, gated event that is dependent on the expression of functional P-selectin ligands on TCPs. Occupancy of intrathymic TCP niches is believed to negatively regulate TCP importation, but the nature of this feedback mechanism is not yet resolved. We show that P-selectin and CCL25 are periodically expressed in the thymus and are essential parts of the thymic gate-keeping mechanism. Periodicity of thymic TCP receptivity and the size of the earliest intrathymic TCP pool were dependent on the presence of functional P-selectin ligand on TCPs. Furthermore, we show that the numbers of peripheral blood lymphocytes directly affected thymic P-selectin expression and TCP receptivity. We identified sphingosine-1-phosphate (S1P) as one feedback signal that could mediate influence of the peripheral lymphocyte pool on thymic TCP receptivity. Our findings suggest a model whereby thymic TCP importation is controlled by both early thymic niche occupancy and the peripheral lymphocyte pool via S1P. PMID:19289576

  3. Current therapeutic developments in atrophic age-related macular degeneration.

    PubMed

    Hanus, Jakub; Zhao, Fangkun; Wang, Shusheng

    2016-01-01

    Age-related macular degeneration (AMD), a degenerative disorder of the central retina, is the leading cause of irreversible blindness in the elderly. The underlying mechanism of the advanced form of dry AMD, also named geographic atrophy (GA) or atrophic AMD, remains unclear. Consequently, no cure is available for dry AMD or GA. The only prevention option currently available is the Age-Related Eye Disease Study (AREDS) formulation, which has been demonstrated to slow down the progression of dry AMD. This review summarises recent advances in therapy for dry AMD and GA. Building on the new understanding of the disease and recent technological breakthroughs, numerous ongoing clinical trials have the goal of meeting the need to cure AMD. Therapeutic agents are being developed to target the key features of the disease, including inhibiting the complement pathway and other inflammatory pathways, reducing oxidative stress and protecting retinal pigment epithelial (RPE) cells, inhibiting lipofuscin and visual cycle, regenerating RPE cells from stem cells and restoring choroidal blood flow. Some of these therapeutic options, especially the stem cell-based therapy, hold great promise, which brings great hope for this devastating blinding disease. PMID:26553922

  4. Long noncoding RNAs in aging and age-related diseases.

    PubMed

    Kour, Sukhleen; Rath, Pramod C

    2016-03-01

    Aging is the universal, intrinsic, genetically-controlled, evolutionarily-conserved and time-dependent intricate biological process characterised by the cumulative decline in the physiological functions and their coordination in an organism after the attainment of adulthood resulting in the imbalance of neurological, immunological and metabolic functions of the body. Various biological processes and mechanisms along with altered levels of mRNAs and proteins have been reported to be involved in the progression of aging. It is one of the major risk factors in the patho-physiology of various diseases and disorders. Recently, the discovery of pervasive transcription of a vast pool of heterogeneous regulatory noncoding RNAs (ncRNAs), including small ncRNAs (sncRNAs) and long ncRNAs (lncRNAs), in the mammalian genome have provided an alternative way to study and explore the missing links in the aging process, its mechanism(s) and related diseases in a whole new dimension. The involvement of small noncoding RNAs in aging and age-related diseases have been extensively studied and recently reviewed. However, lncRNAs, whose function is far less explored in relation to aging, have emerged as a class of major regulators of genomic functions. Here, we have described some examples of known as well as novel lncRNAs that have been implicated in the progression of the aging process and age-related diseases. This may further stimulate research on noncoding RNAs and the aging process.

  5. Exploring age-related brain degeneration in meditation practitioners.

    PubMed

    Luders, Eileen

    2014-01-01

    A growing body of research suggests that meditation practices are associated with substantial psychological as well as physiological benefits. In searching for the biological mechanisms underlying the beneficial impact of meditation, studies have revealed practice-induced alterations of neurotransmitters, brain activity, and cognitive abilities, just to name a few. These findings not only imply a close link between meditation and brain structure, but also suggest possible modulating effects of meditation on age-related brain atrophy. Given that normal aging is associated with significant loss of brain tissue, meditation-induced growth and/or preservation might manifest as a seemingly reduced brain age in meditators (i.e., cerebral measures characteristic of younger brains). Surprisingly, there are only three published studies that have addressed the question of whether meditation diminishes age-related brain degeneration. This paper reviews these three studies with respect to the brain attributes studied, the analytical strategies applied, and the findings revealed. The review concludes with an elaborate discussion on the significance of existing studies, implications and directions for future studies, as well as the overall relevance of this field of research.

  6. Long noncoding RNAs in aging and age-related diseases.

    PubMed

    Kour, Sukhleen; Rath, Pramod C

    2016-03-01

    Aging is the universal, intrinsic, genetically-controlled, evolutionarily-conserved and time-dependent intricate biological process characterised by the cumulative decline in the physiological functions and their coordination in an organism after the attainment of adulthood resulting in the imbalance of neurological, immunological and metabolic functions of the body. Various biological processes and mechanisms along with altered levels of mRNAs and proteins have been reported to be involved in the progression of aging. It is one of the major risk factors in the patho-physiology of various diseases and disorders. Recently, the discovery of pervasive transcription of a vast pool of heterogeneous regulatory noncoding RNAs (ncRNAs), including small ncRNAs (sncRNAs) and long ncRNAs (lncRNAs), in the mammalian genome have provided an alternative way to study and explore the missing links in the aging process, its mechanism(s) and related diseases in a whole new dimension. The involvement of small noncoding RNAs in aging and age-related diseases have been extensively studied and recently reviewed. However, lncRNAs, whose function is far less explored in relation to aging, have emerged as a class of major regulators of genomic functions. Here, we have described some examples of known as well as novel lncRNAs that have been implicated in the progression of the aging process and age-related diseases. This may further stimulate research on noncoding RNAs and the aging process. PMID:26655093

  7. Curcumin, inflammation, ageing and age-related diseases.

    PubMed

    Sikora, E; Scapagnini, Giovanni; Barbagallo, Mario

    2010-01-17

    A Symposium regarding the Pathophysiology of Successful and Unsuccessful Ageing was held in Palermo, Italy between April 7 and 8th 2009. Here the lecture by Sikora with some input from the chairpersons Scapagnini and Barbagallo is summarized. Ageing is manifested by the decreasing health status and increasing probability to acquire age-related disease such as cancer, Alzheimer's disease, atherosclerosis, metabolic disorders and others. They are likely caused by low grade inflammation driven by oxygen stress and manifested by the increased level of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-alpha, encoded by genes activated by the transcription factor NF-kappaB. It is believed that ageing is plastic and can be slowed down by caloric restriction as well as by some nutraceuticals. Accordingly, slowing down ageing and postponing the onset of age-related diseases might be achieved by blocking the NF-kappaB-dependent inflammation. In this review we consider the possibility of the spice curcumin, a powerful antioxidant and anti-inflammatory agent possibly capable of improving the health status of the elderly.

  8. Current Therapeutic Development for Atrophic Age-related Macular Degeneration

    PubMed Central

    Hanus, Jakub; Zhao, Fangkun; Wang, Shusheng

    2016-01-01

    Age-related macular degeneration (AMD), a degenerative disorder of the central retina, is the leading cause of irreversible blindness in the elderly. The underlying mechanism of the advanced form of dry AMD, also named geographic atrophy (GA) or atrophic AMD, remains unclear. Consequently, no cure is available for dry AMD or GA. The only prevention option currently available is the Age Related Eye Disease Study (AREDS) formulation which has been demonstrated to slow down the progression of dry AMD. This review summarizes recent advances in therapy for dry AMD and GA. Building on the new understanding of the disease and recent technological breakthroughs, numerous ongoing clinical trials have the goal of meeting the need to cure AMD. Therapeutic agents are being developed to target the key features of the disease, including inhibiting the complement pathway and other inflammatory pathways, reducing oxidative stress and protecting retinal pigment epithelial (RPE) cells, inhibiting lipofuscin and visual cycle, regenerating RPE cells from stem cells and restoring choroidal blood flow. Some of these therapeutic options, especially the stem-cell based therapy, hold great promise, which brings great hope for this devastating blinding disease. PMID:26553922

  9. Age-related changes to the production of linguistic prosody

    NASA Astrophysics Data System (ADS)

    Barnes, Daniel R.

    The production of speech prosody (the rhythm, pausing, and intonation associated with natural speech) is critical to effective communication. The current study investigated the impact of age-related changes to physiology and cognition in relation to the production of two types of linguistic prosody: lexical stress and the disambiguation of syntactically ambiguous utterances. Analyses of the acoustic correlates of stress: speech intensity (or sound-pressure level; SPL), fundamental frequency (F0), key word/phrase duration, and pause duration revealed that both young and older adults effectively use these acoustic features to signal linguistic prosody, although the relative weighting of cues differed by group. Differences in F0 were attributed to age-related physiological changes in the laryngeal subsystem, while group differences in duration measures were attributed to relative task complexity and the cognitive-linguistic load of these respective tasks. The current study provides normative acoustic data for older adults which informs interpretation of clinical findings as well as research pertaining to dysprosody as the result of disease processes.

  10. Age-Related Deficits in Reality Monitoring of Action Memories

    PubMed Central

    McDaniel, Mark A.; Lyle, Keith B.; Butler, Karin M.; Dornburg, Courtney C.

    2008-01-01

    We describe three theoretical accounts of age-related increases in falsely remembering that imagined actions were performed (Thomas & Bulevich, 2006). To investigate these accounts and further explore age-related changes in reality monitoring of action memories, we used a new paradigm in which actions were (a) imagined-only (b) actually performed, or (c) both imagined and performed. Older adults were more likely than younger adults to misremember the source of imagined-only actions, with older adults’ more often specifying that the action was imagined and also that it was performed. For both age groups, as repetitions of the imagined-only events increased, illusions that the actions were only performed decreased. These patterns suggest that both older and younger adults utilize qualitative characteristics when making reality-monitoring judgments and that repeated imagination produces richer records of both sensory details and cognitive operations. However, sensory information derived from imagination appears to be more similar to that derived from performance for older than younger adults. PMID:18808253

  11. Age-Related Loss of Muscle Mass and Strength

    PubMed Central

    Goldspink, Geoffrey

    2012-01-01

    Age-related muscle wasting and increased frailty are major socioeconomic as well as medical problems. In the quest to extend quality of life it is important to increase the strength of elderly people sufficiently so they can carry out everyday tasks and to prevent them falling and breaking bones that are brittle due to osteoporosis. Muscles generate the mechanical strain that contributes to the maintenance of other musculoskeletal tissues, and a vicious circle is established as muscle loss results in bone loss and weakening of tendons. Molecular and proteomic approaches now provide strategies for preventing age-related muscle wasting. Here, attention is paid to the role of the GH/IGF-1 axis and the special role of the IGFI-Ec (mechano growth factor/MGF) which is derived from the IGF-I gene by alternative splicing. During aging MGF levels decline but when administered MGF activates the muscle satellite (stem) cells that “kick start” local muscle repair and induces hypertrophy. PMID:22506111

  12. Age-related preferences and age weighting health benefits.

    PubMed

    Tsuchiya, A

    1999-01-01

    This paper deals with the relevance of age in the paradigm of quality adjusted life years (QALYs). The first section outlines two rationales for incorporating age weights into QALYs. One of them is based on efficiency concerns; and the other on equity concerns. Both of these are theoretical constructs. The main purpose of this paper is to examine the extent of published empirical support for such age weighting. The second section is a brief survey of nine empirical studies that elicited age-related preferences from the general public. Six of these quantified the strength of the preferences, and these are discussed in more detail in the third section. The analysis distinguishes three kinds of age-related preference: productivity ageism, utilitarian ageism and egalitarian ageism. The relationship between them and their relevance to the two different rationales for age weighting are then explored. It is concluded that, although there is strong prima facie evidence of public support for both types of age weighting, the empirical evidence to support any particular set of weights is at present weak. PMID:10048783

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

    PubMed

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

    2016-09-01

    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. PMID:27495013

  14. HSP27 and 70 expression in thymic epithelial tumors and benign thymic alterations: diagnostic, prognostic and physiologic implications.

    PubMed

    Janik, S; Schiefer, A I; Bekos, C; Hacker, P; Haider, T; Moser, J; Klepetko, W; Müllauer, L; Ankersmit, H J; Moser, B

    2016-01-01

    Thymic Epithelial Tumors (TETs), the most common tumors in the anterior mediastinum in adults, show a unique association with autoimmune Myasthenia Gravis (MG) and represent a multidisciplinary diagnostic and therapeutic challenge. Neither risk factors nor established biomarkers for TETs exist. Predictive and diagnostic markers are urgently needed. Heat shock proteins (HSPs) are upregulated in several malignancies promoting tumor cell survival and metastases. We performed immunohistochemical staining of HSP27 and 70 in patients with TETs (n = 101) and patients with benign thymic alterations (n = 24). Further, serum HSP27 and 70 concentrations were determined in patients with TETs (n = 46), patients with benign thymic alterations (n = 33) and volunteers (n = 49) by using ELISA. HSPs were differentially expressed in histologic types and pathological tumor stages of TETs. Weak HSP tumor expression correlated with worse freedom from recurrence. Serum HSP concentrations were elevated in TETs and MG, correlated with clinical tumor stage and histologic subtype and decreased significantly after complete tumor resection. To conclude, we found HSP expression in the vast majority of TETs, in physiologic thymus and staining intensities in patients with TETs have been associated with prognosis. However, although interesting and promising the role of HSPs in TETs as diagnostic and prognostic or even therapeutic markers need to be further evaluated.

  15. HSP27 and 70 expression in thymic epithelial tumors and benign thymic alterations: diagnostic, prognostic and physiologic implications

    PubMed Central

    Janik, S.; Schiefer, A. I.; Bekos, C.; Hacker, P.; Haider, T.; Moser, J.; Klepetko, W.; Müllauer, L.; Ankersmit, H. J.; Moser, B.

    2016-01-01

    Thymic Epithelial Tumors (TETs), the most common tumors in the anterior mediastinum in adults, show a unique association with autoimmune Myasthenia Gravis (MG) and represent a multidisciplinary diagnostic and therapeutic challenge. Neither risk factors nor established biomarkers for TETs exist. Predictive and diagnostic markers are urgently needed. Heat shock proteins (HSPs) are upregulated in several malignancies promoting tumor cell survival and metastases. We performed immunohistochemical staining of HSP27 and 70 in patients with TETs (n = 101) and patients with benign thymic alterations (n = 24). Further, serum HSP27 and 70 concentrations were determined in patients with TETs (n = 46), patients with benign thymic alterations (n = 33) and volunteers (n = 49) by using ELISA. HSPs were differentially expressed in histologic types and pathological tumor stages of TETs. Weak HSP tumor expression correlated with worse freedom from recurrence. Serum HSP concentrations were elevated in TETs and MG, correlated with clinical tumor stage and histologic subtype and decreased significantly after complete tumor resection. To conclude, we found HSP expression in the vast majority of TETs, in physiologic thymus and staining intensities in patients with TETs have been associated with prognosis. However, although interesting and promising the role of HSPs in TETs as diagnostic and prognostic or even therapeutic markers need to be further evaluated. PMID:27097982

  16. HSP27 and 70 expression in thymic epithelial tumors and benign thymic alterations: diagnostic, prognostic and physiologic implications.

    PubMed

    Janik, S; Schiefer, A I; Bekos, C; Hacker, P; Haider, T; Moser, J; Klepetko, W; Müllauer, L; Ankersmit, H J; Moser, B

    2016-01-01

    Thymic Epithelial Tumors (TETs), the most common tumors in the anterior mediastinum in adults, show a unique association with autoimmune Myasthenia Gravis (MG) and represent a multidisciplinary diagnostic and therapeutic challenge. Neither risk factors nor established biomarkers for TETs exist. Predictive and diagnostic markers are urgently needed. Heat shock proteins (HSPs) are upregulated in several malignancies promoting tumor cell survival and metastases. We performed immunohistochemical staining of HSP27 and 70 in patients with TETs (n = 101) and patients with benign thymic alterations (n = 24). Further, serum HSP27 and 70 concentrations were determined in patients with TETs (n = 46), patients with benign thymic alterations (n = 33) and volunteers (n = 49) by using ELISA. HSPs were differentially expressed in histologic types and pathological tumor stages of TETs. Weak HSP tumor expression correlated with worse freedom from recurrence. Serum HSP concentrations were elevated in TETs and MG, correlated with clinical tumor stage and histologic subtype and decreased significantly after complete tumor resection. To conclude, we found HSP expression in the vast majority of TETs, in physiologic thymus and staining intensities in patients with TETs have been associated with prognosis. However, although interesting and promising the role of HSPs in TETs as diagnostic and prognostic or even therapeutic markers need to be further evaluated. PMID:27097982

  17. Age-related priming effects in social judgments.

    PubMed

    Hess, T M; McGee, K A; Woodburn, S M; Bolstad, C A

    1998-03-01

    Two experiments investigated adult age differences in the impact of previously activated (and thus easily accessible) trait-related information on judgments about people. The authors hypothesized that age-related declines in the efficiency of controlled processing mechanisms during adulthood would be associated with increased susceptibility to judgment biases associated with such information. In each study, different-aged adults made impression judgments about a target, and assimilation of these judgments to trait constructs activated in a previous, unrelated task were examined. Consistent with the authors' hypotheses, older adults were likely to form impressions that were biased toward the primed trait constructs. In contrast, younger adults exhibited greater awareness of the primed information and were more likely to correct for its perceived influence, especially when distinctive contextual cues regarding the source of the primes were available. PMID:9533195

  18. Age-related differences in multiple task monitoring.

    PubMed

    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.

  19. Age-related changes in human vitreous structure.

    PubMed

    Sebag, J

    1987-01-01

    Changes in vitreous structure that occur with aging are important in the pathogenesis of vitreous liquefaction (synchisis senilis), vitreous detachment, and retinal disease. Vitreous morphology was studied in 59 human eyes post-mortem using dark-field horizontal slit illumination of the entire dissected vitreous. In many individuals younger than 30 years, the vitreous was homogeneous in structure. Middle-aged individuals had macroscopic fibers in the central vitreous, which coursed anteroposteriorly and inserted into the vitreous base and the vitreous cortex, posteriorly. During senescence, the vitreous volume was reduced, the vitreous body was collapsed (syneresis), and the fibers were thickened, tortuous, and surrounded by liquid vitreous. This sequence of age-related changes probably results from a progressive reorganization of the hyaluronic acid and collagen molecular networks. Characterization of the molecular events underlying these changes will elucidate the mechanisms of the phenomena of synchisis, syneresis, and detachment, and may provide methods with which to prevent or induce vitreous detachment prophylactically.

  20. Sex- and age-related differences in mathematics.

    PubMed

    Rustemeyer, Ruth; Fischer, Natalie

    2005-08-01

    This study examined sex differences and age-related changes in mathematics based on Eccles's 1985 expectancy-value model of "achievement-related choices" and Dweck's 1986 motivation-process model. We have assessed motivational variables and performance in mathematics for youth in Grades 5, 7, and 9 in a German comprehensive secondary school. Significant sex differences in Grades 7 and 9 were observed even when school marks were controlled for. Furthermore, the results indicated differences between Grade 7 and Grade 9 on most of the motivational variables. Older students show a less favorable motivational pattern. Our results give evidence of the importance of motivational encouragement in mathematics classes, especially for girls and low achieving learners. PMID:16279324

  1. Age-Related Differences in Multiple Task Monitoring

    PubMed Central

    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. PMID:25215609

  2. Gene-Diet Interactions in Age-Related Macular Degeneration.

    PubMed

    Rowan, Sheldon; Taylor, Allen

    2016-01-01

    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 is the only available treatment option for the dry form of the disease known to slow progression of AMD. Despite an excellent understanding of genes and nutrition in AMD, there is remarkably little known about gene-diet interactions that may identify efficacious approaches to treat individuals. This review will summarize our current understanding of gene-diet interactions in AMD with a focus on animal models and human epidemiological studies.

  3. Age-related responses to mild restraint in the rat.

    PubMed

    Rattner, B A; Michael, S D; Altland, P D

    1983-11-01

    Immature, postpubertal, young adult, and middle-aged rats were lightly restrained for 4 h. Relative to untreated controls, restraint uniformly reduced body weight and plasma luteinizing hormone concentration and elevated plasma corticosterone concentration in all age groups. However, restraint increased activities of plasma alanine and aspartate aminotransferase, creatine phosphokinase, and fructose-diphosphate aldolase in only immature and middle-aged animals. This age-related release of tissue enzymes is hypothesized to reflect enhanced responsiveness to catecholamines in immature rats, and possible ischemia related to diminished vasodilatory activity in middle-aged rats. On the basis of these changes, tolerance to restraint in postpubertal and young adults appears to be slightly greater than that of immature and middle-aged rats.

  4. A Revised Hemodynamic Theory of Age-Related Macular Degeneration.

    PubMed

    Gelfand, Bradley D; Ambati, Jayakrishna

    2016-08-01

    Age-related macular degeneration (AMD) afflicts one out of every 40 individuals worldwide, causing irreversible central blindness in millions. The transformation of various tissue layers within the macula in the retina has led to competing conceptual models of the molecular pathways, cell types, and tissues responsible for the onset and progression of AMD. A model that has persisted for over 6 decades is the hemodynamic, or vascular theory of AMD progression, which states that vascular dysfunction of the choroid underlies AMD pathogenesis. Here, we re-evaluate this hypothesis in light of recent advances on molecular, anatomic, and hemodynamic changes underlying choroidal dysfunction in AMD. We propose an updated, detailed model of hemodynamic dysfunction as a mechanism of AMD development and progression. PMID:27423265

  5. MicroRNAs in age-related diseases.

    PubMed

    Dimmeler, Stefanie; Nicotera, Pierluigi

    2013-02-01

    Aging is a complex process that is linked to an increased incidence of major diseases such as cardiovascular and neurodegenerative disease, but also cancer and immune disorders. MicroRNAs (miRNAs) are small non-coding RNAs, which post-transcriptionally control gene expression by inhibiting translation or inducing degradation of targeted mRNAs. MiRNAs target up to hundreds of mRNAs, thereby modulating gene expression patterns. Many miRNAs appear to be dysregulated during cellular senescence, aging and disease. However, only few miRNAs have been so far linked to age-related changes in cellular and organ functions. The present article will discuss these findings, specifically focusing on the cardiovascular and neurological systems.

  6. Molecular pathology of age-related macular degeneration

    PubMed Central

    Ding, Xiaoyan; Patel, Mrinali; Chan, Chi-Chao

    2009-01-01

    Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the world. Although the etiology and pathogenesis of AMD remain largely unclear, a complex interaction of genetic and environmental factors is thought to exist. AMD pathology is characterized by degeneration involving the retinal photoreceptors, retinal pigment epithelium, and Bruch’s membrane, as well as, in some cases, alterations in choroidal capillaries. Recent research on the genetic and molecular underpinnings of AMD brings to light several basic molecular pathways and pathophysiological processes that might mediate AMD risk, progression, and/or response to therapy. This review summarizes, in detail, the molecular pathological findings in both humans and animal models, including genetic variations in CFH, CX3CR1, and ARMS2/HtrA1, as well as the role of numerous molecules implicated in inflammation, apoptosis, cholesterol trafficking, angiogenesis, and oxidative stress. PMID:19026761

  7. Radiation Therapy for Neovascular Age-related Macular Degeneration

    SciTech Connect

    Kishan, Amar U.; Modjtahedi, Bobeck S.; Morse, Lawrence S.; Lee, Percy

    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.

  8. Translational strategies in aging and age-related disease.

    PubMed

    Armanios, Mary; de Cabo, Rafael; Mannick, Joan; Partridge, Linda; van Deursen, Jan; Villeda, Saul

    2015-12-01

    Aging is a risk factor for several of the world's most prevalent diseases, including neurodegenerative disorders, cancer, cardiovascular disease and metabolic disease. Although our understanding of the molecular pathways that contribute to the aging process and age-related disease is progressing through the use of model organisms, how to apply this knowledge in the clinic is less clear. In September, Nature Medicine, in collaboration with the Volkswagen Foundation, hosted a conference at the beautiful Herrenhausen Palace in Hannover, Germany with the goal of broadening our understanding of the aging process and its meaning as a 'risk factor' in disease. Here, several of the speakers at that conference answer questions posed by Nature Medicine.

  9. Targeting MAPK Signaling in Age-Related Macular Degeneration

    PubMed Central

    Kyosseva, Svetlana V.

    2016-01-01

    Age-related macular degeneration (AMD) is a major cause of irreversible blindness affecting elderly people in the world. AMD is a complex multifactorial disease associated with demographic, genetics, and environmental risk factors. It is well established that oxidative stress, inflammation, and apoptosis play critical roles in the pathogenesis of AMD. The mitogen-activated protein kinase (MAPK) signaling pathways are activated by diverse extracellular stimuli, including growth factors, mitogens, hormones, cytokines, and different cellular stressors such as oxidative stress. They regulate cell proliferation, differentiation, survival, and apoptosis. This review addresses the novel findings from human and animal studies on the relationship of MAPK signaling with AMD. The use of specific MAPK inhibitors may represent a potential therapeutic target for the treatment of this debilitating eye disease. PMID:27385915

  10. Translational strategies in aging and age-related disease.

    PubMed

    Armanios, Mary; de Cabo, Rafael; Mannick, Joan; Partridge, Linda; van Deursen, Jan; Villeda, Saul

    2015-12-01

    Aging is a risk factor for several of the world's most prevalent diseases, including neurodegenerative disorders, cancer, cardiovascular disease and metabolic disease. Although our understanding of the molecular pathways that contribute to the aging process and age-related disease is progressing through the use of model organisms, how to apply this knowledge in the clinic is less clear. In September, Nature Medicine, in collaboration with the Volkswagen Foundation, hosted a conference at the beautiful Herrenhausen Palace in Hannover, Germany with the goal of broadening our understanding of the aging process and its meaning as a 'risk factor' in disease. Here, several of the speakers at that conference answer questions posed by Nature Medicine. PMID:26646495

  11. Complement factor H polymorphism and age-related macular degeneration.

    PubMed

    Edwards, Albert O; Ritter, Robert; Abel, Kenneth J; Manning, Alisa; Panhuysen, Carolien; Farrer, Lindsay A

    2005-04-15

    Age-related macular degeneration (AMD) is a common, late-onset, and complex trait with multiple risk factors. Concentrating on a region harboring a locus for AMD on 1q25-31, the ARMD1 locus, we tested single-nucleotide polymorphisms for association with AMD in two independent case-control populations. Significant association (P = 4.95 x 10(-10)) was identified within the regulation of complement activation locus and was centered over a tyrosine-402 --> histidine-402 protein polymorphism in the gene encoding complement factor H. Possession of at least one histidine at amino acid position 402 increased the risk of AMD 2.7-fold and may account for 50% of the attributable risk of AMD.

  12. The Neural Consequences of Age-Related Hearing Loss.

    PubMed

    Peelle, Jonathan E; Wingfield, Arthur

    2016-07-01

    During hearing, acoustic signals travel up the ascending auditory pathway from the cochlea to auditory cortex; efferent connections provide descending feedback. In human listeners, although auditory and cognitive processing have sometimes been viewed as separate domains, a growing body of work suggests they are intimately coupled. Here, we review the effects of hearing loss on neural systems supporting spoken language comprehension, beginning with age-related physiological decline. We suggest that listeners recruit domain general executive systems to maintain successful communication when the auditory signal is degraded, but that this compensatory processing has behavioral consequences: even relatively mild levels of hearing loss can lead to cascading cognitive effects that impact perception, comprehension, and memory, leading to increased listening effort during speech comprehension. PMID:27262177

  13. The genetics of age-related macular degeneration.

    PubMed

    Gorin, M B; Breitner, J C; De Jong, P T; Hageman, G S; Klaver, C C; Kuehn, M H; Seddon, J M

    1999-11-01

    Age-related macular degeneration (AMD) is increasingly recognized as a complex genetic disorder in which one or more genes contribute to an individual's susceptibility for developing the condition. Twin and family studies as well as population-based genetic epidemiologic methods have convincingly demonstrated the importance of genetics in AMD, though the extent of heritability, the number of genes involved, and the phenotypic and genetic heterogeneity of the condition remain unresolved. The extent to which other hereditary macular dystrophies such as Stargardts disease, familial radial drusen (malattia leventinese), Best's disease, and peripherin/RDS-related dystrophy are related to AMD remains unclear. Alzheimer's disease, another late onset, heterogeneous degenerative disorder of the central nervous system, offers a valuable model for identifying the issues that confront AMD genetics.

  14. Age-related differences in arithmetic strategy sequential effects.

    PubMed

    Lemaire, Patrick

    2016-03-01

    In this article, I review a series of new findings concerning how age-related changes in strategic variations are modulated by sequential effects. Sequential effects refer to how strategy selection and strategy execution on current problems are influenced by which strategy is used on immediately preceding problems. Two sequential effects during strategy selection (i.e., strategy revisions and strategy perseverations) and during strategy execution (i.e., strategy switch costs and modulations of poorer strategy effects) are presented. I also discuss how these effects change with age during adulthood. These phenomena are important, as they shed light on arithmetic processes and how these processes change with age during adulthood. In particular, they speak to the role of executive control while participants select and execute arithmetic strategies. Finally, I discuss the implications of sequential effects for theories of strategies and of arithmetic.

  15. Age-related macular degeneration and the complement system.

    PubMed

    Khandhadia, S; Cipriani, V; Yates, J R W; Lotery, A J

    2012-02-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. It is a complex multifactorial disease, and despite new advances in treatment, many patients still succumb to visual impairment. The complement pathway has been implicated in the pathogenesis of many diseases, and recently variants in several genes encoding complement pathway proteins have been associated with AMD. Complement proteins have been found in histological specimens of eyes with AMD. Altered levels of both intrinsic complement proteins and activated products have been found in the circulation of patients with AMD. Complement activation may be triggered by oxidative stress, resulting from retinal exposure to incoming light; indeed an inter-play between these two pathological processes seems to exist. Finally, complement inhibitors are currently being evaluated in clinical trials. This article reviews the role of the complement system in AMD, and the potential of complement inhibition in preventing the devastating blindness resulting from this disease.

  16. The Neural Consequences of Age-Related Hearing Loss.

    PubMed

    Peelle, Jonathan E; Wingfield, Arthur

    2016-07-01

    During hearing, acoustic signals travel up the ascending auditory pathway from the cochlea to auditory cortex; efferent connections provide descending feedback. In human listeners, although auditory and cognitive processing have sometimes been viewed as separate domains, a growing body of work suggests they are intimately coupled. Here, we review the effects of hearing loss on neural systems supporting spoken language comprehension, beginning with age-related physiological decline. We suggest that listeners recruit domain general executive systems to maintain successful communication when the auditory signal is degraded, but that this compensatory processing has behavioral consequences: even relatively mild levels of hearing loss can lead to cascading cognitive effects that impact perception, comprehension, and memory, leading to increased listening effort during speech comprehension.

  17. Growth Hormone Induces Recurrence of Infantile Hemangiomas After Apparent Involution: Evidence of Growth Hormone Receptors in Infantile Hemangioma.

    PubMed

    Munabi, Naikhoba C O; Tan, Qian Kun; Garzon, Maria C; Behr, Gerald G; Shawber, Carrie J; Wu, June K

    2015-01-01

    Infantile hemangiomas (IHs) are the most common benign tumor of infancy, characterized by a natural history of early proliferation in the first months of life to eventual involution during childhood, often with residual fibrofatty tissue. Once involution has been achieved, IHs do not typically recur. We present two cases of exogenous growth hormone therapy resulting in the recurrence of IHs in late childhood, supported by radiological, immunohistochemical, in vitro, and in vivo evidence.

  18. Dietary folate improves age-related decreases in lymphocyte function.

    PubMed

    Field, Catherine J; Van Aerde, Arne; Drager, Kelly L; Goruk, Susan; Basu, Tapan

    2006-01-01

    Although low folate status is thought to be fairly common in the older population, its implication on immunity has not been adequately investigated. Using 11-month-old and 23-month-old male rats (Fisher 344), the present study was undertaken to examine the modifying effects of feeding a control diet (NIH-07) supplemented with folate (35.7 mg/kg) for 3 weeks on the immune cells of spleen and mesenteric lymph node (MLN) origin. The serum concentrations of folate along with vitamin B(12) were elevated in response to the folate supplementation (P<.05). These results were accompanied by an improved proliferative response (stimulation index) to mitogens in both the spleen and MLNs (P<.05). The proportion of T cells in the MLNs, but not in the spleen, was significantly increased in rats fed a diet supplemented with folate. In the spleen, the folate-supplemented diet prevented the age-associated decrease (P<.05) in the production of interferon (IFN)alpha by unstimulated cells and the decrease in T-helper (Th)1/Th2-type response after stimulation with phorbol myristate acetate and ionomycin. In the MLNs, on the other hand, the folate-supplemented diet failed to influence any age-related increase in interleukin (IL)-2, tumor necrosis factor alpha and IFNgamma following stimulation but did result in a significantly increased production of IL-4 (P<.05). Overall, this study provides data suggesting that aging is associated with changes in the proportion of T cells, the ability of immune cells to proliferate and the production of cytokines after stimulation. Supplementing a folate-sufficient diet with additional folate improves proliferative response to mitogens, the distribution of T cells in the MLNs and the age-related changes in cytokine production in the spleen. These results suggest that the dietary folate requirement may be higher in the older population than in the younger population to support immune functions.

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

    PubMed

    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. PMID:26973593

  20. Age-related macular degeneration: Evidence of a major gene

    SciTech Connect

    Bhatt, S.; Warren, C.; Yang, H.

    1994-09-01

    Age-related macular degeneration is a major cause of blindness in developing countries. It remains a very poorly understood disorder. Although environmental and genetic factors have been implicated in its pathogenesis, none have been firmly implicated. The purpose of this study was to use pedigree analysis to evaluate the possible role of a major gene as a determinant of familial aggregation. Information was collected regarding occupation, smoking, sun exposure, associated medical problems and family history. 50 probands with age-related macular degeneration (ARMD) and 39 age, race and sex-matched controls were included in the study. In the ARMD group 15/50 (30%) of probands reported a positive family history; 22 out of 222 first degree relatives over age 60 were reported to be affected. In the control groups, none of the 138 first degree relatives over age 50 had a history of ARMD. This difference is statistically significant (p = 0.0003), indicating that genetic factors may play an important role in the pathogenesis of ARMD. In the ARMD group more siblings as compared to parents (16/127 vs. 5/82) were affected. 5/50 (10%) of the ARMD probands also gave a history of a second degree relative affected with ARMD, compared to none known among the relatives of controls. Data from 50 pedigrees were analyzed by complex segregation analysis under a class A regressive logistic model using the REGD program implemented in the SAGE package. Preliminary results allow rejection of a polygenic model and suggest there is a major gene for ARMD in these families. The inheritance model most compatible with the observed familial aggregation is autosomal recessive. In conclusion, these results are suggestive of a major gene effect in the etiology of ARMD. Identification of a major gene effect is a first step to further pursue linkage analysis and to search for the gene(s) involved in the causation of ARMD.

  1. Age-related vascular stiffening: causes and consequences

    PubMed Central

    Kohn, Julie C.; Lampi, Marsha C.; Reinhart-King, Cynthia A.

    2015-01-01

    Arterial stiffening occurs with age and is closely associated with the progression of cardiovascular disease. Stiffening is most often studied at the level of the whole vessel because increased stiffness of the large arteries can impose increased strain on the heart leading to heart failure. Interestingly, however, recent evidence suggests that the impact of increased vessel stiffening extends beyond the tissue scale and can also have deleterious microscale effects on cellular function. Altered extracellular matrix (ECM) architecture has been recognized as a key component of the pre-atherogenic state. Here, the underlying causes of age-related vessel stiffening are discussed, focusing on age-related crosslinking of the ECM proteins as well as through increased matrix deposition. Methods to measure vessel stiffening at both the macro- and microscale are described, spanning from the pulse wave velocity measurements performed clinically to microscale measurements performed largely in research laboratories. Additionally, recent work investigating how arterial stiffness and the changes in the ECM associated with stiffening contributed to endothelial dysfunction will be reviewed. We will highlight how changes in ECM protein composition contribute to atherosclerosis in the vessel wall. Lastly, we will discuss very recent work that demonstrates endothelial cells (ECs) are mechano-sensitive to arterial stiffening, where changes in stiffness can directly impact EC health. Overall, recent studies suggest that stiffening is an important clinical target not only because of potential deleterious effects on the heart but also because it promotes cellular level dysfunction in the vessel wall, contributing to a pathological atherosclerotic state. PMID:25926844

  2. Genetic risk factors and age-related macular degeneration (AMD)

    PubMed Central

    Mousavi, Maryam; Armstrong, Richard A.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of blindness in individuals older than 65 years of age. It is a multifactorial disorder and identification of risk factors enables individuals to make lifestyle choices that may reduce the risk of disease. Collaboration between geneticists, ophthalmologists, and optometrists suggests that genetic risk factors play a more significant role in AMD than previously thought. The most important genes are associated with immune system modulation and the complement system, e.g., complement factor H (CFH), factor B (CFB), factor C3, and serpin peptidase inhibitor (SERPING1). Genes associated with membrane transport, e.g., ATP-binding cassette protein (ABCR) and voltage-dependent calcium channel gamma 3 (CACNG3), the vascular system, e.g., fibroblast growth factor 2 (FGF2), fibulin-5, lysyl oxidase-like gene (LOXL1) and selectin-P (SELP), and with lipid metabolism, e.g., apolipoprotein E (APOE) and hepatic lipase (LIPC) have also been implicated. In addition, several other genes exhibit some statistical association with AMD, e.g., age-related maculopathy susceptibility protein 2 (ARMS2) and DNA excision repair protein gene (ERCC6) but more research is needed to establish their significance. Modifiable risk factors for AMD should be discussed with patients whose lifestyle and/or family history place them in an increased risk category. Furthermore, calculation of AMD risk using current models should be recommended as a tool for patient education. It is likely that AMD management in future will be increasingly influenced by assessment of genetic risk as such screening methods become more widely available.

  3. Age-related modifications in neural cardiovascular control.

    PubMed

    Ferrari, A U

    1992-09-01

    Integrated cardiovascular responses to a range of different stimuli, as well as the overall, spontaneously occurring variability in blood pressure and heart rate, undergo complex changes with aging. A general trend is that homeostatic control mechanisms lose part of their ability to modulate heart rate and to buffer the concomitant blood pressure variations; the two phenomena are possibly linked by a cause-effect relationship. A detailed analysis of the age-related changes in the major reflex systems reveals a clear-cut impairment in arterial baroreceptor control of the heart rate, but much less pronounced changes in its control of blood pressure, on the other hand, both the hemodynamic and humoral components of the cardiopulmonary reflex appear to be markedly attenuated. The experimental evidence of the mechanisms underlying these changes is still largely incomplete, and it appears that the gaps will have to be filled by a systematic, detailed analysis, i.e., that no generalizations or extrapolations will be possible. Indeed, the data available so far indicate that the age-related alterations are highly non-uniform, some functions undergoing a definite impairment but others being much better preserved and some being even enhanced; thus aging is by no means associated with a generalized decline in cardiovascular functions and should instead be viewed as a complex, highly selective process. These peculiar biological features of the aging phenomena merit further investigation in both the cardiovascular and the other organ systems, in order to verify the possibility that currently unrecognized homeostatic potentials in the elderly subject may be exploited to advance his/her clinical management in health and disease.

  4. Age-Related Neurochemical Changes in the Vestibular Nuclei

    PubMed Central

    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. PMID:26973593

  5. Age-Related Tissue Stiffening: Cause and Effect

    PubMed Central

    Sherratt, Michael J.

    2013-01-01

    Significance Tissue elasticity is severely compromised in aging skin, lungs, and blood vessels. In the vascular and pulmonary systems, respectively, loss of mechanical function is linked to hypertension, which in turn is a risk factor for heart and renal failure, stroke, and aortic aneurysms, and to an increased risk of mortality as a result of acute lung infections. Recent Advances Although cellular mechanisms were thought to play an important role in mediating tissue aging, the reason for the apparent sensitivity of elastic fibers to age-related degradation remained unclear. We have recently demonstrated that compared with type I collagen, a key component of the elastic fiber system, the cysteine-rich fibrillin microfibril is highly susceptible to direct UV exposure in a cell-free environment. We hypothesized therefore that, as a consequence of both their remarkable longevity and cysteine-rich composition, many elastic fiber-associated components will be susceptible to the accumulation of damage by both direct UV radiation and reactive oxygen species-mediated oxidation. Critical Issues Although elastic fiber remodeling is a common feature of aging dynamic tissues, the inaccessibility of most human tissues has hampered attempts to define the molecular causes. Clinical Care Relevance Although, currently, the localized repair of damaged elastic fibers may be effected by the topical application of retinoids and some cosmetic products, future studies may extend the application of systemic transforming growth factor β antagonists, which can prevent cardiovascular remodeling in murine Marfan syndrome, to aging humans. Acellular mechanisms may be key mediators of elastic fiber remodeling and hence age-related tissue stiffening. PMID:24527318

  6. [Quantitative histoenzymatic analysis of the adenohypophysis and adrenal cortex during the early stages of involution].

    PubMed

    Prochukhanov, R A; Rostovtseva, T I

    1977-11-01

    A method of quantitative histenzymatic analysis was applied for determination of the involution changes of the neuroendocrine system. The activity of NAD- and NADP-reductases, acid and alkaline phosphatases, glucose-6-phosphoric dehydrogenase, 3-OH-steroid-dehydrogenase, 11-hydroxysteroid dehydrogenases was investigated in the adenohypophysis and in the adrenal cortex of rats aged 4 and 12 months. There were revealed peculiarities attending the structural-metabolic provision of physiological reconstructions of the neuro-endocrine system under conditions of the estral cycle at the early involution stages. An initial reduction of the cell ular-vascular transport with the retention of the functional activity of the intracellular organoids was demonstrated in ageing animals.

  7. [Functional morphology of the submandibular salivary glands of white rats during aging involution].

    PubMed

    Rybakova, M G

    1979-12-01

    Functional morphology of different zones of submandibular glands of albino rats was studied quantitatively with due regard for the stages of neuroendocrine system involution. It is shown that function of salivary glands during ageing is not altered; cyclic fluctuations with estral cycle phases are maintained similarly to those in young animals. But the basal level of proteins and mucopolysaccharides is reduced, their mean levels being equal to the minimal level in young animals. On the other hand, activation of enzymes responsible for energy and transport processes takes place and their relationships change. The data obtained prove the relationship between salivary and endocrine glands and confirm the viewpoint that in early age involution disintegration occurs between different parameters of the functional activity of salivary glands rather than there take place changes in their function.

  8. Tailoring lighting reflectors to prescribed illuminance distributions: compact partial-involute designs.

    PubMed

    Ong, P T; Gordon, J M; Rabl, A

    1995-12-01

    Reflectors for lighting can be tailored to produce the desired flux maps (illuminance distributions) precisely, from extended light sources, with a calculational procedure called tailored edge-ray designs (TED's). We generalize the TED procedure, which has so far been developed only for flat sources, to tubular sources within partial-involute reflectors. The governing differential equations for the reflectors are solved analytically. We present specific results for the practical problem of producing uniform far-field illuminance in symmetric two-dimensional luminaires. It is demonstrated that, relative to flat-source TED's, these new designs can offer increased uniform core regions, more compact reflectors, and better glare control. We offer a comprehensive analysis of the flux map and geometric properties of partial-involute TED's. Further improvements are possible with hybrid combinations, as we illustrate with several design examples.

  9. Face Gear Drive with Spur Involute Pinion: Geometry, Generation by a Worm, Stress Analysis

    NASA Technical Reports Server (NTRS)

    Litvin, Faydor L.; Fuentes, Alfonso; Zanzi, Claudio; Pontiggia, Matteo; Handschuh, Robert F. (Technical Monitor)

    2002-01-01

    A face gear drive with a spur involute pinion is considered. The generation of the face gear is based on application of a grinding or cutting worm whereas the conventional method of generation is based on application of an involute shaper. An analytical approach is proposed for the determination of: (1) the worm thread surface; (2) avoidance of singularities of the worm thread surface, (air) dressing of the worm; and (3) determination of stresses of the face-gear drive. A computer program for simulation of meshing and contact of the pinion and face-gear has been developed. Correction of machine-tool settings is proposed for reduction of the shift of the bearing contact caused by misalignment. An automatic development of the model of five contacting teeth has been proposed for stress analysis. Numerical examples for illustration of the developed theory are provided.

  10. ZnT2 is a critical mediator of lysosomal-mediated cell death during early mammary gland involution

    PubMed Central

    Hennigar, Stephen R.; Seo, Young Ah; Sharma, Supriya; Soybel, David I.; Kelleher, Shannon L.

    2015-01-01

    Mammary gland involution is the most dramatic example of physiological cell death. It occurs through an initial phase of lysosomal-mediated cell death (LCD) followed by mitochondrial-mediated apoptosis. Zinc (Zn) activates both LCD and apoptosis in vitro. The Zn transporter ZnT2 imports Zn into vesicles and mitochondria and ZnT2-overexpression activates cell death in mammary epithelial cells (MECs). We tested the hypothesis that ZnT2-mediated Zn transport is critical for mammary gland involution in mice. Following weaning, ZnT2 abundance increased in lysosomes and mitochondria, which paralleled Zn accumulation in each of these organelles. Adenoviral expression of ZnT2 in lactating mouse mammary glands in vivo increased Zn in lysosomes and mitochondria and activated LCD and apoptosis, promoting a profound reduction in MECs and alveoli. Injection of TNFα, a potent activator of early involution, into the mammary gland fat pads of lactating mice increased ZnT2 and Zn in lysosomes and activated premature involution. Exposure of cultured MECs to TNFα redistributed ZnT2 to lysosomes and increased lysosomal Zn, which activated lysosomal swelling, cathepsin B release, and LCD. Our data implicate ZnT2 as a critical mediator of cell death during involution and importantly, that as an initial involution signal, TNFα redistributes ZnT2 to lysosomes to activate LCD. PMID:25620235

  11. Spontaneous involution of keratoacanthoma, iconographic documentation and similarity with volcanoes of nature.

    PubMed

    Enei Gahona, Maria Leonor; Machado Filho, Carlos d' Aparecida Santos

    2012-01-01

    Through iconography, we show a case of keratoacanthoma (KA) on the nasal dorsum at two different stages of evolution (maturation and regression) and its similarity with images of the Mount St. Helens volcano and the Orcus Patera crater. Using these illustrations, we highlight why the crateriform aspect of this tumor is included in its classic clinical description. Moreover, we photographically documented the self-involuting tendency of KA, an aspect that is seldom documented in the literature.

  12. Analysis of human breast milk cells: gene expression profiles during pregnancy, lactation, involution, and mastitic infection.

    PubMed

    Sharp, Julie A; Lefèvre, Christophe; Watt, Ashalyn; Nicholas, Kevin R

    2016-05-01

    The molecular processes underlying human milk production and the effects of mastitic infection are largely unknown because of limitations in obtaining tissue samples. Determination of gene expression in normal lactating women would be a significant step toward understanding why some women display poor lactation outcomes. Here, we demonstrate the utility of RNA obtained directly from human milk cells to detect mammary epithelial cell (MEC)-specific gene expression. Milk cell RNA was collected from five time points (24 h prepartum during the colostrum period, midlactation, two involutions, and during a bout of mastitis) in addition to an involution series comprising three time points. Gene expression profiles were determined by use of human Affymetrix arrays. Milk cells collected during milk production showed that the most highly expressed genes were involved in milk synthesis (e.g., CEL, OLAH, FOLR1, BTN1A1, and ARG2), while milk cells collected during involution showed a significant downregulation of milk synthesis genes and activation of involution associated genes (e.g., STAT3, NF-kB, IRF5, and IRF7). Milk cells collected during mastitic infection revealed regulation of a unique set of genes specific to this disease state, while maintaining regulation of milk synthesis genes. Use of conventional epithelial cell markers was used to determine the population of MECs within each sample. This paper is the first to describe the milk cell transcriptome across the human lactation cycle and during mastitic infection, providing valuable insight into gene expression of the human mammary gland. PMID:26909879

  13. Cleavage of Histone 3 by Cathepsin D in the Involuting Mammary Gland

    PubMed Central

    Khalkhali-Ellis, Zhila; Goossens, William; Margaryan, Naira V.; Hendrix, Mary J. C.

    2014-01-01

    The post-lactational regression of mammary gland is a complex multi-step process designed to conserve the biological function of the gland for next pregnancy. This developmental stage is a biological intrigue with great relevance to breast cancer research, and thus has been the subject of intensive scrutiny. Multipronged studies (microarray, proteomics profiling, animal knock-out models) have provided a repertoire of genes critical to involution. However, the caveat of these approaches remains in their failure to reveal post-translational modification(s), an emerging and critical aspect of gene regulation in developmental processes and mammary gland remodeling. The massive surge in the lysosomal enzymes concurrent with the onset of involution has been known for decades, and considered essential for “clearance” purposes. However, functional significance of these enzymes in diverse biological processes distinct from their proteolytic activity is just emerging. Studies from our laboratory had indicated specific post-translational modifications of the aspartyl endopeptidase Cathepsin D (CatD) at distinct stages mammary gland development. This study addresses the biological significance of these modifications in the involution process, and reveals that post-translational modifications drive CatD into the nucleus to cleave Histone 3. The cleavage of Histone 3 has been associated with cellular differentiation and could be critical instigator of involution process. From functional perspective, deregulated expression and increased secretion of CatD are associated with aggressive and metastatic phenotype of breast cancer. Thus unraveling CatD’s physiological functions in mammary gland development will bridge the present gap in understanding its pro-tumorigenic/metastatic functions, and assist in the generation of tailored therapeutic approaches. PMID:25054204

  14. Thymic epithelial cells: working class heroes for T cell development and repertoire selection.

    PubMed

    Anderson, Graham; Takahama, Yousuke

    2012-06-01

    The thymus represents an epithelial-mesenchymal tissue, anatomically structured into discrete cortical and medullary regions that contain phenotypically and functionally distinct stromal cells, as well as thymocytes at defined stages of maturation. The stepwise progression of thymocyte development seems to require serial migration through these distinct thymic regions, where interactions with cortical thymic epithelial cell (cTEC) and medullary thymic epithelial cell (mTEC) subsets take place. Recent work on TEC subsets provides insight into T cell development and selection, such as the importance of tumour necrosis factor (TNF) receptor superfamily members in thymus medulla development, and the specialised antigen processing/presentation capacity of the thymic cortex for positive selection. Here, we summarise current knowledge on the development and function of the thymic microenvironment, paying particular attention to the cortical and medullary epithelial compartments.

  15. Human thymic epithelial primary cells produce exosomes carrying tissue-restricted antigens.

    PubMed

    Skogberg, Gabriel; Lundberg, Vanja; Berglund, Martin; Gudmundsdottir, Judith; Telemo, Esbjörn; Lindgren, Susanne; Ekwall, Olov

    2015-09-01

    Exosomes are nano-sized vesicles released by cells into the extracellular space and have been shown to be present in thymic tissue both in mice and in humans. The source of thymic exosomes is however still an enigma and hence it is not known whether thymic epithelial cells (TECs) are able to produce exosomes. In this work, we have cultured human TECs and isolated exosomes. These exosomes carry tissue-restricted antigens (TRAs), for example, myelin basic protein and desmoglein 3. The presence of TRAs indicates a possible role for thymic epithelium-derived exosomes in the selection process of thymocytes. The key contribution of these exosomes could be to disseminate self-antigens from the thymic epithelia, thus making them more accessible to the pool of maturing thymocytes. This would increase the coverage of TRAs within the thymus, and facilitate the process of positive and negative selection.

  16. Prognostic value of preoperative serum lactate dehydrogenase in thymic carcinoma

    PubMed Central

    Yuan, Zu-Yang; Gao, Shu-Geng; Mu, Ju-Wei; Xue, Qi; Mao, You-Sheng; Wang, Da-Li; Zhao, Jun; Gao, Yu-Shun; Huang, Jin-Feng

    2016-01-01

    Background The prognostic value of serum lactate dehydrogenase (LDH) has been demonstrated in various solid tumors. We attempted to determine whether serum LDH was predictive of survival in thymic carcinoma after surgical resection. Methods Ninety-five patients with thymic carcinoma treated in our hospital between January 2005 and December 2015 were retrospectively enrolled. Serum LDH was measured before surgery and categorized as low or high relative to the upper limit of normal (ULN) (225 U/L). The relationships of serum LDH level and other clinical variables with survival were estimated by Cox regression and Kaplan-Meier survival analysis. Results Serum LDH levels were found to be significantly associated with overall survival (OS) and progression-free survival (PFS) of these patients. The 1-, 3-, and 5-year PFS were 76%, 51%, and 38%, and the 1-, 3- and 5-year OS were 97%, 75%, and 46%, respectively. Univariate analysis found that high serum LDH (>225 U/L) was associated with both lower OS [hazard ratio (HR) =2.710; 95% confidence interval (CI): 1.363–1.5.391; P=0.004] and PFS (HR =3.365; 95% CI: 1.776–6.374; P<0.001). Multivariate analysis found that high serum LDH was associated with lower PFS (HR =2.122; 95% CI: 1.056–4.267; P=0.035). Moreover, high LDH was significantly associated with advanced Masaoka stage (P=0.001). Conclusions High serum LDH (>225 U/L) was an independent predictor of decreased PFS in thymic carcinoma patients. It was also significantly associated with reduced OS, but was not an independent predictor of death in those patients. PMID:27746998

  17. Detection of Human Polyomavirus 7 in human thymic epithelial tumors

    PubMed Central

    Rennspiess, Dorit; Pujari, Sreedhar; Keijzers, Marlies; Abdul-Hamid, Myrurgia A.; Hochstenbag, Monique; Dingemans, Anne-Marie; Kurz, Anna Kordelia; Speel, Ernst-Jan; Haugg, Anke; Pastrana, Diana V.; Buck, Christopher B.; De Baets, Marc H.; zur Hausen, Axel

    2014-01-01

    Introduction Although the molecular genetics possibly underlying the pathogenesis of human thymoma have been extensively studied, its etiology remains poorly understood. Since murine polyomavirus consistently induces thymomas in mice, we assessed the presence of the novel human polyomavirus 7 (HPyV7) in human thymic epithelial tumors. Methods HPyV7-DNA Fluorescence in situ hybridization (FISH), DNA-PCR and immuno-histochemistry (IHC) were performed in 37 thymomas. Of these, 26 were previously diagnosed with myasthenia gravis (MG). In addition, 20 thymic hyperplasias and 20 fetal thymic tissues were tested. Results HPyV7-FISH revealed specific nuclear hybridization signals within the neoplastic epithelial cells of 23 thymomas (62.2%). With some exceptions, the HPyV7-FISH data correlated with the HPyV7-DNA PCR. By IHC large T antigen (LTAg) expression of HPyV7 was detected, and double staining confirmed its expression in the neoplastic epithelial cells. Eighteen of the 26 MG-positive and 7 of the 11 MG-negative thymomas were HPyV7-positive. 40% of the 20 hyperplastic thymi were HPyV7-positive by PCR as confirmed by FISH and IHC in the follicular lymphocytes. All 20 fetal thymi tested HPyV7-negative. Conclusions The presence of HPyV7-DNA and LTAg expression in the majority of thymomas possibly link HPyV7 to human thymomagenesis. Further investigations are needed to elucidate the possible associations of HPyV7 and MG. PMID:25526237

  18. Cholinergic epithelial cell with chemosensory traits in murine thymic medulla.

    PubMed

    Panneck, Alexandra Regina; Rafiq, Amir; Schütz, Burkhard; Soultanova, Aichurek; Deckmann, Klaus; Chubanov, Vladimir; Gudermann, Thomas; Weihe, Eberhard; Krasteva-Christ, Gabriela; Grau, Veronika; del Rey, Adriana; Kummer, Wolfgang

    2014-12-01

    Specialized epithelial cells with a tuft of apical microvilli ("brush cells") sense luminal content and initiate protective reflexes in response to potentially harmful substances. They utilize the canonical taste transduction cascade to detect "bitter" substances such as bacterial quorum-sensing molecules. In the respiratory tract, most of these cells are cholinergic and are approached by cholinoceptive sensory nerve fibers. Utilizing two different reporter mouse strains for the expression of choline acetyltransferase (ChAT), we observed intense labeling of a subset of thymic medullary cells. ChAT expression was confirmed by in situ hybridization. These cells showed expression of villin, a brush cell marker protein, and ultrastructurally exhibited lateral microvilli. They did not express neuroendocrine (chromogranin A, PGP9.5) or thymocyte (CD3) markers but rather thymic epithelial (CK8, CK18) markers and were immunoreactive for components of the taste transduction cascade such as Gα-gustducin, transient receptor potential melastatin-like subtype 5 channel (TRPM5), and phospholipase Cβ2. Reverse transcription and polymerase chain reaction confirmed the expression of Gα-gustducin, TRPM5, and phospholipase Cβ2. Thymic "cholinergic chemosensory cells" were often in direct contact with medullary epithelial cells expressing the nicotinic acetylcholine receptor subunit α3. These cells have recently been identified as terminally differentiated epithelial cells (Hassall's corpuscle-like structures in mice). Contacts with nerve fibers (identified by PGP9.5 and CGRP antibodies), however, were not observed. Our data identify, in the thymus, a previously unrecognized presumptive chemosensitive cell that probably utilizes acetylcholine for paracrine signaling. This cell might participate in intrathymic infection-sensing mechanisms.

  19. Prognostic value of immunohistochemical markers in malignant thymic epithelial tumors

    PubMed Central

    Leisibach, Priska; Schneiter, Didier; Soltermann, Alex; Yamada, Yoshi; Weder, Walter

    2016-01-01

    Background Thymic epithelial tumors (TET) are rare neoplasms with inconsistent treatment strategies. When researching for molecular pathways to find new therapies, the correlation between specific molecular markers and outcome has only rarely been investigated. The aim of this study was to investigate the correlation between survival, metastatic potential and invasiveness of aggressive subtypes of TET and immunohistochemical markers. Methods Overall survival (OS), disease-free survival (DFS), progression-free survival (PFS) and metastasis-free survival (MFS) of patients with WHO type B2/B3 mixed type thymoma (MT), thymoma type B3 (B3) and thymic carcinoma (TC), undergoing surgery [1998–2013] were determined. Tumor specimens were stained using a tissue microarray (TMA) (CD117, CD5, p63, p40, p21, p27, p53, Bcl-2, Ki67, podoplanin, synaptophysin, PTEN and Pax8). Invasive behavior of primary tumors and the presence of extrathoracic metastases were assessed. Results We found in 23 patients included into this study (four MT, ten B3, nine TC) that (I) p21 expression in the cytoplasm significantly correlated with a decrease of OS (P=0.016), PFS (P=0.034) and MFS (P=0.005); (II) MFS was significantly shorter when the combination of p21-low p27-low p53-high was present (P=0.029); and (III) nuclear p27 (P=0.042), Ki-67 (P=0.024) and podoplanin (P=0.05) expression correlated with the presence of extrathoracic metastases. Conclusions The main finding of this study is that cytoplasmic p21 expression negatively influences the outcome of malignant TETs and correlates with metastatic activity. Additionally, selected immunohistochemical markers correlate with the distant metastatic potential of TETs. These results may contribute to the stratification of diagnosis and improvement of treatment strategies for thymic malignancies. PMID:27747012

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

    PubMed Central

    Prada, Nicole; Nasi, Milena; Troiano, Leonarda; Roat, Erika; Pinti, Marcello; Nemes, Elisa; Lugli, Enrico; Ferraresi, Roberta; Ciacci, Luigi; Bertoni, Davide; Biagioni, Ornella; Gibertoni, Milena; Cornia, Cristina; Meschiari, Liviana; Gramazio, Elisabetta; Mariotti, Mauro; Consolo, Ugo; Balli, Fiorella; Cossarizza, Andrea

    2005-01-01

    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. PMID:15715912

  1. Progress on retinal image analysis for age related macular degeneration.

    PubMed

    Kanagasingam, Yogesan; Bhuiyan, Alauddin; Abràmoff, Michael D; Smith, R Theodore; Goldschmidt, Leonard; Wong, Tien Y

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in those over the age of 50 years in the developed countries. The number is expected to increase by ∼1.5 fold over the next ten years due to an increase in aging population. One of the main measures of AMD severity is the analysis of drusen, pigmentary abnormalities, geographic atrophy (GA) and choroidal neovascularization (CNV) from imaging based on color fundus photograph, optical coherence tomography (OCT) and other imaging modalities. Each of these imaging modalities has strengths and weaknesses for extracting individual AMD pathology and different imaging techniques are used in combination for capturing and/or quantification of different pathologies. Current dry AMD treatments cannot cure or reverse vision loss. However, the Age-Related Eye Disease Study (AREDS) showed that specific anti-oxidant vitamin supplementation reduces the risk of progression from intermediate stages (defined as the presence of either many medium-sized drusen or one or more large drusen) to late AMD which allows for preventative strategies in properly identified patients. Thus identification of people with early stage AMD is important to design and implement preventative strategies for late AMD, and determine their cost-effectiveness. A mass screening facility with teleophthalmology or telemedicine in combination with computer-aided analysis for large rural-based communities may identify more individuals suitable for early stage AMD prevention. In this review, we discuss different imaging modalities that are currently being considered or used for screening AMD. In addition, we look into various automated and semi-automated computer-aided grading systems and related retinal image analysis techniques for drusen, geographic atrophy and choroidal neovascularization detection and/or quantification for measurement of AMD severity using these imaging modalities. We also review the existing telemedicine studies which

  2. Age-related changes in deformability of human erythrocytes.

    PubMed

    Sutera, S P; Gardner, R A; Boylan, C W; Carroll, G L; Chang, K C; Marvel, J S; Kilo, C; Gonen, B; Williamson, J R

    1985-02-01

    The present study was designed to further the characterization of age-related changes in the deformability of human erythrocytes. The top (approximately young) and bottom (approximately old) 10% fractions of density-separated red cells from ten normal donors were subjected to graded levels of shear stress in a rheoscope. Measurements were made of steady-state elongation (cells tank treading in a state of dynamic equilibrium) and the time course of shape recovery following abrupt cessation of shear. In parallel with the rheologic experiments, several physical and chemical properties were assayed to determine correlates of mechanical properties. These included mean cell volume, mean corpuscular hemoglobin concentration, type A1 hemoglobin, glucosylation of membrane proteins, and membrane phospholipid and protein concentration. The microrheologic observations revealed that only about 90% of the old cells retained their capacity to tank tread. However, the tank-treading cells elongated less than their younger counterparts at corresponding levels of shear stress, thus demonstrating a reduced level of deformability. Further analysis of the data indicates that increases in membrane viscosity and elastic modulus along with a significant loss in excess surface area contribute to the limitation of the ability of the older cells to change shape.

  3. Aging-related differences in chondrocyte viscoelastic properties.

    PubMed

    Steklov, Nikolai; Srivastava, Ajay; Sung, K L P; Chen, Peter C; Lotz, Martin K; D'Lima, Darryl D

    2009-06-01

    The biomechanical properties of articular cartilage change profoundly with aging. These changes have been linked with increased potential for cartilage degeneration and osteoarthritis. However, less is known about the change in biomechanical properties of chondrocytes with increasing age. Cell stiffness can affect mechanotransduction pathways and may alter cell function. We measured aging-related changes in the biomechanical properties of chondrocytes. Human chondrocytes were isolated from knee articular cartilage within 48 hours after death or from osteochondral specimens obtained from knee arthroplasty. Cells were divided into two age groups: between 18 and 35 years (18 - 35); and greater than 55 years (55+) of age. The 55+ group was further subdivided based on visual grade of osteoarthritis: normal (N) or osteoarthritic (OA). The viscoelastic properties of the cell were measured using the previously described micropipette cell aspiration technique. The equilibrium modulus, instantaneous modulus, and apparent viscosity were significantly higher in the 55+ year age group than in the 18 - 35 age group. On the other hand, no differences were found in the equilibrium modulus, instantaneous modulus, or apparent viscosity between the N and OA groups. The increase in cell stiffness can be attributed to altered mechanical properties of the cell membrane, the cytoplasm, or the cytoskeleton. Increased stiffness has been reported in osteoarthritic chondrocytes, which in turn has been attributed to the actin cytoskeleton. A similar mechanism may be responsible for our finding of increased stiffness in aging chondrocytes. With advancing age, changes in the biomechanical properties of the cell could alter molecular and biochemical responses.

  4. Age-Related Macular Degeneration: A Scientometric Analysis

    PubMed Central

    Ramin, Shahrokh; Soheilian, Masoud; Habibi, Gholamreza; Ghazavi, Roghayeh; Gharebaghi, Reza; Heidary, Fatemeh

    2015-01-01

    Age-related macular degeneration (ARMD) is a major cause of central blindness among working aged adults across the world. Systematic research planning on any subject, including ARMD is in need of solid data regarding previous efforts in this field and to identify the gaps in the research. This study aimed to elucidate the most important trends, directions, and gap in this subject. The data extracted from the Institute for Scientific Information were used to perform a bibliometric analysis of the scientific productions (1993–2013) about ARMD. Specific parameters related to ARMD were analyzed to obtain a view of the topic’s structure, history, and document relationships. Additionally, the trends and authors in the most influential publications were analyzed. The number of articles in this field was found constantly increasing. Most highly cited articles addressed genetic epidemiology and clinical research topics in this field. During the past 3 years, there has been a trend toward biomarker research. Through performing the first scientometric survey on ARMD research, we analyzed the characteristics of papers and the trends in scientific production. We also identified some of the critical gaps in the current research efforts that would help in large-scale research strategic planning. PMID:26060829

  5. Promising new treatments for neovascular age-related macular degeneration.

    PubMed

    Michels, Stephan; Schmidt-Erfurth, Ursula; Rosenfeld, Philip J

    2006-07-01

    Angiogenesis, the growth of new blood vessels from existing blood vessels, is responsible for vision loss in a variety of ophthalmic diseases. In neovascular age-related macular degeneration (AMD), the leading cause for legal blindness in many industrialised countries, abnormal blood vessels grow in the macula and cause blindness. There are a number of factors important in the angiogenic cascade but VEGF-A has been implicated in recent years as the major factor responsible for neovascular and exudative diseases of the eye. Numerous antiangiogenic drugs are in development but anti-VEGF drugs have shown great promise in treating neovascular AMD and other ocular diseases, and many of these drugs have been adopted from oncology where antiangiogenic therapy is gaining wide acceptance. For the first time in neovascular AMD, anti-VEGF drugs have brought the hope of vision improvement to a significant proportion of patients. This review provides an overview on angiogenic mechanisms, potential antiangiogenic treatment strategies and different antiangiogenic drugs with special focus on neovascular AMD.

  6. Radiation therapy for neovascular age-related macular degeneration

    PubMed Central

    Petrarca, Robert; Jackson, Timothy L

    2011-01-01

    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. PMID:21311657

  7. Review of nutrient actions on age-related macular degeneration.

    PubMed

    Zampatti, Stefania; Ricci, Federico; Cusumano, Andrea; Marsella, Luigi Tonino; Novelli, Giuseppe; Giardina, Emiliano

    2014-02-01

    The actions of nutrients and related compounds on age-related macular degeneration (AMD) are explained in this review. The findings from 80 studies published since 2003 on the association between diet and supplements in AMD were reviewed. Antioxidants and other nutrients with an effect on AMD susceptibility include carotenoids (lutein and zeaxanthin, β-carotene), vitamins (vitamin A, E, C, D, B), mineral supplements (zinc, copper, selenium), dietary fatty acids [monounsaturated fatty acids, polyunsaturated fatty acids (PUFA both omega-3 PUFA and omega-6 PUFA), saturated fatty acids and cholesterol], and dietary carbohydrates. The literature revealed that many of these antioxidants and nutrients exert a protective role by functioning synergistically. Specifically, the use of dietary supplements with targeted actions can provide minimal benefits on the onset or progression of AMD; however, this does not appear to be particularly beneficial in healthy people. Furthermore, some supplements or nutrients have demonstrated discordant effects on AMD in some studies. Since intake of dietary supplements, as well as exposure to damaging environmental factors, is largely dependent on population habits (including dietary practices) and geographical localization, an overall healthy diet appears to be the best strategy in reducing the risk of developing AMD. As of now, the precise mechanism of action of certain nutrients in AMD prevention remains unclear. Thus, future studies are required to examine the effects that nutrients have on AMD and to determine which factors are most strongly correlated with reducing the risk of AMD or preventing its progression. PMID:24461310

  8. Age-related changes in skin topography and microcirculation.

    PubMed

    Li, Li; Mac-Mary, Sophie; Marsaut, David; Sainthillier, Jean Marie; Nouveau, Stéphanie; Gharbi, Tijani; de Lacharriere, Olivier; Humbert, Philippe

    2006-03-01

    Skin topography and microvasculature undergo characteristic changes with age. Although several non-invasive bioengineering methods are currently available to measure them quantitatively, few publications have referred to their relationship with age in different anatomical sites. This study was carried out to observe the age-related changes of the skin topography and skin microcirculation. The microrelief was assessed with special processing software from scanning by interference fringe profilometry of silicone replicas performed on two sites (volar forearm and back of hand) on 50 female volunteers (aged 20-74 years who consisted of ten probands in each decade). The superficial vascular network of both sites was assessed by videocapillaroscopy, and the subpapillary vascular plexus was studied with laser Doppler flowmetry. Skin color, which is affected by blood flow, was observed by colorimeter. The skin roughness and the mean height between peak and valley increased with age. There were statistically significant differences between the evaluated sites. This study also shows that the capillary loops in the dermal papillae decrease but the subpapillary plexus increase with age. The interference fringe profilometry associated with videocapillaroscopy may be useful and accurate to measure the efficacy of medical or cosmetic products to delay skin aging.

  9. The Theory Behind the Age-Related Positivity Effect

    PubMed Central

    Reed, Andrew E.; Carstensen, Laura L.

    2012-01-01

    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 and 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. PMID:23060825

  10. The Chromospheric Activity-Age Relation for M Dwarf Stars

    NASA Astrophysics Data System (ADS)

    Silvestri, N. M.; Oswalt, T. D.; Hawley, S. L.

    2000-12-01

    We present preliminary results from our study in which we use moderate resolution spectroscopy to determine the correlation between the chromospheric activity and age of M dwarf stars in wide binary systems. We have observed ~50 M dwarf stars from our sample with the Apache Point Observatory 3.5-m telescope. We measure the ratio of Hα luminosity to the bolometric luminosity (LHα /Lbol) of the M dwarf---a measure of activity that is proven to correlate well with age. This project is unique in that it will extend the chromospheric activity-age relation of low-mass main sequence stars beyond the ages provided by cluster methods. The ages so determined are also independent of the uncertainties in cluster age determinations. The technique has the potential to improve by at least a factor of two the precision and the range over which ages can currently be determined for main sequence stars. Work on this project is supported by the NASA Graduate Student Researchers Program grant NGT-50290 (N.M.S.).

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

    SciTech Connect

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

    1986-03-05

    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 (/sup 3/H)-dexamethasone ((/sup 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 (/sup 3/H)Dex/10/sup 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.

  12. Age-related neural changes in autobiographical remembering and imagining.

    PubMed

    Addis, Donna Rose; Roberts, Reece P; Schacter, Daniel L

    2011-11-01

    Numerous neuroimaging studies have revealed that in young adults, remembering the past and imagining the future engage a common core network. Although it has been observed that older adults engage a similar network during these tasks, it is unclear whether or not they activate this network in a similar manner to young adults. Young and older participants completed two autobiographical tasks (imagining future events and recalling past events) in addition to a semantic-visuospatial control task. Spatiotemporal Partial Least Squares analyses examined whole brain patterns of activity across both the construction and elaboration of autobiographical events. These analyses revealed that that both age groups activated a similar network during the autobiographical tasks. However, some key age-related differences in the activation of this network emerged. During the construction of autobiographical events, older adults showed less activation relative to younger adults, in regions supporting episodic detail such as the medial temporal lobes and the precuneus. Later in the trial, older adults showed differential recruitment of medial and lateral temporal regions supporting the elaboration of autobiographical events, and possibly reflecting an increased role of conceptual information when older adults describe their pasts and their futures.

  13. Parabiosis for the study of age-related chronic disease

    PubMed Central

    Eggel, Alexander; Wyss-Coray, Tony

    2014-01-01

    Summary Modern medicine wields the power to treat large numbers of diseases and injuries most of us would have died from just a hundred years ago. In view of this tremendous achievement, it can seem as if progress has slowed, and we have been unable to impact the most devastating diseases of our time. Chronic diseases of age such as cardiovascular disease, diabetes, osteoarthritis, or Alzheimer’s disease turn out to be of a complexity that may require transformative ideas and paradigms to understand and treat them. Parabiosis, which mimics aspects of the naturally occurring shared blood supply in conjoined twins in humans and certain animals, may just have the power to be such a transformative experimental paradigm. Forgotten and now shunned in many countries, it has contributed to major breakthroughs in tumor biology, endocrinology, and transplantation research in the past century, and a set of new studies in the US and Britain report stunning advances in stem cell biology and tissue regeneration using parabiosis between young and old mice. We review here briefly the history of parabiosis and discuss its utility to study physiological and pathophysiological processes. We argue that parabiosis is a technique that should enjoy wider acceptance and application, and that policies should be revisited especially if one is to study complex age-related, chronic disorders. PMID:24496774

  14. eNOS-uncoupling in age-related erectile dysfunction.

    PubMed

    Johnson, J M; Bivalacqua, T J; Lagoda, G A; Burnett, A L; 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 (BH(4)) on erectile function in the aged rats. Male Fischer 344 'young' (4-month-old) and 'aged' (19-month-old) rats were treated with a BH(4) precursor sepiapterin (10 mg/kg intraperitoneally) or vehicle for 4 days. After 1-day washout, erectile function was assessed in response to electrical stimulation of the cavernous nerve. Endothelial dysfunction (eNOS uncoupling) and oxidative stress (thiobarbituric acid reactive substances, TBARS) were measured by conducting western blot in penes samples. Erectile response was significantly reduced in aged rats, whereas eNOS uncoupling and TBARS production were significantly increased in the aged rat penis compared with young rats. Sepiapterin significantly improved erectile response in aged rats and prevented increase in TBARS production, but did not affect eNOS uncoupling in the penis of aged rats. These findings suggest that aging induces eNOS uncoupling in the penis, resulting in increased oxidative stress and ED. PMID:21289638

  15. eNOS-uncoupling in age-related erectile dysfunction

    PubMed Central

    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 ‘young’ (4-month-old) and ‘aged’ (19-month-old) rats were treated with a BH4 precursor sepiapterin (10 mg/kg intraperitoneally) or vehicle for 4 days. After 1-day washout, erectile function was assessed in response to electrical stimulation of the cavernous nerve. Endothelial dysfunction (eNOS uncoupling) and oxidative stress (thiobarbituric acid reactive substances, TBARS) were measured by conducting western blot in penes samples. Erectile response was significantly reduced in aged rats, whereas eNOS uncoupling and TBARS production were significantly increased in the aged rat penis compared with young rats. Sepiapterin significantly improved erectile response in aged rats and prevented increase in TBARS production, but did not affect eNOS uncoupling in the penis of aged rats. These findings suggest that aging induces eNOS uncoupling in the penis, resulting in increased oxidative stress and ED. PMID:21289638

  16. Automatic age-related macular degeneration detection and staging

    NASA Astrophysics Data System (ADS)

    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.

  17. Age-related hearing loss increases cross-modal distractibility.

    PubMed

    Puschmann, Sebastian; Sandmann, Pascale; Bendixen, Alexandra; Thiel, Christiane M

    2014-10-01

    Recent electrophysiological studies have provided evidence that changes in multisensory processing in auditory cortex cannot only be observed following extensive hearing loss, but also in moderately hearing-impaired subjects. How the reduced auditory input affects audio-visual interactions is however largely unknown. Here we used a cross-modal distraction paradigm to investigate multisensory processing in elderly participants with an age-related high-frequency hearing loss as compared to young and elderly subjects with normal hearing. During the experiment, participants were simultaneously presented with independent streams of auditory and visual input and were asked to categorize either the auditory or visual information while ignoring the other modality. Unisensory sequences without any cross-modal input served as control conditions to assure that all participants were able to perform the task. While all groups performed similarly in these unisensory conditions, hearing-impaired participants showed significantly increased error rates when confronted with distracting cross-modal stimulation. This effect could be observed in both the auditory and the visual task. Supporting these findings, an additional regression analysis indicted that the degree of high-frequency hearing loss significantly modulates cross-modal visual distractibility in the auditory task. These findings provide new evidence that already a moderate sub-clinical hearing loss, a common phenomenon in the elderly population, affects the processing of audio-visual information.

  18. Modifiable risk factors for age-related macular degeneration.

    PubMed

    Guymer, Robyn H; Chong, Elaine Wei-Tinn

    2006-05-01

    Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in Australia and other Western countries. As there is no cure for AMD, and treatments to stop its progression have met with limited success, there is an interest in identifying modifiable risk factors to prevent or slow disease progression. To date, smoking is the only proven modifiable risk factor for AMD. Other factors under study include (i) cardiovascular risk factors such as hypertension, body mass index, and atherosclerosis; and (ii) dietary risk factors including fat and antioxidant intake, but so far these studies have produced conflicting results. Dietary fat in relation to AMD has recently attracted media attention. Despite very limited work supporting an association between vegetable fat and AMD, widespread publicity advocating margarine as a cause of AMD and encouraging use of butter instead has caused confusion and anxiety among sufferers of AMD and the general public, as well as concern among health professionals. The antioxidant carotenoids--lutein and zeaxanthin--found in dark green or yellow vegetables exist in high concentrations in the macula and are hypothesised to play a protective role. Of nine controlled trials of supplementation with carotenoids and other antioxidants, three suggested that various combinations of antioxidants and carotenoids were protective. While a low-fat diet rich in dark green and yellow vegetables is advocated in general, any specific recommendations regarding certain fats or antioxidant supplementation and AMD are not based on consistent findings at this stage. PMID:16646746

  19. Eye Conditions in Older Adults: Age-Related Macular Degeneration.

    PubMed

    Iroku-Malize, Tochi; Kirsch, Scott

    2016-06-01

    Age-related macular degeneration (AMD) causes a progressive loss of photoreceptors in the macula. It is the most common cause of legal blindness in the United States, and some form of AMD is thought to affect more than 9 million individuals. Risk factors include older age, smoking, dyslipidemia, obesity, white race, female sex, and a family history of AMD. There are two types of advanced AMD: nonexudative (dry or geographic atrophy) and exudative (wet or neovascular). Both cause progressive central vision loss with intact peripheral vision. Nonexudative AMD accounts for 80% to 90% of all advanced cases, and more than 90% of patients with severe vision loss have exudative AMD. On ophthalmoscopic examination, early findings include drusen (ie, yellow deposits in the retina). Prominent choroidal vessels, subretinal edema, and/or hemorrhage are seen in wet AMD. Regular eye examinations, visual field testing, fluorescein angiography, and optical coherence tomography are used for diagnosis and to guide management. There is no specific therapy for dry AMD, but antioxidant supplementation may be helpful. Intravitreal injection of a vascular endothelial growth factor inhibitor is the treatment of choice for wet AMD. Optical aids and devices can help to maximize function for patients with AMD. PMID:27348529

  20. Age-related carbonyl stress and erythrocyte membrane protein carbonylation.

    PubMed

    Li, Guolin; Liu, Li; Hu, Hui; Zhao, Qiong; Xie, Fuxia; Chen, Keke; Liu, Shenglin; Chen, Yaqin; Shi, Wang; Yin, Dazhong

    2010-01-01

    Reactive carbonyl species (RCS) have been widely used as indicators of oxidative stress. However, the associations of carbonyl stress with aging process and biochemical alteration of erythrocyte are still poorly understood. Fresh blood samples in vacutainer tubes containing sodium heparinate were obtained from 874 volunteers who were divided into young, adult and old groups based on their age. Plasma RCS and thiols concentrations between different age groups and erythrocyte membrane protein carbonylation in the adult group were detected within 24h of the blood sampling. Results showed that the plasma thiols concentration decreased gradually during aging process, and the p-values between all three groups are less than 0.05. The plasma RCS concentration in different age groups showed a nonlinear association with age. The levels in the young group were slightly higher than the adult group (not significant) and lower than the old group (p < 0.01). The protein carbonylation of erythrocyte membrane was positively correlated with plasma RCS concentration (p < 0.01), but not plasma thiols concentration. We conclude that higher levels of RCS, not lower levels of thiols, in plasma are a direct risk factor for the protein carbonylation of erythrocyte membrane. Owing to the decrease of thiols levels and increase of RCS levels during aging process, a shift from RCS-related redox allostasis to carbonyl stress would contribute to age-related biological dysfunction and even aging process.

  1. Seven New Loci Associated with Age-Related Macular Degeneration

    PubMed Central

    2013-01-01

    Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate understanding of AMD biology and help design new therapies, we executed a collaborative genomewide association study, examining >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 genomic loci associated with AMD with p<5×10−8 and enriched for genes involved in regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include 7 loci reaching p<5×10−8 for the first time, near the genes COL8A1/FILIP1L, IER3/DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9/MIR548A2, and B3GALTL. A genetic risk score combining SNPs from all loci displayed similar good ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD. PMID:23455636

  2. Defining the boundary: age-related changes in childhood amnesia.

    PubMed

    Tustin, Karen; Hayne, Harlene

    2010-09-01

    Childhood amnesia refers to the inability of adults to recall events that occurred during their infancy and early childhood. Although it is generally assumed that children and adolescents also experience childhood amnesia, with limited exceptions, most empirical research on the phenomenon has focused exclusively on adults. Here, we developed a new Timeline procedure to directly compare the early memories reported by children, adolescents, and adults. Overall, the proportion of memories reported before the age of 3 years was greater for the children and adolescents relative to the adults. In addition, the single earliest memory reported by children and adolescents was at a younger age than that reported by adults. In fact, the earliest memories reported by the children and adolescents, but not the adults, were significantly younger than the traditional 3 (1/2)-year-old boundary of childhood amnesia. Regardless of the age of the rememberer, participants' early memories had the same episodic characteristics. We conclude that the boundary and the density of childhood amnesia may increase over the course of human development and that age-related changes in basic memory mechanisms make an important contribution to our understanding of the source of childhood amnesia.

  3. Epigenetic modification of PKMζ rescues aging-related cognitive impairment.

    PubMed

    Chen, Chen; Meng, Shi-Qiu; Xue, Yan-Xue; Han, Ying; Sun, Cheng-Yu; Deng, Jia-Hui; Chen, Na; Bao, Yan-Ping; Zhang, Fei-Long; Cao, Lin-Lin; Zhu, Wei-Guo; Shi, Jie; Song, Wei-Hong; Lu, Lin

    2016-03-01

    Cognition is impacted by aging. However, the mechanisms that underlie aging-associated cognitive impairment are unclear. Here we showed that cognitive decline in aged rats was associated with changes in DNA methylation of protein kinase Mζ (PKMζ) in the prelimbic cortex (PrL). PKMζ is a crucial molecule involved in the maintenance of long-term memory. Using different behavioral models, we confirmed that aged rats exhibited cognitive impairment in memory retention test 24 h after training, and overexpression of PKMζ in the PrL rescued cognitive impairment in aged rats. After fear conditioning, the protein levels of PKMζ and the membrane expression of GluR2 increased in the PrL in young and adult rats but not in aged rats, and the levels of methylated PKMζ DNA in the PrL decreased in all age groups, whereas the levels of unmethylated PKMζ DNA increased only in young and adult rats. We also found that environmentally enriched housing reversed the hypermethylation of PKMζ and restored cognitive performance in aged rats. Inactivation of PKMζ prevented the potentiating effects of environmental enrichment on memory retention in aged rats. These results indicated that PKMζ might be a potential target for the treatment of aging-related cognitive impairment, suggesting a potential therapeutic avenue.

  4. Age-Related Macular Degeneration: A Scientometric Analysis.

    PubMed

    Ramin, Shahrokh; Soheilian, Masoud; Habibi, Gholamreza; Ghazavi, Roghayeh; Gharebaghi, Reza; Heidary, Fatemeh

    2015-01-01

    Age-related macular degeneration (ARMD) is a major cause of central blindness among working aged adults across the world. Systematic research planning on any subject, including ARMD is in need of solid data regarding previous efforts in this field and to identify the gaps in the research. This study aimed to elucidate the most important trends, directions, and gap in this subject. The data extracted from the Institute for Scientific Information were used to perform a bibliometric analysis of the scientific productions (1993-2013) about ARMD. Specific parameters related to ARMD were analyzed to obtain a view of the topic's structure, history, and document relationships. Additionally, the trends and authors in the most influential publications were analyzed. The number of articles in this field was found constantly increasing. Most highly cited articles addressed genetic epidemiology and clinical research topics in this field. During the past 3 years, there has been a trend toward biomarker research. Through performing the first scientometric survey on ARMD research, we analyzed the characteristics of papers and the trends in scientific production. We also identified some of the critical gaps in the current research efforts that would help in large-scale research strategic planning. PMID:26060829

  5. Age-related impairment of mesenchymal progenitor cell function.

    PubMed

    Stolzing, Alexandra; Scutt, Andrew

    2006-06-01

    In most mesenchymal tissues a subcompartment of multipotent progenitor cells is responsible for the maintenance and repair of the tissue following trauma. With increasing age, the ability of tissues to repair themselves is diminished, which may be due to reduced functional capacity of the progenitor cells. The purpose of this study was to investigate the effect of aging on rat mesenchymal progenitor cells. Mesenchymal progenitor cells were isolated from Wistar rats aged 3, 7, 12 and 56 weeks. Viability, capacity for differentiation and cellular aging were examined. Cells from the oldest group accumulated raised levels of oxidized proteins and lipids and showed decreased levels of antioxidative enzyme activity. This was reflected in decreased fibroblast colony-forming unit (CFU-f) numbers, increased levels of apoptosis and reduced proliferation and potential for differentiation. These data suggest that the reduced ability to maintain mesenchymal tissue homeostasis in aged mammals is not purely due to a decline in progenitor cells numbers but also to a loss of progenitor functionality due to the accumulation of oxidative damage, which may in turn be a causative factor in a number of age-related pathologies such as arthritis, tendinosis and osteoporosis.

  6. Age-Related Macular Degeneration: A Scientometric Analysis.

    PubMed

    Ramin, Shahrokh; Soheilian, Masoud; Habibi, Gholamreza; Ghazavi, Roghayeh; Gharebaghi, Reza; Heidary, Fatemeh

    2015-01-01

    Age-related macular degeneration (ARMD) is a major cause of central blindness among working aged adults across the world. Systematic research planning on any subject, including ARMD is in need of solid data regarding previous efforts in this field and to identify the gaps in the research. This study aimed to elucidate the most important trends, directions, and gap in this subject. The data extracted from the Institute for Scientific Information were used to perform a bibliometric analysis of the scientific productions (1993-2013) about ARMD. Specific parameters related to ARMD were analyzed to obtain a view of the topic's structure, history, and document relationships. Additionally, the trends and authors in the most influential publications were analyzed. The number of articles in this field was found constantly increasing. Most highly cited articles addressed genetic epidemiology and clinical research topics in this field. During the past 3 years, there has been a trend toward biomarker research. Through performing the first scientometric survey on ARMD research, we analyzed the characteristics of papers and the trends in scientific production. We also identified some of the critical gaps in the current research efforts that would help in large-scale research strategic planning.

  7. Nutritional Risk Factors for Age-Related Macular Degeneration

    PubMed Central

    Ersoy, Lebriz; Lechanteur, Yara T.; Hoyng, Carel B.; Kirchhof, Bernd; den Hollander, Anneke I.

    2014-01-01

    Purpose. To evaluate the role of nutritional factors, serum lipids, and lipoproteins in late age-related macular degeneration (late AMD). Methods. Intake of red meat, fruit, fish, vegetables, and alcohol, smoking status, and body mass index (BMI) were ascertained questionnaire-based in 1147 late AMD cases and 1773 controls from the European Genetic Database. Serum levels of lipids and lipoproteins were determined. The relationship between nutritional factors and late AMD was assessed using logistic regression. Based on multivariate analysis, area-under-the-curve (AUC) was calculated by receiver-operating-characteristics (ROC). Results. In a multivariate analysis, besides age and smoking, obesity (odds ratio (OR): 1.44, P = 0.014) and red meat intake (daily: OR: 2.34, P = 8.22 × 10−6; 2–6x/week: OR: 1.67, P = 7.98 × 10−5) were identified as risk factors for developing late AMD. Fruit intake showed a protective effect (daily: OR: 0.52, P = 0.005; 2–6x/week: OR: 0.58, P = 0.035). Serum lipid and lipoprotein levels showed no significant association with late AMD. ROC for nutritional factors, smoking, age, and BMI revealed an AUC of 0.781. Conclusion. Red meat intake and obesity were independently associated with increased risk for late AMD, whereas fruit intake was protective. A better understanding of nutritional risk factors is necessary for the prevention of AMD. PMID:25101280

  8. Breed- and age-related differences in canine mammary tumors.

    PubMed

    Kim, Hyun-Woo; Lim, Ha-Young; Shin, Jong-Il; Seung, Byung-Joon; Ju, Jung-Hyung; Sur, Jung-Hyang

    2016-04-01

    Triple-negative breast cancer is a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). It is an important and clinically relevant condition as it has a poor prognosis and is difficult to treat. Basal-like triple-negative cancer is highly prevalent in both African-Americans and adolescents. We therefore examined whether such a cancer likewise occurs in specific breeds and age groups in dogs, focusing on basal-like triple-negative cancer in particular. In this study, 181 samples from dogs with malignant mammary carcinoma from the 5 most common breeds and 2 age groups in Korea were analyzed. Histological classification and molecular subtyping, including assessment of immunohistochemical findings, were carried out. Twenty-five of 28 (89.3%) triple-negative carcinomas were identified as basal-like triple-negative carcinomas. Analysis of associations of classified factors revealed that the shih tzu breed (9/25, 36.0%) and advanced-age (19/25, 76.0%) groups were characterized by higher prevalence of basal-like triple-negative tumors with diverse histological types and of a higher grade. These results suggest that breed- and age-related differences can be identified in canine mammary carcinoma and, notably, in the shih tzu breed and at older ages. Further investigation of these distinguishing characteristics of the shih tzu breed is warranted. PMID:27127342

  9. Oxidative modification of proteins: age-related changes.

    PubMed

    Chakravarti, Bulbul; Chakravarti, Deb N

    2007-01-01

    Aging is a complex biological phenomenon which involves progressive loss of different physiological functions of various tissues of living organisms. It is the inevitable fate of life and is a major risk factor for death and different pathological disorders. Based on a wide variety of studies performed in humans as well as in various animal models and microbial systems, reactive oxygen species (ROS) are believed to play a key role in the aging process. The production of ROS is influenced by cellular metabolic activities as well as environmental factors. ROS can react with all major biological macromolecules such as carbohydrates, nucleic acids, lipids, and proteins. Since, in general, proteins are the key molecules that play the ultimate role in various structural and functional aspects of living organisms, this review will focus on the age-related oxidative modifications of proteins as well as on mechanism for removal or repair of the oxidized proteins. The topics covered include protein oxidation as a marker of oxidative stress, experimental evidence indicating the role of ROS in protein oxidation, protein carbonyl content, enzymatic degradation of oxidized proteins, and effects of caloric restriction on protein oxidation in the context of aging. Finally, we will discuss different strategies which have been or can be undertaken to slow down the oxidative damage of proteins and the aging process.

  10. Endocrine causes of age-related bone loss and osteoporosis.

    PubMed

    Riggs, B Lawrence

    2002-01-01

    Women have an early postmenopausal phase of rapid bone loss that lasts for 5-10 years after menopause, whereas both ageing women and men have a slow continuous phase of bone loss that lasts indefinitely. In women, the rapid phase is mediated mainly by loss of the direct restraining effect of oestrogen on bone cell function, whereas the slow phase is mediated mainly by the loss of oestrogen action on extraskeletal calcium homeostasis leading to net calcium wasting and secondary hyperparathyroidism. Because elderly men have low serum bioavailable oestrogen and testosterone levels, and because recent data suggest that oestrogen is the main sex steroid regulating bone metabolism in men, oestrogen deficiency may also be the principal cause of bone loss in elderly men. Decreased bone formation contributes to bone loss in both genders and may be caused by a decreased production of growth hormone and IGF1 as well as oestrogen and testosterone deficiency. Other changes in endocrine secretion, although present in the elderly, seem less important in the pathophysiology of age-related bone loss and osteoporosis. PMID:11855691

  11. Prevalence of age-related macular degeneration among the elderly

    PubMed Central

    Rasoulinejad, Seyed Ahmad; Zarghami, Amin; Hosseini, Seyed Reza; Rajaee, Neda; Rasoulinejad, Seyed Elahe; Mikaniki, Ebrahim

    2015-01-01

    Background: Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness in elderly population in the developing countries. Previous epidemiological studies revealed various potential modifiable risk factors for this disease. The purpose of this study was to evaluate the prevalence of AMD among elderly living in Babol, North of Iran. Methods: The study population of this cross-sectional study came from the Amirkola Health and Ageing Project (AHAP), the first comprehensive cohort study of the health of people aged 60 years and over in Amirkola, North of Iran. The prevalence of AMD was estimated and its risk was determined using logistic regression analysis (LRA) with regard to variables such as smoking, hyperlipidemia, hypertension and diabetes. Results: Five hundred and five participants with mean age of 71.55±5.9 (ranged 60-89) years entered the study. The prevalence of AMD was 17.6%. There was a significant association between AMD and smoking (P<0.001) but no association was seen with AMD and age, level of education, history of hyperlipidemia, hypertension and diabetes. Multiple LRAs revealed that smoking increased AMD by odds ratio of 5.03 (95% confidence interval 2.47-10.23 p<0.001) as compared to nonsmokers Conclusion: According to our findings, the prevalence of AMD was relatively high and smoking increased the risk of AMD in the elderly population. PMID:26644880

  12. Age-Related Changes in Demand–Withdraw Communication Behaviors

    PubMed Central

    Holley, Sarah R.; Haase, Claudia M.; Levenson, Robert W.

    2013-01-01

    Demand–withdraw communication is a set of conflict-related behaviors in which one partner blames or pressures while the other partner withdraws or avoids. The present study examined age-related changes in these behaviors longitudinally over the course of later life stages. One hundred twenty-seven middle-aged and older long-term married couples were observed at 3 time points across 13 years as they engaged in a conversation about an area of relationship conflict. Husbands’ and wives’ demand–withdraw behaviors (i.e., blame, pressure, withdrawal, avoidance) were objectively rated by trained coders at each time point. Data were analyzed using dyad-level latent growth curve models in a structural equation modeling framework. For both husbands and wives, the results showed a longitudinal pattern of increasing avoidance behavior over time and stability in all other demand and withdraw behaviors. This study supports the notion that there is an important developmental shift in the way that conflict is handled in later life. PMID:23913982

  13. Breed- and age-related differences in canine mammary tumors

    PubMed Central

    Kim, Hyun-Woo; Lim, Ha-Young; Shin, Jong-Il; Seung, Byung-Joon; Ju, Jung-Hyung; Sur, Jung-Hyang

    2016-01-01

    Triple-negative breast cancer is a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). It is an important and clinically relevant condition as it has a poor prognosis and is difficult to treat. Basal-like triple-negative cancer is highly prevalent in both African-Americans and adolescents. We therefore examined whether such a cancer likewise occurs in specific breeds and age groups in dogs, focusing on basal-like triple-negative cancer in particular. In this study, 181 samples from dogs with malignant mammary carcinoma from the 5 most common breeds and 2 age groups in Korea were analyzed. Histological classification and molecular subtyping, including assessment of immunohistochemical findings, were carried out. Twenty-five of 28 (89.3%) triple-negative carcinomas were identified as basal-like triple-negative carcinomas. Analysis of associations of classified factors revealed that the shih tzu breed (9/25, 36.0%) and advanced-age (19/25, 76.0%) groups were characterized by higher prevalence of basal-like triple-negative tumors with diverse histological types and of a higher grade. These results suggest that breed- and age-related differences can be identified in canine mammary carcinoma and, notably, in the shih tzu breed and at older ages. Further investigation of these distinguishing characteristics of the shih tzu breed is warranted. PMID:27127342

  14. Age-related changes in the rat hippocampus.

    PubMed

    Is, Merih; Comunoglu, Nil Ustundag; Comunoglu, Cem; Eren, Bulent; Ekici, Isin Dogan; Ozkan, Ferda

    2008-05-01

    The human brain is uniquely powerful in its cognitive abilities, yet the hippocampal and neocortical circuits that mediate these complex functions are highly vulnerable during aging. In this study, we analyzed age-related changes in the rat hippocampus by studying newborn (1 month), middle-aged (12 months), and older (24 months) male and female Sprague-Dawley rats. We evaluated neuronal dystrophy, neuron scattering, and granulovacuolar degeneration in the hippocampal area using light microscopy, according to age and gender. We detected significant neuronal dystrophy in the CA1, CA2, and CA3 areas in male rats, and in the CA1, CA3, and CA4 areas in female rats. Degenerative changes, indicated by neuron scattering, were observed in the CA1, CA2, and CA3 areas of male and the CA2 and CA4 areas of female rats. Changes in all areas of the hippocampus were observed with increasing age; these changes included neuronal dystrophy and neuron scattering and did not differ significantly between male and female rats.

  15. Eye Conditions in Older Adults: Age-Related Macular Degeneration.

    PubMed

    Iroku-Malize, Tochi; Kirsch, Scott

    2016-06-01

    Age-related macular degeneration (AMD) causes a progressive loss of photoreceptors in the macula. It is the most common cause of legal blindness in the United States, and some form of AMD is thought to affect more than 9 million individuals. Risk factors include older age, smoking, dyslipidemia, obesity, white race, female sex, and a family history of AMD. There are two types of advanced AMD: nonexudative (dry or geographic atrophy) and exudative (wet or neovascular). Both cause progressive central vision loss with intact peripheral vision. Nonexudative AMD accounts for 80% to 90% of all advanced cases, and more than 90% of patients with severe vision loss have exudative AMD. On ophthalmoscopic examination, early findings include drusen (ie, yellow deposits in the retina). Prominent choroidal vessels, subretinal edema, and/or hemorrhage are seen in wet AMD. Regular eye examinations, visual field testing, fluorescein angiography, and optical coherence tomography are used for diagnosis and to guide management. There is no specific therapy for dry AMD, but antioxidant supplementation may be helpful. Intravitreal injection of a vascular endothelial growth factor inhibitor is the treatment of choice for wet AMD. Optical aids and devices can help to maximize function for patients with AMD.

  16. Mechanism of Inflammation in Age-Related Macular Degeneration

    PubMed Central

    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

  17. Caspase-2 Deficiency Enhances Aging-Related Traits in Mice

    PubMed Central

    Zhang, Yingpei; Padalecki, Susan S; Chaudhuri, Asish R; Waal, Eric De; Goins, Beth A; Grubbs, Barry; Ikeno, Yuji; Richardson, Arlan; Mundy, Gregory R; Herman, Brian

    2007-01-01

    Alteration of apoptotic activity has been observed in a number of tissues in aging mammals, but it remains unclear whether and/or how apoptosis may affect aging. Caspase-2 is a member of the cysteine protease family that plays a critical role in apoptosis. To understand the impact of compromised apoptosis function on mammalian aging, we conducted a comparative study on caspase-2 deficient mice and their wild-type littermates with a specific focus on the aging-related traits at advanced ages. We found that caspase-2 deficiency enhanced a number of traits commonly seen in premature aging animals. Loss of caspase-2 was associated with shortened maximum lifespan, impaired hair growth, increased bone loss, and reduced body fat content. In addition, we found that the livers of caspase-2 deficient mice had higher levels of oxidized proteins than those of age-matched wild-type mice, suggesting that caspase-2 deficiency compromised the animal's ability to clear oxidatively damaged cells. Collectively, these results suggest that caspase-2 deficiency affects aging in the mice. This study thus demonstrates for the first time that disruption of a key apoptotic gene has a significant impact on aging. PMID:17188333

  18. Epigenetic modification of PKMζ rescues aging-related cognitive impairment

    PubMed Central

    Chen, Chen; Meng, Shi-Qiu; Xue, Yan-Xue; Han, Ying; Sun, Cheng-Yu; Deng, Jia-Hui; Chen, Na; Bao, Yan-Ping; Zhang, Fei-Long; Cao, Lin-Lin; Zhu, Wei-Guo; Shi, Jie; Song, Wei-Hong; Lu, Lin

    2016-01-01

    Cognition is impacted by aging. However, the mechanisms that underlie aging-associated cognitive impairment are unclear. Here we showed that cognitive decline in aged rats was associated with changes in DNA methylation of protein kinase Mζ (PKMζ) in the prelimbic cortex (PrL). PKMζ is a crucial molecule involved in the maintenance of long-term memory. Using different behavioral models, we confirmed that aged rats exhibited cognitive impairment in memory retention test 24 h after training, and overexpression of PKMζ in the PrL rescued cognitive impairment in aged rats. After fear conditioning, the protein levels of PKMζ and the membrane expression of GluR2 increased in the PrL in young and adult rats but not in aged rats, and the levels of methylated PKMζ DNA in the PrL decreased in all age groups, whereas the levels of unmethylated PKMζ DNA increased only in young and adult rats. We also found that environmentally enriched housing reversed the hypermethylation of PKMζ and restored cognitive performance in aged rats. Inactivation of PKMζ prevented the potentiating effects of environmental enrichment on memory retention in aged rats. These results indicated that PKMζ might be a potential target for the treatment of aging-related cognitive impairment, suggesting a potential therapeutic avenue. PMID:26926225

  19. Adiponectin deficiency exacerbates age-related hearing impairment.

    PubMed

    Tanigawa, T; Shibata, R; Ouchi, N; Kondo, K; Ishii, M; Katahira, N; Kambara, T; Inoue, Y; Takahashi, R; Ikeda, N; Kihara, S; Ueda, H; Murohara, T

    2014-04-24

    Obesity-related disorders are closely associated with the development of age-related hearing impairment (ARHI). Adiponectin (APN) exerts protective effects against obesity-related conditions including endothelial dysfunction and atherosclerosis. Here, we investigated the impact of APN on ARHI. APN-knockout (APN-KO) mice developed exacerbation of hearing impairment, particularly in the high frequency range, compared with wild-type (WT) mice. Supplementation with APN prevented the hearing impairment in APN-KO mice. At 2 months of age, the cochlear blood flow and capillary density of the stria vascularis (SV) were significantly reduced in APN-KO mice as compared with WT mice. APN-KO mice also showed a significant increase in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells in the organ of Corti in the cochlea at 2 months of age. At the age of 6 months, hair cells were lost at the organ of Corti in APN-KO mice. In cultured auditory HEI-OC1 cells, APN reduced apoptotic activity under hypoxic conditions. Clinically, plasma APN levels were significantly lower in humans with ARHI. Multiple logistic regression analysis identified APN as a significant and independent predictor of ARHI. Our observations indicate that APN has an important role in preventing ARHI.

  20. Promising new treatments for neovascular age-related macular degeneration.

    PubMed

    Michels, Stephan; Schmidt-Erfurth, Ursula; Rosenfeld, Philip J

    2006-07-01

    Angiogenesis, the growth of new blood vessels from existing blood vessels, is responsible for vision loss in a variety of ophthalmic diseases. In neovascular age-related macular degeneration (AMD), the leading cause for legal blindness in many industrialised countries, abnormal blood vessels grow in the macula and cause blindness. There are a number of factors important in the angiogenic cascade but VEGF-A has been implicated in recent years as the major factor responsible for neovascular and exudative diseases of the eye. Numerous antiangiogenic drugs are in development but anti-VEGF drugs have shown great promise in treating neovascular AMD and other ocular diseases, and many of these drugs have been adopted from oncology where antiangiogenic therapy is gaining wide acceptance. For the first time in neovascular AMD, anti-VEGF drugs have brought the hope of vision improvement to a significant proportion of patients. This review provides an overview on angiogenic mechanisms, potential antiangiogenic treatment strategies and different antiangiogenic drugs with special focus on neovascular AMD. PMID:16787141

  1. Age-related macular degeneration: experimental and emerging treatments

    PubMed Central

    Hubschman, Jean Pierre; Reddy, Shantan; Schwartz, Steven D

    2009-01-01

    Purpose: This essay reviews the experimental treatments and new imaging modalities that are currently being explored by investigators to help treat patients with age-related macular degeneration (AMD). Design: Interpretative essay. Methods: Literature review and interpretation. Results: Experimental treatments to preserve vision in patients with exudative AMD include blocking vascular endothelial growth factor (VEGF), binding VEGF, and modulating the VEGF receptors. Investigators are also attempting to block signal transduction with receptor tyrosine kinase inhibitors. Experimental treatments for non-exudative AMD include agents that target inflammation, oxidative stress, and implement immune-modulation. The effectiveness of these newer pharmacologic agents has the potential to grow exponentially when used in combination with new and improved imaging modalities that can help identify disease earlier and follow treatment response more precisely. Conclusion: With a better understanding, at the genetic and molecular level, of AMD and the development of superior imaging modalities, investigators are able to offer treatment options that may offer unprecedented visual gains while reducing the need for repetitive treatments. PMID:19668561

  2. Mutations of epigenetic regulatory genes are common in thymic carcinomas.

    PubMed

    Wang, Yisong; Thomas, Anish; Lau, Christopher; Rajan, Arun; Zhu, Yuelin; Killian, J Keith; Petrini, Iacopo; Pham, Trung; Morrow, Betsy; Zhong, Xiaogang; Meltzer, Paul S; Giaccone, Giuseppe

    2014-12-08

    Genetic alterations and etiology of thymic epithelial tumors (TETs) are largely unknown, hampering the development of effective targeted therapies for patients with TETs. Here TETs of advanced-stage patients enrolled in a clinical trial of molecularly-guided targeted therapies were employed for targeted sequencing of 197 cancer-associated genes. Comparative sequence analysis of 78 TET/blood paired samples obtained from 47 thymic carcinoma (TC) and 31 thymoma patients revealed a total of 86 somatic non-synonymous sequence variations across 39 different genes in 33 (42%) TETs. TCs (62%; 29/47) showed higher incidence of somatic non-synonymous mutations than thymomas (13%; 4/31; p < 0.0001). TP53 was the most frequently mutated gene in TETs (n = 13; 17%), especially in TCs (26%), and was associated with a poorer overall survival (p < 0.0001). Genes in histone modification [BAP1 (n = 6; 13%), SETD2 (n = 5; 11%), ASXL1 (n = 2; 4%)], chromatin remodeling [SMARCA4 (n = 2; 4%)], and DNA methylation [DNMT3A (n = 3; 7%), TET2 (n = 2; 4%), WT1 (n = 2; 4%)] pathways were recurrently mutated in TCs, but not in thymomas. Our results suggest a potential disruption of epigenetic homeostasis in TCs, and a substantial difference in genetic makeup between TCs and thymomas. Further investigation is warranted into the roles of epigenetic dysregulation in TC development and its potential for targeted therapy.

  3. Mutations of epigenetic regulatory genes are common in thymic carcinomas

    PubMed Central

    Wang, Yisong; Thomas, Anish; Lau, Christopher; Rajan, Arun; Zhu, Yuelin; Killian, J. Keith; Petrini, Iacopo; Pham, Trung; Morrow, Betsy; Zhong, Xiaogang; Meltzer, Paul S.; Giaccone, Giuseppe

    2014-01-01

    Genetic alterations and etiology of thymic epithelial tumors (TETs) are largely unknown, hampering the development of effective targeted therapies for patients with TETs. Here TETs of advanced-stage patients enrolled in a clinical trial of molecularly-guided targeted therapies were employed for targeted sequencing of 197 cancer-associated genes. Comparative sequence analysis of 78 TET/blood paired samples obtained from 47 thymic carcinoma (TC) and 31 thymoma patients revealed a total of 86 somatic non-synonymous sequence variations across 39 different genes in 33 (42%) TETs. TCs (62%; 29/47) showed higher incidence of somatic non-synonymous mutations than thymomas (13%; 4/31; p < 0.0001). TP53 was the most frequently mutated gene in TETs (n = 13; 17%), especially in TCs (26%), and was associated with a poorer overall survival (p < 0.0001). Genes in histone modification [BAP1 (n = 6; 13%), SETD2 (n = 5; 11%), ASXL1 (n = 2; 4%)], chromatin remodeling [SMARCA4 (n = 2; 4%)], and DNA methylation [DNMT3A (n = 3; 7%), TET2 (n = 2; 4%), WT1 (n = 2; 4%)] pathways were recurrently mutated in TCs, but not in thymomas. Our results suggest a potential disruption of epigenetic homeostasis in TCs, and a substantial difference in genetic makeup between TCs and thymomas. Further investigation is warranted into the roles of epigenetic dysregulation in TC development and its potential for targeted therapy. PMID:25482724

  4. Age-Related Susceptibility of Turkeys to Enteric Viruses.

    PubMed

    Awe, Olusegun O; Kang, Kyung-il; Ibrahim, Mahmoud; Ali, Ahmed; Elaish, Mohamed; Saif, Yehia M; Lee, Chang-Won

    2015-06-01

    Several different enteric viruses have been identified as the causes of gastrointestinal infections in poultry. Enteric virus infections are well characterized in poults, but limited studies have been conducted in older birds. The susceptibility of 2-, 7-, 12-, 30-, and 52-wk-old turkeys to turkey coronavirus (TCoV) and turkey astrovirus (TAstV) was evaluated, as well as the effect of combined infection of TAstV and TCoV in 2-wk-old poults and turkey hens. From cloacal swabs and intestines, TCoV was consistently detected by reverse transcriptase-PCR throughout the experimental period (1-21 days postinoculation [DPI]) from all age groups. In contrast, the last detection point of TAstV gradually decreased to 21, 16, and 12 DPI in birds inoculated at 2, 7, and 12 wk of age, respectively, and viral RNA was rarely detected from cloacal swabs or intestinal contents in turkey hens within 3 DPI. Infection with TAstV alone did not affect body weight in poults or egg production in hens. The combined infection of TAstV and TCoV did not induce more severe clinical signs and pathology than the TCoV infection alone. However, a severe prolonged decrease in egg production (about 50%) was observed in turkey hens in the combined infection group compared with a transient egg production drop in the TCoV-infected hens alone. The underlying mechanism regarding the age-related TAstV susceptibility and the pathogenesis of the TAstV and TCoV coinfection in layer hens needs to be further elucidated. PMID:26473670

  5. Heterogeneity in age-related white matter changes.

    PubMed

    Schmidt, Reinhold; Schmidt, Helena; Haybaeck, Johannes; Loitfelder, Marisa; Weis, Serge; Cavalieri, Margherita; Seiler, Stephan; Enzinger, Christian; Ropele, Stefan; Erkinjuntti, Timo; Pantoni, Leonardo; Scheltens, Philip; Fazekas, Franz; Jellinger, Kurt

    2011-08-01

    White matter changes occur endemically in routine magnetic resonance imaging (MRI) scans of elderly persons. MRI appearance and histopathological correlates of white matter changes are heterogeneous. Smooth periventricular hyperintensities, including caps around the ventricular horns, periventricular lining and halos are likely to be of non-vascular origin. They relate to a disruption of the ependymal lining with subependymal widening of the extracellular space and have to be differentiated from subcortical and deep white matter abnormalities. For the latter a distinction needs to be made between punctate, early confluent and confluent types. Although punctate white matter lesions often represent widened perivascular spaces without substantial ischemic tissue damage, early confluent and confluent lesions correspond to incomplete ischemic destruction. Punctate abnormalities on MRI show a low tendency for progression, while early confluent and confluent changes progress rapidly. The causative and modifying pathways involved in the occurrence of sporadic age-related white matter changes are still incompletely understood, but recent microarray and genome-wide association approaches increased the notion of pathways that might be considered as targets for therapeutic intervention. The majority of differentially regulated transcripts in white matter lesions encode genes associated with immune function, cell cycle, proteolysis, and ion transport. Genome-wide association studies identified six SNPs mapping to a locus on chromosome 17q25 to be related to white matter lesion load in the general population. We also report first and preliminary data that demonstrate apolipoprotein E (ApoE) immunoreactivity in white matter lesions and support epidemiological findings indicating that ApoE is another factor possibly related to white matter lesion occurrence. Further insights come from modern MRI techniques, such as diffusion tensor and magnetization transfer imaging, as they

  6. Age-related changes in the Brazilian woman's smile.

    PubMed

    Correia, Luiza Nayara Almeida Lyra; Reis, Silvia Augusta Braga; Conti, Ana Claudia de Castro Ferreira; Capelozza Filho, Leopoldino; Almeida-Pedrin, Renata Rodrigues

    2016-01-01

    The aim of this research was to evaluate age-related changes in the smile of Brazilian women. The sample consisted of 249 Brazilian women who had not undergone previous orthodontic treatment or facial surgery. They were divided into four groups, according to age: G1 (20-29), G2 (30-39), G3 (40-49) and G4 (50 or older). Standardized front view photographs were taken while smiling and at rest. Measurements were evaluated by ANOVA and post-hoc Tukey. The Chi-square test was applied for qualitative variables. Upper lip thickness at rest and exposure of upper incisors on smiling decreased with age. Most individuals (60.9%) exhibited a medium smile. High smiles were more often seen in G1 (45%) and less frequently in G4 (18.8%), whereas the opposite occurred with the low smile, i.e., G4 (21.9%) and G1 (6.7%). Variations among the groups were observed in the transverse exposure of the teeth on smiling. In G1 and G3, there was a balance between tooth exposures, so that the teeth were exposed as far as the premolars and/or molars. Most of the women (56.3%) in G2 exposed their teeth as far as the first molars on smiling, whereas most of those (40.6%) in G4 exposed their teeth only as far as the first premolars on smiling. As age increased, there was decreased exposure of the upper incisors, decreased upper lip thickness and lower exposure of teeth vertically and transversely.

  7. Genetic and Environmental Factors in Age-Related Hearing Impairment.

    PubMed

    Momi, Sukhleen K; Wolber, Lisa E; Fabiane, Stella Maris; MacGregor, Alex J; Williams, Frances M K

    2015-08-01

    Age-related hearing impairment (ARHI) is a common condition with complex etiology but a recognized genetic component. Heritability estimates for pure tone audiogram-determined hearing ability lie in the range 26-75%. The speech-in-noise (SIN) auditory test, however, may be better at encapsulating ARHI symptoms, particularly the diminished ability to segregate environmental sounds into comprehendible auditory streams. As heritability of SIN has not previously been reported, we explored the genetic and environmental contributions to ARHI determined by SIN in 2,076 twins (87.8% female) aged 18-87 (mean age 54.4). SIN was found to be significantly heritable (A, unadjusted for age=40%; 95% confidence intervals, CI=32%-47%). With age adjustment, heritability fell (A=25%; 95% CI=16-33%), and a relatively strong influence of environmental exposure unshared within twin siblings was identified (E=75%). To explore the environmental aspects further, we assessed the influence of diet (through the Food Frequency Questionnaire, FFQ), smoking (through self-report and cotinine metabolite levels) and alcohol intake (through the FFQ). A negative influence of high cholesterol diet was observed after adjustment (p=.037). A protective effect of raised serum high-density lipoprotein (HDL) cholesterol levels was observed after adjustment (p=.004). This study is the first assessment of the genetic and environmental influence on SIN perception. The findings suggest SIN is less heritable than pure tone audiogram (PTA) ability and highly influenced by the environment unique to each twin. Furthermore, a possible role of dietary fat in the etiology of ARHI is highlighted.

  8. Age-Related Macular Degeneration: Genetics and Biology.

    PubMed

    Kumaramanickavel, Govindasamy

    2016-01-01

    Age-related macular degeneration (AMD), widely prevalent across the globe, is a major stakeholder among adult visual morbidity and blindness, not only in the Western world but also in Asia. Several risk factors have been identified, including critical genetic factors, which were never imagined 2 decades ago. The etiopathogenesis is emerging to demonstrate that immune and complement-related inflammation pathway members chronically exposed to environmental insults could justifiably influence disease morbidity and treatment outcomes. Approximately half a dozen physiological and biochemical cascades are disrupted in the AMD disease genesis, eventually leading to the distortion and disruption of the subretinal space, subretinal pigment epithelium, and Bruch membrane, thus setting off chaos and disorder for signs and symptoms to manifest. Approximately 3 dozen genetic factors have so far been identified, including the recent ones, through powerful genomic technologies and large robust sample sizes. The noteworthy genetic variants (common and rare) are complement factor H, complement factor H-related genes 1 to 5, C3, C9, ARMS2/HTRA1, vascular endothelial growth factor A, vascular endothelial growth factor receptor 2/KDR, and rare variants (show causal link) such as TIMP3, fibrillin, COL4A3, MMP19, and MMP9. Despite the enormous amount of scientific information generated over the years, diagnostic genetic or biomarker tests are still not available for clinicians to understand the natural course of the disease and its management in a patient. However, further research in the field should reduce this gap not only by aiding the clinician but also through the possibilities of clinical intervention with complement pathway-related inhibitors entering preclinical and clinical trials in the near future. PMID:27488064

  9. Gene Therapy for Age-Related Macular Degeneration.

    PubMed

    Constable, Ian Jeffery; Blumenkranz, Mark Scott; Schwartz, Steven D; Barone, Sam; Lai, Chooi-May; Rakoczy, Elizabeth Piroska

    2016-01-01

    The purpose of this article was to evaluate safety and signals of efficacy of gene therapy with subretinal rAAV.sFlt-1 for wet age-related macular degeneration (wet AMD). A phase 1 dose-escalating single-center controlled unmasked human clinical trial was followed up by extension of the protocol to a phase 2A single-center trial. rAAV.sFlt-1 vector was used to deliver a naturally occurring anti-vascular endothelial growth factor agent, sFlt-1, into the subretinal space. In phase 1, step 1 randomized 3 subjects to low-dose rAAV.sFlt-1 (1 × 10 vector genomes) and 1 subject to the control arm; step 2 randomized an additional 3 subjects to treatment with high-dose rAAV.sFlt-1 (1 × 10 vector genomes) and 1 subject to the control arm. Follow-up studies demonstrated that rAAV.sFlt-1 was well tolerated with a favorable safety profile in these elderly subjects with wet AMD. Subretinal injection was highly reproducible, and no drug-related adverse events were reported. Procedure-related adverse events were mild and self-resolving. Two phakic patients developed cataract and underwent cataract surgery. Four of the 6 patients responded better than the small control group in this study and historical controls in terms of maintaining vision and a relatively dry retina with zero ranibizumab retreatments per annum. Two patients required 1 ranibizumab injection over the 52-week follow-up period. rAAV.sFlt-1 gene therapy may prove to be a potential adjunct or alternative to conventional intravitreal injection for patients with wet AMD by providing extended delivery of a naturally occurring antiangiogenic protein. PMID:27488071

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

    PubMed

    Kovacs, Gabor G; 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; Dickson, Dennis W

    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

  11. Neuropharmacology of depression in aging and age-related diseases.

    PubMed

    Gareri, Pietro; De Fazio, Pasquale; De Sarro, Giovambattista

    2002-02-01

    Depression in the elderly is nowadays a predominant health care problem, mainly due to the progressive aging of the population. It results from psychosocial stress, polypathology, as well as some biochemical changes which occur in the aged brain and can lead to cognitive impairments, increased symptoms from medical illness, higher utilization of health care services and increased rates of suicide and non-suicide mortality. Depression may be also caused by a various number of drugs currently administered; this is remarkable especially in elderly people, where polypathology is often associated with polypharmacotherapy. However, the pathogenesis of geriatric depression is not well understood; major depression may arise from dysfunction of the limbic-hypothalamic-pituitary-adrenal axis. Some clinical observations also suggest that striato-frontal dysfunction is associated with late life depression. A number of hypotheses have been made, focusing that mood disturbances are probably linked to a disturbed central metabolism of monoamines 5-hydroxytryptamine, noradrenaline and dopamine; however most of this knowledge is derived from animal models. Parkinson's and Alzheimer's diseases are age-related diseases associated to decreased activity or brain lesions in the orbital frontal cortex and basal ganglia. These observations lead to the hypothesis that the dysfunction of one or more of the cortical basal ganglia-thalamic neuronal loops are involved in the pathophysiology of primary and secondary depression. This dysfunction may be mediated by decreased serotonin release and probably, also by reduction in serotonin receptors. Development of novel approaches such as dynamic brain imaging methods, together with indirect knowledge coming from the effects of new antidepressants, will increase the understanding of neurochemistry of depression in old age. PMID:12039452

  12. Factors Associated With Age-related Hearing Impairment

    PubMed Central

    Moon, Il Joon; Byun, Hayoung; Woo, Sook-young; Gwak, Geum-Youn; Hong, Sung Hwa; Chung, Won-Ho; Cho, Yang-Sun

    2015-01-01

    Abstract Age-related hearing impairment (ARHI) is a complex degenerative disease in the elderly. As multiple factors interact during the development of ARHI, it is important to elucidate the major influencing factors to understand and prevent ARHI. We aimed to identify risk factors associated with the development of ARHI with a retrospective cohort from 2001 to 2010. The records of the adult subjects over 40 years of age who consecutively underwent a comprehensive health checkup including pure-tone audiometry at the Health Promotion Center were reviewed. During this period, 1560 subjects who underwent pure-tone audiometry more than twice, had no other otologic diseases, and were followed-up more than 2 years were included. A pure-tone average (PTA: 0.5, 1, 2, 4 kHz) was calculated. Development of ARHI was defined as a PTA at follow-up more than 10 dB greater than the baseline PTA. Times to the first development of ARHI were investigated. Overall, 12.7% of subjects developed ARHI within the first 4 years. High blood ionized calcium (hazard ratio [HR] 0.084), albumin (HR 0.239), systolic blood pressure (HR 0.577), thyroid hormone (T3) (HR 0.593), and alpha fetoprotein levels (HR 0.883) were associated with decreased hazard for the development of ARHI. In contrast, high blood high-density lipoprotein (HR 2.105), uric acid (HR 1.684), total protein (HR 1.423), and total bilirubin levels (HR 1.220) were potential risk factors for the development of ARHI. Development of ARHI is common among the aged population, and a variety of factors may interact during this process. The results of this study can be used for counseling of adults at high-risk of developing ARHI with regard to regular audiological check-up. PMID:26512592

  13. The Age-Related Orientational Changes of Human Semicircular Canals

    PubMed Central

    Lyu, Hui-Ying; Chen, Ke-Guang; Yin, Dong-Ming; Hong, Juan; Yang, Lin; Zhang, Tian-Yu; Dai, Pei-Dong

    2016-01-01

    Objectives Some changes are found in the labyrinth anatomy during postnatal development. Although the spatial orientation of semicircular canals was thought to be stable after birth, we investigated the age-related orientational changes of human semicircular canals during development. Methods We retrospectively studied the computed tomography (CT) images of both ears of 76 subjects ranged from 1 to 70 years old. They were divided into 4 groups: group A (1–6 years), group B (7–12 years), group C (13–18 years), and group D (>18 years). The anatomical landmarks of the inner ear structures were determined from CT images. Their coordinates were imported into MATLAB software for calculating the semicircular canals orientation, angles between semicircular canal planes and the jugular bulb (JB) position. Differences between age groups were analyzed using multivariate statistics. Relationships between variables were analyzed using Pearson analysis. Results The angle between the anterior semicircular canal plane and the coronal plane, and the angle between the horizontal semicircular canal plane and the coronal plane were smaller in group D than those in group A (P<0.05). The JB position, especially the anteroposterior position of right JB, correlated to the semicircular canals orientation (P<0.05). However, no statistically significant differences in the angles between ipsilateral canal planes among different age groups were found. Conclusion The semicircular canals had tendencies to tilt anteriorly simultaneously as a whole with age. The JB position correlated to the spatial arrangement of semicircular canals, especially the right JB. Our calculation method helps detect developmental and pathological changes in vestibular anatomy. PMID:27090280

  14. Glycolysis in Patients with Age-Related Macular Degeneration

    PubMed Central

    Yokosako, Kanako; Mimura, Tatsuya; Funatsu, Hideharu; Noma, Hidetaka; Goto, Mari; Kamei, Yuko; Kondo, Aki; Matsubara, Masao

    2014-01-01

    Purpose: Retinal adenosine triphosphate is mainly produced via glycolysis, so inhibition of glycolysis may promote the onset and progression of age-related macular degeneration (AMD). When glycolysis is inhibited, pyruvate is metabolized by lactic acid fermentation instead of entering the mitochondrial tricarboxylic acid (TCA) cycle. We measured urinary pyruvate and lactate levels in patients with AMD. Methods: Eight patients with typical AMD (tAMD group) and 9 patients with polypoidal choroidal vasculopathy (PCV group) were enrolled. Urinary levels of pyruvate, lactate, α-hydroxybutyrate, and β-hydroxybutyrate were measured in all patients. Results: The mean urinary levels of pyruvate and lactate were 8.0 ± 2.8 and 7.5 ± 8.3 μg/mg creatinine (reference values: 0.5-6.6 and 0.0-1.6), respectively, with the mean increase over the reference value being 83.6 ± 51.1% and 426.5 ± 527.8%, respectively. In 12 patients (70.6%), the lactate/pyruvate ratio was above the reference range. Urinary levels of α-hydroxybutyrate and β-hydroxybutyrate were decreased by -31.9 ± 15.2% and -33.1 ± 17.5% compared with the mean reference values. There were no significant differences of any of these glycolysis metabolites between the tAMD and PCV groups. Multivariate analysis revealed that none of the variables tested, including patient background factors (age, hypertension, diabetes, hyperlipidemia, cerebrovascular disease, alcohol, smoking, visual acuity, and AMD phenotype), were significantly associated with the lactate/pyruvate ratio. Conclusion: A high lactate/pyruvate ratio is a well-known marker of mitochondrial impairment, and it indicates poor oxidative function in AMD. Our results suggest that increased lactate levels may be implicated in the pathogenesis of AMD. PMID:25191529

  15. Age-related decline in global form suppression.

    PubMed

    Wiegand, Iris; Finke, Kathrin; Töllner, Thomas; Starman, Kornelija; Müller, Hermann J; Conci, Markus

    2015-12-01

    Visual selection of illusory 'Kanizsa' figures, an assembly of local elements that induce the percept of a whole object, is facilitated relative to configurations composed of the same local elements that do not induce a global form--an instance of 'global precedence' in visual processing. 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-local task requiring selection of either a 'global' Kanizsa- or a 'local' non-Kanizsa configuration (in the presence of the respectively other configuration) by analyzing event-related lateralizations (ERLs). Behaviorally, older participants showed a more pronounced global-precedence effect. Electrophysiologically, this effect was accompanied by an early (150-225 ms) 'positivity posterior contralateral' (PPC), which was elicited for older, but not younger, participants, when the target was a non-Kanizsa configuration and the Kanizsa figure a distractor (rather than vice versa). In addition, timing differences in the subsequent (250-500 ms) posterior contralateral negativity (PCN) indicated that attentional resources were allocated faster to Kanizsa, as compared to non-Kanizsa, 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 and switching to the required local state of attentional resolution. PMID:26498865

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

    PubMed Central

    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

  17. Population Distributions of Thymic Function in Adults: Variation by Sociodemographic Characteristics and Health Status.

    PubMed

    Feinstein, Lydia; Ferrando-Martínez, Sara; Leal, Manuel; Zhou, Xuan; Sempowski, Gregory D; Wildman, Derek E; Uddin, Monica; Aiello, Allison E

    2016-01-01

    The thymus is critical for mounting an effective immune response and maintaining health. However, epidemiologic studies characterizing thymic function in the population setting are lacking. Using data from 263 adults in the Detroit Neighborhood Health Study, we examined thymic function as measured by the number of signal joint T-cell receptor excision circles (sjTREC) and assessed associations with established indicators of physiological health. Overall, increasing age and male gender were significantly associated with reduced thymic function. Adjusting for covariates, individuals with elevated levels of the pro-inflammatory biomarkers C-reactive protein (β: -0.50 [95% CI: -0.82, -0.18] for moderate elevation, β: -0.29 [95% CI: -0.59, 0.00] for high elevation) and interleukin-6 (β: -0.60 [95% CI: -0.92, -0.28] for moderate elevation, β: -0.43 [95% CI: -0.77, -0.08] for severe elevation) also had lower thymic function. Compared to individuals with a BMI < 25, individuals who were overweight (β: 0.36 [95% CI: 0.07, 0.64]) or obese (β: 0.27 [95% CI: -0.03, 0.56]) had higher thymic function. Differences by self-rated health were not statistically significant. Our findings underscore demographic- and health-related gradients in thymic function among adult residents of Detroit, suggesting thymic function may be an important biomarker of health status in adults at the population level. PMID:27337555

  18. Thymic emigration patterns in patients with type 2 diabetes treated with metformin

    PubMed Central

    Dworacki, Grzegorz; Urazayev, Olzhas; Bekmukhambetov, Yerbol; Iskakova, Saule; Frycz, Bartosz A; Jagodziński, Paweł P; Dworacka, Marzena

    2015-01-01

    Recent data suggest that thymic output, which provides the naive T cells necessary for the normal functioning of T-cell-dependent immunosurveillance cellular immunity including anti-cancer protection, can be disturbed in the course of type 2 diabetes. Metformin, an anti-diabetic drug commonly confirmed as an agent with many potential anti-cancer activities, might be helpful in this immune correction. The profile of thymic output was evaluated in the current study on the basis of the signal-joint T-cell receptor excision circle (sjTREC) concentration in peripheral blood polymorphonuclear cells and thymic emigrant content in peripheral blood evaluated from CD127 and/or CD132 antigen expression. It was revealed that recent thymic emigrants and more differentiated CD127+ CD132+ cell populations were decreased among naive T cells and CD8+ T cells, whereas RTE count was increased in CD4+ T cells, and the CD127+ CD132+ cell population was less numerous than in non-diabetic participants. Terminally differentiated thymic emigrants, i.e. CD127− CD132+ cells, were increased in naive T cells and in CD8+ T cells. Metformin affects mainly the early phases of thymic export, increasing CD127+ CD132− and CD127+ CD132+ cell populations in naive T cells and the CD127+ CD132− population in CD4+ T lymphocytes. It could be concluded that type 2 diabetes deteriorates thymic immunostasis. The decreased thymic output could be compensated by metformin, especially with regard to CD4+ naive T cells. It is the first time that therapy with metformin has been documented by us as particularly useful in the control and normalization of thymus function, regarding correction of early populations of thymic emigrants. PMID:26271466

  19. New Treatment Greatly Improves Prognosis for Patients with AMD (Age-Related Macular Degeneration)

    MedlinePlus

    ... turn JavaScript on. Feature: Age-related Macular Degeneration New Treatment Greatly Improves Prognosis for Patients with AMD ... Eye Institute Photo Courtesy of: NEI In a new study of nearly 650 people with age-related ...

  20. Sex steroid ablation: an immuno-regenerative strategy for immunocompromised patients

    PubMed Central

    Velardi, Enrico; Dudakov, Jarrod A.; van den Brink, Marcel R.M.

    2016-01-01

    Age related decline in thymic function is a well-described process that results in reduced T cell development and thymic output of new naïve T cells. Thymic involution leads to reduced response to vaccines and new pathogens in otherwise healthy individuals; however, reduced thymic function is particularly detrimental in clinical scenarios where the immune system is profoundly depleted such as after chemotherapy, radiotherapy, infection and shock. Poor thymic function and restoration of immune competence has been correlated with increased risk of opportunistic infections, tumor relapse and autoimmunity. Apart from their primary role in sex dimorphism, sex steroid levels profoundly affect the immune system in general and, in fact, age-related thymic involution has been at least partially attributed to the increase of sex steroids at puberty. Subsequently it has been demonstrated that removal of sex steroids, or sex steroid ablation (SSA), triggers physiologic changes that ultimately led to thymic re-growth and improved T cell reconstitution in settings of hematopoietic stem cell transplant (HSCT). Although the cellular and molecular process underlying these regenerative effects are still poorly understood, SSA clearly represents an attractive therapeutic approach to enhance thymic function and restore immune competence in immunodeficient individuals. PMID:26039214

  1. Invasive Thymoma Protruding into the Superior Vena Cava through the Thymic Vein

    PubMed Central

    Yoshimura, Takashi; Matsubara, Yoshito; Yasuhara, Yumiko; Terada, Yasuji

    2015-01-01

    We report a rare case of protrusion of an invasive thymoma with intraluminal growth through the thymic vein into the superior vena cava (SVC) without direct invasion of the vessel walls. The tumor and left brachiocephalic vein were resected, and the tumor in the SVC was removed with temporal bypass of the right brachiocephalic vein and right auricle. Histopathological finding showed that the thymoma had protruded via a thymic vein. During resection of a thymoma, a detailed examination of thymic vein is necessary to ensure that no tumor tissue remains in the vessels. PMID:26299398

  2. In Vitro and In Situ Characterization of Fish Thymic Nurse Cells

    PubMed Central

    Álvarez, Francisco; López-Fierro, Pilar; Razquin, Blanca E.; Villena, Alberto J.; Zapata, Agustín G.

    1996-01-01

    We present an enzyme- and immuno-cytochemical, and ultrastructural characterization of trout thymic nurse cells (TNCs). Our data suggest that isolated trout thymic multicellular complexes are epithelial cells with acidic compartments that may be involved in the processing of antigens and in the generation of the MHC-II proteins that these cell express, and also that isolated TNCs are the In Vitro equivalent of the pale and intermediate electronlucent epithelial cells located in the inner zone of the trout thymus, constituting indirect evidence of the phylogenetical relationships of the inner zone of the teleost thymus with the thymic cortex of higher vertebrates. PMID:8828008

  3. Common cell biologic and biochemical changes in aging and age-related diseases of the eye: Toward new therapeutic approaches to age-related ocular diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reviews of information about age related macular degeneration (AMD), cataract, and glaucoma make it apparent that while each eye tissue has its own characteristic metabolism, structure and function, there are common perturbations to homeostasis that are associated with age-related dysfunction. The c...

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

    PubMed Central

    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

  5. Age-related alterations in retinal neurovascular and inflammatory transcripts

    PubMed Central

    Van Kirk, Colleen A.; VanGuilder, Heather D.; Young, Megan; Farley, Julie A.; Sonntag, William E.

    2011-01-01

    factor [Pedf]) displayed patterns of expression dissimilar to that previously demonstrated with diabetes. Conclusions The commonalities in retinal age-related and diabetes-induced molecular alterations provide support for the hypothesis that diabetes and aging engage some common para-inflammatory processes. However, these results also demonstrate that while the retinal genomic response to diabetes and aging share commonalities, they are not superimposable phenotypes. The observed changes in retinal gene expression provide further evidence of retinal alterations in neurovascular and inflammatory processes across the adult rat lifespan; this is indicative of para-inflammation that may contribute to the functional impairments that occur with advanced age. The data also suggest the potential for an additive effect of aging and diabetes in the development of diabetic complications. PMID:21633715

  6. A twin study on age-related macular degeneration.

    PubMed Central

    Meyers, S M

    1994-01-01

    A prospective twin study on age-related macular degeneration (AMD) recruited 83 monozygotic pairs, 28 dizygotic pairs, and one triplet set from 1986 through 1993. Zygosity was determined by genetic testing of red cell markers, HLA antigens, or specific DNA loci. There were no twin pairs in which I collected data on only one twin. To decrease ascertainment bias, after 1991 the recruitment notice did not mention AMD, and I did not ask about a history of eye disease before the eye examination. Because of this, twin pairs recruited from 1986 through 1991 were statistically analyzed separately from those after January 1, 1992. From 1986 through 1991, 23 twin pairs were recruited; 11 monozygotic and 2 dizygotic pairs had nonAMD retinal changes or no retinal abnormalities, 9 monozygotic pairs with AMD were all concordant, and 1 dizygotic pair was discordant for basal laminar drusen. The concordance rate of AMD did not differ significantly between monozygotic and dizygotic twin pairs (P = .10) for 1986 through 1991. In 1992 and 1993, 88 twin pairs and one triplet set were recruited; 49 monozygotic and 19 dizygotic pairs had nonAMD retinal changes or no retinal abnormalities, 14 monozygotic pairs with AMD were all concordant, and 2 of 7 dizygotic pairs were concordant for AMD. The nonidentical triplets (1 with and 2 without AMD) were categorized as one of the discordant dizygotic pairs in the statistical evaluation. In nontwin age-matched (within 2 or 5 years of age) or age- and sex-matched sibling pairs the concordance rate of AMD ranged from 16% to 25%. The concordance rate of AMD was significantly higher in monozygotic than in dizygotic twins (P = .001) for 1992 and 1993. The concordance rate was higher for monozygotic twin pairs recruited in 1992 and 1993 than in any of the four subsets of nontwin age-method or age- and sex-matched sibling pairs (P < .0001). Overall, from 1986 through 1993, 23 of 23 monozygotic and 2 of 8 dizygotic twin pairs were concordant for AMD

  7. WNT signaling suppression in the senescent human thymus.

    PubMed

    Ferrando-Martínez, Sara; Ruiz-Mateos, Ezequiel; Dudakov, Jarrod A; Velardi, Enrico; Grillari, Johannes; Kreil, David P; Muñoz-Fernandez, M Ángeles; van den Brink, Marcel R M; Leal, Manuel

    2015-03-01

    Human thymus is completely developed in late fetal stages and its function peaks in newborns. After the first year of life, the thymus undergoes a progressive atrophy that dramatically decreases de novo T-lymphocyte maturation. Hormonal signaling and changes in the microRNA expression network are identified as underlying causes of human thymus involution. However, specific pathways involved in the age-related loss of thymic function remain unknown. In this study, we analyzed differential gene-expression profile and microRNA expression in elderly (70 years old) and young (less than 10 months old and 11 years old) human thymic samples. Our data have shown that WNT pathway deregulation through the overexpression of different inhibitors by the nonadipocytic component of the human thymus stimulates the age-related involution. These results are of particular interest because interference of WNT signaling has been demonstrated in both animal models and in vitro studies, with the three major hallmarks of thymic involution: (i) epithelial structure disruption, (ii) adipogenic process, and (iii) thymocyte development arrest. Thus, our results suggest that secreted inhibitors of the WNT pathway could be explored as a novel therapeutical target in the reversal of the age-related thymic involution.

  8. Primary cilia distribution and orientation during involution of the bovine mammary gland.

    PubMed

    Biet, J; Poole, C A; Stelwagen, K; Margerison, J K; Singh, K

    2016-05-01

    The regulation of mammary gland involution occurs through multiple levels including environmental factors, hormones, and local intramammary signals. Primary cilia (PC) are signaling organelles that sense biochemical and biophysical extracellular stimuli and are vital for cellular and tissue function. The aim of this study was to examine the distribution, incidence, and orientation of PC. Furthermore, we determined changes in expression levels of the signal transducer and activator of transcription (STAT)6 at the onset of bovine mammary gland involution. Mammary tissue was collected from pasture-fed, primiparous, nonpregnant Friesian dairy cows at mid lactation (n=5 per group) killed 6-h after milking (lactating controls) and during involution after 7 and 28 d of nonmilking (NM). Fluorescent immunohistochemistry and confocal microscopy of tissue sections showed that PC were present on luminal secretory epithelial cells (SEC), myoepithelial cells (MEC), and stromal fibroblast cells (SFC). Furthermore, in all 3 experimental groups, different PC positions or orientations relative to the cell surface were identified on SEC and MEC, which projected toward the lumen and were either straight, bent, or deflected against the apical cell surface, whereas PC in SFC were confined to the interalveolar space. However, by 28-d NM, fewer PC projected into the luminal space and most appeared deflected or projected toward the interalveolar space. Furthermore, by 28-d NM, with the increase in stromal connective tissue, more PC were detected within the interalveolar and interlobular stroma. At 28-d NM, we observed a decrease in luminal cilia relative to the total number of cilia. The number of ciliated cells in the total fraction (SEC, MEC, and SFC) was the same for all 3 groups, although in the luminal fraction (SEC and MEC), PC per nuclei increased by 28-d NM relative to lactation. At all 3 stages, we detected variations in shape and orientation of PC within the same alveolus, with

  9. [Age-related Macular Degeneration in the Japanese].

    PubMed

    Yoshimura, Nagahisa

    2016-03-01

    Age-related macular degeneration (AMD) in the Japanese often shows different clinical features from those described in Caucasians. For example, we often observe choroidal neovascularization (CNV) in elderly patients without drusen in the fundus. The high incidence of polypoidal choroidal vasculopathy (PCV) in AMD among Japanese is well-known. The reason why such differences occur in clinical manifestations of AMD has been one of my main interests. In this review article, I will discuss the characteristics of AMD in the Japanese population, as found in our recent study. I. Prevalence and clinical characteristics of AMD in the Japanese population. Cohort studies are important to determine the prevalence and incidence of diseases. In Japan, cohort studies began to be carried out rather late compared with Western countries. Although good cohort studies from Japan are reported in the literature, the size of the cohorts was not sufficiently large to determine the prevalence of AMD. However, a recent meta-analysis of Asian cohorts has shown that the prevalence of late AMD in Asians is not different from that reported in Caucasians. On the other hand, the prevalence of early AMD appears lower in the Japanese than in Caucasians. Recently, we have published the results of the Nagahama Cohort study. In this cohort study, we found a high prevalence of drusen. It seems that the incidence of dry AMD is likely to increase among Japanese. In Japan, most retina specialists classify AMD into three categories : typical AMD, PCV, and retinal angiomatous proliferation (RAP). However, there are no definite diagnostic criteria to distinguish between the three conditions. To compare the clinical features of Japanese and Western cases of AMD, and to determine the incidence of the three types of AMD, we exchanged data about 100 consecutive cases between Kyoto University and Centre d'Ophtalmologie de Paris, France. Interestingly, the diagnoses made by the two institutes were not always in

  10. [Age-related Macular Degeneration in the Japanese].

    PubMed

    Yoshimura, Nagahisa

    2016-03-01

    Age-related macular degeneration (AMD) in the Japanese often shows different clinical features from those described in Caucasians. For example, we often observe choroidal neovascularization (CNV) in elderly patients without drusen in the fundus. The high incidence of polypoidal choroidal vasculopathy (PCV) in AMD among Japanese is well-known. The reason why such differences occur in clinical manifestations of AMD has been one of my main interests. In this review article, I will discuss the characteristics of AMD in the Japanese population, as found in our recent study. I. Prevalence and clinical characteristics of AMD in the Japanese population. Cohort studies are important to determine the prevalence and incidence of diseases. In Japan, cohort studies began to be carried out rather late compared with Western countries. Although good cohort studies from Japan are reported in the literature, the size of the cohorts was not sufficiently large to determine the prevalence of AMD. However, a recent meta-analysis of Asian cohorts has shown that the prevalence of late AMD in Asians is not different from that reported in Caucasians. On the other hand, the prevalence of early AMD appears lower in the Japanese than in Caucasians. Recently, we have published the results of the Nagahama Cohort study. In this cohort study, we found a high prevalence of drusen. It seems that the incidence of dry AMD is likely to increase among Japanese. In Japan, most retina specialists classify AMD into three categories : typical AMD, PCV, and retinal angiomatous proliferation (RAP). However, there are no definite diagnostic criteria to distinguish between the three conditions. To compare the clinical features of Japanese and Western cases of AMD, and to determine the incidence of the three types of AMD, we exchanged data about 100 consecutive cases between Kyoto University and Centre d'Ophtalmologie de Paris, France. Interestingly, the diagnoses made by the two institutes were not always in

  11. ON THE ROLE OF INVOLUTIONS IN THE DISCONTINUOUS GALERKIN DISCRETIZATION OF MAXWELL AND MAGNETOHYDRODYNAMIC SYSTEMS

    NASA Technical Reports Server (NTRS)

    Barth, Timothy

    2005-01-01

    The role of involutions in energy stability of the discontinuous Galerkin (DG) discretization of Maxwell and magnetohydrodynamic (MHD) systems is examined. Important differences are identified in the symmetrization of the Maxwell and MHD systems that impact the construction of energy stable discretizations using the DG method. Specifically, general sufficient conditions to be imposed on the DG numerical flux and approximation space are given so that energy stability is retained These sufficient conditions reveal the favorable energy consequence of imposing continuity in the normal component of the magnetic induction field at interelement boundaries for MHD discretizations. Counterintuitively, this condition is not required for stability of Maxwell discretizations using the discontinuous Galerkin method.

  12. A Hemispherical-Involute Cavity Receiver for Stirling Engine Powered by a Xenon Arc Solar Simulator

    NASA Astrophysics Data System (ADS)

    Li, Zhi-Gang; Tang, Da-Wei; Li, Tie; Du, Jing-Long

    2011-05-01

    We develop a solar simulator composed of multiple xenon arc lamps combined with a faceted paraboloidal dish concentrator to drive a Stirling engine in our laboratory for all-weather indoor testing. Experiments and numerical analysis are performed to determine the radiation flux and temperature distributions on the solar receiver surface. Based on the theoretical results, we present a receiver design for a solar Stirling engine with involute tubes closely conforming to the imaginary hemisphere to obtain a substantially uniform temperature field and a high solar-thermal efficiency of 67.1%.

  13. Involutive morphological modifications in the rat adrenal glomerular zone after a low-sodium diet.

    PubMed

    Palacios, G

    1978-05-15

    We have studied glomerular zone involution in the rat's adrenal gland after a period of hyperfunction brought about by a low-sodium diet. The changes observed in this zone effect those organoids that are more directly involved in steroid genesis; mitochondria, smooth endoplasmic reticulum and liposomes. The Golgi complexes appear very developed, often, showing, a positive acid phosphatase activity. Lysosomes suffered a considerable increase in their number, and carried out their digestive function on liposomes. All those changes discussed here are seen as an accomodation of this zone to the new normofunctional situation.

  14. Rathke's cleft cyst: A case report of recurrence and spontaneous involution.

    PubMed

    Rasmussen, Zachary; Abode-Iyamah, Kingsley O; Kirby, Patricia; Greenlee, Jeremy D W

    2016-10-01

    Rathke's cleft cysts (RCC) are sellar lesions that typically remain asymptomatic throughout life. Symptomatic patients present with headache, visual disturbance and/or pituitary dysfunction and are treated with resection. We present a 61-year-old woman diagnosed with RCC which was resected twice then recurred before undergoing spontaneous resolution. RCC are often managed without surgical intervention. Some of these lesions may spontaneously resolve without surgical intervention while others may become symptomatic. In patients with asymptomatic recurrent RCC conservative management is recommended. Spontaneous involution may occur following initial resection and recurrence of RCC.

  15. LTβR controls thymic portal endothelial cells for haematopoietic progenitor cell homing and T-cell regeneration.

    PubMed

    Shi, Yaoyao; Wu, Weiwei; Chai, Qian; Li, Qingqing; Hou, Yu; Xia, Huan; Ren, Boyang; Xu, Hairong; Guo, Xiaohuan; Jin, Caiwei; Lv, Mengjie; Wang, Zhongnan; Fu, Yang-Xin; Zhu, Mingzhao

    2016-01-01

    Continuous thymic homing of haematopoietic progenitor cells (HPCs) via the blood is critical for normal T-cell development. However, the nature and the differentiation programme of specialized thymic endothelial cells (ECs) controlling this process remain poorly understood. Here using conditional gene-deficient mice, we find that lymphotoxin beta receptor (LTβR) directly controls thymic ECs to guide HPC homing. Interestingly, T-cell deficiency or conditional ablation of T-cell-engaged LTβR signalling results in a defect in thymic HPC homing, suggesting the feedback regulation of thymic progenitor homing by thymic products. Furthermore, we identify and characterize a special thymic portal EC population with features that guide HPC homing. LTβR is essential for the differentiation and homeostasis of these thymic portal ECs. Finally, we show that LTβR is required for T-cell regeneration on irradiation-induced thymic injury. Together, these results uncover a cellular and molecular pathway that governs thymic EC differentiation for HPC homing. PMID:27493002

  16. LTβR controls thymic portal endothelial cells for haematopoietic progenitor cell homing and T-cell regeneration.

    PubMed

    Shi, Yaoyao; Wu, Weiwei; Chai, Qian; Li, Qingqing; Hou, Yu; Xia, Huan; Ren, Boyang; Xu, Hairong; Guo, Xiaohuan; Jin, Caiwei; Lv, Mengjie; Wang, Zhongnan; Fu, Yang-Xin; Zhu, Mingzhao

    2016-08-05

    Continuous thymic homing of haematopoietic progenitor cells (HPCs) via the blood is critical for normal T-cell development. However, the nature and the differentiation programme of specialized thymic endothelial cells (ECs) controlling this process remain poorly understood. Here using conditional gene-deficient mice, we find that lymphotoxin beta receptor (LTβR) directly controls thymic ECs to guide HPC homing. Interestingly, T-cell deficiency or conditional ablation of T-cell-engaged LTβR signalling results in a defect in thymic HPC homing, suggesting the feedback regulation of thymic progenitor homing by thymic products. Furthermore, we identify and characterize a special thymic portal EC population with features that guide HPC homing. LTβR is essential for the differentiation and homeostasis of these thymic portal ECs. Finally, we show that LTβR is required for T-cell regeneration on irradiation-induced thymic injury. Together, these results uncover a cellular and molecular pathway that governs thymic EC differentiation for HPC homing.

  17. LTβR controls thymic portal endothelial cells for haematopoietic progenitor cell homing and T-cell regeneration

    PubMed Central

    Shi, Yaoyao; Wu, Weiwei; Chai, Qian; Li, Qingqing; Hou, Yu; Xia, Huan; Ren, Boyang; Xu, Hairong; Guo, Xiaohuan; Jin, Caiwei; Lv, Mengjie; Wang, Zhongnan; Fu, Yang-Xin; Zhu, Mingzhao

    2016-01-01

    Continuous thymic homing of haematopoietic progenitor cells (HPCs) via the blood is critical for normal T-cell development. However, the nature and the differentiation programme of specialized thymic endothelial cells (ECs) controlling this process remain poorly understood. Here using conditional gene-deficient mice, we find that lymphotoxin beta receptor (LTβR) directly controls thymic ECs to guide HPC homing. Interestingly, T-cell deficiency or conditional ablation of T-cell-engaged LTβR signalling results in a defect in thymic HPC homing, suggesting the feedback regulation of thymic progenitor homing by thymic products. Furthermore, we identify and characterize a special thymic portal EC population with features that guide HPC homing. LTβR is essential for the differentiation and homeostasis of these thymic portal ECs. Finally, we show that LTβR is required for T-cell regeneration on irradiation-induced thymic injury. Together, these results uncover a cellular and molecular pathway that governs thymic EC differentiation for HPC homing. PMID:27493002

  18. Activation of human lymphocytes by supernatants from human thymic epithelium.

    PubMed Central

    Goust, J M; Vesole, D H; Fudenberg, H H

    1979-01-01

    Supernatants from human thymic epithelial cells (TS) were found to have a mitogenic effect on cultured human peripheral blood mononuclear cells and to potentiate their responses to lectins. This was not observed with culture supernatants from the human cell lines AV-3 and HeLa or from the murine cell line L-929. The maximum potentiating effects were observed with pokeweed mitogen (PWM) and phytohaemagglutinin (PHA), whereas the response to concanavalin A (Con A) was only slightly enhanced. TS also potentiated the mixed lymphocyte culture (MLC) response of normal T cells and thymocytes cultured with mitomycin C-treated B lymphoid cell lines. The mitogenic effect of TS was time-dependent and paralleled the appearance of lymphoid colonies in semi-solid agar. Chromatographical separation of concentrated serum-free TS on Sephadex G-100 yielded an active fraction of molecular weight 15,000--25,000 which had all the activities of unseparated TS. PMID:160851

  19. Activation of human lymphocytes by supernatants from human thymic epithelium.

    PubMed

    Goust, J M; Vesole, D H; Fudenberg, H H

    1979-11-01

    Supernatants from human thymic epithelial cells (TS) were found to have a mitogenic effect on cultured human peripheral blood mononuclear cells and to potentiate their responses to lectins. This was not observed with culture supernatants from the human cell lines AV-3 and HeLa or from the murine cell line L-929. The maximum potentiating effects were observed with pokeweed mitogen (PWM) and phytohaemagglutinin (PHA), whereas the response to concanavalin A (Con A) was only slightly enhanced. TS also potentiated the mixed lymphocyte culture (MLC) response of normal T cells and thymocytes cultured with mitomycin C-treated B lymphoid cell lines. The mitogenic effect of TS was time-dependent and paralleled the appearance of lymphoid colonies in semi-solid agar. Chromatographical separation of concentrated serum-free TS on Sephadex G-100 yielded an active fraction of molecular weight 15,000--25,000 which had all the activities of unseparated TS. PMID:160851

  20. [Complete resection for giant thymic carcinoma after simultaneous combination chemotherapy].

    PubMed

    Ueki, Tomoyuki; Ueshima, Y; Kurioka, H; Enoki, Y; Hosokawa, Y

    2005-04-01

    A 19-year-old man visited our hospital complaining of dyspnea. Chest X-ray and computed tomography (CT) showed a huge mass in the right anterior mediastinum. We diagnosed this as invasive thymoma by microscopic examination of specimens obtained by echo-guided needle biopsy. The patient underwent 6 courses chemotherapy [1st course : carboplatin (CBDCA) + doxorubicin hydrochloride (DXR) + vincristine sulfate (VCR) + cyclophosphamide (CPA), 2nd, 3rd-6th course : cisplatin (CDDP) + ADM + VCR + CPA]. At achievement of partial response (the reduction rate of the tumor size : 91.4%), the tumor was completely resected. The pathological examination of the resected specimens yielded a diagnosis of large cell carcinoma. Preoperative chemotherapy with ADOC regimen may be effective in advanced thymic carcinoma.

  1. Augmentation of mitogen responsiveness in human lymphocytes by a humoral factor obtained from thymic epithelial cultures.

    PubMed Central

    Hensen, E J; Hoefsmit, E C; Van Den Tweel, J G

    1978-01-01

    Supernatants derived from thymic epithelial cultures were studied for their effect in augmenting mitogen responsiveness in human thymocytes and lymphocytes. Incubation of these cells for 20 hr in diluted supernatants obtained from 14 to 25 day old cultures of thymic epithelium resulted in a significant increase in the response to Con A. The epithelial nature of the cells was confirmed by electron microscopy. Supernatants from fibroblast cultures or thymic epithelial cultures overgrown by fibroblasts were not effective, nor were supernatants from secondary epithelial outgrowths. The molecular weight of the active fraction appeared to be between 17,000 and 45,000 daltons. The data indicated that human thymus epithelium produced one or more humoral factors which were identical to, or shared properties with, thymic hormones. Images FIG. 1 p312-a PMID:307466

  2. TNF superfamily members play distinct roles in shaping the thymic stromal microenvironment.

    PubMed

    Bichele, Rudolf; Kisand, Kai; Peterson, Pärt; Laan, Martti

    2016-04-01

    The differentiation and proper function of thymic epithelial cells (TECs) depend on various tumor necrosis factor superfamily (TNFSF) signals that are needed to maintain the thymic stromal microenvironment. Nevertheless, the direct transcriptional effects of these signals on TECs remain unclear. To address this issue, we stimulated murine embryonic thymus tissue with selected TNFSF ligands and performed a gene expression profiling study. We show that Aire expression is a direct and specific effect of RANKL stimulation, whereas LTβ and TNFα are major inducers of chemokines in the thymic stroma and we propose differential NF-κB binding as one possible cause of these gene expression patterns. Our work provides further insight into the complex molecular pathways that shape the thymic microenvironment and maintain central tolerance. PMID:27011037

  3. [Intravenous immunoglobulin therapy in Morvan syndrome secondary to recurrent thymic carcinoma].

    PubMed

    Horta Baas, Gabriel

    2015-11-25

    Morvan's syndrome is a rare autoimmune channelopathy. A case of Morvan's syndrome is presented as a paraneoplastic syndrome associated to the recurrence of a well-differentiated thymic carcinoma, which showed a good clinical response to treatment with intravenous immunoglobulin.

  4. Safety and Tolerability Study of AAV2-sFLT01 in Patients With Neovascular Age-Related Macular Degeneration (AMD)

    ClinicalTrials.gov

    2016-10-20

    Macular Degeneration; Age-Related Maculopathies; Age-Related Maculopathy; Maculopathies, Age-Related; Maculopathy, Age-Related; Retinal Degeneration; Retinal Neovascularization; Gene Therapy; Therapy, Gene; Eye Diseases

  5. Comparative anatomical studies on the thyroid and thymic arteries. VI. Diprotodont marsupials.

    PubMed

    Yamasaki, Masahiro

    2016-06-01

    The thyroid and thymic arteries in 44 specimens from 18 species belonging to the diprotodont marsupials were investigated. The results were compared with those of polyprotodont marsupials, suncuses, rats, rabbits, guinea pigs, and man. The superior thyroid artery was constant in three superfamily groups. The inferior thyroid artery was extremely rare. The superior thymic artery arising from the thyrocervical trunk was observed in 1 phalangeroid and 2 macropodoids, and that arising from the vertebral artery occurred in 1 macropodoid. The middle thymic artery occurred in 1 phalangeroid, but was abundant in macropodoids. The inferior thymic artery was constant in koalas and phalangeroids, but was absent in half of the macropodoids. The thyroid ima, middle thymothyroid, and the supreme thymic arteries were absent in all diprotodonts. In addition to the usual thymus, diprotodonts have the superficial cervical thymus, which is only shared with guinea pigs. The superior superficial cervical thymic artery was absent in koalas and in half of the macropodoids, but was abundant in the phalangeroids. Conversely, the inferior superficial cervical thymic artery was constant in koalas and was dominant in the macropodoids. These results show that variations in the arterial patterns for both organs were much more prevalent in macropodoids than in phalangeroids, while the arterial patterns in koalas were characteristic. As a whole, the arteries for both organs were more complex in diprotodonts than in polyprotodonts or rats, but more simple than those in rabbits or man. The superior superficial cervical thymic arteries, which showed various patterns, were compared with those in guinea pigs. PMID:26472114

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

    SciTech Connect

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

    1985-02-01

    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 /sup 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.

  7. Phase II Study of Carboplatin and Paclitaxel in Advanced Thymoma and Thymic Carcinoma

    PubMed Central

    Lemma, Girum L.; Lee, Ju-Whei; Aisner, Seena C.; Langer, Corey J.; Tester, William J.; Johnson, David H.; Loehrer, Patrick J.

    2011-01-01

    Purpose The purpose of this study was to evaluate the impact of carboplatin and paclitaxel in patients with advanced previously untreated thymoma and thymic carcinoma. Patients and Methods We conducted a prospective multicenter study in patients with unresectable thymoma (n = 21) or thymic carcinoma (n = 23). Patients were treated with carboplatin (area under the curve, 6) plus paclitaxel (225 mg/m2) every 3 weeks for a maximum of six cycles. The primary end point of this trial was to evaluate the objective response rate. Results From February 2001 through January 2008, 46 patients were enrolled. Thirteen patients had grade 4 or greater toxicity, mostly neutropenia. Using RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria, three complete responses (CRs) and six partial responses (PRs; objective response rate [ORR], 42.9%; 90% CI, 24.5% to 62.8%) were observed in the thymoma cohort; 10 patients had stable disease. For patients with thymic carcinoma, no CRs and five PRs (ORR, 21.7%; 90% CI, 9.0% to 40.4%) were observed; 12 patients had stable disease. Progression-free survival (PFS) was 16.7 (95% CI, 7.2 to 19.8) and 5.0 (95% CI, 3.0 to 8.3) months for thymoma and thymic carcinoma cohorts, respectively. To date, only seven patients (33.3%) with thymoma have died, compared with 16 patients (69.6%) with thymic carcinoma. Median survival time was 20.0 months (95% CI, 5.0 to 43.6 months) for patients with thymic carcinoma, but it has not been reached for patients with thymoma. Conclusion Carboplatin plus paclitaxel has moderate clinical activity for patients with thymic malignancies, but this seems less than expected with anthracycline-based therapy. Patients with thymic carcinoma have poorer PFS and overall survival than patients with thymoma. PMID:21502559

  8. FSP1+ fibroblast subpopulation is essential for the maintenance and regeneration of medullary thymic epithelial cells

    PubMed Central

    Sun, Lina; Sun, Chenming; Liang, Zhanfeng; Li, Hongran; Chen, Lin; Luo, Haiying; Zhang, Hongmei; Ding, Pengbo; Sun, Xiaoning; Qin, Zhihai; Zhao, Yong

    2015-01-01

    Thymic epithelial cells (TECs) form a 3-dimentional network supporting thymocyte development and maturation. Besides epithelium and thymocytes, heterogeneous fibroblasts are essential components in maintaining thymic microenvironments. However, thymic fibroblast characteristics, development and function remain to be determined. We herein found that thymic non-hematopoietic CD45-FSP1+ cells represent a unique Fibroblast specific protein 1 (FSP1)—fibroblast-derived cell subset. Deletion of these cells in FSP1-TK transgenic mice caused thymus atrophy due to the loss of TECs, especially mature medullary TECs (MHCIIhigh, CD80+ and Aire+). In a cyclophosphamide-induced thymus injury and regeneration model, lack of non-hematopoietic CD45-FSP1+ fibroblast subpopulation significantly delayed thymus regeneration. In fact, thymic FSP1+ fibroblasts released more IL-6, FGF7 and FSP1 in the culture medium than their FSP1- counterparts. Further experiments showed that the FSP1 protein could directly enhance the proliferation and maturation of TECs in the in vitro culture systems. FSP1 knockout mice had significantly smaller thymus size and less TECs than their control. Collectively, our studies reveal that thymic CD45-FSP1+ cells are a subpopulation of fibroblasts, which is crucial for the maintenance and regeneration of TECs especially medullary TECs through providing IL-6, FGF7 and FSP1. PMID:26445893

  9. Bioengineering Thymus Organoids to Restore Thymic Function and Induce Donor-Specific Immune Tolerance to Allografts

    PubMed Central

    Fan, Yong; Tajima, Asako; Goh, Saik Kia; Geng, Xuehui; Gualtierotti, Giulio; Grupillo, Maria; Coppola, Antonina; Bertera, Suzanne; Rudert, William A; Banerjee, Ipsita; Bottino, Rita; Trucco, Massimo

    2015-01-01

    One of the major obstacles in organ transplantation is to establish immune tolerance of allografts. Although immunosuppressive drugs can prevent graft rejection to a certain degree, their efficacies are limited, transient, and associated with severe side effects. Induction of thymic central tolerance to allografts remains challenging, largely because of the difficulty of maintaining donor thymic epithelial cells in vitro to allow successful bioengineering. Here, the authors show that three-dimensional scaffolds generated from decellularized mouse thymus can support thymic epithelial cell survival in culture and maintain their unique molecular properties. When transplanted into athymic nude mice, the bioengineered thymus organoids effectively promoted homing of lymphocyte progenitors and supported thymopoiesis. Nude mice transplanted with thymus organoids promptly rejected skin allografts and were able to mount antigen-specific humoral responses against ovalbumin on immunization. Notably, tolerance to skin allografts was achieved by transplanting thymus organoids constructed with either thymic epithelial cells coexpressing both syngeneic and allogenic major histocompatibility complexes, or mixtures of donor and recipient thymic epithelial cells. Our results demonstrate the technical feasibility of restoring thymic function with bioengineered thymus organoids and highlight the clinical implications of this thymus reconstruction technique in organ transplantation and regenerative medicine. PMID:25903472

  10. Bioengineering Thymus Organoids to Restore Thymic Function and Induce Donor-Specific Immune Tolerance to Allografts.

    PubMed

    Fan, Yong; Tajima, Asako; Goh, Saik Kia; Geng, Xuehui; Gualtierotti, Giulio; Grupillo, Maria; Coppola, Antonina; Bertera, Suzanne; Rudert, William A; Banerjee, Ipsita; Bottino, Rita; Trucco, Massimo

    2015-07-01

    One of the major obstacles in organ transplantation is to establish immune tolerance of allografts. Although immunosuppressive drugs can prevent graft rejection to a certain degree, their efficacies are limited, transient, and associated with severe side effects. Induction of thymic central tolerance to allografts remains challenging, largely because of the difficulty of maintaining donor thymic epithelial cells in vitro to allow successful bioengineering. Here, the authors show that three-dimensional scaffolds generated from decellularized mouse thymus can support thymic epithelial cell survival in culture and maintain their unique molecular properties. When transplanted into athymic nude mice, the bioengineered thymus organoids effectively promoted homing of lymphocyte progenitors and supported thymopoiesis. Nude mice transplanted with thymus organoids promptly rejected skin allografts and were able to mount antigen-specific humoral responses against ovalbumin on immunization. Notably, tolerance to skin allografts was achieved by transplanting thymus organoids constructed with either thymic epithelial cells coexpressing both syngeneic and allogenic major histocompatibility complexes, or mixtures of donor and recipient thymic epithelial cells. Our results demonstrate the technical feasibility of restoring thymic function with bioengineered thymus organoids and highlight the clinical implications of this thymus reconstruction technique in organ transplantation and regenerative medicine.

  11. Thymic anlage is colonized by progenitors restricted to T, NK, and dendritic cell lineages.

    PubMed

    Masuda, Kyoko; Itoi, Manami; Amagai, Takashi; Minato, Nagahiro; Katsura, Yoshimoto; Kawamoto, Hiroshi

    2005-03-01

    It remains controversial whether the thymus-colonizing progenitors are committed to the T cell lineage. A major problem that has impeded the characterization of thymic immigrants has been that the earliest intrathymic progenitors thus far identified do not necessarily represent the genuine thymic immigrants, because their developmental potential should have been influenced by contact with the thymic microenvironment. In the present study, we examined the developmental potential of the ontogenically earliest thymic progenitors of day 11 murine fetus. These cells reside in the surrounding mesenchymal region and have not encountered thymic epithelial components. Flow cytometric and immunohistochemical analyses demonstrated that these cells are exclusively Lin(-)c-kit(+)IL-7R(+). Limiting dilution analyses disclosed that the progenitors with T cell potential were abundant, while those with B cell potential were virtually absent in the region of day 11 thymic anlage. Clonal analyses reveled that they are restricted to T, NK, and dendritic cell lineages. Each progenitor was capable of forming a large number of precursors that may clonally accommodate highly diverse TCRbeta chains. These results provide direct evidence that the progenitors restricted to the T/NK/dendritic cell lineage selectively immigrate into the thymus.

  12. [Treatment of exudative age-related macular degeneration].

    PubMed

    Yuzawa, M

    2000-12-01

    I PROPHYLACTIC TREATMENT: We followed 75 eyes contralateral to eyes with exudative age-related macular degeneration (AMD), using indocyanine green angiography (IA), for more than one year. Hyperfluorescent areas in the late phase of IA were seen in 19 eyes at the initial examination, and in 25 eyes during follow-up. Exudative AMD developed in 9 of the 25 eyes. Using timetable analysis, we estimated that 11% of these 27 eyes developed AMD within one year and 55% within three years. The hyperfluorescent areas seen on IA appeared to be latent choroidal neovascularization (CNV) under the retinal pigment epithelium. We propose that photocoagulation aimed at hyperfluorescent areas should be considered in such cases. We performed prophylactic laser photocoagulation in 21 eyes, which were then followed up for at least six months. These eyes all had 10 or more serous drusen within 1,500 microns of the fovea and did not show hyperfluorescence, suggesting latent CNV in the late phase of IA. The majority or a small fraction of the serous drusen disappeared in 48% and 18% of the 21 eyes, respectively. CNV appeared adjacent to the laser scar in one eye (5%). Judging from these results, it is important to establish a method of definitively abolishing drusen and preventing the development of CNV. II TREATMENT OF CNV: Of 229 eyes which showed occult CNV in fluorescein angiography (FA), 124 eyes (54%) showed classic CNV outside the fovea on IA. One hundred and two of the 124 eyes (45%) underwent laser photocoagulation. We evaluated indocyanine green guided laser photocoagulation of extrafoveal CNV in 139 eyes. The success rate was 81% at 3 months after laser photocoagulation. This was estimated using timetable analyses to have decreased to 78% at one year and 71% at three years. Eighty percent of successfully treated eyes showed maintained or improved visual acuity. These results did not differ significantly from those obtained with laser photocoagulation based on FA findings. When

  13. Practices related to postpartum uterine involution in the Western Highlands of Guatemala

    PubMed Central

    Radoff, K.A.; Thompson, Lisa M.; Bly, KC; Romero, Carolina

    2013-01-01

    Background Guatemala has the third highest level of maternal mortality in Latin America. Postpartum haemorrhage is the main cause of maternal mortality. In rural Guatemala, most women rely on Traditional Birth Attendants (TBAs) during labour, delivery, and the postpartum period. Little is known about current postpartum practices that may contribute to uterine involution provided by Mam- and Spanish-speaking TBAs in the Western Highlands of Guatemala. Methods a qualitative study was conducted with 39 women who participated in five focus groups in the San Marcos Department of Guatemala. Questions regarding postpartum practices were discussed during four focus groups of TBAs and one group of auxiliary nurses. Results three postpartum practices believed to aid postpartum uterine involution were identified: use of the chuj (Mam) (Spanish, temazcal), a traditional wood-fired sauna-bath used by Mam-speaking women; herbal baths and teas; and administration of biomedicines. Conclusions TBAs provide the majority of care to women during childbirth and the postpartum period and have developed a set of practices to prevent and treat postpartum haemorrhage. Integration of these practices may prove an effective method to reduce maternal morbidity and mortality in the Western Highlands of Guatemala. PMID:22762787

  14. Controlled intracellular proteolysis during postpartal involution of the uterus: characterization and regulation of an alkaline proteinase.

    PubMed

    Roth, M; Hoechst, M; Afting, E G

    1981-01-01

    The postpartal involution of the uterus is predominantly due to cellular hypotrophy. This implies an intracellular proteolytic system which must be carefully controlled pre and post partum. We have characterized and partially purified a proteinase with an alkaline pH-optimum of activity and a proteinase inhibitor protein which inhibits this proteinase very strongly. The alkaline proteinase copurifies with the actomyosin complex of the uterine myometrium and degrades the actomyosin complex with a concomitant loss of its myosin-ATPase activity. The alkaline proteinase is a very labile enzyme, markedly sensitive to SH-group modifying agents and has very high molecular weight at the present state of purification. This proteolytic enzyme could specifically be separated from the main components of the actomyosin complex by extraction with low ionic strength phosphate buffers. The proteinase inhibitor protein may control the activity of this alkaline proteinase during pregnancy and involution. The inhibitor protein raises 15-fold during pregnancy, possibly blocks important steps of intracellular proteolysis and permits organ growth. The dramatic fall of the inhibitor protein activity after parturition, which precedes the loss of weight, could release the proteolytic system, including the alkaline proteinase, and permits controlled intracellular degradation.

  15. New modeling method of spiral bevel gears with spherical involute based on CATIA

    NASA Astrophysics Data System (ADS)

    Hong, Zhaobin; Yang, Zhaojun; Zhang, Xuecheng; Wang, Yankun

    2010-12-01

    Based on the generating principle of generating line of spiral bevel gears with spherical involute, a new method for building the model of spiral bevel gears with spherical involute is presented by utilizing the modules of part design, assembly design and kinematic simulation in CATIA. In the part design module of CATIA, the models of base cone, tangent surface, and generating line are built respectively. And the built models are assembled in the assembly environment; the simulation of pure rolling is accomplished in the environment of kinematics; and the model of the gear surface is built using the function of tracks. Then the solid model of the spiral bevel gear is built through the functions of transferring the model's file format, multi-section sweep and solid fill. Finally, the analysis to the performance of the bevel gear transmission is conducted. In the environment of the assembly design, the solid model of the gearwheel and the pinion are inserted respectively, and then the assembly is accomplished by applying the constraints. And in the environment of kinematics, the meshing simulation of the bevel gear pair is accomplished by applying angle drive. The research indicates that this method can build the model of spiral bevel gears accurately and rapidly, and the model can illustrate the gearing correctly.

  16. New modeling method of spiral bevel gears with spherical involute based on CATIA

    NASA Astrophysics Data System (ADS)

    Hong, Zhaobin; Yang, Zhaojun; Zhang, Xuecheng; Wang, Yankun

    2011-05-01

    Based on the generating principle of generating line of spiral bevel gears with spherical involute, a new method for building the model of spiral bevel gears with spherical involute is presented by utilizing the modules of part design, assembly design and kinematic simulation in CATIA. In the part design module of CATIA, the models of base cone, tangent surface, and generating line are built respectively. And the built models are assembled in the assembly environment; the simulation of pure rolling is accomplished in the environment of kinematics; and the model of the gear surface is built using the function of tracks. Then the solid model of the spiral bevel gear is built through the functions of transferring the model's file format, multi-section sweep and solid fill. Finally, the analysis to the performance of the bevel gear transmission is conducted. In the environment of the assembly design, the solid model of the gearwheel and the pinion are inserted respectively, and then the assembly is accomplished by applying the constraints. And in the environment of kinematics, the meshing simulation of the bevel gear pair is accomplished by applying angle drive. The research indicates that this method can build the model of spiral bevel gears accurately and rapidly, and the model can illustrate the gearing correctly.

  17. Infusions of casein hydrolyzates into the mammary gland disrupt tight junction integrity and induce involution in cows.

    PubMed

    Shamay, A; Shapiro, F; Leitner, G; Silanikove, N

    2003-04-01

    Milk stasis triggers local stimuli, which make the tight junctions leak and trigger involution. The aim of the study was to test the hypothesis that casein hydrolyzates compromise tight junction integrity and dry-off milk secretion in dairy cows. Six repeated doses of casein hydrolyzates after each milking during 3 d caused drastic changes in mammary secretion and composition, which were associated with irreversible cessation of milk secretion. No such changes were recorded in the control glands that had been treated with nonhydrolyzed casein. Treatment with casein hydrolyzates disturbed tight junction integrity within 8 h (as indicated by changes in Na+ and K+ concentrations), reduced the concentrations of lactose precipitously, activated the plasmin activator-plasminogen-plasmin system, and induced the secretion of immunoglobulin type G and lactoferrin. At the end of the 3-d treatments, we stopped milking the experimental and control glands. Milk composition 19 d later was similar in the experimental and control glands and was consistent with the composition expected in fully involuted glands. We conclude that casein hydrolyzates are among the milk-borne factors that cause the disruption of tight junction integrity and induce involution in cows. The process induced by casein hydrolyzate was more rapid and synchronized than the involution induced at drying-off. PMID:12741550

  18. Description of spectral properties of a generalized spectral problem with involution for differentiation operator of the second order

    NASA Astrophysics Data System (ADS)

    Sadybekov, Makhmud A.; Sarsenbi, Abdizhahan; Tengayeva, Aizhan

    2016-08-01

    In this paper, we consider a spectral problem for a model differential operator of the second order with involution. The operator is given by a differential expression ℓu = -u″(-x) and boundary conditions of the general form. A criterion of the basis property of systems of eigenfunctions of the operator is set in the sense of coefficients of the boundary conditions.

  19. Mechanical strain induces involution-associated events in mammary epithelial cells

    PubMed Central

    Quaglino, Ana; Salierno, Marcelo; Pellegrotti, Jesica; Rubinstein, Natalia; Kordon, Edith C

    2009-01-01

    Background Shortly after weaning, a complex multi-step process that leads to massive epithelial apoptosis is triggered by tissue local factors in the mouse mammary gland. Several reports have demonstrated the relevance of mechanical stress to induce adaptive responses in different cell types. Interestingly, these signaling pathways also participate in mammary gland involution. Then, it has been suggested that cell stretching caused by milk accumulation after weaning might be the first stimulus that initiates the complete remodeling of the mammary gland. However, no previous report has demonstrated the impact of mechanical stress on mammary cell physiology. To address this issue, we have designed a new practical device that allowed us to evaluate the effects of radial stretching on mammary epithelial cells in culture. Results We have designed and built a new device to analyze the biological consequences of applying mechanical stress to cells cultured on flexible silicone membranes. Subsequently, a geometrical model that predicted the percentage of radial strain applied to the elastic substrate was developed. By microscopic image analysis, the adjustment of these calculations to the actual strain exerted on the attached cells was verified. The studies described herein were all performed in the HC11 non-tumorigenic mammary epithelial cell line, which was originated from a pregnant BALB/c mouse. In these cells, as previously observed in other tissue types, mechanical stress induced ERK1/2 phosphorylation and c-Fos mRNA and protein expression. In addition, we found that mammary cell stretching triggered involution associated cellular events as Leukemia Inhibitory Factor (LIF) expression induction, STAT3 activation and AKT phosphorylation inhibition. Conclusion Here, we show for the first time, that mechanical strain is able to induce weaning-associated events in cultured mammary epithelial cells. These results were obtained using a new practical and affordable device

  20. Involvement of Different networks in mammary gland involution after the pregnancy/lactation cycle: Implications in breast cancer.

    PubMed

    Zaragozá, Rosa; García-Trevijano, Elena R; Lluch, Ana; Ribas, Gloria; Viña, Juan R

    2015-04-01

    Early pregnancy is associated with a reduction in a woman's lifetime risk for breast cancer. However, different studies have demonstrated an increase in breast cancer risk in the years immediately following pregnancy. Early and long-term risk is even higher if the mother age is above 35 years at the time of first parity. The proinflammatory microenvironment within the mammary gland after pregnancy renders an "ideal niche" for oncogenic events. Signaling pathways involved in programmed cell death and tissue remodeling during involution are also activated in breast cancer. Herein, the major signaling pathways involved in mammary gland involution, signal transducer and activator of transcription (STAT3), nuclear factor-kappa B (NF-κB), transforming growth factor beta (TGFβ), and retinoid acid receptors (RARs)/retinoid X receptors (RXRs), are reviewed as part of the complex network of signaling pathways that crosstalk in a contextual-dependent manner. These factors, also involved in breast cancer development, are important regulatory nodes for signaling amplification after weaning. Indeed, during involution, p65/p300 target genes such as MMP9, Capn1, and Capn2 are upregulated. Elevated expression and activities of these proteases in breast cancer have been extensively documented. The role of these proteases during mammary gland involution is further discussed. MMPs, calpains, and cathepsins exert their effect by modification of the extracellular matrix and intracellular proteins. Calpains, activated in the mammary gland during involution, cleave several proteins located in cell membrane, lysosomes, mitochondria, and nuclei favoring cell death. Besides, during this period, Capn1 is most probably involved in the modulation of preadipocyte differentiation through chromatin remodeling. Calpains can be implicated in cell anchoring loss, providing a proper microenvironment for tumor growth. A better understanding of the role of any of these proteases in tumorigenesis may

  1. Ontogeny of Rat Thymic Epithelium Defined by Monoclonal Anticytokeratin Antibodies

    PubMed Central

    Jovanović, Suzana; Vasiljevski, Milijana; Dujić, Aleksandar

    1990-01-01

    Ontogenetic study on the expression of cytokeratin (CK) polypeptides within particular subsets of rat thymic epithelial cells (TEC) has been performed by a large panel of anti-CK monoclonal antibodies (mAbs) using the streptavidin-biotin immunoperoxidase method. Simultaneous presence of two or more CK subunits in the same TEC has been demonstrated by double immunoflouorescence labeling. The obtained results showed that the expression of CK polypeptides in fetal and neonatal thymus differed from the adult patterns. The main difference was observed in expression of CK10, 18, and 19 polypeptides. During fetal ontogeny, CK10 and 18 are markers for most medullary TEC or a subset of medullary TEC, respectively, whereas CK19 is mainly a pan-TEC marker. In the adult animals, they are localized in the cortical and a subset of medullary TEC (CK18), subcapsular/perivascular and some medullary TEC (CK19), or in a subset of medullary TEC and Hasall’s corpuscles (HC) (CK10). The switch in their expression in the cortex was observed during the first two weeks of postnatal life. PMID:1726554

  2. Thymic regulation of the hypothalamic-pituitary-gonadal axis.

    PubMed

    Hall, N R; O'Grady, M P; Menzies, R A

    1992-04-01

    The thymus gland and the cells that it regulates produce a number of soluble factors that are capable of indirectly modulating the immune system via reproductive neuroendocrine circuits. Studies dating to the turn of the century were designed to evaluate the effects of partially purified thymic extracts in treating various reproductive disorders as well as changes in gonadal tissue weights. More recent studies have focused on the chemical nature of the factors responsible for regulating reproductive function. A number of factors have been described. These include thymosin beta 4 which has been found to stimulate the release of luteinizing hormone releasing hormone and luteinizing hormone (LH). Other factors such as interleukin-1 (IL-1) have been found to inhibit the release of these two peptides. IL-1 has also been found to alter the expression of LH receptors in rat granulosa cells. Certain interferons have been found capable of suppressing estrogen and progesterone release. While many of the studies have been carried out using adult animal models, there is increasing evidence that exposure to cytokines during early development can have long lasting if not permanent effects upon the reproductive axis. These and related topics are the subject of this review.

  3. Surgical Approaches for Stage IVA Thymic Epithelial Tumors.

    PubMed

    Shapiro, Mark; Korst, Robert J

    2014-01-14

    Thymic epithelial tumors (TET) are rare mediastinal neoplasms that can metastasize to the pleural space (stage IVA). Complete surgical resection remains the backbone of therapy for patients with early stage TET, however, the role of surgery in the management of patients with stage IVA disease is not fully defined. Published reports in this regard are mainly small, retrospective, and uncontrolled, with unclear inclusion criteria. Surgical options to manage pleural disease include metastasectomy, extrapleural pneumonectomy, and metastasectomy/pleurectomy combined with heated intrapleural chemotherapy. The choice of the most appropriate surgical strategy needs to be individualized according to the quantity and location of disease, the patient's overall condition, as well as operator and institutional expertise. In the majority of cases, metastasectomy of pleural implants will be sufficient to achieve a complete resection. The available literature suggests that in selected patients with stage IVA TET, delivery of neoadjuvant chemotherapy followed by complete resection is a viable treatment option that can be associated with long-term survival.

  4. Thymic Selection of T Cells as Diffusion with Intermittent Traps

    NASA Astrophysics Data System (ADS)

    Košmrlj, Andrej

    2011-04-01

    T cells orchestrate adaptive immune responses by recognizing short peptides derived from pathogens, and by distinguishing them from self-peptides. To ensure the latter, immature T cells (thymocytes) diffuse within the thymus gland, where they encounter an ensemble of self-peptides presented on (immobile) antigen presenting cells. Potentially autoimmune T cells are eliminated if the thymocyte binds sufficiently strongly with any such antigen presenting cell. We model thymic selection of T cells as a random walker diffusing in a field of immobile traps that intermittently turn "on" and "off". The escape probability of potentially autoimmune T cells is equivalent to the survival probability of such a random walker. In this paper we describe the survival probability of a random walker on a d-dimensional cubic lattice with randomly placed immobile intermittent traps, and relate it to the result of a well-studied problem where traps are always "on". Additionally, when switching between the trap states is slow, we find a peculiar caging effect for the survival probability.

  5. Sex hormones have pervasive effects on thymic epithelial cells

    PubMed Central

    Dumont-Lagacé, Maude; St-Pierre, Charles; Perreault, Claude

    2015-01-01

    The goal of our study was to evaluate at the systems-level, the effect of sex hormones on thymic epithelial cells (TECs). To this end, we sequenced the transcriptome of cortical and medullary TECs (cTECs and mTECs) from three groups of 6 month-old mice: males, females and males castrated at four weeks of age. In parallel, we analyzed variations in the size of TEC subsets in those three groups between 1 and 12 months of age. We report that sex hormones have pervasive effects on the transcriptome of TECs. These effects were exquisitely TEC-subset specific. Sexual dimorphism was particularly conspicuous in cTECs. Male cTECs displayed low proliferation rates that correlated with low expression of Foxn1 and its main targets. Furthermore, male cTECs expressed relatively low levels of genes instrumental in thymocyte expansion (e.g., Dll4) and positive selection (Psmb11 and Ctsl). Nevertheless, cTECs were more abundant in males than females. Accumulation of cTECs in males correlated with differential expression of genes regulating cell survival in cTECs and cell differentiation in mTECs. The sexual dimorphism of TECs highlighted here may be mechanistically linked to the well-recognized sex differences in susceptibility to infections and autoimmune diseases. PMID:26250469

  6. A Microfabricated Segmented-Involute-Foil Regenerator for Enhancing Reliability and Performance of Stirling Engines

    NASA Technical Reports Server (NTRS)

    Ibrahim, Mounir; Danila, Daniel; Simon, Terrence; Mantell, Susan; Sun, Liyong; Gadeon, David; Qiu, Songgang; Wood, Gary; Kelly, Kevin; McLean, Jeffrey

    2007-01-01

    An actual-size microfabricated regenerator comprised of a stack of 42 disks, 19 mm diameter and 0.25 mm thick, with layers of microscopic, segmented, involute-shaped flow channels was fabricated and tested. The geometry resembles layers of uniformly-spaced segmented-parallel-plates, except the plates are curved. Each disk was made from electro-plated nickel using the LiGA process. This regenerator had feature sizes close to those required for an actual Stirling engine but the overall regenerator dimensions were sized for the NASA/Sunpower oscillating-flow regenerator test rig. Testing in the oscillating-flow test rig showed the regenerator performed extremely well, significantly better than currently used random-fiber material, producing the highest figures of merit ever recorded for any regenerator tested in that rig over its approximately 20 years of use.

  7. Generation and Computerized Simulation of Meshing and Contact of Modified Involute Helical Gears

    NASA Technical Reports Server (NTRS)

    Litvin, Faydor L.; Chen, Ningxin; Lu, Jian

    1995-01-01

    The design and generation of modified involute helical gears that have a localized and stable bearing contact, and reduced noise and vibration characteristics are described. The localization of the bearing contact is achieved by the mismatch of the two generating surfaces that are used for generation of the pinion and the gear. The reduction of noise and vibration will be achieved by application of a parabolic function of transmission errors that is able to absorb the almost linear function of transmission errors caused by gear misalignment. The meshing and contact of misaligned gear drives can be analyzed by application of computer programs that have been developed. The computations confirmed the effectiveness of the proposed modification of the gear geometry. A numerical example that illustrates the developed theory is provided.

  8. Mechanistically linking age-related diseases and dietary carbohydrate via autophagy and the ubiquitin proteolytic systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiological data indicate that consuming diets that deliver sugar to the blood rapidly (called high glycemic index, GI) is associated with enhanced risk for age-related diseases such as cardiovascular disease, type 2 diabetes, cataract and age-related macular degeneration (AMD). These debilities...

  9. College Students' Attitudes towards Age-Related Changes in Physical Appearance.

    ERIC Educational Resources Information Center

    Kanter, Allison; Agliata, Daniel; Tantleff-Dunn, Stacey

    The aim of this study was to identify factors associated with young adults' concerns about age related changes in body image and their anticipated impact on psychosocial functioning. One hundred and sixty-seven college students completed the Body Image and Aging Survey, designed to assess age related issues in body image, the Peer Dieting Survey,…

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

    ERIC Educational Resources Information Center

    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…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  12. Role of thymic peptides as transmitters between the neuroendocrine and immune systems.

    PubMed

    Dardenne, M

    1999-10-01

    Thymic peptides, a heterogenous family of polypeptidic hormones synthesized within the thymus, not only exert important regulatory effects within both the immune and neuroendocrine systems but are also themselves subject to control by hormones derived from the hypothalamic-pituitary-adrenal axis (HPA) and other endocrine glands. Regarding thymic hormonal function, thymulin production is up-regulated by several hormones, including prolactin, growth hormone and thyroid hormones. Other aspects of the physiology of thymic epithelial cells can also be modulated by hormones and neuropeptides, particularly cytokeratin expression, cell growth and production of extracellular matrix proteins, thus characterizing the pleiotrophic action of these molecules on the thymic epithelium. Conversely, thymic-derived peptides also regulate hormone release from the HPA axis and may act directly on target endocrine glands of this axis, modulating gonadal tissues. In addition, it has recently been shown that thymulin can modulate some peripheral nervous sensory functions, including those related to sensitivity to pain. According to the dose given, thymulin induces or reduces hyperalgesia related to both mechanical and thermal nociceptors and thus represents an important interface between the immune, endocrine and nervous systems.

  13. Effect of Bcl11b genotypes and {gamma}-radiation on the development of mouse thymic lymphomas

    SciTech Connect

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

    2008-08-22

    Bcl11b is a haploinsufficient tumor suppressor gene and expressed in many tissues such as thymus, brain and skin. Irradiated Bcl11b{sup +/-} heterozygous mice mostly develop thymic lymphomas, but the preference of Bcl11b inactivation for thymic lymphomas remains to be addressed. We produced Bcl11b{sup +/-} heterozygous and Bcl11b wild-type mice of p53{sup +/-} background and compared their incidence of {gamma}-ray induced thymic lymphomas. Majority of the tumors in p53{sup +/-} mice were skin tumors, and only 5 (36%) of the 14 tumors were thymic lymphomas. In contrast, Bcl11b{sup +/-}p53{sup +/-} 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 {gamma}-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.

  14. [The genetic variability of complement system in pathogenesis of age-related macular degeneration].

    PubMed

    Kubicka-Trząska, Agnieszka; Karska-Basta, Izabella; Dziedzina, Sylwia; Sanak, Marek

    2015-01-01

    Age-related macular degeneration is the leading cause of irreversible central vision impairment in people aged over 50 in developed countries. Age-related macular degeneration is a complex disease derived from environmental, immune and genetic factors. The complement pathway has been implicated in the pathogenesis of many diseases. Recently, variants in several genes, such as complement H (CFH), complement factor B (CFB), complement 2 (C2), and complement 3 (C3), encoding complement pathway proteins, have been identified as associated with age-related macular degeneration. However, the associations between these genes and age-related macular degeneration varied due to genetic variation within populations and various ethnics groups. The strongest association was found between the age-related macular degeneration and SNP Y402H rs 1061170 variant of CFH gene, which is present in 30% to 50% of age-related macular degeneration patients in Caucasian population and which is a risk factor for the development of age-related macular degeneration. Cohort studies showed that polymorphism Arg102Gly (SNP rs 2230199) of C3 protein could serve as a high-risk genetic marker for the development of age-related macular degeneration. Other rare variants of C3 (Lys155Gln, Lys65Gln, Arg735Trp, Ser1619Arg), may also be associated with a high incidence of age-related macular degeneration in some ethnic groups. A protective haplotype of variants E318D and IVS10 in the C2 gene as well as L9H and R320 in the BF were associated with age-related macular degeneration but only in Caucasians. The genetic findings in age-related macular degeneration patients stress the importance of detailed phenotyping to identify age-related macular degeneration subtypes, which may be associated with the presence of different polymorphisms and various environmental risk factors in any population. Further studies may be helpful to improve the effectiveness of prophylaxis and therapeutic options in age-related

  15. Measles virus infection of thymic epithelium in the SCID-hu mouse leads to thymocyte apoptosis.

    PubMed Central

    Auwaerter, P G; Kaneshima, H; McCune, J M; Wiegand, G; Griffin, D E

    1996-01-01

    Mortality from measles is caused mostly by secondary infections associated with the depression of cellular immunity. The mechanism of immune suppression and the role of virus strain differences on the immune system are incompletely understood. SCID-hu mice were used to determine the effects of virulent, wild-type (Chicago-1) and avirulent, vaccine (Moraten) strains of measles virus (MV) on the human thymus in vivo. Chicago-1 replicated rapidly, with a 100-fold decrease in numbers of thymocytes, whereas Moraten replicated slowly, without significant thymocyte death. Productive MV infection occurred not in thymocytes but in thymic epithelial and myelomonocytic cells. Wild-type MV infection of thymic stromata leads to induction of thymocyte apoptosis and may contribute to a long-term alteration of immune responses. The extent of thymic disruption reflects the virulence of the virus, and therefore the SCID-hu mouse may serve as the first small animal model for the study of MV pathogenesis. PMID:8648708

  16. Trimodality Therapy for an Advanced Thymic Carcinoma With Both Aorta and Vena Cava Invasion.

    PubMed

    Momozane, Tohru; Inoue, Masayoshi; Shintani, Yasushi; Funaki, Soichiro; Kawamura, Tomohiro; Minami, Masato; Shirakawa, Yukitoshi; Kuratani, Toru; Sawa, Yoshiki; Okumura, Meinoshin

    2016-08-01

    A case of locally advanced thymic carcinoma that was successfully resected with the great vessels after chemoradiation therapy is reported. A 57-year-old man with Masaoka stage III thymic carcinoma received two cycles of cisplatin/docetaxel and 60 Gy irradiation. The response was stable disease with 19% size reduction, and a radical resection with the ascending aorta and superior vena cava with the patient under circulatory arrest with the use of cardiopulmonary bypass was performed. The postoperative course was uneventful, and the patient has been free of disease for 28 months. Trimodality therapy with use of a cardiovascular surgical procedure might be a valuable option in locally advanced thymic carcinoma. PMID:27449450

  17. Eph/Ephrins-Mediated Thymocyte–Thymic Epithelial Cell Interactions Control Numerous Processes of Thymus Biology

    PubMed Central

    García-Ceca, Javier; Alfaro, David; Montero-Herradón, Sara; Tobajas, Esther; Muñoz, Juan José; Zapata, Agustín G.

    2015-01-01

    Numerous studies emphasize the relevance of thymocyte–thymic epithelial cell (TECs) interactions for the functional maturation of intrathymic T lymphocytes. The tyrosine kinase receptors, Ephs (erythropoietin-producing hepatocyte kinases) and their ligands, ephrins (Eph receptor interaction proteins), are molecules known to be involved in the regulation of numerous biological systems in which cell-to-cell interactions are particularly relevant. In the last years, we and other authors have demonstrated the importance of these molecules in the thymic functions and the T-cell development. In the present report, we review data on the effects of Ephs and ephrins in the functional maturation of both thymic epithelial microenvironment and thymocyte maturation as well as on their role in the lymphoid progenitor recruitment into the thymus. PMID:26167166

  18. Thymic Origin Neuroendocrine Carcinoma Metastasizing to the Orbit in an Otherwise Asymptomatic Patient.

    PubMed

    MacLean, Kyle D; Cole, Scott C; Ford, Joshua R; Owen, Leah; Mamalis, Nick; Patel, Bhupendra C K

    2016-01-01

    A 39-year-old man without a significant medical history developed headaches, OS swelling, and limited left-sided ocular motility. An ultrasound of the left orbit and head MRI revealed a retro-orbital mass. A partial left anterior orbitotomy with partial resection was performed, and histopathologic examination of the resected tumor portion was suggestive of a neuroendocrine carcinoma. A large, anterior mediastinal mass was found on chest imaging, and the patient was diagnosed with a primary thymic neuroendocrine tumor. To the authors' knowledge, this is the first report of an otherwise healthy patient presenting with the mass effects of a thymic neuroendocrine carcinoma metastasis to the orbital tissues before detection of the primary thymic malignancy.

  19. Histologic and immunohistochemical characterization of thymic epithelial tumours in the dog.

    PubMed

    Burgess, K E; DeRegis, C J; Brown, F S; Keating, J H

    2016-06-01

    Thymic epithelial tumour (TET) histologic subclassification has not been well described in the veterinary literature as it has in humans. The objective of this study was to identify and describe TET subtypes in dogs and to determine the utility of immunohistochemistry (IHC) in differentiating these subtypes. Samples were reviewed and classified according to a modified World Health Organization (WHO) criteria for human tumours of thymic origin. Signallment, presenting signs, treatment and survival data was collected from medical records. Histologic review confirmed the same subtypes as described in humans. Presence of high stage disease, pleomorphism, mitotic figures and capsular invasion was more common in atypical thymomas and thymic carcinomas than in thymomas. IHC was performed for GLUT-1, CD5, CD117 and CK8/18; however, this was not useful in classifying the tumours. PMID:27144380

  20. Role of thymic epithelial cells in lymphoid depletion after experimental infection with the noncytopathogenic BVDV1 strain 7443.

    PubMed

    Raya, A I; Gomez-Villamandos, J C; Bautista, M J

    2015-03-01

    Thymic epithelial cells could play an important role in lymphoid depletion during bovine viral diarrhea virus (BVDV) infection. To evaluate this hypothesis, we examined proliferation of lymphocytes, expression of cytokeratins by thymic epithelial cells, and ultrastructural features at sequential time points after experimental infection of colostrum-deprived calves with the noncytopathogenic BVDV1 strain 7443. Ten clinically healthy Friesian calves were used. Eight were inoculated with the virus, and 2 were used as uninfected controls. Calves were sedated and euthanized in batches between 3 and 14 days postinoculation. At necropsy, thymus samples were collected for structural, immunohistochemical, and ultrastructural study. Thymic lymphoid depletion was accompanied by a decrease in lymphocyte proliferation and immunohistochemical and ultrastructural changes in thymic epithelial cells. Immunohistochemical and ultrastructural results reflect a disturbance of the thymic epithelial cell network, which may explain the decrease in lymphocyte proliferation by defective thymocyte-epithelial cell interactions. PMID:24842487

  1. Diesel Exhaust Particle-Exposed Human Bronchial Epithelial Cells Induce Dendritic Cell Maturation and Polarization via Thymic Stromal Lymphopoietin

    PubMed Central

    Bleck, Bertram; Tse, Doris B.; Curotto de Lafaille, Maria A.; Zhang, Feijie

    2009-01-01

    Human exposure to air pollutants, including ambient particulate matter, has been proposed as a mechanism for the rise in allergic disorders. Diesel exhaust particles, a major component of ambient particulate matter, induce sensitization to neoallergens, but the mechanisms by which sensitization occur remain unclear. We show that diesel exhaust particles upregulate thymic stromal lymphopoietin in human bronchial epithelial cells in an oxidant-dependent manner. Thymic stromal lymphopoietin induced by diesel exhaust particles was associated with maturation of myeloid dendritic cells, which was blocked by anti-thymic stromal lymphopoietin antibodies or silencing epithelial cell-derived thymic stromal lymphopoietin. Dendritic cells exposed to diesel exhaust particle-treated human bronchial epithelial cells induced Th2 polarization in a thymic stromal lymphopoietin-dependent manner. These findings provide new insight into the mechanisms by which diesel exhaust particles modify human lung mucosal immunity. PMID:18049884

  2. Immunosenescence and vaccination of the elderly II. New strategies to restore age-related immune impairment.

    PubMed

    Ongrádi, J; Stercz, B; Kövesdi, Valéria; Vértes, L

    2009-12-01

    One of the greatest health-care challenges in the elderly is to ensure that vaccination against infections are optimally effective, but vaccination can only be effective if cells that are capable of responding are still present in the repertoire. The reversing of immunosenescence could be achieved by improving immune responses or altering vaccine formulation. Recent vaccination strategies in the elderly exert low effectiveness. Nutritional interventions and moderate exercise delay T cell senescence. Telomerase activity and expression of toll-like receptors can be improved by chemotherapy. Reversion of thymic atrophy could be achieved by thymus transplantation, depletion of accumulated dysfunctional naive T cells and herpesvirus-specific exhausted memory cells. Administration of immunostimulatory and anti-inflammatory cytokines show the best practical approach. Reduced dendritic cell activity and co-receptor expression might be increased by interleukin (IL)-2 administration. IL-7 protects both B and T lymphocytes, but IL-2, IL-10, keratinocyte growth factor, thymic stromal lymphopoietin, as well as leptin and growth hormone also have a stimulatory effect on thymopoiesis. In animals, several strategies have been explored to produce more efficacious vaccines including high dose vaccines, DNA vaccines with immunostimulatory patch, virosomal vaccines and vaccines containing new adjuvants. Hopefully, one of these approaches will be translated into human therapy in a short time.

  3. Insight into normal thymic activity by assessment of peripheral blood samples.

    PubMed

    Machnes-Maayan, Diti; Lev, Atar; Katz, Uriel; Mishali, David; Vardi, Amir; Simon, Amos J; Somech, Raz

    2015-03-01

    The thymus is a highly specialized organ for T cell receptor (TCR) rearrangement and selection mechanisms that ensure the formation of functional and self-tolerant cells. Little is known about how peripheral blood assessment of thymic function reflects thymus activity during infancy. We compared thymic function-related markers in the thymus with those in peripheral blood in order to check their correlations. We concomitantly blood samples from immunocompetent infants who underwent cardiac surgery that involved thymectomy. The studied thymic markers included TCR excision circles (TRECs), four different TCRD (TCR delta chain) gene rearrangements, the TCR repertoire, regulatory T cells (Tregs, defined as the CD4+CD25+FOXP3+ cell population) and real-time quantitative polymerase chain reaction (RQ-PCR) mRNA expression of forkhead box P3 (FOXP3). Twenty patients were enrolled in this study. Their mean age at the time of the surgery was 3 months/5 days ± 3 months/18 days. There was a significant correlation between thymic and peripheral blood levels of TREC, all four TCRD gene rearrangements and the amount of Tregs. The levels of these parameters were significantly higher in the thymus than those detected in the peripheral blood. The TCR repertoire distribution in both samples was similar. FOXP3 mRNA levels in the thymus and peripheral blood correlated well. Our findings demonstrated a strong and significant correlation between peripheral blood and intra-thymic activity parameters during infancy. Assessment of these parameters in peripheral blood can be used to accurately estimate different intra-thymic capacities for assessing T cell function in health and disease.

  4. Genetic evidence for common pathways in human age-related diseases.

    PubMed

    Johnson, Simon C; Dong, Xiao; Vijg, Jan; Suh, Yousin

    2015-10-01

    Aging is the single largest risk factor for chronic disease. Studies in model organisms have identified conserved pathways that modulate aging rate and the onset and progression of multiple age-related diseases, suggesting that common pathways of aging may influence age-related diseases in humans as well. To determine whether there is genetic evidence supporting the notion of common pathways underlying age-related diseases, we analyzed the genes and pathways found to be associated with five major categories of age-related disease using a total of 410 genomewide association studies (GWAS). While only a small number of genes are shared among all five disease categories, those found in at least three of the five major age-related disease categories are highly enriched for apoliprotein metabolism genes. We found that a more substantial number of gene ontology (GO) terms are shared among the 5 age-related disease categories and shared GO terms include canonical aging pathways identified in model organisms, such as nutrient-sensing signaling, translation, proteostasis, stress responses, and genome maintenance. Taking advantage of the vast amount of genetic data from the GWAS, our findings provide the first direct evidence that conserved pathways of aging simultaneously influence multiple age-related diseases in humans as has been demonstrated in model organisms.

  5. Physiology and therapeutic potential of the thymic peptide thymulin.

    PubMed

    Reggiani, Paula C; Schwerdt, Jose I; Console, Gloria M; Roggero, Eduardo A; Dardenne, Mireille; Goya, Rodolfo G

    2014-01-01

    Thymulin is a thymic hormone exclusively produced by the epithelial cells of the thymus. After its discovery and initial characterization in the '70s, it was demonstrated that the production and secretion of thymulin are strongly influenced by the neuro-endocrine system. Conversely, a growing body of evidence, to be reviewed here, suggests that thymulin is a hypophysiotropic peptide. Additionally, a substantial body of information pointing to thymulin and a synthetic analog as anti-inflammatory and analgesic peptides in the central nervous system brain and other organs will be also reviewed. In recent years, a synthetic DNA sequence encoding a biologically active analog of thymulin, metFTS, was constructed and cloned in a number of adenovectors. These include bidirectional regulatable Tet-Off vector systems that simultaneously express metFTS and green fluorescent protein and that can be down-regulated reversibly by the addition of the antibiotic doxycycline. A number of recent studies indicate that gene therapy for thymulin may be an effective therapeutic strategy to prevent some of the hormonal and reproductive abnormalities that typically appear in congenitally athymic (nude) mice, used as a suitable model of neuroendocrine and reproductive aging. Summing up, this article briefly reviews the publications on the physiology of the thymulin-neuroendocrine axis and the anti-inflammatory properties of the molecule and its analog. The availability of novel biotechnological tools should boost basic studies on the molecular biology of thymulin and should also allow an assessment of the potential of gene therapy to restore circulating thymulin levels in thymodeficient animal models and eventually, in humans. PMID:24588820

  6. Age-Related Degeneration of the Egg-Laying System Promotes Matricidal Hatching in Caenorhabditis elegans

    PubMed Central

    Pickett, Christopher L.; Kornfeld, Kerry

    2014-01-01

    Summary The identification and characterization of age-related degenerative changes is a critical goal because it can elucidate mechanisms of aging biology and contribute to understanding interventions that promote longevity. Here we document a novel, age-related degenerative change in C. elegans hermaphrodites, an important model system for the genetic analysis of longevity. Matricidal hatching—intra-uterine hatching of progeny that causes maternal death—displayed an age-related increase in frequency and affected ∼70% of mated, wild-type hermaphrodites. The timing and incidence of matricidal hatching were largely independent of the levels of early and total progeny production and the duration of male exposure. Thus, matricidal hatching appears to reflect intrinsic age-related degeneration of the egg-laying system rather than use-dependent damage accumulation. Consistent with this model, mutations that extend longevity by causing dietary restriction significantly delayed matricidal hatching, indicating age-related degeneration of the egg-laying system is controlled by nutrient availability. To identify the underlying tissue defect, we analyzed serotonin signaling that triggers vulval muscle contractions. Mated hermaphrodites displayed an age-related decline in the ability to lay eggs in response to exogenous serotonin, indicating that vulval muscles and/or a further downstream function that is necessary for egg-laying degenerate in an age-related manner. By characterizing a new, age-related degenerative event displayed by C. elegans hermaphrodites, these studies contribute to understanding a frequent cause of death in mated hermaphrodites and establish a model of age-related reproductive complications that may be relevant to the birthing process in other animals such as humans. PMID:23551912

  7. [Cervical thymic cysts are a rare cause of neck masses in children and adolescents].

    PubMed

    Jørgensen, Rasmus Langelund; Larsen, Stine Rosenkilde; Bay, Mette; Godballe, Christian

    2014-10-01

    Cervical thymic cysts are rare benign unilateral lesions of the neck most often diagnosed in male children less than ten years of age. To date, less than 200 cases have been described. We report a case with a typical presentation in an 8-year-old boy. To our knowledge this is the first reported case in Denmark for almost three decades. Cervical thymic cysts represent a clinical challenge as no diagnostic non-invasive test or imaging is available. The cyst was successfully removed by surgical excision and a final histological diagnosis obtained. PMID:25331660

  8. [Thymic ectopia and parathyroid tissue in the pangolin (Manis tricuspis Rafinesque)].

    PubMed

    Bureau, J P; Senelar, R; Serrou, B; Kreher, P

    1975-09-01

    Thymic ectopies are under study in 45 Pangolin's thyroids (Manis tricuspis Rafinesque). Their frequency seems to be independent of the sex of the animal but this frequency also appears to be in relation to the age of the animal. The topographic and morphological studies suggest a close relationship between these inclusions made out of thymic tissue and the presence of parathyroid islets included into the thyroid capsule. Some pictures, showing a connection between parathyroid cells and thymis parenchym elements, plead in favour of a functional interelation between these different structures as the Mc Manus experiments suggest it.

  9. Ontogeny of rat thymic macrophages. Phenotypic characterization and possible relationships between different cell subsets.

    PubMed Central

    Vicente, A; Varas, A; Moreno, J; Sacedón, R; Jiménez, E; Zapata, A G

    1995-01-01

    In the present study we combined electron microscopy, immunohistology and primary stromal cell cultures to analyse the ontogeny of rat thymic macrophages (M phi) in an attempt to clarify the relationships between the different macrophage cell subsets described in adult rat thymus. Although phagocytic cells were observed in 15-day-old fetal thymus, monoclonal antibodies (mAb) which recognize different adult macrophage types were unable to identify positive cells until the end of embryonic life. However, our in vitro results from primary thymic stromal cell cultures of 16-day-old fetal rats, and the phenotyping of enriched thymic CD2- cell suspensions, demonstrated that monocyte-like cells which strongly expressed major histocompatibility complex (MHC) class II molecules colonized the embryonic thymus early, giving rise later to distinct macrophage subsets. During the process of maturation, macrophage precursors gradually lost their MHC class II expression, acquired other surface markers (CD45, Thy-1, CD25, CD4, etc.) and increased the acid phosphatase activity. In this respect, ED1+ macrophages, which appeared for the first time in the last stages of embryonic life, consisted of a MHC class II molecule-expressing phagocytic cell population, presumably involved in the elimination of non-selected cortical thymocytes, and of non-phagocytic cells which, in the thymic cortex, might differentiate to ED2+ macrophages throughout ED1+ED2lo/med and ED1+ ED2high intermediate cell stages, observed in vitro in 16-day-old fetal thymic stromal cell cultures. At the end of embryonic life and during the postnatal period the numbers of thymic macrophages increased, particularly in the medulla and corticomedullary border (CMZ), and more slowly in the thymic cortex. This increase was presumably due to the arrival, through perivascular spaces, of new macrophage progenitors, rather than in situ proliferation of pre-existent mature macrophages. The possible function of different thymic

  10. Isolation and identification of a new thymic peptide from calf thymus.

    PubMed

    Qin, Xi-Ming; Duan, Ming-Xing; Deng, Bin; Liu, Xi-Cheng; Zhang, Qiang-Zhe; Liu, Zheng; He, Hong-Xuan

    2004-08-01

    Various thymic peptides (including thymulin, thymic humoral factor, thymopoietin, etc.) play important roles in the process of T cell maturation and development. We isolated a new peptide from calf thymus and named it thymus activity factor II (TAF-II). A yield of 0.92 mg of TAF-II was purified from 500 g calf thymus. Analysis by LC/MSD-Trap showed the amino acid sequence of this hexapeptide to be Glu-Ala-Lys-Ser-Gln-Gly-OH with molecular weight 618.5 daltons. We have also begun to investigate the influence of TAF-II.

  11. The Bst locus on mouse chromosome 16 is associated with age-related subretinal neovascularization

    PubMed Central

    Smith, Richard S.; John, Simon W. M.; Zabeleta, Adriana; Davisson, Muriel T.; Hawes, Norman L.; Chang, Bo

    2000-01-01

    Ocular neovascularization is the leading cause of blindness in developed countries and often causes rapid loss of vision in age-related macular degeneration. Acute visual loss is most often due to hemorrhage from new vessels that have extended from the choroid into the subretinal space. Growth of abnormal vessels beneath the retina in this condition is known as subretinal neovascularization (SRN). Age-related animal models of macular degeneration and SRN have not been described. Current animal models of SRN depend on chemical or physical stimuli to initiate growth of subretinal vessels. The genes responsible for age-related human macular degeneration with SRN have not been firmly identified. We report an angiogenic phenotype in Bst/+ mice that is age-related, clinically evident, and resembles human SRN. This represents a spontaneous, genetically determined model of SRN. Bst/+ mice offer the possibility of exploring the molecular mechanisms of SRN without the need for exogenous agents. PMID:10681427

  12. Aging Changes in Retinal Microglia and their Relevance to Age-related Retinal Disease.

    PubMed

    Ma, Wenxin; Wong, Wai T

    2016-01-01

    Age-related retinal diseases, such as age-related macular degeneration (AMD) and glaucoma, contain features of chronic retinal inflammation that may promote disease progression. However, the relationship between aging and neuroinflammation is unclear. Microglia are long-lived, resident immune cells of the retina, and mediate local neuroinflammatory reactions. We hypothesize that aging changes in microglia may be causally linked to neuroinflammatory changes underlying age-dependent retinal diseases. Here, we review the evidence for (1) how the retinal microglial phenotype changes with aging, (2) the factors that drive microglial aging in the retina, and (3) aging-related changes in microglial gene expression. We examine how these aspects of microglial aging changes may relate to pathogenic mechanisms of immune dysregulation driving the progression of age-related retinal disease. These relationships can highlight microglial aging as a novel target for the prevention and treatment of retinal disease.

  13. From mind wandering to involuntary retrieval: Age-related differences in spontaneous cognitive processes.

    PubMed

    Maillet, David; Schacter, Daniel L

    2016-01-01

    The majority of studies that have investigated the effects of healthy aging on cognition have focused on age-related differences in voluntary and deliberately engaged cognitive processes. Yet many forms of cognition occur spontaneously, without any deliberate attempt at engaging them. In this article we review studies that have assessed age-related differences in four such types of spontaneous thought processes: mind-wandering, involuntary autobiographical memory, intrusive thoughts, and spontaneous prospective memory retrieval. These studies suggest that older adults exhibit a reduction in frequency of both mind-wandering and involuntary autobiographical memory, whereas findings regarding intrusive thoughts have been more mixed. Additionally, there is some preliminary evidence that spontaneous prospective memory retrieval may be relatively preserved in aging. We consider the roles of age-related differences in cognitive resources, motivation, current concerns and emotional regulation in accounting for these findings. We also consider age-related differences in the neural correlates of spontaneous cognitive processes.

  14. Age-related differences in neurotoxicity produced by organophosphorus and N-methyl carbamate pesticides

    EPA Science Inventory

    Potential pesticide effects in infants and toddlers have received much attention in the scientific literature and the public media, including the concern for increased response to acute or shortterm exposures. Age-related differences in the acute neurotoxicity of acetylcholinest...

  15. AGE-RELATED GENE EXPRESSION CHANGES IN HUMAN SKIN FIBROBLASTS INDUCED BY MMS

    EPA Science Inventory

    Age-Related Gene Expression Changes In Human Skin Fibroblasts Induced By methyl methanesulfonate. Geremy W. Knapp, Alan H. Tennant, and Russell D. Owen. Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory, U. S. Environmental Prote...

  16. Genetic variants in mammary development, prolactin signalling and involution pathways explain considerable variation in bovine milk production and milk composition

    PubMed Central

    2014-01-01

    Background The maintenance of lactation in mammals is the result of a balance between competing signals from mammary development, prolactin signalling and involution pathways. Dairy cattle are an interesting case study to investigate the effect of polymorphisms that affect the function of genes in these pathways. In dairy cattle, lactation yields and milk composition (for example protein percentage and fat percentage) are routinely recorded, and these vary greatly between individuals. In this study, we test 8058 single nucleotide polymorphisms in or close to genes in these pathways for association with milk production traits and determine the proportion of variance explained by each pathway, using data on 16 812 dairy cattle, including Holstein-Friesian and Jersey bulls and cows. Results Single nucleotide polymorphisms close to genes in the mammary development, prolactin signalling and involution pathways were significantly associated with milk production traits. The involution pathway explained the largest proportion of genetic variation for production traits. The mammary development pathway also explained additional genetic variation for milk volume, fat percentage and protein percentage. Conclusions Genetic variants in the involution pathway explained considerably more genetic variation in milk production traits than expected by chance. Many of the associations for single nucleotide polymorphisms in genes in this pathway have not been detected in conventional genome-wide association studies. The pathway approach used here allowed us to identify some novel candidates for further studies that will be aimed at refining the location of associated genomic regions and identifying polymorphisms contributing to variation in lactation volume and milk composition. PMID:24779965

  17. Involution of the auditory neuro-epithelium in a tiger (Panthera tigris) and a jaguar (Panthera onca).

    PubMed

    Ulehlová, L; Burda, H; Voldrich, L

    1984-01-01

    Numerical atrophy of the hair cells of the organ of Corti of the inner ear in a 14-year-old tiger and a 17-year-old jaguar is described. The decrease in number of sensory hair cells is considered to represent physiological atrophy caused by the process of ageing. The findings are compared with previous observations on man, guinea-pigs, shrews, and bats. The development of the physiological involution of the hearing neuro-epithelium is discussed.

  18. A new role of SNAI2 in postlactational involution of the mammary gland links it to luminal breast cancer development

    DOE PAGES

    Castillo-Lluva, Sonia; Hontecillas-Prieto, Lourdes; Blanco-Gómez, Adrian; del Mar Sáez-Freire, María; García-Cenador, Begona; García-Criado, Javier; Pérez-Andrés, Martín; Orfao, Alberto; Cañamero, Marta; Mao, Jian-Hua; et al

    2015-06-22

    Breast cancer is a major cause of mortality in women. The transcription factor SNAI2 has been implicated in the pathogenesis of several types of cancer, including breast cancer of basal origin. Here we show that SNAI2 is also important in the development of breast cancer of luminal origin in MMTV-ErbB2 mice. SNAI2 deficiency leads to longer latency and fewer luminal tumors, both of these being characteristics of pretumoral origin. These effects were associated with reduced proliferation and a decreased ability to generate mammospheres in normal mammary glands. However, the capacity to metastasize was not modified. Under conditions of increased ERBB2more » oncogenic activity after pregnancy plus SNAI2 deficiency, both pretumoral defects-latency and tumor load-were compensated. However, the incidence of lung metastases was dramatically reduced. Furthermore, SNAI2 was required for proper postlactational involution of the breast. At 3 days post lactational involution, the mammary glands of Snai2-deficient mice exhibited lower levels of pSTAT3 and higher levels of pAKT1, resulting in decreased apoptosis. Abundant noninvoluted ducts were still present at 30 days post lactation, with a greater number of residual ERBB2+ cells. These results suggest that this defect in involution leads to an increase in the number of susceptible target cells for transformation, to the recovery of the capacity to generate mammospheres and to an increase in the number of tumors. In conclusion, our work demonstrates the participation of SNAI2 in the pathogenesis of luminal breast cancer, and reveals an unexpected connection between the processes of postlactational involution and breast tumorigenesis in Snai2-null mutant mice.« less

  19. A new role of SNAI2 in postlactational involution of the mammary gland links it to luminal breast cancer development

    SciTech Connect

    Castillo-Lluva, Sonia; Hontecillas-Prieto, Lourdes; Blanco-Gómez, Adrian; del Mar Sáez-Freire, María; García-Cenador, Begona; García-Criado, Javier; Pérez-Andrés, Martín; Orfao, Alberto; Cañamero, Marta; Mao, Jian-Hua; Gridley, Thomas; Castellanos-Martín, Andres; Pérez-Losada, Jesus

    2015-06-22

    Breast cancer is a major cause of mortality in women. The transcription factor SNAI2 has been implicated in the pathogenesis of several types of cancer, including breast cancer of basal origin. Here we show that SNAI2 is also important in the development of breast cancer of luminal origin in MMTV-ErbB2 mice. SNAI2 deficiency leads to longer latency and fewer luminal tumors, both of these being characteristics of pretumoral origin. These effects were associated with reduced proliferation and a decreased ability to generate mammospheres in normal mammary glands. However, the capacity to metastasize was not modified. Under conditions of increased ERBB2 oncogenic activity after pregnancy plus SNAI2 deficiency, both pretumoral defects-latency and tumor load-were compensated. However, the incidence of lung metastases was dramatically reduced. Furthermore, SNAI2 was required for proper postlactational involution of the breast. At 3 days post lactational involution, the mammary glands of Snai2-deficient mice exhibited lower levels of pSTAT3 and higher levels of pAKT1, resulting in decreased apoptosis. Abundant noninvoluted ducts were still present at 30 days post lactation, with a greater number of residual ERBB2+ cells. These results suggest that this defect in involution leads to an increase in the number of susceptible target cells for transformation, to the recovery of the capacity to generate mammospheres and to an increase in the number of tumors. In conclusion, our work demonstrates the participation of SNAI2 in the pathogenesis of luminal breast cancer, and reveals an unexpected connection between the processes of postlactational involution and breast tumorigenesis in Snai2-null mutant mice.

  20. Controlled processes account for age-related decrease in episodic memory.

    PubMed

    Vanderaspoilden, Valérie; Adam, Stéphane; der Linden, Martial Van; Morais, José

    2007-05-01

    A decrease in controlled processes has been proposed to be responsible for age-related episodic memory decline. We used the Process Dissociation Procedure, a method that attempts to estimate the contribution of controlled and automatic processes to cognitive performance, and entered both estimates in regression analyses. Results indicate that only controlled processes explained a great part of the age-related variance in a word recall task, especially when little environmental support was offered. PMID:16860766

  1. Altered Hippocampal Transcript Profile Accompanies an Age-Related Spatial Memory Deficit in Mice

    ERIC Educational Resources Information Center

    Verbitsky, Miguel; Yonan, Amanda L.; Malleret, Gael; Kandel, Eric R.; Gilliam, T. Conrad; Pavlidis, Paul

    2004-01-01

    We have carried out a global survey of age-related changes in mRNA levels in the 57BL/6NIA mouse hippocampus and found a difference in the hippocampal gene expression profile between 2-month-old young mice and 15-month-old middle-aged mice correlated with an age-related cognitive deficit in hippocampal-based explicit memory formation. Middle-aged…

  2. The Digital Ageing Atlas: integrating the diversity of age-related changes into a unified resource.

    PubMed

    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.

  3. The Digital Ageing Atlas: integrating the diversity of age-related changes into a unified resource

    PubMed Central

    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. PMID:25232097

  4. Age-related differences in brain activity in the subsequent memory paradigm: a meta-analysis.

    PubMed

    Maillet, David; Rajah, M Natasha

    2014-09-01

    Healthy aging is associated with declines in episodic memory. This reduction is thought to be due in part to age-related differences in encoding-related processes. In the current study, we performed an activation likelihood estimation meta-analysis of functional magnetic resonance imaging (fMRI) studies assessing age-related differences in the neural correlates of episodic encoding. Only studies using the subsequent memory paradigm were included. We found age-related under-recruitment of occipital and fusiform cortex, but over-recruitment in a set of regions including bilateral middle/superior frontal gyri, anterior medial frontal gyrus, precuneus and left inferior parietal lobe. We demonstrate that all of the regions consistently over-recruited by older adults during successful encoding exhibit either direct overlap, or occur in close vicinity to regions consistently involved in unsuccessful encoding in young adults. We discuss the possibility that this overall pattern of age-related differences represents an age-related shift in focus: away from perceptual details, and toward evaluative and personal thoughts and feelings during memory tasks. We discuss whether these age-related differences in brain activation benefit performance in older adults, and additional considerations.

  5. Association of age-related macular degeneration and reticular macular disease with cardiovascular disease.

    PubMed

    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.

  6. [Age-related macular degeneration as a local manifestation of atherosclerosis - a novel insight into pathogenesis].

    PubMed

    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.

  7. Contesting the dogma of an age-related heat shock response impairment: implications for cardiac-specific age-related disorders.

    PubMed

    Carnemolla, Alisia; Labbadia, John P; Lazell, Hayley; Neueder, Andreas; Moussaoui, Saliha; Bates, Gillian P

    2014-07-15

    Ageing is associated with the reduced performance of physiological processes and has been proposed as a major risk factor for disease. An age-related decline in stress response pathways has been widely documented in lower organisms. In particular, the heat shock response (HSR) becomes severely compromised with age in Caenorhabditis elegans. However, a comprehensive analysis of the consequences of ageing on the HSR in higher organisms has not been documented. We used both HS and inhibition of HSP90 to induce the HSR in wild-type mice at 3 and 22 months of age to investigate the extent to which different brain regions, and peripheral tissues can sustain HSF1 activity and HS protein (HSP) expression with age. Using chromatin immunoprecipitation, quantitative reverse transcription polymerase chain reaction, western blotting and enzyme linked immunosorbent assay (ELISA), we were unable to detect a difference in the level or kinetics of HSP expression between young and old mice in all brain regions. In contrast, we did observe an age-related reduction in chaperone levels and HSR-related proteins in the heart. This could result in a decrease in the protein folding capacity of old hearts with implications for age-related cardiac disorders.

  8. A study of the chick thymus microenvironment during development: analysis by monoclonal antibodies against thymic epithelium.

    PubMed

    Paz, P; Sánchez, A; Melcón, C; Fernández, J G; Chamorro, C A

    1993-02-01

    The process of T-lymphocyte differentiation within the thymus involves a series of molecular interactions. In this work we have carried out an analysis of the chick thymus microenvironment in order to evaluate its heterogeneity during development. We have produced 11 monoclonal antibodies whose staining patterns detected by the immunoperoxidase technique allowed us to divide them into five groups. A first group (E19-E2, P0-E5, and P15-T1) binds to thymic medullary stroma showing a reticular pattern on medullary epithelial cells and whose significance would be related to thymic stromal secretion. The second group of monoclonal antibodies (P15-T3) stains thymic corpuscles of 10- and 15-day chicks. The third group of antibodies includes P0-E1, P0-E3, P5-A6, and P15-T2 whose staining pattern is both medullary and cortical. The fourth group (P10-HB1 and P10-HB2) binds to thymic stromal and cortical thymocytes, and the fifth group (P5-A1) is characterized by the staining of medullary vessels of 5-day chicks. These five groups of monoclonal antibodies corroborate the existence of an antigenic diversity of the chick thymus microenvironment. Their possible relationships with T-cell differentiation and stromal-thymocyte interactions are discussed.

  9. Role of Defective Thymic Function in Onset of Ganciclovir-Resistant Cytomegalovirus after Cord Blood Transplantation

    PubMed Central

    Martín, Carmen; Romero-Sánchez, María C.; Ferrando-Martínez, Sara; Martínez, Francisco; Rivero, Antonio; Torres, Antonio; Solana, Rafael; Torre-Cisneros, Julián

    2012-01-01

    A case of recurrent cytomegalovirus reactivations in a cytomegalovirus-seropositive woman who received allogeneic cord blood transplantation is described. Thirteen months posttransplantation, her CD3+ T cell count was extremely low whereas natural killer cells represented 66% of her total lymphocytes. She showed defective thymic function that might contribute to the onset of valganciclovir resistance. PMID:23054743

  10. Role of defective thymic function in onset of ganciclovir-resistant cytomegalovirus after cord blood transplantation.

    PubMed

    Cantisán, Sara; Martín, Carmen; Romero-Sánchez, María C; Ferrando-Martínez, Sara; Martínez, Francisco; Rivero, Antonio; Torres, Antonio; Solana, Rafael; Torre-Cisneros, Julián

    2012-12-01

    A case of recurrent cytomegalovirus reactivations in a cytomegalovirus-seropositive woman who received allogeneic cord blood transplantation is described. Thirteen months posttransplantation, her CD3(+) T cell count was extremely low whereas natural killer cells represented 66% of her total lymphocytes. She showed defective thymic function that might contribute to the onset of valganciclovir resistance.

  11. Requirement of Stat3 Signaling in the Postnatal Development of Thymic Medullary Epithelial Cells.

    PubMed

    Satoh, Rumi; Kakugawa, Kiyokazu; Yasuda, Takuwa; Yoshida, Hisahiro; Sibilia, Maria; Katsura, Yoshimoto; Levi, Ben; Abramson, Jakub; Koseki, Yoko; Koseki, Haruhiko; van Ewijk, Willem; Hollander, Georg A; Kawamoto, Hiroshi

    2016-01-01

    Thymic medullary regions are formed in neonatal mice as islet-like structures, which increase in size over time and eventually fuse a few weeks after birth into a continuous structure. The development of medullary thymic epithelial cells (TEC) is dependent on NF-κB associated signaling though other signaling pathways may contribute. Here, we demonstrate that Stat3-mediated signals determine medullary TEC cellularity, architectural organization and hence the size of the medulla. Deleting Stat3 expression selectively in thymic epithelia precludes the postnatal enlargement of the medulla retaining a neonatal architecture of small separate medullary islets. In contrast, loss of Stat3 expression in cortical TEC neither affects the cellularity or organization of the epithelia. Activation of Stat3 is mainly positioned downstream of EGF-R as its ablation in TEC phenocopies the loss of Stat3 expression in these cells. These results indicate that Stat3 meditated signal via EGF-R is required for the postnatal development of thymic medullary regions. PMID:26789017

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

    SciTech Connect

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

    2009-06-05

    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.

  13. Stimulatory effect of thymic factor(s) on steroidogenesis in cultured rat granulosa cells.

    PubMed

    Uzumcu, M; Akira, S; Lin, Y C

    1992-01-01

    Thymic cells from immature female rats were isolated and used for production of thymic cell culture conditioned medium (TCM). Granulosa cells were obtained from immature diethylstilbestrol (DES)-treated rats. TCM stimulated basal progesterone and estradiol secretion from the granulosa cells in a dose and time dependent manner. Maximal stimulation of progesterone production occurred at 48 hours of incubation, during which period TCM caused approximately 5 times more progesterone secretion than heart cell conditioned medium (HCM) or mock extract (ME). The maximum progesterone secretion by granulosa cells occurred when they were exposed to 48% TCM causing 7 times more progesterone secretion than controls. Under the same maximum stimulatory conditions, however, TCM only approximately doubled estradiol secretion compared to concentrations secreted in the presence of HCM or ME. Thus, the effect of TCM on progesterone secretion was more prominent than its effect on estradiol secretion. The stimulatory action of TCM was not mimicked by HCM, thymosin-alpha 1 or thymulin. Furthermore, the stimulatory action of TCM on steroidogenesis did not appear to be mediated by the cAMP system. The stimulatory factor(s) in TCM were heat, acid and acetone labile, but could not be sedimented by activated charcoal. Thus, the present study demonstrates that the secretory product(s) of thymic epithelial cells can stimulate steroidogenesis in cultured rat granulosa cells. Our data imply that thymic factor(s) may have a direct effect on ovarian function.

  14. Generalised hyperpigmentation caused by ectopic adrenocorticotropic hormone syndrome with recurrent thymic neuroendocrine carcinoma.

    PubMed

    Moon, Hye-Rim; Won, Chong Hyun; Chang, Sung Eun; Lee, Mi Woo; Choi, Jee Ho; Moon, Kee Chan

    2015-05-01

    Ectopic adrenocorticotropic hormone (ACTH) syndrome is a rare cause of generalised hyperpigmentation. The clinical features are due to the excessive ectopic secretion of adenocorticotropin by diverse neuroendocrine or non-endocrine tumours. Here, we describe a rare case of ectopic ACTH syndrome developing from recurring thymic neuroendocrine carcinoma, which first presented as generalised hyperpigmentation.

  15. Patterned Contractile Forces Promote Epidermal Spreading and Regulate Segment Positioning during Drosophila Head Involution.

    PubMed

    Czerniak, Natalia Dorota; Dierkes, Kai; D'Angelo, Arturo; Colombelli, Julien; Solon, Jérôme

    2016-07-25

    Epithelial spreading is a fundamental mode of tissue rearrangement occurring during animal development and wound closure. It has been associated either with the collective migration of cells [1, 2] or with actomyosin-generated forces acting at the leading edge (LE) and pulling the epithelial tissue [3, 4]. During the process of Drosophila head involution (HI), the epidermis spreads anteriorly to envelope the head tissues and fully cover the embryo [5]. This results in epidermal segments of equal width that will give rise to the different organs of the fly [6]. Here we perform a quantitative analysis of tissue spreading during HI. Combining high-resolution live microscopy with laser microsurgery and genetic perturbations, we show that epidermal movement is in part, but not solely, driven by a contractile actomyosin cable at the LE. Additional driving forces are generated within each segment by a gradient of actomyosin-based circumferential tension. Interfering with Hedgehog (Hh) signaling can modulate this gradient, thus suggesting the involvement of polarity genes in the regulation of HI. In particular, we show that disruption of these contractile forces alters segment widths and leads to a mispositioning of segments. Within the framework of a physical description, we confirm that given the geometry of the embryo, a patterned profile of active circumferential tensions can indeed generate propelling forces and control final segment position. Our study thus unravels a mechanism by which patterned tensile forces can regulate spreading and positioning of epithelial tissues. PMID:27397891

  16. Nonlinear analysis of hydraulic buckling instability of ANS involute fuel plates

    SciTech Connect

    Sartory, W.K.

    1993-03-01

    The hydraulic buckling instability of the involute fuel plates and hydraulic coolant channels in the Advanced Neutron Source (ANS) uranium fission reactor is analyzed nonlinearly using the commercial ABAQUS finite element computer program for the fuel plates in conjunction with a user-written element for the two-dimensional fluid flow in the coolant channels. This methodology has been used for several purposes, including determination of the effect of the aluminum-clad plate plastic behavior and the effect of three-dimensional plate temperature distributions on hydraulic buckling. The present report concentrates on a study of the effect of hydraulic channel imperfections on buckling. The specific form of imperfection considered is an error in fluid channel thickness that is uniform within any one channel but that varies from one channel to the next. The calculated bifurcation (linear buckling) coolant velocity is about 45 m/s, whereas the present design coolant velocity is 25 m/s. At the design velocity, the calculated fluid-induced plate deflection due to the imperfection is somewhat less in magnitude and opposite in direction from the imperfection itself.

  17. LOXL2-mediated matrix remodeling in metastasis and mammary gland involution.

    PubMed

    Barker, Holly E; Chang, Joan; Cox, Thomas R; Lang, Georgina; Bird, Demelza; Nicolau, Monica; Evans, Holly R; Gartland, Alison; Erler, Janine T

    2011-03-01

    More than 90% of cancer patient mortality is attributed to metastasis. In this study, we investigated a role for the lysyl oxidase-related enzyme lysyl oxidase-like 2 (LOXL2) in breast cancer metastasis, in both patient samples and in vivo models. Analysis of a published microarray data set revealed that LOXL2 expression is correlated with metastasis and decreased survival in patients with aggressive breast cancer. In immunocompetent or immunocompromised orthotopic and transgenic breast cancer models we showed that genetic, chemical or antibody-mediated inhibition of LOXL2 resulted in decreased metastasis. Mechanistic investigations revealed that LOXL2 promotes invasion by regulating the expression and activity of the extracellular proteins tissue inhibitor of metalloproteinase-1 (TIMP1) and matrix metalloproteinase-9 (MMP9). We found that LOXL2, TIMP1, and MMP9 are coexpressed during mammary gland involution, suggesting they function together in glandular remodeling after weaning. Finally, we found that LOXL2 is highly expressed in the basal/myoepithelial mammary cell lineage, like many other genes that are upregulated in basal-like breast cancers. Our findings highlight the importance of LOXL2 in breast cancer progression and support the development of anti-LOXL2 therapeutics for the treatment of metastatic breast cancer.

  18. Involution of juvenile nasopharyngeal angiofibroma with intracranial extension. A case report with computed tomographic assessment.

    PubMed

    Jacobsson, M; Petruson, B; Ruth, M; Svendsen, P

    1989-02-01

    In September 1979 the patient, a man born in 1964, noticed pain and swelling of the right cheek in combination with periods of epistaxis. A computed tomographic scan revealed a tumor extending from the middle of the right nasal cavity into the right maxillary antrum and up toward the orbital floor with destruction of the medial and lateral walls of the antrum and continuing into the sphenoid sinus on the right side and dorsal to the pterygoid process up under the base of the skull. Angiography showed arterial supply mainly from the right external carotid artery, but also from the right internal carotid artery and the left external carotid artery. The process was diagnosed as a juvenile nasopharyngeal angiofibroma. In spite of two attempts at resection of the tumor and arterial embolization, the tumor progressed intracranially. Further operative attempts were decided against, and the patient was followed with repeated computed tomographic scans. The tumor eventually became involuted; eight years after the initial diagnosis, there was no evidence of computed tomographic scans of intracranial growth of the tumor.

  19. Primary polyoma virus-induced murine thymic epithelial tumors. A tumor model of thymus physiology.

    PubMed Central

    Hoot, G. P.; Kettman, J. R.

    1989-01-01

    Thymic tumors were induced in C3'/Bittner mice by neonatal inoculation with polyoma virus. The objective of this study was to identify the phenotypes of the cells within the tumors and to attempt to determine the origin of the neoplastic cell population(s). At the ultrastructural level, the neoplastic cells resembled normal thymic epithelium with tonofilaments and desmosomes. Immunoperoxidase staining demonstrated the presence of cytokeratin, Iak, -beta 2-microglobulin, -asialo-GM1, the thymic cortical epithelial marker ER-TR4, and the medullary epithelial marker ER-TR5. Islands of normal cortical thymocytes supported by residual normal cortical epithelium and acid phosphatase-positive cortical macrophages were interspersed in the tumors. Residual islands of normal medullary architecture with nonspecific esterase-positive IDCs were rarely identified in tumors. Most lymphocytes in the tumors were normal immature cortical thymocytes with the phenotype Tdt+, PNA+, Thy 1.2bright, Ly-1dull, H-2Kkdull, ThB+, J11d+, and Lyt-2+L3T4+. Lymphocytes in the tumors were steroid-sensitive like normal thymocytes. The proportions of Lyt-2+L3T4- and Lyt-2-L3T4+ cells were generally larger in the tumors than in normal thymus and reflected the higher frequency of lymphocytes in the tumors capable of proliferating in vitro in response to Con A plus IL-2. The data were consistent with the hypothesis that the neoplasia originates from thymic epithelium that is interspersed with normal, developing thymic lymphocytes. Images Figure 4 p[688]-a Figure 1 Figure 2 Figure 3 p687-a Figure 7 PMID:2552813

  20. Medullary thymic epithelium expresses a ligand for CTLA4 in situ and in vitro

    SciTech Connect

    Nelson, A.J.; Hosier, S.; Farr, A.G. ); Brady, W.; Linsley, P.S. )

    1993-09-01

    A fusion protein consisting of the extracellular domain of CTLA4 and an Ig C[gamma]1 chain (CTLA4-Ig) was used to examine the distribution of the ligands for CTLA4 within the murine thymus and to characterize the nature of these ligands. Two-color immunofluorescence of thymus tissue revealed binding of the fusion protein to medullary thymic epithelial cells and dendritic cells within the corticomedullary and medullary areas of the thymus. Medullary cells binding the fusion protein also expressed MHC class II products and ICAM-1. Thymus tissue sections treated with cross-linking fixatives, such as glutaraldehyde, paraformaldehyde, or 1-ethyl-3(d dimethylaminopropyl)-carbodiimide no longer bound the CTLA4 fusion protein, indicating that binding was very sensitive to the tertiary structure of the tissue ligand. The ability of thymic tissue to bind the fusion protein was developmentally regulated. At day 14 of gestation, only scattered single cells were labeled. Clusters of labeled cells, which were detected by day 16 of gestation, increased in frequency with advancing gestational age. Consistent with the in situ labeling studies. CTLA4-lg also labeled several thymic epithelial cell lines previously shown to have a medullary phenotype. Polymerase chain reaction analysis of mRNA extracted from these cells indicated they contained mRNA for B7, a known counter receptor for CTLA4 and CD28. Immunoprecipitation of [sup 125]I-labeled thymic epithelial cells with the CTLA4-Ig detected a M[sub r] 65,000 to 70,000 species under reducing conditions, consistent with previous studies of B7. These data suggest that the ligand for CTLA4 expressed by thymic epithelial cells in vitro is B7 and that the expression of this ligand in situ is largely restricted to the medullary compartment and is associated with epithelial cells and dendritic cells.

  1. Relationship between Ah receptor-mediated polychlorinated biphenyl (PCB)-induced humoral immunosuppression and thymic atrophy.

    PubMed

    Silkworth, J B; Antrim, L

    1985-12-01

    Thymic atrophy and humoral immunosuppression by certain polychlorinated biphenyls is associated with the aromatic hydrocarbon (Ah) receptor in mice. We examined the relationship between these two toxic effects. 3,3',4,4'-Tetrachlorobiphenyl (TCB), which causes immunosuppression and thymic atrophy, and 2,3,3',4,4',5-hexachlorobiphenyl, which causes immunosuppression without thymic atrophy, were administered i.p. to C57BL/6 mice at 0, 35 and 350 mumol/kg b.wt. 2 days before i.v. immunization with 10 micrograms of Escherichia coli lipopolysaccharide. Both congeners caused significant suppression of the day 4 anti-lipopolysaccharide plaque-forming cell response/spleen (less than or equal to 46% of control). TCB (350 mumol/kg) was also administered 2 days before either a primary or secondary i.p. immunization with sheep erythrocytes. TCB treatment before primary immunization had no effects on the day 5 secondary response, whereas treatment before the secondary immunization significantly inhibited both day 5 immunoglobulin M and immunoglobulin G plaque-forming cells (less than 10 and less than 2% of control, respectively) and decreased serum antibody. TCB administered either 8 or 2 days before or 2 or 4 days after immunization with sheep erythrocytes demonstrated that significant suppression of both plaque-forming cells and serum antibody could occur without thymic atrophy. Immunity was most impaired when TCB was given 2 days before immunization. These results demonstrate that thymic atrophy does not always accompany the severe immunosuppression caused by Ah receptor ligands and suggests that it may not be a sensitive measure of Ah receptor-mediated immunosuppression. The data also suggests that differentiation of B lymphocytes into antibody producing cells is impaired during Ah receptor-mediated gene activation.

  2. FOXN1: A Master Regulator Gene of Thymic Epithelial Development Program

    PubMed Central

    Romano, Rosa; Palamaro, Loredana; Fusco, Anna; Giardino, Giuliana; Gallo, Vera; Del Vecchio, Luigi; Pignata, Claudio

    2013-01-01

    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 thymic epithelial cells (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 post-natal thymus. An inborn null mutation in FOXN1 leads to Nude/severe combined immunodeficiency (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. PMID:23874334

  3. [Pharmacological therapy of age-related macular degeneration based on etiopathogenesis].

    PubMed

    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

  4. [Pharmacological therapy of age-related macular degeneration based on etiopathogenesis].

    PubMed

    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

  5. Stromal Fibroblast in Age-Related Cancer: Role in Tumorigenesis and Potential as Novel Therapeutic Target

    PubMed Central

    Elkhattouti, Abdelouahid; Hassan, Mohamed; Gomez, Christian R.

    2015-01-01

    Incidence of most common cancers increases with age due to accumulation of damage to cells and tissues. Stroma, the structure close to the basement membrane, is gaining increased attention from clinicians and researchers due to its increasingly, yet incompletely understood role in the development of age-related cancer. With advanced age, stroma generates a pro-tumorigenic microenvironment, exemplified by the senescence-associated secretory phenotype (SASP). Components of the SASP, such as cytokines, chemokines, and high energy metabolites are main drivers of age-related cancer initiation and sustain its progression. Our purpose is to provide insight into the mechanistic role of the stroma, with particular emphasis on stromal fibroblasts, on the development of age-related tumors. We also present evidence of the potential of the stroma as target for tumor therapy. Likewise, a rationale for age-related antitumor therapy targeting the stroma is presented. We expect to foster debate on the underlining basis of age-related cancer pathobiology. We also would like to promote discussion on novel stroma-based anticancer therapeutic strategies tailored to treat the elderly. PMID:26284191

  6. A Systematic Investigation into Aging Related Genes in Brain and Their Relationship with Alzheimer's Disease.

    PubMed

    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.

  7. Age-related infertility and unexplained infertility: an intricate clinical dilemma.

    PubMed

    Somigliana, Edgardo; Paffoni, Alessio; Busnelli, Andrea; Filippi, Francesca; Pagliardini, Luca; Vigano, Paola; Vercellini, Paolo

    2016-07-01

    A diagnosis of unexplained infertility is commonly made when clinical investigations fail to identify any obvious barriers to conception. As a consequence, unexplained infertility includes several heterogeneous conditions, one being women with age-related infertility. However, the latter represent a peculiar and different situation. Women with age-related infertility may have a different prognosis and may benefit from different treatments. Unfortunately, since fecundity declines with age, discerning between unexplained infertility and age-related infertility becomes more and more difficult as the woman's age increases. In this opinion, with the use of a mathematical model we show that the rate of false positive diagnoses of unexplained infertility increases rapidly after 35 years of age. Using a threshold of 2 years of unfruitful, regular unprotected intercourse, this rate exceeds 50% in women starting pregnancy seeking after 37 years. The scenario is much worse using a threshold of 1 year. From a clinical perspective, extrapolating results obtained in a population of young women with unexplained infertility to those with age-related infertility is not justified. It is noteworthy that, if Assisted Reproductive Technologies are unable to overcome age-related infertility, the older women erroneously labeled with unexplained infertility may receive inappropriate therapies. These may expose women to unjustified risks and waste financial resources. Unfortunately, the available literature about older women is scanty and does not provide valid evidence. Randomized controlled trials aimed at identifying the most suitable clinical management of older women with a normal infertility work-up are pressingly needed. PMID:27060173

  8. Stromal Fibroblast in Age-Related Cancer: Role in Tumorigenesis and Potential as Novel Therapeutic Target.

    PubMed

    Elkhattouti, Abdelouahid; Hassan, Mohamed; Gomez, Christian R

    2015-01-01

    Incidence of most common cancers increases with age due to accumulation of damage to cells and tissues. Stroma, the structure close to the basement membrane, is gaining increased attention from clinicians and researchers due to its increasingly, yet incompletely understood role in the development of age-related cancer. With advanced age, stroma generates a pro-tumorigenic microenvironment, exemplified by the senescence-associated secretory phenotype (SASP). Components of the SASP, such as cytokines, chemokines, and high energy metabolites are main drivers of age-related cancer initiation and sustain its progression. Our purpose is to provide insight into the mechanistic role of the stroma, with particular emphasis on stromal fibroblasts, on the development of age-related tumors. We also present evidence of the potential of the stroma as target for tumor therapy. Likewise, a rationale for age-related antitumor therapy targeting the stroma is presented. We expect to foster debate on the underlining basis of age-related cancer pathobiology. We also would like to promote discussion on novel stroma-based anticancer therapeutic strategies tailored to treat the elderly. PMID:26284191

  9. Aging assessment of reactor instrumentation and protection system components. Aging-related operating experiences

    SciTech Connect

    Gehl, A.C.; Hagen, E.W.

    1992-07-01

    A study of the aging-related operating experiences throughout a five-year period (1984--1988) of six generic instrumentation modules (indicators, sensors, controllers, transmitters, annunciators, and recorders) was performed as a part of the Nuclear Plant Aging Research Program. The effects of aging from operational and environmental stressors were characterized from results depicted in Licensee Event Reports (LERs). The data are graphically displayed as frequency of events per plant year for operating plant ages from 1 to 28 years to determine aging-related failure trend patterns. Three main conclusions were drawn from this study: (1) Instrumentation and control (I&C) modules make a modest contribution to safety-significant events: 17% of LERs issued during 1984--1988 dealt with malfunctions of the six I&C modules studied, and 28% of the LERs dealing with these I&C module malfunctions were aging related (other studies show a range 25--50%); (2) Of the six modules studied, indicators, sensors, and controllers account for the bulk (83%) of aging-related failures; and (3) Infant mortality appears to be the dominant aging-related failure mode for most I&C module categories (with the exception of annunciators and recorders, which appear to fail randomly).

  10. A Systematic Investigation into Aging Related Genes in Brain and Their Relationship with Alzheimer's Disease.

    PubMed

    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. PMID:26937969

  11. Profiling age-related epigenetic markers of stomach adenocarcinoma in young and old subjects.

    PubMed

    Kim, Byoung-Chul; Jeong, Hyoung Oh; Park, Daeui; Kim, Chul-Hong; Lee, Eun Kyeong; Kim, Dae Hyun; Im, Eunok; Kim, Nam Deuk; Lee, Sunghoon; Yu, Byung Pal; Bhak, Jong; Chung, Hae Young

    2015-01-01

    The purpose of our study is to identify epigenetic markers that are differently expressed in the stomach adenocarcinoma (STAD) condition. Based on data from The Cancer Genome Atlas (TCGA), we were able to detect an age-related difference in methylation patterns and changes in gene and miRNA expression levels in young (n = 14) and old (n = 70) STAD subjects. Our analysis identified 323 upregulated and 653 downregulated genes in old STAD subjects. We also found 76 miRNAs with age-related expression patterns and 113 differentially methylated genes (DMGs), respectively. Our further analysis revealed that significant upregulated genes (n = 35) were assigned to the cell cycle, while the muscle system process (n = 27) and cell adhesion-related genes (n = 57) were downregulated. In addition, by comparing gene and miRNA expression with methylation change, we identified that three upregulated genes (ELF3, IL1β, and MMP13) known to be involved in inflammatory responses and cell growth were significantly hypomethylated in the promoter region. We further detected target candidates for age-related, downregulated miRNAs (hsa-mir-124-3, hsa-mir-204, and hsa-mir-125b-2) in old STAD subjects. This is the first report of the results from a study exploring age-related epigenetic biomarkers of STAD using high-throughput data and provides evidence for a complex clinicopathological condition expressed by the age-related STAD progression.

  12. Mesenchymal stem cells: a revolution in therapeutic strategies of age-related diseases.

    PubMed

    Peng, Yan; Huang, Sha; Cheng, Biao; Nie, Xiaohu; Enhe, Jirigala; Feng, Changjiang; Fu, Xiaobing

    2013-01-01

    The great evolutionary biologist Theodosius Dobzhansky once said: "Nothing in biology makes sense except in the light of evolution". Aging is a complex biological phenomenon and the factors governing the process of aging and age-related diseases are only beginning to be understood, oxidative stress, telomere shortening in DNA components and genetic changes were shown to be the mainly regulating mechanisms during the recent decades. Although a considerable amount of both animal and clinical data that demonstrate the extensive and safe use of mesenchymal stromal cells (MSCs) is available, the precise summarization and identification of MSCs in age-related diseases remains a challenge. Along this line, this review discussed several typical age-related diseases for which MSCs have been proved to confer protection and put forward a hypothesis for the association among MSCs and age-related diseases from an evolutionary perspective. Above all, we hope further and more research efforts could be aroused to elucidate the role and mechanisms that MSCs involved in the age-related diseases.

  13. Bivalent separation into univalents precedes age-related meiosis I errors in oocytes

    PubMed Central

    Sakakibara, Yogo; Hashimoto, Shu; Nakaoka, Yoshiharu; Kouznetsova, Anna; Höög, Christer; Kitajima, Tomoya S.

    2015-01-01

    The frequency of chromosome segregation errors during meiosis I (MI) in oocytes increases with age. The two-hit model suggests that errors are caused by the combination of a first hit that creates susceptible crossover configurations and a second hit comprising an age-related reduction in chromosome cohesion. This model predicts an age-related increase in univalents, but direct evidence of this phenomenon as a major cause of segregation errors has been lacking. Here, we provide the first live analysis of single chromosomes undergoing segregation errors during MI in the oocytes of naturally aged mice. Chromosome tracking reveals that 80% of the errors are preceded by bivalent separation into univalents. The set of the univalents is biased towards balanced and unbalanced predivision of sister chromatids during MI. Moreover, we find univalents predisposed to predivision in human oocytes. This study defines premature bivalent separation into univalents as the primary defect responsible for age-related aneuploidy. PMID:26130582

  14. Genetics and age-related macular degeneration: a practical review for the clinician

    PubMed Central

    Schwartz, Stephen G; Hampton, Blake M; Kovach, Jaclyn L; Brantley, Milam A

    2016-01-01

    Age-related macular degeneration is a complex disease, with both genetic and environmental risk factors interacting in unknown ways. Currently, 52 gene variants within 34 loci have been significantly associated with age-related macular degeneration. Two well-studied major genes are complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2). There exist several commercially available tests that are proposed to stratify patients into high-risk and low-risk groups, as well as predict response to nutritional supplementation. However, at present, the bulk of the available peer-reviewed evidence suggests that genetic testing is more useful as a research tool than for clinical management of patients. PMID:27445455

  15. Understanding Age-Related Changes in Skeletal Muscle Metabolism: Differences Between Females and Males.

    PubMed

    Gheller, Brandon J F; Riddle, Emily S; Lem, Melinda R; Thalacker-Mercer, Anna E

    2016-07-17

    Skeletal muscle is the largest metabolic organ system in the human body. As such, metabolic dysfunction occurring in skeletal muscle impacts whole-body nutrient homeostasis. Macronutrient metabolism changes within the skeletal muscle with aging, and these changes are associated in part with age-related skeletal muscle remodeling. Moreover, age-related changes in skeletal muscle metabolism are affected differentially between males and females and are likely driven by changes in sex hormones. Intrinsic and extrinsic factors impact observed age-related changes and sex-related differences in skeletal muscle metabolism. Despite some support for sex-specific differences in skeletal muscle metabolism with aging, more research is necessary to identify underlying differences in mechanisms. Understanding sex-specific aging skeletal muscle will assist with the development of therapies to attenuate adverse metabolic and functional outcomes.

  16. Mitochondrial ROS regulate oxidative damage and mitophagy but not age-related muscle fiber atrophy

    PubMed Central

    Sakellariou, Giorgos K.; Pearson, Timothy; Lightfoot, Adam P.; Nye, Gareth A.; Wells, Nicola; Giakoumaki, Ifigeneia I.; Vasilaki, Aphrodite; Griffiths, Richard D.; Jackson, Malcolm J.; McArdle, Anne

    2016-01-01

    Age-related loss of skeletal muscle mass and function is a major contributor to morbidity and has a profound effect on the quality of life of older people. The potential role of age-dependent mitochondrial dysfunction and cumulative oxidative stress as the underlying cause of muscle aging remains a controversial topic. Here we show that the pharmacological attenuation of age-related mitochondrial redox changes in muscle with SS31 is associated with some improvements in oxidative damage and mitophagy in muscles of old mice. However, this treatment failed to rescue the age-related muscle fiber atrophy associated with muscle atrophy and weakness. Collectively, these data imply that the muscle mitochondrial redox environment is not a key regulator of muscle fiber atrophy during sarcopenia but may play a key role in the decline of mitochondrial organelle integrity that occurs with muscle aging. PMID:27681159

  17. Progressive Bidirectional Age-Related Changes in Default Mode Network Effective Connectivity across Six Decades

    PubMed Central

    Li, Karl; Laird, Angela R.; Price, Larry R.; McKay, D. Reese; Blangero, John; Glahn, David C.; Fox, Peter T.

    2016-01-01

    The default mode network (DMN) is a set of regions that is tonically engaged during the resting state and exhibits task-related deactivation that is readily reproducible across a wide range of paradigms and modalities. The DMN has been implicated in numerous disorders of cognition and, in particular, in disorders exhibiting age-related cognitive decline. Despite these observations, investigations of the DMN in normal aging are scant. Here, we used blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) acquired during rest to investigate age-related changes in functional connectivity of the DMN in 120 healthy normal volunteers comprising six, 20-subject, decade cohorts (from 20–29 to 70–79). Structural equation modeling (SEM) was used to assess age-related changes in inter-regional connectivity within the DMN. SEM was applied both using a previously published, meta-analytically derived, node-and-edge model, and using exploratory modeling searching for connections that optimized model fit improvement. Although the two models were highly similar (only 3 of 13 paths differed), the sample demonstrated significantly better fit with the exploratory model. For this reason, the exploratory model was used to assess age-related changes across the decade cohorts. Progressive, highly significant changes in path weights were found in 8 (of 13) paths: four rising, and four falling (most changes were significant by the third or fourth decade). In all cases, rising paths and falling paths projected in pairs onto the same nodes, suggesting compensatory increases associated with age-related decreases. This study demonstrates that age-related changes in DMN physiology (inter-regional connectivity) are bidirectional, progressive, of early onset and part of normal aging. PMID:27378909

  18. Dizziness and Imbalance in the Elderly: Age-related Decline in the Vestibular System.

    PubMed

    Iwasaki, Shinichi; Yamasoba, Tatsuya

    2015-02-01

    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

  19. Dizziness and Imbalance in the Elderly: Age-related Decline in the Vestibular System

    PubMed Central

    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

  20. Adverse Childhood Experiences and Adult Risk Factors for Age-Related Disease

    PubMed Central

    Danese, Andrea; Moffitt, Terrie E.; Harrington, HonaLee; Milne, Barry J.; Polanczyk, Guilherme; Pariante, Carmine M.; Poulton, Richie; Caspi, Avshalom

    2013-01-01

    Objective To understand why children exposed to adverse psychosocial experiences are at elevated risk for age-related disease, such as cardiovascular disease, by testing whether adverse childhood experiences predict enduring abnormalities in stress-sensitive biological systems, namely, the nervous, immune, and endocrine/metabolic systems. Design A 32-year prospective longitudinal study of a representative birth cohort. Setting New Zealand. Participants A total of 1037 members of the Dunedin Multidisciplinary Health and Development Study. Main Exposures During their first decade of life, study members were assessed for exposure to 3 adverse psychosocial experiences: socioeconomic disadvantage, maltreatment, and social isolation. Main Outcome Measures At age 32 years, study members were assessed for the presence of 3 age-related-disease risks: major depression, high inflammation levels (high-sensitivity C-reactive protein level >3 mg/L), and the clustering of metabolic risk biomarkers (overweight, high blood pressure, high total cholesterol, low high-density lipoprotein cholesterol, high glycated hemoglobin, and low maximum oxygen consumption levels. Results Children exposed to adverse psychosocial experiences were at elevated risk of depression, high inflammation levels, and clustering of metabolic risk markers. Children who had experienced socioeconomic disadvantage (incidence rate ratio, 1.89; 95% confidence interval, 1.36–2.62), maltreatment (1.81; 1.38–2.38), or social isolation (1.87; 1.38–2.51) had elevated age-related-disease risks in adulthood. The effects of adverse childhood experiences on age-related-disease risks in adulthood were nonredundant, cumulative, and independent of the influence of established developmental and concurrent risk factors. Conclusions Children exposed to adverse psychosocial experiences have enduring emotional, immune, and metabolic abnormalities that contribute to explaining their elevated risk for age-related disease. The

  1. Age-Related Differences in Cortical Thickness Vary by Socioeconomic Status.

    PubMed

    Piccolo, Luciane R; Merz, Emily C; He, Xiaofu; Sowell, Elizabeth R; Noble, Kimberly G

    2016-01-01

    Recent findings indicate robust associations between socioeconomic status (SES) and brain structure in children, raising questions about the ways in which SES may modify structural brain development. In general, cortical thickness and surface area develop in nonlinear patterns across childhood and adolescence, with developmental patterns varying to some degree by cortical region. Here, we examined whether age-related nonlinear changes in cortical thickness and surface area varied by SES, as indexed by family income and parental education. We hypothesized that SES disparities in age-related change may be particularly evident for language- and literacy-supporting cortical regions. Participants were 1148 typically-developing individuals between 3 and 20 years of age. Results indicated that SES factors moderate patterns of age-associated change in cortical thickness but not surface area. Specifically, at lower levels of SES, associations between age and cortical thickness were curvilinear, with relatively steep age-related decreases in cortical thickness earlier in childhood, and subsequent leveling off during adolescence. In contrast, at high levels of SES, associations between age and cortical thickness were linear, with consistent reductions across the age range studied. Notably, this interaction was prominent in the left fusiform gyrus, a region that is critical for reading development. In a similar pattern, SES factors significantly moderated linear age-related change in left superior temporal gyrus, such that higher SES was linked with steeper age-related decreases in cortical thickness in this region. These findings suggest that SES may moderate patterns of age-related cortical thinning, especially in language- and literacy-supporting cortical regions. PMID:27644039

  2. Progressive Bidirectional Age-Related Changes in Default Mode Network Effective Connectivity across Six Decades.

    PubMed

    Li, Karl; Laird, Angela R; Price, Larry R; McKay, D Reese; Blangero, John; Glahn, David C; Fox, Peter T

    2016-01-01

    The default mode network (DMN) is a set of regions that is tonically engaged during the resting state and exhibits task-related deactivation that is readily reproducible across a wide range of paradigms and modalities. The DMN has been implicated in numerous disorders of cognition and, in particular, in disorders exhibiting age-related cognitive decline. Despite these observations, investigations of the DMN in normal aging are scant. Here, we used blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) acquired during rest to investigate age-related changes in functional connectivity of the DMN in 120 healthy normal volunteers comprising six, 20-subject, decade cohorts (from 20-29 to 70-79). Structural equation modeling (SEM) was used to assess age-related changes in inter-regional connectivity within the DMN. SEM was applied both using a previously published, meta-analytically derived, node-and-edge model, and using exploratory modeling searching for connections that optimized model fit improvement. Although the two models were highly similar (only 3 of 13 paths differed), the sample demonstrated significantly better fit with the exploratory model. For this reason, the exploratory model was used to assess age-related changes across the decade cohorts. Progressive, highly significant changes in path weights were found in 8 (of 13) paths: four rising, and four falling (most changes were significant by the third or fourth decade). In all cases, rising paths and falling paths projected in pairs onto the same nodes, suggesting compensatory increases associated with age-related decreases. This study demonstrates that age-related changes in DMN physiology (inter-regional connectivity) are bidirectional, progressive, of early onset and part of normal aging. PMID:27378909

  3. Age-Related Differences in Cortical Thickness Vary by Socioeconomic Status

    PubMed Central

    He, Xiaofu; Sowell, Elizabeth R.; Noble, Kimberly G.

    2016-01-01

    Recent findings indicate robust associations between socioeconomic status (SES) and brain structure in children, raising questions about the ways in which SES may modify structural brain development. In general, cortical thickness and surface area develop in nonlinear patterns across childhood and adolescence, with developmental patterns varying to some degree by cortical region. Here, we examined whether age-related nonlinear changes in cortical thickness and surface area varied by SES, as indexed by family income and parental education. We hypothesized that SES disparities in age-related change may be particularly evident for language- and literacy-supporting cortical regions. Participants were 1148 typically-developing individuals between 3 and 20 years of age. Results indicated that SES factors moderate patterns of age-associated change in cortical thickness but not surface area. Specifically, at lower levels of SES, associations between age and cortical thickness were curvilinear, with relatively steep age-related decreases in cortical thickness earlier in childhood, and subsequent leveling off during adolescence. In contrast, at high levels of SES, associations between age and cortical thickness were linear, with consistent reductions across the age range studied. Notably, this interaction was prominent in the left fusiform gyrus, a region that is critical for reading development. In a similar pattern, SES factors significantly moderated linear age-related change in left superior temporal gyrus, such that higher SES was linked with steeper age-related decreases in cortical thickness in this region. These findings suggest that SES may moderate patterns of age-related cortical thinning, especially in language- and literacy-supporting cortical regions. PMID:27644039

  4. Unexpected thymic hyperplasia in transgenic mice harboring a neuronal promoter fused with simian virus 40 large T antigen.

    PubMed Central

    Botteri, F M; van der Putten, H; Wong, D F; Sauvage, C A; Evans, R M

    1987-01-01

    The hypothalamic peptide growth hormone-releasing factor (GRF) regulates the secretion and production of growth hormone from the anterior pituitary (M. C. Gelato and G. R. Merriam, Annu. Rev. Physiol. 48:569-591). To study GRF gene regulation, transgenic mice were generated that harbor the human GRF promoter fused to the coding sequences from the simian virus 40 early region. These mice had normal hypothalamic functions but unexpectedly suffered from severe thymic hyperplasia. Immunohistochemical analysis revealed that large T antigen was expressed in the thymic epithelial cells. These cells have endocrine properties and are known to produce thymic hormones [corrected]. The thymic hyperplasia was the apparent consequence of inappropriate production of T-cell maturation factors by epithelial cells and could involve increased self renewal of apparently normal T stem cells in the thymus. Images PMID:3118193

  5. Thymic epithelial cell expansion through matricellular protein CYR61 boosts progenitor homing and T-cell output.

    PubMed

    Emre, Yalin; Irla, Magali; Dunand-Sauthier, Isabelle; Ballet, Romain; Meguenani, Mehdi; Jemelin, Stephane; Vesin, Christian; Reith, Walter; Imhof, Beat A

    2013-01-01

    Thymic epithelial cells (TEC) are heterogeneous stromal cells that generate microenvironments required for the formation of T cells within the thymus. Defects in TEC lead to immunodeficiency or autoimmunity. Here we identify TEC as the major source of cysteine-rich protein 61 (CYR61), a matricellular protein implicated in cell proliferation and migration. Binding of CYR61 to LFA-1, ICAM-1 and integrin α6 supports the adhesion of TEC and thymocytes as well as their interaction. Treatment of thymic lobes with recombinant CYR61 expands the stromal compartment by inducing the proliferation of TEC and activates Akt signalling. Engraftment of CYR61-overexpressing thymic lobes into athymic nude mice drastically boosts the yield of thymic output via expansion of TEC. This increases the space for the recruitment of circulating hematopoietic progenitors and the development of T cells. Our discovery paves the way for therapeutic interventions designed to restore thymus stroma and T-cell generation.

  6. Thymic epithelial cell expansion through matricellular protein CYR61 boosts progenitor homing and T-cell output

    NASA Astrophysics Data System (ADS)

    Emre, Yalin; Irla, Magali; Dunand-Sauthier, Isabelle; Ballet, Romain; Meguenani, Mehdi; Jemelin, Stephane; Vesin, Christian; Reith, Walter; Imhof, Beat A.

    2013-11-01

    Thymic epithelial cells (TEC) are heterogeneous stromal cells that generate microenvironments required for the formation of T cells within the thymus. Defects in TEC lead to immunodeficiency or autoimmunity. Here we identify TEC as the major source of cysteine-rich protein 61 (CYR61), a matricellular protein implicated in cell proliferation and migration. Binding of CYR61 to LFA-1, ICAM-1 and integrin α6 supports the adhesion of TEC and thymocytes as well as their interaction. Treatment of thymic lobes with recombinant CYR61 expands the stromal compartment by inducing the proliferation of TEC and activates Akt signalling. Engraftment of CYR61-overexpressing thymic lobes into athymic nude mice drastically boosts the yield of thymic output via expansion of TEC. This increases the space for the recruitment of circulating hematopoietic progenitors and the development of T cells. Our discovery paves the way for therapeutic interventions designed to restore thymus stroma and T-cell generation.

  7. The Potential of Chitosan and Its Derivatives in Prevention and Treatment of Age-Related Diseases

    PubMed Central

    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

  8. "Older is always better": Age-related differences in vocabulary scores across 16 years.

    PubMed

    Ben-David, Boaz M; Erel, Hadas; Goy, Huiwen; Schneider, Bruce A

    2015-12-01

    Cross-sectional studies of cognitive aging compare age groups at 1 time point. It is unclear from such studies whether age-related cognitive differences remain stable across time. We present a cross-sectional investigation of vocabulary scores of 2,000 younger and older adults collected across 16 years, using the same laboratory and protocol. We found a steady decrease with year of testing and an advantage for older adults. An additive relation between age group and year of testing implied that age-related differences in vocabulary are independent of changes over time, suggesting that younger and older adults are similarly affected by changes in word usage.

  9. The potential of chitosan and its derivatives in prevention and treatment of age-related diseases.

    PubMed

    Kerch, Garry

    2015-04-01

    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.

  10. [Soft tissue enhancement with injectable fillers for correction of age related folds and wrinkles].

    PubMed

    Hönig, J; Fricke, M

    2005-12-01

    Injectable fillers for facial soft tissue enhancement have been developed and used for decades for the correction of age related folds and wrinkles. Many of the disadvantages of xenogenic and prior exogenous materials have been overcome with the advent of autologous and synthetic alternative materials. Autologous and synthetic injectable fillers herald a new era in the treatment of the aging face. Therefore this article will give an in-depth look at the implant choice, surgical approach, and possible complications and will provide a review of current injectable fillers for age related facial soft tissue augmentation.

  11. [Relationship between educational level and dementia: social factor and age-related chronic disease].

    PubMed

    Dartigues, J-F; Foubert-Samier, A; Helmer, C

    2013-08-01

    Dementia is an age-related chronic syndrome, whose the first cause is a neurodegenerative disease: Alzheimer's disease (AD). In spite of some controversies, educational level is now considered as a major risk factor for dementia and AD. The protective effect of a high level of education could be related to a preservation of cognitive reserve and a reinforcement of brain reserve. Moreover, subjects with a high level of education have a better access to health care and a better management of vascular risk factors. With the general improvement of the educational level, the age-related incidence of AD and dementia should decrease in the future.

  12. Improved word recognition for observers with age-related maculopathies using compensation filters

    NASA Technical Reports Server (NTRS)

    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.

  13. Fatty old hearts: role of cardiac lipotoxicity in age-related cardiomyopathy

    PubMed Central

    Drosatos, Konstantinos

    2016-01-01

    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. PMID:27558317

  14. Protease and protease inhibitory activity in pregnant and postpartum involuting uterus

    SciTech Connect

    Milwidsky, A.; Beller, U.; Palti, Z.; Mayer, M.

    1982-08-15

    The presence of two distinct proteolytic activities in the rat uterus was confirmed with /sup 14/C-labeled globin used as a sensitive protein substrate and following release of label into the trichloroacetic acid-soluble supernatant fraction. Protease I is a cytoplasmic acid protease while protease II is associated with the pellet fraction, can be extracted by 0.6 M sodium chloride, and is active at pH 7.0. Protease I activity is low during pregnancy and markedly increases at term achieving maximal activity at day 3 post partum with a subsequent decline to preterm activity values. Lactation did not affect the uterine protease I activity. Protease II activity is not significantly different during pregnancy, at term, and post partum. The presence of an inhibitor of protease I was suggested by a decrease in enzyme activity with an increased cytosolic protein concentration. The inhibitor also lessened bovine trypsin activity but had no effect on protease II. Although its inhibitory potency on trypsin fluctuated during the various uterine physiologic stages, these changes appeared to be statistically insignificant. Human uterine samples were also found to contain the two protease activities with similar changes in protease I post partum. It is suggested that, both in the rat and in man, uterine involution post partum is associated with a marked increase in activity of acid cytosolic protease, while a particulate neutral protease and a soluble inhibitor of trypsin, which are also present in uterine cells, do not appear to play a significant role in the dissolution of uterine tissues after parturition.

  15. Pre-transplant thymic function is associated with the risk of cytomegalovirus disease after solid organ transplantation.

    PubMed

    Gracia-Ahufinger, I; Ferrando-Martínez, S; Montejo, M; Muñoz-Villanueva, M C; Cantisán, S; Rivero, A; Solana, R; Leal, M; Torre-Cisneros, J

    2015-05-01

    Cytomegalovirus (CMV) disease is an important complication in solid organ transplant recipients. Thymic function in adults is associated with specific T-cell immunity. Pre-transplant thymic function was analysed in 75 solid organ transplant patients by the use of nested PCR. The primary outcome was the incidence of CMV disease 12 months after transplantation. Using multivariable logistic regression, we studied whether pre-transplant thymic function is an independent risk factor for CMV disease after transplantation. Thymic function was related to the risk of CMV disease in CMV-seropositive recipients. In these recipients, pre-transplant thymic function of <9.5 (OR 11.27, 95% CI 1.11-114.43, p 0.040) and the use of thymoglobulin (OR 8.21, 95% CI 1.09-61.84, p 0.041) were independent risk factors for CMV disease at 12 months after transplantation. Patients with pre-transplant thymic function values of <9.5 had a higher subsequent incidence of CMV disease (24%) than patients with values of ≥ 9.5 (3%) (log-rank test: 5.727; p 0.017). The positive and negative predictive values of these pre-transplant thymic function cut-offs were 0.24 (95% CI 0.10-0.45) and 0.97 (95% CI 0.82-1.00), respectively. Pre-transplant thymic function in CMV-seropositive candidates could be useful in determining the risk of post-transplant CMV disease in solid organ transplant patients, selecting a group of low-risk candidates.

  16. Adenocarcinoma of the thymus, enteric type: report of 2 cases, and proposal for a novel subtype of thymic carcinoma.

    PubMed

    Moser, Bernhard; Schiefer, Ana Iris; Janik, Stefan; Marx, Alexander; Prosch, Helmut; Pohl, Wolfgang; Neudert, Barbara; Scharrer, Anke; Klepetko, Walter; Müllauer, Leonhard

    2015-04-01

    We report 2 cases of primary thymic adenocarcinoma with enteric differentiation. One carcinoma occurred in a 41-year-old man as a 7-cm-diameter cystic tumor and the other one in a 39-year-old woman as a 6-cm-diameter solid mass. Both tumors were located in the anterior mediastinum. Clinical staging did not reveal any extrathymic tumor. Histologically, the tumors were classified as adenocarcinoma, not otherwise specified, and a mucinous (colloid) carcinoma, respectively. Immunohistochemically, both tumors were positive for cytokeratin 20 (CK20), CDX2, and carcinoembryonic antigen, reflecting enteric differentiation. A review of the literature on 43 other cases of primary thymic adenocarcinomas suggested 11 further cases with enteric differentiation, as assessed by CK20 and/or CDX2 expression. We propose that thymic adenocarcinoma with enteric differentiation represents a novel subtype of thymic carcinoma. It is mostly of mucinous morphology and frequently associated with thymic cysts. The clinical outcome is variable. Recognition of primary thymic adenocarcinoma with enteric differentiation is helpful for the differentiation from metastatic disease, mainly from the gastrointestinal tract. PMID:25517960

  17. Adenocarcinoma of the thymus, enteric type: report of 2 cases, and proposal for a novel subtype of thymic carcinoma.

    PubMed

    Moser, Bernhard; Schiefer, Ana Iris; Janik, Stefan; Marx, Alexander; Prosch, Helmut; Pohl, Wolfgang; Neudert, Barbara; Scharrer, Anke; Klepetko, Walter; Müllauer, Leonhard

    2015-04-01

    We report 2 cases of primary thymic adenocarcinoma with enteric differentiation. One carcinoma occurred in a 41-year-old man as a 7-cm-diameter cystic tumor and the other one in a 39-year-old woman as a 6-cm-diameter solid mass. Both tumors were located in the anterior mediastinum. Clinical staging did not reveal any extrathymic tumor. Histologically, the tumors were classified as adenocarcinoma, not otherwise specified, and a mucinous (colloid) carcinoma, respectively. Immunohistochemically, both tumors were positive for cytokeratin 20 (CK20), CDX2, and carcinoembryonic antigen, reflecting enteric differentiation. A review of the literature on 43 other cases of primary thymic adenocarcinomas suggested 11 further cases with enteric differentiation, as assessed by CK20 and/or CDX2 expression. We propose that thymic adenocarcinoma with enteric differentiation represents a novel subtype of thymic carcinoma. It is mostly of mucinous morphology and frequently associated with thymic cysts. The clinical outcome is variable. Recognition of primary thymic adenocarcinoma with enteric differentiation is helpful for the differentiation from metastatic disease, mainly from the gastrointestinal tract.

  18. Expression of vascular endothelial growth factor receptors and their ligands in rat uterus during the postpartum involution period.

    PubMed

    Sağsöz, H; Liman, N; Alan, E

    2015-07-01

    Vascular endothelial growth factor (VEGF) and its specific receptors, FLt1/fms, Flk1/KDR and FLt4, play important roles in vasculogenesis, and physiological and pathological angiogenesis. Whether angiogenic growth factors are involved in regulating angiogenic processes during the postpartum involution period (PP) of the rat uterus is unknown. We used immunohistochemistry to analyze the expression levels of VEGF, the fms-like tyrosine kinase 1 (FLt1/fms), the kinase insert domain-containing region 1 (Flk1/KDR), Fms-related tyrosine kinase 4 (FLt4) and vascular endothelial growth inhibitor (VEGI) in the rat uterus during the days 1, 3, 5, 10 and 15 of the PP to determine the temporal and spatial expressions of VEGF and its receptors during the PP. Throughout the PP, cytoplasmic and membrane staining of VEGI, VEGF and their receptors were observed in the lumens, crypts and glandular epithelial cells as well as in connective tissue and vascular endothelial and smooth muscle cells in the endometrium. We found that the intensity of the immunoreactions in the endometrium varied with the morphological changes that occurred during involution. Immunoreactions for VEGI, VEGF and their receptor, Flk1/KDR, in the luminal epithelial cells were stronger than those in the glandular epithelial and stromal cells, particularly during PP 1, 3 and 5, which suggests that these peptides may contribute to re-epithelialization of the endometrium. On the other hand, Flt1/fms immunoreactivity was strong mainly in the stromal cells during the PP. The presence of VEGF and its receptors (FLt1/fms, Flk1/KDR, FLt4) in the stromal cells and blood vessels during the PP suggests that they may contribute to regulating stromal repair and angiogenesis in the involuting uterus of the rat.

  19. Mechanisms of Age-Related Decline in Memory Search across the Adult Life Span

    ERIC Educational Resources Information Center

    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. Age-Related Impairments in the Revision of Syntactic Misanalyses: Effects of Prosody

    ERIC Educational Resources Information Center

    Titone, Debra A.; Koh, Christine K.; Kjelgaard, Margaret M.; Bruce, Stephanie; Speer, Shari R.; Wingfield, Arthur

    2006-01-01

    Two experiments examined whether young and older adults differ in comprehending sentences that contain temporary syntactic closure ambiguities. Experiment 1 examined age-related differences using the Auditory Moving Window (AMW) task, in which sentences were presented in a segment-by-segment self-paced fashion. Experiment 2 examined age-related…

  1. A systematic review on zinc for the prevention and treatment of age-related macular degeneration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  2. Lutein and Age-Related Ocular Disorders in the Older Adult: A Review

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lutein, a carotenoid found in dark green, leafy vegetables, has been implicated as being protective against the acquired ocular diseases, such as cataracts and age-related macular degeneration. In the eye, lutein may act as an antioxidant and as a blue light filter to protect the underlying tissues ...

  3. Correcting age-related changes in the face by use of injectable fillers and neurotoxins.

    PubMed

    Rubin, Mark G; Cox, Sue Ellen; Kaminer, Michael S; Solish, Nowell

    2014-06-01

    Many patients seeking rejuvenation treatment have readily apparent age-related changes in facial features. Others exhibit more subtle changes that nonetheless can be corrected to achieve a more youthful appearance. In the following article, four specialists in aesthetic dermatology discuss how injectable hyaluronic acid-based fillers and neurotoxins can achieve rejuvenation without surgery.

  4. Age-related differences in acute neurotoxicity produced by mevinphos, monocrotophos, dicrotophos, and phosphamidon

    EPA Science Inventory

    Age-related differences in the acute neurotoxicity of cholinesterase (ChE)-inhibiting pesticides have been well-studied for a few organophosphates, but not for many others. In this study, we directly compared dose-responses using brain and red blood cell (RBC) ChE measurements, a...

  5. Adaptation to Low Vision Caused by Age-Related Macular Degeneration: A Case Study

    ERIC Educational Resources Information Center

    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…

  6. The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases.

    PubMed

    Maessen, Dionne E M; Stehouwer, Coen D A; Schalkwijk, Casper G

    2015-06-01

    The formation and accumulation of advanced glycation endproducts (AGEs) are related to diabetes and other age-related diseases. Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is the major precursor in the formation of AGEs. MGO is mainly formed as a byproduct of glycolysis. Under physiological circumstances, MGO is detoxified by the glyoxalase system into D-lactate, with glyoxalase I (GLO1) as the key enzyme in the anti-glycation defence. New insights indicate that increased levels of MGO and the major MGO-derived AGE, methylglyoxal-derived hydroimidazolone 1 (MG-H1), and dysfunctioning of the glyoxalase system are linked to several age-related health problems, such as diabetes, cardiovascular disease, cancer and disorders of the central nervous system. The present review summarizes the mechanisms through which MGO is formed, its detoxification by the glyoxalase system and its effect on biochemical pathways in relation to the development of age-related diseases. Although several scavengers of MGO have been developed over the years, therapies to treat MGO-associated complications are not yet available for application in clinical practice. Small bioactive inducers of GLO1 can potentially form the basis for new treatment strategies for age-related disorders in which MGO plays a pivotal role.

  7. Age-Related Hearing Loss: Quality of Care for Quality of Life

    ERIC Educational Resources Information Center

    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…

  8. Nutritional interventions protect against age-related deficits in behavior: from animals to humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aged rats show impaired performance on motor and cognitive tasks. Similar changes in behavior occur in humans with age, and the development of methods to retard or reverse these age-related neuronal and behavioral deficits could increase healthy aging and decrease health care costs. In the present s...

  9. Psychosocial Intervention for Age-Related Macular Degeneration: A Pilot Project

    ERIC Educational Resources Information Center

    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.

  10. The Psychosocial Impact of Closed-Circuit Televisions on Persons with Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Huber, Jessica G.; Jutai, Jeffrey W.; Strong, J. Graham; Plotkin, Ann D.

    2008-01-01

    Closed-circuit televisions (CCTVs) are used by many elderly people who have age-related macular degeneration (AMD). The functional vision of 68 participants, which was measured immediately after they adopted CCTVs, suggested successful outcomes, but the psychosocial impact of the use of CCTVs did not peak until a month later. The findings help…

  11. Lighting Needs and Lighting Comfort During Reading with Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Fosse, Per; Valberg, Arne

    2004-01-01

    This study investigated the effects of changes in luminance on the oral reading speeds of 13 participants with age-related macular degeneration (AMD) and a control group of six age-matched persons with typical vision. For the AMD participants, self-reports of light preferences were also recorded. In the AMD group, reading rates depended on light…

  12. A Qualitative Analysis of Reading Rehabilitation of Persons with Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Feely, Mary; Vetere, Arlene; Myers, Lynn B.

    2007-01-01

    One of the most prevalent visual impairments of people aged 60 and older is age-related macular degeneration (AMD), which ranks third globally as a cause of visual impairment (World Health Organization, 2006). The purpose of this study was to conduct a tentative subjective assessment of eccentric viewing by persons with AMD. The authors recruited…

  13. Ability of university-level education to prevent age-related decline in emotional intelligence

    PubMed Central

    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

  14. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease

    PubMed Central

    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.

    2016-01-01

    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. PMID:27534441

  15. Age-Related Changes in Duration Reproduction: Involvement of Working Memory Processes

    ERIC Educational Resources Information Center

    Baudouin, Alexia; Vanneste, Sandrine; Pouthas, Viviane; Isingrini, Michel

    2006-01-01

    The aim of the present research was to study age-related changes in duration reproduction by differentiating the working memory processes underlying this time estimation task. We compared performances of young and elderly adults in a duration reproduction task performed in simple and concurrent task conditions. Participants were also administered…

  16. Age-Related and Sex-Related Differences in Hand and Pinch Grip Strength in Adults

    ERIC Educational Resources Information Center

    Puh, Urska

    2010-01-01

    The purpose of the study was to quantify age-related changes in hand grip strength and three types of pinch grip strength (key pinch, tip pinch, and palmar pinch) among male and female participants. The study included 199 healthy participants (100 females, 99 males) aged 20-79 years, who were divided into four age groups. The Baseline Hydraulic…

  17. NPY antagonism reduces adiposity and attenuates age-related imbalance of adipose tissue metabolism.

    PubMed

    Park, Seongjoon; Fujishita, Chika; Komatsu, Toshimitsu; Kim, Sang Eun; Chiba, Takuya; Mori, Ryoichi; Shimokawa, Isao

    2014-12-01

    An orexigenic hormone, neuropeptide Y (NPY), plays a role not only in the hypothalamic regulation of appetite, but also in the peripheral regulation of lipid metabolism. However, the intracellular mechanisms triggered by NPY to regulate lipid metabolism are poorly understood. Here we report that NPY deficiency reduces white adipose tissue (WAT) mass and ameliorates the age-related imbalance of adipose tissue metabolism in mice. Gene expression involved in adipogenesis/lipogenesis was found to decrease, whereas proteins involved in lipolysis increased in gonadal WAT (gWAT) of NPY-knockout mice. These changes were associated with an activated SIRT1- and PPARγ-mediated pathway. Moreover, the age-related decrease of de novo lipogenesis in gWAT and thermogenesis in inguinal WAT was inhibited by NPY deficiency. Further analysis using 3T3-L1 cells showed that NPY inhibited lipolysis through the Y1 receptor and enhanced lipogenesis following a reduction in cAMP response element-binding protein (CREB) and SIRT1 protein expression. Therefore, NPY appears to act as a key regulator of adipose tissue metabolism via the CREB-SIRT1 signaling pathway. Taken together, NPY deficiency reduces adiposity and ameliorates the age-related imbalance of adipose tissue metabolism, suggesting that antagonism of NPY may be a promising target for drug development to prevent age-related metabolic diseases.

  18. Cognitive Abilities Explaining Age-Related Changes in Time Perception of Short and Long Durations

    ERIC Educational Resources Information Center

    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…

  19. Children's Recognition of Fairness and Others' Welfare in a Resource Allocation Task: Age Related Changes

    ERIC Educational Resources Information Center

    Rizzo, Michael T.; Elenbaas, Laura; Cooley, Shelby; Killen, Melanie

    2016-01-01

    The present study investigated age-related changes regarding children's (N = 136) conceptions of fairness and others' welfare in a merit-based resource allocation paradigm. To test whether children at 3- to 5-years-old and 6- to 8-years-old took others' welfare into account when dividing resources, in addition to merit and equality concerns,…

  20. Age-Related Differences in Reaction Time Task Performance in Young Children

    ERIC Educational Resources Information Center

    Kiselev, Sergey; Espy, Kimberlay Andrews; Sheffield, Tiffany

    2009-01-01

    Performance of reaction time (RT) tasks was investigated in young children and adults to test the hypothesis that age-related differences in processing speed supersede a "global" mechanism and are a function of specific differences in task demands and processing requirements. The sample consisted of 54 4-year-olds, 53 5-year-olds, 59 6-year-olds,…

  1. Diagnosis of Age-Related Cardiovascular Disorders | NCI Technology Transfer Center | TTC

    Cancer.gov

    Researchers at the NIH, National Institute on Aging, Cardiovascular Biology Unit-Vascular Group have discovered a method for the diagnosis and prognosis of cardiovascular aging, and is seeking parties interested in in-licensing or collaborative research to co-develop, evaluate, or commercialize novel methods for diagnosing age-related cardiovascular disorders.

  2. Age-related changes to the neural correlates of working memory which emerge after midlife

    PubMed Central

    Macpherson, Helen N.; White, David J.; Ellis, Kathryn A.; Stough, Con; Camfield, David; Silberstein, Richard; Pipingas, Andrew

    2014-01-01

    Previous research has indicated that the neural processes which underlie working memory change with age. Both age-related increases and decreases to cortical activity have been reported. This study investigated which stages of working memory are most vulnerable to age-related changes after midlife. To do this we examined age-differences in the 13 Hz steady state visually evoked potential (SSVEP) associated with a spatial working memory delayed response task. Participants were 130 healthy adults separated into a midlife (40–60 years) and an older group (61–82 years). Relative to the midlife group, older adults demonstrated greater bilateral frontal activity during encoding and this pattern of activity was related to better working memory performance. In contrast, evidence of age-related under activation was identified over left frontal regions during retrieval. Findings from this study suggest that after midlife, under-activation of frontal regions during retrieval contributes to age-related decline in working memory performance. PMID:24795625

  3. The short-wavelength mechanisms of Stiles in age-related macular degeneration.

    PubMed

    Hubschman, J P; Vola, J L; Conrath, J; Berros, P; Hougrand, F

    1998-11-01

    Clinical measurements by the increment-threshold technique of W.S. Stiles are reported in five cases of age-related macular degeneration. Measurements were made on a modified Tübingen perimeter using 1 degree, short-wavelength targets presented on a red field.

  4. Knowledge and Use of Low Vision Services Among Persons with Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Casten, Robin J.; Maloney, Eileen K.; Rovner, Barry W.

    2005-01-01

    Visual impairment (blindness or low vision) is a leading cause of disability among older adults and is most often due to age-related macular degeneration (AMD). It is predicted that 2.95 million people will have AMD by 2020 (Eye Diseases Prevalence Research Group, 2004). Unfortunately, there is no cure for AMD, nor can lost vision be restored.…

  5. Age-related behavioral effects of methomyI in Brown Norway rats.

    EPA Science Inventory

    Methomyl is a cholinesterase-inhibiting carbamate pesticide that is used in the field on cotton and a variety of fruits and vegetables. Concerns have been raised generally about age-related differences in susceptibility to cholinesterase-inhibiting pesticides, especially for chil...

  6. Heritability of Anxious-Depressive and Withdrawn Behavior: Age-Related Changes during Adolescence

    ERIC Educational Resources Information Center

    Lamb, Diane J.; Middeldorp, Christel M.; van Beijsterveldt, Catarina E. M.; Bartels, Meike; van der Aa, Niels; Polderman, Tinca J. C.; Boomsma, Dorret I.

    2010-01-01

    Objective: To explain the differential course of anxiety and depression in individuals from childhood to adulthood by examining age-related changes in the genetic and environmental etiology of anxious and depressive symptoms. Method: A sample of 1470, 1839, and 2023 Dutch twins aged 12, 14, and 16 years reported on symptoms of anxious depression…

  7. Pentosidine Accumulation in Human Oocytes and Their Correlation to Age-Related Apoptosis

    PubMed Central

    Matsumine, Miki; Shibata, Noriyuki; Ishitani, Ken; Kobayashi, Makio; Ohta, Hiroaki

    2008-01-01

    Age-related atresia of ovarian follicles is characterized by apoptosis of the constituent cells. Recent studies have indicated that dysfunction of the proteasome and endoplasmic reticulum and subsequent apoptosis in the presence of oxidative stress have relevance to aging. The aim of this study was to assess the involvement of these processes in age-related follicular atresia. Formalin-fixed, paraffin-embedded sections of ovaries obtained at surgery from 74 women (age: 21–54 y) were examined with the terminal deoxynucleotidyl transferase-mediated, dUTP-biotin nick-end labeling (TUNEL) method and an immunohistochemical technique. Primary antibodies used in immunohistochemistry were against pentosidine, ubiquitin and caspase 12. Histological localization of these substances in oocytes was observed by light microscopy, and labeling indices of these cells were evaluated by regression analysis. Positive signals for pentosidine, ubiquitin, caspase 12, and TUNEL were detectable in oocytes of the primordial, primary and their atretic follicles. Regression analysis revealed an age-related increase in the labeling indices for pentosidine, ubiquitin, caspase 12, and TUNEL. These results suggest that pentosidine accumulation in human oocytes is related to apoptosis and increases with age. Further studies will be necessary to clarify the involvement of pentosidine accumulation, proteasome inhibition, and endoplasmic reticulum stress in age-related apoptosis of oocytes in human ovaries. PMID:18787640

  8. Shared and Unique Genetic and Environmental Influences on Aging-Related Changes in Multiple Cognitive Abilities

    ERIC Educational Resources Information Center

    Tucker-Drob, Elliot M.; Reynolds, Chandra A.; Finkel, Deborah; Pedersen, Nancy L.

    2014-01-01

    Aging-related declines occur in many different domains of cognitive function during middle and late adulthood. However, whether a global dimension underlies individual differences in changes in different domains of cognition and whether global genetic influences on cognitive changes exist is less clear. We addressed these issues by applying…

  9. Age-related clinical and microbiological characteristics of enteric fever in India.

    PubMed

    Walia, Mandeep; Gaind, Rajni; Paul, Premila; Mehta, Rajesh; Aggarwal, Pushpa; Kalaivani, Mani

    2006-10-01

    A retrospective, hospital-based study at Safdarjang Hospital, India, was undertaken between January 1999 and December 2003 to estimate age-related epidemiological, clinical and microbiological characteristics in enteric fever cases. A total of 750 blood-culture-proven cases of enteric fever were studied. The majority of cases occurred in children aged 5-12 years and 24.8% of cases were in children up to 5 years of age. Salmonella serotypes showed an age-related predilection, with paratyphoid fever more common in adults. Classically-described clinical features of the disease were comparable among patients under and above 5 years of age. Hepatomegaly, anaemia and complications in general were more frequent in children up to 5 years of age. The antimicrobial resistance pattern, irrespective of Salmonella serotype, did not reveal a statistically significant difference across age groups for the different antibiotics tested. Multidrug resistance was seen only in Salmonella enterica serotype Typhi but not in S. Paratyphi A isolates. However, resistance to nalidixic acid was comparable in both serotypes. Age-related differences of serotype isolation rates, clinical presentation and associated complications are noteworthy for better case management and policy planning. More epidemiological studies regarding reasons for age-related differential serotype patterns would enable and guide public health strategies to contain enteric fever in endemic locations. PMID:16766005

  10. The potential effects of meditation on age-related cognitive decline: a systematic review.

    PubMed

    Gard, Tim; Hölzel, Britta K; Lazar, Sara W

    2014-01-01

    With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline.

  11. Age-related alterations to immune parameters in Labrador retriever dogs.

    PubMed

    Blount, Daniel G; Pritchard, David I; Heaton, Paul R

    2005-12-15

    In order to assess age-related changes in the immune status of Labrador retriever dogs, leukocyte phenotypes, lymphocyte proliferative capacity, and serum antibody levels were measured in four cohorts of dogs, ranging from 2 to 10 years of age. Absolute numbers of white blood cells, lymphocytes, monocytes, granulocytes, and CD3+, CD4+, CD8+ and CD21+ lymphocytes significantly decreased with increasing age. Relative percentages of lymphocytes and CD4 cells were significantly decreased, and relative percentages of granulocytes and CD8 cells significantly increased, with age. The CD4:CD8 ratio showed a significant age-related decrease. Proliferative responses of T-cells to mitogens in whole-blood cultures either increased (Concanavalin A) or remained the same (phytohemagglutinin) with age when data was normalised to allow for differences in responding cell number. Similarly, normalised data of proliferative response to anti-CD3 stimulation together with phorbol 12-myristate 13-acetate showed an age-related increase. Serum levels of total IgA significantly increased with age whereas total IgG levels remained unchanged. These observations illustrate a significant change to a number of immune parameters with age. However, further work is required to determine whether the differences reported here are sufficient to cause overt or functional immune senescence in Labrador retriever dogs. PMID:16105688

  12. Age-related spatial working memory deficits in homing pigeons (Columba livia).

    PubMed

    Coppola, Vincent J; Hough, Gerald; Bingman, Verner P

    2014-12-01

    The hippocampus is particularly susceptible to age-related degeneration that, like hippocampal lesions, is thought to lead to age-related decline in spatial memory and navigation. Lesions to the avian hippocampal formation (HF) also result in impaired spatial memory and navigation, but the relationship between aging and HF-dependent spatial cognition is unknown. To investigate possible age-related decline in avian spatial cognition, the current study investigated spatial working memory performance in older homing pigeons (10+ years of age). Pigeons completed a behavioral procedure nearly identical to the delayed spatial, win-shift procedure in a modified radial arm maze that has been previously used to study spatial working memory in rats and pigeons. The results revealed that the older pigeons required a greater number of choices to task completion and were less accurate with their first 4 choices as compared to younger pigeons (1-2 years of age). In addition, older pigeons were more likely to adopt a stereotyped sampling strategy, which explained in part their impaired performance. To the best of our knowledge, this study is the first to demonstrate an age-related impairment of HF-dependent, spatial memory in birds. Implications and future directions of the findings are discussed.

  13. A novel radial water tread maze tracks age-related cognitive decline in mice

    PubMed Central

    Pettan-Brewer, Christina; Touch, Dylan V.; Wiley, Jesse C.; Hopkins, Heather C.; Rabinovitch, Peter S.; Ladiges, Warren C.

    2013-01-01

    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. PMID:24106580

  14. Cortical complexity as a measure of age-related brain atrophy.

    PubMed

    Madan, Christopher R; Kensinger, Elizabeth A

    2016-07-01

    The structure of the human brain changes in a variety of ways as we age. While a sizeable literature has examined age-related differences in cortical thickness, and to a lesser degree, gyrification, here we examined differences in cortical complexity, as indexed by fractal dimensionality in a sample of over 400 individuals across the adult lifespan. While prior studies have shown differences in fractal dimensionality between patient populations and age-matched, healthy controls, it is unclear how well this measure would relate to age-related cortical atrophy. Initially computing a single measure for the entire cortical ribbon, i.e., unparcellated gray matter, we found fractal dimensionality to be more sensitive to age-related differences than either cortical thickness or gyrification index. We additionally observed regional differences in age-related atrophy between the three measures, suggesting that they may index distinct differences in cortical structure. We also provide a freely available MATLAB toolbox for calculating fractal dimensionality. PMID:27103141

  15. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease.

    PubMed

    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.

  16. Network strategies to understand the aging process and help age-related drug design

    PubMed Central

    2009-01-01

    Recent studies have demonstrated that network approaches are highly appropriate tools for understanding the extreme complexity of the aging process. Moreover, the generality of the network concept helps to define and study the aging of technological and social networks and ecosystems, which may generate novel concepts for curing age-related diseases. The current review focuses on the role of protein-protein interaction networks (inter-actomes) in aging. Hubs and inter-modular elements of both interactomes and signaling networks are key regulators of the aging process. Aging induces an increase in the permeability of several cellular compartments, such as the cell nucleus, introducing gross changes in the representation of network structures. The large overlap between aging genes and genes of age-related major diseases makes drugs that aid healthy aging promising candidates for the prevention and treatment of age-related diseases, such as cancer, atherosclerosis, diabetes and neurodegenerative disorders. We also discuss a number of possible research options to further explore the potential of the network concept in this important field, and show that multi-target drugs (representing 'magic-buckshots' instead of the traditional 'magic bullets') may become an especially useful class of age-related drugs in the future. PMID:19804610

  17. Guidelines for the Evaluation of Dementia and Age-Related Cognitive Change

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Dementia in its many forms is a leading cause of functional limitation among older adults worldwide and will continue to ascend in global health importance as populations continue to age and effective cures remain elusive. The following guidelines were developed for psychologists who perform evaluations of dementia and age-related cognitive…

  18. Stress Constellations and Coping Styles of Older Adults with Age-Related Visual Impairment

    ERIC Educational Resources Information Center

    Lee, Kyoung Othelia; Brennan, Mark

    2006-01-01

    Narrative data from two earlier studies of adaptation to age-related visual impairment were examined for constellations of stressors and coping styles. In the course of previous qualitative analyses, the researchers identified stress and coping codes according to behavioral, psychological, and social domains using a grounded theory approach. In…

  19. Diminishing risk for age related macular degeneration with nutrition: A current view

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Clinical hallmarks of AMD are observed in one third of the elderly in industrialized countries. Preventative interventions through dietary modification are attractive strategies because they are more affordable...

  20. Intake of zinc and antioxidant micronutrients and early age-related maculopathy lesions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Macular degeneration, the end stage of age-related maculopathy (ARM), is the leading cause of legal blindness worldwide, and few modifiable risk factors are known. The high concentration of carotenoids in the macula, plus evidence linking oxidative stress to ARM, and carotenoids to antioxidation, ge...