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Increasing Evidence Points (increasing + evidence_point)
Selected AbstractsHypothalamic,endocrine aspects in Huntington's diseaseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2006Ĺsa Petersén Abstract Huntington's disease (HD) is a hereditary and fatal disorder caused by an expanded CAG triplet repeat in the HD gene, resulting in a mutant form of the protein huntingtin. Wild-type and mutant huntingtin are expressed in most tissues of the body but the normal function of huntingtin is not fully known. In HD, the neuropathology is characterized by intranuclear and cytoplasmic inclusions of huntingtin aggregates, and cell death primarily in striatum and cerebral cortex. However, hypothalamic atrophy occurs at early stages of HD with loss of orexin- and somatostatin-containing cell populations. Several symptoms of HD such as sleep disturbances, alterations in circadian rhythm, and weight loss may be due to hypothalamic dysfunction. Endocrine changes including increased cortisol levels, reduced testosterone levels and increased prevalence of diabetes are found in HD patients. In HD mice, alterations in the hypothalamic,pituitary,adrenal axis occurs as well as pancreatic ,-cell and adipocyte dysfunction. Increasing evidence points towards important pathology of the hypothalamus and the endocrine system in HD. As many neuroendocrine factors are secreted into the cerebrospinal fluid, blood and urine, it is possible that their levels may reflect the disease state in the central nervous system. Investigating neuroendocrine changes in HD opens up the possibility of finding biomarkers to evaluate future therapies for HD, as well as of identifying novel targets for therapeutic interventions. [source] Estradiol levels in prepubertal boys and girls , analytical challengesINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 5 2004Katrine Bay Summary Increasing evidence points at an important function of low concentrations of estradiol (E2) in prepubertal boys and girls. E2 serum levels in prepubertal children are, however, often immeasurable in conventional E2 assays. This strongly hampers further investigation of the physiological relevance of E2 in children. In addition, there is an increasing concern of the potential effect of exposure to endocrine disrupters with estrogenic or antiandrogenic activity on pubertal development. A requirement of assessing the instance for this concern, adds further to the demands for applicable methodologies for the evaluation of the sensitivity of the organism to low E2 concentrations. Traditionally, E2 is measured by use of the radioimmunoassay (RIA). As an ultrasensitive alternative to the RIA, a recombinant cell bioassay has been developed. In this review, methodological aspects for these methods of analysis are examined and their applicability for evaluation of low E2 serum concentrations in children is estimated. Furthermore, available data on E2 levels in prepubertal boys and girls are evaluated and discussed, taking into consideration the limitations of the methods of analysis. In conclusion, there is a pronounced demand for new and improved methods of analysis for accurate and sensitive evaluation of low concentrations of E2. [source] Challenging conventional wisdom: The etiologic role of dopamine oxidative stress in Parkinson's diseaseMOVEMENT DISORDERS, Issue 3 2005J. Eric Ahlskog PhD Abstract Oxidative stress is well documented in Parkinson's disease (PD) and has been attributed to dopamine oxidative metabolism. However, evidence of oxidative stress is found in a variety of neurodegenerative disorders, suggesting that more general factors are responsible or that cytodestructive processes secondarily generate oxyradical products. Increasing evidence points away from dopamine metabolism as an important contributor to PD neurodegeneration. Predictions from the dopamine oxidative stress hypothesis of PD reveal multiple inconsistencies. Although the clinical and therapeutic importance of the nigrostriatal dopaminergic system is undeniable, PD neuropathology is much more widespread. © 2004 Movement Disorder Society [source] Prevalence of familial malignancy in a prospectively screened cohort of patients with lymphoproliferative disordersBRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2008Jennifer R. Brown Summary Increasing evidence points to a heritable contribution in the development of lymphoma. The goal of this study was to determine the rate of familial lymphoproliferative malignancy among consecutive lymphoma patients presenting to a tertiary care center and to enrol families with multiple affected first-degree relatives on a data and tissue collection study. Beginning in 2004 all new patients presenting to the Dana-Farber Cancer Institute with non-Hodgkin (NHL) or Hodgkin lymphoma (HL) or chronic lymphocytic leukaemia (CLL) were asked to complete a one-page self-administered family history questionnaire. 55·4% of 1948 evaluable patients reported a first-degree relative with a malignancy, with the highest rate among CLL probands. Lymphoid malignancies were particularly common, with 9·4% of all probands reporting a first-degree relative with a related lymphoproliferative disorder (LPD). This frequency was again highest for CLL, at 13·3% of CLL probands, compared to 8·8% of NHL probands and 5·9% of HL probands (P = 0·002). The prevalence of CLL was significantly increased in parents of CLL probands (P < 0·05), and a greater risk of NHL was seen in fathers of NHL probands than in mothers (P = 0·026). We conclude that familial aggregation of LPDs is common among newly diagnosed patients, varies significantly by diagnosis and contributes meaningfully to the population disease burden. [source] Keratinisation status and cytokeratins of the human Meibomian gland epitheliumACTA OPHTHALMOLOGICA, Issue 2009E KNOP Purpose The Meibomian gland (MG) is an indispensable component of the functional anatomy of the ocular surface. Increasing evidence points to a high impact of hyper-keratinisation as a major cause of obstructive MG dysfunction (MGD) and evaporative dry eye. Information of normal keratinisation status and cytokeratin composition of the human MG is limited. Methods Conjunctival whole-mount specimens including the lid margin from ten body donors of older age were embedded in paraffin. Serial sections were stained by H&E and Masson-Goldner stain and by immunohistochemistry with an antibody panel to cytokeratins. Results In conventional stains, the MG shows distinct similarities with the pilo-sebaceous unit of the cilia. The keratinised skin epithelium extended into the terminal part of the MG excretory duct similar to the hair follicle. Preliminary IHC results showed that the epithelium was positive there for the skin keratin CK10. Along the central duct the keratinisation CK10 expression was gradually lost similar to keratinisation marker involucrin. However, filaggrin, a marker for incipient stages of keratinisation and located in keratohyalin granules continued in the superficial layer of the duct epithelium all along the Meibomian central ductal system. CK14 a marker for basal undifferentiated cells showed a homogenous expression all along the basal cell layer of the MG ducts and the acini. Conclusion The MG shares similarities with the cilia in embryology, in structure and in the cytokeratin composition. It can hence be regarded as a "hair without a hair shaft". All parts of the MG ducts have signs of incipient keratinisation and preserve a commitment to keratinisation. Upregulation in MGD explain hyper-keratinisation as a typical event in obstructive MGD. [source] Individual differences, environmental scanning, innovation framing, and champion behavior: key predictors of project performanceTHE JOURNAL OF PRODUCT INNOVATION MANAGEMENT, Issue 1 2001Jane M. Howell Although increasing evidence points to the importance of champions for keeping product innovation ideas alive and thriving, little is known about how champions identify potential product innovation ideas, how they present these ideas to gain much needed support from key stakeholders, and their impact on innovation project performance over time. Jane M. Howell and Christine M. Shea address this knowledge gap by using measures of individual differences, environmental scanning, innovation framing and champion behavior to predict the performance of 47 product innovation projects. Champion behavior was defined as expressing confidence in the innovation, involving and motivating others to support the innovation, and persisting under adversity. Interviews with 47 champions were conducted to collect information about the innovation projects and the champions' tendency to frame the innovation as an opportunity or threat. Survey data were obtained from three sources: 47 champions provided information on their personal characteristics (locus of control and breadth of interest) and activities (environmental scanning), 47 division managers subjectively assessed project performance at two points in time, and 237 innovation team members rated the frequency of champion behavior. The results revealed that an internal locus of control orientation was positively related to framing the innovation as an opportunity, and breadth of interest was positively related to environmental scanning. Environmental scanning of documents and framing the innovation as a threat was negatively related to champion behavior, while environmental scanning through people was positively related to champion behavior. Champion behavior positively predicted project performance over a one-year interval. Overall, the findings suggest that in scanning the environment for new ideas, the most effective source of information is the champion's personal network of people inside and outside the organization. Also, the simple labeling of an idea as a threat appears to diminish a champion's perceived influence and erode credibility in promoting an innovation. From the perspective of division managers, champions make a positive contribution to project performance over time, reinforcing the crucial role that champions play in new product development process. [source] | ||||||||||