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Selected AbstractsMRI identification of the rostral-caudal pattern of pathology within the corpus callosum in the cuprizone mouse modelJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 3 2008Qi-Zhu Wu BS Abstract Purpose To characterize and compare histological and MRI-based changes within the corpus callosum (CC) in the cuprizone mouse model of multiple sclerosis (MS). Materials and Methods A total of 12 C57/BL6 mice were fed cuprizone from eight weeks of age for four weeks. One cohort of six cuprizone and two control mice were scanned with a T2-weighted (T2W) sequence. The other cohort of six cuprizone and four control mice were scanned using a dual-echo sequence for T2-mapping and a diffusion-weighted sequence with two orthogonal diffusion encoding directions to calculate water diffusivities parallel and perpendicular to the CC fiber (apparent diffusion coefficients [ADC], and ADC,). After the mice were killed, the rostral-caudal pattern of CC demyelination and other pathologies were examined using Luxol Fast Blue, neurofilament staining, and immunohistochemistry for microglia and were correlated with MRI. Results In contrast to control mice, T2W imaging (T2WI) hyperintensity, reduced ADC,, and elevated ADC, were detected in the CC of cuprizone-fed mice, particularly in the caudal segment. The T2 value was increased in the entire CC. Marked demyelination, as well as axonal injury, microglia accumulation, and cellular infiltration were found in the caudal section of the cuprizone mouse CC. The rostral-caudal pattern of abnormalities within the CC in MRI measurements correlated well with histopathological findings. Conclusion Noninvasive MRI using quantitative T2 and ADC mapping accurately characterized the rostral-caudal pattern of CC demyelination and other pathologies in cuprizone challenged mice, and thus could provide an effective way to assess the structural response to experimental therapeutics being designed for the treatment of MS. J. Magn. Reson. Imaging 2007. © 2007 Wiley-Liss, Inc. [source] More or Less Unequal?GENDER, WORK & ORGANISATION, Issue 1 2007Evidence on the Pay of Men, Women from the British Birth Cohort Studies Gender pay differences are not merely a problem for women returning to work and part-time employees, but also for those in full-time, continuous careers. In data from cohort studies, the gender wage gap for full-time workers in their early thirties fell between 1978 and 2000. This equalization reflects improvements in women's education and experience rather more than a move towards equal treatment. Indeed, had the typical woman full-timer in 2000 been paid at men's rates she would have actually received higher pay than the typical man. Within one cohort, passing from age 33 to 42, gender inequality increased. This was partly due to differences in the qualifications and experience of the women in employment at those points, but unequal treatment also rose among women employed full time at both ages. [source] Dimorphic growth patterns and sex-specific reaction norms in the butterfly Lycaena hippothoe sumadiensisJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 2 2001K. Fischer Directly developing larvae of the butterfly Lycaena hippothoe sumadiensis exhibited two growth strategies with one cohort passing four larval instars at high growth rates, and the other five instars at lower growth rates. The 4-instar-cohort displayed decreased development times, in combination with slightly reduced pupal and adult weights. In addition to adjustment of growth rate, omitting a larval instar may comprise a further mechanism to decrease development time when needed. Using the 4-instar-cohort, sex-related differences in reaction norms were investigated over a temperature gradient. At high temperatures, protandrous males showed early emergence at a reduced size, whereas weight of females remained similar throughout. These differences suggest that large size is more important for female than for male fitness. The pattern is similar to that previously reported for alpine L. tityrus, indicating that sex-specific reaction norms might be widespread in species living under severe time constraints. [source] Differential and Age-Dependent Effects of Maternal Deprivation on the Hypothalamic-Pituitary-Adrenal Axis of Brown Norway Rats from Youth to SenescenceJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2001J. O. Workel Abstract In this study, the hypothesis was tested that infants deprived from maternal care show persistent changes in hypothalamic-pituitary-adrenal activity. For this purpose, we studied the effect of maternal deprivation in one cohort of the healthy ageing Brown Norway rat strain showing still more than 80% survival rate at 32 months of age. Three-day-old male Brown Norway rats were either maternally deprived for 24 h or remained with the dam. In 3, 12 and 30,32 months (young, adult, senescent) deprived rats and their nondeprived littermates (controls), we determined basal resting and stress-induced plasma adrenocorticotropic hormone (ACTH) and corticosterone as well as corticotropin releasing hormone (CRH) mRNA expression in the paraventricular nucleus (PVN) of the hypothalamus. Mineralocorticoid (MR) and glucocorticoid receptors (GR) in hippocampus and PVN were also assessed using in vitro cytosol binding and in situ hybridization. The effect of ageing per se showed that in the control nondeprived Brown Norway rats, basal corticosterone and ACTH concentrations did not change during life. However, with age, the corticosterone response to novelty stress became progressively attenuated, but prolonged, while there was an age-related increase in the ACTH response. CRH mRNA expression in PVN decreased with age. Hippocampal MR binding and MR mRNA expression in the dentate gyrus were reduced at senescence, as were the GR binding capacities in hippocampus and hypothalamus. Maternal deprivation did not affect survival rate, body weight, nor adrenal weight of the ageing Brown Norway rats. Basal corticosterone and ACTH levels were not affected by deprivation, except for a rise in basal corticosterone concentrations at 3 months. At this age, the corticosterone output in response to novelty was attenuated in the deprived rats. In contrast, a striking surge in novelty stress-induced corticosterone output occurred at midlife while, at senescence, the corticosterone and ACTH responses were attenuated again in the deprived animals, particularly after the more severe restraint stressor. CRH mRNA expression was reduced only during adulthood in the deprived animals. After maternal deprivation, the MR mRNA in dentate gyrus showed a transient midlife rise. GR binding in hypothalamus and hippocampus GR binding was reduced in young rats while, in the senescent deprived animals, a reduced GRmRNA expression was observed in PVN and hippocampal CA1. In conclusion, in the Brown Norway rat, ageing causes a progressive decline in corticosterone output after stress, which is paralleled at senescence by decreased MR and GR mRNA expression in hippocampus and hypothalamus. The long-term effects of maternal deprivation become manifest differently at different ages and depend on test conditions. The deprivation effect culminates in a midlife corticosterone surge and results at senescence in a strongly reduced corticosterone output. [source] Medical students' personality characteristics and academic performance: a five-factor model perspectiveMEDICAL EDUCATION, Issue 11 2002Filip Lievens Objectives, This study investigates: (1) which personality traits are typical of medical students as compared to other students, and (2) which personality traits predict medical student performance in pre-clinical years. Design, This paper reports a cross-sectional inventory study of students in nine academic majors and a prospective longitudinal study of one cohort of medical students assessed by inventory during their first preclinical year and by university examination at the end of each pre-clinical year. Subjects and methods In 1997, a combined total of 785 students entered medical studies courses in five Flemish universities. Of these, 631 (80·4%) completed the NEO-PI-R (i.e. a measure of the Five-Factor Model of Personality). This was also completed by 914 Year 1 students of seven other academic majors at Ghent University. Year end scores for medical students were obtained for 607 students in Year 1, for 413 in Year 2, and for 341 in Year 3. Results, Medical studies falls into the group of majors where students score highest on extraversion and agreeableness. Conscientiousness (i.e. self-achievement and self-discipline) significantly predicts final scores in each pre-clinical year. Medical students who score low on conscientiousness and high on gregariousness and excitement-seeking are significantly less likely to sit examinations successfully. Conclusions, The higher scores for extraversion and agreeableness, two dimensions defining the interpersonal dynamic, may be beneficial for doctors' collaboration and communication skills in future professional practice. Because conscientiousness affects examination results and can be reliably assessed at the start of a medical study career, personality assessment may be a useful tool in student counselling and guidance. [source] Essential tremor , Neurodegenerative or nondegenerative disease towards a working definition of ET,MOVEMENT DISORDERS, Issue 14 2009Günther Deuschl MD Abstract Essential tremor (ET) is a syndrome of tremor in posture and movement, but recent studies have revealed additional cerebellar motor disturbances, cognitive disturbances, personality changes, hearing loss, and olfactory deficits. Even dementia and shortened life expectancy were found in one cohort. Recent postmortem studies have found limited Lewy body pathology in some patients and Purkinje cell loss with torpedoes and Bergmann gliosis in others. These findings have led to the hypothesis that ET is a syndrome produced by at least two neurodegenerative diseases with more widespread clinical consequences than previously appreciated. We review the evidence for and against this hypothesis and conclude that studies purporting to support this hypothesis have failed to control for age-associated comorbidities, depression, medications, and other confounding factors. We propose the alternative hypothesis that abnormal neuronal oscillation is the fundamental abnormality in ET, and the well-documented cerebellar signs and symptoms, the controversial non-motor signs, and even the cerebellar pathology of ET could be caused by this oscillation. A major problem for many studies is the lack of a diagnostic gold standard. Lacking such a standard, we propose a subclassification of ET into three categories: hereditary ET, sporadic ET, and senile ET, which we believe will help researchers resolve many of the controversies in this field. © 2009 Movement Disorder Society [source] Phase I clinical trial using peptide vaccine for human vascular endothelial growth factor receptor 2 in combination with gemcitabine for patients with advanced pancreatic cancerCANCER SCIENCE, Issue 2 2010Motoki Miyazawa Vascular endothelial growth factor receptor 2 (VEGFR2) is an essential factor in tumor angiogenesis and in the growth of pancreatic cancer. Immunotherapy using epitope peptide for VEGFR2 (VEGFR2-169) that we identified previously is expected to improve the clinical outcome. Therefore, a phase I clinical trial combining of VEGFR2-169 with gemcitabine was conducted for patients with advanced pancreatic cancer. Patients with metastatic and unresectable pancreatic cancer were eligible for the trial. Gemcitabine was administered at a dose of 1000 mg/m2 on days 1, 8, and 15 in a 28-day cycle. The VEGFR2-169 peptide was subcutaneously injected weekly in a dose-escalation manner (doses of 0.5, 1, and 2 mg/body, six patients/one cohort). Safety and immunological parameters were assessed. No severe adverse effect of grade 4 or higher was observed. Of the 18 patients who completed at least one course of the treatment, 15 (83%) developed immunological reactions at the injection sites. Specific cytotoxic T lymphocytes (CTL) reacting to the VEGFR2-169 peptide were induced in 11 (61%) of the 18 patients. The disease control rate was 67%, and the median overall survival time was 8.7 months. This combination therapy for pancreatic cancer patients was tolerable at all doses. Peptide-specific CTL could be induced by the VEGFR2-169 peptide vaccine at a high rate, even in combination with gemcitabine. From an immunological point of view, the optimal dose for further clinical trials might be 2 mg/body or higher. This trial was registered with ClinicalTrial.gov (no. NCT 00622622). (Cancer Sci 2009) [source] | ||||||||||