41 research outputs found

    HOXB13 is co-localized with androgen receptor to suppress androgen-stimulated prostate-specific antigen expression

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    During the prostate cancer (PCa) development and its progression into hormone independency, androgen receptor (AR) signals play a central role by triggering the regulation of target genes, including prostate-specific antigen. However, the regulation of these AR-mediated target genes is not fully understood. We have previously demonstrated a unique role of HOXB13 homeodomain protein as an AR repressor. Expression of HOXB13 was highly restricted to the prostate and its suppression dramatically increased hormone-activated AR transactivation, suggesting that prostate-specific HOXB13 was a highly potent transcriptional regulator. In this report, we demonstrated the action mechanism of HOXB13 as an AR repressor. HOXB13 suppressed androgen-stimulated AR activity by interacting with AR. HOXB13 did neither bind to AR responsive elements nor disturb nuclear translocation of AR in response to androgen. In PCa specimen, we also observed mutual expression pattern of HOXB13 and AR. These results suggest that HOXB13 not only serve as a DNA-bound transcription factor but play an important role as an AR-interacting repressor to modulate hormone-activated androgen receptor signals. Further extensive studies will uncover a novel mechanism for regulating AR-signaling pathway to lead to expose new role of HOXB13 as a non-DNA-binding transcriptional repressor

    Collagenous Gastritis in A Korean Child : A Case Report

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    Collagenous gastritis, a counterpart of collagenous colitis, is an extremely rare disorder. The first case of collagenous gastritis in a Korean boy in his pre-teens who had been receiving treatment for refractory iron deficiency anemia has been reported. The patient had been suffering from intermittent abdominal pain, recurrent blood-tinged vomiting and poor oral intake. The gastric endoscopy revealed diffuse cobble-stone appearance of the mucosa with easy touch bleeding throughout the stomach but no abnormalities in the esophagus, duodenum, and colon. Pathologic examination of the gastric biopsies from the antrum, body and cardia showed a subepithelial collagen deposition with entrapped dilated capillaries, moderate infiltrates of lymphoplasma cells and eosinophils of the lamina propria, and marked hypertrophy of the muscularis mucosa. The collagen deposition appeared as discontinuous bands with focally irregular extension into the deeper part of the antral mucosa. It measured up to 150 µm. Helicobacter pylori infection was not detected. The biopsies from the duodenum, esophagus and colon revealed no pathologic abnormalities

    Parametric POMDPs for planning in continuous state spaces

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    This thesis is concerned with planning and acting under uncertainty in partially-observable continuous domains. In particular, it focusses on the problem of mobile robot navigation given a known map. The dominant paradigm for robot localisation is to use Bayesian estimation to maintain a probability distribution over possible robot poses. In contrast, control algorithms often base their decisions on the assumption that a single state, such as the mode of this distribution, is correct. In scenarios involving significant uncertainty, this can lead to serious control errors. It is generally agreed that the reliability of navigation in uncertain environments would be greatly improved by the ability to consider the entire distribution when acting, rather than the single most likely state. The framework adopted in this thesis for modelling navigation problems mathematically is the Partially Observable Markov Decision Process (POMDP). An exact solution to a POMDP problem provides the optimal balance between reward-seeking behaviour and information-seeking behaviour, in the presence of sensor and actuation noise. Unfortunately, previous exact and approximate solution methods have had difficulty scaling to real applications. The contribution of this thesis is the formulation of an approach to planning in the space of continuous parameterised approximations to probability distributions. Theoretical and practical results are presented which show that, when compared with similar methods from the literature, this approach is capable of scaling to larger and more realistic problems. In order to apply the solution algorithm to real-world problems, a number of novel improvements are proposed. Specifically, Monte Carlo methods are employed to estimate distributions over future parameterised beliefs, improving planning accuracy without a loss of efficiency. Conditional independence assumptions are exploited to simplify the problem, reducing computational requirements. Scalability is further increased by focussing computation on likely beliefs, using metric indexing structures for efficient function approximation. Local online planning is incorporated to assist global offline planning, allowing the precision of the latter to be decreased without adversely affecting solution quality. Finally, the algorithm is implemented and demonstrated during real-time control of a mobile robot in a challenging navigation task. We argue that this task is substantially more challenging and realistic than previous problems to which POMDP solution methods have been applied. Results show that POMDP planning, which considers the evolution of the entire probability distribution over robot poses, produces significantly more robust behaviour when compared with a heuristic planner which considers only the most likely states and outcomes

    The Mediterranean diet: Effects on proteins that mediate fatty acid metabolism in the colon

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88101/1/j.1753-4887.2011.00439.x.pd

    Collagenous gastritis

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    A Comparative Clinicopathologic Study of Collagenous Gastritis in Children and Adults

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    Collagenous gastritis is a rare condition characterized by surface epithelial damage, subepithelial collagen deposition, and a lamina propria inflammatory infiltrate. Previous studies have proposed 2 clinicopathologic subtypes: (1) children (18 y of age or younger) presenting with severe anemia, nodular gastric mucosa, and isolated gastric disease; and (2) adults with chronic watery diarrhea that is associated with diffuse collagenous involvement of the gastrointestinal tract. However, notable exceptions exist. In fact, broad variability in clinical presentation, etiology, treatment and disease course has been reported. To better define the clinicopathologic features of collagenous gastritis, we have collected 10 pediatric and 21 adult cases and describe their clinical, endoscopic, pathologic, and follow-up findings. Both children and adults presented with similar clinical symptoms such as anemia (50%, 35%, respectively), epigastric/abdominal pain (50%, 45%), and diarrhea (40%, 55%). Concomitant immune disorders were identified in 2 (20%) children and 3 (14%) adults. Further, 7 of 17 (41%) adults were taking medications associated with other immune-related gastrointestinal diseases including olmesartan and antidepressants. Histologically, there were no differences between children and adults with collagenous gastritis in the location of gastric involvement, mean collagenous layer thickness, and prominence of eosinophils (P > 0.05). Extragastric collagenous involvement was also seen with comparable frequencies in each cohort (44%, 59%). Follow-up information was available for 22 of 31 (71%) patients and ranged from 2 to 122 months (mean, 33.6mo). Despite medical management in most cases, persistence of symptoms or collagenous gastritis on subsequent biopsies was seen in 100% of children and 82% of adults. Of note, treatment for 1 adult patient involved cessation of olmesartan resulting in resolution of both symptoms and subepithelial collagen deposition on subsequent biopsies. Contrary to prior reports, no clinicopathologic differences were identified among pediatric and adult patients with collagenous gastritis. Whereas collagenous gastritis remains an enigmatic condition, our findings suggest that immune abnormalities and medications, such as olmesartan, may be possible triggers. However, current treatment options have had limited success and, thus, highlight the need for improved therapeutic regimens
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