Rb induces a proliferative arrest and curtails Brn-2 expression in retinoblastoma cells

BACKGROUND: Retinoblastoma is caused by loss of the Rb protein in early retinal cells. Although numerous Rb functions have been identified, Rb effects that specifically relate to the suppression of retinoblastoma have not been defined. RESULTS: In this study, we examined the effects of restoring Rb to Y79 retinoblastoma cells, using novel retroviral and lentiviral vectors that co-express green fluorescent protein (GFP). The lentiviral vector permitted transduction with sufficient efficiency to perform biochemical analyses. Wild type Rb (Rb(WT)) and to a lesser extent the low penetrance mutant Rb(661W )induced a G0/G1 arrest associated with induction of p27(KIP1 )and repression of cyclin E1 and cyclin E2. Microarray analyses revealed that in addition to down-regulating E2F-responsive genes, Rb repressed expression of Brn-2 (POU3F2), which is implicated as an important transcriptional regulator in retinal progenitor cells and other neuroendocrine cell types. The repression of Brn-2 was a specific Rb effect, as ectopic p27 induced a G0/G1 block, but enhanced, rather than repressed, Brn-2 expression. CONCLUSION: In addition to Rb effects that occur in many cell types, Rb regulates a gene that selectively governs the behavior of late retinal progenitors and related cells

Early Detection of Ovarian Cancer with Conventional and Contrast-Enhanced Transvaginal Sonography: Recent Advances and Potential Improvements

Recently, there have been several major technical advances in the sonographic diagnosis of ovarian cancer in its early stages. These include improved assessment of tumor morphology with transvaginal sonography (TVS), and detection and characterization of tumor neovascularity with transvaginal color Doppler sonography (TV-CDS) and contrast-enhanced transvaginal sonography (CE-TVS). This paper will discuss and illustrate these improvements and describe how they enhance detection of early-stage ovarian cancer. Our initial experience with parametric mapping of CE-TVS will also be mentioned

Perinatal Cat and Dog Exposure and the Risk of Asthma and Allergy in the Urban Environment: A Systematic Review of Longitudinal Studies

Background. The literature is contradictory concerning pet exposure and the risk of development of asthma and other allergic diseases. Using longitudinal studies, we aimed to systematically review the impact of pet ownership in the critical perinatal period as a risk factor for allergies in childhood. Methods. Medline database was searched for urban cohort studies with perinatal exposure to cats and/or dogs and subsequent asthma or allergic disease. Results. Nine articles, comprising 6498 participants, met inclusion criteria. Six found a reduction in allergic disease associated with perinatal exposure to dogs or, cats or dogs. One study found no association. Two found increased risk only in high-risk groups. Conclusion. Longitudinal studies in urban populations suggest that perinatal pets, especially dogs, may reduce the development of allergic disease in those without a family history of allergy. Other unmeasured factors such as pet-keeping choices in allergic families may be confounding the association seen in these high-risk families, and further study is required

Pharmacokinetic analysis of topotecan after superselective ophthalmic artery infusion and periocular administration in a porcine mode

Purpose: To characterize the vitreous and plasma pharmacokinetics of topotecan after ophthalmic artery infusion (OAI) subsequent to superselective artery catheterization and to compare it with periocular injection (POI). Methods: The ophthalmic artery of 4 pigs was catheterized and 1 mg of topotecan infused over a period of 30 minutes. The contralateral eye was subsequently used for administering topotecan by POI. Serial vitreous specimens were obtained by microdialysis and plasma samples collected and assayed for total and lactone topotecan. Results: Maximum total topotecan concentration in the vitreous (median, range) was significantly higher after OAI compared with POI (131.8 ng/mL [112.9–138.7] vs. 13.6 ng/mL [5.5–15.3], respectively; P , 0.005). Median vitreous exposure calculated as area under the curve for total topotecan attained after OAI was significantly higher than after POI (299.8 nghour/mL [247.6–347.2] and 48.9 nghour/mL [11.8–63.4], respectively; P , 0.05). The vitreous to plasma exposure ratio was 29 after OAI and 3.4 after POI. Systemic exposure for total topotecan was low after both modalities of administration, with a trend to be lower after OAI compared with POI (10.6 nghour/mL [6.8–13.4] vs. 18.7 nghour/mL [6.3–21.7]; P = 0.54). Conclusion: Superselective OAI resulted in significantly higher vitreous concentrations and exposure and a trend toward lower systemic exposure than POI.Fil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Buitrago, Emiliano. Universidad de Buenos Aires; ArgentinaFil: Ceciliano, Alejandro. No especifíca;Fil: Fandino, Adriana C.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Asprea, Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Sierre, Sergio. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Abramson, David H.. No especifíca;Fil: Bramuglia, Guillermo Federico. Universidad de Buenos Aires; ArgentinaFil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentin

Pharmacokinetic analysis of topotecan after superselective ophthalmic artery infusion and periocular administration in a porcine mode

Purpose: To characterize the vitreous and plasma pharmacokinetics of topotecan after ophthalmic artery infusion (OAI) subsequent to superselective artery catheterization and to compare it with periocular injection (POI). Methods: The ophthalmic artery of 4 pigs was catheterized and 1 mg of topotecan infused over a period of 30 minutes. The contralateral eye was subsequently used for administering topotecan by POI. Serial vitreous specimens were obtained by microdialysis and plasma samples collected and assayed for total and lactone topotecan. Results: Maximum total topotecan concentration in the vitreous (median, range) was significantly higher after OAI compared with POI (131.8 ng/mL [112.9–138.7] vs. 13.6 ng/mL [5.5–15.3], respectively; P , 0.005). Median vitreous exposure calculated as area under the curve for total topotecan attained after OAI was significantly higher than after POI (299.8 nghour/mL [247.6–347.2] and 48.9 nghour/mL [11.8–63.4], respectively; P , 0.05). The vitreous to plasma exposure ratio was 29 after OAI and 3.4 after POI. Systemic exposure for total topotecan was low after both modalities of administration, with a trend to be lower after OAI compared with POI (10.6 nghour/mL [6.8–13.4] vs. 18.7 nghour/mL [6.3–21.7]; P = 0.54). Conclusion: Superselective OAI resulted in significantly higher vitreous concentrations and exposure and a trend toward lower systemic exposure than POI.Fil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Buitrago, Emiliano. Universidad de Buenos Aires; ArgentinaFil: Ceciliano, Alejandro. No especifíca;Fil: Fandino, Adriana C.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Asprea, Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Sierre, Sergio. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Abramson, David H.. No especifíca;Fil: Bramuglia, Guillermo Federico. Universidad de Buenos Aires; ArgentinaFil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentin

自己中心座標に基づく観光用ナビゲーション

電気通信大学201

Quantum Nonlocality without Entanglement

We exhibit an orthogonal set of product states of two three-state particles that nevertheless cannot be reliably distinguished by a pair of separated observers ignorant of which of the states has been presented to them, even if the observers are allowed any sequence of local operations and classical communication between the separate observers. It is proved that there is a finite gap between the mutual information obtainable by a joint measurement on these states and a measurement in which only local actions are permitted. This result implies the existence of separable superoperators that cannot be implemented locally. A set of states are found involving three two-state particles which also appear to be nonmeasurable locally. These and other multipartite states are classified according to the entropy and entanglement costs of preparing and measuring them by local operations.Comment: 27 pages, Latex, 6 ps figures. To be submitted to Phys. Rev. A. Version 2: 30 pages, many small revisions and extensions, author added. Version 3: Proof in Appendix D corrected, many small changes; final version for Phys. Rev. A Version 4: Report of Popescu conjecture modifie

Improving rigid fiberoptic intubation: a comparison of the Bonfils Intubating Fiberscope™ with a novel modification

<p>Abstract</p> <p>Background</p> <p>The Bonfils intubating fiberscope has a limited upward tip angle of 40° and requires retromolar entry into the hypopharynx. These factors may make its use less desirable when managing the difficult airway because most anesthesia providers are well versed in midline oral intubation rather than the lateral retromolar approach. The <it>Center for Advanced Technology and Telemedicine </it>at the University of Nebraska Medical Center has developed a novel fiberscope with a more anterior 60° curve to allow for easier midline insertion and intubation. The objective of this work was to evaluate the novel fiberscope, in comparison to the Bonfils intubating fiberscope, in terms of use and function in difficult airway intubation.</p> <p>Methods</p> <p>Twenty-two anesthesia providers participated in simulated intubations of a difficult airway mannequin to compare the Bonfils intubating fiberscope with the novel curved Boedeker intubating fiberscope. The intubations were assessed based upon the following variables: recorded Cormack Lehane airway scores, requests for cricoid pressure, time to intubation, number of intubation attempts and success or failure of the procedure.</p> <p>Results</p> <p>Participants using the Bonfils fiberscope recorded an average Cormack Lehane (CL) airway score of 1.67 ± 1.02 (median = 1); with the novel fiberscope, the recorded average airway grade improved to 1.18 ± 0.50 (median = 1). The difference in airway scores was not statistically significant (p = 0.34; Fishers Exact Test comparing CL grades 1&2 vs. 3&4). There was, however, a statistically significant difference in intubation success rates between the two devices. With the Bonfils fiberscope, 68% (15/22) of participants were successful in intubation compared to a 100% success rate in intubation with the novel fiberscope (22/22) (p = 0.008). After the intubation trial, the majority of participants (95%) indicated a preference for the novel fiberscope (n = 20).</p> <p>Conclusions</p> <p>With this data, we can infer that the novel fiberscope curvature appears to improve or maintain the quality of an intubation attempt (airway score, cricoid pressure requirement, intubation time, number of attempts, placement success). The data indicate that the novel fiberscope offers a superior intubation experience to currently available best practices. The instrument was well received and would be welcomed by most study participants should the device become clinically available in the future.</p

Paracetamol use in early life and asthma: prospective birth cohort study

Objective To determine if use of paracetamol in early life is an independent risk factor for childhood asthma