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21.
Giselle L. Saulnier Sholler Eugene W. Gerner Genevieve Bergendahl Robert B. MacArthur Alyssa VanderWerff Takamaru Ashikaga Jeffrey P. Bond William Ferguson William Roberts Randal K. Wada Don Eslin Jacqueline M. Kraveka Joel Kaplan Deanna Mitchell Nehal S. Parikh Kathleen Neville Leonard Sender Timothy Higgins Masao Kawakita Kyoko Hiramatsu Shun-suke Moriya André S. Bachmann 《PloS one》2015,10(5)
BackgroundNeuroblastoma (NB) is the most common cancer in infancy and most frequent cause of death from extracranial solid tumors in children. Ornithine decarboxylase (ODC) expression is an independent indicator of poor prognosis in NB patients. This study investigated safety, response, pharmacokinetics, genetic and metabolic factors associated with ODC in a clinical trial of the ODC inhibitor difluoromethylornithine (DFMO) ± etoposide for patients with relapsed or refractory NB.ConclusionsDFMO doses of 500-1500mg/m2/day are safe and well tolerated in children with relapsed NB. Children with the minor T allele at rs2302616 of the ODC gene with relapsed or refractory NB had higher levels of urinary polyamine markers and responded better to therapy containing DFMO, compared to those with the major G allele at this locus. These findings suggest that this patient subset may display dependence on polyamines and be uniquely susceptible to therapies targeting this pathway.
Trial Registration
Clinicaltrials.gov NCT#01059071 相似文献22.
Smita Jaiswal Kenneth Smith Alejandro Ramirez Marcia Woda Pamela Pazoles Leonard D Shultz Dale L Greiner Michael A Brehm Anuja Mathew 《Experimental biology and medicine (Maywood, N.J.)》2015,240(1):67-78
The development of small animal models that elicit human immune responses to dengue virus (DENV) is important since prior immunity is a major risk factor for developing severe dengue disease. This study evaluated anti-DENV human antibody (hAb) responses generated from immortalized B cells after DENV-2 infection in NOD-scid IL2rγnull mice that were co-transplanted with human fetal thymus and liver tissues (BLT-NSG mice). DENV-specific human antibodies predominantly of the IgM isotype were isolated during acute infection and in convalescence. We found that while a few hAbs recognized the envelope protein produced as a soluble recombinant, a number of hAbs only recognized epitopes on intact virions. The majority of the hAbs isolated during acute infection and in immune mice were serotype-cross-reactive and poorly neutralizing. Viral titers in immune BLT-NSG mice were significantly decreased after challenge with a clinical strain of dengue. DENV-specific hAbs generated in BLT-NSG mice share some of the characteristics of Abs isolated in humans with natural infection. Humanized BLT-NSG mice provide an attractive preclinical platform to assess the immunogenicity of candidate dengue vaccines. 相似文献
23.
The contribution of poor finger force control to age-related decline in manual dexterity is above and beyond ubiquitous behavioral slowing. Altered control of the finger forces can impart unwanted torque on the object affecting its orientation, thus impairing manual performance. Anodal transcranial direct current stimulation (tDCS) over primary motor cortex (M1) has been shown to improve the performance speed on manual tasks in older adults. However, the effects of anodal tDCS over M1 on the finger force control during object manipulation in older adults remain to be fully explored. Here we determined the effects of anodal tDCS over M1 on the control of grip force in older adults while they manipulated an object with an uncertain mechanical property. Eight healthy older adults were instructed to grip and lift an object whose contact surfaces were unexpectedly made more or less slippery across trials using acetate and sandpaper surfaces, respectively. Subjects performed this task before and after receiving anodal or sham tDCS over M1 on two separate sessions using a cross-over design. We found that older adults used significantly lower grip force following anodal tDCS compared to sham tDCS. Friction measured at the finger-object interface remained invariant after anodal and sham tDCS. These findings suggest that anodal tDCS over M1 improved the control of grip force during object manipulation in healthy older adults. Although the cortical networks for representing objects and manipulative actions are complex, the reduction in grip force following anodal tDCS over M1 might be due to a cortical excitation yielding improved processing of object-specific sensory information and its integration with the motor commands for production of manipulative forces. Our findings indicate that tDCS has a potential to improve the control of finger force during dexterous manipulation in older adults. 相似文献
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Jing T Wu L Borgmann K Surendran S Ghorpade A Liu J Xiong H 《Biochemical and biophysical research communications》2010,402(2):241-246
Astrocytes play an important role in astrocyte-neuron homeostasis. In HIV-1-infected brain, interleukin 1 beta (IL-1β) activation of astrocytes contributes to neurodegeneration. However, the molecular mechanisms underlying IL-1β-activated-astrocytes-induced neurodegeneration in HIV-1-infected brain are largely unknown. We hypothesize that secretory factors from the activated astrocytes affect N-methyl-d-aspartate (NMDA) receptor, a major pathway implicated in HIV-1-associated neurodegeneration. To test this hypothesis, we studied effects of IL-1β-stimulated astrocyte conditioned medium (ACM+) for its ability to activate NR1a/NR2B receptors expressed on Xenopus oocytes. Astrocytes treated with IL-1β 20 ng/ml for 24 h induced CXCL8, CCL2, MMP1 and MMP7. Pressure ejection of the ACM(+) produced an inward current in NR1a/NR2B-expressing oocytes. The inward current produced by ACM(+) was blocked by NMDA receptor antagonist, APV but not by non-NMDA receptor antagonist, CNQX. These results suggest that IL-1β stimulated astrocytes activate NR1a/NR2B receptors which may have implications in HIV-1-associated neurodegeneration. 相似文献
26.
Shwiff SA Sterner RT Jay MT Parikh S Bellomy A Meltzer MI Rupprecht CE Slate D 《Journal of wildlife diseases》2007,43(2):251-257
The direct and indirect costs of suspected human rabies exposure were estimated for San Luis Obispo and Santa Barbara counties, California, USA. Clinic, hospital, and county public health records (1998-2002) were examined to determine direct costs for postexposure prophylaxis (PEP), and 55 (41%) former patients were contacted to voluntarily provide estimates of their indirect costs associated with receiving PEP. Additional costs due to public health and animal control personnel responses to rabid animals were collected, including diagnostic testing and wages. The mean total cost of a suspected human rabies exposure was $3,688, the direct costs per case were $2,564, and the indirect costs were $1,124 of that total. About one third of the total cost for suspected human rabies exposure was attributed to indirect costs (e.g., lost wages, transportation, and day-care fees), most of which were not reimbursable to the patient. 相似文献
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28.
Anand C Umranikar C Shintre P Damle A Kale J Joshi J Watve M 《Journal of biosciences》2007,32(4):769-774
Many species of animal-pollinated flowers are known to vary widely in the nectar content of flowers. Some proportion of flowers
in many species is apparently nectarless, and such flowers are believed to be ‘cheaters’. Cheating may explain a part of the
variability in nectar content. If cheating exists as a qualitatively different strategy then we expect bimodality in the distribution
of nectar content of flowers. It has been shown in a multispecies study that gregarious species have a higher proportion of
cheater flowers. We studied the frequency distribution of total nectar sugar in two gregariously flowering species Lantana camara and Utricularia purpurascens, which differed in other floral and ecological characters. At the population level, both the species showed significant bimodality
in the total sugar content of flowers. The obvious sources of heterogeneity in the data did not explain bimodality. In Lantana camara, bimodality was observed within flowers of some of the individual plants sampled. In Utricularia purpurascens the proportion of nectarless flowers was more in high-density patches, suggesting that the gregariousness hypothesis may
work within a species as well. The results support the hypothesis of cheating as a distinct strategy since two distinct types
of flowers were observed in both the species. The effect of density in Utricularia purpurascens also supports the gregariousness hypothesis. 相似文献
29.
Economic principles motivating social attention in humans 总被引:1,自引:0,他引:1
Hayden BY Parikh PC Deaner RO Platt ML 《Proceedings. Biological sciences / The Royal Society》2007,274(1619):1751-1756
We know little about the processes by which we evaluate the opportunity to look at another person. We propose that behavioural economics provides a powerful approach to understanding this basic aspect of social attention. We hypothesized that the decision process culminating in attention to another person follows the same economic principles that govern choices about rewards such as food, drinks and money. Specifically, such rewards are discounted as a function of time, are tradable for other rewards, and reinforce work. Behavioural and neurobiological evidence suggests that looking at other people can also be described as rewarding, but to what extent these economic principles apply to social orienting remains unknown. Here, we show that the opportunity to view pictures of the opposite sex is discounted by delay to viewing, substitutes for money and reinforces work. The reward value of photos of the opposite sex varied with physical attractiveness and was greater in men, suggesting differential utility of acquiring visual information about the opposite sex in men and women. Together, these results demonstrate that choosing whom to look at follows a general set of economic principles, implicating shared neural mechanisms in both social and non-social decision making. 相似文献
30.
Manju George GuoGuang Ying Mark A Rainey Aharon Solomon Pankit T Parikh Qingshen Gao Vimla Band Hamid Band 《BMC cell biology》2007,8(1):3