Repression of stress-responsive genes by FIERY2, a novel transcriptional regulator in Arabidopsis   总被引：15，自引：0，他引：15       下载免费PDF全文

Xiong L  Lee H  Ishitani M  Tanaka Y  Stevenson B  Koiwa H  Bressan RA  Hasegawa PM  Zhu JK 《Proceedings of the National Academy of Sciences of the United States of America》2002,99(16):10899-10904

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R S Midgley  D J Kerr  K T Flaherty  J P Stevenson  S E Pratap  K M Koch  D A Smith  M Versola  R A Fleming  C Ward  P J O'Dwyer  M R Middleton 《Annals of oncology》2007,18(12):2025-2029

BACKGROUND: This study determined the optimally tolerated regimen (OTR) of oral lapatinib administered in combination with infusional 5-fluorouracil (5-FU), leucovorin and irinotecan (FOLFIRI) and assessed the safety, tolerability and pharmacokinetics of the combination. PATIENTS AND METHODS: Twenty-five patients were enrolled; 12 patients were treated at three dose levels to determine OTR; then 13 patients were treated at OTR to evaluate the pharmacokinetics of the combination. RESULTS: The 2-weekly OTR comprised lapatinib 1250 mg/day with irinotecan 108 mg/m(2) (day 1) and leucovorin 200 mg/m(2), 5-FU bolus 240 mg/m(2) and 5-FU infusion 360 mg/m(2) (days 1 and 2); doses of 5-FU and irinotecan represent a 40% reduction in dose compared to conventional FOLFIRI. Dose-limiting toxicities were grade 3 diarrhoea and grade 4 neutropenia. Co-administration of lapatinib increased the area under the plasma concentration-time curve of SN-38, the active metabolite of irinotecan, by an average of 41%; no other pharmacokinetic interactions were observed. Of 19 patients evaluable for disease response assessment, four patients had partial response and nine patients had stable disease. CONCLUSION: The combination of lapatinib and FOLFIRI is safe and demonstrates clinical activity; the documented PK interaction can effectively be compensated by lowering the doses of 5-FU and irinotecan. This regime may be further tested in a phase II trial.  相似文献   

    

Juan Campos‐Perez  Jason Rice  David Escors  Mary Collins  Alex Paterson  Freda K. Stevenson 《International journal of cancer. Journal international du cancer》2013,133(6):1400-1407

The cancer/testis antigen NY‐ESO‐1 contains an immunodominant HLA‐A2‐binding peptide (SLLMWITQC), designated S9C, an attractive target for vaccination against several human cancers. As cysteine contains a reactive ? SH, the oxidation status of exogenous synthetic peptide is uncertain. We have designed tolerance‐breaking DNA fusion vaccines incorporating a domain of tetanus toxin fused to tumor‐derived peptide sequences (p.DOM‐peptide), placed at the C‐terminus for optimal immunogenicity. In a “humanized” HLA‐A2 preclinical model, p.DOM‐S9C primed S9C‐specific CD8+ T cells more effectively than adjuvanted synthetic peptide. A DNA vaccine encoding the full NY‐ESO‐1 sequence alone induced only weak S9C‐specific responses, amplified by addition of DOM sequence. The analog peptide (SLLMWITQL ) also primed peptide‐specific CD8+ T cells, again increased by DNA delivery. Importantly, T cells induced by S9C‐encoding DNA vaccines killed tumor cells expressing endogenous NY‐ESO‐1. Only a fraction of T cells induced by the S9L‐encoding DNA vaccines was able to recognize S9C and kill tumor cells. These data indicate that DNA vaccines mimic posttranslational modifications of ? SH‐containing peptides expressed by tumor cells. Instability of synthetic peptides and the potential dangers of analog peptides contrast with the ability of DNA vaccines to induce high levels of tumor‐lytic peptide‐specific CD8+ T cells. These findings encourage clinical exploration of this vaccine strategy to target NY‐ESO‐1.  相似文献   

    

Jan Kujala  Claire Stevenson  Riitta Salmelin 《Human brain mapping》2015,36(7):2455-2469

Electrophysiological oscillatory coherence between brain regions has been proposed to facilitate functional long‐range connectivity within neurocognitive networks. This notion is supported by intracortical recordings of coherence in singled‐out corticocortical connections in the primate cortex. However, the manner in which this operational principle manifests in the task‐sensitive connectivity that supports human naturalistic performance remains undercharacterized. Here, we demonstrate task‐sensitive reconfiguration of global patterns of coherent connectivity in association with a set of easier and more demanding naturalistic tasks, ranging from picture comparison to speech comprehension and object manipulation. Based on whole‐cortex neuromagnetic recording in healthy behaving individuals, the task‐sensitive component of long‐range corticocortical coherence was mapped at spectrally narrow‐band oscillatory frequencies between 6 and 20 Hz (theta to alpha and low‐beta bands). This data‐driven cortical mapping unveiled markedly distinct and topologically task‐relevant spatiospectral connectivity patterns for the different tasks. The results demonstrate semistable oscillatory states relevant for neurocognitive processing. The present findings decisively link human behavior to corticocortical coherence at oscillatory frequencies that are widely thought to convey long‐range, feedback‐type neural interaction in cortical functional networks. Hum Brain Mapp 36:2455–2469, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. .  相似文献   

    

Talwalkar SC  Kambhampati SB  Whitehouse R  Lang Stevenson AI  Freemont A 《Skeletal radiology》2005,34(6):351-354

Chondromas are tumours that develop in relation to the periosteum and, although they are common around the knee, most reports deal with soft tissue chondromas in para-articular locations or intracortical tumours in extra-articular regions. We report a rare case of an intra-articular chondroma in a 16-year-old boy of Asian origin developing in the region of the medial femoral condyle of the femur and extending into the femoral sulcus and the patellofemoral joint.  相似文献   

    

Kathryn M. McMillan PhD  Moneeb Ehtesham MD  Charles B. Stevenson MD  Michael L. Edgeworth MD  Reid C. Thompson MD  Ronald R. Price PhD 《Journal of magnetic resonance imaging : JMRI》2009,29(2):251-257

Purpose

To use T2‐weighted images to detect tumor invasion when comparing normal individuals to groups of gliomablastoma multiforme (GBM) patients with varying levels of CXCR4, a chemokine receptor that promotes tumor migration.

Materials and Methods

T2‐weighted images were acquired preoperatively in 22 treatment‐naïve GBM patients. Two groups were formed based on the expression levels of CXCR4. A third group of normal volunteers was used for comparison. Each image was segmented to obtain four different clusters for tissue types identified as white matter, basal ganglia, gray matter/edema and cerebrospinal fluid (CSF)/tumor. Signal intensity histograms were formed for each cluster and compared between groups.

Results

In every cluster the GBM groups displayed significantly higher standard deviations of intensity distributions when compared to normal subjects. Significant differences in skewness were found between normal subjects and GBM patients in the white matter, basal ganglia, and CSF/tumor. Further, when the two groups of GBM patients were compared the CXCR4‐high group was found to have a significant shift in the median intensity values in the cluster containing gray matter and peritumoral edema.

Conclusion

T2 signal intensity histograms in normal subjects differ significantly from those obtained from GBM groups, suggesting widespread dissemination of disease. J. Magn. Reson. Imaging 2009;29:251–257. © 2009 Wiley‐Liss, Inc.  相似文献   

    

Ehud J. Schmidt  Zion T. H. Tse  Tobias R. Reichlin  Gregory F. Michaud  Ronald D. Watkins  Kim Butts‐Pauly  Raymond Y. Kwong  William Stevenson  Jeffrey Schweitzer  Israel Byrd  Charles L. Dumoulin 《Magnetic resonance in medicine》2014,71(3):1197-1209

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Saunders KJ  McClelland JF  Richardson PM  Stevenson M 《Developmental medicine and child neurology》2008,50(1):33-37

Accommodation is often reduced in cerebral palsy (CP). Knowledge about accommodative facility is valuable when investigating a child's visual needs and developing strategies for education. With normal accommodation, changing focus from distance to near results in pupil constriction. We compared quality of near pupil responses (NPR) with objective measures of accommodative function obtained with dynamic retinoscopy (DR) to investigate the utility of NPR in indicating accommodative facility. NPR and accommodative function of 90 children with CP (56 males, 34 females; median age 11y, range 4-18y) were assessed. A total of 93% of participants had spastic CP (71.3% bilateral involvement, 28.7% hemiplegia). The severity of motor impairment ranged from very mild (n=7) to severe (no independent walking, n=28). NPR was classified subjectively as normal, reduced, or absent and compared with DR measures of accommodative response. A total of 9.8% of pupil responses were judged absent, 25.6% reduced, and 64.6% normal. Participants with reduced or absent pupil responses demonstrated significantly poorer levels of accommodation with DR (one-way analysis of variance p<0.01). Sensitivity and specificity of NPR in identifying participants with reduced accommodation were 83% (95% confidence interval [CI] 65.5-92.4%) and 72% (95% CI 58.4-82.0%) respectively. NPR provides a rapid, useful indicator of accommodative function in children with CP.  相似文献   

    

Matlock A. Jeffries  Madison Donica  Lyle W. Baker  Michael E. Stevenson  Anand C. Annan  Mary Beth Humphrey  Judith A. James  Amr H. Sawalha 《Arthritis u0026amp; Rheumatology》2014,66(10):2804-2815

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Ryan S  Stevenson K  Hassell AB 《Musculoskeletal care》2007,5(3):119-129

Objective: To introduce a new method of assessment; an observed structured clinical examination (OSCE) into a postgraduate course for rheumatology clinical nurse specialists. Method: The OSCE was introduced into a physical assessment module, which focused on the nurses' ability to perform an examination of patients' shoulders, knees and hands. A modified blueprinting exercise was used to ensure adequate sampling of the different components of the syllabus. This resulted in five active stations and one rest station. The active stations included history-taking, physical examination of the shoulder, knee and hand complexes and multidisciplinary management plans. To enhance authenticity real, rather than simulated, patients were used where practical. Results: All 11 students passed all stations, the lowest score related to history-taking and the highest score related to devising a management plan. All 11 students rated the OSCE a worthwhile experience reflecting the learning outcomes of the module and recommended that the OSCE should be used to assess the next cohort of students. Eight students found the OSCE too ‘anxiety-provoking’ and did not want this method of assessment to be used in other modules. All examiners felt this mode of assessment was more valid than the previous assessment format of a viva on a single patient. Conclusion: This was the first time an OSCE was used in a postgraduate course to assess the physical examination skills of rheumatology nurse specialists. The course faculty, examiners and students found it was a reliable and valid means of assessment. Copyright © 2007 John Wiley & Sons, Ltd.  相似文献