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11.
An acquired G-CSF receptor mutation results in increased proliferation of CMML cells from a patient with severe congenital neutropenia. 总被引:1,自引:0,他引:1
M Germeshausen H Schulze C Kratz L Wilkens R Repp K Shannon K Welte M Ballmaier 《Leukemia》2005,19(4):611-617
Severe congenital neutropenia (CN) is characterized by a maturation arrest of myelopoiesis at the promyelocyte stage. Treatment with pharmacological doses of recombinant human granulocyte colony-stimulating factor (rh-G-CSF) stimulates neutrophil production and decreases the risk of major infectious complications. However, approximately 15% of CN patients develop myeloid malignancies that have been associated with somatic mutations in the G-CSF receptor (G-CSFR) and RAS genes as well as with acquired monosomy 7. We report a CN patient with chronic myelomonocytic leukemia (CMML) who never received rh-G-CSF. Molecular analysis demonstrated a somatic G-CSFR mutation (C2390T), which led to expression of a truncated G-CSFR protein in the CMML. Normal G-CSFR expression was unexpectedly absent in primary and cultured CMML. In addition, CMML cells showed monosomy 7 and an oncogenic NRAS mutation. In vitro culture revealed a G-CSF-dependent proliferation of CMML cells, which subsequently differentiated along the monocytic/macrophage lineage. Our results provide direct evidence for the in vivo expression of a truncated G-CSFR in leukemic cells, which emerged in the absence of rh-G-CSF treatment and transduces proliferative signals. 相似文献
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13.
Lurie G Wilkens LR Thompson PJ McDuffie KE Carney ME Terada KY Goodman MT 《Cancer causes & control : CCC》2009,20(1):47-55
Ovarian cancer is influenced by exogenous and endogenous estrogens as suggested by experimental and epidemiological evidence.
Estrogen receptor beta is a predominant estrogen receptor in the normal ovary. Polymorphisms in the estrogen receptor beta
gene (ESR2) might influence epithelial ovarian risk through regulation of cell proliferation and apoptosis. This population-based case–control
study included 313 women with epithelial ovarian carcinoma and 574 controls, frequency-matched on age and ethnicity. Unconditional
logistic regression was used to test associations of rs1271572, rs1256030, rs1256031, and rs3020450 ESR2 genotypes with ovarian cancer risk. Compared to homozygous common allele carriers, homozygous carriers of variant alleles
for rs1271572 [odds ratio (OR) = 1.79, 95% confidence interval (CI):1.15–2.79, p global = 0.01] and rs1256030 [OR = 1.67, CI: 1.08–2.59, p global = 0.04], and women with haplotypes, including variant alleles of rs1271572, rs1256030, and rs1256031 SNPs [OR = 1.75,
CI: 1.17–2.63, p global = 0.007], had significantly increased risk of ovarian carcinoma. The association of the rs1271572 genotype was strongest
among women who had never used contraceptive steroids (p for interaction = 0.04). Our data suggest that ESR2 might be a susceptibility marker for epithelial ovarian cancer. 相似文献
14.
Rica Dela Cruz Eric Wolfe Kim M. Yonemori Marie K. Fialkowski Lynne R. Wilkens Patricia Coleman Sunema Lameko-Mua Emihner Johnson Daisy Gilmatam Cecilia Sigrah Moria Shomour Shelley Remengesau Julia Alfred Mark Acosta Reynolette Ettienne Jonathan Deenik Aflague Tanisha Kristina Abello Salazar Rachel Novotny Carol J. Boushey 《Hawai'i Journal of Medicine & Public Health》2022,81(9):247
Indigenous peoples of the Pacific have seen major shifts in dietary patterns due to foreign colonization, which introduced an array of new foods. Today, foods considered traditional and acculturated are consumed in various extents. However, the definitions and identity of traditional versus acculturated foods has become unclear as many introduced foods have been incorporated into Pacific cultures. The purpose of this study was to capture culturally relevant definitions of traditional, acculturated, and locally grown foods among 10 jurisdictions of the US-Affiliated Pacific (USAP) region with a focus on fruits and vegetables. Questionnaires were used to capture definitions of these terms, and to identify a list of foods (n=121) as traditional, acculturated, and/or locally grown in addition to classify them into food groups (ie, fruit, vegetable, starch, and/or grain). For the most part, definitions of traditional, acculturated, and locally grown were agreed upon by participating USAP jurisdictions, with some supplementary caveats presented by different jurisdictions. More foods were identified as acculturated (n=75) than traditional (n=37). Fruits (n=55) were the most frequent designation and about a third were vegetables (n=44). The majority of the jurisdictions reported growing at least half of the food items. This is the first study to identify and classify foods of the Pacific from the perspective of those indigenous to the USAP region. Understanding these similarities and differences in how food is classified and identified, through the lens of those from the Pacific, is crucial for nutrition education, and understanding what foods are locally grown is important for future sustainability. 相似文献
15.
Cheryl L. Albright Alana D. Steffen Rachel Novotny Claudio R. Nigg Lynne R. Wilkens Kara Saiki 《Women & health》2013,53(3):265-291
During the postpartum period, ethnic minority women have higher rates of inactivity/under-activity than white women. The Nā Mikimiki (“the active ones”) Project is designed to increase moderate-to-vigorous physical activity over 18 months among multiethnic women with infants 2–12 months old. The study was designed to test, via a randomized controlled trial, the effectiveness of a tailored telephone counseling of moderate-to-vigorous physical activity intervention compared to a print/website materials-only condition. Healthy, underactive women (mean age = 32 ± 5.6 years) with a baby (mean age = 5.7 ± 2.8 months) were enrolled from 2008–2009 (N = 278). Of the total sample, 84% were ethnic minority women, predominantly Asian–American and Native Hawaiian. Mean self-reported baseline level of moderate-to-vigorous physical activity was 40 minutes/week with no significant differences by study condition, ethnicity, infant's age, maternal body mass index, or maternal employment. Women had high scores on perceived benefits, self-efficacy, and environmental support for exercise but low scores on social support for exercise. This multiethnic sample's demographic and psychosocial characteristics and their perceived barriers to exercise were comparable to previous physical activity studies conducted largely with white postpartum women. The Nā Mikimiki Project's innovative tailored technology-based intervention and unique population are significant contributions to the literature on moderate-to-vigorous physical activity in postpartum women. 相似文献
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17.
Rune Wilkens Alexandra Wilson Peter N. Burns Subrata Ghosh Stephanie R. Wilson 《Ultrasound in medicine & biology》2018,44(11):2189-2198
A small population of patients with severe Crohn's disease (CD) exhibit atypical lack of intensity decline on intestinal contrast-enhanced ultrasound. From a retrospective CD cohort examined with contrast-enhanced ultrasound, 104 patients were identified. Twenty study patients with severe active disease exhibited high peak enhancement (>23 dB) and minimal decline. From the same cohort, 84 control patients also exhibited high peak enhancement >23dB, but with typical intensity decline. Patient outcomes were assessed. Time–intensity curve analysis revealed a significantly higher (p < 0.0001) area under the curve (44.7 ± 1.5 dB·s), washout time and intensities at 60s and 120s in the study population compared with controls (40.0 ± 1.1 dB·s). Study patients had a worse overall outcome with surgery in 30% versus 10% (p?=?0.027) during follow-up. Heightened enhancement with lack of decline on contrast-enhanced ultrasound suggests microbubbles are stuck within the inflamed bowel wall for an extended period. This observation occurs in patients with severe disease and a bad outcome. 相似文献
18.
In the accompanying article (Part I), a method is described to determine acoustic cavitation probabilities in tissue-mimicking materials (TMMs) using a high-intensity focused ultrasound (HIFU) transducer for both inducing and detecting the acoustic cavitation events, and its suitability for different sonication modes like continuous wave, single pulses (with pulse lengths from microseconds to milliseconds) and repeated burst signals is discussed. In Part II, the use of the method for a systematic study of the dependence of the acoustic cavitation thresholds in 3% (by weight) agar phantoms on the temporal sonication parameters is discussed. The values obtained at a frequency of 1.06?MHz, ranging from (0.58?±?0.12)?MPa for a 3-s continuous wave mode sonication to (5.2?±?1.0)?MPa for single shots with a length of 10 wave cycles, are discussed and interpreted on the basis of literature values and their self-consistency. 相似文献
19.
Ollberding NJ Maskarinec G Conroy SM Morimoto Y Franke AA Cooney RV Wilkens LR Le Marchand L Goodman MT Hernandez BY Henderson BE Kolonel LN 《Blood》2012,119(24):5817-5823
This analysis examined the association of non-Hodgkin lymphoma (NHL) with prediagnostic carotenoid levels, a marker for a diet rich in fruits and vegetables. We conducted a nested case-control study within the Multiethnic Cohort with 271 NHL cases and 538 controls matched on sex, ethnicity, location (Hawaii or Los Angeles), birth year, date and time of blood draw, and hours fasting before blood draw. Serum carotenoid levels were obtained by high-pressure liquid chromatography with photodiode array detection. Conditional logistic regression was used to calculate odds ratios (ORs) according to tertiles of serum carotenoids and trend tests using continuous variables. Higher total serum carotenoids (OR(T3 vs T1) = 0.66 [0.46-0.96]; P(trend) = .02), lycopene (OR = 0.54 [0.38-0.78]; P(trend) = .003), and α-cryptoxanthin (OR = 0.53 [0.36-0.78]; P(trend) = .003) were associated with a lower risk of NHL. For retinol (OR = 0.90 [0.61-1.33]; P(trend) = .04), a statistically significant inverse linear trend was detected. Risk estimates remained unchanged with adjustment for NHL risk factors and were similar in analyses stratified by sex and ethnicity; heterogeneity with NHL subtype was detected only for β-carotene. Other carotenoids, including α-carotene, β-carotene, lutein, β-cryptoxanthin, and zeaxanthin, showed no association with risk. These data provide support for a protective role of carotenoid-rich fruits and vegetables in the etiology of NHL. 相似文献
20.
Brittney Murray Rohan Wagle Nuria Amat‐Alarcon Alisha Wilkens Paul Stephens Elaine H. Zackai Elizabeth Goldmuntz Hugh Calkins Matthew A. Deardorff Daniel P. Judge M.D. 《American journal of medical genetics. Part A》2013,161(2):371-376
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a familial form of cardiomyopathy typically caused by mutations in genes that encode an element of the cardiac desmosome. Branchio‐oculo‐facial syndrome (BOFS) is a craniofacial disorder caused by TFAP2A mutations. In a family segregating ARVD/C, some members also had features of BOFS. Genetic testing for ARVD/C identified a mutation in PKP2, encoding plakophilin‐2, a component of the cardiac desmosome. Evaluation of dysmorphology by chromosome microarray (CMA) identified a 4.4 Mb deletion at chromosome 6p24 that included both TFAP2A and DSP, encoding desmoplakin, an additional component of the cardiac desmosome implicated in ARVD/C. A family member with both the 6p24 deletion and PKP2 mutation had more severe cardiac dysfunction. These findings suggest that this contiguous gene deletion contributes to both ARVD/C and BOFS, and that DSP haploinsufficiency may contribute to cardiomyopathy. This family provides a clinical example that underscores the need for careful evaluation in clinical scenarios where genetic heterogeneity is known to exist. Finally, it suggests that individuals with unexplained cardiomyopathy and dysmorphic facial features may benefit from CMA analysis. © 2013 Wiley Periodicals, Inc. 相似文献