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141.
Minnucci G Amicarelli G Salmoiraghi S Spinelli O Guinea Montalvo ML Giussani U Adlerstein D Rambaldi A 《Haematologica》2012,97(9):1394-1400
Background The identification of the JAK2V617F mutation is mandatory in the diagnostic work-up of Philadelphia chromosome-negative myeloproliferative neoplasms. Several molecular techniques to detect this mutation are currently available, but each of them has some limits. DESIGN AND METHODS: We set up a novel molecular method for the identification of the JAK2V617F mutation based on an allele-specific loop-mediated amplification, not polymerase chain reaction analysis. This innovative technique amplifies DNA targets under isothermal conditions with high specificity, efficiency and rapidity. The method does not require either a thermal cycler or gel separation and the DNA amplification reaction is visible to the naked eye and can be monitored by turbidimetry. This method was validated on DNA from cell lines as well as from patients with myeloproliferative neoplasms. The results were compared with those obtained by conventional polymerase chain reaction methods. RESULTS: This assay detects, within 1 hour, the JAK2V617F mutation down to an allele burden of 0.1-0.01%. All samples positive by polymerase chain reaction (n=146) proved positive when tested by allele-specific loop-mediated amplification and none of the 80 negative controls gave false positive results. In addition, six patients with essential thrombocythemia previously diagnosed as being JAK2V617F negative by polymerase chain reaction analysis were found to be positive (at a low level) by allele-specific loop-mediated amplification. Furthermore, this assay discriminated the amount of JAK2V617F tumor allele within intervals of positivity, above 50%, between 50% and 10% and below 10%. Conclusions Allele-specific loop-mediated amplification is a simple, robust and easily applicable method for the molecular diagnosis and monitoring of JAK2V617F mutation in patients with chronic myeloproliferative neoplasms. 相似文献
142.
Anli Liu Kelly Werner Subhojit Roy John Q. Trojanowski Ursula Morgan-Kane Bruce L. Miller 《Neurocase》2013,19(3):235-247
Patients presenting with left-sided FTLD syndromes sometimes develop a new preoccupation with art, greater attention to visual stimuli, and increased visual creativity. We describe the case of a 53-year-old, right-handed man with a history of bipolar disorder who presented with language and behavior impairments characteristic of FTLD, then developed motor symptoms consistent with a second diagnosis of amyotrophic lateral sclerosis. Though the patient had never created visual art before, he developed a compulsion for painting beginning at the earliest stages of his disease, and continued producing art daily until he could no longer lift a paintbrush because of his motor deficits. Upon autopsy, he was found to have ubiquitin and TDP43-positive inclusions with MND pathology. This case study details the patient's longitudinal neuropsychological, emotional, behavioral, and motor symptoms, along with structural imaging, neurologic, and neuropathologic findings. Multiple examples of the patient's art are depicted throughout all stages of his illness, and the possible cognitive, behavioral, and neurologic correlates of his new-onset visual artistry are discussed. 相似文献
143.
144.
Cristian Patrick Zeni Silzá Tramontina Thamis Aline Zeni Roberta Coelho Gabriel Pheula Julio Bernardi Ursula Maldaner Talita Lopes Silva Angélica Salatino-Oliveira Mara Hutz Luis Augusto Rohde 《Revista brasileira de psiquiatria (S?o Paulo, Brazil : 1999)》2013,35(1):44-50
ObjectivesTo assess the role of the Val66Met polymorphism at the brain-derived neurotrophic factor (BDNF) gene on the performance of children and adolescents with bipolar disorder [juvenile bipolar disorder (JBD)] on the Wisconsin Card Sorting Test (WCST).MethodsChildren and adolescents were assessed by the K-SADS-PL and a clinical evaluation for BD and comorbid conditions. Manic and depressive symptoms were assessed with the Young Mania Rating Scale and the Children Depression Rating Scale – Reviewed. The Val66Met polymorphism at the BDNF was genotyped from a blood sample. Patients’ IQ and executive functions were assessed by a standard cognitive flexibility test (WCST).ResultsFifty-three subjects were included in the study. No significant difference was observed between the Val/Val and Val/Met+Met/Met groups on any WCST scores in the MANCOVA (F48,5 = .76; p = .59; Perseverative Errors, p = .66; Nonperseverative Errors, p = .58; Categories Completed, p = .34; Attempts to Reach First Category, p=.64; and Percentage of Conceptual Level Responses, p = .99).ConclusionsOur findings from this sample of children and adolescents with BD do not replicate results from studies of adults and suggest the existence of differences in the neurobiology of this disorder across the life cycle. Investigations of larger samples are necessary to confirm these data. 相似文献
145.
Wilfried Pott ?zgür Albayrak Anke Hinney Johannes Hebebrand Ursula Pauli-Pott 《Obesity facts》2013,6(1):109-115
ObjectiveRecent case reports suggest a link between reduced melanocortinergic tone and both obesity and attention deficit / hyperactivity disorder (ADHD). We present the case of a 13-year-old, male, obese MC4R mutation carrier with ADHD.Case ReportThe boy carries a heterozygous mutation in the melanocortin 4 receptor gene (MC4R; Met281Val), that leads to a reduced receptor function. Dominant mutations of this type represent major gene effects for obesity. He participated in a lifestyle intervention program for obesity and received treatment with the selective norepinephrine re-uptake inhibitor atomoxetine for 31 months. The boy markedly reduced his BMI from 47.2 to 29.6 kg/m².ConclusionAtomoxetine proved to efficiently reduce weight in a severely obese MC4R mutation carrier with ADHD. We briefly discuss possible mechanisms for our observation, including evidence for the functional connectivity between melanocortinergic, dopaminergic, and norepinephrinergic brain circuitries.Key Words: Pharmacogenetics, Brain-derived neurotrophic factor, Weight loss, Appetite control, Methylphenidate 相似文献
146.
147.
Andreas Pollreisz Gregor S. Reiter Hrvoje Bogunovic Lukas Baumann Astrid Jakob Ferdinand G. Schlanitz Stefan Sacu Cynthia Owsley Kenneth R. Sloan Christine A. Curcio Ursula Schmidt-Erfurth 《Investigative ophthalmology & visual science》2021,62(2)
PurposeTo refine estimates of macular soft drusen abundance in eyes with age-related macular degeneration (AMD) and evaluate hypotheses about drusen biogenesis, we investigated topographic distribution and growth rates of drusen by optical coherence tomography (OCT). We compared results to retinal features with similar topographies (cone density and macular pigment) in healthy eyes.MethodsIn a prospective study, distribution and growth rates of soft drusen in eyes with AMD were identified by human observers in OCT volumes and analyzed with computer-assistance. Published histologic data for macular cone densities (n = 12 eyes) and in vivo macular pigment optical density (MPOD) measurements in older adults with unremarkable maculae (n = 31; 62 paired eyes, averaged) were revisited. All values were normalized to Early Treatment Diabetic Retinopathy Study (ETDRS) subfield areas.ResultsSixty-two eyes of 44 patients were imaged for periods up to 78 months. Soft drusen volume per unit volume at baseline is 24.6-fold and 2.3-fold higher in the central ETDRS subfield than in outer and inner rings, respectively, and grows most prominently there. Corresponding ratios (central versus inner and central versus outer) for cone density in donor eyes is 13.3-fold and 5.1-fold and for MPOD, 24.6 and 23.9-fold, and 3.6 and 3.6-fold.ConclusionsNormalized soft drusen volume in AMD eyes as assessed by OCT is ≥ 20-fold higher in central ETDRS subfields than in outer rings, paralleling MPOD distribution in healthy eyes. Data on drusen volume support this metric for AMD risk assessment and clinical trial outcome measure. Alignment of different data modalities support the ETDRS grid for standardizing retinal topography in mechanistic studies of drusen biogenesis. 相似文献
148.
Caroline Stellbaum Yunus Ayral Andreas Morguet Heinz-Peter Schultheiss Ursula Rauch 《Cardiovascular Revascularization Medicine》2012,13(3):159-166
BackgroundDifferent methods are available for quantifying platelet function inhibition. Measuring vasodilator-stimulated phosphoprotein (VASP) phosphorylation is currently the most specific method for assessing the clopidogrel effect. The aim of our study was to compare different tests in view of a clinically applicable bedside test. Further, we examined whether doubling the clopidogrel dose to 150 mg/d in clopidogrel low-responder would lead to a reduction in platelet reactivity.Methods and resultsADP-, ADP Hs-, and TRAP-induced platelet aggregation were measured by impedance aggregometry in 100 patients with CAD and 18 healthy controls. Moreover, platelet aggregation was assessed by flow cytometrical detection of VASP-phosphorylation and surface P-selectin in a subgroup of 34 patients and in healthy controls. Another 10 patients with CAD, identified as low-responder, were treated with a clopidogrel dose of 150 mg/d. Thereafter, ADP-induced platelet aggregation was assessed by impedance aggregometry. Significant correlations were observed between ADP-induced platelet aggregation assessed by VASP-phosphorylation and by impedance aggregometry. Doubling the dose of clopidogrel to 150 mg/d was associated with a reduction of ADP-induced platelet aggregation in only 60% of the patients.ConclusionsImpedance aggregometry is a valuable bedside test to assess platelet function inhibition. Doubling the clopidogrel dose is not effective to reduce high on-treatment platelet reactivity in almost half of these patients, pointing to the need of a more powerful platelet inhibitor. 相似文献
149.
Michelle L Frost PhD Amelia E Moore Musib Siddique Glen M Blake Didier Laurent Babul Borah Ursula Schramm Marie‐Anne Valentin Theodore C Pellas Paul K Marsden Paul J Schleyer Ignac Fogelman 《Journal of bone and mineral research》2013,28(6):1337-1347
The functional imaging technique of 18F‐fluoride positron emission tomography (18F‐PET) allows the noninvasive quantitative assessment of regional bone formation at any skeletal site, including the spine and hip. The aim of this study was to determine if 18F‐PET can be used as an early biomarker of treatment efficacy at the hip. Twenty‐seven treatment‐naive postmenopausal women with osteopenia were randomized to receive teriparatide and calcium and vitamin D (TPT group, n = 13) or calcium and vitamin D only (control group, n = 14). Subjects in the TPT group were treated with 20 µg/day teriparatide for 12 weeks. 18F‐PET scans of the proximal femur, pelvis, and lumbar spine were performed at baseline and 12 weeks. The plasma clearance of 18F‐fluoride to bone, Ki, a validated measurement of bone formation, was measured at four regions of the hip, lumbar spine, and pelvis. A significant increase in Ki was observed at all regions of interest (ROIs), including the total hip (+27%, p = 0.002), femoral neck (+25%, p = 0.040), hip trabecular ROI (+21%, p = 0.017), and hip cortical ROI (+51%, p = 0.001) in the TPT group. Significant increases in Ki in response to TPT were also observed at the lumbar spine (+18%, p = 0.001) and pelvis (+42%, p = 0.001). No significant changes in Ki were observed for the control group. Changes in BMD and bone turnover markers were consistent with previous trials of teriparatide. In conclusion, this is the first study to our knowledge to demonstrate that 18F‐PET can be used as an imaging biomarker for determining treatment efficacy at the hip as early as 12 weeks after initiation of therapy. 相似文献
150.
Ursula Eberhardt Henry J. Beker Jan Vesterholt Karolina Dukik Grit Walther Jordi Vila Samantha Fernández Brime 《Fungal Diversity》2013,58(1):103-126
This paper addresses section Theobromina within the genus Hebeloma (Agaricales). We recognise seven European species within this section, three of which are described as new: Hebeloma alboerumpens, H. griseopruinatum and H. parvicystidiatum. The first two of these species appear to be ectomycorrhizal with Cistaceae: Cistus and Helianthemum. Hebeloma parvicystidiatum is more likely to be in mycorrhizal association with Quercus spp. We also provide a key to the European species within sect. Theobromina and an updated key of known Hebeloma associates of Cistus. Molecular analyses based on multiple loci further illustrate the distinctness of the newly described taxa and provide molecular evidence, supporting the morphological evidence, for the relationship that exists among species of this section. The ITS is the only one from the sequenced loci that, alongside with morphology, distinguishes among all of the species of sect. Theobromina. The section gains most of its molecular support from the MCM7 locus, followed by RPB2. 相似文献