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Jaime Vengoechea Aditi S Parikh Shulin Zhang Flora Tassone 《European journal of human genetics : EJHG》2012,20(11):1197-1200
Loss-of-function due to expansion of a CGG repeat located in the 5''UTR of the FMR1 gene is the most frequent cause of fragile X syndrome. Less than 1% of individuals with fragile X syndrome have been reported to have a partial or full deletion or point mutation of the FMR1 gene. However, whether a copy number gain of the FMR1 gene could result in certain clinical phenotypes has not been fully investigated. Here, we report the case of a child who presented with developmental delay starting at 9 months of age, fine motor and speech delay, progressive seizures since 18 months of age and hyperactivity. Molecular workup identified a de novo microduplication in the Xq27.3 region, including the FMR1 gene and the ASFMR1 gene. The expression level of the FMR1 gene in peripheral blood did not differ from that of the controls. In addition, an inherited 363-kb duplication on the chromosome 1q44 region and an inherited deletion of 168 kb on the chromosome 4p15.31 region were detected. It is not clear whether these inherited copy number variations (CNVs) also have a modifying role in the clinical phenotype of this patient. 相似文献
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Stimulation of adrenergic activity by desipramine enhances hematopoietic stem and progenitor cell mobilization along with G‐CSF in multiple myeloma: A pilot study
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Aditi Shastri Anjali Budhathoki Stefan K. Barta Noah Kornblum Olga Derman Ramakrishna Battini Radha Raghupathy Amit K. Verma Paul S. Frenette Ira Braunschweig Murali Janakiram 《American journal of hematology》2017,92(10):1047-1051
Hematopoietic stem cell (HSC) release is positively regulated by the sympathetic nervous system through the β3 adrenergic receptor. Preclinical studies have demonstrated that the combination of desipramine and G‐CSF resulted in improved HSC mobilization. Here, we present the results of an open‐label single‐arm pilot study in patients with multiple myeloma undergoing autologous stem cell transplantation (ASCT) to assess the safety and efficacy of desipramine combined with G‐SCF to induce HSC mobilization. The primary endpoint was safety of the combination including engraftment kinetics. The secondary endpoint was the proportion of patients who collected ≥5 × 106 CD34+ cells/kg. Outcomes were compared with historical matched controls during the same time period with multiple myeloma mobilized with G‐CSF. All study patients received desipramine 100 mg daily for 7 days, starting 4 days prior to G‐CSF administration (D‐3) and continued taking it along with G‐CSF for a total of 7 days. Six of ten patients enrolled completed the protocol with minimal side effects. All of them achieved the target collection of 5 × 106 CD34 cells/kg in a median of 1.5 apheresis session with two patients needing additional plerixafor (16%), while 11 out of 13 patients (85%) achieved the target of 5 × 106 CD34 cells/kg in the historical control group in a median of 2 apheresis procedures and seven patients needed plerixafor (54%). The combination of desipramine and G‐CSF is safe and signals improved mobilization over G‐CSF alone, providing a possible alternative means of mobilization that needs further investigation. 相似文献
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Leishmania donovani causes visceral leishmaniasis (VL) by infecting the monocyte/macrophage lineage and residing inside specialized structures known as parasitophorous vacuoles. The protozoan parasite has adopted several means of escaping the host immune response, with one of the major methods being deactivation of host macrophages. Previous reports highlight dampened macrophage signaling, defective antigen presentation due to increased membrane fluidity, and the downregulation of several genes associated with L. donovani infection. We have reported previously that the defective antigen presentation in infected hamsters could be corrected by a single injection of a cholesterol-containing liposome. Here we show that cholesterol in the form of a liposomal formulation can stimulate the innate immune arm and reactivate macrophage function. Augmented levels of reactive oxygen species (ROS) and reactive nitrogen intermediates (RNI), along with proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), corroborate intracellular parasite killing. Cholesterol incorporation kinetics is favored in infected macrophages more than in normal macrophages. Such an enhanced cholesterol uptake is associated with preferential apoptosis of infected macrophages in an endoplasmic reticulum (ER) stress-dependent manner. All these events are coupled with mitogen-activated protein (MAP) kinase activation, while inhibition of such pathways resulted in increased parasite loads. Hence, liposomal cholesterol is a potential facilitator of the macrophage effector function in favor of the host, independently of the T-cell arm. 相似文献
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Raphael Jakubovic Joel Ramjist Shaurya Gupta Daipayan Guha Arjun Sahgal F. Stuart Foster Victor X.D. Yang 《Ultrasound in medicine & biology》2018,44(11):2379-2387
High frequency micro-ultrasound (µUS) transducers with central frequencies up to 50?MHz facilitate dynamic visualization of patient anatomy with minimal disruption of the surgical work flow. Micro-ultrasound improves spatial resolution over conventional ultrasound imaging from millimeter to micrometer, but compromises depth penetration. This trade-off is sufficient during an open surgery in which the bone is removed and theultrasound probe can be placed into the surgical cavity. By fusing µUS with pre-operative imaging and tracking the ultrasound probe intra-operatively using our optical topographic imaging technology, we can provide dynamic feedback during surgery, thus affecting clinical decision making. We present our initial experience using high-frequency µUS imaging during spinal procedures. Micro-ultrasound images were obtained in five spinal procedures. Medical rationale for use of µUS was provided for each patient. Surgical procedures were performed using the standard clinical practice with bone removal to facilitate real-time ultrasound imaging of the soft tissue. During surgery, the µUS probe was registered to the pre-operative computed tomography and magnetic resonance images. Images obtained comprised five spinal decompression surgeries (four tumor resections, one cystic synovial mass). Micro-ultrasound images obtained during spine surgery delineated exquisite detailing of the spinal anatomy including white matter and gray matter tracts and nerve roots and allowed accurate assessment of the extent of decompression/tumor resection. In conclusion, tracked µUS enables real-time imaging of the surgical cavity, conferring significant qualitative improvement over conventional ultrasound. 相似文献
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Maria Bindu Bagh Ishita Guha Thakurta Mallika Biswas Prajna Behera Sasanka Chakrabarti 《Biogerontology》2011,12(2):119-131
A combination of antioxidants (N-acetyl cysteine, α-lipoic acid, and α-tocopherol) was selected for long term oral supplementation
study in rats for protective effects on age-related mitochondrial alterations in the brain. Four groups of rats were chosen:
young control (6–7 months); aged rats (22–24 months); aged rats (22–24 months) on daily antioxidant supplementation from 18 month
onwards and young rats (6–7 months) on daily antioxidant supplementation from 2 month onwards. The brain mitochondrial functional
parameters, status of antioxidant enzymes and accumulation of oxidative damage markers were measured in the four groups of
rats. A significant decrease in complex IV activity and a loss of transmembrane potential and phosphorylation capacity along
with an increased accumulation of oxidative damage markers and compromised antioxidant enzyme status were noticed in aged
rat brain mitochondria as compared to that in young controls, but in aged rats supplemented with oral antioxidants the mitochondrial
alterations were largely prevented. Antioxidant supplementation in young rats had no effect on mitochondrial parameters investigated
in this study. The results have implications in biochemical and functional deficits of brain during aging as well as in neurodegenerative
disorders. 相似文献
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