125 research outputs found

    On Gromov's Waist of the Sphere Theorem

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    The goal of this paper is to give a detailed and complete proof of M. Gromov's waist of the sphere theorem.Comment: 34 pages, 1 figur

    Generalized tonic colonic seizure followed by loss of consciousness early after using low dose of tramadol: A case report

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    Introduction: Despite high efficacy and safety of tramadol as a pain relieving analgesic, some minor side effects have been reported following its consumption. However, very rarely, serious and life-threatening side effects may appear following administration of tramadol. Case Presentation: This research describes a case of tramadol poisoning that appeared with acute seizure needing emergent and intensive cares. In the described case, using a low dose of tramadol (200 mg, orally), the patient experienced generalized tonic colonic seizure followed by loss of consciousness and shoulder dislocation due to trauma, requiring admission to the intensive care unit. Conclusions: As shown in the study, even using a low dose of tramadol might lead to acute generalized seizure with loss of consciousness and the need for intensive care. © 2018, Anesthesiology and Pain Medicine

    Congenital goiter in North of Iran: A case report

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    Congenital goiter (CG) is one of the rarest disorders observed in a newborn at birth diagnosed with hypothyroidism. Considering the simultaneity of pregnancy and baby's hypothyroidism at birth, the goiter can be caused by diabetes during pregnancy and hypothyroidism emergence in the baby. © 2020 The Authors. Clinical Case Reports published by John Wiley & Sons Lt

    Expression profile of Wnt molecules in leukemic cells from Iranian patients with acute myeloblastic leukemia

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    Background: Wnt molecules play a key role in growth, proliferation and development of some embryonic and adult organs as well as hematopoietic stem cells. Wnt signaling pathways are aberrantly activated in many tumor types, including solid tumors and hematologic malignancies. Objective: To investigate the expression profile of a large number of Wnt genes in leukemic cells from Iranian patients with acute myeloblastic leukemia. Methods: RT-PCR method was used to determine the Wnt genes expression in bone marrow (BM) and/or peripheral blood (PB) samples from 16 patients with AML and PB samples of 36 normal subjects. Results: Among 14 Wnt molecules included in this study, Wnt-7A and Wnt-10A were significantly down-regulated (p = 0.002 and p < 0.0001, respectively) and Wnt-3 was significantly over-expressed (p < 0.02) in AML patients compared to normal subjects. No significant association was found between Wnt expression and FAB classification of the patients. Conclusion: Our results demonstrated for the first time aberrant expression of Wnt-7A, Wnt-10A and Wnt-3 genes in Iranian AML patients. This may be of relevance to the tumorigenesis process in this malignancy

    Fc receptor-like 1-5 molecules are similarly expressed in progressive and indolent clinical subtypes of B-cell chronic lymphocytic leukemia

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    Fc receptor-like (FCRL) 1-5 molecules are exclusively expressed in B-cells and have recently been considered as potential targets for immunotherapy of B-cell malignancies. In this study, the expression pattern of FCRL1-5 molecules was investigated in Iranian patients with B-cell chronic lymphocytic leukemia (B-CLL). Our RT-PCR results have demonstrated that all FCRL molecules, except FCRL4, were expressed in the vast majority of the patients with B-CLL. However, comparison of the relative mRNA expression levels of FCRL between B-CLL (n = 86) and elderly normal subjects (n = 10) revealed significantly lower expression levels of FCRLl (p < 0.0001), FCRL3 (p = 0.01) and FCRL4 (p = 0.002), but not FCRL2 or FCRL5, in cases with B-CLL. No significant differences were observed between the indolent and progressive subtypes of patients with B-CLL. Comparison between the mutated and unmutated subtypes revealed a significantly higher expression level of FCRL3 (p = 0.017) in patients with mutated CLL. Surface and intracytoplasmic expression of FCRL1, 2, 4 and 5 in leukemic cells of 12 patients by flow cytometry revealed similar results to those obtained by RT-PCR with a few exceptions. Thus, while FCRL4 was expressed in only 2 samples at intracytoplasmic level, FCRL1 and 2 were expressed in the majority of samples, both at surface and intracytoplasm. FCRL5 protein was also detected in 10 samples, but surface expression was confirmed in only 2. Analysis of B-cells from 5 normal subjects by flow cytometry revealed higher expression levels of FCRL molecules compared to CLL. Our results indicate differential expression of FCRL molecules in B-CLL and suggest the potential implication of FCRL1 and 2 for immunotherapeutic interventions. © 2008 Wiley-Liss, Inc

    Global investigation of protein–protein interactions in yeast Saccharomyces cerevisiae using re-occurring short polypeptide sequences

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    Protein–protein interaction (PPI) maps provide insight into cellular biology and have received considerable attention in the post-genomic era. While large-scale experimental approaches have generated large collections of experimentally determined PPIs, technical limitations preclude certain PPIs from detection. Recently, we demonstrated that yeast PPIs can be computationally predicted using re-occurring short polypeptide sequences between known interacting protein pairs. However, the computational requirements and low specificity made this method unsuitable for large-scale investigations. Here, we report an improved approach, which exhibits a specificity of ∼99.95% and executes 16 000 times faster. Importantly, we report the first all-to-all sequence-based computational screen of PPIs in yeast, Saccharomyces cerevisiae in which we identify 29 589 high confidence interactions of ∼2 × 107 possible pairs. Of these, 14 438 PPIs have not been previously reported and may represent novel interactions. In particular, these results reveal a richer set of membrane protein interactions, not readily amenable to experimental investigations. From the novel PPIs, a novel putative protein complex comprised largely of membrane proteins was revealed. In addition, two novel gene functions were predicted and experimentally confirmed to affect the efficiency of non-homologous end-joining, providing further support for the usefulness of the identified PPIs in biological investigations

    Plasma protein N-glycosylation is associated with cardiovascular disease, nephropathy, and retinopathy in type 2 diabetes

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    Introduction Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality. Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System).Research design and methods Blood plasma samples and technical replicates were pipetted into 96-well plates in a randomized manner. Peptide:N-glycosidase F (PNGase F) was used to release N-glycans, whereafter sialic acids were derivatized for stabilization and linkage differentiation. After total area normalization, 68 individual glycan compositions were quantified in total and were used to calculate 45 derived traits which reflect structural features of glycosylation. Associations of glycan features with prevalent and incident microvascular or macrovascular complications were tested in logistic and Cox regression in both independent cohorts and the results were meta-analyzed.Results Our results demonstrated similarities between incident and prevalent complications. The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34x10(-11)), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70x10(-6)). Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.Conclusions These findings may provide a glance on how TPNG patterns change before complications emerge, paving the way for future studies on prediction biomarkers and potentially disease mechanisms.Molecular Epidemiolog

    Peripheral T-lymphocytes express WNT7A and its restoration in leukemia-derived lymphoblasts inhibits cell proliferation

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    <p>Abstract</p> <p>Background</p> <p>WNT7a, a member of the Wnt ligand family implicated in several developmental processes, has also been reported to be dysregulated in some types of tumors; however, its function and implication in oncogenesis is poorly understood. Moreover, the expression of this gene and the role that it plays in the biology of blood cells remains unclear. In addition to determining the expression of the <it>WNT7A </it>gene in blood cells, in leukemia-derived cell lines, and in samples of patients with leukemia, the aim of this study was to seek the effect of this gene in proliferation.</p> <p>Methods</p> <p>We analyzed peripheral blood mononuclear cells, sorted CD3 and CD19 cells, four leukemia-derived cell lines, and blood samples from 14 patients with Acute lymphoblastic leukemia (ALL), and 19 clinically healthy subjects. Reverse transcription followed by quantitative Real-time Polymerase chain reaction (qRT-PCR) analysis were performed to determine relative <it>WNT7A </it>expression. Restoration of WNT7a was done employing a lentiviral system and by using a recombinant human protein. Cell proliferation was measured by addition of WST-1 to cell cultures.</p> <p>Results</p> <p>WNT7a is mainly produced by CD3 T-lymphocytes, its expression decreases upon activation, and it is severely reduced in leukemia-derived cell lines, as well as in the blood samples of patients with ALL when compared with healthy controls (<it>p </it>≤0.001). By restoring <it>WNT7A </it>expression in leukemia-derived cells, we were able to demonstrate that WNT7a inhibits cell growth. A similar effect was observed when a recombinant human WNT7a protein was used. Interestingly, restoration of <it>WNT7A </it>expression in Jurkat cells did not activate the canonical Wnt/β-catenin pathway.</p> <p>Conclusions</p> <p>To our knowledge, this is the first report evidencing quantitatively decreased <it>WNT7A </it>levels in leukemia-derived cells and that <it>WNT7A </it>restoration in T-lymphocytes inhibits cell proliferation. In addition, our results also support the possible function of <it>WNT7A </it>as a tumor suppressor gene as well as a therapeutic tool.</p
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