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Find video protocols related to scientific articles indexed in Pubmed.
Chronic myelogenous leukemia, version 1.2015.
J Natl Compr Canc Netw
PUBLISHED: 11-02-2014
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Chronic myelogenous leukemia (CML) is usually diagnosed in the chronic phase. Untreated chronic phase CML will eventually progress to advanced phase (accelerated or blast phase) CML. Tyrosine kinase inhibitors (TKIs) have been shown to induce favorable response rates in patients with accelerated and blast phase CML. The addition of TKIs to chemotherapy has also been associated with improved outcomes in patients with blast phase CML. Allogeneic hematopoietic stem cell transplant remains a potentially curative option for patients with advanced phase CML, although treatment with a course of TKIs will be beneficial as a bridge to transplant. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with advanced phase CML.
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Clinicopathological and molecular features of myeloid sarcoma as initial presentation of therapy-related myeloid neoplasms: a single institution experience.
Int. J. Hematol.
PUBLISHED: 06-29-2014
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Therapy-related myeloid neoplasms (t-MN) have a common origin in prior cytotoxic therapy and/or radiation. These neoplasms include therapy-related acute myeloid leukemia, myelodysplastic syndrome (t-MDS), and myelodysplastic/myeloproliferative neoplasms (t-MDS/MPN). Myeloid sarcoma (MS), on the other hand, is a rare disease manifesting as an extramedullary collection of immature cells of myeloid lineage. Rarer still is therapy-related MS (t-MS), which has not been adequately studied due to its rarity and its lack of recognition as a unique entity among other t-MN. Here, we report what is to our knowledge the first case series of t-MS, with the aim of investigating and establishing salient clinicopathological and molecular features of this entity.
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Trisomy 21-Associated Transient Abnormal Myelopoiesis Involving the Maternal Space of the Placenta: A Case Report and Literature Review.
Pediatr. Dev. Pathol.
PUBLISHED: 06-27-2014
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Abstract We report a case of a Trisomy 21 male newborn with transient abnormal myelopoiesis (TAM) at birth whose placenta showed extravasated fetal blasts in the perivillous (maternal) space. Concern for possible maternal spread of fetal malignancy prompted a Kleihauer-Betke test and flow cytometric analysis of the maternal peripheral blood, on postpartum day 2. Notably, no evidence of persistence of fetal cells in the maternal blood was identified, a finding that likely reflected successful maternal immunologic clearance of the fetal blasts and erythrocytes, and/or blast cellular fragility and limited viability. Ours is the first report documenting maternal peripheral blood follow-up evaluation of this disorder in the English literature. We discuss our case in the context of a comprehensive review of fetoneonatal solid tumor and leukemic proliferative disorders with placental involvement and evidence of maternal metastasis.
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Out with the bad and in with the good; red cell exchange, white cell reduction, and platelet reduction.
J Clin Apher
PUBLISHED: 03-23-2014
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Automated techniques for red cell [red blood cell (RBC)] exchange or depletion of malignant cells from the peripheral blood have allowed patients with life-threatening conditions to survive long enough to receive definitive treatment. Examples of such conditions include acute chest syndrome in sickle cell disease (SCD) or acute respiratory insufficiency due to leukostasis in acute leukemia. Conversely, other patients with SCD undergo RBC exchanges on a chronic basis to maintain a reasonable quality of life and prevent another stroke. In this review, we will discuss the techniques as well as indications for RBC exchange, leukocytapheresis, and thrombocytapheresis. To illustrate the uses of these therapeutic apheresis procedures, the authors included a summary of the most common diagnoses that comprise their use.
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Nasal endoscope: an armamentarium in the management of sinonasal inverted papilloma.
Indian J Otolaryngol Head Neck Surg
PUBLISHED: 02-17-2014
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Sinonasal inverted papillomas (SIP) are unique group of locally aggressive benign neoplastic lesions arising from mucosa of sinonasal tract with potential for recurrences and known association with squamous cell carcinoma in 5-15 % of cases. This study was conducted was to assess the efficacy and usefulness of the nasal endoscope in treating SIP. We reviewed 28 biopsy proven cases of SIPs that were treated at our hospital between June 2009 and September 2013. Average patient age was 46 years. Fourteen were treated by transnasal endoscopic excision of tumor with noted recurrence of 21.43 %. Thirteen were treated by endoscopic assisted open surgery which had 23 % recurrence. Three patients had malignant inverted papillomas, of whom two (7 %) were found to have synchronous squamous cell carcinoma and one (3.6 %) had metachronous squamous cell carcinoma. No evidence of recurrence was found in rest during our follow up. The endoscopic approach is the preferred method for the treatment of the majority of inverted papillomas. Powered instrumentation is extremely useful to achieve good results. Although significant number of cases was done by external approach by lateral rhinotomy, the endoscopic assistance is required to ensure complete removal of the tumour to reduce the recurrence rates. Close follow up of the patient for a longer period of time is necessary for the early detection of recurrence and to allow for surgical salvage.
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Soluble CD25 in serum: a potential marker for subclinical macrophage activation syndrome in patients with active systemic onset juvenile idiopathic arthritis.
Int J Rheum Dis
PUBLISHED: 01-13-2014
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Laboratory and immunological abnormalities seen in overt macrophage activation syndrome (MAS) may be observed in patients with untreated new onset systemic onset juvenile idiopathic arthritis (SoJIA). We investigated the prevalence of clinical and traditional laboratory markers of MAS as well as soluble CD163 and soluble interleukin (IL)-2R? (CD25) in active SoJIA patients.
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Chronic Myelogenous Leukemia, Version 1.2014.
J Natl Compr Canc Netw
PUBLISHED: 11-15-2013
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The 2014 NCCN Clinical Practice Guidelines in Oncology for Chronic Myelogenous Leukemia recommend quantitative reverse-transcription polymerase chain reaction (QPCR) standardized to International Scale (IS) as the preferred method for monitoring molecular response to tyrosine kinase inhibitor (TKI) therapy. A BCR-ABL1 transcript level of 10% or less (IS) is now included as the response milestone at 3 and 6 months. Change of therapy to an alternate TKI is recommended for patients with BCR-ABL1 transcript levels greater than 10% (IS) at 3 months after primary treatment with imatinib. Continuing the same dose of TKI or switching to an alternate TKI are options for patients with BCR-ABL1 transcript levels greater than 10% (IS) at 3 months after primary treatment with dasatinib or nilotinib. The guidelines recommend 6-month evaluation with QPCR (IS) for patients with BCR-ABL1 transcript levels greater than 10% at 3 months. Monitoring with QPCR (IS) every 3 months is recommended for all patients, including those who meet response milestones at 3, 6, 12, and 18 months (BCR-ABL1 transcript level ?10% [IS] at 3 and 6 months, complete cytogenetic response at 12 and 18 months).
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Examining racial differences in diffuse large B-cell lymphoma presentation and survival.
Leuk. Lymphoma
PUBLISHED: 06-19-2013
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We performed a retrospective cohort analysis of 701 (533 white and 144 black) patients with diffuse large B-cell lymphoma (DLBCL) treated at two referral centers in southern United States between 1981 and 2010. Median age of diagnosis for blacks was 50 years vs. 57 years for whites (p < 0.001). A greater percentage of blacks presented with elevated lactate dehydrogenase levels, B-symptoms and performance status ? 2. More whites (8%) than blacks (3%) had a positive family history of lymphoma (p = 0.048). There were no racial differences in the use of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone; 52% black vs. 47% white, p = 0.73). While black race predicted worse survival among patients treated with CHOP (hazard ratio [HR] 1.8, p < 0.001), treatment with R-CHOP was associated with improved survival irrespective of race (HR 0.61, p = 0.01). Future studies should examine biological differences that may underlie the observed racial differences in presentation and outcome.
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Structural basis for the modulation of the neuronal voltage-gated sodium channel NaV1.6 by calmodulin.
Sci Rep
PUBLISHED: 06-05-2013
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The neuronal-voltage gated sodium channel (VGSC), Na(V)1.6, plays an important role in propagating action potentials along myelinated axons. Calmodulin (CaM) is known to modulate the inactivation kinetics of Na(V)1.6 by interacting with its IQ motif. Here we report the crystal structure of apo-CaM:Na(V)1.6IQ motif, along with functional studies. The IQ motif of Na(V)1.6 adopts an ?-helical conformation in its interaction with the C-lobe of CaM. CaM uses different residues to interact with Na(V)1.6IQ motif depending on the presence or absence of Ca²?. Three residues from Na(V)1.6, Arg1902, Tyr1904 and Arg1905 were identified as the key common interacting residues in both the presence and absence of Ca²?. Substitution of Arg1902 and Tyr1904 with alanine showed a reduced rate of Na(V)1.6 inactivation in electrophysiological experiments in vivo. Compared with other CaM:Na(V) complexes, our results reveal a different mode of interaction for CaM:Na(V)1.6 and provides structural insight into the isoform-specific modulation of VGSCs.
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Cardiac device-related invasive aspergilloma assessed by live/real time three-dimensional transthoracic echocardiography.
Echocardiography
PUBLISHED: 05-11-2013
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Cardiac device-related infection caused by Aspergillus species is a rare finding associated with high mortality. Prompt recognition and treatment is imperative, but difficult as blood cultures are often negative and diagnosis requires a high index of suspicion. Live/real time three-dimensional transthoracic echocardiography (3DTTE) provides incremental knowledge in the characterization of valvular vegetations. Here, we provide a detailed description of an invasive cardiac device-related infection caused by Aspergillus fumigatus using 3DTTE. Findings described here highlight the role for 3DTTE in the prompt diagnosis of invasive cardiac Aspergillus infections as well as surgical planning in such cases.
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Structural basis for the interaction of unstructured neuron specific substrates neuromodulin and neurogranin with Calmodulin.
Sci Rep
PUBLISHED: 02-21-2013
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Neuromodulin (Nm) and neurogranin (Ng) are neuron-specific substrates of protein kinase C (PKC). Their interactions with Calmodulin (CaM) are crucial for learning and memory formation in neurons. Here, we report the structure of IQ peptides (24aa) of Nm/Ng complexed with CaM and their functional studies with full-length proteins. Nm/Ng and their respective IQ peptides are intrinsically unstructured; however, upon binding with CaM, IQ motifs adopt a helical conformation. Ser41 (Ser36) of Nm (Ng) is located in a negatively charged pocket in the apo CaM and, when phosphorylated, it will repel Nm/Ng from CaM. These observations explain the mechanism by which PKC-induced Ser phosphorylation blocks the association of Nm/Ng with CaM and interrupts several learning- and memory-associated functions. Moreover, the present study identified Arg as a key CaM interacting residue from Nm/Ng. This residue is crucial for CaM-mediated function, as evidenced by the inability of the Ng mutant (Arg-to-Ala) to potentiate synaptic transmission in CA1 hippocampal neurons.
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A novel trans conformation of ligand-free calmodulin.
PLoS ONE
PUBLISHED: 01-29-2013
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Calmodulin (CaM) is a highly conserved eukaryotic protein that binds specifically to more than 100 target proteins in response to calcium (Ca(2+)) signal. CaM adopts a considerable degree of structural plasticity to accomplish this physiological role; however, the nature and extent of this plasticity remain to be fully understood. Here, we report the crystal structure of a novel trans conformation of ligand-free CaM where the relative disposition of two lobes of CaM is different, a conformation to-date not reported. While no major structural changes were observed in the independent N- and C-lobes as compared with previously reported structures of Ca(2+)/CaM, the central helix was tilted by ~90° at Arg75. This is the first crystal structure of CaM to show a drastic conformational change in the central helix, and reveals one of several possible conformations of CaM to engage with its binding partner.
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Reactivation of Old Scars in an Elderly Man Revealing Löfgrens Syndrome.
Case Rep Rheumatol
PUBLISHED: 01-10-2013
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Here, we report the case of a 55-year-old man with reactivation of old cutaneous scars associated with a febrile illness, episcleritis, polyarthralgias, erythema nodosum and hilar adenopathy. High-resolution computed tomography (HRCT) revealed right paratracheal, bilateral hilar, and subcarinal lymphadenopathy without any nodular densities in both lung fields. A scar biopsy revealed multiple noncaseating granulomas and confirmed the diagnosis of sarcoidosis. A short course of oral steroids led to regression of systemic symptoms, and the scars returned to baseline size. This patient represented a rare case of simultaneous Löfgrens syndrome and scar sarcoidosis.
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Linkers in the structural biology of protein-protein interactions.
Protein Sci.
PUBLISHED: 01-08-2013
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Linkers or spacers are short amino acid sequences created in nature to separate multiple domains in a single protein. Most of them are rigid and function to prohibit unwanted interactions between the discrete domains. However, Gly-rich linkers are flexible, connecting various domains in a single protein without interfering with the function of each domain. The advent of recombinant DNA technology made it possible to fuse two interacting partners with the introduction of artificial linkers. Often, independent proteins may not exist as stable or structured proteins until they interact with their binding partner, following which they gain stability and the essential structural elements. Gly-rich linkers have been proven useful for these types of unstable interactions, particularly where the interaction is weak and transient, by creating a covalent link between the proteins to form a stable protein-protein complex. Gly-rich linkers are also employed to form stable covalently linked dimers, and to connect two independent domains that create a ligand-binding site or recognition sequence. The lengths of linkers vary from 2 to 31 amino acids, optimized for each condition so that the linker does not impose any constraints on the conformation or interactions of the linked partners. Various structures of covalently linked protein complexes have been described using X-ray crystallography, nuclear magnetic resonance and cryo-electron microscopy techniques. In this review, we evaluate several structural studies where linkers have been used to improve protein quality, to produce stable protein-protein complexes, and to obtain protein dimers.
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Cyclobacterium qasimii sp. nov., a psychrotolerant bacterium isolated from Arctic marine sediment.
Int. J. Syst. Evol. Microbiol.
PUBLISHED: 10-28-2011
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A novel Gram-stain-negative, horseshoe-shaped, non-motile bacterium, designated strain M12-11B(T), was isolated from a marine sediment sample collected at a depth of 200 m from Kongsfjorden, Svalbard. The colony colour was orangish red due to the presence of carotenoids. Fatty acids were dominated by branched and unsaturated fatty acids (90.8 %), with a high abundance of iso-C(15 : 0) (14.9 %), anteiso-C(15 : 0) (11.4 %), iso-C(15 : 1) G (13.1 %), C(15 : 1)?6c (5.4 %), C(17 : 1)?6c (6.7 %), summed feature 3 (C(16 : 1)?7c and/or C(16 : 1)?6c; 9.3 %) and summed feature 9 (10-methyl C(16 : 0) and/or iso-C(17 : 1)?9c; 5.9 %). Strain M12-11B(T) contained MK-7 as the major respiratory quinone. The polar lipids consisted of phosphatidylcholine, phosphatidylethanolamine, one unidentified aminolipid and three unidentified lipids. Based on 16S rRNA gene sequence similarities, the type strains of Cyclobacterium amurskyense, Cyclobacterium marinum and Cyclobacterium lianum were most closely related to M12-11B(T) with sequence similarities of 98.2, 96.8 and 93.3 %, respectively. Other members of the family Cyclobacteriaceae had sequence similarities of <92.0 %. However, DNA-DNA hybridization with Cyclobacterium amurskyense KCTC 12363(T) and Cyclobacterium marinum DSM 745(T) showed relatedness values of only 24.5 and 32.5 % with respect to strain M12-11B(T). Based on the results of DNA-DNA hybridization experiments and phenotypic and chemotaxonomic data, it appears that strain M12-11B(T) represents a novel species of the genus Cyclobacterium, for which the name Cyclobacterium qasimii sp. nov. is proposed; the type strain is M12-11B(T) (= KCTC 23011(T) = NBRC 106168(T)) and it has a DNA G+C content of 40.5 mol%.
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Oceanisphaera arctica sp. nov., isolated from Arctic marine sediment, and emended description of the genus Oceanisphaera.
Int. J. Syst. Evol. Microbiol.
PUBLISHED: 10-14-2011
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A novel Gram-staining-negative, coccoid, non-motile bacterium, designated strain V1-41(T), was isolated from a sample of marine sediment collected, at a depth of 200 m, from Kongsfjorden (an inlet on the west coast of Spitsbergen, an island that forms part of the Svalbard archipelago in the Arctic Ocean). The strain formed cream-brown colonies on marine agar. Cells of the novel strain were positive in tests for catalase, oxidase, lysine decarboxylase and ornithine decarboxylase activities but negative for gelatinase and lipase activities. They hydrolysed aesculin, starch and urea, but not casein or DNA. Most of the cellular fatty acids were medium-chain and saturated (37.1%) or long-chain and unsaturated (27.8%), with C(12:0) (37.1%), C(18:1)?7c, and summed features 2 (19.3%) and 3 (24.1%) predominating. The major respiratory quinone was Q-8. The polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, two unidentified aminophospholipids, four unidentified phospholipids and one other unidentified lipid. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the novel strains closest known relatives were Oceanisphaera litoralis DSM 15406(T) (98.5% sequence similarity) and Oceanisphaera donghaensis BL1(T) (98.3%). In DNA-DNA hybridizations, however, the levels of relatedness between strain V1-41(T) and O. litoralis DSM 15406(T) and between the novel strain and O. donghaensis DSM 17589(T) were found to be only 19% and 29%, respectively. Based on these low levels of similarity at the DNA-DNA level and the phenotypic and chemotaxonomic differences from O. litoralis DSM 15406(T) and O. donghaensis DSM 17589(T), strain V1-41(T) represents a novel species of the genus Oceanisphaera for which the name Oceanisphaera arctica sp. nov. is proposed. The type strain is V1-41(T) (?=?CCUG 58690(T)?=?KCTC 23013(T)?=?NBRC 106171(T)).
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Distinct classes of c-Kit-activating mutations differ in their ability to promote RUNX1-ETO-associated acute myeloid leukemia.
Blood
PUBLISHED: 09-21-2011
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The t(8;21) RUNX1-ETO translocation is one of the most frequent cytogenetic abnormalities in acute myeloid leukemia (AML). In RUNX1-ETO(+) patient samples, differing classes of activating c-KIT receptor tyrosine kinase mutations have been observed. The most common (12%-48%) involves mutations, such as D816V, which occur in the tyrosine kinase domain, whereas another involves mutations within exon 8 in a region mediating receptor dimerization (2%-13% of cases). To test whether distinct subtypes of activating c-KIT mutations differ in their leukemogenic potential in association with RUNX1-ETO, we used a retroviral transduction/transplantation model to coexpress RUNX1-ETO with either c-Kit(D814V) or c-Kit(T417I?418-419) in murine hematopoietic stem/progenitor cells used to reconstitute lethally irradiated mice. Analysis of reconstituted animals showed that RUNX1-ETO;c-Kit(D814V) coexpression resulted in 3 nonoverlapping phenotypes. In 45% of animals, a transplantable AML of relatively short latency and frequent granulocytic sarcoma was noted. Other mice exhibited a rapidly fatal myeloproliferative phenotype (35%) or a lethal, short-latency pre-B-cell leukemia (20%). In contrast, RUNX1-ETO;c-Kit(T417I?418-419) coexpression promoted exclusively AML in a fraction (51%) of reconstituted mice. These observations indicate that c-Kit(D814V) promotes a more varied and aggressive leukemic phenotype than c-Kit(T417I?418-419), which may be the result of differing potencies of the activating c-Kit alleles.
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Extramedullary hematopoiesis: an unusual finding in subdural hematomas.
Case Rep Pathol
PUBLISHED: 06-30-2011
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We present a case of a 59-year-old man who was found to have clusters of hyperchromatic, small, round nucleated cells within a subdural hematoma removed after a skull fracture. Immunohistochemistry study confirmed that the cells were hematopoietic components predominantly composed of normoblasts. In this paper, we describe the clinical and pathological findings. A brief review of published information on extramedullary hematopoiesis in subdural hematoma and the mechanisms of pathogenesis are also discussed. While extramedullary hematopoiesis is seen anecdotally by neuropathologists in chronic subdural hematomas, only a few cases are documented in the literature. Furthermore, extramedullary hematopoiesis in subdural hematoma can pose a diagnostic challenge for general pathologists who encounter subdural hematoma evacuations seldom in their surgical pathology practices.
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Acute induction of autophagy as a novel strategy for cardioprotection: getting to the heart of the matter.
Autophagy
PUBLISHED: 04-01-2011
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There is no question that necrosis and apoptosis contribute to cardiomyocyte death in the setting of myocardial ischemia-reperfusion. Indeed, considerable effort and resources have been invested in the development of novel therapies aimed at attenuating necrotic and apoptotic cell death, with the ultimate goal of applying these strategies to reduce infarct size and improve outcome in patients suffering acute myocardial infarction (MI) or heart attack. However, an issue that remains controversial is the role of autophagy in determining the fate of ischemic-reperfused cardiomyocytes: i.e., is induction of autophagy detrimental or protective? Recent data from our group obtained in the clinically relevant, in vivo swine model of acute MI provides novel evidence of a positive association between pharmacological upregulation of autophagy (achieved by administration of chloramphenicol succinate (CAPS)) and increased resistance to myocardial ischemia-reperfusion injury.
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Metastatic inflammatory myofibroblastic tumor identified by EUS-FNA in mediastinal lymph nodes with ancillary FISH studies for ALK rearrangement.
Diagn. Cytopathol.
PUBLISHED: 01-12-2011
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Inflammatory myofibroblastic tumor (IMT) is an exquisitely rare neoplasm with a low incidence of metastasis. Previously, cytologic diagnosis of this entity, by fine needle aspiration (FNA) or endoscopic ultrasound guided fine needle aspiration (EUS-FNA), was challenging, if not impossible. However, advancements in the field of molecular pathology, the applications of which have lagged in cytopathology relative to other disciplines, now makes diagnosis possible. Here we report a case of pulmonary inflammatory myofibroblastic tumor with mediastinal nodal metastasis in a 74-year-old man, definitively diagnosed by EUS-FNA utilizing morphologic, immunohistochemical, and molecular findings, including fluorescent in situ hybridization studies for ALK gene rearrangement. This case report demonstrates the value of ancillary molecular studies to assist in the diagnosis of rare neoplasms, including those at sites of metastasis.
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Profound cardioprotection with chloramphenicol succinate in the swine model of myocardial ischemia-reperfusion injury.
Circulation
PUBLISHED: 09-15-2010
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Emerging evidence suggests that "adaptive" induction of autophagy (the cellular process responsible for the degradation and recycling of proteins and organelles) may confer a cardioprotective phenotype and represent a novel strategy to limit ischemia-reperfusion injury. Our aim was to test this paradigm in a clinically relevant, large animal model of acute myocardial infarction.
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Retraction. Oceanisphaera arctica sp. nov., isolated from a marine sediment of Kongsfjorden, Svalbard, Arctic.
Int. J. Syst. Evol. Microbiol.
PUBLISHED: 08-24-2010
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A novel Gram-negative, coccoid shaped, non-motile bacterium, designated strain V1-41T, was isolated from a marine sediment sample collected at a depth of 200 m from Kongsfjorden, Svalbard, Arctic. The cell suspension was brownish. Cells of the strain V1-41T are positive for catalase, oxidase, lysine decarboxylase and ornithine decarboxylase and negative for gelatinase and lipase. Cells of V1-41T hydrolyze esculin, starch and urea but not casein and DNA. The fatty acids were dominated by saturated fatty acids (81.9%), with a high abundance of C12 : 0 (44.5%), anteiso-C14 : 0 (12%), C15 : 0 (7%), C16 : 0 (16.6%), and C16 : 1omega9c (17.7%). Strain V1-41T contains MK-4 and one unidentified quinone as the major respiratory quinones and diphosphatidylglycerol and phosphatidylglycerol make up the phospholipid composition. The 16S rRNA gene sequence analysis indicated that Oceanisphaera litoralis and Oceanisphaera donghaensis are the closest related species, with a sequence similarity of 98.3 and 98.5 % respectively with strain V1-41T. But, DNA-DNA hybridization with Oceanisphaera litoralis DSM 15406T and Oceanisphaera donghaensis DSM 17589T showed a relatedness of only 19 and 29% with respect to strain V1-41T. Based on the low level of similarity at the DNA-DNA level and phenotypic and chemotaxonomic differences with Oceanisphaera litoralis DSM 15406T and Oceanisphaera donghaensis DSM 17589T strain V1-41T is proposed as a novel species of the genus Oceanisphaera, for which the name Oceanisphaera arctica sp. nov. is proposed. The type strain of Oceanisphaera arctica sp. nov. is V1-41T (=KCTC 23013T = NBRC 106171T).
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Development of combination tapered fiber-optic biosensor dip probe for quantitative estimation of interleukin-6 in serum samples.
J Biomed Opt
PUBLISHED: 08-09-2010
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A combination tapered fiber-optic biosensor (CTFOB) dip probe for rapid and cost-effective quantification of proteins in serum samples has been developed. This device relies on diode laser excitation and a charged-coupled device spectrometer and functions on a technique of sandwich immunoassay. As a proof of principle, this technique was applied in a quantitative estimation of interleukin IL-6. The probes detected IL-6 at picomolar levels in serum samples obtained from a patient with lupus, an autoimmune disease, and a patient with lymphoma. The estimated concentration of IL-6 in the lupus sample was 5.9 ± 0.6 pM, and in the lymphoma sample, it was below the detection limit. These concentrations were verified by a procedure involving bead-based xMAP technology. A similar trend in the concentrations was observed. The specificity of the CTFOB dip probes was assessed by analysis with receiver operating characteristics. This analysis suggests that the dip probes can detect 5-pM or higher concentration of IL-6 in these samples with specificities of 100%. The results provide information for guiding further studies in the utilization of these probes to quantify other analytes in body fluids with high specificity and sensitivity.
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Phase II study of dose-intense chemotherapy with sequential topoisomerase-targeting regimens with irinotecan/oxaliplatin followed by etoposide/carboplatin in chemotherapy naive patients with extensive small cell lung cancer.
Lung Cancer
PUBLISHED: 05-14-2010
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Topoisomerase inhibitors are active agents in small cell lung cancer (SCLC), and preclinical models indicate that sequential administration of a topoisomerase I inhibitor followed by a topoisomerase II inhibitor can result in enhanced cytotoxicity.
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Intranasal eosinophilic angiocentric fibrosis: a case report and review.
Head Neck Pathol
PUBLISHED: 02-15-2010
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Eosinophilc angiocentric fibrosis is a rare fibrosing vasculitis of unknown etiology that is progressive and potentially disfiguring. It has a predilection for the upper airways presenting most commonly as an obstructing mass lesion that is diagnosed histologically. Thus far, it has been nonfatal in the more than 40 reported cases; however, subglottic and ocular involvement has resulted in significant morbidity in several patients. Treatment has been challenging with persistent disease in most cases. The current case is a prototypical presentation with a limited nasal septal lesion providing the opportunity to discuss clinically relevant issues and increase awareness.
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Quantitative Estimation of IL-6 in Serum/Plasma Samples Using a Rapid and Cost-Effective Fiber-Optic dip-probe.
Proc Soc Photo Opt Instrum Eng
PUBLISHED: 01-23-2010
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A rapid and cost-effective combination tapered fiber-optic biosensor (CTFOB) dip-probe was used for quantitative estimation of interleukin (IL)-6 in serum/plasma samples. Sandwich immunoassay was used as the detection technique. Probes could successfully detect presence of IL-6 in two serum samples, non-neoplastic autoimmune patient (lupus) sample and lymphoma patient sample. The estimated amount of IL-6 in lupus patient sample was 4.8 ± 0.9 pM and in lymphoma patient sample was 2 ± 1 pM. It is demonstrated that the developed CTFOB dip-probe is capable of quantitative estimation of proteins in serum/plasma samples with high specificity.
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Solitary plaque on the scalp as a primary manifestation of Hodgkin lymphoma: a case report and review of the literature.
J. Cutan. Pathol.
PUBLISHED: 09-25-2009
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Cutaneous Hodgkin lymphoma is infrequent and typically occurs after extensive involvement of the lymph nodes. The condition decreased significantly in incidence in the past two decades, likely owing to the new treatment protocols composed of chemotherapy, radiotherapy and stem cell transplantation. Nevertheless, recognition of this uncommon but significant disease manifestation is important from a prognostic and therapeutic perspective. We are sharing a recent case of Hodgkin lymphoma where the primary presentation appeared as a solitary plaque on the left side of the occipital scalp, clinically suspected to represent a ruptured follicular cyst. The patient underwent excisional biopsy. Histological assessment revealed Hodgkin lymphoma affecting the skin. Radiological studies showed no regional lymphadenopathy. However, two enlarged lymph nodes were identified in the mediastinum and were positron emission tomography avid. The patient underwent systemic treatment without further histopathological examination of these two lymph nodes. Not being clear if these enlarged two lymph nodes were related to his cutaneous disease or not, we cannot be sure if the patient was afflicted either by primary cutaneous Hodgkin lymphoma or by secondary cutaneous involvement because of hematogenous spread. In either case, primary or secondary cutaneous Hodgkin disease is an extreme rarity. The literature is critically reviewed.
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Synthesis and evaluation of a novel class of G-quadruplex-stabilizing small molecules based on the 1,3-phenylene-bis(piperazinyl benzimidazole) system.
Biochemistry
PUBLISHED: 09-08-2009
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Achieving stabilization of telomeric DNA in G-quadruplex conformation by various organic compounds has been an important goal for the medicinal chemists seeking to develop new anticancer agents. Several compounds are known to stabilize G-quadruplexes. However, relatively few are known to induce their formation and/or alter the topology of the preformed quadruplex DNA. Herein, four compounds having the 1,3-phenylene-bis(piperazinyl benzimidazole) unit as a basic skeleton have been synthesized, and their interactions with the 24-mer telomeric DNA sequences from Tetrahymena thermophilia d(T(2)G(4))(4) have been investigated using high-resolution techniques such as circular dichroism (CD) spectropolarimetry, CD melting, emission spectroscopy, and polyacrylamide gel electrophoresis. The data obtained, in the presence of one of three ions (Li(+), Na(+), or K(+)), indicate that all the new compounds have a high affinity for G-quadruplex DNA, and the strength of the binding with G-quadruplex depends on (i) phenyl ring substitution, (ii) the piperazinyl side chain, and (iii) the type of monovalent cation present in the buffer. Results further suggest that these compounds are able to abet the conversion of the intramolecular quadruplex into parallel stranded intermolecular G-quadruplex DNA. Notably, these compounds are also capable of inducing and stabilizing the parallel stranded quadruplex from randomly structured DNA in the absence of any stabilizing cation. The kinetics of the structural changes induced by these compounds could be followed by recording the changes in the CD signal as a function of time. The implications of the findings mentioned above are discussed in this paper.
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Bacterial diversity and bioprospecting for cold-active lipases, amylases and proteases, from culturable bacteria of kongsfjorden and Ny-alesund, Svalbard, Arctic.
Curr. Microbiol.
PUBLISHED: 06-19-2009
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Culturable bacterial diversity of seven marine sediment samples of Kongsfjorden and a sediment and a soil sample from Ny-Alesund, Svalbard, Arctic was studied. The bacterial abundance in the marine sediments of Kongsfjorden varied marginally (0.5 x 10(3)-1.3 x 10(4) cfu/g sediment) and the bacterial number in the two samples collected from the shore of Ny-Alesund also was very similar (0.6 x 10(4) and 3.4 x 10(4), respectively). From the nine samples a total of 103 bacterial isolates were obtained and these isolates could be grouped in to 47 phylotypes based on the 16S rRNA gene sequence belonging to 4 phyla namely Actinobacteria, Bacilli, Bacteroidetes and Proteobacteria. Representatives of the 47 phylotypes varied in their growth temperature range (4-37 degrees C), in their tolerance to NaCl (0.3-2 M NaCl) and growth pH range (2-11). Representatives of 26 phylotypes exhibited amylase and lipase activity either at 5 or 20 degrees C or at both the temperatures. A few of the representatives exhibited amylase and/or lipase activity only at 5 degrees C. None of the phylotypes exhibited protease activity. Most of the phylotypes (38) were pigmented. Fatty acid profile studies indicated that short chain fatty acids, unsaturated fatty acids, branched fatty acids, the cyclic and the cis fatty acids are predominant in the psychrophilic bacteria.
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Bacterial diversity and bioprospecting for cold-active enzymes from culturable bacteria associated with sediment from a melt water stream of Midtre Lovenbreen glacier, an Arctic glacier.
Res. Microbiol.
PUBLISHED: 05-15-2009
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Culturable bacterial diversity of Midtre Lovenbreen glacier, an Arctic glacier, was studied using 12 sediment samples collected from different points, along a transect, from the snout of Midtre Lovenbreen glacier up to the convergence point of the melt water stream with the sea. Bacterial abundance appeared to be closer to the convergence point of the glacial melt water stream with the sea than at the snout of the glacier. A total of 117 bacterial strains were isolated from the sediment samples. Based on 16S rRNA gene sequence analyses, the isolates (n=117) could be categorised in to 32 groups, with each group representing a different taxa belonging to 4 phyla (Actinobacteria, Bacilli, Flavobacteria and Proteobacteria). Representatives of the 32 groups varied in their growth temperature range (4-37 degrees C), in their tolerance to NaCl (0.1-1M NaCl) and in the growth pH range (2-13). Only 14 of 32 representative strains exhibited amylase, lipase and (or) protease activity and only one isolate (AsdM4-6) showed all three enzyme activities at 5 and 20 degrees C respectively. More than half of the isolates were pigmented. Fatty acid profile studies indicated that short-chain fatty acids, unsaturated fatty acids, branched fatty acids, cyclic and cis fatty acids are predominant in the psychrophilic bacteria.
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Primary cutaneous peripheral T-cell lymphoma with aberrant coexpression of CD20: case report and review of the literature.
Am J Dermatopathol
PUBLISHED: 03-26-2009
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We report an unusual case of primary cutaneous T-cell lymphoma in a 45-year-old male showing expression of the B-cell marker CD20. The lesion presented as a large plaque on the right shin and rapidly developed into additional lesions on the right lower leg and right anterior chest. Despite therapy, bone involvement was discovered at 1 year after initial presentation. Punch biopsy of the right leg revealed a diffuse, atypical dermal lymphocytic infiltrate with papillary edema and no epidermotropism. The atypical cells strongly expressed the T-cell markers CD3, CD2, and CD43, with additional expression of cytotoxic T-cell markers CD8, cytotoxic granule-associated RNA binding protein (TIA-1), and granzyme B and loss of CD7 by immunohistochemistry (IHC). In addition, the atypical cells with the above phenotype exhibited moderate expression of CD20 by IHC. Coexpression of CD8 and CD20 in the atypical cells was confirmed by a dual-labeled IHC stain. Clonal rearrangements of the T-cell receptor gamma- and beta-chain genes were detected by polymerase chain reaction; however, there was no expression of T-cell receptor beta-chain identified by IHC. In conclusion, we present a case a of CD8-positive primary cutaneous T-cell lymphoma with CD20 expression, exhibiting aggressive behavior.
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Prevalence of elevated hemoglobin A2 measured by the CAPILLARYS system.
Am. J. Clin. Pathol.
PUBLISHED: 01-23-2009
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Hemoglobin (Hb) A2 electrophoresis has been used for prenatal screening for the beta-thalassemia trait (betaTT). We retrospectively reviewed Hb capillary electrophoresis performed in our laboratory. We found that of the 122 cases showing elevated HbA2 levels, 79 cases were due to hemoglobinopathies, mostly HbS. Review of the RBC indices suggested that 3 of 36 cases with elevation of HbA2 in the HbAA-pregnancy group had betaTT and 29 had normal RBC indices; data were not available for 4 patients. Among 7 cases with elevation of HbA2 in the HbAA-other group, 5 had betaTT and 2 were normal. The number of patients without betaTT but with HbA2 elevation in the pregnant group was significantly higher than that in the nonpregnant group. When a higher HbA2 cutoff (3.5%) was used, only 3 pregnant patients without betaTT had HbA2 elevation, similar to the nonpregnant group. We found that a significant number of pregnant women with mild HbA2 elevation had no evidence of betaTT, compared with the nonpregnant group.
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Bortezomib successfully reduces monoclonal serum free light chain levels in a patient with recurrent myeloma and cast nephropathy in the renal transplant.
Clin Transpl
PUBLISHED: 01-01-2009
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Bortezomib can be used to successfully treat acute kidney injury in the renal transplant allograft due to light chain cast nephropathy from recurrent multiple myeloma.
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Adult onset Stills disease: experience from a tertiary care rheumatology unit.
Int J Rheum Dis
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Adult-onset Stills disease (AOSD) is a rare chronic inflammatory disorder presenting with prolonged fever and polyarthritis.
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Antarctic ice core samples: culturable bacterial diversity.
Res. Microbiol.
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Culturable bacterial abundance at 11 different depths of a 50.26 m ice core from the Tallaksenvarden Nunatak, Antarctica, varied from 0.02 to 5.8 × 10(3) CFU ml(-1) of the melt water. A total of 138 bacterial strains were recovered from the 11 different depths of the ice core. Based on 16S rRNA gene sequence analyses, the 138 isolates could be categorized into 25 phylotypes belonging to phyla Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria. All isolates had 16S rRNA sequences similar to previously determined sequences (97.2-100%). No correlation was observed in the distribution of the isolates at the various depths either at the phylum, genus or species level. The 25 phylotypes varied in growth temperature range, tolerance to NaCl, growth pH range and ability to produce eight different extracellular enzymes at either 4 or 18 °C. Iso-, anteiso-, unsaturated and saturated fatty acids together constituted a significant proportion of the total fatty acid composition.
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Elemental mapping by Dawn reveals exogenic H in Vestas regolith.
Science
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Using Dawns Gamma Ray and Neutron Detector, we tested models of Vestas evolution based on studies of howardite, eucrite, and diogenite (HED) meteorites. Global Fe/O and Fe/Si ratios are consistent with HED compositions. Neutron measurements confirm that a thick, diogenitic lower crust is exposed in the Rheasilvia basin, which is consistent with global magmatic differentiation. Vestas regolith contains substantial amounts of hydrogen. The highest hydrogen concentrations coincide with older, low-albedo regions near the equator, where water ice is unstable. The young, Rheasilvia basin contains the lowest concentrations. These observations are consistent with gradual accumulation of hydrogen by infall of carbonaceous chondrites--observed as clasts in some howardites--and subsequent removal or burial of this material by large impacts.
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Extracavitary KSHV-associated large B-Cell lymphoma: a distinct entity or a subtype of primary effusion lymphoma? Study of 9 cases and review of an additional 43 cases.
Am. J. Surg. Pathol.
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Primary effusion lymphoma (PEL) is a rare form of aggressive B-cell lymphoma in HIV patients, which typically presents with lymphomatous effusions in the body cavities without forming mass lesions. PEL is associated with Kaposi sarcoma-associated herpesvirus (KSHV) (also called human herpesvirus-8) with distinct clinical and pathologic features. Rare cases of KSHV-associated large B-cell lymphoma (KSHV-LBL) have been observed in the lymph nodes or extranodal sites without lymphomatous effusions during the course of disease. KSHV-LBL is generally similar to classic PEL on the basis of the clinical presentation (HIV(+) male), morphology (immunoblastic, plasmablastic, or anaplastic), immunophenotype (CD45(+), CD20(-), CD79a(-), CD30(+), CD138(+), and EMA(+)), presence of Epstein-Barr virus infection, and clonal immunoglobulin gene rearrangements. However, it is not clear whether KSHV-LBL is a distinct entity or represents part of the spectrum of classic PEL; in particular, there is no consensus diagnostic term for KSHV-LBL. In this study, we investigated the clinicopathologic features of 9 cases of KSHV-LBL from our files. An additional 43 such cases and 84 cases of classic PEL from the English literature were reviewed and compared with each other. In contrast to the classic PEL, KSHV-LBL had a very significant lower expression of CD45 (74% vs. 94%, P=0.004) but significant higher expression of CD20 (17% vs. 5%, P=0.04) and CD138 (70% vs. 38%, P=0.05). KSHV-LBL also had slightly higher positivity of CD79a (23% vs. 5%, P=0.13) and immunoglobulin light chain expression, although the difference was not statistically significant [? chain (12% vs. 0%) and ? chain (31% vs. 21%)]. The expressions of EMA and CD30 were slightly lower in KSHV-LBL compared with those observed in PEL (57% vs. 75% and 63% vs. 76%, respectively). Interestingly, 29% (10/34) of cases of KSHV-LBL revealed aberrant CD3 expression, which may mislead to a diagnosis of T-cell lymphoma, particularly anaplastic large cell lymphoma in combination with the anaplastic morphology and expression of CD30 and EMA. Although KSHV-LBL shows different clinical presentations and some variations in immunophenotype from classic PEL, it is still uncertain, on the basis of our findings, whether it is justifiable to separate them as 2 distinct entities. Nevertheless, we feel it is necessary to have a consensus diagnostic term, and we recommend a tentative one as "KSHV-associated large B-cell lymphoma (KSHV-LBL)" to replace many different names previously used.
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Endoscopic ultrasound and endobronchial ultrasound-guided fine-needle aspiration of deep-seated lymphadenopathy: Analysis of 1338 cases.
Cytojournal
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We retrospectively studied 1338 samples of lymph nodes obtained by endoscopic and endobronchial ultrasound-guided fine needle aspiration biopsy (EUS and EBUS-FNAB) with an objective of characterizing the utility of this diagnostic modality in the assessment of deep-seated lymphadenopathy. The secondary aims were to establish the utility in the diagnosis of lymphoma and to determine the number of passes required to obtain adequate cellularity for flow cytometric analysis.
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Color and albedo heterogeneity of Vesta from Dawn.
Science
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Multispectral images (0.44 to 0.98 ?m) of asteroid (4) Vesta obtained by the Dawn Framing Cameras reveal global color variations that uncover and help understand the north-south hemispherical dichotomy. The signature of deep lithologies excavated during the formation of the Rheasilvia basin on the south pole has been preserved on the surface. Color variations (band depth, spectral slope, and eucrite-diogenite abundance) clearly correlate with distinct compositional units. Vesta displays the greatest variation of geometric albedo (0.10 to 0.67) of any asteroid yet observed. Four distinct color units are recognized that chronicle processes--including impact excavation, mass wasting, and space weathering--that shaped the asteroids surface. Vestas color and photometric diversity are indicative of its status as a preserved, differentiated protoplanet.
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CD138 (syndecan-1) expression in bone-forming tumors.
Am. J. Clin. Pathol.
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CD138 (syndecan-1), a cell surface proteoglycan, is sensitive and specific for plasmacytic differentiation in hematologic disorders. Expression of CD138 has been observed in a majority of epithelial neoplasms and, rarely, soft tissue tumors. However, its expression in bone tumors has not been evaluated. We studied CD138 expression in 27 osteosarcomas, 12 benign bone-forming tumors (osteoid osteoma and osteoblastoma), and 17 reactive bone cases. CD138 expression was also evaluated in a tissue microarray (TMA) constructed from 24 osteosarcomas, 24 chondrosarcomas, 12 giant cell tumors of bone, and 9 normal bone samples. Membranous expression of CD138 was found in an average of 31% of osteosarcoma cases (16/51; 14/27 [52%] in in-house cases; 2/24 [8%] in TMA cases) and in 83% of osteoid osteoma/osteoblastoma cases (10/12). Subsequent immunoglobulin ? and ? stains were negative in the CD138+ cases. All cases of chondrosarcoma, giant cell tumor of bone, and normal/reactive bone tested were nonreactive with anti-CD138. Our results show that CD138 reactivity for neoplastic cells in bone is not a definitive marker for plasmacytic origin, and caution is required to interpret CD138+ cells from a bony lesion for which a hematologic etiology has not been established.
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