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Find video protocols related to scientific articles indexed in Pubmed.
Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation for GATA2 Deficiency.
Biol. Blood Marrow Transplant.
PUBLISHED: 08-09-2014
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We treated 14 patients with GATA2 deficiency using a nonmyeloablative allogeneic hematopoietic stem cell transplantation regimen. Four patients received peripheral blood stem cells from matched related donors (MRD), 4 patients received peripheral blood stem cells from matched unrelated donors (URD), 4 patients received hematopoietic stem cells from umbilical cord blood donors (UCB), and 2 patients received bone marrow cells from haploidentical related donors. MRD and URD recipients received conditioning with 3 days of fludarabine and 200 cGy total body irradiation (TBI). Haploidentical related donor recipients and UCB recipients received cyclophosphamide and 2 additional days of fludarabine along with 200 cGY TBI. MRD, URD, and UCB recipients received tacrolimus and sirolimus for post-transplantation immunosuppression, whereas haploidentical recipients received high-dose cyclophosphamide followed by tacrolimus and mycophenolate mofetil. Eight patients are alive with reconstitution of the severely deficient monocyte, B cell, and natural killer cell populations and reversal of the clinical phenotype at a median follow-up of 3.5 years. Two patients (1 URD recipient and 1 UCB recipient) rejected the donor graft and 1 MRD recipient relapsed with myelodysplastic syndrome after transplantation. We are currently using a high-dose conditioning regimen with busulfan and fludarabine in patients with GATA2 deficiency to achieve more consistent engraftment and eradication of the malignant myeloid clones.
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Protective effects of middle school comprehensive sex education with family involvement.
J Sch Health
PUBLISHED: 03-11-2014
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School-based comprehensive sex education programs can reduce early adolescents' risky sexual behavior. The purpose of this study was to assess the effectiveness of a 3-year comprehensive sex education program in delaying vaginal sex for middle school students and whether the family component of the intervention contributes to its effectiveness.
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A panel of biomarkers is associated with increased risk of the presence and progression of atherosclerosis in women with systemic lupus erythematosus.
PUBLISHED: 01-23-2014
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An increased frequency of atherosclerosis (ATH) in systemic lupus erythematosus (SLE) is well-documented but not fully explained by the presence of traditional cardiac risk factors. Several nontraditional biomarkers, including proinflammatory high-density lipoprotein (piHDL) and leptin, have been individually associated with subclinical ATH in SLE. The aim of this study was to examine whether these and other biomarkers can be combined into a risk profile, the Predictors of Risk for Elevated Flares, Damage Progression, and Increased Cardiovascular Disease in Patients with SLE (PREDICTS), that could be used to better predict future progression of ATH.
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Choice of method for endotoxin detection depends on nanoformulation.
Nanomedicine (Lond)
PUBLISHED: 12-20-2013
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Aims: Many nanoparticles interfere with traditional tests to quantify endotoxin. The aim of this study was to compare the performance of limulus amoebocyte lysate (LAL) formats on clinical-grade nanoformulations, to determine whether there were disparate results among formats and to test the applicability of an alternative bioassay (the macrophage activation test [MAT]) for resolving discrepancies, if observed. Materials & methods: Clinical-grade nanoformulations were tested using turbidimetric, gel-clot and chromogenic LAL. Formulations that cause a discrepancy among LAL tests were also tested by the MAT. Results & conclusion: The gel-clot LAL method cannot be relied upon to resolve discrepancies among LAL tests for certain nanoformulations. No one LAL format was shown to be optimal for all the tested clinical-grade nanoformulations. The tested alternative bioassay (the MAT) was useful for verifying LAL findings, but only for those nanoformulations not carrying/including cytotoxic drugs. Original submitted 1 March 2013; Revised submitted 13 August 2013.
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Family homework and school-based sex education: delaying early adolescents sexual behavior.
J Sch Health
PUBLISHED: 10-22-2013
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Early sexual activity can undermine adolescents future school success and health outcomes. The purpose of this study was to assess the role of a family homework component of a comprehensive sex education intervention in delaying sexual initiation for early adolescents and to explore what social and contextual factors prevent adolescents from completing these family homework activities.
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Preferential binding to Elk-1 by SLE-associated IL10 risk allele upregulates IL10 expression.
PLoS Genet.
PUBLISHED: 10-01-2013
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Immunoregulatory cytokine interleukin-10 (IL-10) is elevated in sera from patients with systemic lupus erythematosus (SLE) correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s) and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA) (P?=?2.7×10??, OR?=?1.30), but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively), and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G) allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1) detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele upregulates IL10 expression and confers increased risk for SLE in European Americans.
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Adolescents religious discordance with mothers: is there a connection to sexual risk behavior during emerging adulthood?
J Prim Prev
PUBLISHED: 08-07-2013
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This study longitudinally investigates the relationship between adolescent/mother religious discordance and emerging adult sexual risk-taking 6-7 years later. We used Social Control Theory to examine the level and direction of concordance using data from Wave I and Wave III of the Add Health Study, focusing on constructs of religious importance, frequency of prayer, and attendance at religious services. We found that higher levels of adolescent/mother discordance in religious importance were related to increased emerging adult sexual risk-taking compared to those with similar levels adolescent/mother religiosity, but this occurred only when mothers reported higher levels of religious importance than their children. In contrast, adolescents reporting higher frequency of prayer than their mothers reported lower levels of sexual risk-taking than those with similar frequency of adolescent/mother prayer. These findings suggest that the protective effects of family religious socialization can be interrupted. However, this influence of religious difference on sexual risk-behavior operates differently depending on the direction and level of religious difference. Even in emerging adulthood, a period marked by distance from childhood values and institutions, religious difference with a parent remains a meaningful influence.
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Common pitfalls in nanotechnology: lessons learned from NCIs Nanotechnology Characterization Laboratory.
Integr Biol (Camb)
PUBLISHED: 06-26-2013
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The Nanotechnology Characterization Laboratorys (NCL) unique set-up has allowed our lab to handle and test a variety of nanoparticle platforms intended for the delivery of cancer therapeutics and/or imaging contrast agents. Over the last six years, the NCL has characterized more than 250 different nanomaterials from more than 75 different investigators. These submitted nanomaterials stem from a range of backgrounds and experiences, including government, academia and industry. This has given the NCL a unique and valuable opportunity to observe trends in nanoparticle safety and biocompatibility, as well as note some of the common mistakes and oversights of nanoformulation. While not exhaustive, this article aims to share some of the most common pitfalls observed by the NCL as they relate to nanoparticle synthesis, purification, characterization and analysis.
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Plasma levels of osteopontin identify patients at risk for organ damage in systemic lupus erythematosus.
Arthritis Res. Ther.
PUBLISHED: 01-02-2013
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ABSTRACT: INTRODUCTION: Osteopontin (OPN) has been implicated as a mediator of Th17 regulation via type I interferon (IFN) receptor signaling and in macrophage activity at sites of tissue repair. This study assessed whether increased circulating plasma OPN (cOPN) precedes development of organ damage in pediatric systemic lupus erythematosus (pSLE) and compared it to circulating plasma neutrophil gelatinase-associated lipocalin (cNGAL), a predictor of increased SLE disease activity. METHODS: cOPN and cNGAL were measured in prospectively followed pSLE (n = 42) and adult SLE (aSLE; n = 23) patients and age-matched controls. Time-adjusted cumulative disease activity and disease damage were respectively assessed using adjusted-mean SLE disease activity index (SLEDAI) (AMS) and SLICC/ACR damage index (SDI). RESULTS: Compared to controls, elevated cOPN and cNGAL were observed in pSLE and aSLE. cNGAL preceded worsening SLEDAI by 3-6 months (P = 0.04), but was not associated with increased 6-month AMS. High baseline cOPN, which was associated with high IFNalpha activity and expression of autoantibodies to nucleic acids, positively correlated with 6-month AMS (r = 0.51 and 0.52, P = 0.001 and 0.01 in pSLE and aSLE, respectively) and was associated with SDI increase at 12 months in pSLE (P = 0.001). Risk factors for change in SDI in pSLE were cOPN (OR 7.5, 95% CI [2.9-20], P = 0.03), but not cNGAL, cumulative prednisone, disease duration, immunosuppression use, gender or ancestry using univariate and multivariate logistic regression. The area under the curve (AUC) when generating the receiver-operating characteristic (ROC) of baseline cOPN sensitivity and specificity for the indication of SLE patients with an increase of SDI over a 12 month period is 0.543 (95% CI 0.347-0.738; positive predictive value 95% and negative predictive value 38%). CONCLUSION: High circulating OPN levels preceded increased cumulative disease activity and organ damage in SLE patients, especially in pSLE, and its value as a predictor of poor outcome should be further validated in large longitudinal cohorts.
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High plasma leptin levels confer increased risk of atherosclerosis in women with systemic lupus erythematosus, and are associated with inflammatory oxidised lipids.
Ann. Rheum. Dis.
PUBLISHED: 06-13-2011
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Patients with systemic lupus erythematosus (SLE) are at increased risk of atherosclerosis, even after accounting for traditional risk factors. High levels of leptin and low levels of adiponectin are associated with both atherosclerosis and immunomodulatory functions in the general population.
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Association of PPP2CA polymorphisms with systemic lupus erythematosus susceptibility in multiple ethnic groups.
Arthritis Rheum.
PUBLISHED: 05-19-2011
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T cells from patients with systemic lupus erythematosus (SLE) express increased amounts of PP2Ac, which contributes to decreased production of interleukin-2 (IL-2). Because IL-2 is important in the regulation of several aspects of the immune response, it has been proposed that PP2Ac contributes to the expression of SLE. This study was designed to determine whether genetic variants of PPP2AC are linked to the expression of SLE and specific clinical manifestations and account for the increased expression of PP2Ac.
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Association of a functional IRF7 variant with systemic lupus erythematosus.
Arthritis Rheum.
PUBLISHED: 03-02-2011
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A previous genome-wide association study conducted in a population of European ancestry identified rs4963128, a KIAA1542 single-nucleotide polymorphism (SNP) 23 kb telomeric to IRF7 (the gene for interferon regulatory factor 7 [IRF-7]), to be strongly associated with systemic lupus erythematosus (SLE). This study was undertaken to investigate whether genetic polymorphism within IRF7 is a risk factor for the development of SLE.
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Osteoporosis prevention.
Curr Opin Rheumatol
PUBLISHED: 01-22-2011
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Patients with osteoporosis suffer from the morbidity and mortality associated with resultant fractures. The number of persons at risk for fractures is increasing as the US population ages. This review addresses preventive strategies that can be used to decrease the risk of minimal trauma fractures.
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Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility.
PLoS Genet.
PUBLISHED: 01-18-2011
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Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Variants of genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) within the chromosome 1q32 locus linked to SLE, have been associated with multiple human diseases and may contribute to dysregulated complement activation predisposing to SLE. We assessed 60 SNPs covering the CFH-CFHRs region for association with SLE in 15,864 case-control subjects derived from four ethnic groups. Significant allelic associations with SLE were detected in European Americans (EA) and African Americans (AA), which could be attributed to an intronic CFH SNP (rs6677604, in intron 11, P(meta)?=?6.6×10(-8), OR?=?1.18) and an intergenic SNP between CFHR1 and CFHR4 (rs16840639, P(meta)?=?2.9×10(-7), OR?=?1.17) rather than to previously identified disease-associated CFH exonic SNPs, including I62V, Y402H, A474A, and D936E. In addition, allelic association of rs6677604 with SLE was subsequently confirmed in Asians (AS). Haplotype analysis revealed that the underlying causal variant, tagged by rs6677604 and rs16840639, was localized to a ~146 kb block extending from intron 9 of CFH to downstream of CFHR1. Within this block, the deletion of CFHR3 and CFHR1 (CFHR3-1?), a likely causal variant measured using multiplex ligation-dependent probe amplification, was tagged by rs6677604 in EA and AS and rs16840639 in AA, respectively. Deduced from genotypic associations of tag SNPs in EA, AA, and AS, homozygous deletion of CFHR3-1? (P(meta)?=?3.2×10(-7), OR?=?1.47) conferred a higher risk of SLE than heterozygous deletion (P(meta)?=?3.5×10(-4), OR?=?1.14). These results suggested that the CFHR3-1? deletion within the SLE-associated block, but not the previously described exonic SNPs of CFH, might contribute to the development of SLE in EA, AA, and AS, providing new insights into the role of complement regulators in the pathogenesis of SLE.
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Sex-specific association of X-linked Toll-like receptor 7 (TLR7) with male systemic lupus erythematosus.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 08-23-2010
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Systemic lupus erythematosus (SLE) is a multisystem, autoimmune disease that predominantly affects women. Previous findings that duplicated Toll-like receptor 7 (Tlr7) promotes lupus-like disease in male BXSB mice prompted us to evaluate TLR7 in human SLE. By using a candidate gene approach, we identified and replicated association of a TLR7 3UTR SNP, rs3853839 (G/C), with SLE in 9,274 Eastern Asians (P(combined) = 6.5 x 10(-10)), with a stronger effect in male than female subjects [odds ratio, male vs. female = 2.33 (95% CI = 1.64-3.30) vs. 1.24 (95% CI = 1.14-1.34); P = 4.1 x 10(-4)]. G-allele carriers had increased TLR7 transcripts and more pronounced IFN signature than C-allele carriers; heterozygotes had 2.7-fold higher transcripts of G-allele than C-allele. These data established a functional polymorphism in type I IFN pathway gene TLR7 predisposing to SLE, especially in Chinese and Japanese male subjects.
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Importance of race and ethnicity: an exploration of Asian, Black, Latino, and multiracial adolescent identity.
Cultur Divers Ethnic Minor Psychol
PUBLISHED: 05-05-2010
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This mixed-method study used a grounded theory approach to explore the meanings underlying the importance that adolescents attach to their racial-ethnic identities. The sample consisted of 923 9th- to 12th-grade students from Black, Latino, Asian, and multiracial backgrounds. Thematic findings identified a broad range of explanations for adolescents racial-ethnic centrality, ranging from pride and cultural connection to ambivalence and colorblind attitudes. While racial-ethnic groups differed in reported levels of racial-ethnic centrality, few group differences were identified in participants thematic explanations, with the exception of racial-ethnic and gender differences for Positive Regard and Disengagement. These findings highlight the diversity of meanings that adolescents attribute to their racial-ethnic centrality as well as the many commonalities among adolescents across gender and racial-ethnic groups.
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Dysfunctional, pro-inflammatory HDL directly upregulates monocyte PDGFR?, chemotaxis and TNF? production.
Clin. Immunol.
PUBLISHED: 04-14-2010
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Accelerated atherosclerosis is a major co-morbid condition in autoimmune diseases. Monocytes are the main immune cell involved in atherosclerosis initiation. We hypothesized that dysfunctional, pro-inflammatory HDL (piHDL), which occurs in approximately half of SLE patients, might directly influence monocyte gene expression and function. SLE subjects were stratified into three groups: 1) carotid artery plaque+piHDL+,2) plaque-piHDL+,and 3) plaque-piHDL- (n=18/group). PDGFR? was upregulated in primary monocytes from plaque+piHDL+patients and in THP-1 cells acutely treated in vitro with piHDL compared to normal HDL. THP-1 chemotaxis was enhanced after treatment with piHDL versus normal HDL. Abnormal migration was restored to normal levels by treatment with imatinib or an apoJ mimetic peptide. Increased piHDL-mediated TNF? protein levels were reduced with both inhibitors. Dysfunctional piHDL directly influences expression of a small number of transcripts and proteins, and piHDL inhibition through reducing piHDL oxidation or blocking PDGFR? kinase activity restored normal monocyte chemotaxis.
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Low physical activity is associated with proinflammatory high-density lipoprotein and increased subclinical atherosclerosis in women with systemic lupus erythematosus.
Arthritis Care Res (Hoboken)
PUBLISHED: 03-02-2010
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To investigate the association between physical activity, functional activity of high-density lipoprotein (HDL), and subclinical cardiovascular disease in patients with systemic lupus erythematosus (SLE).
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Dysfunctional proinflammatory high-density lipoproteins confer increased risk of atherosclerosis in women with systemic lupus erythematosus.
Arthritis Rheum.
PUBLISHED: 08-01-2009
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Women with systemic lupus erythematosus (SLE) have an increased risk of atherosclerosis. Identification of at-risk patients and the etiology underlying atherosclerosis in SLE remain elusive. The antioxidant capacity of normal high-density lipoproteins (HDLs) is lost during inflammation, and these dysfunctional HDLs might predispose individuals to atherosclerosis. The aim of this study was to determine whether dysfunctional proinflammatory HDL (piHDL) is associated with subclinical atherosclerosis in SLE.
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Race, context, and privilege: white adolescents explanations of racial-ethnic centrality.
J Youth Adolesc
PUBLISHED: 07-29-2009
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This mixed-methods exploratory study examined the diverse content and situated context of White adolescents racial-ethnic identities. The sample consisted of 781 9th-12th grade White adolescents from three New England schools, which varied in racial and economic make-up. Open-ended responses provided a range of thematic categories regarding the importance of race-ethnicity to the adolescents identities, representing the diverse ideologies of White adolescents explanations, ranging from colorblind claims to ethnic pride. This study also found significant relationships between racial-ethnic identity importance (centrality) and parents education for White adolescents. These findings highlight the diversity of White adolescents understanding of their racial-ethnic identities and the importance of context in shaping racial-ethnic centrality.
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Lupus arthritis.
Best Pract Res Clin Rheumatol
PUBLISHED: 07-14-2009
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Arthritis in systemic lupus erythematosus (SLE) is one of the most common disease manifestations. Nearly all joints can be affected by SLE, but hand and knee involvement are the most typical. Periarticular structures can be inflamed leading to tendonitis, tenosynovitis and tendon rupture. Avascular necrosis (AVN) also occurs causing joint pain and disability, typically in larger joints such as the hip and knee. This article addresses the clinical features of arthritis in lupus and an approach to the differential diagnosis. Treatment strategies include nonsteroidal anti-inflammatories, corticosteroids, anti-malarials and a variety of immunosuppressive medications.
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Novel autoantibodies against the activated coagulation factor IX (FIXa) in the antiphospholipid syndrome that interpose the FIXa regulation by antithrombin.
J. Immunol.
PUBLISHED: 01-22-2009
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We previously reported that some human antiphospholipid Abs (aPL) in patients with the antiphospholipid syndrome (APS) bind to the homologous enzymatic domains of thrombin and the activated coagulation factor X (FXa). Moreover, some of the reactive Abs are prothrombotic and interfere with inactivation of thrombin and FXa by antithrombin (AT). Considering the enzymatic domain of activated coagulation factor IX (FIXa) is homologous to those of thrombin and FXa, we hypothesized that some aPLs in APS bind to FIXa and hinder AT inactivation of FIXa. To test this hypothesis, we searched for IgG anti-FIXa Abs in APS patients. Once the concerned Abs were found, we studied the effects of the Ab on FIXa inactivation by AT. We found that 10 of 12 patient-derived monoclonal IgG aPLs bound to FIXa and that IgG anti-FIXa Abs in APS patients were significantly higher than those in normal controls (p < 0.0001). Using the mean + 3 SD of 30 normal controls as the cutoff, the IgG anti-FIXa Abs were present in 11 of 38 (28.9%) APS patients. Importantly, 4 of 10 FIXa-reactive monoclonal aPLs (including the B2 mAb generated against beta(2)-glycoprotein I significantly hindered AT inactivation of FIXa. More importantly, IgG from two positive plasma samples were found to interfere with AT inactivation of FIXa. In conclusion, IgG anti-FIXa Ab occurred in approximately 30% of APS patients and could interfere with AT inactivation of FIXa. Because FIXa is an upstream procoagulant factor, impaired AT regulation of FIXa might contribute more toward thrombosis than the dysregulation of the downstream FXa and thrombin.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.