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Find video protocols related to scientific articles indexed in Pubmed.
Cell culture adaptation mutations in foot-and-mouth disease virus serotype A capsid proteins: implications for receptor interactions.
J. Gen. Virol.
PUBLISHED: 11-09-2014
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In this study we describe the adaptive changes fixed on the capsid of several foot-and-mouth disease virus serotype A strains during propagation in cell monolayers. Viruses passaged extensively in three cell lines (BHK-21, LFBK and IB-RS-2), consistently gained positively charged amino acids in the putative heparan sulfate-binding pocket (VP2 ?E-?F loop, VP1 C terminus and VP3 ?-B knob), surrounding the five-fold symmetry axis (VP1 ?F-?G loop) and at other discrete sites on the capsid (VP3 ?G-?H loop, VP1 C terminus, VP2 ?C strand and VP1 ?G-?H loop). A lysine insertion in the VP1 ?F-?G loop of two of the BHK-21 adapted viruses supports the biological advantage of positively charged residues acquired in cell culture. The charge transitions occurred irrespective of cell line suggesting their possible role in ionic interaction with ubiquitous negatively charged cell surface molecules such as glycosaminoglycans (GAG). This was supported by the ability of the cell culture-adapted variants to replicate in the integrin-deficient, GAG-positive CHO-K1 cells and their superior fitness in competition assays compared to the lower passage viruses with wild-type genotypes. Substitutions fixed in the VP1 ?G-?H loop (-3, -2 and +2 'RGD' positions) or in the structural element known to be juxtaposed against that loop (VP1 ?B-?C loop) suggest their possible role in modulating the efficiency and specificity of interaction of 'RGD' motif with ?V-integrin receptors. The nature and location of the substitutions described in this study could be applied in the rapid cell culture adaptation of viral strains for vaccine production.
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In vitro activity of 'Mexican Arnica' Heterotheca inuloides Cass natural products and some derivatives against Giardia intestinalis.
Parasitology
PUBLISHED: 11-04-2014
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SUMMARY Giardiasis is a gastrointestinal disease that affects humans and other animals caused by parasitic protists of the genus Giardia. Giardia intestinalis (Syn. Giardia lamblia; Giardia duodenalis) infections can cause acute or chronic diarrhoea, dehydration, abdominal discomfort and weight loss. Metronidazole is the most widely used drug for treating giardiasis. Although effective, metronidazol has undesirable secondary effects. Plants used in traditional medicine as antidiarrhoeals or antiparasitics may represent alternative sources for new compounds to treat giardiasis. Heterotheca inuloides Cass. (Asteraceae/Compositae) plant is widely used in Mexican traditional medicine. The following secondary metabolites were isolated from H. inuloides flowers: 7-hydroxy-3,4-dihydrocadalene (1), 7-hydroxycadalene (2), 3,7-dihydroxy-3(4H)-isocadalen-4-one (3), 1R,4R-hydroxy-1,2,3,4-tetrahydrocadalen-15-oic acid (4), quercetin (5), quercetin-3,7,3'-trimethyl ether (6), quercetin-3,7,3',4'-tetramethyl ether (7) and eriodictyol-7,4'-dimethyl ether (8). The activity of these compounds against Giardia intestinalis trophozoites was assessed in vitro as was the activity of the semisynthetic compounds 7-acetoxy-3,4-dihydrocadalene (9), 7-benzoxy-3,4-dihydrocadalene (10), 7-acetoxycadalene (11), 7-benzoxycadalene (12), quercetin pentaacetate (13) and 7-hydroxycalamenene (14). Among these, 7-hydroxy-3,4-dihydrocadalene (1) and 7-hydroxycalamenene (14) were the most active, whereas the remaining compounds showed moderate or no activity. The G. intestinalis trophozoites exposed to compound 1 showed marked changes in cellular architecture along with ultrastructural disorganization. The aim of this study was to evaluate the giardicidal activity of selected H. inuloides metabolites and some semisynthetic derivatives using an in vitro experimental model of giardiasis.
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Values of Impulse Oscillometry in Healthy Mexican Children and Adolescents.
Respir Care
PUBLISHED: 10-23-2014
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The impulse oscillometry system (IOS) is increasingly used to evaluate lung function, but individual results must be compared with appropriate reference values. We aimed to obtain such reference values in Mexican children and adolescents.
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Cutaneous Alternaria infectoria infection diagnosed by molecular techniques in a renal transplant patient.
Clin. Lab.
PUBLISHED: 10-09-2014
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Organ transplant recipients under immunosuppressive therapy have a highly increased risk of opportunistic fungal infections. Cutaneous infection caused by Alternaria species are relatively rare in humans and most cases reported in the literature are in immunocompromised individuals. We report here on a 33-year old male renal transplant patient with diabetes mellitus who presented with cutaneous alternariosis caused by Alternaria infectoria, two years after the transplant. The diagnosis was performed by real-time polymerase chain reaction assay and histopathologic examination. The extension of the lesion under itraconazole treatment required treatment consisting of a combination of surgical excision and liposomal amphotericin B.
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Migraine and risk of hemorrhagic stroke: a study based on data from general practice.
J Headache Pain
PUBLISHED: 10-06-2014
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We investigated the association between hemorrhagic stroke and migraine using data from The Health Improvement Network database.
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[Analysis of the prevalence of scoliosis and associated factors in a population of mexican schoolchildren using sifting techniques].
Gac Med Mex
PUBLISHED: 10-03-2014
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It is known that in the last decade, spinal disorders are increasing among children, and this generates high concern in areas of healthcare and educational stakeholders to develop preventative strategies to help curb this trend. This paper intends to go a step further in this direction and to explore factors associated with the presence of scoliosis hump, thus contributing to a better approach in the treatment and prevention of this disease in Mexican schools.
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Osteoprotegerin CGA haplotype protection against cerebrovascular complications in anti-CCP negative patients with rheumatoid arthritis.
PLoS ONE
PUBLISHED: 09-03-2014
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Rheumatoid arthritis is an inflammatory disease with high incidence of cardiovascular disease due to accelerated atherosclerosis. Osteoprotegerin (OPG) has been associated with increased risk of atherosclerotic disease in the general population. Several polymorphisms in the OPG gene with functional effects on cardiovascular disease in non-rheumatic individuals have been described. Therefore, we aimed to analyze the effect of three of these functional OPG polymorphisms on the risk of cardiovascular disease in a large and well-characterized cohort of Spanish patients with rheumatoid arthritis.
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Early events in the pathogenesis of foot-and-mouth disease in pigs; identification of oropharyngeal tonsils as sites of primary and sustained viral replication.
PLoS ONE
PUBLISHED: 09-03-2014
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A time-course study was performed to elucidate the early events of foot-and-mouth disease virus (FMDV) infection in pigs subsequent to simulated natural, intra-oropharyngeal, inoculation. The earliest detectable event was primary infection in the lingual and paraepiglottic tonsils at 6 hours post inoculation (hpi) characterized by regional localization of viral RNA, viral antigen, and infectious virus. At this time FMDV antigen was localized in cytokeratin-positive epithelial cells and CD172a-expressing leukocytes of the crypt epithelium of the paraepiglottic tonsils. De novo replication of FMDV was first detected in oropharyngeal swab samples at 12 hpi and viremia occurred at 18-24 hpi, approximately 24 hours prior to the appearance of vesicular lesions. From 12 through 78 hpi, microscopic detection of FMDV was consistently localized to cytokeratin-positive cells within morphologically characteristic segments of oropharyngeal tonsil crypt epithelium. During this period, leukocyte populations expressing CD172a, SLA-DQ class II and/or CD8 were found in close proximity to infected epithelial cells, but with little or no co-localization with viral proteins. Similarly, M-cells expressing cytokeratin-18 did not co-localize with FMDV proteins. Intra-epithelial micro-vesicles composed of acantholytic epithelial cells expressing large amounts of structural and non-structural FMDV proteins were present within crypts of the tonsil of the soft palate during peak clinical infection. These findings inculpate the paraepiglottic tonsils as the primary site of FMDV infection in pigs exposed via the gastrointestinal tract. Furthermore, the continuing replication of FMDV in the oropharyngeal tonsils during viremia and peak clinical infection with no concurrent amplification of virus occurring in the lower respiratory tract indicates that these sites are the major source of shedding of FMDV from pigs.
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Rheumatoid Arthritis: Genetic Variants as Biomarkers of Cardiovascular Disease.
Curr. Pharm. Des.
PUBLISHED: 08-25-2014
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Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with premature mortality, severe morbidity, and functional impairment leading to considerable financial burden for both patients and society. Since disease progression and complications can differ from one patient to another, genetic markers are of potential relevance for identifying those individuals at a higher risk of more severe disease. RA is a complex polygenic disease. Cardiovascular (CV) disease due to accelerated atherogenesis is the most common cause of premature mortality in patients with RA. Several studies support the implication of genetic factors in the development of CV disease in RA. In addition to the strong association between alleles of the HLA-DRB1*04 shared epitope and both subclinical and clinically evident CV disease, genes implicated in inflammation and metabolism, such as TNFA, MTHFR, and CCR5, seem to be associated with a higher risk of CV disease in patients with RA. We propose the use of these genetic variants as molecular biomarkers that could help to predict disease outcome at diagnosis of RA and, therefore, to optimize the treatment and management of other risk factors from an early stage of the disease.
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Melanoma: diagnosis, staging, and treatment. Consensus group recommendations.
Adv Ther
PUBLISHED: 08-22-2014
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The incidence of malignant melanoma is increasing worldwide. In Spain, its incidence is increasing faster than any other cancer type, with a 5-year survival rate of about 85%. The impact and characteristics of malignant melanoma in the Spanish population can be ascertained from the national melanoma registry of the Academia Española de Dermatología y Venereología. This review presents consensus group recommendations for the diagnosis, staging and treatment of malignant melanoma in Spain. Incidence and mortality are discussed, as well as evaluation of various prevention and treatment strategies. Prognostic factors, such as BRAF and C-KIT mutations, which are expected to become routine staging procedures over the next few years, are outlined, especially in relation to treatment options. The use of recently approved targeted agents such as ipilimumab, a cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitor, and vemurafenib, a BRAF inhibitor, in metastatic disease are also discussed.
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Acral Mycosis Fungoides With Epidermal Microvesiculation Mucinosis.
Am J Dermatopathol
PUBLISHED: 07-23-2014
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: Mycosis fungoides (MF) is the most common type of primary cutaneous T-cell lymphoma. This entity may present with a wide spectrum of clinicopathological manifestations and mimic different dermatoses. Among its histopathological variants, spongiosis is an infrequent finding, and spongiotic microvesiculation is particularly rare. Mucinous deposition is a common event in folliculosebaceous units of folliculotropic MF but rarely described within the epidermis. Herein, we report a patient with eczematous palmoplantar lesions whereby the histological, immunohistochemical, and molecular studies confirmed to be a unique case of MF showing epidermal microvesiculation mucinosis.
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Expression of porcine fusion protein IRF7/3(5D) efficiently controls foot-and-mouth disease virus replication.
J. Virol.
PUBLISHED: 07-16-2014
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Several studies have demonstrated that the delivery of type I, II, or III interferons (IFNs) by inoculation of a replication-defective human adenovirus 5 (Ad5) vector expressing IFNs can effectively control foot-and-mouth disease (FMD) in cattle and swine during experimental infections. However, relatively high doses are required to achieve protection. In this study, we identified the functional properties of a porcine fusion protein, poIRF7/3(5D), as a biotherapeutic and enhancer of IFN activity against FMD virus (FMDV). We showed that poIRF7/3(5D) is a potent inducer of type I IFNs, including alpha IFN (IFN-?), IFN-?, and IFN-? but not type III IFN (interleukin-28B), without inducing cytotoxicity. Expression of poIRF7/3(5D) significantly and steadily reduced FMDV titers by up to 6 log10 units in swine and bovine cell lines. Treatment with an IFN receptor inhibitor (B18R) combined with an anti-IFN-? antibody neutralized the antiviral activity in the supernatants of cells transduced with an Ad5 vector expressing poIRF7/3(5D) [Ad5-poIRF7/3(5D)]. However, several transcripts with known antiviral function, including type I IFNs, were still highly upregulated (range of increase, 8-fold to over 500-fold) by poIRF7/3(5D) in the presence of B18R. Furthermore, the sera of mice treated with Ad5-poIRF7/3(5D) showed antiviral activity that was associated with the induction of high levels of IFN-? and resulted in complete protection against FMDV challenge at 6, 24, or 48 h posttreatment. This study highlights for the first time the antiviral potential of Ad5-poIRF7/3(5D) in vitro and in vivo against FMDV.
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Unit of measurement used and parent medication dosing errors.
Pediatrics
PUBLISHED: 07-14-2014
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Adopting the milliliter as the preferred unit of measurement has been suggested as a strategy to improve the clarity of medication instructions; teaspoon and tablespoon units may inadvertently endorse nonstandard kitchen spoon use. We examined the association between unit used and parent medication errors and whether nonstandard instruments mediate this relationship.
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Regulatory and functional connection of microphthalmia-associated transcription factor and anti-metastatic pigment epithelium derived factor in melanoma.
Neoplasia
PUBLISHED: 07-13-2014
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Pigment epithelium-derived factor (PEDF), a member of the serine protease inhibitor superfamily, has potent anti-metastatic effects in cutaneous melanoma through its direct actions on endothelial and melanoma cells. Here we show that PEDF expression positively correlates with microphthalmia-associated transcription factor (MITF) in melanoma cell lines and human samples. High PEDF and MITF expression is characteristic of low aggressive melanomas classified according to molecular and pathological criteria, whereas both factors are decreased in senescent melanocytes and naevi. Importantly, MITF silencing down-regulates PEDF expression in melanoma cell lines and primary melanocytes, suggesting that the correlation in the expression reflects a causal relationship. In agreement, analysis of Chromatin immunoprecipitation coupled to high throughput sequencing (ChIP-seq) data sets revealed three MITF binding regions within the first intron of SERPINF1, and reporter assays demonstrated that the binding of MITF to these regions is sufficient to drive transcription. Finally, we demonstrate that exogenous PEDF expression efficiently halts in vitro migration and invasion, as well as in vivo dissemination of melanoma cells induced by MITF silencing. In summary, these results identify PEDF as a novel transcriptional target of MITF and support a relevant functional role for the MITF-PEDF axis in the biology of melanoma.
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Analysis of gene expression changes in peach leaves in response to Plum pox virus infection using RNA-Seq.
Mol. Plant Pathol.
PUBLISHED: 07-04-2014
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Differences in gene expression were studied after Plum pox virus (PPV, sharka disease) infection in peach GF305 leaves with and without sharka symptoms using RNA-Seq. For each sample, more than 80% of 100-nucleotide paired-end (PE) Illumina reads were aligned on the peach reference genome. In the symptomatic sample, a significant proportion of reads were mapped to PPV reference genomes (1.04% compared with 0.00002% in non-symptomatic leaves), allowing for the ultra-deep assembly of the complete genome of the PPV isolate used (9775 nucleotides, missing only 11 nucleotides at the 5' genome end). In addition, significant alternative splicing events were detected in 359 genes and 12?990 single nucleotide polymorphisms (SNPs) were identified, 425 of which could be annotated. Gene ontology annotation revealed that the high-ranking mRNA target genes associated with the expression of sharka symptoms are mainly related to the response to biotic stimuli, to lipid and carbohydrate metabolism and to the negative regulation of catalytic activity. A greater number of differentially expressed genes were observed in the early asymptomatic phase of PPV infection in comparison with the symptomatic phase. These early infection events were associated with the induction of genes related to pathogen resistance, such as jasmonic acid, chitinases, cytokinin glucosyl transferases and Lys-M proteins. Once the virus had accumulated, the overexpression of Dicer protein 2a genes suggested a gene silencing plant response that was suppressed by the virus HCPro and P1 proteins. These results illustrate the dynamic nature of the peach-PPV interaction at the transcriptome level and confirm that sharka symptom expression is a complex process that can be understood on the basis of changes in plant gene expression.
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Mutation of Thermoanaerobacter ethanolicus secondary alcohol dehydrogenase at Trp-110 affects stereoselectivity of aromatic ketone reduction.
Org. Biomol. Chem.
PUBLISHED: 07-03-2014
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Alcohol dehydrogenases (ADHs) are enzymes that catalyze the reversible reduction of carbonyl compounds to their corresponding alcohols. We have been studying a thermostable, nicotinamide-adenine dinucleotide phosphate (NADP(+))-dependent, secondary ADH from Thermoanaerobacter ethanolicus (TeSADH). In the current work, we expanded our library of TeSADH and adopted the site-saturation mutagenesis approach in creating a comprehensive mutant library at W110. We used phenylacetone as a model substrate to study the effectiveness of our library because this substrate showed low enantioselectivity in our previous work when reduced using W110A TeSADH. Five of the newly designed W110 mutants reduced phenylacetone at >99.9% ee, and two of these mutants exhibit an enantiomeric ratio (E-value) of over 100. These five mutants also reduced 1-phenyl-2-butanone and 4-phenyl-2-butanone to their corresponding (S)-configured alcohols in >99.9% ee. These new mutants of TeSADH will likely have synthetic utility for reduction of aromatic ketones in the future.
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Measurement of thermal diffusivities of silver nanoparticle colloidal suspensions by means of a frequency-resolved thermal lensing approach.
Opt Lett
PUBLISHED: 07-01-2014
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A frequency-resolved thermal lensing (TL) approach to measure thermal diffusivity properties of both diluted liquid solutions and silver nanoparticle colloidal suspensions is demonstrated. The experiment is based on a classical two-color pump-probe TL configuration, which is adapted to measure the induced TL signal as a function of the chopping frequency of the pump beam. Because of the thermal diffusivity lengths in the samples, the TL signal decreases exponentially with the increment of the frequency. The exponential decay factor can be associated with the thermal diffusivity of the medium. Measurements are performed on diluted liquid solutions and silver nanoparticles suspended in a PVP solution. A suitable fitting to a theoretical model based on the Fresnel diffraction approximation of the experimental data is obtained. This work demonstrates the feasibility of using this approach for the thermal characterization of nanoparticles in liquid solutions. Thermal diffusivity as low as 0.094×10(-7)??m2 ?s(-1) can be estimated by using this approach.
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Ribosomic DNA intergenic spacer 1 region is useful when identifying Candida parapsilosis spp. complex based on high-resolution melting analysis.
Med. Mycol.
PUBLISHED: 05-20-2014
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The epidemiology of Candida parapsilosis and the closely related species C. orthopsilosis and C. metapsilosis has changed in recent years, justify the need to identify this complex at the species level. In this study we investigate the intergenic spacer 1 (IGS1) of the ribosomal DNA (rDNA) to evaluate the utility of this gene region as a phylogenetic molecular marker and the suitability of a high-resolution melting (HRM) strategy based on this region for identification of members of the C. parapsilosis spp. complex. We sequenced the IGS1 and the internal transcribed spacer (ITS) regions of the rDNA from 33 C. parapsilosis sensu lato strains. Although both regions are useful in identifying species, comparative sequence analysis showed that the diversity in the IGS1 region was higher than in the ITS sequences. We also developed an HRM analysis that reliably identifies C. parapsilosis spp. complex based on the amplification of 70 bp in the IGS1 region. All isolates were correctly identified with a confidence interval >98%. Our results demonstrate that HRM analysis based on the IGS1 region is a powerful tool for distinguishing C. parapsilosis from cryptic species.
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In vitro comparison between cortical and cortico-cancellous femoral suspension devices for anterior cruciate ligament reconstruction: implications for mobilization.
Knee Surg Sports Traumatol Arthrosc
PUBLISHED: 05-02-2014
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To analyse the capability of cortical and cortical-cancellous suspension devices to provide a strong fixation in order to follow an aggressive early mobilization protocol.
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Analysis of two autoimmunity genes, IRAK1 and MECP2, in giant cell arteritis.
Clin. Exp. Rheumatol.
PUBLISHED: 04-07-2014
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The Xq28 region, containing IRAK and MECP2, represent a common susceptibility locus for a high number of autoimmune diseases. Our aim in the present study was to evaluate the influence of the IRAK1 and MECP2 autoimmunity-associated genetic variants in the giant cell arteritis (GCA) susceptibility and its clinical subphenotypes.
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Body fatness in relation to physical activity and selected socioeconomic parameters of adolescents aged 15-17 years in Merida, Yucatan.
Ann. Hum. Biol.
PUBLISHED: 03-24-2014
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Abstract Background: Increasing rates of overweight and obesity in adolescents are major concerns in many countries, including Mexico.
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Interferon regulatory factor 5 genetic variants are associated with cardiovascular disease in patients with rheumatoid arthritis.
Arthritis Res. Ther.
PUBLISHED: 03-11-2014
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Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased cardiovascular (CV) disease risk. Interferon regulatory factor 5 (IRF5) is a regulator of type I interferon induction. Recently, researchers have described an association between multiple single-nucleotide polymorphisms of the IRF5 gene and some rheumatic disorders. In this study, we aimed to evaluate whether three different haplotype blocks within the IRF5 locus which have been shown to alter the protein function are involved in the risk of CV events occurring in Spanish RA patients.
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Incidence of physical disability related to musculoskeletal disorders in the elderly: Results from a primary-care based registry.
Arthritis Care Res (Hoboken)
PUBLISHED: 02-27-2014
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Objetive: to estimate the incidence of musculoskeletal-related acute physical disability in the elderly (APDE). Methods: A primary care-based registry was established in Madrid's Health Area 7 from October 1(th) , 2005 to September 31 (th) , 2006. We included all persons over 65 years, non-institutionalized, covered by the health cards assigned to the participating general practitioners (GPs). A case of APDE was defined as moderate mobility alteration in the disability level within the Rosser's classification System, in the last three months, related to a musculoskeletal cause. Incidence rates (IR) were estimated per 10,000 by direct standardisation with a 95% confidence interval. Results: Eight primary care centres and 23 GPs participated in the registry, covering an area of 8,546 elderly. In the inclusion year, the GPs identified 147 new APDE cases, in 106 patients. The annual estimated incidence of APDE was 331 cases per 10,000 (95% CI: 280-389) and the incidence rate of new patients with a APDE episode was 239 (95%CI: 196-288); IR was higher in women (344 cases; 95% CI: 279.8-423.0) than in men (207; 95% CI: 127.0-338.2). Conclusions: The incidence estimate of acute physical disability related to Musculoskeletal disorders in elderly should help us to dimension the magnitude of this health problem, as the first step to establish a specific practice for the recovery of cases and for the prevention of lost of functioning, mobility and dependency. © 2014 American College of Rheumatology.
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High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci.
Ann. Rheum. Dis.
PUBLISHED: 02-18-2014
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A highly polygenic aetiology and high degree of allele-sharing between ancestries have been well elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data.
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Morphologic and phenotypic characteristics of myocarditis in two pigs infected by foot-and mouth disease virus strains of serotypes O or A.
Acta Vet. Scand.
PUBLISHED: 02-17-2014
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Myocarditis is often cited as the cause of fatalities associated with foot-and-mouth disease virus (FMDV) infection. However, the pathogenesis of FMDV-associated myocarditis has not been described in detail. The current report describes substantial quantities of FMDV in association with a marked mononuclear inflammatory reaction, interstitial edema and cardiomyocyte degeneration in the myocardium of two pigs that died during acute infection with either of two different strains of FMDV. Despite similar clinical progression, there was a marked variation in morphological characteristics of myocarditis with a significant difference in intensity of myocardial inflammation between the two cases. Phenotypic characterization of leukocyte populations revealed that in both cases, the inflammatory infiltrate consisted mainly of combinations of CD172a+, CD163+ and CD44+ cells, with a distinct subset of CD8+ cells, but with consistent lack of detection of CD3+ and CD21+ cells. This suggests that the FMDV-associated acute myocardial inflammation in the two observed cases consisted mainly of leukocytes of monocyte lineage, with a distinct population of CD8+ cells which, based on lack of CD3 detection in serial sections, are likely to represent NK cells.
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A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides.
Ann. Rheum. Dis.
PUBLISHED: 02-14-2014
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Rheumatoid arthritis (RA) patients can be classified based on presence or absence of anticitrullinated peptide antibodies (ACPA) in their serum. This heterogeneity among patients may reflect important biological differences underlying the disease process. To date, the majority of genetic studies have focused on the ACPA-positive group. Therefore, our goal was to analyse the genetic risk factors that contribute to ACPA-negative RA.
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Lack of association between ABO, PPAP2B, ADAMST7, PIK3CG, and EDNRA and carotid intima-media thickness, carotid plaques, and cardiovascular disease in patients with rheumatoid arthritis.
Mediators Inflamm.
PUBLISHED: 02-13-2014
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Rheumatoid arthritis (RA) is a polygenic disease associated with accelerated atherosclerosis and increased cardiovascular (CV) mortality. Recent studies have identified the ABO rs579459, PPAP2B rs17114036, and ADAMTS7 rs3825807 polymorphisms as genetic variants associated with coronary artery disease and the PIK3CG rs17398575 and EDNRA rs1878406 polymorphisms as the most significant signals related to the presence of carotid plaque in nonrheumatic Caucasian individuals. Accordingly, we evaluated the potential relationship between these 5 polymorphisms and subclinical atherosclerosis (assessed by carotid intima-media thickness (cIMT) and presence/absence of carotid plaques) and CV disease in RA.
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Phylogeographic characteristics of vesicular stomatitis New Jersey viruses circulating in Mexico from 2005 to 2011 and their relationship to epidemics in the United States.
Virology
PUBLISHED: 01-15-2014
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We analyzed the phylogenetic and time-space relationships (phylodynamics) of 181 isolates of vesicular stomatitis New Jersey virus (VSNJV) causing disease in Mexico and the United States (US) from 2005 through 2012. We detail the emergence of a genetic lineage in southern Mexico causing outbreaks in central Mexico spreading into northern Mexico and eventually into the US. That emerging lineage showed higher nucleotide sequence identity (99.5%) than that observed for multiple lineages circulating concurrently in southern Mexico (96.8%). Additionally, we identified 58 isolates from Mexico that, unlike previous isolates from Mexico, grouped with northern Central America clade II viruses. This study provides the first direct evidence for the emergence and northward migration of a specific VSNJV genetic lineage from endemic areas in Mexico causing VS outbreaks in the US. In addition we document the emergence of a Central American VSNJV genetic lineage moving northward and causing outbreaks in central Mexico.
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Polyamine transport inhibitors: design, synthesis, and combination therapies with difluoromethylornithine.
J. Med. Chem.
PUBLISHED: 01-09-2014
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The development of polyamine transport inhibitors (PTIs), in combination with the polyamine biosynthesis inhibitor difluoromethylornithine (DFMO), provides a method to target cancers with high polyamine requirements. The DFMO+PTI combination therapy results in sustained intracellular polyamine depletion and cell death. A series of substituted benzene derivatives were evaluated for their ability to inhibit the import of spermidine in DFMO-treated Chinese hamster ovary (CHO) and L3.6pl human pancreatic cancer cells. Several design features were discovered which strongly influenced PTI potency, sensitivity to amine oxidases, and cytotoxicity. These included changes in (a) the number of polyamine chains appended to the ring system, (b) the polyamine sequence, (c) the attachment linkage of the polyamine to the aryl core, and (d) the presence of a terminal N-methyl group. Of the series tested, the optimal design was N(1),N(1'),N(1?)-(benzene-1,3,5-triyltris(methylene))tris(N(4)-(4-(methylamino)butyl)butane-1,4-diamine, 6b, which contained three N-methylhomospermidine motifs. This PTI exhibited decreased sensitivity to amine oxidases and low toxicity as well as high potency (EC50 = 1.4 ?M) in inhibiting the uptake of spermidine (1 ?M) in DFMO-treated L3.6pl human pancreatic cancer cells.
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Genetics of rheumatoid arthritis contributes to biology and drug discovery.
Yukinori Okada, Di Wu, Gosia Trynka, Towfique Raj, Chikashi Terao, Katsunori Ikari, Yuta Kochi, Koichiro Ohmura, Akari Suzuki, Shinji Yoshida, Robert R Graham, Arun Manoharan, Ward Ortmann, Tushar Bhangale, Joshua C Denny, Robert J Carroll, Anne E Eyler, Jeffrey D Greenberg, Joel M Kremer, Dimitrios A Pappas, Lei Jiang, Jian Yin, Lingying Ye, Ding-Feng Su, Jian Yang, Gang Xie, Ed Keystone, Harm-Jan Westra, Tonu Esko, Andres Metspalu, Xuezhong Zhou, Namrata Gupta, Daniel Mirel, Eli A Stahl, Dorothée Diogo, Jing Cui, Katherine Liao, Michael H Guo, Keiko Myouzen, Takahisa Kawaguchi, Marieke J H Coenen, Piet L C M van Riel, Mart A F J van de Laar, Henk-Jan Guchelaar, Tom W J Huizinga, Philippe Dieudé, Xavier Mariette, S Louis Bridges, Alexandra Zhernakova, René E M Toes, Paul P Tak, Corinne Miceli-Richard, So-Young Bang, Hye-Soon Lee, Javier Martín, Miguel A González-Gay, Luis Rodriguez-Rodriguez, Solbritt Rantapää-Dahlqvist, Lisbeth Arlestig, Hyon K Choi, Yoichiro Kamatani, Pilar Galán, Mark Lathrop, , Steve Eyre, John Bowes, Anne Barton, Niek de Vries, Larry W Moreland, Lindsey A Criswell, Elizabeth W Karlson, Atsuo Taniguchi, Ryo Yamada, Michiaki Kubo, Jun S Liu, Sang-Cheol Bae, Jane Worthington, Leonid Padyukov, Lars Klareskog, Peter K Gregersen, Soumya Raychaudhuri, Barbara E Stranger, Philip L De Jager, Lude Franke, Peter M Visscher, Matthew A Brown, Hisashi Yamanaka, Tsuneyo Mimori, Atsushi Takahashi, Huji Xu, Timothy W Behrens, Katherine A Siminovitch, Shigeki Momohara, Fumihiko Matsuda, Kazuhiko Yamamoto, Robert M Plenge.
Nature
PUBLISHED: 01-07-2014
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A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ?10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2 - 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation, cis-acting expression quantitative trait loci and pathway analyses--as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes--to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
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Liquid medication dosing errors in children: role of provider counseling strategies.
Acad Pediatr
PUBLISHED: 01-04-2014
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To examine the degree to which recommended provider counseling strategies, including advanced communication techniques and dosing instrument provision, are associated with reductions in parent liquid medication dosing errors.
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Prognosis impact of the lymph node ratio in patients with colon adenocarcinoma: a single-centre experience.
J Gastrointest Cancer
PUBLISHED: 01-03-2014
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Recently, the positive lymph node ratio (LNR) is considered a new prognostic parameter on survival and time to progression for patients with colon cancer. The aim of this study was to determine the prognostic impact of the LNR as an independent factor for overall survival (OS) and disease-free survival (DFS) in patients with colon cancer regardless of their clinical stage.
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Foot-and-mouth disease virus virulence in cattle is co-determined by viral replication dynamics and route of infection.
Virology
PUBLISHED: 01-02-2014
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Early events in the pathogenesis of foot-and-mouth disease virus (FMDV) infection in cattle were investigated through aerosol and intraepithelial lingual (IEL) inoculations of a cDNA-derived FMDV-A24 wild type virus (FMDV-WT) or a mutant derived from the same clone (FMDV-Mut). After aerosolization of FMDV-WT, primary infection sites had significantly greater quantities of FMDV, viral RNA, and type I/III interferon (IFN) activity compared to corresponding tissues from cattle infected with FMDV-Mut. Additionally, FMDV-WT-infected cattle had marked induction of systemic IFN activity in serum. In contrast, FMDV-Mut aerosol-infected cattle did not manifest systemic IFN response nor had viremia. Interestingly, IEL inoculation of FMDV-Mut in cattle restored the virulent phenotype and systemic IFN response. These data indicate that the attenuated phenotype in cattle is associated with decreased replicative efficiency, reflected by decreased innate response. However, attenuation is abrogated by bypassing the common primary infection sites, inducing accelerated viral replication at the inoculation site.
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A Candidate Gene Approach Identifies an IL33 Genetic Variant as a Novel Genetic Risk Factor for GCA.
PLoS ONE
PUBLISHED: 01-01-2014
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Increased expression of IL-33 and its receptor ST2, encoded by the IL1RL1 gene, has been detected in the inflamed arteries of giant cell arteritis (GCA) patients. The aim of the present study was to investigate for the first time the potential influence of the IL33 and IL1RL1 loci on GCA predisposition.
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PIM Kinases as Potential Therapeutic Targets in a Subset of Peripheral T Cell Lymphoma Cases.
PLoS ONE
PUBLISHED: 01-01-2014
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Currently, there is no efficient therapy for patients with peripheral T cell lymphoma (PTCL). The Proviral Integration site of Moloney murine leukemia virus (PIM) kinases are important mediators of cell survival. We aimed to determine the therapeutic value of PIM kinases because they are overexpressed in PTCL patients, T cell lines and primary tumoral T cells. PIM kinases were inhibited genetically (using small interfering and short hairpin RNAs) and pharmacologically (mainly with the pan-PIM inhibitor (PIMi) ETP-39010) in a panel of 8 PTCL cell lines. Effects on cell viability, apoptosis, cell cycle, key proteins and gene expression were evaluated. Individual inhibition of each of the PIM genes did not affect PTCL cell survival, partially because of a compensatory mechanism among the three PIM genes. In contrast, pharmacological inhibition of all PIM kinases strongly induced apoptosis in all PTCL cell lines, without cell cycle arrest, in part through the induction of DNA damage. Therefore, pan-PIMi synergized with Cisplatin. Importantly, pharmacological inhibition of PIM reduced primary tumoral T cell viability without affecting normal T cells ex vivo. Since anaplastic large cell lymphoma (ALK+ ALCL) cell lines were the most sensitive to the pan-PIMi, we tested the simultaneous inhibition of ALK and PIM kinases and found a strong synergistic effect in ALK+ ALCL cell lines. Our findings suggest that PIM kinase inhibition could be of therapeutic value in a subset of PTCL, especially when combined with ALK inhibitors, and might be clinically beneficial in ALK+ ALCL.
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Identification of Quercus agrifolia (coast live oak) resistant to the invasive pathogen Phytophthora ramorum in native stands using Fourier-transform infrared (FT-IR) spectroscopy.
Front Plant Sci
PUBLISHED: 01-01-2014
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Over the last two decades coast live oak (CLO) dominance in many California coastal ecosystems has been threatened by the alien invasive pathogen Phytophthora ramorum, the causal agent of sudden oak death. In spite of high infection and mortality rates in some areas, the presence of apparently resistant trees has been observed, including trees that become infected but recover over time. However, identifying resistant trees based on recovery alone can take many years. The objective of this study was to determine if Fourier-transform infrared (FT-IR) spectroscopy, a chemical fingerprinting technique, can be used to identify CLO resistant to P. ramorum prior to infection. Soft independent modeling of class analogy identified spectral regions that differed between resistant and susceptible trees. Regions most useful for discrimination were associated with carbonyl group vibrations. Additionally, concentrations of two putative phenolic biomarkers of resistance were predicted using partial least squares regression; >99% of the variation was explained by this analysis. This study demonstrates that chemical fingerprinting can be used to identify resistance in a natural population of forest trees prior to infection with a pathogen. FT-IR spectroscopy may be a useful approach for managing forests impacted by sudden oak death, as well as in other situations where emerging or existing forest pests and diseases are of concern.
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Ungulate vehicle collisions in a peri-urban environment: consequences of transportation infrastructures planned assuming the absence of ungulates.
PLoS ONE
PUBLISHED: 01-01-2014
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Ungulate vehicle collisions (UVC) provoke serious damage, including human casualties, and a large number of measures have been developed around the world to avoid collisions. We analyse the main factors involved in UVC in a road network built in the absence of ungulates, where mitigation structures to avoid UVC were not adequately considered. Ungulate population greatly increased during the last two decades and now Roe Deer and Wild Boars are widely distributed over the study area, but even after this increase, the road network was not adapted to avoid UVC. A total of 235 Roe Deer (RDVC) and 153 Wild Boar vehicle collisions (WBVC) were recorded between January 2008 and December 2011. We randomly selected 289 sample points (87 RDVC, 60 WBVC and 142 controls) separated by at least 500 metres from the next closest point and measured 19 variables that could potentially influence the vehicle collisions. We detected variations in the frequency of RDVC on a monthly basis, and WBVC was higher at weekends but no significant differences were detected on a monthly basis. UVC were more likely to occur at locations where sinuosity of the road, velocity, surface of shrub and deciduous forest area were greater, the presence of fences entered with positive relationship and distance to the nearest building was less. RDVC were more likely to occur at locations where timber forest area increased and distance to the nearest building decreased and WBVC was related to open fields cover and also to the presence of fences. Sinuosity and velocity entered in both cases as significant factors. Major roads, in which the traffic volume is greater and faster, caused more accidents with ungulates than secondary roads. Nowadays, the high frequency of ungulate road-kills deserves a new strategy in order to adapt infrastructure and adopt mitigation measures.
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Genetic risk scores and number of autoantibodies in patients with rheumatoid arthritis.
Ann. Rheum. Dis.
PUBLISHED: 12-17-2013
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Certain HLA-DRB1 alleles and single-nucleotide polymorphisms (SNPs) are associated with rheumatoid arthritis (RA). Our objective was to examine the combined effect of these associated variants, calculated as a cumulative genetic risk score (GRS) on RA predisposition, as well as the number of autoantibodies (none, one or two present).
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Orthopedic surgery in rheumatoid arthritis in the era of biologic therapy.
J. Rheumatol.
PUBLISHED: 09-15-2013
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To analyze sociodemographic and clinic-related factors associated with the use of orthopedic surgical procedures in rheumatoid arthritis (RA), focusing on the potential role of new biologic therapies.
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Circumscribed palmar hypokeratosis associated to a burn scar.
Am J Dermatopathol
PUBLISHED: 09-14-2013
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Circumscribed palmar or plantar hypokeratosis is a volar depression characterized by a circular area of well-circumscribed and erythematous skin on the palm or sole. It is a benign condition that occurs mainly as an asymptomatic lesion on the thenar or hypothenar areas of the palm of middle-aged or elderly patients. Since its first description 1 decade ago, the pathogenesis of this entity still remains unclear. Herein we report the first case of a circumscribed palmar hypokeratosis lesion associated to a burn scar, which corroborates the hypothesis of an acquired disorder caused by trauma.
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Correlates of colorectal cancer screening among Hispanics: Results from the 2008 Puerto Rico behavioral risk factor surveillance system survey.
P R Health Sci J
PUBLISHED: 06-21-2013
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Colorectal cancer (CRC) is the second most commonly diagnosed cancer in Puerto Rico (PR). Given the lack of information on cancer screening behavior, we identified factors associated with CRC screening among adults aged >or= 50 years in PR.
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Eosinophilic fasciitis as a manifestation of a cutaneous T-cell lymphoma not otherwise specified.
Am J Dermatopathol
PUBLISHED: 06-14-2013
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Eosinophilic fasciitis (EF) is a rare entity characterized by symmetrical and painful thickness and induration of the skin, especially localized on forearms and thorax and generally accompanied by eosinophilia. Although several reports indicate the relationship between EF and hematological disorders such as aplastic anemia, polycythemia vera, or myelomonocytic leukemia, the association with lymphomas is extremely rare. Only a few cases of EF have been previously described preceding or concomitant to the Hodgkin disease, peripheral T-cell lymphoma, B-cell lymphoma, and mycosis fungoides. We report for the first time a 76-year-old man with an EF associated with a peripheral T-cell lymphoma not otherwise specified. We review the relationship between both conditions. In conclusion, we present a unique case of EF as a manifestation of a T-cell lymphoma not otherwise specified. The present case demonstrates the importance of clinical and radiological studies in those cases of EF to rule out a visceral, lymph node, or cutaneous lymphoma.
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Negative affect in systemic sclerosis.
Rheumatol. Int.
PUBLISHED: 06-11-2013
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Negative affect appears frequently in rheumatic diseases, but studies about their importance and prevalence in systemic sclerosis patients are scarce, and the results are inconclusive separately. We conducted a comprehensive search on April 2013 of PubMed, Medline, and PsycINFO databases to identify original research studies published. A total of 48 studies were included in this systematic review. We found negative emotions have very high levels in these patients, compared to both healthy population other chronic rheumatic patients assessed with the same instruments and cutoffs. Depression has been, of the three negative emotions that we approach to in this review, the most widely studied in systemic sclerosis, followed by anxiety. Despite the fact that anger is a common emotion in these diseases is poorly studied. Methodologic issues limited the ability to draw strong conclusions from studies of predictors. Disease-specific symptoms (swollen joints, gastrointestinal and respiratory symptoms and digital ulcers) and factors related to physical appearance were associated with negative emotions. Interdisciplinary care and biopsychosocial approach would have a great benefit in the clinical management of these patients.
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Characterization of a chimeric foot-and-mouth disease virus bearing a bovine rhinitis B virus leader proteinase.
Virology
PUBLISHED: 06-10-2013
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Bovine rhinitis B virus (BRBV) shares many motifs and sequence similarities with foot-and-mouth disease virus (FMDV). This study examined if the BRBV leader proteinase (L(pro) ) could functionally replace that of FMDV. A mutant A24LBRV3DYR FMDV engineered with the BRBV L(pro) and an antigenic marker in the 3D polymerase exhibited growth properties and eIF4G cleavage similar to parental A24WT virus. The A24LBRV3DYR type I interferon activity in infected bovine cells resembled that of A24LL virus that lacks L(pro), but this effect was less pronounced for A24LBRV3DYR infected porcine cells. In vivo studies showed that the A24LBRV3DYR virus was attenuated in cattle, and exhibited low virulence in pigs exposed by direct contact. The mutant virus induced protective immunity in cattle against challenge with parental A24WT. These results provide evidence that L(pro) of different Aphthoviruses are not fully functionally interchangeable and have roles that may depend on the nature of the infected host.
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Nutritional status of Maya children, their mothers, and their grandmothers residing in the City of Merida, Mexico: revisiting the leg-length hypothesis.
Am. J. Hum. Biol.
PUBLISHED: 06-10-2013
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To test the hypothesis that leg length-relative-to-stature is a more sensitive indicator of nutrition and health than is total height (HT) or sitting height (SH) in a sample of 109 triads of urban Maya children (6.0-8.99 years), their mothers, and maternal grandmothers from Merida, Mexico.
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Detection of BRAF V600 mutations in metastatic melanoma: comparison of the Cobas 4800 and Sanger sequencing assays.
J Mol Diagn
PUBLISHED: 06-03-2013
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Detection of the BRAF V600E mutation is required for use of the BRAF inhibitor, vemurafenib, in patients with metastatic melanoma. Although the Roche Cobas 4800 BRAF V600 Mutation Test is approved, it detects primarily the single-nucleotide V600E mutation and could miss other potentially relevant V600 mutations. To assess the detection rate of the cobas assay for V600 mutations in clinical specimens, we compared the results of this assay with Sanger sequencing in 295 melanoma FFPE samples. Twenty samples were excluded because of invalid results on the cobas (n = 3), sequencing (n = 15), or both (n = 2). V600 mutations were detected by the cobas test in 96 (34.9%) of 275 samples and by Sanger sequencing in 118 (42.9%) of 275 samples. Thus, relative to Sanger sequencing, the cobas test exhibited 80.5% sensitivity (95% CI, 72.4% to 86.6%) and 99.4% specificity (95% CI, 96.5% to 99.9%). Of 23 samples with positive sequencing results but negative cobas results, 21 harbored dinucleotide mutations (V600E in 6, V600K in 10, and V600R in 5); the other two involved single-nucleotide mutations (V600E and V600G). These findings indicate that the cobas assay may miss many V600 mutations in clinical specimens. In our study, the addition of Sanger sequencing for samples with negative cobas results increased the detection rate to 42.9%. This approach could help maximize the number of patients who benefit from BRAF inhibitor treatment.
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Variations of the origin of the arcuate artery.
J Am Podiatr Med Assoc
PUBLISHED: 05-24-2013
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The purpose of this study was to investigate the origin of the arcuate artery.
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Rapid authentication of concord juice concentration in a grape juice blend using Fourier-Transform infrared spectroscopy and chemometric analysis.
Food Chem
PUBLISHED: 04-26-2013
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Concord grape juice is associated with many health benefits, and so it can be sold at a premium price. However, there is currently no method to verify the percent composition of Concord grape juice in grape juice blends. In order to guard against potential adulteration, a rapid method for authentication is required. Fourier Transform infrared (FT-IR) spectroscopy was used to develop a model which predicts the percent composition of Concord grape juice. The model was based on a training set of 64 samples with Concord concentrations ranging from 50% to 100%. Data was collected on an external validation set with a standard error of prediction of 5.6% using 7 factors. The results suggest the feasibility of using FT-IR coupled with chemometrics as a production-scale tool for authentication claims of Concord in grape juice blends, protecting consumers and businesses against deceptive labelling.
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A partial deletion in non-structural protein 3A can attenuate foot-and-mouth disease virus in cattle.
Virology
PUBLISHED: 04-26-2013
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The role of non-structural protein 3A of foot-and-mouth disease virus (FMDV) on the virulence in cattle has received significant attention. Particularly, a characteristic 10-20 amino acid deletion has been implicated as responsible for virus attenuation in cattle: a 10 amino acid deletion in the naturally occurring, porcinophilic FMDV O1 Taiwanese strain, and an approximately 20 amino acid deletion found in egg-adapted derivatives of FMDV serotypes O1 and C3. Previous reports using chimeric viruses linked the presence of these deletions to an attenuated phenotype in cattle although results were not conclusive. We report here the construction of a FMDV O1Campos variant differing exclusively from the highly virulent parental virus in a 20 amino acid deletion between 3A residues 87-106, and its characterization in vitro and in vivo. We describe a direct link between a deletion in the FMDV 3A protein and disease attenuation in cattle.
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Benign atypical intravascular CD30(+) T-cell proliferation: a reactive condition mimicking intravascular lymphoma.
Am J Dermatopathol
PUBLISHED: 04-02-2013
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CD30 is a transmembrane glycoprotein molecule usually expressed in activated B and T cells. Although it has been considered a reliable marker for CD30 lymphomas, reactive inflammatory disorders may contain a significant number of CD30 cells mimicking lymphoproliferative disorders clinically or histologically. Intravascular lymphoma is a rare variant of non-Hodgkin lymphoma that can involve the skin in 40% of the patients. The majority of cases show a B-cell phenotype, and only a minority of cases are of T-cell or NK-cell origin. Moreover, 2 aggressive cases of intravascular large T-cell lymphoma have been described with a CD30 phenotype. Herein, we report 2 patients with skin lesions showing an atypical intravascular CD30 T-cell proliferation. Both the patients did not present systemic disease and therefore exhibit a favorable outcome. To the best of our knowledge, this is the second report in the literature of a benign intravascular CD30 T-cell proliferation that represents an intriguing differential diagnosis for intravascular lymphoma.
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HPV Direct Flow CHIP: a new human papillomavirus genotyping method based on direct PCR from crude-cell extracts.
J. Virol. Methods
PUBLISHED: 03-26-2013
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HPV Direct Flow CHIP is a newly developed test for identifying 18 high-risk and 18 low-risk human papillomavirus (HPV) genotypes. It is based on direct PCR from crude-cell extracts, automatic flow-through hybridization, and colorimetric detection. The aim of this study was to evaluate the performance of HPV Direct Flow CHIP in the analysis of 947 samples from routine cervical screening or the follow-up of abnormal Pap smears. The specimens were dry swab samples, liquid-based cytology samples, or formalin-fixed paraffin-embedded tissues. The genotype distribution was in agreement with known epidemiological data for the Spanish population. Three different subgroups of the samples were also tested by Linear Array (LA) HPV Genotyping Test (n=108), CLART HPV2 (n=82), or Digene Hybrid Capture 2 (HC2) HPV DNA Test (n=101). HPV positivity was 73.6% by HPV Direct Flow CHIP versus 67% by LA, 65.9% by HPV Direct Flow CHIP versus 59.8% by CLART, and 62.4% by HPV Direct Flow CHIP versus 42.6% by HC2. HPV Direct Flow CHIP showed a positive agreement of 88.6% with LA (k=0.798), 87.3% with CLART (k=0.818), and 68.2% with HC2 (k=0.618). In conclusion, HPV Direct Flow CHIP results were comparable with those of the other methods tested. Although further investigation is needed to compare the performance of this new test with a gold-standard reference method, these preliminary findings evidence the potential value of HPV Direct Flow CHIP in HPV vaccinology and epidemiology studies.
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A continuous bovine kidney cell line constitutively expressing bovine ?v?6 integrin has increased susceptibility to foot-and-mouth disease virus.
J. Clin. Microbiol.
PUBLISHED: 03-20-2013
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Foot-and-mouth disease (FMD) is a worldwide problem limiting the trade of animals and their products from affected countries. The rapid isolation, serotyping, and vaccine matching of FMD virus from disease outbreaks is critical for enabling the implementation of effective vaccination programs and to stop the spread of infection during outbreaks. Some primary cells have been shown to be highly susceptible to most strains of FMD virus (FMDV) but are difficult and expensive to prepare and maintain. Since the ?V?6 integrin is a principal receptor for FMDV, we transduced a bovine kidney cell line to stably express both the ?V and ?6 bovine integrin subunits. This stable cell line (LFBK-?V?6) showed ?6 expression and enhanced susceptibility to FMDV infection for ? 100 cell passages. LFBK-?V?6 cells were highly sensitive for detecting all serotypes of FMDV from experimentally infected animals, including the porcinophilic FMDV strain O/TAW/97. In comparison to other cell types that are currently used for virus isolation, LFBK-?V?6 cells were more effective at detecting FMDV in clinical samples, supporting their use as a more sensitive tool for virus isolation.
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Diffuse dermal angiomatosis of the breast: clinical and histopathological features.
Int. J. Dermatol.
PUBLISHED: 03-14-2013
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INTRODUCTION: Diffuse dermal angiomatosis is an entity in the spectrum of reactive angiomatoses characterized by erythematous plaques that mainly affect the lower extremities of patients with a personal history of peripheral vascular disease. Involvement of the breast is a rare event that has only been described as single cases in women with large breasts. OBJECTIVE: Our main aim is to report three rare cases of diffuse dermal angiomatosis of the breast and to better define their clinical, histopathological, and immunohistochemical characteristics. Comorbidities and management will also be discussed. METHODS: A retrospective search of patients with the diagnosis of diffuse dermal angiomatosis of the breast was made. Databases of three hospitals, Hospital 12 de Octubre (Madrid, Spain), Hospital La Fe (Valencia, Spain), and Clinica Dermatologica, University of Genoa (Italy), were included in the analysis. RESULTS: Three middle-aged women who were heavy smokers were found. Physical examination revealed several livedoid plaques on both breasts. Painful ulceration over the violaceous lesions was observed in two cases. Histological features included a diffuse proliferation of spindle-shaped endothelial cells with focal small vessel formation occupying the full thickness of the dermis with scanty extravasated erythrocytes, showing positivity for CD31, CD34, and SMA-? and negativity for D2-40. Management was focused on a strict control of comorbidities, especially on the cessation of smoking habit that led to a conspicuous improvement in all patients. CONCLUSIONS: We describe all those clinicopathologic features that define diffuse dermal angiomatosis of the breast, which should be considered a distinctive variant into the group of cutaneous angiomatoses. In our experience, a strict control of smoking habit must be the first step in the management of this entity.
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Rapid assessment of quality parameters in processing tomatoes using hand-held and benchtop infrared spectrometers and multivariate analysis.
J. Agric. Food Chem.
PUBLISHED: 02-19-2013
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Two portable infrared sensors were evaluated for the rapid determination of quality parameters in processing tomatoes. A total of 370 hot-break juices were prepared from ?40 processing tomato varieties grown in 5 California counties. The levels of sugars, acids, soluble solids, titratable acidity, and pH in these juices were determined using standard reference methods. Juices were processed, filtered, and directly applied to the FT-IR crystal (15-40 ?L) to obtain spectra. Partial least-squares regression (PLSR) was used to generate correlation models, both calibration and validation. The PLS validation models showed good ability (Rval > 0.80; <10% SEP) in estimating the sugars, acids, and especially soluble solids in tomato for both the transmission DialPath portable system and benchtop unit using triple-bounce attenuated total reflectance (ATR). The IR portable unit may provide the tomato processing industry with an efficient method for in-plant, high throughput quantification of quality parameters in tomatoes.
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Nesidioblastosis. A case of hyperplasia of the islets of Langerhans in the adult.
Pancreatology
PUBLISHED: 02-05-2013
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Nesidioblastosis is a rare disease caused by hyperplasia of pancreatic islets, developing a state of hypoglycemia due to an increase in the insulin production. It is the leading cause of hyperinsulinic hypoglycemia in childhood, whereas in adults it only represents the 0.5-5% of cases. The pathogenesis is still unknown. We have studied several genetic mutations associated with dependent potassium channel of ATP present in the beta cells of the pancreas, as well as in patients underwent bariatric surgery because of the metabolic changes involved.
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Application of hand-held and portable infrared spectrometers in bovine milk analysis.
J. Agric. Food Chem.
PUBLISHED: 01-31-2013
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A simple and fast method for the detection and quantification of milk adulteration was developed using portable and hand-held infrared (IR) spectrometers. Milk samples were purchased from local supermarkets (Columbus, OH, USA) and spiked with tap water, whey, hydrogen peroxide, synthetic urine, urea, and synthetic milk in different concentrations. Spectral data were collected using mid-infrared (MIR) and near-infrared (NIR) spectrometers. Soft independent modeling of class analogy (SIMCA) classification models exhibited tight and well-separated clusters allowing the discrimination of control from adulterated milk samples. Partial least-squares regression (PLSR) was used to estimate adulteration levels, and results showed high coefficients of determination (R(2)) and low standard errors of prediction (SEP). Classification and quantification models indicated that the tested MIR systems were superior to NIR systems in monitoring milk adulteration. This method can be potentially used as an alternative to traditional methods due to their simplicity, sensitivity, low energy cost, and portability.
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Benign cutaneous neural tumors.
Semin Diagn Pathol
PUBLISHED: 01-19-2013
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Benign cutaneous neural neoplasms are one of the most frequent benign mesenchymal tumors in the skin. Because peripheral sheath nerve is composed of different cells, the tumors raised in these structures are varied and usually contain many of these cells. Most of these tumors are easy to diagnose, as usually present characteristic features well-recognized and express -specific immunohistochemical proteins. However, there are so many infrequent variants that many times require distinction from others spindle-cell tumors including melanoma. The tumors differ from one another by displaying a different proportion and arrangement of the various constituents of a peripheral nerve. In this article, we present the most characteristic clinical and histopathological features of many of these frequent benign cutaneous neural tumors including their uncommon variants.
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Health-related quality of life as a main determinant of access to rheumatologic care.
Rheumatol. Int.
PUBLISHED: 01-11-2013
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To evaluate a rheumatology outpatient consultation access system for new patients. New patients seen from April 2005 to April 2006 at our rheumatology clinic (n = 4,460) were included and classified according to their appointment type: ordinary appointments (OA) to be seen within 30 days, urgent appointments (UA) and work disability appointments (WDA) to be seen within 3 days. Age, sex, diagnosis, and health-related quality of life (HRQoL) as determined by the Rosser Index were recorded. Logistic regression models were run to identify factors that contribute to each type of appointment. OA was the method of access for 1,938 new patients, while 1,194 and 1,328 patients were seen through WDA and UA appointments, respectively. Younger male patients, and those with microcrystalline arthritis, sciatica, shoulder, back, or neck pain, were more likely to use the faster access systems (UA or WDA), whereas patients with a degenerative disease were mainly seen through OA (<0.001). Subjects with poor (3.96; 95 % CI, 2.8-5.5) or very poor HRQoL (70.8; 95 % CI, 14.9-334) were strongly associated to visiting a rheumatologist through the WDA or UA access systems, respectively, compared to OA. Age, gender, diagnosis, and mainly health-related quality of life are associated with the referral pattern of access to rheumatologic outpatient care. Among new patients subjects with the worst HRQoL were more likely to access with faster methods (UA or WDA) than those with better HRQoL.
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SMAD3 rs17228212 Gene Polymorphism Is Associated with Reduced Risk to Cerebrovascular Accidents and Subclinical Atherosclerosis in Anti-CCP Negative Spanish Rheumatoid Arthritis Patients.
PLoS ONE
PUBLISHED: 01-01-2013
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Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV) disease. Previous genome-wide association studies have described SMAD3 rs17228212 polymorphism as an important signal associated with CV events. The aim of the present study was to evaluate for the first time the relationship between this gene polymorphism and the susceptibility to CV manifestations and its potential association with the presence of subclinical atherosclerosis assessed by the evaluation of carotid intima-media thickness (cIMT) in patients with RA.
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Association of CD247 polymorphisms with rheumatoid arthritis: a replication study and a meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2013
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Given the role of CD247 in the response of the T cells, its entailment in autoimmune diseases and in order to better clarify the role of this gene in RA susceptibility, we aimed to analyze CD247 gene variants previously associated with other autoimmune diseases (rs1052237, rs2056626 and rs864537) in a large independent European Caucasian population. However, no evidence of association was found for the analyzed CD247 single-nucleotide polymorphisms (SNPs) with RA and with the presence/absence of anti-cyclic citrullinated polypeptide. We performed a meta-analysis including previously published GWAS data from the rs864537 variant, revealing an overall genome-wide significant association between this CD247 SNP and RA with anti-CCP (OR?=?0.90, CI 95%?=?0.87-0.93, Poverall?=?2.1×10(-10)). Our results show for first time a GWAS-level association between this CD247 polymorphism and RA risk.
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Mechanisms of foot-and-mouth disease virus tropism inferred from differential tissue gene expression.
PLoS ONE
PUBLISHED: 01-01-2013
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Foot-and-mouth disease virus (FMDV) targets specific tissues for primary infection, secondary high-titer replication (e.g. foot and mouth where it causes typical vesicular lesions) and long-term persistence at some primary replication sites. Although integrin ?V?6 receptor has been identified as primary FMDV receptors in animals, their tissue distribution alone fails to explain these highly selective tropism-driven events. Thus, other molecular mechanisms must play roles in determining this tissue specificity. We hypothesized that differences in certain biological activities due to differential gene expression determine FMDV tropism and applied whole genome gene expression profiling to identify genes differentially expressed between FMDV-targeted and non-targeted tissues in terms of supporting primary infection, secondary replication including vesicular lesions, and persistence. Using statistical and bioinformatic tools to analyze the differential gene expression, we identified mechanisms that could explain FMDV tissue tropism based on its association with differential expression of integrin ?V?6 heterodimeric receptor (FMDV receptor), fibronectin (ligand of the receptor), IL-1 cytokines, death receptors and the ligands, and multiple genes in the biological pathways involved in extracellular matrix turnover and interferon signaling found in this study. Our results together with reported findings indicate that differences in (1) FMDV receptor availability and accessibility, (2) type I interferon-inducible immune response, and (3) ability to clear virus infected cells via death receptor signaling play roles in determining FMDV tissue tropism and the additional increase of high extracellular matrix turnover induced by FMDV infection, likely via triggering the signaling of highly expressed IL-1 cytokines, play a key role in the pathogenesis of vesicular lesions.
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Direct analysis and identification of pathogenic Lichtheimia species by matrix-assisted laser desorption ionization-time of flight analyzer-mediated mass spectrometry.
J. Clin. Microbiol.
PUBLISHED: 11-30-2011
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Zygomycetes of the order Mucorales can cause life-threatening infections in humans. These mucormycoses are emerging and associated with a rapid tissue destruction and high mortality. The resistance of Mucorales to antimycotic substances varies between and within clinically important genera such as Mucor, Rhizopus, and Lichtheimia. Thus, an accurate diagnosis before onset of antimycotic therapy is recommended. Matrix-assisted laser desorption ionization (MALDI)-time of flight (TOF) mass spectrometry (MS) is a potentially powerful tool to rapidly identify infectious agents on the species level. We investigated the potential of MALDI-TOF MS to differentiate Lichtheimia species, one of the most important agents of mucormycoses. Using the Bruker Daltonics FlexAnalysis (version 3.0) software package, a spectral database library with m/z ratios of 2,000 to 20,000 Da was created for 19 type and reference strains of clinically relevant Zygomycetes of the order Mucorales (12 species in 7 genera). The database was tested for accuracy by use of 34 clinical and environmental isolates of Lichtheimia comprising a total of five species. Our data demonstrate that MALDI-TOF MS can be used to clearly discriminate Lichtheimia species from other pathogenic species of the Mucorales. Furthermore, the method is suitable to discriminate species within the genus. The reliability and robustness of the MALDI-TOF-based identification are evidenced by high score values (above 2.3) for the designation to a certain species and by moderate score values (below 2.0) for the discrimination between clinically relevant (Lichtheimia corymbifera, L. ramosa, and L. ornata) and irrelevant (L. hyalospora and L. sphaerocystis) species. In total, all 34 strains were unequivocally identified by MALDI-TOF MS with score values of >1.8 down to the generic level, 32 out of 34 of the Lichtheimia isolates (except CNM-CM 5399 and FSU 10566) were identified accurately with score values of >2 (probable species identification), and 25 of 34 isolates were identified to the species level with score values of >2.3 (highly probable species identification). The MALDI-TOF MS-based method reported here was found to be reproducible and accurate, with low consumable costs and minimal preparation time.
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Evidence for PTPN22 R620W polymorphism as the sole common risk variant for rheumatoid arthritis in the 1p13.2 region.
J. Rheumatol.
PUBLISHED: 10-01-2011
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The PTPN22 rs2476601 genetic variant has been associated with rheumatoid arthritis (RA) and other autoimmune diseases. Some reports suggest that this single-nucleotide polymorphism (SNP) may not be the only causal variant in the region of PTPN22. Our aim was to identify new independent RA-associated common gene variants in the PTPN22 region.
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