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Find video protocols related to scientific articles indexed in Pubmed.
Moderating effect of communication difficulty on the relationship between depression and pain: a study on community-dwelling older adults in Hong Kong.
Aging Ment Health
PUBLISHED: 10-16-2014
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Objectives: This study examined the relationship between depression and pain, and the moderating effect of communication difficulty on this relationship, among community-dwelling older adults in Hong Kong. Method: We used logistic regression to analyze secondary data regarding 12,402 Chinese older adults applying for long-term care service in Hong Kong in 2012. Results: Approximately 30% of participants were depressed and 37% experienced communication difficulty. Depression was associated with increased pain. Communication difficulty was found to moderate the relationship between depression and pain. Pain scores increased more when individuals who experienced communication difficulty reported being depressed, compared to those who did not experience communication difficulty. Conclusion: The moderating effect of communication difficulty may be explained by the interaction between depression and communication difficulty. Participants who were depressed and concurrently experienced communication difficulty may be more likely to catastrophize their pain and may tend to report or experience more pain. Health care professionals need to be aware of the different effects of communication difficulty on the pain experiences of older adults. Psychosocial intervention may be provided to minimize older adults' communication barriers to pain management.
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Report of the Jumpstarting Brain Tumor Drug Development Coalition and FDA clinical trials neuroimaging endpoint workshop (January 30, 2014, Bethesda MD).
Neuro-oncology
PUBLISHED: 10-15-2014
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On January 30, 2014, a workshop was held on neuroimaging endpoints in high-grade glioma. This workshop was sponsored by the Jumpstarting Brain Tumor Drug Development Coalition, consisting of the National Brain Tumor Society, the Society for Neuro-Oncology, Accelerate Brain Cancer Cure, and the Musella Foundation for Research and Information, and conducted in collaboration with the Food and Drug Administration. The workshop included neuro-oncologists, neuroradiologists, radiation oncologists, neurosurgeons, biostatisticians, patient advocates, and representatives from industry, clinical research organizations, and the National Cancer Institute. This report summarizes the presentations and discussions of that workshop and the proposals that emerged to improve the Response Assessment in Neuro-Oncology (RANO) criteria and standardize neuroimaging parameters.
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Biweekly cetuximab and first-line chemotherapy in chinese patients with k-ras wild-type colorectal cancers.
South Asian J Cancer
PUBLISHED: 08-20-2014
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The efficacy and safety of using combination chemotherapy with cetuximab as first-line treatment in patients with K-ras wild-type colorectal cancers has been well established. In general, weekly cetuximab was given with biweekly chemotherapy FOLFOX-4 or FOLFIRI, synchronizing them would be appealed to both patients and health care professionals.
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Design and Synthesis of an Inositol Phosphate Analog Based on Computational Docking Studies.
Tetrahedron
PUBLISHED: 08-12-2014
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A virtual library of 54 inositol analog mimics of In(1,4,5)P3 has been docked, scored, and ranked within the binding site of human inositol 1,4,5-trisphosphate 3-kinase A (IP3-3KA). Chemical synthesis of the best scoring structure that also met distance criteria for 3'-OH to -P in Phosphate has been attempted along with the synthesis of (1S,2R,3S,4S)-3-fluoro-2,4-dihydroxycyclohexanecarboxylic acid as an inositol analog, useful for non-invasive visualization and quantitation of IP3-3KA enzymatic activity.
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Domestic helpers as moderators of spousal caregiver distress.
J Gerontol B Psychol Sci Soc Sci
PUBLISHED: 04-17-2014
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Although domestic helpers increasingly play a role in elder care in many societies, there is a lack of research on their influence on caregiver distress. This study aimed to examine the influence of domestic helpers on the relationship between stressors (the care needs of frail elders and spousal provision of care) and spousal caregivers' psychological distress.
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The impact of loneliness on the relationship between depression and pain of Hong Kong Chinese terminally ill patients.
J Palliat Med
PUBLISHED: 04-09-2014
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Depression and pain often coexist in terminally ill patients, but few studies have examined their relationship among larger samples. Other psychosocial factors experienced by patients may become barriers to pain management and affect the relationship between depression and pain.
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Perfusion and diffusion characteristics of cervical cancer based on intraxovel incoherent motion MR imaging-a pilot study.
Eur Radiol
PUBLISHED: 03-20-2014
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To investigate the tissue characteristics of cervical cancer based on the intravoxel incoherent motion (IVIM) model and to assess the IVIM parameters in tissue differentiation in the female pelvis.
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Delta-24-RGD oncolytic adenovirus elicits anti-glioma immunity in an immunocompetent mouse model.
PLoS ONE
PUBLISHED: 01-01-2014
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Emerging evidence suggests anti-cancer immunity is involved in the therapeutic effect induced by oncolytic viruses. Here we investigate the effect of Delta-24-RGD oncolytic adenovirus on innate and adaptive anti-glioma immunity.
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Molecular subtypes of glioblastoma are relevant to lower grade glioma.
PLoS ONE
PUBLISHED: 01-01-2014
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Gliomas are the most common primary malignant brain tumors in adults with great heterogeneity in histopathology and clinical course. The intent was to evaluate the relevance of known glioblastoma (GBM) expression and methylation based subtypes to grade II and III gliomas (ie. lower grade gliomas).
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Associations Between Secondary Caregivers Supportive Behavior and Psychological Distress of Primary Spousal Caregivers of Cognitively Intact and Impaired Elders.
Gerontologist
PUBLISHED: 12-25-2013
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Purpose of the Study: This study examined associations between the availability and types of supportive behavior provided by secondary caregivers and the psychological distress of primary spousal caregivers of cognitively intact and impaired elders.
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Proactive infection control measures to prevent nosocomial transmission of carbapenem-resistant Enterobacteriaceae in a non-endemic area.
Chin. Med. J.
PUBLISHED: 11-30-2013
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Identification of hospitalized carbapenem-resistant Enterobacteriaceae (CRE)-positive patient is important in preventing nosocomial transmission. The objective of this study was to illustrate the implementation of proactive infection control measures in preventing nosocomial transmission of CRE in a healthcare region of over 3200 beds in Hong Kong between October 1, 2010 and December 31, 2011.
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Altered Intersubunit Communication Is the Molecular Basis for Functional Defects of Pathogenic p97 Mutants.
J. Biol. Chem.
PUBLISHED: 11-06-2013
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The human AAA ATPase p97 is a molecular chaperone essential in cellular proteostasis. Single amino acid substitutions in p97 have been linked to a clinical multiple-disorder condition known as inclusion body myopathy associated with Pagets disease of the bone and frontotemporal dementia. How the mutations affect the molecular mechanism that governs the function of p97 remains unclear. Here, we show that within the hexameric ring of a mutant p97, D1 domains fail to regulate their respective nucleotide-binding states, as evidenced by the lower amount of prebound ADP, weaker ADP binding affinity, full occupancy of adenosine-5-O-(3-thiotriphosphate) binding, and elevated overall ATPase activity, indicating a loss of communication among subunits. Defective communication between subunits is further illustrated by altered conformation in the side chain of residue Phe-360 that probes into the nucleotide-binding pocket from a neighboring subunit. Consequently, conformations of N domains in a hexameric ring of a mutant p97 become uncoordinated, thus impacting its ability to process substrate.
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X-linked glycogen storage disease IXa manifested in a female carrier due to skewed X chromosome inactivation.
Clin. Chim. Acta
PUBLISHED: 07-15-2013
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Glycogen storage disease (GSD) is a group of inherited metabolic disorders due to enzymatic deficiency involved in glycogen breakdown. In various subtypes of GSD, GSD IXa is an X-linked recessive disorder, which only manifested in males. Here, we report a case of X-linked GSD IXa manifested in a female Chinese patient accompanying a skewed X-chromosome inactivation (XCI).
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Biomarker-based adaptive trials for patients with glioblastoma--lessons from I-SPY 2.
Neuro-oncology
PUBLISHED: 07-14-2013
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The traditional clinical trials infrastructure may not be ideally suited to evaluate the numerous therapeutic hypotheses that result from the increasing number of available targeted agents combined with the various methodologies to molecularly subclassify patients with glioblastoma. Additionally, results from smaller screening studies are rarely translated to successful larger confirmatory studies, potentially related to a lack of efficient control arms or the use of unvalidated surrogate endpoints. Streamlining clinical trials and providing a flexible infrastructure for biomarker development is clearly needed for patients with glioblastoma. The experience developing and implementing the I-SPY studies in breast cancer may serve as a guide to developing such trials in neuro-oncology.
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Complication rates of central compartment dissection in papillary thyroid cancer.
ANZ J Surg
PUBLISHED: 06-29-2013
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The benefits of central compartment dissection (CCD) in papillary thyroid carcinoma (PTC) are still debatable and should be weighed against its potential risks. We aim to compare the complication rates in total thyroidectomy with and without CCD for patients with PTC.
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Elevated circulating adipocyte-fatty acid binding protein levels predict incident cardiovascular events in a community-based cohort: a 12-year prospective study.
J Am Heart Assoc
PUBLISHED: 03-26-2013
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Obesity is closely associated with various cardiovascular diseases (CVDs). Adipose tissue inflammation and perturbation of adipokine secretion may contribute to the pathogenesis of CVD. This study aimed to evaluate whether the 2 most abundant adipokines, adipocyte-fatty acid binding protein (A-FABP) and adiponectin, are independent risk factors predisposing to CVD.
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Structural basis for the specific recognition of dual receptors by the homopolymeric pH 6 antigen (Psa) fimbriae of Yersinia pestis.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 01-02-2013
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The pH 6 antigen (Psa) of Yersinia pestis consists of fimbriae that bind to two receptors: ?1-linked galactosyl residues in glycosphingolipids and the phosphocholine group in phospholipids. Despite the ubiquitous presence of either moiety on the surface of many mammalian cells, Y. pestis appears to prefer interacting with certain types of human cells, such as macrophages and alveolar epithelial cells of the lung. The molecular mechanism of this apparent selectivity is not clear. Site-directed mutagenesis of the consensus choline-binding motif in the sequence of PsaA, the subunit of the Psa fimbrial homopolymer, identified residues that abolish galactosylceramide binding, phosphatidylcholine binding, or both. The crystal structure of PsaA in complex with both galactose and phosphocholine reveals separate receptor binding sites that share a common structural motif, thus suggesting a potential interaction between the two sites. Mutagenesis of this shared structural motif identified Tyr126, which is part of the choline-binding consensus sequence but is found in direct contact with the galactose in the structure of PsaA, important for both receptor binding. Thus, this structure depicts a fimbrial subunit that forms a polymeric adhesin with a unique arrangement of dual receptor binding sites. These findings move the field forward by providing insights into unique types of multiple receptor-ligand interactions and should steer research into the synthesis of dual receptor inhibitor molecules to slow down the rapid progression of plague.
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Pro-inflammatory adipokines as predictors of incident cancers in a chinese cohort of low obesity prevalence in Hong Kong.
PLoS ONE
PUBLISHED: 01-01-2013
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Cytokines released from adipose tissues induce chronic low-grade inflammation, which may enhance cancer development. We investigated whether indices of obesity and circulating adipokine levels could predict incident cancer risk.
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Phenylketonuria in Hong Kong Chinese: a call for hyperphenylalaninemia newborn screening in the Special Administrative Region, China.
Chin. Med. J.
PUBLISHED: 09-22-2011
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Hyperphenylalaninemia is one of the commonest inborn errors of metabolism affecting approximately 1 in 15,000 livebirths. Among Chinese, BH4 deficiency leading to hyperphenylalaninemia is much commoner than in Caucasians. Exact diagnosis is important for the treatment and genetic counseling. In 2000, newborn screening for phenylketonuria is mandatory by law in China throughout the whole country. However, it is not yet included in the newborn screening program of the Hong Kong Special Administrative Region, China. Published data on hyperphenylalaninemia among HongKong Chinese are largely lacking. We report a 1-year-old Hong Kong Chinese girl with severe 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency. The patient presented with infantile hypotonia and was misdiagnosed as cerebral palsy. She had very mild hyperphenylalaninemia (95 ?mol/L), significantly high phenylalnine-to-tyrosine ratio (3.1), and elevated prolactin of 1109 mIU/L. Genetic analysis confirmed a homozygous known disease-causing mutation PTS NM_000317.1:c.259C>T; NP_000308.1: p.P87S in the proband. In our local experience, while the estimated prevalence of hyperphenylalaninemia due to PTPS deficiency was reported to be 1 in 29,542 live births, not a single case of phenylalanine hydroxylase deficiency has been reported. Furthermore, there is a general lack of awareness of inherited metabolic diseases in the community as well as among the medical professionals. Very often, a low index of clinical suspicion will lead to delay in diagnosis, multiple unnecessary and costly investigations, prolonged morbidity and anxiety to the family affected. We strongly recommend that expanded newborn screening for hyperphenylalaninemia should be implemented for every baby born in the Hong Kong Special Administrative Region, China.
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Psychological distress among Chinese adult-child caregivers: the effects of behavioral and cognitive components of care.
Home Health Care Serv Q
PUBLISHED: 08-18-2011
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This study examined the effects of behavioral and cognitive components of care on caregivers psychological distress among adult children who were the primary caregivers of frail older adults living in the community in Hong Kong. The sample was drawn from a 2008 data set that was used to determine the eligibility for long-term care in Hong Kong. Logistic regressions evaluated the association between caregiver psychological distress and the behavioral and cognitive components of care with a range of covariates. About 35% of the caregivers showed signs of psychological distress. Caregivers who provided more care for instrumental activities of daily living (IADLs), demonstrated a greater intensity of care, lived with the care recipient, or became dissatisfied with the amount of support received from other family members and friends were more likely to express psychological distress. Providing emotional support to the care recipient and being unable to continue providing care were negatively associated with psychological distress, after controlling for the sociodemographic status and health status of the care recipient.
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Study of the PM?? concentration variations along two intra-urban roads within a compact city.
Environ Monit Assess
PUBLISHED: 07-15-2011
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Eighty-five measurement campaigns were performed repeatedly to compare the concentration variation profiles along two intra-urban roads-one with open configuration and the other with street canyon effect. Fixed-effects panel data analysis was applied for formulating a model to express the PM(10) concentrations along intra-urban roads in terms of parameters like nearby central monitoring data, traffic counts and meteorological conditions with an objective to analyze the PM(10) concentration variation patterns along the two roads. Our findings reveal that traffic intensity and metrological conditions exert influence on concentration variation for both types of road configurations while wind velocity only affect the pollutants removal effectiveness of open road configuration. Further analysis unveils that the PM(10) concentration distribution profiles within a compact city environment are not always uniform and are dependent on the road configuration. Considerable PM(10) concentration differences were observed along the street canyon, and 70% of their variations are attributed to variations in their road aspect ratios. By contrast, no significant concentration difference is observed at open road configurations.
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Novel nonsense CDC73 mutations in Chinese patients with parathyroid tumors.
Fam. Cancer
PUBLISHED: 07-07-2011
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Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is an autosomal dominant disease characterized by the occurrences of parathyroid tumors and ossifying fibroma of maxilla/mandible. It is caused by mutations in CDC73 gene and mutation carriers are at increased risk of parathyroid carcinoma. Hyperparathyroidism could be the sole manifestation. We reported two Chinese patients having parathyroid neoplasm with equivocal malignant potential and parathyroid carcinoma respectively with both germline and somatic CDC73 mutations detected. Both of them presented with severe hypercalcemia and primary hyperparathyroidism with no other HPT-JT associated tumors and negative family history. We identified one novel germline mutation CDC73 NM_024529.4: c.1475G > A; NP_078805.3: p.Trp492X and one novel somatic mutation CDC73 NM_024529.4: c.142G > T; NP_078805.3: p.Glu48X. The other germline mutation CDC73 NM_024529.4: c.226C > T; NP_078805.3: p.Arg76X and somatic mutation CDC73 NM_024529.4: c.85delG; NP_078805.3: p.Glu29SerfsX8 were previously reported. This is the first report of CDC73 mutations in the Chinese population. Genetic analysis is reliable to confirm the underlying hereditary basis of hyperparathyroidism. By identification of mutations, the patient and the family members could benefit from regular surveillance for early detection of tumors.
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Fatal viral infection-associated encephalopathy in two Chinese boys: a genetically determined risk factor of thermolabile carnitine palmitoyltransferase II variants.
J. Hum. Genet.
PUBLISHED: 06-23-2011
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Influenza-associated encephalopathy (IAE) is a potentially fatal neurological complication of influenza infection usually in the presence of high and persistent fever. Thermolabile carnitine palmitoyltransferase II enzyme (CPT-II) predisposes IAE, so far only described in Japanese. As the genetic origins of Japanese and Chinese are alike, similar genetic risk factors in CPT-II are expected. We report the first two unrelated Chinese patients of thermolabile CPT-II variants that underlain the persistent high fever-triggered viral infection-associated encephalopathy, multi-organ failure and death. Elevated (C16:0+C18:1)/C2 acylcarnitines ratio and the CPT2 susceptibility variant allele [p.Phe352Cys; p.Val368Ile] were detected. The asymptomatic family members of one patient also had abnormal long-chain acylcarnitines. In our experience of biochemical genetics, the elevated (C16:0+C18:1)/C2 acylcarnitines ratio is unusual and specific for thermolabile CPT-II variants. Allele frequency of [p.Phe352Cys; p.Val368Ile] among Hong Kong Chinese was 0.104, similar to Japanese data, and [p.Phe352Cys] has not been reported in Caucasians. This may explain the Asian-specific phenomenon of thermolabile CPT-II-associated IAE. We successfully demonstrated the thermolabile CPT-II variants in patients with viral infection-associated encephalopathy in another Asian population outside Japanese. The condition is likely under-recognized. With our first cases, it is envisaged that more cases will be diagnosed in subsequent years. The exact pathogenic mechanism of how other factors interplay with thermolabile CPT-II variants and high fever leading to IAE, is yet to be elucidated. Fasting and decreased intake during illness may aggravate the disease. Further studies including high risk and neonatal screening are warranted to investigate its expressivity, penetrance and temperature-dependent behaviors in thermolabile CPT-II carriers. This may lead to discovery of the therapeutic golden window by aggressive antipyretics and L-carnitine administration in avoiding the high mortality and morbidity of IAE.
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An attenuated strain of Bacillus anthracis (CDC 684) has a large chromosomal inversion and altered growth kinetics.
BMC Genomics
PUBLISHED: 05-11-2011
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An isolate originally labeled Bacillus megaterium CDC 684 was found to contain both pXO1 and pXO2, was non-hemolytic, sensitive to gamma-phage, and produced both the protective antigen and the poly-D-glutamic acid capsule. These phenotypes prompted Ezzell et al., (J. Clin. Microbiol. 28:223) to reclassify this isolate to Bacillus anthracis in 1990.
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Analysis of inborn errors of metabolism: disease spectrum for expanded newborn screening in Hong Kong.
Chin. Med. J.
PUBLISHED: 05-06-2011
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Data of classical inborn errors of metabolism (IEM) of amino acids, organic acids and fatty acid oxidation are largely lacking in Hong Kong, where mass spectrometry-based expanded newborn screening for IEM has not been initiated. The current study aimed to evaluate the approximate incidence, spectrum and other characteristics of classical IEM in Hong Kong, which would be important in developing an expanded newborn screening program for the local area.
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Systemic sclerosis is an independent risk factor for increased coronary artery calcium deposition.
Arthritis Rheum.
PUBLISHED: 05-04-2011
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Endothelial dysfunction and inflammation are pathogenic mechanisms common to systemic sclerosis (SSc) and atherosclerosis. This study was undertaken to examine the relationship between coronary atherosclerosis, as assessed by the coronary artery calcium score (CACS), and conventional cardiovascular and disease-specific risk factors in SSc patients.
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Molecular basis of von Hippel-Lindau syndrome in Chinese patients.
Chin. Med. J.
PUBLISHED: 03-03-2011
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Von Hippel-Lindau (VHL) syndrome is an autosomal dominant familial cancer syndrome predisposing the affected individuals to multiple tumours in various organs. The genetic basis of VHL in Southern Chinese is largely unknown. In this study, we characterized the mutation spectrum of VHL in nine unrelated Southern Chinese families.
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Graft suturing for lenticule dislocation after descemet stripping automated endothelial keratoplasty.
J Ophthalmic Vis Res
PUBLISHED: 02-28-2011
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To report the mid-term outcomes of graft suturing in a patient with lenticule dislocation after Descemet stripping automated endothelial keratoplasty (DSAEK).
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Non-invasive screening of HLA-DPA1 and HLA-DPB1 alleles for persistent hepatitis B virus infection: susceptibility for vertical transmission and toward a personalized approach for vaccination and treatment.
Clin. Chim. Acta
PUBLISHED: 01-24-2011
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Polymorphisms in the major histocompatibility complex (MHC) and non-MHC genes were recently reported to be associated with persistent hepatitis B virus (HBV) infection and host response to hepatitis B vaccine in Asian populations. We aimed to confirm the associations in Chinese population and develop a non-invasive screening method for the risk loci.
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Ischemic stroke related to intracranial branch atheromatous disease and comparison with large and small artery diseases.
J. Neurol. Sci.
PUBLISHED: 01-07-2011
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The mechanism of ischemic stroke in intracranial branch atheromatous disease (BAD) is different from large artery atherothrombotic disease (LAD) or lacunar infarction (LACI). The concept of BAD is underused in clinical practice and research.
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Maraviroc is a substrate for OATP1B1 in vitro and maraviroc plasma concentrations are influenced by SLCO1B1 521 T>C polymorphism.
Pharmacogenet. Genomics
PUBLISHED: 11-19-2010
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Organic anion transporting polypeptides (OATPs) are emerging as major determinants of pharmacokinetics for numerous drugs, with the 1B1 isoform-mediating hepatic uptake. The 521 T>C polymorphism has been correlated earlier with higher plasma concentrations of several drugs and the aim of this study was to determine whether this polymorphism influences trough concentrations of maraviroc.
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Raltegravir is a substrate for SLC22A6: a putative mechanism for the interaction between raltegravir and tenofovir.
Antimicrob. Agents Chemother.
PUBLISHED: 11-15-2010
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The identification of transporters of the HIV integrase inhibitor raltegravir could be a factor in an understanding of the pharmacokinetic-pharmacodynamic relationship and reported drug interactions of raltegravir. Here we determined whether raltegravir was a substrate for ABCB1 or the influx transporters SLCO1A2, SLCO1B1, SLCO1B3, SLC22A1, SLC22A6, SLC10A1, SLC15A1, and SLC15A2. Raltegravir transport by ABCB1 was studied with CEM, CEM(VBL100), and Caco-2 cells. Transport by uptake transporters was assessed by using a Xenopus laevis oocyte expression system, peripheral blood mononuclear cells, and primary renal cells. The kinetics of raltegravir transport and competition between raltegravir and tenofovir were also investigated using SLC22A6-expressing oocytes. Raltegravir was confirmed to be an ABCB1 substrate in CEM, CEM(VBL100), and Caco-2 cells. Raltegravir was also transported by SLC22A6 and SLC15A1 in oocyte expression systems but not by other transporters studied. The K(m) and V(max) for SLC22A6 transport were 150 ?M and 36 pmol/oocyte/h, respectively. Tenofovir and raltegravir competed for SLC22A6 transport in a concentration-dependent manner. Raltegravir inhibited 1 ?M tenofovir with a 50% inhibitory concentration (IC(50)) of 14.0 ?M, and tenofovir inhibited 1 ?M raltegravir with an IC(50) of 27.3 ?M. Raltegravir concentrations were not altered by transporter inhibitors in peripheral blood mononuclear cells or primary renal cells. Raltegravir is a substrate for SLC22A6 and SLC15A1 in the oocyte expression system. However, transport was limited compared to endogenous controls, and these transporters are unlikely to have a great impact on raltegravir pharmacokinetics.
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Molecular interaction of flagellar export chaperone FliS and cochaperone HP1076 in Helicobacter pylori.
FASEB J.
PUBLISHED: 06-25-2010
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Flagellar export chaperone FliS prevents premature polymerization of flagellins and is critical for flagellar assembly and bacterial colonization. Previously, a yeast 2-hybrid study identified various FliS-associated proteins in Helicobacter pylori, but the implications of these interactions are not known. Here we demonstrate the biophysical interaction of FliS (HP0753) and the uncharacterized protein HP1076 from H. pylori. HP1076 possesses a cochaperone activity that promotes the folding and chaperone activity of FliS. We further determined the crystal structures of FliS, HP1076, and the binary complex at 2.7, 1.8, and 2.7 ? resolution, respectively. HP1076 adopts a helix-rich bundle structure and interestingly shares a similar fold with a flagellin homologue, hook-associated protein, and FliS. The FliS-HP1076 complex revealed an extensive electrostatic and hydrophobic binding interface, which is distinct from the flagellin binding pocket in FliS. The helical stacking interaction between HP1076 and FliS suggests that HP1076 stabilizes 2 ? helices of FliS and therefore the overall structure of the bundle. Our findings provide new insights into flagellar export chaperones and may have implications for other secretion chaperones in the type III secretion system.
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Chronic hepatitis C genotype 6 responds better to pegylated interferon and ribavirin combination therapy than genotype 1.
J. Gastroenterol. Hepatol.
PUBLISHED: 05-25-2010
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Chronic hepatitis C genotype 6 is common in Hong Kong, especially among i.v. drug abusers. Responses of these patients to combination of pegylated interferon and ribavirin treatment were inconsistent and the numbers of patients involved in previous studies were small. We performed a retrospective study to compare the therapeutic responses of this regimen in patients infected with genotype 6 and genotype 1.
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A novel ATP-dependent conformation in p97 N-D1 fragment revealed by crystal structures of disease-related mutants.
EMBO J.
PUBLISHED: 04-26-2010
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Mutations in p97, a major cytosolic AAA (ATPases associated with a variety of cellular activities) chaperone, cause inclusion body myopathy associated with Pagets disease of the bone and frontotemporal dementia (IBMPFD). IBMPFD mutants have single amino-acid substitutions at the interface between the N-terminal domain (N-domain) and the adjacent AAA domain (D1), resulting in a reduced affinity for ADP. The structures of p97 N-D1 fragments bearing IBMPFD mutations adopt an atypical N-domain conformation in the presence of Mg(2+).ATPgammaS, which is reversible by ADP, showing for the first time the nucleotide-dependent conformational change of the N-domain. The transition from the ADP- to the ATPgammaS-bound state is accompanied by a loop-to-helix conversion in the N-D1 linker and by an apparent re-ordering in the N-terminal region of p97. X-ray scattering experiments suggest that wild-type p97 subunits undergo a similar nucleotide-dependent N-domain conformational change. We propose that IBMPFD mutations alter the timing of the transition between nucleotide states by destabilizing the ADP-bound form and consequently interfere with the interactions between the N-domains and their substrates.
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Selective isolation of Yersinia pestis from plague-infected fleas.
J. Microbiol. Methods
PUBLISHED: 03-29-2010
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We evaluated Yersinia CIN agar for the isolation of Yersinia pestis from infected fleas. CIN media is effective for the differentiation of Y. pestis from flea commensal flora and is sufficiently inhibitory to other bacteria that typically outcompete Y. pestis after 48 h of growth using less selective media.
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HIV protease inhibitors are substrates for OATP1A2, OATP1B1 and OATP1B3 and lopinavir plasma concentrations are influenced by SLCO1B1 polymorphisms.
Pharmacogenet. Genomics
PUBLISHED: 01-07-2010
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OATP1B1 and OATP1B3 are major hepatic drug transporters whilst OATP1A2 is mainly located in the brain but is also located in liver and several other organs. These transporters affect the distribution and clearance of many endobiotics and xenobiotics and have been reported to have functional single nucleotide polymorphisms (SNPs). We have assessed the substrate specificities of these transporters for a panel of antiretrovirals and investigated the effects of SNPs within these transporters on the pharmacokinetics of lopinavir.
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Intracellular accumulation of efavirenz and nevirapine is independent of P-glycoprotein activity in cultured CD4 T cells and primary human lymphocytes.
J. Antimicrob. Chemother.
PUBLISHED: 09-11-2009
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Interaction of antiretrovirals with drug transporters such as P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), breast cancer resistance protein (BCRP) and solute carrier organic anion transporter (SLCO) may influence the emergence of viral mutants by altering intracellular drug concentrations. Here we characterize the effect of transporter expression in a variety of cell types such as control CEM, CEM(VBL) (P-gp-overexpressing), CEM(E1000) (MRP1-overexpressing), MT4, control MDCKII, MDCKII(MDR1) (P-gp-overexpressing) and peripheral blood mononuclear cells (PBMCs) on the uptake of [(14)C]efavirenz and [(3)H]nevirapine. We also investigated the lipophilicity of [(14)C]efavirenz and [(3)H]nevirapine.
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Intracellular boosting of darunavir using known transport inhibitors in primary PBMC.
Br J Clin Pharmacol
PUBLISHED: 09-11-2009
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ABCB1, some ABCCs and SLCOs have been reported to affect the intracellular accumulation of various protease inhibitors in vitro and ex vivo. Darunavir is the most recently licensed protease inhibitor and we sought to investigate the ability of transport inhibitors to influence its intracellular accumulation in lymphocytes from healthy volunteers.
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Purification, crystallization and preliminary X-ray diffraction analysis of disease-related mutants of p97.
Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun.
PUBLISHED: 07-14-2009
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The human type II AAA+ protein p97 participates in various cellular activities, presumably through its involvement in the ubiquitin-proteasome degradation pathway. Mutations in p97 have been implicated in patients with inclusion-body myopathy associated with Pagets disease of the bone and frontotemporal dementia (IBMPFD). In this work, three mutant p97 N-D1 fragments, R86A, R95G and R155H, were crystallized in the presence of ATPgammaS with PEG 3350 as a main precipitant, yielding two different crystal forms. The R155H mutant crystal belonged to space group R3, with unit-cell parameters in the hexagonal setting of a = b = 134.2, c = 182.9 angstrom, and was merohedrally twinned, with an estimated twin fraction of 0.34. The crystals of the R86A and R95G mutants belonged to space group P1, with similar unit-cell parameters of a = 90.89, b = 102.6, c = 107.2 angstrom, alpha = 97.5, beta = 90.6, gamma = 91.5 degrees and a = 92.76, b = 103.7, c = 107.7 angstrom , alpha = 97.7, beta = 91.9, gamma = 89.7 degrees, respectively.
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Molecular characterization of low pathogenic avian influenza viruses, isolated from food products imported into Singapore.
Vet. Microbiol.
PUBLISHED: 04-04-2009
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We have completed the genetic characterization of all eight gene segments for four low pathogenic avian influenza (LPAI) viruses. The objective of this study was to detect the presence of novel signatures that may serve as early warning indicators of the conversion of LPAI viruses to high pathogenic avian influenza (HPAI) viruses. This study included three H5N2 and one H5N3 viruses that were isolated from live poultry imported into Singapore as part of the national avian influenza virus (AIV) surveillance program. Based on the molecular criterion of the World Organisation for Animal Health (OIE), sequence analysis with the translated amino acid (aa) sequence of the hemagglutinin (HA) gene revealed the absence of multibasic aa at the HA cleavage site, identifying all four virus isolates as LPAI. Detailed phylogenetic tree analyses using the HA and neuraminidase (NA) genes clustered these isolates in the Eurasian H5 lineage, but away from the HPAI H5 subtypes. This analysis further revealed that the internal genes clustered to different avian and swine subtypes, suggesting that the four isolates may possibly share their ancestry with these different influenza subtypes. Our results suggest that the four LPAI isolates in this study contained mainly avian signatures, and the phylogenetic tree for the internal genes further suggests the potential for reassortment with other different circulating avian subtypes. This is the first comprehensive report on the genetic characterization of LPAI H5N2/3 viruses isolated in South-East Asia.
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Maternally inherited Leigh syndrome: an unusual cause of infantile apnea.
Sleep Breath
PUBLISHED: 02-09-2009
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Leigh Syndrome is an uncommon cause of infantile apnea.
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Engineered glucagon-like peptide-1-producing hepatocytes lower plasma glucose levels in mice.
Am. J. Physiol. Endocrinol. Metab.
PUBLISHED: 02-03-2009
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Glucagon-like peptide (GLP)-1 is an incretin hormone with well-characterized antidiabetic properties, including glucose-dependent stimulation of insulin secretion and enhancement of beta-cell mass. GLP-1 agonists have recently been developed and are now in clinical use for the treatment of type 2 diabetes. Rapid degradation of GLP-1 by enzymes including dipeptidyl-peptidase (DPP)-IV and neutral endopeptidase (NEP) 24.11, along with renal clearance, contribute to a short biological half-life, necessitating frequent injections to maintain therapeutic efficacy. Gene therapy may represent a promising alternative approach for achieving long-term increases in endogenous release of GLP-1. We have developed a novel strategy for glucose-regulated production of GLP-1 in hepatocytes by expressing a DPP-IV-resistant GLP-1 peptide in hepatocytes under control of the liver-type pyruvate kinase promoter. Adenoviral delivery of this construct to hepatocytes in vitro resulted in production and secretion of bioactive GLP-1 as measured by a luciferase-based bioassay developed to detect the NH2-terminally modified GLP-1 peptide engineered for this study. Transplantation of encapsulated hepatocytes into CD-1 mice resulted in an increase in plasma GLP-1 levels that was accompanied by a significant reduction in fasting plasma glucose levels. The results from this study demonstrate that a gene therapy approach designed to induce GLP-1 production in hepatocytes may represent a novel strategy for long-term secretion of bioactive GLP-1 for the treatment of type 2 diabetes.
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Pre-Columbian origins for North American anthrax.
PLoS ONE
PUBLISHED: 01-28-2009
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Disease introduction into the New World during colonial expansion is well documented and had a major impact on indigenous populations; however, few diseases have been associated with early human migrations into North America. During the late Pleistocene epoch, Asia and North America were joined by the Beringian Steppe ecosystem which allowed animals and humans to freely cross what would become a water barrier in the Holocene. Anthrax has clearly been shown to be dispersed by human commerce and trade in animal products contaminated with Bacillus anthracis spores. Humans appear to have brought B. anthracis to this area from Asia and then moved it further south as an ice-free corridor opened in central Canada approximately 13,000 ybp. In this study, we have defined the evolutionary history of Western North American (WNA) anthrax using 2,850 single nucleotide polymorphisms (SNPs) and 285 geographically diverse B. anthracis isolates. Phylogeography of the major WNA B. anthracis clone reveals ancestral populations in northern Canada with progressively derived populations to the south; the most recent ancestor of this clonal lineage is in Eurasia. Our phylogeographic patterns are consistent with B. anthracis arriving with humans via the Bering Land Bridge. This northern-origin hypothesis is highly consistent with our phylogeographic patterns and rates of SNP accumulation observed in current day B. anthracis isolates. Continent-wide dispersal of WNA B. anthracis likely required movement by later European colonizers, but the continents first inhabitants may have seeded the initial North American populations.
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Development of a prototype of the tele-localisation system in radiotherapy using personal digital assistant via wireless communication.
J Med Imaging Radiat Oncol
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In localisation of radiotherapy treatment field, the oncologist is present at the simulator to approve treatment details produced by the therapist. Problems may arise if the oncologist is not available and the patient requires urgent treatment. The development of a tele-localisation system is a potential solution, where the oncologist uses a personal digital assistant (PDA) to localise the treatment field on the image sent from the simulator through wireless communication and returns the information to the therapist after his or her approval. Our team developed the first tele-localisation prototype, which consisted of a server workstation (simulator) for the administration of digital imaging and communication in medicine localisation images including viewing and communication with the PDA via a Wi-Fi network; a PDA (oncologists site) installed with the custom-built programme that synchronises with the server workstation and performs treatment field editing. Trial tests on accuracy and speed of the prototype system were conducted on 30 subjects with the treatment regions covering the neck, skull, chest and pelvis. The average time required in performing the localisation using the PDA was less than 1.5?min, with the blocked field longer than the open field. The transmission speed of the four treatment regions was similar. The average physical distortion of the images was within 4.4% and the accuracy of field size indication was within 5.3%. Compared with the manual method, the tele-localisation system presented with an average deviation of 5.5%. The prototype system fulfilled the planned objectives of tele-localisation procedure with reasonable speed and accuracy.
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Structural analysis of cytochrome bc1 complexes: implications to the mechanism of function.
Biochim. Biophys. Acta
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The cytochrome bc1 complex (bc1) is the mid-segment of the cellular respiratory chain of mitochondria and many aerobic prokaryotic organisms; it is also part of the photosynthetic apparatus of non-oxygenic purple bacteria. The bc1 complex catalyzes the reaction of transferring electrons from the low potential substrate ubiquinol to high potential cytochrome c. Concomitantly, bc1 translocates protons across the membrane, contributing to the proton-motive force essential for a variety of cellular activities such as ATP synthesis. Structural investigations of bc1 have been exceedingly successful, yielding atomic resolution structures of bc1 from various organisms and trapped in different reaction intermediates. These structures have confirmed and unified results of decades of experiments and have contributed to our understanding of the mechanism of bc1 functions as well as its inactivation by respiratory inhibitors. This article is part of a Special Issue entitled: Respiratory complex III and related bc complexes.
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The use of high-resolution melting analysis for rapid spa typing on methicillin-resistant Staphylococcus aureus clinical isolates.
J. Microbiol. Methods
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Methicillin-resistant Staphylococcus aureus (MRSA) has been endemic in Hong Kong for three decades. This study evaluated the practical use of high-resolution melting (HRM) real-time PCR analysis on MRSA staphylococcal Protein A (spa) typing on local MRSA isolates. Among 55 clinical MRSA isolates collected in 2011, 12 different spa types were observed by the conventional PCR-sequencing method including the locally predominant spa type t1081 and two locally predominant community acquired MRSA spa types t019 and t437. By using the HRM method, it could differentiate all 12 spa genotypes by distinct melting curves and HRM difference plot analysis. These two methods demonstrated 100% concordance whereas the HRM method required only 3h of turnaround time and one-fifth of reagent cost compared to the conventional method. Our study confirmed that the cost effective and rapid HRM typing approach is practically useful for MRSA community transmission monitoring and nosocomial outbreak control in Hong Kong.
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Trajectories of social engagement and depressive symptoms among long-term care facility residents in Hong Kong.
Age Ageing
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although social engagement and depressive symptoms are important concerns for long-term care facility residents, the dynamic relationship between them has not been adequately studied.
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Electronic chemical pathology consultation service and dried blood spot metabolic screening in hospital patients.
J. Clin. Pathol.
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Inborn errors of metabolism (IEM) are an unpopular and difficult subject and most clinicians are unfamiliar with them. Although chemical pathologists have a long-standing practice in advising test strategy and result interpretation especially from primary care, such consultations are usually informal, unstructured and those related to IEM are infrequently requested. This study aims to provide a formal electronic consultation service and to apply tandem mass spectrometry-based dried blood spot metabolic screening (DBSM) as a rapid first-line test for patients suspected of IEM.
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BMP-dependent serosa and amnion specification in the scuttle fly Megaselia abdita.
Development
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Bone morphogenetic protein (BMP) signaling is an essential factor in dorsoventral patterning of animal embryos but how BMP signaling evolved with fundamental changes in dorsoventral tissue differentiation is unclear. Flies experienced an evolutionary reduction of extra-embryonic tissue types from two (amniotic and serosal tissue) to one (amnionserosal tissue). BMP-dependent amnioserosa specification has been studied in Drosophila melanogaster. However, the mechanisms of serosal and amniotic tissue specification in less diverged flies remain unknown. To better understand potential evolutionary links between BMP signaling and extra-embryonic tissue specification, we examined the activity profile and function of BMP signaling in serosa and amnion patterning of the scuttle fly Megaselia abdita (Phoridae) and compared the BMP activity profiles between M. abdita and D. melanogaster. In blastoderm embryos of both species, BMP activity peaked at the dorsal midline. However, at the beginning of gastrulation, peak BMP activity in M. abdita shifted towards prospective amnion tissue. This transition correlated with the first signs of amnion differentiation laterally adjacent to the serosa anlage. Marker-assisted analysis of six BMP signaling components (dpp, gbb, scw, tkv, sax, sog) by RNA interference revealed that both serosa and amnion specification of M. abdita are dependent on BMP activity. Conversely, BMP gain-of-function experiments caused sharpened expression boundaries of extra-embryonic target genes indicative of positive feedback. We propose that changes in the BMP activity profile at the beginning of gastrulation might have contributed to the reduction of extra-embryonic tissue types during the radiation of cyclorrhaphan flies.
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Characterization of crystals of an antibody-recognition fragment of the cancer differentiation antigen mesothelin in complex with the therapeutic antibody MORAb-009.
Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun.
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The mesothelin-specific monoclonal antibody MORAb-009 is capable of blocking the binding of mesothelin to CA-125 and displays promising anticancer potential. It is currently undergoing clinical trials. In order to understand the basis of the interaction between MORAb-009 and mesothelin at atomic resolution, both the Fab fragment of MORAb-009 and the complex between the Fab and an N-terminal fragment of mesothelin (residues 7-64) were crystallized. The crystals of the Fab diffracted X-rays to 1.75?Å resolution and had the symmetry of space group P4(1)2(1)2, with unit-cell parameters a = b = 140.6, c = 282.0?Å. The crystals of the mesothelin-Fab complex diffracted to 2.6?Å resolution and belonged to the hexagonal space group P6(4), with unit-cell parameters a = b = 146.2, c = 80.9?Å. Structural analyses of these molecules are in progress.
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Molecular diagnosis for a fatal case of very long-chain acyl-CoA dehydrogenase deficiency in Hong Kong Chinese with a novel mutation: a preventable death by newborn screening.
Diagn. Mol. Pathol.
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Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is one of the most common fatty acid oxidation defects that cause sudden unexpected deaths in infants. The death attributed to VLCAD deficiency can be prevented by early diagnosis with expanded newborn screening using tandem mass spectrometry. A favorable outcome can be achieved with early diagnosis and prompt treatment. However, such newborn screening has not yet been available in Hong Kong. We report a 2-month-old boy who succumbed 5 hours after admission with the diagnosis of VLCAD deficiency confirmed by genetic analysis performed after death. The patient was compound heterozygous for a novel splicing mutation ACADVL NM_000018.2:c.277+2T>G; NC_000017.10:g.7123997T>G and a known disease-causing mutation ACADVL NM_000018.2:c.388_390del; NP_000009.1: p.Glu130del. Family screening was performed for at-risk siblings. The rapid downhill course of the patient clearly illustrates the need of newborn screening for early diagnosis. Our patient was asymptomatic before metabolic decompensation. However, once metabolic decompensation occurred, rapid deterioration and death followed, which obviated the opportunity to diagnose and treat. The only way to save these patients lives and improve their outcome is early diagnosis and appropriate treatment. Therefore, we strongly urge the implementation of newborn screening using tandem mass spectrometry for VLCAD deficiency and other highly treatable inborn errors of metabolism in Hong Kong.
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Molecular epidemiologic investigation of an anthrax outbreak among heroin users, Europe.
Emerging Infect. Dis.
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In December 2009, two unusual cases of anthrax were diagnosed in heroin users in Scotland. A subsequent anthrax outbreak in heroin users emerged throughout Scotland and expanded into England and Germany, sparking concern of nefarious introduction of anthrax spores into the heroin supply. To better understand the outbreak origin, we used established genetic signatures that provided insights about strain origin. Next, we sequenced the whole genome of a representative Bacillus anthracis strain from a heroin user (Ba4599), developed Ba4599-specific single-nucleotide polymorphism assays, and genotyped all available material from other heroin users with anthrax. Of 34 case-patients with B. anthracis-positive PCR results, all shared the Ba4599 single-nucleotide polymorphism genotype. Phylogeographic analysis demonstrated that Ba4599 was closely related to strains from Turkey and not to previously identified isolates from Scotland or Afghanistan, the presumed origin of the heroin. Our results suggest accidental contamination along the drug trafficking route through a cutting agent or animal hides used to smuggle heroin into Europe.
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Recognition of mesothelin by the therapeutic antibody MORAb-009: structural and mechanistic insights.
J. Biol. Chem.
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Mesothelin is a tumor differentiation antigen that is highly expressed in many epithelial cancers, with limited expression in normal human tissues. Binding of mesothelin on normal mesothelial cells lining the pleura or peritoneum to the tumor-associated cancer antigen 125 (CA-125) can lead to heterotypic cell adhesion and tumor metastasis within the pleural and peritoneal cavities. This binding can be prevented by MORAb-009, a humanized monoclonal antibody against mesothelin currently under clinical trials. We show here that MORAb-009 recognizes a non-linear epitope that is contained in the first 64-residue fragment of the mesothelin. We further demonstrate that the recognition is independent of glycosylation state of the protein but sensitive to the loss of a disulfide bond linking residues Cys-7 and Cys-31. The crystal structure of the complex between the mesothelin N-terminal fragment and Fab of MORAb-009 at 2.6 ? resolution reveals an epitope encompassing multiple secondary structural elements of the mesothelin, including residues from helix ?1, the loops linking helices ?1 and ?2, and between helices ?4 and ?5. The mesothelin fragment has a compact, right-handed superhelix structure consisting of five short helices and connecting loops. A residue essential for complex formation has been identified as Phe-22, which projects its side chain into a hydrophobic niche formed on the antibody recognition surface upon antigen-antibody contact. The overlapping binding footprints of both the monoclonal antibody and the cancer antigen CA-125 explains the therapeutic effect and provides a basis for further antibody improvement.
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A novel mechanism of control of NF?B activation and inflammation involving A2B adenosine receptors.
J. Cell. Sci.
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The nuclear factor kappa B (NF?B) pathway controls a variety of processes, including inflammation, and thus, the regulation of NF?B has been a continued focus of study. Here, we report a newly identified regulation of this pathway, involving direct binding of the transcription factor NF?B1 (the p105 subunit of NF?B) to the C-terminus of the A(2B) adenosine receptor (A(2B)AR), independent of ligand activation. Intriguingly, binding of A(2B)AR to specific sites on p105 prevents polyubiquitylation and degradation of p105 protein. Ectopic expression of the A(2B)AR increases p105 levels and inhibits NF?B activation, whereas p105 protein levels are reduced in cells from A(2B)AR-knockout mice. In accordance with the known regulation of expression of anti- and pro-inflammatory cytokines by p105, A(2B)AR-null mice generate less interleukin (IL)-10, and more IL-12 and tumor necrosis factor (TNF-?). Taken together, our results show that the A(2B)AR inhibits NF?B activation by physically interacting with p105, thereby blocking its polyubiquitylation and degradation. Our findings unveil a surprising function for the A(2B)AR, and provide a novel mechanistic insight into the control of the NF?B pathway and inflammation.
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Structural and functional deviations in disease-associated p97 mutants.
J. Struct. Biol.
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Missense mutations that occur at the interface between two functional domains in the AAA protein p97 lead to suboptimal performance in its enzymatic activity and impaired intracellular functions, causing human disorders such as inclusion body myopathy associated with Pagets disease of the bone and frontotemporal dementia (IBMPFD). Much progress has been made in characterizing these mutants at cellular, sub-cellular and molecular levels, gaining a substantial understanding of the involvement of p97 in various cellular pathways. At the tissue level, patient biopsies revealed co-localization of p97 with pathologic proteineous inclusions and rimmed vacuoles, which can be reproduced in various cellular and animal models of IBMPFD. At the subcellular level, alterations in p97s ability to bind various adaptor proteins have been demonstrated for some but not all binding partners. Biochemical and biophysical characterizations of pathogenic p97 revealed altered nucleotide binding properties in the D1-domains compared to the wild type. Structural studies showed that mutant p97 are capable of undergoing a uniform transition in the N-domain from a Down- to an Up-conformation in the presence of ATP?S, while in the wild-type p97, this conformational change can only be demonstrated in solutions but not in crystals. These structural and biochemical analyses of IBMPFD mutants shed new light into the mechanism of p97 function.
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Apparent diffusion coefficient histogram analysis stratifies progression-free and overall survival in patients with recurrent GBM treated with bevacizumab: a multi-center study.
J. Neurooncol.
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We have tested the predictive value of apparent diffusion coefficient (ADC) histogram analysis in stratifying progression-free survival (PFS) and overall survival (OS) in bevacizumab-treated patients with recurrent glioblastoma multiforme (GBM) from the multi-center BRAIN study. Available MRIs from patients enrolled in the BRAIN study (n = 97) were examined by generating ADC histograms from areas of enhancing tumor on T1 weighted post-contrast images fitted to a two normal distribution mixture curve. ADC classifiers including the mean ADC from the lower curve (ADC-L) and the mean lower curve proportion (LCP) were tested for their ability to stratify PFS and OS by using Cox proportional hazard ratios and the Kaplan-Meier method with log-rank test. Mean ADC-L was 1,209 × 10(-6)mm(2)/s ± 224 (SD), and mean LCP was 0.71 ± 0.23 (SD). Low ADC-L was associated with worse outcome. The hazard ratios for 6-month PFS, overall PFS, and OS in patients with less versus greater than mean ADC-L were 3.1 (95 % confidence interval: 1.6, 6.1; P = 0.001), 2.3 (95 % CI: 1.3, 4.0; P = 0.002), and 2.4 (95 % CI: 1.4, 4.2; P = 0.002), respectively. In patients with ADC-L <1,209 and LCP >0.71 versus ADC-L >1,209 and LCP <0.71, there was a 2.28-fold reduction in the median time to progression, and a 1.42-fold decrease in the median OS. The predictive value of ADC histogram analysis, in which low ADC-L was associated with poor outcome, was confirmed in bevacizumab-treated patients with recurrent GBM in a post hoc analysis from the multi-center (BRAIN) study.
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Personalized medicine switching from insulin to sulfonylurea in permanent neonatal diabetes mellitus dictated by a novel activating ABCC8 mutation.
Diagn. Mol. Pathol.
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Neonatal diabetes mellitus (NDM) is a rare but important condition affecting approximately 1 in 100,000 newborns. Permanent form requires life-long treatment with difficulties in long-term compliance and metabolic complications. Exact genetic diagnosis can enable improved outcome and patient satisfaction by switching insulin injection to oral sulfonylureas. Successful cases have been reported with most experience on the KCNJ11-mutated permanent form. Here we report a successful experience in an ABCC8-mutated infant with permanent NDM.
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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.