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Find video protocols related to scientific articles indexed in Pubmed.
Genomic Alterations in the RB Pathway Indicate Prognostic Outcomes of Early-Stage Lung Adenocarcinoma.
Clin. Cancer Res.
PUBLISHED: 10-09-2014
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Purpose: To better understand the complete genomic architecture of lung adenocarcinoma (LA). Experimental Design: We used array experiments to determine copy number variations and sequenced the complete exomes of the 247 LA tumor samples along with matched normal cells obtained from the same patients. Fully annotated clinical data were also available, providing an unprecedented opportunity to assess the impact of genomic alterations on clinical outcomes. Results: We discovered that genomic alternations in the RB pathway are associated with significantly shorter disease-free survival in early-stage LA patients. This association was also observed in our independent validation cohort. The current treatment guidelines for early-stage LA patients recommend follow-up without adjuvant therapy after complete resection, except for high-risk patients. However, our findings raise the interesting possibility that additional clinical interventions might provide medical benefits to early-stage LA patients with genomic alterations in the RB pathway. When examining the association between genomic mutation and histological subtype, we uncovered the characteristic genomic signatures of various histological subtypes. Notably, the solid and the micropapillary subtypes demonstrated great diversity in the mutated genes, while the mucinous subtype exhibited the most unique landscape. This suggests that a more tailored therapeutic approach should be used to treat LA patients. Conclusion: Our analysis of the genomic and clinical data for 247 LAs should help provide a more comprehensive genomic portrait of LA, define molecular signatures of LA subtypes, and lead to the discovery of useful prognostic markers that could be used in personalized treatments for early-stage LA patients.
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Epidemiology and clinical features of toxigenic culture-confirmed hospital-onset Clostridium difficile infection: a multicentre prospective study in tertiary hospitals of South Korea.
J. Med. Microbiol.
PUBLISHED: 09-03-2014
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Hypervirulent Clostridium difficile strains, most notably BI/NAP1/027, have been increasingly emerging in Western countries as local epidemics. We performed a prospective multicentre observational study from December 2011 to May 2012 to identify recent incidences of toxigenic culture-confirmed hospital-onset C. difficile infections (CDI) and their associated clinical characteristics in South Korea. Patients suspected of having been suffering from CDI more than 48 h after admission and aged ?20 years were prospectively enrolled and provided loose stool specimens. Toxigenic C. difficile culture (anaerobic culture+toxin A/B/binary gene PCR) and PCR ribotyping were performed in one central laboratory. We enrolled 98 toxigenic culture-confirmed CDI-infected patients and 250 toxigenic culture-negative participants from three hospitals. The incidence of toxigenic culture-confirmed hospital-onset CDI cases was 2.7 per 10?000 patient-days. The percentage of severe CDI cases was relatively low at only 3.1?%. UK ribotype 018 was the predominant type (48.1?%). There were no hypervirulent BI/NAP1/027 isolates identified. The independent risk factors for toxigenic culture-confirmed hospital-onset CDI were invasive procedure (odds ratio (OR) 7.3, P?=?0.003) and past CDI history within 3 months (OR 28.5, P?=?0.003). In conclusion, the incidence and severity of CDI in our study were not higher than reported in Western countries.
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Embedding the shapes of regions of interest into a Clinical Document Architecture document.
Health Informatics J
PUBLISHED: 08-22-2014
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Sharing a medical image visually annotated by a region of interest with a remotely located specialist for consultation is a good practice. It may, however, require a special-purpose (and most likely expensive) system to send and view them, which is an unfeasible solution in developing countries such as Vietnam. In this study, we design and implement interoperable methods based on the HL7 Clinical Document Architecture and the eXtensible Markup Language Stylesheet Language for Transformation standards to seamlessly exchange and visually present the shapes of regions of interest using web browsers. We also propose a new integration architecture for a Clinical Document Architecture generator that enables embedding of regions of interest and simultaneous auto-generation of corresponding style sheets. Using the Clinical Document Architecture document and style sheet, a sender can transmit clinical documents and medical images together with coordinate values of regions of interest to recipients. Recipients can easily view the documents and display embedded regions of interest by rendering them in their web browser of choice.
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Microglial AGE-albumin is critical in promoting alcohol-induced neurodegeneration in rats and humans.
PLoS ONE
PUBLISHED: 08-20-2014
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Alcohol is a neurotoxic agent, since long-term heavy ingestion of alcohol can cause various neural diseases including fetal alcohol syndrome, cerebellar degeneracy and alcoholic dementia. However, the molecular mechanisms of alcohol-induced neurotoxicity are still poorly understood despite numerous studies. Thus, we hypothesized that activated microglial cells with elevated AGE-albumin levels play an important role in promoting alcohol-induced neurodegeneration. Our results revealed that microglial activation and neuronal damage were found in the hippocampus and entorhinal cortex following alcohol treatment in a rat model. Increased AGE-albumin synthesis and secretion were also observed in activated microglial cells after alcohol exposure. The expressed levels of receptor for AGE (RAGE)-positive neurons and RAGE-dependent neuronal death were markedly elevated by AGE-albumin through the mitogen activated protein kinase pathway. Treatment with soluble RAGE or AGE inhibitors significantly diminished neuronal damage in the animal model. Furthermore, the levels of activated microglial cells, AGE-albumin and neuronal loss were significantly elevated in human brains from alcoholic indivisuals compared to normal controls. Taken together, our data suggest that increased AGE-albumin from activated microglial cells induces neuronal death, and that efficient regulation of its synthesis and secretion is a therapeutic target for preventing alcohol-induced neurodegeneration.
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Protuberant Fibro-osseous Lesions of the Temporal Bone: Two Additional Case Reports.
Am. J. Surg. Pathol.
PUBLISHED: 08-15-2014
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The most commonly encountered fibro-osseous lesions of the skull bone are fibrous dysplasia and ossifying fibroma. Two cases of a unique "protuberant fibro-osseous lesion of the temporal bone" were first described by Selesnick and colleagues in 1999, and 2 further cases were reported in 2010 under the name "Bullough lesion". We recently found 2 new cases of this rare entity. Two Korean female patients aged 70 and 54 years presented with slow growing postauricular masses without pain or tenderness for 6 and 7 years, respectively. Computed tomography revealed a 2.9 cm calcified mass in the temporal bone of the first patient, and a 5.5 cm enhancing mass with internal cartilaginous matrix in the temporal bone of the second patient. Intramedullary or intracranial extension was not found in either case, and en bloc removals were performed. Microscopically, multiple round to oval osseous islands were scattered throughout the bland fibrous stroma in both cases. The osseous islands varied in size and were lamellar or woven, without osteoblastic rimming, and surrounded by fibroblastic bands. Neither patient has shown evidence of postoperative recurrence for 18 months. The location, histology, and clinical course of these 2 cases were identical to the 4 cases previously reported, although age and sex varied. The lesions were tested for the R201H mutation in the GNAS gene, which is present in fibrous dysplasia. No mutations were found, suggesting a different genetic background for these lesions.
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Off-treatment virologic relapse and outcomes of re-treatment in chronic hepatitis B patients who achieved complete viral suppression with oral nucleos(t)ide analogs.
BMC Infect. Dis.
PUBLISHED: 08-13-2014
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The durability of off-treatment virologic responses has not been fully elucidated in chronic hepatitis B (CHB) patients who have previously achieved complete virologic suppression with nucleos(t)ide analog (NA) therapy. This study aimed to assess off-treatment virologic relapse rates and to characterize the outcomes of subsequent re-treatment in CHB patients who have discontinued oral NA following complete virologic suppression.
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Mdm2 and p53 Expression in Radiation-Induced Sarcomas of the Head and Neck: Comparison with De Novo Sarcomas.
Korean J Pathol
PUBLISHED: 06-30-2014
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The pathogenesis of radiation-induced sarcomas (RISs) is not well known. In RIS, TP53 mutations are frequent, but little is known about Mdm2-p53 interaction, which is a recent therapeutic target of sarcomas.
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Clinical Document Architecture integration system to support patient referral and reply letters.
Health Informatics J
PUBLISHED: 06-24-2014
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Many Clinical Document Architecture (CDA) referrals and reply documents have been accumulated for patients since the deployment of the Health Information Exchange System (HIES) in Korea. Clinical data were scattered in many CDA documents and this took too much time for physicians to read. Physicians in Korea spend only limited time per patient as insurances in Korea follow a fee-for-service model. Therefore, physicians were not allowed sufficient time for making medical decisions, and follow-up care service was hindered. To address this, we developed CDA Integration Template (CIT) and CDA Integration System (CIS) for the HIES. The clinical items included in CIT were defined reflecting the Korean Standard for CDA Referral and Reply Letters and requests by physicians. CIS integrates CDA documents of a specified patient into a single CDA document following the format of CIT. Finally, physicians were surveyed after CIT/CIS adoption, and they indicated overall satisfaction.
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Reciprocal regulation of adipocyte and osteoblast differentiation of mesenchymal stem cells by Eupatorium japonicum prevents bone loss and adiposity increase in osteoporotic rats.
J Med Food
PUBLISHED: 06-13-2014
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Pathological increases in adipogenic potential with decreases in osteogenic differentiation occur in osteoporotic bone marrow cells. Previous studies have shown that bioactive materials isolated from natural products can reciprocally regulate adipogenic and osteogenic fates of bone marrow cells. In this study, we showed that Eupatorium japonicum stem extracts (EJE) suppressed lipid accumulation and inhibited the expression of adipocyte markers in multipotent C3H10T1/2 and primary bone marrow cells. Conversely, EJE stimulated alkaline phosphatase activity and induced the expression of osteoblast markers in C3H10T1/2 and primary bone marrow cells. Daily oral administration of 50 mg/kg of EJE for 6 weeks to ovariectomized rats prevented body weight increase and bone mineral density decrease. Finally, activity-guided fractionation led to the identification of coumaric acid and coumaric acid methyl ester as bioactive anti-adipogenic and pro-osteogenic components in EJE. Taken together, our data indicate a promising possibility of E. japonicum as a functional food and as a therapeutic intervention for preventing osteoporosis and bone fractures.
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Physician Attitudes toward the Herpes Zoster Vaccination in South Korea.
Infect Chemother
PUBLISHED: 06-02-2014
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This survey investigated Korean physician attitudes toward the herpes zoster (HZ) vaccine. A total of 400 physicians answered a self-reported questionnaire. Most physicians knew that HZ poses a significant socioeconomic burden and had good knowledge about HZ and its vaccine. Physicians who did not recommend HZ vaccine were concerned about costs (90.7%, 78/86) and doubted the effectiveness of the vaccine (58.1%, 50/86). Patient demand had a profound effect on physicians decisions; 84.9% (73/86) of them who said not recommending HZ vaccine reported that they would provide the vaccine upon patient request. In conclusion, educational initiatives should be targeted toward both physicians and patients.
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Comparison of the immunogenicity and safety of the conventional subunit, MF59-adjuvanted, and intradermal influenza vaccines in the elderly.
Clin. Vaccine Immunol.
PUBLISHED: 05-14-2014
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The influenza vaccination is known as the most effective method for preventing influenza infection and its complications in the elderly. Conventional subunit (Agrippal S1; Novartis), MF59-adjuvanted (Fluad; Novartis), and intradermal (IDflu15; Sanofi Pasteur) influenza vaccines are widely used throughout South Korea. However, few comparative studies evaluating the safety and immunogenicity of these vaccines are available. Prior to the beginning of the 2011-2012 influenza season, 335 healthy elderly volunteers randomly received one of three seasonal trivalent influenza vaccines, the conventional subunit, MF59-adjuvanted, or intradermal influenza vaccine. Serum hemagglutination-inhibiting antibody levels were measured at the time of vaccination and at 1 and 6 months after vaccination. Adverse events were recorded prospectively. A total of 113 conventional subunit, 111 MF59-adjuvanted, and 111 intradermal influenza vaccine volunteers were followed up during a 6-month postvaccination period. One month after vaccination, all three vaccines satisfied Committee for Medical Products for Human Use (CHMP) immunogenicity criteria for the A/H1N1 and A/H3N2 strains but not for the B strain. Compared with the subunit vaccine, the intradermal vaccine exhibited noninferiority, while the MF59-adjuvanted vaccine exhibited superiority. Furthermore, the MF59-adjuvanted vaccine was more immunogenic against the A/H3N2 strain than was the subunit vaccine up to 6 months postvaccination. The most common local and systemic reactions to the conventional subunit, MF59-adjuvanted, and intradermal influenza vaccines were pain at the injection site (7.1%, 10.8%, and 6.3%, respectively) and generalized myalgia (0.9%, 8.1%, and 5.4%, respectively). Local and systemic reactions were similar among the three vaccine groups. MF59-adjuvanted vaccine exhibited superior immunogenicity compared with a conventional subunit vaccine and had a comparable safety profile. For older adults, the MF59-adjuvanted vaccine is preferable for providing superior immunogenicity.
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Structural basis of the phosphorylation dependent complex formation of neurodegenerative disease protein Ataxin-1 and RBM17.
Biochem. Biophys. Res. Commun.
PUBLISHED: 05-10-2014
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Spinocerebellar Ataxia Type1 (SCA1) is a dominantly inherited neurodegenerative disease and belongs to polyglutamine expansion disorders. The polyglutamine expansion in Ataxin-1 (ATXN1) is responsible for SCA1 pathology. ATXN1 forms at least two distinct complexes with Capicua (CIC) or RNA-binding motif protein 17 (RBM17). The wild-type ATXN1 dominantly forms a complex with CIC and the polyglutamine expanded form of ATXN1 favors to form a complex with RBM17. The phosphorylation of Ser776 in ATXN1 is critical for SCA1 pathology and serves as a binding platform for RBM17. However, the molecular basis of the phospho-specific binging of ATXN1 to RBM17 is not delineated. Here, we present the modeled structure of RBM17 bound to the phosphorylated ATXN1 peptide. The structure reveals the phosphorylation specific interaction between ATXN1 and RBM17 through a salt-bridge network. Furthermore, the modeled structure and the interactions between RBM17 and ATXN1 were validated through mutagenesis study followed by Surface Plasmon Resonance binding experiments. This work delineates the molecular basis of the interaction between RBM17 and the phosphorylated form of ATXN1, which is critical for SCA1 pathology. Furthermore, the structure of RBM17 and pATXN1 peptide might be utilized to target RBM17-ATXN1 interaction to modulate SCA1 pathogenesis.
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Enhanced classification for high-throughput data with an optimal projection and hybrid classifier.
Int J Data Min Bioinform
PUBLISHED: 05-03-2014
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High-throughput screening technologies recently developed allow scientists to conduct millions of biological and medical tests simultaneously and rapidly. A major bottleneck for the analysis is to reduce the inherent high dimensionality for subsequent analysis. Principal Component Analysis (PCA) is a popular tool for dimensionality reduction by selecting typically a few Principal Components (PCs) ranked by their variances, eigenvalues. Since this selection approach is not always effective in reducing dimensionality, we consider a different ranking criterion, the canonical variate criterion. To further enhance the classification performance, we propose an integrated classification framework to combine the criterion and two hybrid classification methods and compare with several popular classification methods using leave-one-out cross-validation. For illustration, three real high-throughput data sets are considered and analysed to illustrate the methods.
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Primary mesenchymal tumors of the pancreas: single-center experience over 16 years.
Pancreas
PUBLISHED: 04-19-2014
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Primary mesenchymal tumors of the pancreas are extremely rare and no comprehensive study of this class of tumors has been previously performed.
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A Case of IgG4-Related Lung Disease Presenting as Interstitial Lung Disease.
Tuberc Respir Dis (Seoul)
PUBLISHED: 04-17-2014
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Intrathoracic involvement of immunoglobulin G4 (IgG4)-related disease has recently been reported. However, a subset of the disease presenting as interstitial lung disease is rare. Here, we report a case of a 35-year-old man with IgG4-related lung disease with manifestations similar to those of interstitial lung disease. Chest computed tomography showed diffuse ground glass opacities and rapidly progressive pleural and subpleural fibrosis in both upper lobes. Histological findings showed diffuse interstitial lymphoplasmacytic infiltration with an increased number of IgG4-positive plasma cells. Serum levels of IgG and IgG4 were also increased. The patient was diagnosed with IgG4-related lung disease, treated with anti-inflammatory agents, and showed improvement. Lung involvement of IgG4-related disease can present as interstitial lung disease and, therefore, should be differentiated when evaluating interstitial lung disease.
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Adenocarcinoma arising from intracranial recurrent mature teratoma and featuring mutated KRAS and wild-type BRAF genes.
Neuropathology
PUBLISHED: 04-08-2014
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Malignant transformation or recurrence of intracranial mature teratoma is an extremely rare occurrence, compared to the usual ovarian counterpart. Previously, yolk sac tumor elements have been considered to be selective progenitors of enteric-type adenocarcinoma arising from intracranial germ cell tumors. However, the present case demonstrates the occurrence of enteric-type adenocarcinoma in recurrent intracranial mature cystic teratoma 12 years after gross total removal, a case of which has not previously been documented in the literature. The 11.5-cm long, dura mater-based tumor on the right fronto-temporal lobe displaced the brain; however, the patient had no neurologic symptoms or discomfort other than pus-like discharge on the scalp. Microscopic examinations revealed a small focus of adenocarcinoma and dysplastic colonic mucosa in the mature cystic teratoma. No immature elements were seen. The cystic wall was almost denuded and showed an exuberant xanthogranulomatous reaction with foreign-body type giant cells engulfing keratin materials and cholesterol clefts, suggesting that chronic inflammation due to repeated cyst wall rupture and the previous resection may contribute to malignant transformation. The adenocarcinoma showed strong immunohistochemical expression of CK20 and p53, but CK7 in patches. The molecular profile of the adenocarcinoma showed a mutation in KRAS and wild-type BRAF, which might be associated with malignant transformation of intracranial mature teratomas. In conclusion, the intracranial mature teratomas should require long-term follow-up, and clinicians, radiologists and pathologists should be aware of the potential for malignant progression of recurrent intracranial mature cystic teratoma despite gross total resection and no neurologic symptoms.
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Prognostic significance of biallelic loss of PTEN in clear cell renal cell carcinoma.
J. Urol.
PUBLISHED: 03-21-2014
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We investigated the clinical implications of biallelic loss of PTEN in clear cell renal cell carcinoma and whether PTEN biallelic loss would induce p53 dependent cellular senescence.
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Pulmonary toxocariasis mimicking invasive aspergillosis in a patient with ulcerative colitis.
Korean J. Parasitol.
PUBLISHED: 03-19-2014
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A 45-year-old-male who had underlying ulcerative colitis and presented with fever and dry cough. Initially, the patient was considered to have invasive aspergillosis due to a positive galactomannan assay. He was treated with amphotericin B followed by voriconazole. Nevertheless, the patient deteriorated clinically and radiographically. The lung biopsy revealed eosinophilic pneumonia, and ELISA for Toxocara antigen was positive, leading to a diagnosis of pulmonary toxocariasis. After a 10-day treatment course with albendazole and adjunctive steroids, the patient recovered completely without any sequelae. Pulmonary toxocariasis may be considered in patients with subacute or chronic pneumonia unresponsive to antibiotic agents, particularly in cases with eosinophilia.
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Indero: intergenerational trauma and resilience between Burundian former child soldiers and their children.
Fam Process
PUBLISHED: 03-17-2014
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Since many former child soldiers are aging and having children of their own, this study aimed to understand how the effects of trauma are passed to the next generation. In this qualitative study, semistructured interviews, focus groups, and observations were conducted with 25 former child soldiers and 15 matched civilian parents. Analysis used a grounded-theory approach. Trauma may be transmitted from former child soldiers to their offspring via (a) the effect on indero (how to raise a child); (b) severe parental emotional distress; and (c) community effects. Incorporating themes of indero values on how to raise children, the effects of parental posttraumatic stress and depressive symptoms on offspring, and the stigma associated with the families of former child soldiers may provide key areas of intervention in mental healing.
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A Case of Post-radiotherapy Urethral Stricture with Spontaneous Bladder Rupture, Mimicking Obstructive Uropathy due to Cancer Metastasis.
Electrolyte Blood Press
PUBLISHED: 03-12-2014
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Non-traumatic, spontaneous urinary bladder rupture is a rare complication of urethral stricture. Furthermore, its symptoms are often nonspecific, and misdiagnosis is common. The authors experienced a case of urethral stricture with spontaneous bladder rupture and bilateral hydronephrosis, mimicking obstructive uropathy attributed to cancer metastasis. A 55-year-old woman was admitted with abdominal pain and distension, oliguria, and an elevated serum creatinine level. She had undergone radical hysterectomy for uterine cervical cancer and received post-operative concurrent chemoradiation therapy 13 years previously. Non-contrast enhanced computed tomography showed massive ascites and bilateral hydronephrosis. The initial diagnosis was acute kidney injury due to obstructive uropathy caused by malignant disease. After improvement of her renal function by bilateral percutaneous nephrostomy catheterization, contrast-enhanced computed tomography and a cytologic examination of ascites showed no evidence of malignancy. However, during retrograde pyelography, a severe urethral stricture was found, and subsequent cystography showed leakage of contrast into the peritoneal cavity and cystoscopy revealed a defect of the posterior bladder wall. After urethral dilatation and primary closure of the bladder wall, acute kidney injury and ascites were resolved.
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Ethanol Mediates Cell Cycle Arrest and Apoptosis in SK-N-SH Neuroblastoma Cells.
J Cancer Prev
PUBLISHED: 03-04-2014
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The mechanisms of cell or organ damage by chronic alcohol consumption are still poorly understood. The present study aimed to investigate the role of the mitogen-activated protein kinases during ethanol-induced damage to SK-N-SH neuroblastoma cells.
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Is It Possible to Evaluate the Parameters of Cervical Sagittal Alignment on Cervical CT scan?
Spine
PUBLISHED: 03-04-2014
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Study Design. Retrospective analysis of existing cervical radiographsObjective. The purpose of this study was to analyze the relationship of the parameters of cervical sagittal alignment between those obtained from cervical CT and those obtained from X-ray, as well as to determine which parameter would help predict physiological lordosis of the cervical spine.Summary of Background Data. Sagittal balance in the cervical spine is as important as the pelvic incidence and is related to the concept of T1 slope. However, many articles including this article based on unclear cervical X-ray radiographs could weakly explain the parameters. To overcome the fundamental limitation of X-ray radiographs, our institution reported the strong correlation between T1 slope and cervical lordosis on the cervical dimensional CT radiographs like result by checking by the cervical X-ray radiographs.Methods. A retrospective analysis of data from 50 asymptomatic adults who had both Cervical CT radiographs and cervical X-ray taken at the same time. The T1 slope, Cobb`s angle C2-7, Necktilt and Thoracic inlet angle obtained from the CT radiographs and X-ray were assessed.Results. The T1slope on X-ray (T1SX) was significantly correlated with the T1slope on CT (T1SCT). The mean of the T1SX was larger than the mean of the T1SCT (3.3 ± 6.1 degrees). More cervical spine lordosis was evident on the cervical X-ray than in the cervical CT (5.93 ± 9.0 degrees). No significant difference was seen between the TIAX and the TIACT (TIAX - TIACT, -0.1 ± 7.6, p = 0.959).Conclusion. This difference may be due to the differing effect of gravity upon the spine between the upright versus the supine position. Accordingly, TIA and T1S may be used as a guide for the assessment of sagittal balance of the cervical spine.
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Spinal subdural hematoma following meningioma removal operation.
Korean J Spine
PUBLISHED: 03-03-2014
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Although blood contamination of cerebrospinal fluid (CSF) after an intracranial operation can occur, the development of a symptomatic spinal hematoma after craniotomy has been anecdotally reported and it is uncommon reported after a supratentorial meningioma removal operation. We report a case of spinal subdural hematoma following a supratentorial meningioma removal operation and discuss the mechanism of spinal subdural hematoma (SSDH) development. A 54-year-old woman presented with lumbago and radicular pain on both legs 4 days after a right parietooccipital craniotomy for meningioma removal. Only the straight leg raising sign was positive on neurologic examination but the magnetic resonance imaging (MRI) demonstrated a lumbosacral spinal subdural hematoma. The patient received serial lumbar tapping, after which her symptoms showed improvement.
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Binge alcohol promotes hypoxic liver injury through a CYP2E1-HIF-1?-dependent apoptosis pathway in mice and humans.
Free Radic. Biol. Med.
PUBLISHED: 02-24-2014
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Binge drinking, a common pattern of alcohol ingestion, is known to potentiate liver injury caused by chronic alcohol abuse. This study was aimed to investigate the effects of acute binge alcohol on hypoxia-inducible factor-1? (HIF-1?)-mediated liver injury and roles of alcohol metabolizing enzymes in alcohol-induced hypoxia and hepatotoxicity. Mice and human specimens assigned as binge or non-binge group were analyzed for blood alcohol concentration (BAC), alcohol metabolizing enzymes, HIF-1?-related protein nitration and apoptosis. Binge alcohol promoted acute liver injury in mice with elevated levels of ethanol-inducible cytochrome P450-2E1 (CYP2E1) and hypoxia, both of which were co-localized in centrilobular areas. We observed positive correlations among elevated BAC, CYP2E1, and HIF-1? in mice and humans exposed to binge alcohol. The CYP2E1 protein levels (r=0.629, p=0.001) and activities (r=0.641, p=0.001) showed significantly positive correlation with BACs in human livers. HIF-1? levels were also positively correlated with BACs (r=0.745, p<0.001) or CYP2E1 activities (r=0.792, p<0.001) in humans. Binge alcohol promoted protein nitration and apoptosis with significant correlations observed between inducible nitric oxide synthase and BACs, CYP2E1, or HIF-1? in human specimens. Binge alcohol-induced HIF-1? activation and subsequent protein nitration or apoptosis seen in wild-type were significantly alleviated in the corresponding Cyp2e1-null mice while pretreatment with an HIF-1? inhibitor PX-478 prevented HIF-1? elevation with a trend of decreased levels of 3-nitrotyrosine and apoptosis, supporting the roles of CYP2E1and HIF-1? in binge alcohol-mediated protein nitration and hepatotoxicity. Thus binge alcohol promotes acute liver injury in mice and humans at least partly through a CYP2E1-HIF-1?-dependent apoptosis pathway.
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Etiology and clinical outcomes of acute respiratory virus infection in hospitalized adults.
Infect Chemother
PUBLISHED: 02-24-2014
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Etiologies and clinical profiles of acute respiratory viral infections need to be clarified to improve preventive and therapeutic strategies.
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Functional roles of protein nitration in acute and chronic liver diseases.
Oxid Med Cell Longev
PUBLISHED: 02-12-2014
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Nitric oxide, when combined with superoxide, produces peroxynitrite, which is known to be an important mediator for a number of diseases including various liver diseases. Peroxynitrite can modify tyrosine residue(s) of many proteins resulting in protein nitration, which may alter structure and function of each target protein. Various proteomics and immunological methods including mass spectrometry combined with both high pressure liquid chromatography and 2D PAGE have been employed to identify and characterize nitrated proteins from pathological tissue samples to determine their roles. However, these methods contain a few technical problems such as low efficiencies with the detection of a limited number of nitrated proteins and labor intensiveness. Therefore, a systematic approach to efficiently identify nitrated proteins and characterize their functional roles is likely to shed new insights into understanding of the mechanisms of hepatic disease pathophysiology and subsequent development of new therapeutics. The aims of this review are to briefly describe the mechanisms of hepatic diseases. In addition, we specifically describe a systematic approach to efficiently identify nitrated proteins to study their causal roles or functional consequences in promoting acute and chronic liver diseases including alcoholic and nonalcoholic fatty liver diseases. We finally discuss translational research applications by analyzing nitrated proteins in evaluating the efficacies of potentially beneficial agents to prevent or treat various diseases in the liver and other tissues.
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Ossified soft tissue recurrence of giant cell tumor of the bone: four case reports with follow-up radiographs, CT, ultrasound, and MR images.
Skeletal Radiol.
PUBLISHED: 02-09-2014
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Giant cell tumor (GCT) of the bone is a benign tumor with a high incidence of recurrence. The majority of recurrence occurs in the bone, typically where curettage was performed previously. Soft tissue recurrence is much less common and often shows ossification at the periphery of the soft tissue mass. We report four cases of ossified soft tissue recurrence of giant cell tumor of the bone after surgery at follow-up examination using plain radiography, ultrasound, CT, and MR imagings. Imaging findings of soft tissue recurrence with peripheral or central ossification were reviewed with pathologic correlation. To the best of our knowledge, this is the first report to describe soft tissue tumor recurrence with ossification illustrated and monitored at various imaging modalities over an extended follow-up period.
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Aldehyde dehydrogenase 2 deficiency ameliorates alcoholic fatty liver but worsens liver inflammation and fibrosis in mice.
Hepatology
PUBLISHED: 01-29-2014
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Aldehyde dehydrogenase 2 (ALDH2) is the major enzyme that metabolizes acetaldehyde produced from alcohol metabolism. Approximately 40-50% of East Asians carry an inactive ALDH2 gene and exhibit acetaldehyde accumulation after alcohol consumption. However, the role of ALDH2 deficiency in the pathogenesis of alcoholic liver injury remains obscure. In the present study, wild-type and ALDH2(-/-) mice were subjected to ethanol feeding and/or carbon tetrachloride (CCl4 ) treatment, and liver injury was assessed. Compared with wild-type mice, ethanol-fed ALDH2(-/-) mice had higher levels of malondialdehyde-acetaldehyde (MAA) adduct and greater hepatic inflammation, with higher hepatic interleukin (IL)-6 expression but surprisingly lower levels of steatosis and serum alanine aminotransferase (ALT). Higher IL-6 levels were also detected in ethanol-treated precision-cut liver slices from ALDH2(-/-) mice and in Kupffer cells isolated from ethanol-fed ALDH2(-/-) mice than those levels in wild-type mice. In vitro incubation with MAA enhanced the lipopolysaccharide (LPS)-mediated stimulation of IL-6 production in Kupffer cells. In agreement with these findings, hepatic activation of the major IL-6 downstream signaling molecule signal transducer and activator of transcription 3 (STAT3) was higher in ethanol-fed ALDH2(-/-) mice than in wild-type mice. An additional deletion of hepatic STAT3 increased steatosis and hepatocellular damage in ALDH2(-/-) mice. Finally, ethanol-fed ALDH2(-/-) mice were more prone to CCl4 -induced liver inflammation and fibrosis than ethanol-fed wild-type mice.
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A cluster of lung injury associated with home humidifier use: clinical, radiological and pathological description of a new syndrome.
Thorax
PUBLISHED: 01-28-2014
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Over a few months in the spring of 2011, a cluster of patients with severe respiratory distress were admitted to our intensive care unit (ICU). Household clustering was also observed. Extensive laboratory investigations failed to detect an infectious cause.
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Epigenetics: an emerging player in gastric cancer.
World J. Gastroenterol.
PUBLISHED: 01-07-2014
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Cancers, like other diseases, arise from gene mutations and/or altered gene expression, which eventually cause dysregulation of numerous proteins and noncoding RNAs. Changes in gene expression, i.e., upregulation of oncogenes and/or downregulation of tumor suppressor genes, can be generated not only by genetic and environmental factors but also by epigenetic factors, which are inheritable but nongenetic modifications of cellular chromosome components. Identification of the factors that contribute to individual cancers is a prerequisite to a full understanding of cancer mechanisms and the development of customized cancer therapies. The search for genetic and environmental factors has a long history in cancer research, but epigenetic factors only recently began to be associated with cancer formation, progression, and metastasis. Epigenetic alterations of chromatin include DNA methylation and histone modifications, which can affect gene-expression profiles. Recent studies have revealed diverse mechanisms by which chromatin modifiers, including writers, erasers and readers of the aforementioned modifications, contribute to the formation and progression of cancer. Furthermore, functional RNAs, such as microRNAs and long noncoding RNAs, have also been identified as key players in these processes. This review highlights recent findings concerning the epigenetic alterations associated with cancers, especially gastric cancer.
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Clinical significance of NQO1 polymorphism and expression of p53, SOD2, PARP1 in limited-stage small cell lung cancer.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Small cell lung cancer (SCLC) is one of highly aggressive cancers with poor prognosis. Unfortunately, there are as yet no molecular targets that can be exploited to prolong survival in patients with SCLC. This study aimed to investigate possible molecular markers associated with prognosis in limited-stage small cell lung cancer (LS-SCLC).
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Impact of preceding flu-like illness on the serotype distribution of pneumococcal pneumonia.
PLoS ONE
PUBLISHED: 01-01-2014
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Even though the pathogenicity and invasiveness of pneumococcus largely depend on capsular types, the impact of serotypes on post-viral pneumococcal pneumonia is unknown.
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Age- and influenza activity-stratified case definitions of influenza-like illness: experience from hospital-based influenza surveillance in South Korea.
PLoS ONE
PUBLISHED: 01-01-2014
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This study aims to identify clinical case definitions of influenza with higher accuracy in patients stratified by age group and influenza activity using hospital-based surveillance system.
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Dynamic anchoring of the 3-end of the guide strand controls the target dissociation of Argonaute-guide complex.
J. Am. Chem. Soc.
PUBLISHED: 10-31-2013
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Argonaute (Ago) is the catalytic core of small RNA-based gene regulation. Despite plenty of mechanistic studies on Ago, the dynamical aspects and the mechanistic determinants of target mRNA binding and dissociation of Ago-guide strand remain unclear. Here, by using single-molecule fluorescence resonance energy transfer (FRET) assays and Thermus thermophilus Ago (TtAgo), we reveal that the 3-end of the guide strand dynamically anchors at and releases from the PAZ domain of Ago, and that the 3-end anchoring of the guide strand greatly accelerates the target dissociation by destabilizing the guide-target duplex. Our results indicate that the target binding/dissociation of Ago-guide is executed through the dynamic interplays among Ago, guide, and target.
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Cucurbitacin B and cucurbitacin I suppress adipocyte differentiation through inhibition of STAT3 signaling.
Food Chem. Toxicol.
PUBLISHED: 10-26-2013
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Cucurbitacin B, a member of the cucurbitaceae family, can act as a STAT3 signaling inhibitor to regulate the growth of hepatocellular carcinoma. STAT3 signaling has been shown to inhibit adipocyte differentiation through C/EBP? and PPAR?. Based on these studies, we hypothesized that cucurbitacin B would prevent PPAR? mediated adipocyte differentiation through STAT3 signaling. To test this hypothesis, mesenchymal C3H10T1/2 and 3T3-L1 preadipocyte cells were treated with a sub-cytotoxic concentration of cucurbitacin B. Cucurbitacin B treatment inhibits lipid accumulation and expression of adipocyte markers including PPAR? and its target genes in a dose-dependent manner. Cucurbitacin B treatment impairs STAT3 signaling as manifested by reduced phosphorylation of STAT3 and suppression of STAT3 target gene expression in preadipocytes. The anti-adipogenic effects of cucurbitacin B are significantly blunted in cells with STAT3 silenced by introducing small interfering RNA. Finally, our data show that cucurbitacin I, another cucurbitacin family member, also inhibits adipocyte differentiation by suppressing STAT3 signaling. Together, our data suggest the possibility of utilizing cucurbitacins as a new strategy to treat metabolic diseases and implicate STAT3 as a new target for the development of functional foods and drugs.
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Effectiveness of the influenza vaccine at preventing hospitalization due to acute exacerbation of cardiopulmonary disease in Korea from 2011 to 2012.
Hum Vaccin Immunother
PUBLISHED: 10-25-2013
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There is a lack of targeted studies to validate the effectiveness of influenza vaccination on the reduction in influenza-related hospitalizations among patients with co-morbidities. In this study, we estimate the effectiveness of influenza vaccination on preventing hospitalizations in persons with cardiopulmonary disease and establish an evidence base for recommendations on influenza vaccination in this population. During the influenza epidemic in 2011-2012, we performed a multicenter, retrospective case-control study. Cases were patients hospitalized due to acute exacerbation of asthma, COPD, ischemic heart disease (IHD), and congestive heart failure (CHF). Controls were selected from outpatients who visited study hospitals but who were not hospitalized. Cases and controls were matched 1:1 based on age, gender, and date of hospital visit. Conditional logistic regression analyses were used to determine the effectiveness of vaccination. Between 25 December 2011 and 5 May 2012, 828 of each hospitalized and control subjects were identified. The influenza vaccination rate of the hospitalized and non-hospitalized patients was 54.2% and 60.4%, respectively (P = 0.006). The overall vaccine effectiveness for preventing hospitalization was 33.7% [95% confidence interval (CI) 14.0-49.0%; P = 0.002]. Conditional logistic regression analysis showed that influenza vaccination significantly reduced the risk of hospitalization, especially due to acute exacerbation of IHD and CHF, in patients aged 65 y and older. The estimated vaccine effectiveness in these patients was 56.0% (95% CI 32.1-71.4%, P = 0.002). Influenza vaccination was associated with a reduction in the risk of hospitalization due to acute exacerbation of cardiopulmonary disease. We recommend the vaccine be given primarily to patients with underlying cardiovascular disease, particularly those 65 y of age and older.
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Improving chronic disease management with mobile health platform.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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In modern society, aging and chronic disease is becoming common phenomenon due to the increasing numbers of elderly patients. To best treat this growing segment of the population, medical care should be based on constant vital sign monitoring. In this study, we propose a mobile vital sign measurement and data collection system for chronic disease management? And we implemented a middle ware using Multi-Agent platform in SOS (Self-Organizing System) platform that transmits patient clinical data for services. We also implemented a HL7 messaging interface for interoperability of clinical data exchange. We propose health services on a self-organized software platform.
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Preliminary comparison of mHealth architectures based on MU2 criteria.
Stud Health Technol Inform
PUBLISHED: 08-08-2013
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Mobile Health (MH) is a hot topic in the health IT industry because it can make a big difference in healthcare services. Before adopting Mobile Health technology, however, we must ensure that it provides safe and reliable services to users and it should be evaluated by authoritative criteria. In US, Electronic Health Record (EHR) systems are evaluated through Meaningful Use (MU). Although MU focuses on EHR systems, it cant be thought of without MH. So in this paper we derive proper evaluation criteria for MH from MU criteria and evaluate existing MH architectures that are currently being surveyed in ISO/AWI TR 17522 - Provisions for Health Applications on Mobile/Smart Devices.
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A viral histone h4 joins to eukaryotic nucleosomes and alters host gene expression.
J. Virol.
PUBLISHED: 08-07-2013
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A viral histone H4 (CpBV-H4) is encoded in a polydnavirus, Cotesia plutellae bracovirus. Its predicted amino acid sequence is highly homologous to that of host insect histone H4 except for an extended N-terminal tail containing 38 amino acids with nine lysine residues. Its expression induces an immunosuppression of target insects by suppressing immune-associated genes, presumably through an epigenetic control. This study analyzed its molecular interaction with eukaryotic host nucleosomes and subsequent regulation of host gene expression. Purified recombinant CpBV-H4 could associate with nucleosomal components (H2A, H2B, H3, and H4) and form an octamer. Transient expression of CpBV-H4 in an insect, Tribolium castaneum, was performed by microinjection of a recombinant expression vector and confirmed by both reverse transcriptase PCR (RT-PCR) and immunoblotting assays. Under this transient expression condition, total RNAs were extracted and read by a deep-sequencing technique. Annotated transcripts were classified into different gene ontology (GO) categories and compared with those of control insects injected with a truncated CpBV-H4. Target genes manipulated by CpBV-H4 expression showing significant differences (fold changes > 10(9)) included all GO categories, including development and immune-associated genes. When the target genes were physically mapped, they were found to be scattered on entire chromosomes of T. castaneum. In addition, chromatin immunoprecipitation against CpBV-H4 determined 16 nucleosome sites (P < 10(-5)) of the viral histone incorporation, which were noncoding regions near DNA-binding and inducible genes. These findings suggest that the viral histone H4 alters host gene expression by a direct molecular interaction with insect nucleosomes.
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CYP2E1 potentiates binge alcohol-induced gut leakiness, steatohepatitis, and apoptosis.
Free Radic. Biol. Med.
PUBLISHED: 08-05-2013
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Ethanol-inducible cytochrome P450 2E1 (CYP2E1) contributes to increased oxidative stress and steatosis in chronic alcohol-exposure models. However, its role in binge ethanol-induced gut leakiness and hepatic injury is unclear. This study was aimed at investigating the role of CYP2E1 in binge alcohol-induced gut leakiness and the mechanisms of steatohepatitis. Female wild-type (WT) and Cyp2e1-null mice were treated with three doses of binge ethanol (WT-EtOH or Cyp2e1-null-EtOH) (6g/kg oral gavage at 12-h intervals) or dextrose (negative control). Intestinal histology of only WT-EtOH exhibited epithelial alteration and blebbing of lamina propria, and liver histology obtained at 6h after the last ethanol dose showed elevated steatosis with scattered inflammatory foci. These were accompanied by increased levels of serum endotoxin, hepatic enterobacteria, and triglycerides. All these changes, including the intestinal histology and hepatic apoptosis, determined by TUNEL assay, were significantly reversed when WT-EtOH mice were treated with the specific inhibitor of CYP2E1 chlormethiazole and the antioxidant N-acetylcysteine, both of which suppressed oxidative markers including intestinal CYP2E1. WT-EtOH also exhibited elevated amounts of serum TNF-?, hepatic cytokines, CYP2E1, and lipid peroxidation, with decreased levels of mitochondrial superoxide dismutase and suppressed aldehyde dehydrogenase 2 activity. Increased hepatocyte apoptosis with elevated levels of proapoptotic proteins and decreased levels of active (phosphorylated) p-AKT, p-AMPK, and peroxisome proliferator-activated receptor-?, all of which are involved in fat metabolism and inflammation, were observed in WT-EtOH. These changes were significantly attenuated in the corresponding Cyp2e1-null-EtOH mice. These data indicate that both intestinal and hepatic CYP2E1 induced by binge alcohol seems critical in binge alcohol-mediated increased nitroxidative stress, gut leakage, and endotoxemia; altered fat metabolism; and inflammation contributing to hepatic apoptosis and steatohepatitis.
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Hospital-based influenza morbidity and mortality surveillance system for influenza-like illnesses: a comparison with national influenza surveillance systems.
Influenza Other Respir Viruses
PUBLISHED: 07-24-2013
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The Hospital-based Influenza Morbidity and Mortality (HIMM) surveillance system is an emergency room (ER)-based influenza surveillance system in Korea that was established in 2011. The system was established under the assumption that integrated clinical and virologic surveillance could be performed rapidly and easily at seven tertiary hospitals ER. Here, we assessed the correlation between data generated from the HIMM surveillance system and the Korean national influenza surveillance systems during the 2011-2012 influenza season using cross-correlation analysis and found strong correlations. Rapid antigen-test-based HIMM surveillance would predict the start of influenza epidemic earlier than pre-existing influenza-like-illness-based surveillance.
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Assessing the detection capacity of microarrays as bio/nanosensing platforms.
Biomed Res Int
PUBLISHED: 07-17-2013
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Microarray is one of the most powerful detection systems with multiplexing and high throughput capability. It has significant potential as a versatile biosensing platform for environmental monitoring, pathogen detection, medical therapeutics, and drug screening to name a few. To date, however, microarray applications are still limited to preliminary screening of genome-scale transcription profiling or gene ontology analysis. Expanding the utility of microarrays as a detection tool for various biological and biomedical applications requires information about performance such as the limits of detection and quantification, which are considered as an essential information to decide the detection sensitivity of sensing devices. Here we present a calibration design that integrates detection limit theory and linear dynamic range to obtain a performance index of microarray detection platform using oligonucleotide arrays as a model system. Two different types of limits of detection and quantification are proposed by the prediction or tolerance interval for two common cyanine fluorescence dyes, Cy3 and Cy5. Besides oligonucleotide, the proposed method can be generalized to other microarray formats with various biomolecules such as complementary DNA, protein, peptide, carbohydrate, tissue, or other small biomolecules. Also, it can be easily applied to other fluorescence dyes for further dye chemistry improvement.
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Activation of PPAR? by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury.
Biochem. Biophys. Res. Commun.
PUBLISHED: 05-14-2013
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Acute lung injury (ALI) is a major cause of mortality and morbidity worldwide. The activation of peroxisome proliferator-activated receptor-? (PPAR?) by its ligands, which include Wy-14643, has been implicated as a potential anti-inflammatory therapy. To address the beneficial efficacy of Wy-14643 for ALI along with systemic inflammation, the in vivo role of PPAR? activation was investigated in a mouse model of lipopolysaccharide (LPS)-induced ALI. Using age-matched Ppara-null and wild-type mice, we demonstrate that the activation of PPAR? by Wy-14643 attenuated LPS-mediated ALI. This was evidenced histologically by the significant alleviation of inflammatory manifestations and apoptosis observed in the lung tissues of wild-type mice, but not in the corresponding Ppara-null mice. This protective effect probably resulted from the inhibition of LPS-induced increases in pro-inflammatory cytokines and nitroxidative stress levels. These results suggest that the pharmacological activation of PPAR? might have a therapeutic effect on LPS-induced ALI.
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Evaluation of the solitaire system in a canine arterial thromboembolic occlusion model: is it safe for the endothelium?
Interv Neuroradiol
PUBLISHED: 04-28-2013
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The Solitaire system has recently been increasingly used for acute stroke treatment in which the endothelial safety immediately after its use has not been evaluated. This study was performed to evaluate the endothelial status when using a Solitaire system in a canine arterial occlusion model. Thromboembolic occlusion of both internal maxillary arteries was achieved in five mongrel dogs. In each animal, the Solitaire system (ev3, Irvine, CA, USA) was used for primary thrombectomy on the right side and for temporary stenting on the left side. Efficacy was assessed by comparing the recanalization rates, and safety was assessed using angiographic and microscopic assessments. Endothelial injuries were evaluated with light microscopy (LM) and scanning electron microscopy (SEM). Successful revascularizations were observed following primary thrombectomy in all five animals (100%) and after temporary stenting in two (40%). There was no incidence of vasospasm or vessel perforation in either group. Distal migration of the clot occurred in two animals that underwent primary thrombectomy. Endothelial injury was seen after primary thrombectomy in two animals (40%) and after temporary stenting in one (20%). The lesions presented as defects of the internal elastic lamina on LM and denudation of the wavy endothelial surface on SEM. During mechanical thrombectomy, the Solitaire system can cause endothelial injury both in primary thrombectomy and temporary stenting. Primary thrombectomy is likely to have a higher recanalization rate with increased endothelial injury.
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Early stage high-content HIV diagnosis based on concurrent monitoring of actin cytoskeleton, CD3, CD4, and CD8.
Anal. Chem.
PUBLISHED: 04-25-2013
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Antiretroviral treatment can reduce the death rate of human immunodeficiency virus (HIV) infection, and its effectiveness is maximized at the early stage of HIV infection. The present study demonstrates an early stage high-content HIV diagnosis based on multicolor concurrent monitoring of CD4, CD8, and CD3 coreceptors and F-actin cytoskeleton using quantum dot (Qdot)-antibody conjugates at the single cell level. Artificial HIV infection of peripheral blood mononuclear cells (PBMCs) was achieved by the treatment of PBMCs with gp120 glycoproteins. Using the present system, it was determined that the CD4/CD8 ratios of normal PBMCs obtained from the blood samples of 11 adults were in the range of 1.04 to 1.52 as a result of the quantitative counting of single PBMCs while the CD4/CD8 ratios of artificial HIV-infected PBMCs were from 0.045 to 0.63. In addition, the structural changes of actin filament alignments in PBMCs bound to gp120 proteins were clearly observed by the multicolor single cell imaging system. This approach suggests a new model of accurate early stage HIV diagnosis simultaneously providing information on actin cytoskeleton and subtypes of PBMCs as well as their CD4/CD8 ratios.
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Clinical and economic burden of invasive pneumococcal disease in adults: a multicenter hospital-based study.
BMC Infect. Dis.
PUBLISHED: 04-14-2013
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Streptococcus pneumoniae causes a broad spectrum of illnesses ranging from mild upper respiratory tract infections to invasive pneumococcal disease (IPD). Quantitative data on the burden of pneumococcal disease, important for the establishment of appropriate vaccination strategies, is currently lacking in adults.
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Case-control study of the effectiveness of the 2010-2011 seasonal influenza vaccine for prevention of laboratory-confirmed influenza virus infection in the Korean adult population.
Clin. Vaccine Immunol.
PUBLISHED: 04-10-2013
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We evaluated the effectiveness of the 2010-2011 seasonal influenza vaccine for preventing laboratory-confirmed influenza in a South Korean population. A retrospective case-control study was conducted among patients who visited selected hospitals from September 2010 to May 2011. A total of 483 laboratory-confirmed influenza patients were included in the analysis as case subjects. For each case patient, two types of control patients were chosen at a ratio of 1:1:1, and 966 control subjects were selected. Vaccine effectiveness (VE) was defined as 100 × (1 - odds ratio for influenza in vaccinated versus nonvaccinated persons). The VE of the 2010-2011 seasonal influenza vaccine was 49.5% to 45.8% for both influenza A and B viruses and 50.8% to 47.2% for influenza A virus, according to the control type. The age-specific adjusted VE was 50.8% to 46.5% among subjects aged 19 to 49 years and 58.7% to 63.3% among those aged 50 to 64 years, according to the control type. Statistically significant VE was not found among those aged ?65 years or against influenza B virus. The 2010-2011 seasonal influenza vaccine was effective for preventing laboratory-confirmed influenza, especially for influenza A virus, in a South Korean population. Evidence of the effectiveness of the influenza vaccine in older adults or against influenza B virus was not found.
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Long-term and cross-reactive immunogenicity of inactivated trivalent influenza vaccine in the elderly: MF59-adjuvanted vaccine versus unadjuvanted vaccine.
J. Med. Virol.
PUBLISHED: 03-25-2013
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Elderly people are at great risk for influenza-related serious complications. However, influenza vaccine-induced antibodies are believed to decline more rapidly in the elderly. This study was designed to evaluate the long-term and cross-reactive immunogenicity among those aged ?65 years for two seasonal trivalent influenza vaccines during the 2009-2010 influenza season. One vaccine had the MF59 adjuvant, while the other did not contain an adjuvant. Serum hemagglutinin inhibition (HI) titers were determined pre-vaccination and at 1 and 6 months post-vaccination. Of the 100 subjects, 95 (95%) were followed-up for 1 month after vaccination, and 76 (76%) were followed-up for 6 months after vaccination. Both vaccines met the European Medicines Agency (EMA) criteria 1 month after vaccination. However, seroprotection for influenza B was not satisfactory, with a rate of 55.3% for the MF59 adjuvant vaccine and 47.9% for the vaccine without adjuvant. At 6 months post-vaccination, the MF59-adjuvanted vaccine showed a higher seroprotection rate than the unadjuvanted vaccine. At this point, the MF59-adjuvanated vaccine still met the criteria of EMA for A/H1N1 (62.5% vs. 55.5%, P?=?0.64) and A/H3N2 (72.5% vs. 47.2%, P?=?0.04). Both vaccines showed excellent cross-reactive immunogenicity for influenza A/Solomon Island/3/2006 (H1N1) and A/Wisconsin/67/2005 (H3N2), without significant differences. In comparison, cross-reactive immunogenicity was not remarkable for the A/California/7/2009 (H1N1) and A/New Caledonia/20/1999 (H1N1) strains, which have a greater antigenic distance. In conclusion, the MF59-adjuvanted influenza vaccine showed superior long-term immunogenicity in the elderly compared to the unadjuvanted vaccine. However, cross-reactive immunogenicity was not remarkably enhanced with the MF59 adjuvant.
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Pneumococcal vaccine and opsonic pneumococcal antibody.
J. Infect. Chemother.
PUBLISHED: 03-22-2013
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Streptococcus pneumoniae is a major human pathogen responsible for the majority of bacterial pneumonia cases as well as invasive pneumococcal diseases with high mortality and morbidity. Use of conjugate vaccines targeting the pneumococcal capsule has dramatically reduced the incidence of invasive diseases, and there are active efforts to further improve the conjugate vaccines. However, in children new pneumococcal vaccines can no longer be tested with placebo-based clinical trials because effective vaccines are currently available. Thus, vaccine studies must depend on surrogate markers of vaccine efficacy. Although traditional antibody levels (e.g., ELISA) are useful as a surrogate marker of protection, they have limitations, and a bioassay measuring the capacity of antibodies to opsonize pneumococci has been developed. This opsonophagocytosis assay (OPA) replicates the in vivo mechanism of antibody protection and should therefore better reflect protection by vaccine-induced antibodies. Technical improvements of OPA have made this bioassay rapid, multiplexed, and practical for analyzing small samples including those from children. Strong correlations between ELISA and OPA have been observed in many studies of young children. However, poor correlations have been found in some important clinical situations (such as determination of protection by cross-reactive antibodies) and populations (such as elderly adults and immunodeficient patients). In these settings, OPA has become a useful supplementary measure of pneumococcal vaccine immunogenicity. Current efforts to standardize OPA will further expand its uses.
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Long-term immunogenicity of the influenza vaccine at reduced intradermal and full intramuscular doses among healthy young adults.
Clin Exp Vaccine Res
PUBLISHED: 03-21-2013
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To prepare for vaccine shortages under an influenza pandemic, several antigen-sparing strategies have been investigated. This study was aimed to evaluate the immunogenicity of influenza vaccine at reduced intradermal and full intramuscular dose.
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Butein is a novel anti-adipogenic compound.
J. Lipid Res.
PUBLISHED: 03-06-2013
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Rhus verniciflua Stokes (RVS) has been used as a traditional herbal medicine for its various biological activities including anti-adipogenic effects. Activity-guided separation led to the identification of the anti-adipogenic functions of butein. Butein, a novel anti-adipogenic compound, robustly suppressed lipid accumulation and inhibited expression of adipogenic markers. Molecular studies showed that activated transforming growth factor-? (TGF-?) and suppressed signal transducer and activator of transcription 3 (STAT3) signaling pathways were mediated by butein. Analysis of the temporal expression profiles suggests that TGF-? signaling precedes the STAT3 in the butein-mediated anti-adipogenic cascade. Small interfering RNA-mediated silencing of STAT3 or SMAD2/3 blunted the inhibitory effects of butein on adipogenesis indicating that an interaction between two signaling pathways is required for the action of butein. Upon butein treatments, stimulation of TGF-? signaling was still preserved in STAT3 silenced cells, whereas regulation of STAT3 signaling by butein was significantly impaired in SMAD2/3 silenced cells, further showing that TGF-? acts upstream of STAT3 in the butein-mediated anti-adipogenesis. Taken together, the present study shows that butein, a novel anti-adipogenic compound from RVS, inhibits adipocyte differentiation through the TGF-? pathway followed by STAT3 and peroxisome proliferator-activated receptor ? signaling, further implicating potential roles of butein in TGF-?- and STAT3-dysregulated diseases.
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Eicosanoids in metabolic syndrome.
Adv. Pharmacol.
PUBLISHED: 02-26-2013
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Chronic persistent inflammation plays a significant role in disease pathology of cancer, cardiovascular disease, and metabolic syndrome (MetS). MetS is a constellation of diseases that include obesity, diabetes, hypertension, dyslipidemia, hypertriglyceridemia, and hypercholesterolemia. Nonalcoholic fatty liver disease (NAFLD) is associated with many of the MetS diseases. These metabolic derangements trigger a persistent inflammatory cascade, which includes production of lipid autacoids (eicosanoids) that recruit immune cells to the site of injury and subsequent expression of cytokines and chemokines that amplify the inflammatory response. In acute inflammation, the transcellular synthesis of antiinflammatory eicosanoids resolve inflammation, while persistent activation of the autacoid-cytokine-chemokine cascade in metabolic disease leads to chronic inflammation and accompanying tissue pathology. Many drugs targeting the eicosanoid pathways have been shown to be effective in the treatment of MetS, suggesting a common linkage between inflammation, MetS and drug metabolism. The cross-talk between inflammation and MetS seems apparent because of the growing evidence linking immune cell activation and metabolic disorders such as insulin resistance, dyslipidemia, and hypertriglyceridemia. Thus modulation of lipid metabolism through either dietary adjustment or selective drugs may become a new paradigm in the treatment of metabolic disorders. This review focuses on the mechanisms linking eicosanoid metabolism to persistent inflammation and altered lipid and carbohydrate metabolism in MetS.
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Clinical and microbiological characteristics of vancomycin-resistant enterococci with the VanD phenotype and vanA genotype.
Jpn. J. Infect. Dis.
PUBLISHED: 02-23-2013
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Vancomycin-resistant enterococci (VRE) strains with the VanD phenotype and vanA genotype (VanD-vanA) have been reported in Asian countries. The VanD phenotype is characterized by low-level resistance to vancomycin and susceptibility or intermediate resistance to teicoplanin. We retrospectively determined the risk factors, clinical outcomes, and virulence factors for VanD-vanA VRE (20 patients colonized with Enterococcus faecium) compared to VanA-vanA VRE (20 patients colonized with E. faecium). Multiple VRE colonizations and recent glycopeptide use were related to the presence of the VanA phenotype. There were no significant differences between patients colonized with VanD-vanA VRE and VanA-vanA VRE for duration of hospital stay, duration of intensive care unit stay, or hospital mortality. The esp gene was identified from all enterococci, while 90% of VanD-vanA VRE isolates and 95% of VanA-vanA VRE isolates were positive for the hyl gene. VanA-vanA VRE was subsequently isolated from sequential samples in 8 of 20 patients (40%) with VanD-vanA VRE. All of these patients had received glycopeptides during the interval between sample collection, and 2 of 8 paired isolates (VanD-vanA VRE and VanA-vanA VRE) were closely related subtypes according to pulsed-field gel electrophoresis analysis. In conclusion, VanD-vanA VRE isolates might represent an unstable, heterogeneous population that can convert to the VanA phenotype after exposure to glycopeptides.
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The comparative morphometric study of the posterior cranial fossa : what is effective approaches to the treatment of Chiari malformation type 1?
J Korean Neurosurg Soc
PUBLISHED: 02-14-2013
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The objective of this study was to investigate changes in the posterior cranial fossa in patients with symptomatic Chiari malformation type I (CMI) compared to a control group.
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Clinical and molecular epidemiological features of hemorrhagic fever with renal syndrome in Korea over a 10-year period.
J. Clin. Virol.
PUBLISHED: 02-12-2013
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Laboratory diagnosis of hemorrhagic fever with renal syndrome (HFRS), an infectious disease caused by rodent-borne hantaviruses in Asia and Europe, depends primarily on serological methods. Since the advent of such serodiagnostic tests, few reports are available about the clinical and molecular epidemiological features of HFRS.
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Robust protein nitration contributes to acetaminophen-induced mitochondrial dysfunction and acute liver injury.
Free Radic. Biol. Med.
PUBLISHED: 02-12-2013
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Acetaminophen (APAP), a widely used analgesic/antipyretic agent, can cause liver injury through increased nitrative stress, leading to protein nitration. However, the identities of nitrated proteins and their roles in hepatotoxicity are poorly understood. Thus, we aimed at studying the mechanism of APAP-induced hepatotoxicity by systematic identification and characterization of nitrated proteins in the absence or presence of an antioxidant, N-acetylcysteine (NAC). The levels of nitrated proteins markedly increased at 2h in mice exposed to a single APAP dose (350mg/kg ip), which caused severe liver necrosis at 24h. Protein nitration and liver necrosis were minimal in mice exposed to nontoxic 3-hydroxyacetanilide or animals co-treated with APAP and NAC. Mass-spectral analysis of the affinity-purified nitrated proteins identified numerous mitochondrial and cytosolic proteins, including mitochondrial aldehyde dehydrogenase, Mn-superoxide dismutase, glutathione peroxidase, ATP synthase, and 3-ketoacyl-CoA thiolase, involved in antioxidant defense, energy supply, or fatty acid metabolism. Immunoprecipitation followed by immunoblot with anti-3-nitrotyrosine antibody confirmed that the aforementioned proteins were nitrated in APAP-exposed mice but not in NAC-cotreated mice. Consistently, NAC cotreatment significantly restored the suppressed activity of these enzymes. Thus, we demonstrate a new mechanism by which many nitrated proteins with concomitantly suppressed activity promotes APAP-induced mitochondrial dysfunction and hepatotoxicity.
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Significance of HPV-58 infection in women who are HPV-positive, cytology-negative and living in a country with a high prevalence of HPV-58 infection.
PLoS ONE
PUBLISHED: 02-05-2013
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Cervical cytology and human papillomavirus (HPV) DNA co-testing is recommended as a screening method for detecting cervical lesions. However, for women who are HPV-positive but cytology-negative, the appropriate management and significance of HPV-58 infection remain unknown.
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Outpatient-based pneumococcal vaccine campaign and survey of perceptions about pneumococcal vaccination in patients and doctors.
Yonsei Med. J.
PUBLISHED: 02-01-2013
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Despite the ready availability of pneumococcal vaccine, vaccination rates are quite low in South Korea. This study was designed to assess perceptions and awareness about pneumococcal vaccines among subjects at risk and find strategies to increases vaccine coverage rates.
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Long-term immunogenicity of the pandemic influenza A/H1N1 2009 vaccine among health care workers: influence of prior seasonal influenza vaccination.
Clin. Vaccine Immunol.
PUBLISHED: 01-30-2013
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Health care workers (HCWs) are at great risk of influenza infection and transmission. Vaccination for seasonal influenza is routinely recommended, but this strategy should be reconsidered in a pandemic situation. Between October 2009 and September 2010, a multicenter study was conducted to assess the long-term immunogenicity of the A/H1N1 2009 monovalent influenza vaccine among HCWs compared to non-health care workers (NHCWs). The influence of prior seasonal influenza vaccination was also assessed with respect to the immunogenicity of pandemic H1N1 influenza vaccine. Serum hemagglutinin inhibition titers were determined prevaccination and then at 1, 6, and 10 months after vaccination. Of the 360 enrolled HCW subjects, 289 participated in the study up to 10 months after H1N1 monovalent influenza vaccination, while 60 of 65 NHCW subjects were followed up. Seroprotection rates, seroconversion rates, and geometric mean titer (GMT) ratios fulfilled the European Unions licensure criteria for influenza A/California/7/2009 (H1N1) at 1 month after vaccination in both the HCWs and NHCWs, without any significant difference. At 6 months after vaccination, the seroprotection rate was more significantly lowered among the NHCWs than among the HCWs (P < 0.01). Overall, postvaccination (1, 6, and 10 months after vaccination) GMTs for A/California/7/2009 (H1N1) were significantly lower among the seasonal influenza vaccine recipients than among the nonrecipients (P < 0.05). In conclusion, HCWs should be encouraged to receive an annual influenza vaccination, considering the risk of repeated exposure. However, prior reception of seasonal influenza vaccine showed a negative influence on immunogenicity for the pandemic A/H1N1 2009 influenza vaccine.
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Dichloromethane extracts of Sophora japonica L. stimulate osteoblast differentiation in mesenchymal stem cells.
Nutr Res
PUBLISHED: 01-29-2013
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Sophora japonica L. fruit prevents bone loss by inhibiting osteoclast activity. We hypothesized that S japonica L. extracts could promote osteoblast differentiation. To test this hypothesis, we investigated the effect of S japonica L. on osteoblast differentiation and identified the bioactive compound(s) from S japonica L. The mature fruit of S japonica L. was partitioned with ethanol, hexane, dichloromethane (DCM), ethyl acetate, and butanol, and their effects were tested on osteoblast differentiation of C3H10T1/2 cells. DCM fractionated extracts were identified as the most osteogenic fractions. DCM fractionated extracts dose-dependently stimulated alkaline phosphatase activity and matrix mineralization. The DCM fractions also induced expression of osteoblast markers such as alkaline phosphatase, osterix, and osteocalcin in C3H10T1/2 and primary bone marrow cells. Genistein was found abundantly in the DCM fractions. Furthermore, the genistein and DCM fractions similarly modulated the expression of estrogen target genes and were both active in transfection assays that measured estrogen agonistic activity. Finally, pharmacological inhibition by treatment with an estrogen receptor antagonist or specific inhibition of gene expression by small interference RNAs targeted to estrogen receptor-? abolished the effects of the DCM extracts, further supporting the idea that the genistein in the DCM extracts mediated the pro-osteogenic effects. Taken together, we identified genistein as the key phytoestrogen responsible for the effects of S japonica L. on osteoblast differentiation.
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Perceptions of Tetanus-diphteria-acellular pertussis (Tdap) Vaccination among Korean Women of Childbearing Age.
Infect Chemother
PUBLISHED: 01-25-2013
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The number of cases of pertussis reported has increased gradually in the last decade. Pertussis vaccination is the most effective strategy for the prevention of infection. Despite the fact that young infants are at the highest risk for pertussis, the rate of tetanus-diphtheria-acellular pertussis (Tdap) vaccination is presumed to be very low among women of childbearing age in Korea. The purpose of this study was to investigate the perceptions of women of childbearing age regarding Tdap vaccination in Korea.
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Depression Among HIV-infected Patients in Korea: Assessment of Clinical Significance and Risk Factors.
Infect Chemother
PUBLISHED: 01-17-2013
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With prolonged life expectancies, mental illness has emerged as a disabling disorder among people with HIV.
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Hospital-based influenza surveillance in Korea: hospital-based influenza morbidity and mortality study group.
J. Med. Virol.
PUBLISHED: 01-16-2013
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Influenza epidemics occur annually with variations in size and severity. Hospital-based Influenza Morbidity & Mortality was established to monitor influenza epidemics and their severity, which is composed of two surveillance systems: emergency room-based and inpatient-based surveillance. Regarding emergency room-based surveillance, influenza-like illness index (influenza-like illness cases per 1,000 emergency room-visiting subjects), number of laboratory-confirmed cases and the distribution of influenza types were estimated weekly. Inpatient-based surveillance included monitoring for hospitalization, complications, and mortality. The emergency room influenza-like illness index correlated well with the number of laboratory-confirmed influenza cases, and showed a bimodal peak at Week 4 (179.2/1,000 emergency room visits) and Weeks 13-14 (169.6/1,000 emergency room visits) of 2012. Influenza A was the predominant strain during the first epidemic peak, while influenza B was isolated exclusively during the second peak. In 2011-2012 season, the mean admission rate of emergency room-visiting patients with influenza-like illness was 16.3% without any increase over the epidemic period. Among the hospitalized patients with influenza, 33.6% (41 out of 122 patients) were accompanied by complications, and pneumonia (28.7%, 35 out of 122 patients) was the most common. Most fatal cases were caused by influenza A (96.2%) after the first epidemic peak. In conclusion, Hospital-based Influenza Morbidity & Mortality was effective for monitoring the trends in circulating influenza activity concurrently with its severity. In the 2011-2012 season, the influenza epidemic persisted for a ? 5-month period, with a bimodal peak of influenza A and B in sequence. Overall, influenza A was more severe than influenza B.
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Increased nitroxidative stress promotes mitochondrial dysfunction in alcoholic and nonalcoholic fatty liver disease.
Oxid Med Cell Longev
PUBLISHED: 01-09-2013
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Increased nitroxidative stress causes mitochondrial dysfunctions through oxidative modifications of mitochondrial DNA, lipids, and proteins. Persistent mitochondrial dysfunction sensitizes the target cells/organs to other pathological risk factors and thus ultimately contributes to the development of more severe disease states in alcoholic and nonalcoholic fatty liver disease. The incidences of nonalcoholic fatty liver disease continuously increase due to high prevalence of metabolic syndrome including hyperlipidemia, hypercholesterolemia, obesity, insulin resistance, and diabetes. Many mitochondrial proteins including the enzymes involved in fat oxidation and energy supply could be oxidatively modified (including S-nitrosylation/nitration) under increased nitroxidative stress and thus inactivated, leading to increased fat accumulation and ATP depletion. To demonstrate the underlying mechanism(s) of mitochondrial dysfunction, we employed a redox proteomics approach using biotin-N-maleimide (biotin-NM) as a sensitive biotin-switch probe to identify oxidized Cys residues of mitochondrial proteins in the experimental models of alcoholic and acute liver disease. The aims of this paper are to briefly describe the mechanisms, functional consequences, and detection methods of mitochondrial dysfunction. We also describe advantages and limitations of the Cys-targeted redox proteomics method with alternative approaches. Finally, we discuss various applications of this method in studying oxidatively modified mitochondrial proteins in extrahepatic tissues or different subcellular organelles and translational research.
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Korean population genetic data and concordance for the PowerPlex® ESX 17, AmpFlSTR Identifiler®, and PowerPlex® 16 systems.
Forensic Sci Int Genet
PUBLISHED: 01-09-2013
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In case of paternity or maternity investigations with short tandem repeat (STR) analysis, deficient cases, missing person, or mutations are encountered and common STRs cannot provide sufficient forensic parameters. Thus, it is recommended that additional STRs are needed to complement conventional analysis for more reliable forensic information. We analyzed variation of 23 STRs contained in the new PowerPlex(®) ESX 17 kit (Promega) and two conventional kits of the AmpFlSTR Identifiler(®) (Applied Biosystems) and PowerPlex(®) 16 systems (Promega) in 452 randomly chosen individuals from Korea to provide an expanded and reliable Korean database. Allele frequencies and forensic parameters were used to evaluate suitability and robustness of the new kit for forensic genetic analysis as well as in concordance studies. The combined probability of match for the 16 loci in the PowerPlex(®) ESX 17 system was 2.76×10(-20). One genotyping discrepancy due to a null allele was observed at the D18S51 locus (the concordant rate=99.99%), showing a primer-binding site mutation in the sequence of the locus (G-to-A substitution at position 146 of Genbank accession number JX018211). Thus, the new kit is a valuable forensic tool and is suitable to extend the Korean population genetic data obtained with well-established polymerase chain reaction multiplex-kits of the AmpFlSTR Identifiler(®) and PowerPlex(®) 16 systems.
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Low level of immunity against hepatitis A among Korean adolescents: vaccination rate and related factors.
Am J Infect Control
PUBLISHED: 01-08-2013
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We evaluated the current vaccination rate and immunity in the Korean adolescent population and analyzed their parents attitudes toward hepatitis A virus (HAV) vaccination.
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Finding and characterizing mammary analogue secretory carcinoma of the salivary gland.
Korean J Pathol
PUBLISHED: 01-08-2013
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A new tumor entity of the salivary glands, mammary analogue secretory carcinoma (MASC) with ETV6-NTRK3 translocation, has recently been proposed. MASC was originally diagnosed as adenocarcinoma, not otherwise specified (ANOS), or acinic cell carcinoma (AciCC) by the current World Health Organization classification. We aimed to identify MASC cases by molecular tests, and to characterize their clinical, histological, and immunohistochemical features.
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Clinical implications of pneumococcal serotypes: invasive disease potential, clinical presentations, and antibiotic resistance.
J. Korean Med. Sci.
PUBLISHED: 01-08-2013
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Streptococcus pneumoniae can asymptomatically colonize the nasopharynx and cause a diverse range of illnesses. This clinical spectrum from colonization to invasive pneumococcal disease (IPD) appears to depend on the pneumococcal capsular serotype rather than the genetic background. According to a literature review, serotypes 1, 4, 5, 7F, 8, 12F, 14, 18C, and 19A are more likely to cause IPD. Although serotypes 1 and 19A are the predominant causes of invasive pneumococcal pneumonia, serotype 14 remains one of the most common etiologic agents of non-bacteremic pneumonia in adults, even after 7-valent pneumococcal conjugate vaccine (PCV7) introduction. Serotypes 1, 3, and 19A pneumococci are likely to cause empyema and hemolytic uremic syndrome. Serotype 1 pneumococcal meningitis is prevalent in the African meningitis belt, with a high fatality rate. In contrast to the capsule type, genotype is more closely associated with antibiotic resistance. CC320/271 strains expressing serotype 19A are multidrug-resistant (MDR) and prevalent worldwide in the era of PCV7. Several clones of MDR serotype 6C pneumococci emerged, and a MDR 6D clone (ST282) has been identified in Korea. Since the pneumococcal epidemiology of capsule types varies geographically and temporally, a nationwide serosurveillance system is vital to establishing appropriate vaccination strategies for each country.
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What is Visualize?

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

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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.