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Find video protocols related to scientific articles indexed in Pubmed.
Mortality prediction by acute kidney injury biomarkers in comparison with serum creatinine.
Biomarkers
PUBLISHED: 10-01-2014
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Abstract Objectives: To investigate the performance of acute kidney injury (AKI) biomarkers for mortality prediction. Materials and methods: Cutoff values of urinary L-type fatty acid-binding protein (L-FABP) and N-acetyl-?-d-glucosaminidase (NAG) for AKI diagnosis in ICU were determined in the derivation cohort. The performance of these AKI biomarkers for mortality prediction was evaluated in the validation cohort with stratification of serum-creatinine based AKI diagnosis. Results: Mortality in the AKI patients diagnosed by serum creatinine was increased remarkably when urinary L-FABP and NAG were positive. Conclusions: These AKI biomarkers can specifically detect high-risk patients among creatinine-base diagnosed AKI.
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The human bitter taste receptor hTAS2R39 is the primary receptor for the bitterness of theaflavins.
Biosci. Biotechnol. Biochem.
PUBLISHED: 06-26-2014
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We purified several hundred mgs of four major theaflavins (theaflavin, theaflavin-3-O-gallate, theaflavin-3'-O-gallate, and theaflavin-3,3'-O-digallate). Among the 25 hTAS2Rs expressed in HEK293T cells, hTAS2R39 and hTAS2R14 were activated by theaflavins. Both hTAS2R39 and hTAS2R14 responded to theaflavin-3'-O-gallate. In addition, hTAS2R39 was activated by theaflavin and theaflavin-3,3'-O-gallate, but not by theaflavin-3-O-gallate. In contrast, hTAS2R14 responded to theaflavin-3-O-gallate.
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Perioperative plasma neutrophil gelatinase-associated lipocalin measurement in patients who undergo left ventricular assist device implantation surgery.
Circ. J.
PUBLISHED: 06-13-2014
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Perioperative complication of end-organ injury including acute kidney injury (AKI) is a frequent and severe problem for patients undergoing left ventricular assist device (LVAD) implantation. This study evaluated an emerging AKI biomarker, plasma neutrophil gelatinase-associated lipocalin (NGAL), in a LVAD implantation cohort.
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Thiol modification by bioactivated polyphenols and its potential role in skin inflammation.
Biosci. Biotechnol. Biochem.
PUBLISHED: 05-28-2014
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In the present study, we evaluated the modifying behavior of simple phenolic compounds on the sulfhydryl groups of glutathione and proteins. The catechol-type polyphenols, including protocatechuic acid, but neither the monophenols nor O-methylated catechol, can modify the sulfhydryl groups in a phenol oxidase-dependent manner. The possible involvement of polyphenol bioactivation in the enhancement of skin inflammation was also suggested.
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The prognosis of osteosarcoma occurring as second malignancy of childhood cancers may be favorable: experience of two cancer centers in Japan.
Int. J. Clin. Oncol.
PUBLISHED: 05-23-2014
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Osteosarcoma as second malignancy of childhood cancers rarely occurs, and its clinical characteristics are unclear.
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Lateral suboccipital retrosigmoid approach with tentorial incision for petroclival meningiomas: technical note.
J Neurol Surg B Skull Base
PUBLISHED: 05-02-2014
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Introduction?The resection of petroclival meningiomas presents great neurosurgical challenges. Although multiple surgical approaches have been developed, the retrosigmoid route tends to be used to address tumors that are predominantly located in the posterior fossa. Our modification of the lateral suboccipital retrosigmoid approach with the placement of a tentorial incision yields good visualization of the supratentorial part of the tumor around the midbrain. Methods?We treated four patients, one with primary and three with recurrent petroclival meningioma, by our modified approach. After lateral suboccipital craniotomy, the infratentorial part of the tumor was removed after detaching it from the tentorial surface. The cerebellar tentorium was then carefully incised from the supracerebellar angle, taking care not to damage the superior cerebellar artery and trochlear nerve. Results?The operative field surrounding the midbrain was widened by this procedure, and safe dissection of the tumor from the brainstem and other neurovascular structures was performed with direct observation of the interface. Conclusions?Our approach is a useful modification of the retrosigmoid approach to petroclival meningiomas. It facilitates the safe resection of the supratentorial part of the tumor in the ambient cistern behind the tentorium.
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Structural specificity of electric potentials in the coulometric-array analysis of catechins and theaflavins.
J Clin Biochem Nutr
PUBLISHED: 04-02-2014
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We have established a novel method to evaluate the redox properties of tea polyphenols by HPLC-coulometric-array analysis. We plotted the quantity of electricity (µC) on the vertical axis and the electric potential (mV), adjusted with the associated palladium reference electrode, on the horizontal axis to provide "quantity versus potential (QP) plot". The patterns of the plots correspond to the derivative of a hydrodynamic voltammogram or a current-voltage curve, with the electric potentials of the peaks in the QP plot corresponding to the half-wave potentials in the current-voltage curve. We confirmed that catechins and theaflavins are oxidized depending on the electric potentials of their partial structures, and found that all compounds showing a peak at 0 mV in the QP plots produce hydrogen peroxide (H2O2) during the autoxidation process.
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Impact of infiltrative growth on the outcome of patients with undifferentiated pleomorphic sarcoma and myxofibrosarcoma.
J Surg Oncol
PUBLISHED: 01-23-2014
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Infiltrative growth, frequently observed in undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS), is often associated with a positive surgical margin as well as a local failure. The purpose of our study was to determine whether the radiographic growth patterns were associated with the outcomes of patients with UPS and MFS.
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Safranal, a novel protein tyrosine phosphatase 1B inhibitor, activates insulin signaling in C2C12 myotubes and improves glucose tolerance in diabetic KK-Ay mice.
Mol Nutr Food Res
PUBLISHED: 01-02-2014
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Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling by tyrosine dephosphorylation of insulin receptor, and its increased activity and expression is implicated in the pathogenesis of insulin resistance. Hence, PTP1B inhibition is anticipated to improve insulin resistance in type 2 diabetic subjects. The aim of this study was to find a novel PTP1B inhibitor from medicinal food and to evaluate its antidiabetic effects.
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Depressive symptoms of female nursing staff working in stressful environments and their association with serum creatine kinase and lactate dehydrogenase - a preliminary study.
Biopsychosoc Med
PUBLISHED: 01-01-2014
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The activity of creatine kinase (CK) in serum has recently been reported to be potentially associated with several types of depression. The aim of this study is to evaluate whether serum enzymes, including CK, vary even in a healthy population with depressive symptoms caused by work-related stress. We gave questionnaires and blood examinations to 93 healthy female nursing home workers and did an enzyme-linked immunosorbent assay for the quantitative detection of CK isozyme muscle-type M chain (CK-MM) in serum.
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The proportion of clinically relevant alarms decreases as patient clinical severity decreases in intensive care units: a pilot study.
BMJ Open
PUBLISHED: 09-12-2013
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To determine (1) the proportion and number of clinically relevant alarms based on the type of monitoring device; (2) whether patient clinical severity, based on the sequential organ failure assessment (SOFA) score, affects the proportion of clinically relevant alarms and to suggest; (3) methods for reducing clinically irrelevant alarms in an intensive care unit (ICU).
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Applicability of the prehospital termination of resuscitation rule in an area dense with hospitals in Tokyo: a single-center, retrospective, observational study: Is the pre hospital TOR rule applicable in Tokyo?
Am J Emerg Med
PUBLISHED: 09-08-2013
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It is unclear whether the prehospital termination of resuscitation (TOR) rule is applicable in specific situations such as in areas extremely dense with hospitals.
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Plasma neutrophil gelatinase-associated lipocalin in acute kidney injury superimposed on chronic kidney disease after cardiac surgery: a multicenter prospective study.
Crit Care
PUBLISHED: 06-21-2013
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Plasma neutrophil gelatinase-associated lipocalin (NGAL) is reportedly useful for post-cardiac surgery acute kidney injury (AKI). Although chronic kidney disease (CKD) is a strong risk factor for AKI development, no clinical evaluation of plasma NGAL has specifically examined AKI occurring in patients with CKD. This study evaluated plasma NGAL in AKI superimposed on CKD after cardiac surgery.
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Adult-onset seizures in a patient with Down syndrome and portosystemic shunt.
Brain Dev.
PUBLISHED: 03-26-2013
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Objective: The prevalence of epilepsy in patients with Down syndrome (DS) is 5-13%, which is higher than the prevalence in the general population. Transient hyperammonemia is often observed following seizure, but it typically resolves within a day. Here, we describe the case a 37-year-old woman who had DS and a history of adult-onset epilepsy and was admitted to our hospital with recurrent seizures. After admission, her ammonia levels fluctuated without any apparent cause, and dynamic computed tomography revealed a portosystemic shunt. The findings suggest that her seizures possibly precipitated from hyperammonemia secondary to a portosystemic shunt, and we reviewed the relevant literature. Methods: We conducted PubMed, Web of Science, and EMBASE searches without language restrictions for articles published between 1970 and February 2013. Results: In addition to the present case, 7 cases were ultimately included in this review. Four patients were newborns, 2 patients were 1month old, and 1 patient was 3years old. No adult cases were described until now. Conclusion: Adult patients with DS diagnosed with epilepsy are not routinely assessed for portosystemic venous shunts. Measuring ammonia levels in patients with DS the day after admission would help detect portosystemic shunts, even if the patients have been previously diagnosed with epilepsy. Practice Implications: If ammonia levels fluctuate without any apparent cause after seizure, dynamic computed tomography should be performed, especially for patients with DS, whether or not they have been previously diagnosed with epilepsy.
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Endotoxin adsorption by polymyxin B column or intraaortic balloon pumping use for severe septic cardiomyopathy.
Am J Emerg Med
PUBLISHED: 02-08-2013
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Septic patients often have low cardiac output. Some of them present severe cardiac dysfunction such as septic cardiomyopathy. However, no well-known and effective treatment for septic cardiomyopathy exists. The effect of endotoxin adsorption by polymyxin B–immobilized fiber column–direct hemoperfusion (PMX-DHP) and intraaortic balloon pumping (IABP) for septic shock remains uncertain. We experienced 2 very contrastive case reports of severe septic cardiomyopathy. We experienced 2 cases of severe septic cardiomyopathy with refractory shock. Case 1 with colon perforation presented refractory shock 6 hours after PMX-DHP, and IABP immediately improved her hemodynamics. In contrast, IABP had no effect at all in case 2 with viral enteritis, but PMXDHP improved her blood pressure and stroke volume markedly. The probability of impaired coronary microcirculation and relative bradycardia is the least required conditions for IABP use in severe septic cardiomyopathy. Meanwhile, PMX-DHP could be a good option for septic cardiomyopathy because of its fewer complications.
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Non-specific protein modifications by a phytochemical induce heat shock response for self-defense.
PLoS ONE
PUBLISHED: 02-05-2013
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Accumulated evidence shows that some phytochemicals provide beneficial effects for human health. Recently, a number of mechanistic studies have revealed that direct interactions between phytochemicals and functional proteins play significant roles in exhibiting their bioactivities. However, their binding selectivities to biological molecules are considered to be lower due to their small and simple structures. In this study, we found that zerumbone, a bioactive sesquiterpene, binds to numerous proteins with little selectivity. Similar to heat-denatured proteins, zerumbone-modified proteins were recognized by heat shock protein 90, a constitutive molecular chaperone, leading to heat shock factor 1-dependent heat shock protein induction in hepa1c1c7 mouse hepatoma cells. Furthermore, oral administration of this phytochemical up-regulated heat shock protein expressions in the livers of Sprague-Dawley rats. Interestingly, pretreatment with zerumbone conferred a thermoresistant phenotype to hepa1c1c7 cells as well as to the nematode Caenorhabditis elegans. It is also important to note that several phytochemicals with higher hydrophobicity or electrophilicity, including phenethyl isothiocyanate and curcumin, markedly induced heat shock proteins, whereas most of the tested nutrients did not. These results suggest that non-specific protein modifications by xenobiotic phytochemicals cause mild proteostress, thereby inducing heat shock response and leading to potentiation of protein quality control systems. We considered these bioactivities to be xenohormesis, an adaptation mechanism against xenobiotic chemical stresses. Heat shock response by phytochemicals may be a fundamental mechanism underlying their various bioactivities.
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Prognostic Factors in Elderly Osteosarcoma Patients: A Multi-institutional Retrospective Study of 86 Cases.
Ann. Surg. Oncol.
PUBLISHED: 01-30-2013
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The occurrence of osteosarcoma in elderly patients has recently been increasing, and the outcome is poor. This multi-institutional retrospective study was conducted to investigate clinical features and prognostic factors in patients older than 40 years with osteosarcoma.
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New biomarker panel of plasma neutrophil gelatinase-associated lipocalin and endotoxin activity assay for detecting sepsis in acute kidney injury.
J Crit Care
PUBLISHED: 01-11-2013
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Septic acute kidney injury (AKI) shows an unacceptably high mortality rate. Detection of sepsis is important for the clinical management of AKI patients. This study was undertaken to evaluate 2 biomarkers of neutrophil gelatinase-associated lipocalin (NGAL) and endotoxin activity (EA) assay and their combination for detecting sepsis in AKI.
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Development of information systems and clinical decision support systems for emergency departments: a long road ahead for Japan.
Emerg Med J
PUBLISHED: 01-08-2013
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Emergency care services face common challenges worldwide, including the failure to identify emergency illnesses, deviations from standard treatments, deterioration in the quality of medical care, increased costs from unnecessary testing, and insufficient education and training of emergency personnel. These issues are currently being addressed by implementing emergency department information systems (EDIS) and clinical decision support systems (CDSS). Such systems have been shown to increase the efficiency and safety of emergency medical care. In Japan, however, their development is hindered by a shortage of emergency physicians and insufficient funding. In addition, language barriers make it difficult to introduce EDIS and CDSS in Japan that have been created for an English-speaking market. This perspective addresses the key events that motivated a campaign to prioritise these services in Japan and the need to customise EDIS and CDSS for its population.
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Bronchial ulceration as a prognostic indicator for varicella pneumonia: case report and systematic literature review.
J. Clin. Virol.
PUBLISHED: 01-04-2013
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Adult varicella pneumonia is a common and serious complication of varicella zoster virus (VZV) infection in pregnant woman and immunocompromised individuals, with mortality rates of 30-50%. The poor prognosis is attributable to very aggressive disease progression and delayed onset of treatment. Here, we present a case of varicella pneumonia in a 69-year-old woman following long-term immunosuppressive treatment for kidney transplant. Respiratory failure developed within 3 d after admission for skin rash, and the patient died 28 d later despite acyclovir and foscarnet treatment. The autopsy showed extensive mucosal airway ulcerations from the pharynx to the main bronchi and numerous VZV-infected cells. We searched PubMed, Web of Science, and EMBASE (1980 through February 2012), as well as several medical report databases created by Japanese healthcare professionals, for all reported cases of varicella pneumonia for which bronchoscopy findings were documented. Twenty-four cases were included and we found that patients with limited or shallow ulcers had favorable outcomes, whereas patients with vast and deep ulcerations had fatal outcomes. These findings indicate that bronchoscopy findings, particularly those showing bronchial involvement, may be useful for evaluating varicella pneumonia.
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Primary T-cell/histiocyte-rich B-cell lymphoma arising in the trigeminal ganglion in a patient with rheumatoid arthritis.
Brain Tumor Pathol
PUBLISHED: 04-29-2011
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We report a cased of a 68-year-old man with primary T-cell/histiocyte-rich B-cell lymphoma (T/HRBCL) that arose in the trigeminal ganglion. He had a 30-year history of rheumatoid arthritis and presented with progressive left facial pain that had started 3 weeks earlier. Magnetic resonance imaging (MRI) revealed an enhanced mass in the trigeminal ganglion and swelling of the distal part of the trigeminal root. The tumor, subtotally resected via the left anterior petrosal approach, was composed of proliferating CD30- and CD79-positive atypical large polygonal cells with hyperchromatic single or multiple nuclei. CD3-positive small lymphoid cells and CD68-positive histiocytic cells were intermingled with the neoplastic cells. These findings were compatible with T/HRBCL. After whole-brain radiation, his facial pain improved and he was discharged. Postoperatively, he developed transient left sixth nerve paresis. This is the first report of this rare type of B-cell lymphoma arising from the trigeminal ganglion. We posit that his prolonged immunosuppressive treatment for rheumatoid arthritis contributed to its development.
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Posttraumatic stress symptom (PTSS) and posttraumatic growth (PTG) in parents of childhood, adolescent and young adult patients with high-grade osteosarcoma.
Int. J. Clin. Oncol.
PUBLISHED: 04-18-2011
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Posttraumatic stress symptom (PTSS) and posttraumatic growth (PTG) were surveyed in parents of childhood, adolescent and young adult patients with high-grade osteosarcoma.
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Interaction of epicatechin gallate with phospholipid membranes as revealed by solid-state NMR spectroscopy.
Biochim. Biophys. Acta
PUBLISHED: 01-27-2011
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Epicatechin gallate (ECg), a green tea polyphenol, has various physiological effects. Our previous nuclear Overhauser effect spectroscopy (NOESY) study using solution NMR spectroscopy demonstrated that ECg strongly interacts with the surface of phospholipid bilayers. However, the dynamic behavior of ECg in the phospholipid bilayers has not been clarified, especially the dynamics and molecular arrangement of the galloyl moiety, which supposedly has an important interactive role. In this study, we synthesized [13C]-ECg, in which the carbonyl carbon of the galloyl moiety was labeled by 13C isotope, and analyzed it by solid-state NMR spectroscopy. Solid-state 31P NMR analysis indicated that ECg changes the gel-to-liquid-crystalline phase transition temperature of DMPC bilayers as well as the dynamics and mobility of the phospholipids. In the solid-state 13C NMR analysis under static conditions, the carbonyl carbon signal of the [13C]-ECg exhibited an axially symmetric powder pattern. This indicates that the ECg molecules rotate about an axis tilting at a constant angle to the bilayer normal. The accurate intermolecular-interatomic distance between the labeled carbonyl carbon of [13C]-ECg and the phosphorus of the phospholipid was determined to be 5.3±0.1 Å by 13C-(31)P rotational echo double resonance (REDOR) measurements. These results suggest that the galloyl moiety contributes to increasing the hydrophobicity of catechin molecules, and consequently to high affinity of galloyl-type catechins for phospholipid membranes, as well as to stabilization of catechin molecules in the phospholipid membranes by cation-? interaction between the galloyl ring and quaternary amine of the phospholipid head-group.
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Subfrontal schwannoma mimicking neuroblastoma: case report.
Skull Base Rep
PUBLISHED: 01-17-2011
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Computed tomography (CT), performed in a healthy 28-year-old man after minor head injury, detected a frontal base tumor. Neurological examination revealed left hyposmia. On magnetic resonance imaging scans, there was a heterogeneously enhanced tumor located in the left paramedian frontal base with extension into the left ethmoid sinus. Angiography showed a hypervascular mass in the left anterior cranial fossa; it was mainly fed by the left ethmoidal artery. Positron emission tomography scanning showed moderate accumulation of 11-methylmethionine and low accumulation of 18-fluorodeoxyglucose (FDG) at the tumor site. Bone image CT disclosed compressive, nondestructive deformation of the left frontal base. The preoperative diagnosis was olfactory neuroblastoma or meningioma. The tumor was totally resected via bifrontal craniotomy. The tumor was histologically diagnosed as typical schwannoma; it was positive for S-100 protein. We report a rare subfrontal schwannoma with extension into the nasal cavity that mimicked neuroblastoma. Low FDG accumulation and compressive deformation of the anterior skull base may help in the differential diagnosis of these tumors.
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(-)-Epigallocatechin-3-gallate suppresses growth of AZ521 human gastric cancer cells by targeting the DEAD-box RNA helicase p68.
Free Radic. Biol. Med.
PUBLISHED: 01-17-2011
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(-)-Epigallocatechin-3-gallate (EGCG), the most abundant and biologically active polyphenol in green tea, induces apoptosis and suppresses proliferation of cancer cells by modulating multiple signal transduction pathways. However, the fundamental mechanisms responsible for these cancer-preventive effects have not been clearly elucidated. Recently, we found that EGCG can covalently bind to cysteine residues in proteins through autoxidation and subsequently modulate protein function. In this study, we demonstrate the direct binding of EGCG to cellular proteins in AZ521 human gastric cancer cells by redox-cycle staining. We comprehensively explored the binding targets of EGCG from EGCG-treated AZ521 cells by proteomics techniques combined with the boronate-affinity pull-down method. The DEAD-box RNA helicase p68, which is overexpressed in a variety of tumor cells and plays an important role in cancer development and progression, was identified as a novel EGCG-binding target. Exposure of AZ521 cells to EGCG lowered the p68 level dose dependently. The present findings show that EGCG inhibits AZ521 cell proliferation by preventing ?-catenin oncogenic signaling through proteasomal degradation of p68 and provide a new perspective on the molecular mechanism of EGCG action.
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Human serum albumin as an antioxidant in the oxidation of (-)-epigallocatechin gallate: participation of reversible covalent binding for interaction and stabilization.
Biosci. Biotechnol. Biochem.
PUBLISHED: 01-07-2011
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Human serum albumin (HSA) contributes to the stabilization of (-)-epigallocatechin gallate (EGCg) in serum. We characterize in the present study the mechanisms for preventing EGCg oxidation by HSA. EGCg was stable in human serum or buffers with HSA, but (-)-epigallocatechin (EGC) was unstable. We show by comparing EGCg and EGC in a neutral buffer that EGCg had a higher binding affinity than EGC. This indicates that the galloyl moiety participated in the interaction of EGCg with HSA and that this interaction was of critical importance in preventing EGCg oxidation. The binding affinity of EGCg for HSA and protein carbonyl formation in HSA were enhanced in an alkaline buffer. These results suggest the reversible covalent modification of EGCg via Schiff-base formation, and that the immobilization of EGCg to HSA, through the formation of a stable complex, prevented the polymerization and decomposition of EGCg in human serum.
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Covalent binding of tea catechins to protein thiols: the relationship between stability and electrophilic reactivity.
Biosci. Biotechnol. Biochem.
PUBLISHED: 12-07-2010
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In this study, we investigated the relationship between the stability of catechins and their electrophilic reactivity with proteins. The stability of catechins was evaluated by HPLC analysis. Catechol-type catechins were stable in a neutral buffer, but pyrogallol-type catechins, such as (-)-epigallocatechin gallate (EGCg), were unstable. The electrophilic reactivity of catechins with thiol groups in a model peptide and a protein was confirmed by both mass spectrometry and electrophoresis/blotting with redox-cycling staining. In a comparison of several catechins, pyrogallol-type catechins had higher reactivity with protein thiols than catechol-type catechins. The instability and reactivity of EGCg were enhanced in an alkaline pH buffer. The reactivity of EGCg was reduced by antioxidants due to their ability to prevent EGCg autoxidation. These results indicate that the instability against oxidation of catechins is profoundly related to their electrophilic reactivity. Consequently, the difference in these properties of tea catechins can contribute to the magnitude of their biological activities.
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Acute epidural hematoma in a patient with Glanzmanns thrombasthenia: case report.
Neurol. Med. Chir. (Tokyo)
PUBLISHED: 10-30-2010
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A 7-year-old girl with Glanzmanns thrombasthenia (GT) fell and hit her head against a table. Within 2 hours she began to vomit and became drowsy. On admission to our hospital her Glasgow Coma Scale score was 13. Computed tomography (CT) on admission showed acute epidural hematoma in the left posterior fossa. We administered platelets, performed emergent lateral suboccipital craniotomy, and totally removed the epidural hematoma. Postoperative CT showed no evidence of hematoma or re-bleeding. She was discharged without neurological deficits 14 days after the operation. GT is a platelet aggregation disorder due to a functional loss of platelet membrane glycoprotein IIb/IIIa. The present patient with GT underwent successful emergency craniotomy after platelet transfusion.
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Influence of the galloyl moiety in tea catechins on binding affinity for human serum albumin.
J. Nutr. Sci. Vitaminol.
PUBLISHED: 08-25-2010
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The major catechins of green tea extract are (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECg), and (-)-epigallocatechin gallate (EGCg). Recent research has indicated that catechins form complexes with human serum albumin (HSA) in blood, and differences in their binding affinity toward HSA are believed to modulate their bioavailability. In this study, we kinetically investigated the interaction between the catechins and HSA immobilized on a quartz-crystal microbalance (QCM). The association constants obtained from the frequency changes of QCM revealed interactions of ECg and EGCg with HSA that are 100 times stronger than those of EC and EGC. Furthermore, comparisons of these catechins by native-gel electrophoresis/blotting with redox-cycling staining revealed that, in a phosphate buffer, ECg and EGCg have a higher binding affinity toward HSA than EC and EGC. These observations indicate that catechins with a galloyl moiety have higher binding affinities toward HSA than catechins lacking a galloyl moiety.
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Crystal structures of glycinamide ribonucleotide synthetase, PurD, from thermophilic eubacteria.
J. Biochem.
PUBLISHED: 08-16-2010
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Glycinamide ribonucleotide synthetase (GAR-syn, PurD) catalyses the second reaction of the purine biosynthetic pathway; the conversion of phosphoribosylamine, glycine and ATP to glycinamide ribonucleotide (GAR), ADP and Pi. In the present study, crystal structures of GAR-syns from Thermus thermophilus, Geobacillus kaustophilus and Aquifex aeolicus were determined in apo forms. Crystal structures in ligand-bound forms were also determined for G. kaustophilus and A. aeolicus proteins. In general, overall structures of GAR-syns are similar to each other. However, the orientations of the B domains are varied among GAR-syns and the MD simulation suggested the mobility of the B domain. Furthermore, it was demonstrated that the B loop in the B domain fixes the position of the ?- and ?- phosphate groups of the bound ATP. The structures of GAR-syns and the bound ligands were compared with each other in detail, and structures of GAR-syns with full ligands, as well as the possible reaction mechanism, were proposed.
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Structural characteristics of green tea catechins for formation of protein carbonyl in human serum albumin.
Bioorg. Med. Chem.
PUBLISHED: 05-13-2010
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Catechins are polyphenolic antioxidants found in green tea leaves. Recent studies have reported that various polyphenolic compounds, including catechins, cause protein carbonyl formation in proteins via their pro-oxidant actions. In this study, we evaluate the formation of protein carbonyl in human serum albumin (HSA) by tea catechins and investigate the relationship between catechin chemical structure and its pro-oxidant property. To assess the formation of protein carbonyl in HSA, HSA was incubated with four individual catechins under physiological conditions to generate biotin-LC-hydrazide labeled protein carbonyls. Comparison of catechins using Western blotting revealed that the formation of protein carbonyl in HSA was higher for pyrogallol-type catechins than the corresponding catechol-type catechins. In addition, the formation of protein carbonyl was also found to be higher for the catechins having a galloyl group than the corresponding catechins lacking a galloyl group. The importance of the pyrogallol structural motif in the B-ring and the galloyl group was confirmed using methylated catechins and phenolic acids. These results indicate that the most important structural element contributing to the formation of protein carbonyl in HSA by tea catechins is the pyrogallol structural motif in the B-ring, followed by the galloyl group. The oxidation stability and binding affinity of tea catechins with proteins are responsible for the formation of protein carbonyl, and consequently the difference in these properties of each catechin may contribute to the magnitude of their biological activities.
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Polycomb group molecule PHC3 regulates polycomb complex composition and prognosis of osteosarcoma.
Cancer Sci.
PUBLISHED: 04-07-2010
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Polyhomeotic homolog 3 (PHC 3) is a member of the human polycomb complex and has been regarded as a candidate tumor suppressor of osteosarcoma. In the present paper, we performed a mutation survey and PHC3 expression analysis by quantitative real-time PCR using 10 osteosarcoma cell lines and 42 primary osteosarcoma samples. Relative PHC3 expression values of clinical samples were analyzed with clinical outcomes, and it was suggested that lower PHC3-expressing patients had significantly worse overall survival. Relative PHC3 values of clinical samples were less than those of normal bone tissues, whereas they were greater than those of cell lines. By denaturing high performance liquid chromatography analysis and direct sequencing, we found a PHC3 missense mutation in U2OS cells, which resulted in arginine56 to proline substitution. The same point mutation existed in four of 42 primary osteosarcoma samples. Regarding functional analysis, PHC3 expression significantly suppressed the colony formation of tumor cells. Intriguingly, polycomb repressive complex 1 members, Bmi1 and Ring1b proteins, were reduced in PHC3-expressing osteosarcoma cells. Deletion mutant PHC3 expression suggested that the carboxyl terminus of PHC3 has a role in suppression; the above-mentioned point mutation of PHC3 also lost inhibitory activities. Conversely, Bmi1 expression reduced PHC3 at the mRNA level and induced the proliferation of osteosarcoma cells. Taken together, we confirmed the role of PHC3 as a tumor suppressor in osteosarcoma cells and found that PHC3-dependent tumor suppression may be caused by modification of the composition of polycomb repressive complex 1 in cancer cells.
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Proteomic identification of serum proteins associated with stress-induced gastric ulcers in fasted rats.
Biosci. Biotechnol. Biochem.
PUBLISHED: 04-07-2010
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Several physical and psychological stresses frequently become triggers for gastrointestinal disorders such as ulcer. In this study, we tried to identify serum proteins as potential biomarkers for the evaluation of stress-induced gastric ulcer. By proteomic analysis using rats with gastric ulcer induced by water immersion and restraint (WIR) stress as an animal model, we found quantitative changes in several serum proteins, including creatine kinase muscle M chain (CK-M) and apolipoprotein A-IV (ApoA4) in the stressed rats. On western blotting and enzyme-linked immunosorbent assay (ELISA), we confirmed that serum CK-M was remarkably increased by WIR stress. However, ApoA4 appeared to be decreased by fasting, but not WIR stress, which is usually applied prior to WIR stress. The findings suggest that these two serum proteins might be useful as biomarkers, CK-M for stress-induced gastric ulcer and ApoA4 for starvation.
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Pro-oxidant action of pyrroloquinoline quinone: characterization of protein oxidative modifications.
Biosci. Biotechnol. Biochem.
PUBLISHED: 03-07-2010
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Pyrroloquinoline quinone (PQQ), a putative essential nutrient, is a redox modulator in cell and animal models. Here we characterized PQQ-induced protein oxidative modifications in a model peptide and protein, and we propose that the mechanism of protein modification by PQQ is redox cycling-mediated oxidation. PQQ may contribute to the regulation of intracellular protein functions through its prooxidant action.
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Multicenter phase II trial assessing effectiveness of imatinib mesylate on relapsed or refractory KIT-positive or PDGFR-positive sarcoma.
J Orthop Sci
PUBLISHED: 01-31-2010
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Imatinib myselate is a molecularly targeted drug that inhibits Abl tyrosine kinase, as well as type III tyrosine kinase receptors such as platelet-derived growth factor receptor (PDGFR), KIT, colony-stimulating factor 1 receptor (CSF-1R), and discoidin domain receptor (DDR). Ph1 chromosome-positive chronic myeloid leukemias (CMLs), KIT-positive gastrointestinal stromal tumors (GISTs), and PDGFR-positive dermatofibrosarcoma protuberans (DFSP) have been reported to be responsive to imatinib treatment. We conducted a multicenter Phase II trial of imatinib in patients with relapsed or refractory KIT-positive (excluding GISTs) or PDGFR-positive sarcomas.
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A new method for the detection and characterization of alpha-lipoic acid mixed disulphides.
Free Radic. Res.
PUBLISHED: 01-30-2010
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Alpha-lipoic acid (LA) acts as a direct regulator of intracellular redox status through the formation of mixed disulphides. However, as this is reversible, the evidence for the mixed disulphides has not been obtained. This study established a method for the detection and characterization of mixed disulphides by mass spectrometry (MS) and was the first to provide direct evidence for their formation. When cysteine methyl ester was incubated with LA in the presence of iodeacetamide (IAA), a mixed disulphide with mono carbamidomethylation was observed. MS/MS analysis indicated that the LA forms a mixed disulphide with the cysteinyl sulphydryls, while the other sulphydryl group is the carbamidomethylated. The same results were obtained from the incubation of sulfphydryl peptides such as glutathione with LA in the presence of IAA. These results may provide further biological evidence that LA is a potential modifier of intracellular sulphydryls through mixed disulfide formation.
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Psychosocial outcomes in long-term survivors of high-grade osteosarcoma: a Japanese single-center experience.
Anticancer Res.
PUBLISHED: 10-23-2009
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The psychosocial outcomes in long-term survivors of osteosarcoma were investigated.
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Catechol type polyphenol is a potential modifier of protein sulfhydryls: development and application of a new probe for understanding the dietary polyphenol actions.
Chem. Res. Toxicol.
PUBLISHED: 09-12-2009
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The oxidation of dietary polyphenols with a catechol structure leads to the formation of an o-quinone structure, which rapidly reacts with sulfhydryls such as glutathione and protein cysteine residues. This modification may be important for understanding the redox regulation of cell functions by polyphenols. In this study, to investigate the catechol modification of protein sulfhydryls, we used 3,4-dihydroxyphenyl acetic acid (DPA) as a model catechol compound and developed a new probe to directly detect protein modification by catechol type polyphenols using a biotinylated DPA (Bio-DPA). The oxidation-dependent electrophilic reactivity of DPA with peptide sulfhydryls was confirmed by both mass spectrometry and nuclear magnetic resonance spectroscopy. When RL34 cells were treated with Bio-DPA, the significant incorporation of Bio-DPA into a 40 kDa protein was observed by Western blot analysis. The band was identified by mass spectrometry as the cytoskeletal protein, beta-actin. This identification was confirmed by the pull-down assay with anti-beta-actin antibody. To examine the reactivity of the catechol type polyphenols, such as flavonoids, to endogenous beta-actin, RL34 cells were coexposed to Bio-DPA and the flavonoids quercetin, (-)-epicatechin, and (-)-epicatechin gallate. Upon exposure of the cells to Bio-DPA in the presence of the flavonoids, we observed a significant decrease in the DPA-modified beta-actin. These results indicate that beta-actin is one of the major targets of protein modification by catechol type polyphenols and that Bio-DPA is an useful probe for understanding the redox regulation by dietary polyphenols. Furthermore, Keap1, a scaffold protein to the actin cytoskeleton controlling cytoprotective enzyme genes, was also identified as another plausible target of the catechol type polyphenols by oxidative modification of the intracellular sulfhydryls. These results provide an alternative approach to understand that catechol type polyphenol is a potential modifier of redox-dependent cellular events through sulfhydryl modification.
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Lansoprazole, a proton pump inhibitor, mediates anti-inflammatory effect in gastric mucosal cells through the induction of heme oxygenase-1 via activation of NF-E2-related factor 2 and oxidation of kelch-like ECH-associating protein 1.
J. Pharmacol. Exp. Ther.
PUBLISHED: 07-23-2009
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Induction of heme oxygenase-1 (HO-1) expression has been associated with cytoprotective and anti-inflammatory actions of lansoprazole, a proton pump inhibitor, but the underlying molecular mechanisms remain largely unresolved. In this study, we investigate the role of transcriptional NF-E2-related factor 2 (Nrf2), its phosphorylation/activation, and oxidation of Kelch-like ECH-associating protein 1 (Keap1) in lansoprazole-induced HO-1 up-regulation using cultured gastric epithelial cells (rat gastric mucosal cell line, RGM-1). HO-1 expression of RGM-1 cells was markedly enhanced in a time- and dose-dependent manner by the treatment with lansoprazole, and this up-regulation of HO-1 contributed to the inhibition of chemokine production from stimulated RGM-1 cells. Transfection of Nrf2-siRNA suppressed the lansoprazole-induced HO-1. An electrophoretic mobility shift assay showed increases in the nuclear translocation and stress-response elements (StRE) binding activity of Nrf2 proteins in RGM-1 cells treated with lansoprazole. Furthermore, in RGM-1 cells transfected with HO-1 enhancer luciferase reporter plasmid containing mutant StRE, lansoprazole-induced HO-1 reporter gene activity was diminished. Lansoprazole promoted the phosphorylation of extracellular signal-regulated kinase (ERK), and lansoprazole-induced HO-1 up-regulation was suppressed by U0126, an ERK-specific inhibitor. Phosphorylated Nrf2 protein was detected in the phosphoprotein fraction purified by a Pro-Q Diamond Phosphoprotein Enrichment kit. Finally, an oxidative form of the Keap1 protein was detected in lansoprazole-treated RGM-1 cells by analyzing S-oxidized proteins using biotinylated cysteine as a molecular probe. These results indicate that lansoprazole up-regulates HO-1 expression in rat gastric epithelial cells, and the up-regulated HO-1 contributes to the anti-inflammatory effects of the drug. Phosphorylation of ERK and Nrf2, activation and nuclear translocation of Nrf2, and oxidation of Keap1 are all involved in the lansoprazole-induced HO-1 up-regulation.
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Autopsy report on pseudo-Bartter syndrome with renal calcification induced by diuretics and diet pills.
BMJ Case Rep
PUBLISHED: 05-25-2009
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A woman in her mid-forties had repeated vomiting and diarrhoea accompanied by muscle weakness soon after she started taking seven different diet pills imported from Thailand. After she had taken the pills for 8 days, respiratory depression progressed rapidly to arrest. Blood tests at the Emergency Department showed severe hypokalaemia with metabolic alkalosis. We diagnosed that she had developed pseudo-Bartter syndrome from the findings based on ionic abnormalities and high renin and aldosterone levels, and hyperplasia of the juxtaglomerular apparatus. A postmortem blood analysis indicated subtherapeutic levels of furosemide. We concluded that the patient died from pseudo-Bartter syndrome, which was triggered by chronic self-administration of furosemide and aggravated by the diet pills. This is the first pseudo-Bartter syndrome autopsy report to show histological localisation of calcification in the kidneys.
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Albumin stabilizes (-)-epigallocatechin gallate in human serum: binding capacity and antioxidant property.
Mol Nutr Food Res
PUBLISHED: 05-14-2009
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(-)-Epigallocatechin gallate (EGCg) is the major component of green tea and is known to show strong biological activity, although it can be easily oxidized under physiological conditions. In this study, we indicate that EGCg is stable in human serum and that human serum albumin (HSA) stabilizes EGCg under aerobic condition. Although EGCg is usually decomposed within 1 h in aqueous solution at neutral pH, EGCg in serum and phosphate buffer (pH 7.4) containing HSA was stable over 1 h, even at neutral and slightly alkaline pH. Under these conditions, EGCg binds to HSA non-covalently. The sulfhydryl group acts as an antioxidant for EGCg oxidation. Incubation of EGCg with HSA is accompanied by the oxidation of a free sulfhydryl group in HSA. These results suggest that the antioxidant property and the binding capacity of HSA contribute to the stabilization of EGCg in human serum.
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Metastasis of malignant struma ovarii to the lumbar spine.
J Clin Neurosci
PUBLISHED: 04-05-2009
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A 32-year-old woman with a solitary metastasis to the lumbar spine from a struma ovarii was treated surgically with tumour extirpation and anterior spinal reconstruction. Metastasis may occur when a patient has had prior surgery to remove this rare tumour.
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Recently intensified chemotherapy for high-grade osteosarcoma may affect fertility in long-term male survivors.
Anticancer Res.
PUBLISHED: 04-01-2009
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To investigate the marital status and fertility in long-term survivors of high-grade osteosarcoma.
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Multiinstitutional phase II study of neoadjuvant chemotherapy for osteosarcoma (NECO study) in Japan: NECO-93J and NECO-95J.
J Orthop Sci
PUBLISHED: 03-13-2009
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Osteosarcoma is the most frequent primary malignant bone tumor. In Europe and the United States, its prognosis has been greatly improved by the use of multimodal treatment, including preoperative and postoperative chemotherapy as well as surgery. In Japan, however, only a few clinical studies on osteosarcoma have been carried out.
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[Extranodal marginal zone lymphoma of the dura: a case report].
No Shinkei Geka
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The authors present the case of a 65-year-old woman who initially was diagnosed as having intracranial dural B-cell malignant lymphoma. She survived more than 9 years after surgery and radiation. We re-examined the specimens pathologically. Histological findings confirmed an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) that showed numerous IgG4-positive plasma cells. MALT lymphomas are already recognized as a distinct clinico-pathological entity. A primary dural MALT lymphoma is very rare and has a favorable clinical outcome, and patients are expected to have an excellent long-term survival with local therapy alone.
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Sudden cardiac arrest caused by tuberculous pericarditis with hemorrhagic pericardial effusion.
Intern. Med.
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As tuberculosis still exists in Japan, tuberculous pericarditis is a major health issue. Tuberculous pericarditis is difficult to diagnose and leads to poor outcomes when left untreated. We herein report the case of a patient who was admitted to the hospital after undergoing resuscitation for cardiopulmonary arrest. Mycobacterium tuberculosis was detected in his hemorrhagic pericardial fluid and tuberculous pericarditis was diagnosed. The administration of antituberculous medication resulted in marked improvements. A diagnosis of tuberculous pericarditis, in addition to other causes such as malignant tumors, should therefore be considered in the differential diagnosis for cases presenting with hemorrhagic pericardial effusion, even in those involving sudden cardiac arrest.
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Pyrroloquinoline quinone, a novel protein tyrosine phosphatase 1B inhibitor, activates insulin signaling in C2C12 myotubes and improves impaired glucose tolerance in diabetic KK-A(y) mice.
Biochem. Biophys. Res. Commun.
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Insulin resistance is a pathological hallmark of type 2 diabetes mellitus and is characterized by defects in insulin signaling. Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling by tyrosine dephosphorylation of insulin receptor, and increased activity and expression of PTP1B is implicated in the pathogenesis of insulin resistance. Therefore, inhibition of PTP1B is anticipated to improve insulin resistance in type 2 diabetic subjects. Pyrroloquinoline quinone (PQQ), a redox cofactor for bacterial dehydrogenases, inhibits PTP1B to oxidatively modify the catalytic cysteine through its redox cycling activity. Here, we report that PQQ induces the ligand-independent activation of insulin signaling by inhibiting cellular PTP1B and enhances glucose uptake through the translocation of glucose transporter 4 in mouse C2C12 myotubes. Furthermore, we demonstrated that oral administration of PQQ improved impaired glucose tolerance in type 2 diabetic KK-A(y) mice. Our results strongly suggest that PQQ can be useful in anti-diabetic treatment for type 2 diabetic subjects.
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Efficacy of carbon-ion radiotherapy and high-dose chemotherapy for patients with unresectable Ewings sarcoma family of tumors.
Int. J. Clin. Oncol.
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Treatment for unresectable Ewings sarcoma family of tumors (ESFT) is a formidable challenge because of its high tendency for local and distant failure. Recently, carbon-ion radiotherapy (CIRT) has been applied to unresectable bone and soft tissue sarcoma. Additionally, high-dose chemotherapy (HDC) with stem cell rescue has been used to improve the survival of patients with relapsed ESFT. Here we report our experience with CIRT and HDC in the treatment of unresectable ESFT.
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Mild elevation of urinary biomarkers in prerenal acute kidney injury.
Kidney Int.
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Prerenal acute kidney injury (AKI) is thought to be a reversible loss of renal function without structural damage. Although prerenal and intrinsic AKI frequently coexist in clinical situations, serum creatinine and urine output provide no information to support their differentiation. Recently developed biomarkers reflect tubular epithelial injury; therefore, we evaluated urinary biomarker levels in an adult mixed intensive care unit (ICU) cohort of patients who had been clinically evaluated as having prerenal AKI. Urinary L-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), N-acetyl-?-D-glucosaminidase (NAG), and albumin in patients with prerenal AKI showed modest but significantly higher concentrations than in patients with non-AKI. We also conducted a proof-of-concept experiment to measure urinary biomarker excretion in prerenal AKI caused by volume depletion. Compared with cisplatinum and ischemia-reperfusion models in mice, volume depletion in mice caused a modest secretion of L-FABP and NGAL into urine with more sensitive response of L-FABP than that of NGAL. Although no histological evidence of structural damage was identified by light microscopy, partial kidney hypoxia was found by pimonidazole incorporation in the volume depletion model. Thus, our study suggests that new AKI biomarkers can detect mild renal tubular damage in prerenal acute kidney injury.
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Pyrroloquinoline quinone stimulates epithelial cell proliferation by activating epidermal growth factor receptor through redox cycling.
Free Radic. Biol. Med.
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Pyrroloquinoline quinone (PQQ), a redox cofactor for bacterial dehydrogenases, has been implicated to be an important nutrient in mammals functioning as a potent growth factor. However, the underlying molecular mechanisms have not been elucidated. The present study revealed that PQQ induces the activation (tyrosine autophosphorylation) of epidermal growth factor receptor (EGFR) and its downstream signaling in a ligand-independent manner, leading to increased cellular proliferation in an epithelial cell line A431. PQQ inhibited protein tyrosine phosphatase 1B (PTP1B), which negatively regulates the EGFR signaling by tyrosine dephosphorylation, to oxidatively modify the catalytic cysteine through its redox cycling activity to generate H(2)O(2). PQQ-inducible intracellular ROS production and EGFR activation were significantly suppressed by the pre-treatment with antioxidants. The intracellular redox state regulates the EGFR signaling through the redox-sensitive catalytic cysteine of PTP1B and modulates cell proliferation. Our data suggest that PQQ may stimulate epithelial cell proliferation by activating EGFR by oxidation and subsequent inactivation of PTP1B via its redox cycling. Our results provide novel insight into the mechanisms by which PQQ may function as a growth factor to contribute to mammalian growth.
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SYT-SSX breakpoint peptide vaccines in patients with synovial sarcoma: a study from the Japanese Musculoskeletal Oncology Group.
Cancer Sci.
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In the present study, we evaluated the safety and effectiveness of SYT-SSX-derived peptide vaccines in patients with advanced synovial sarcoma. A 9-mer peptide spanning the SYT-SSX fusion region (B peptide) and its HLA-A*2402 anchor substitute (K9I) were synthesized. In Protocols A1 and A2, vaccines with peptide alone were administered subcutaneously six times at 14-day intervals. The B peptide was used in Protocol A1, whereas the K9I peptide was used in Protocol A2. In Protocols B1 and B2, the peptide was mixed with incomplete Freunds adjuvant and then administered subcutaneously six times at 14-day intervals. In addition, interferon-? was injected subcutaneously on the same day and again 3 days after the vaccination. The B peptide and K9I peptide were used in Protocols B1 and B2, respectively. In total, 21 patients (12 men, nine women; mean age 43.6 years) were enrolled in the present study. Each patient had multiple metastatic lesions of the lung. Thirteen patients completed the six-injection vaccination schedule. One patient developed intracerebral hemorrhage after the second vaccination. Delayed-type hypersensitivity skin tests were negative in all patients. Nine patients showed a greater than twofold increase in the frequency of CTLs in tetramer analysis. Recognized disease progression occurred in all but one of the nine patients in Protocols A1 and A2. In contrast, half the 12 patients had stable disease during the vaccination period in Protocols B1 and B2. Of note, one patient showed transient shrinkage of a metastatic lesion. The response of the patients to the B protocols is encouraging and warrants further investigation.
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Redox cycling of 1,2-naphthoquinone by thioredoxin1 through Cys32 and Cys35 causes inhibition of its catalytic activity and activation of ASK1/p38 signaling.
Chem. Res. Toxicol.
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1,2-Naphthoquinone (1,2-NQ) is an atmospheric chemical capable of (1) redox cycling with electron donors and (2) covalent modification of nucleophilic groups on proteins. In the present study, we investigated its interaction with the redox protein, thioredoxin1 (Trx1), which led to oxidative stress-dependent cell damage. In experiments with purified wild-type Trx1 and its double mutant (32S/35S Trx1), we found that incubation of Trx1 with 1,2-NQ resulted in a redox cycling reaction, generating superoxide and hydrogen peroxide involving Cys32 and Cys35 and an arylation reaction resulting in covalent modification of Lys85 together with a loss of Trx activity. A significant fraction of the lost Trx1 activity following interaction with 1,2-NQ was restored by dithiothreitol. Exposure of RAW264.7 cells to 1,2-NQ generated reactive oxygen species (ROS) and caused a decrease in Trx activity. Trx is a negative regulator of apoptosis signal-regulating kinase 1 (ASK1), and under the conditions of the experiment, 1,2-NQ activated ASK1 and p38, leading to PARP cleavage and apoptotic cell death that were blocked by pretreatment with polyethylene glycol-catalase. These results suggest that Trx1 readily undergoes oxidative modification by 1,2-NQ through the proximal thiols Cys32 and Cys35. It seems likely that ROS production concomitant with decline in cellular Trx activity plays a role in the activation of ASK1/p38 signaling to promote apoptotic cell death cause by 1,2-NQ exposure.
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