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Find video protocols related to scientific articles indexed in Pubmed.
Breast reconstruction using free posterior medial thigh perforator flaps: intraoperative anatomical study and clinical results.
Plast. Reconstr. Surg.
PUBLISHED: 10-28-2014
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The free posterior medial thigh perforator flap is a fasciocutaneous flap on the posterior and medial thigh, based on perforators from the deep femoral vessels. In this study, the authors evaluated the anatomical basis of posterior and medial thigh perforators from the deep femoral vessels.
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[Current status of adjuvant chemotherapy in patients with p-Stage II and p-Stage III gastric cancer].
Gan To Kagaku Ryoho
PUBLISHED: 08-19-2014
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The results of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer(ACTS-GC)demonstrated that postoperative chemotherapy using S-1 is a standard treatment in Japan for patients with p-Stage II and p-Stage III gastric cancer. We retrospectively reviewed the effect of adjuvant chemotherapy received by 47 patients with p-Stage II and p-Stage III gastric cancer between January 2007 and June 2012. Our hospital is a local university hospital with a high intensive care unit. S-1 monotherapy was administered to 32 patients(adjuvant S-1 group, 68.1%); 22 patients(68.8%)among them completed one year of therapy without any modification to the administration schedule. A total of 8 patients(25.0%)experienced grade 3 adverse events, and 9 patients required a dose reduction, a modification of the administration schedule, or termination of the therapy. S-1 was not administrated to 15 patients(no adjuvant S-1 group, 31.9%); among these patients, 12(80.0%) were not administered S-1 because of their advanced age and comorbidity. The 3-year overall survival rate was 89.3% in the adjuvant S-1 group and 77.1% in the no adjuvant S-1 group. The completion rate of S-1 and survival rate were high for patients in the adjuvant S-1 group, which was similar to the results of the ACTS-GC. However, 25 of 47 patients(53.2%) with p-Stage II and p-Stage III gastric cancer did not improve after sufficient adjuvant therapy; therefore, it is important to develop new treatment strategies for these patients.
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Colorectal laterally spreading tumors show characteristic expression of cell polarity factors, including atypical protein kinase C ?/?, E-cadherin, ?-catenin and basement membrane component.
Oncol Lett
PUBLISHED: 06-20-2014
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Colorectal flat-type tumors include laterally spreading tumors (LSTs) and flat depressed-type tumors. The former of which shows a predominant lateral spreading growth rather than an invasive growth. The present study examined the morphological characteristics of LSTs, in comparison with polypoid- or flat depressed-type tumors, along with the expression of atypical protein kinase C (aPKC) ?/?, a pivotal cell polarity regulator, and the hallmarks of cell polarity, as well as with type IV collagen, ?-catenin and E-cadherin. In total, 37 flat-type (24 LSTs and 13 flat depressed-type tumors) and 20 polypoid-type colorectal tumors were examined. The LSTs were classified as 15 LST adenoma (LST-A) and nine LST cancer in adenoma (LST-CA). An immunohistochemical examination was performed on aPKC ?/?, type IV collagen, ?-catenin and E-cadherin. The LST-A and -CA showed a superficial replacing growth pattern, with expression of ?-catenin and E-cadherin in the basolateral membrane and type IV collagen along the basement membrane. In addition, 86.6% of LST-A and 55.6% of LST-CA showed aPKC ?/? expression of 1+ (weak to normal intensity staining in the cytoplasm compared with the normal epithelium). Furthermore, ~45% of the polypoid-type adenomas showed 2+ (moderate intensity staining in the cytoplasm and/or nucleus) and 66.7% of the polypoid-type cancer in adenoma were 3+ (strong intensity staining in the cytoplasm and nucleus). A statistically significant positive correlation was observed between the expression of aPKC ?/? and ?-catenin (r=0.842; P<0.001), or type IV collagen (r=0.823; P<0.001). The LSTs showed a unique growth pattern, different from the expanding growth pattern presented by a polypoid tumor and invasive cancer. The growth characteristics of LST appear to be caused by adequate coexpression of ?-catenin, type IV collagen and aPKC ?/?.
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Protein tagging reveals new insights into signaling in flagella.
J. Cell Biol.
PUBLISHED: 03-05-2014
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In this issue, Oda et al. (2014. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201312014) use mutant analysis, protein tagging, and cryoelectron tomography to determine the detailed location of components in flagellar radial spokes-a complex of proteins that connect the peripheral microtubule doublets to the central pair. Remarkably, this approach revealed an interaction between radial spokes and the central pair based on geometry rather than a specific signaling mechanism, highlighting the importance of studying a system in three dimensions.
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Prognostic factors and causes of death in patients cured of esophageal cancer.
Ann. Surg. Oncol.
PUBLISHED: 02-08-2014
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The number of patients cured of esophageal cancer after esophagectomy is gradually increasing owing to advances in surgical techniques, perioperative management, and adjuvant therapies. This study assessed the clinical course and sought to identify the prognostic factors of these patients.
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[Urgent gastrectomy in a patient who developed perforated gastric cancer during preoperative chemotherapy with S-1 plus cisplatin].
Gan To Kagaku Ryoho
PUBLISHED: 01-16-2014
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A 66 -year-old man presenting with a chief complaint of upper abdominal pain was diagnosed as having an advanced adenocarcinoma, type 2, of the lower third of the stomach after endoscopy was performed. An abdominal computed tomography( CT)scan revealed 4 lymph node metastases at the infrapyloric nodes(station No. 6)and the nodes around the proximal splenic artery(station No. 11p)and the abdominal aorta(station No. 16a2). The clinical stage was determined to be T3(SS)N2M1(LYM), Stage IV. Gastrectomy with D2 plus para-aortic node dissection was scheduled after 2 courses of S-1 plus cisplatin(CDDP)with curative intent. On day 14 after starting S-1 therapy, the patient complained of severe abdominal pain and peritoneal irritation of acute onset. Because the abdominal CT scan showed a large amount of intra-abdominal free air, we performed an urgent laparotomy with a tentative diagnosis of perforation of the gastric cancer. On laparotomy, we found a perforated malignant ulcer, 5 cm in maximum diameter, in the lesser curvature of the stomach; therefore, distal gastrectomy with D1 plus lymphadenectomy and reconstruction using the Roux-en-Y method were performed. At the end of the surgery, a macroscopic residual tumor remained in the para-aortic lymph node. The postoperative course was uneventful, and the patient was discharged on day 23 after surgery. In the present case, despite the performance of urgent gastrectomy while the patient was receiving strong chemotherapy, perioperative management was successful, with no serious postoperative complication or adverse events as a result of the chemotherapy.
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Is early enteral nutrition initiated within 24 hours better for the postoperative course in esophageal cancer surgery?
J Clin Med Res
PUBLISHED: 01-09-2014
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Early enteral nutrition within 24 h after surgery has become a recommended procedure. In the present study, we retrospectively examined whether initiating EN within 24 h after esophagectomy improves the postoperative course.
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Structure of dimeric axonemal dynein in cilia suggests an alternative mechanism of force generation.
Cytoskeleton (Hoboken)
PUBLISHED: 01-08-2014
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The mechanism by which the two different heads of the ciliary outer dynein arm produce force to translocate the microtubule during beating is still unknown. In this report we use cryo-electron tomography and image processing to analyze the conformational changes and the relative abundance of each conformation of the two dynein heads from mouse respiratory cilia. In the absence of nucleotides the majority of dynein dimers are in the apo form and both heads are tightly packed, whereas they are dissociated and move independently in the presence of nucleotides. The head of the external outer arm dynein heavy chain has a diagonal shift toward both the neighboring B-tubule and the proximal end of the axoneme, while the head of the internal heavy chain shifts only longitudinally toward the proximal end. In the presence of nucleotides a significant number of the dynein dimers have two heads overlapped in the proximal shifting form or overlapped in the apo form. During ciliary bending axonemal dynein translocates microtubules by moving with short steps and two heads stay at the same position longer than cytoplasmic dynein. This demonstrates that the step of the outer arm dynein dimer is not dominated by the hand-over-hand motion, but also indicates the difference between axonemal dynein and cytoplasmic dynein.
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Cholesterol-diethylenetriaminepentaacetate complexed with thulium ions integrated into bicelles to increase their magnetic alignability.
J Phys Chem B
PUBLISHED: 11-18-2013
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Lanthanides have been used for several decades to increase the magnetic alignability of bicelles. DMPE-DTPA (1,2-dimyristoyl-sn-glycero-3-phospho-ethanolamine-diethylenetriaminepentaacetate) is commonly applied to anchor the lanthanides into the bicelles. However, because DMPE-DTPA has the tendency to accumulate at the highly curved edge region of the bicelles and if located there does not contribute to the magnetic orientation energy, we have tested cholesterol-DTPA complexed with thulium ions (Tm(3+)) as an alternative chelator to increase the magnetic alignability. Differential scanning calorimetric (DSC) measurements indicate the successful integration of cholesterol-DTPA into a DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) bilayer. Cryo transmission electron microscopy and small-angle neutron scattering (SANS) measurements show that the disklike structure, that is, bicelles, is maintained if cholesterol-DTPA·Tm(3+) is integrated into a mixture of DMPC, cholesterol, and DMPE-DTPA·Tm(3+). The size of the bicelles is increased compared to the size of the bicelles obtained from mixtures without cholesterol-DTPA·Tm(3+). Magnetic-field-induced birefringence and SANS measurements in a magnetic field show that with addition of cholesterol-DTPA·Tm(3+) the magnetic alignability of these bicelles is significantly increased compared to bicelles composed of DMPC, cholesterol, and DMPE-DTPA·Tm(3+) only.
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Early-onset brain metastases in a breast cancer patient after pathological complete response to neoadjuvant chemotherapy.
Anticancer Res.
PUBLISHED: 11-14-2013
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Breast cancer patients who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) usually have a favourable prognosis. We report on a patient with early metastases to the brain after achieving pCR. The primary tumour was 7.0 cm in diameter with axillary lymph node metastases, hormone receptor-negative, human epidermal growth factor receptor-2-positive (3+), and histological grade 2 with 60% of cells positive for Ki-67. The patient underwent NAC followed by surgery, and achieved pCR. Five months after surgery, during adjuvant treatment with trastuzumab, she developed headache and dizziness. Brain imaging revealed multiple metastatic brain tumours. She received whole-brain radiotherapy followed by lapatinib and capecitabine therapy. At 7 months after surgery, she remains alive with a persistent mild headache. Physicians should be aware of the possibility of early brain metastases, and consider new treatment strategies to prevent brain metastases in high-risk patients who achieve pCR.
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Is early enteral nutrition better for postoperative course in esophageal cancer patients?
Nutrients
PUBLISHED: 08-02-2013
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We retrospectively examined esophageal cancer patients who received enteral nutrition (EN) to clarify the validity of early EN compared with delayed EN. A total of 103 patients who underwent transthoracic esophagectomy with three-field lymphadenectomy for esophageal cancer were entered. Patients were divided into two groups; Group E received EN within postoperative day 3, and Group L received EN after postoperative day 3. The clinical factors such as days for first fecal passage, the dose of postoperative albumin infusion, differences of serum albumin value between pre- and postoperation, duration of systematic inflammatory response syndrome (SIRS), incidence of postoperative infectious complication, and use of total parenteral nutrition (TPN) were compared between the groups. The statistical analyses were performed using Mann-Whitney U test and Chi square test. The statistical significance was defined as p < 0.05. Group E showed fewer days for the first fecal passage (p < 0.01), lesser dose of postoperative albumin infusion (p < 0.01), less use of TPN (p < 0.01), and shorter duration of SIRS (p < 0.01). However, there was no significant difference in postoperative complications between the two groups. Early EN started within 3 days after esophagectomy. It is safe and valid for reduction of albumin infusion and TPN, for promoting early recovery of intestinal movement, and for early recovery from systemic inflammation.
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Nilotinib for treatment of gastrointestinal stromal tumors: out of the equation?
Expert Opin Pharmacother
PUBLISHED: 07-09-2013
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Imatinib, a selective tyrosine kinase inhibitor (TKI), is currently the standard treatment for unresectable and metastatic gastrointestinal stromal tumors (GISTs). However, the disease control time by imatinib is limited due to intolerance or resistance. Nilotinib , a second-generation TKI, is expected to show enhanced clinical efficacy against advanced GIST.
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Treatment for Perforated Gastric Ulcer: a Multi-institutional Retrospective Review.
J. Gastrointest. Surg.
PUBLISHED: 07-08-2013
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The optimal treatment for patients with perforated gastric ulcer (PGU) remains controversial. This study therefore investigated the treatment status for this disease in clinical practice.
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Two-step laparoscopic surgery for a patient with synchronous double cancer of the colon and stomach accompanied by severe chronic obstructive pulmonary disease.
Case Rep Surg
PUBLISHED: 05-29-2013
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Laparoscopic treatment strategies for synchronous intra-abdominal malignancies have not yet been standardized. We report a successful case of two-step laparoscopic surgery for synchronous double cancer of the colon and stomach accompanied by severe chronic obstructive pulmonary disease (COPD). A 66-year-old man with COPD was diagnosed as having advanced colon cancer and early gastric cancer. On admission, he could not go upstairs (Grade III according to the Hugh-Jones classification) and his forced expiratory volume in 1 second was 600?mL (35.9%). The patient initially underwent laparoscopy-assisted sigmoidectomy with D3 lymphadenectomy, followed by laparoscopy-assisted distal gastrectomy with D1 lymphadenectomy 68 days later. The patients each postoperative course was uneventful with no pulmonary complications, and the patient was discharged 9 and 11 days after the first and second operations, respectively. The present case demonstrates that two-step laparoscopic surgery may be a safe and feasible surgical procedure for high-risk patients with synchronous intra-abdominal malignancies.
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Cervical lymph node dissection for clinically submucosal carcinoma of the thoracic esophagus.
Ann. Surg. Oncol.
PUBLISHED: 05-28-2013
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The purposes of this study were to clarify the risk factors for supraclavicular lymph node (SCLN) metastasis and the survival benefit from cervical lymph node (LN) dissections in patients with clinically submucosal (cT1b) carcinoma of the thoracic esophagus.
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3D structural analysis of flagella/cilia by cryo-electron tomography.
Meth. Enzymol.
PUBLISHED: 03-19-2013
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Three dimensional arrangement of proteins inside the axoneme is essential information to elucidate the flagellar/ciliary bending mechanism. Cryo-electron tomography provides structural information in situ at ~30 Å resolution and thus is a suitable method for flagella/cilia research. The biggest challenge in cryo-electron tomography is the low signal-to-noise ratio. Therefore, subtomogram averaging, an in silico processing step to detect identical structural units based on 3D image analysis, aligns them three dimensionally and average is required to improve the signal-to-noise ratio. When structural units are not exactly identical, they must be classified. In this chapter, we describe our strategy to extract, align, classify, and average molecular structures from cryo-electron tomograms of flagella/cilia, utilizing longitudinal periodicity and pseudo-ninefold symmetry in the axoneme.
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Randomized controlled trial of toremifene 120 mg compared with exemestane 25 mg after prior treatment with a non-steroidal aromatase inhibitor in postmenopausal women with hormone receptor-positive metastatic breast cancer.
BMC Cancer
PUBLISHED: 01-26-2013
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BACKGROUND: After the failure of a non-steroidal aromatase inhibitor (nsAI) for postmenopausal patients with metastatic breast cancer (mBC), it is unclear which of various kinds of endocrine therapy is the most appropriate. A randomized controlled trial was performed to compare the efficacy and safety of daily toremifene 120 mg (TOR120), a selective estrogen receptor modulator, and exemestane 25 mg (EXE), a steroidal aromatase inhibitor. The primary end point was the clinical benefit rate (CBR). The secondary end points were objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicity. METHODS: Initially, a total of 91 women was registered in the study and randomly assigned to either TOR120 (n = 46) or EXE (n = 45) from October 2008 to November 2011. Three of the 46 patients in the TOR120 arm were not received treatment, 2 patients having withdrawn from the trial by their preference and one having been dropped due to administration of another SERM. RESULTS: When analyzed after a median observation period of 16.9 months, the intention-to-treat analysis showed that there were no statistical difference between TOR120 (N = 46) and EXE (n = 45) in terms of CBR (41.3% vs. 26.7%; P = 0.14), ORR (10.8% vs. 2.2%; P = 0.083), and OS (Hazard ratio, 0.60; P = 0.22). The PFS of TOR120 was longer than that of EXE, the difference being statistically significant (Hazard ratio, 0.61, P = 0.045). The results in treatment-received cohort (N = 88) were similar to those in ITT cohort. Both treatments were well-tolerated with no severe adverse events, although the treatment of 3 of 43 women administered TOR120 was stopped after a few days because of nausea, general fatigue, hot flush and night sweating. CONCLUSIONS: TOR120, as a subsequent endocrine therapy for mBC patients who failed non-steroidal AI treatment, could potentially be more beneficial than EXE.Trial registration number: UMIN000001841 URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000001797&language=J.
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Collapsin response mediator protein 2 is involved in regulating breast cancer progression.
Breast Cancer
PUBLISHED: 01-21-2013
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BACKGROUND: Altered expression of collapsin response mediator proteins (CRMPs) has been reported in several malignant tumors, including downregulation of CRMP1 in lung cancer and upregulation of CRMP2 in colorectal cancer. This study aimed to investigate the relationship between CRMP expression and clinicopathological characteristics in patients with breast cancer. METHODS: Twenty-two breast cancer and four normal breast tissues were used to assess CRMP mRNA expression. The average expression level of each CRMP (CRMP1-5) mRNA was analyzed in a subset of breast cancer specimens and compared with that in normal breast tissue by real-time quantitative reverse-transcription polymerase chain reaction. Furthermore, 173 breast cancer specimens and matching normal breast controls were used for immunohistochemistry based on the tissue microarray technique. Levels of CRMP2 and phosphorylated CRMP2 protein were assessed, and possible correlations between the clinicopathological characteristics were evaluated. RESULTS: The expression of CRMP2 mRNA was significantly decreased in breast cancer tissues, while that of the other CRMPs was similar between normal and breast cancer tissues. Immunohistochemistry revealed that CRMP2 protein expression was also decreased in breast cancer tissues (P < 0.001). Phosphorylated CRMP2 was observed in the nuclei of breast cancer cells but not in normal mammary cells (P < 0.001). Furthermore, nuclear phosphorylated CRMP2 expression was increased in proportion to the histological grade and triple-negative subtype. CONCLUSIONS: Reduced CRMP2 expression and elevated expression of nuclear phosphorylated CRMP2 may be associated with breast cancer progression.
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Pearl microstructure and expression of shell matrix protein genes MSI31 and MSI60 in the pearl sac epithelium of Pinctada fucata by in situ hybridization.
PLoS ONE
PUBLISHED: 01-14-2013
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Expression patterns of the shell matrix protein genes MSI31 and MSI60 in the pearl sac epithelium were examined by in situ hybridization 38 days after implantation, and related to pearl quality. A pearl sac that produced a nacreous pearl showed very weak expression of MSI31 and strong expression of MSI60. A pearl sac, which yielded a prismatic pearl, strongly expressed MSI31 and very weakly expressed MSI60. In a complex pearl, whose surface consisted of a mosaic of both nacreous and prismatic layers, the expression pattern of MSI31 and MSI60 similarly corresponded to the underlying surface structures of the pearl. A nacreous pearl whose pearl sac showed strong MSI31 expression had an entirely nacreous surface composed of a laminar structure with unusual tablet growth at the corresponding site. MSI31 and MSI60 are the major components of the shell matrix proteins of the nacreous and prismatic layers. Clearly, high expression of MSI31 does not always result in prismatic secretion. These observations cannot be explained solely on the basis of the expression patterns of MSI31 and MSI60. We propose that, in addition to the MSI genes that form the prismatic and nacreous layers, upstream from these genes there are regulatory master genes that determine whether a nacreous layer (aragonite) or a prismatic layer (calcite) is formed.
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High expression of ATP-binding cassette transporter ABCC11 in breast tumors is associated with aggressive subtypes and low disease-free survival.
Breast Cancer Res. Treat.
PUBLISHED: 01-04-2013
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ATP-binding cassette (ABC) transporters are membrane proteins that efflux various compounds from cells, including chemotherapeutic agents, and are known to affect multidrug resistance. Recent reports disagree on whether ABCC11 is a risk factor for breast tumorigenesis, but its expression in breast cancer is poorly investigated. We hypothesized that both frequency and expression levels of ABC transporters in breast tumors would vary by cancer subtype, and be associated with prognosis. Here, we constructed a tissue microarray breast tumor samples from 281 patients, and analyzed expressions of ABCB1, ABCC1, ABCC11, and ABCG2 immunohistochemically. Breast cancer subtypes were determined by immunohistochemistry of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). Protein expression was correlated to clinicopathological characteristics, clinical follow-up, and pathological complete response to neoadjuvant chemotherapy. The tissue microarray comprised 191 luminal A (68.0 %), 17 luminal B (6.0 %), 27 HER2 (9.6 %), and 46 triple-negative (16.4 %) samples. ABCC1 and ABCC11 expressions were associated with significantly shorter disease-free survival (P = 0.027 and P = 0.003, respectively). ABCC1, ABCC11, and ABCG2, but not ABCB1, were expressed significantly more, and more frequently, in aggressive subtypes. Patients with HER2+ and triple-negative tumor subtypes that expressed high levels of ABCC11 had significantly worse disease-free survival (P = 0.017 and P < 0.001, respectively). We have shown, for the first time, that ABCC1, ABCC11, and ABCG2 are highly expressed in aggressive breast cancer subtypes, and that tumor ABCC11 expression is associated with poor prognosis.
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Cryoelectron tomography of radial spokes in cilia and flagella.
J. Cell Biol.
PUBLISHED: 11-07-2011
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Radial spokes (RSs) are ubiquitous components in the 9 + 2 axoneme thought to be mechanochemical transducers involved in local control of dynein-driven microtubule sliding. They are composed of >23 polypeptides, whose interactions and placement must be deciphered to understand RS function. In this paper, we show the detailed three-dimensional (3D) structure of RS in situ in Chlamydomonas reinhardtii flagella and Tetrahymena thermophila cilia that we obtained using cryoelectron tomography (cryo-ET). We clarify similarities and differences between the three spoke species, RS1, RS2, and RS3, in T. thermophila and in C. reinhardtii and show that part of RS3 is conserved in C. reinhardtii, which only has two species of complete RSs. By analyzing C. reinhardtii mutants, we identified the specific location of subsets of RS proteins (RSPs). Our 3D reconstructions show a twofold symmetry, suggesting that fully assembled RSs are produced by dimerization. Based on our cryo-ET data, we propose models of subdomain organization within the RS as well as interactions between RSPs and with other axonemal components.
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[Treatment strategy for marginally resectable GIST].
Gan To Kagaku Ryoho
PUBLISHED: 08-11-2011
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Gastrointestinalstromaltumors (GIST)are occasionally found as large abdominal tumors at presentation. However, the best treatment approach for such large and marginally resectable GISTs remains unclear. The survival of patients with clinically malignant GISTs or GISTs with incomplete resection was as short as 1-2 years. Imatinib, a KIT kinase inhibitor, shows promise as a preoperative treatment for marginally resectable GIST, because it exhibits potent antitumor activity for unresectable and metastatic GISTs. Data obtained from imatinib therapy for advanced GISTs indicate that preoperative treatment with 400 mg of imatinib daily for 6-12 months is recommended, although no standard regimen has been established so far. Positron emission tomography is useful for the early assessment of the efficacy of preoperative imatinib treatment, a critical step for the management of patients with marginally resectable GIST. Two case studies have shown the safety and strong antitumor activity of preoperative imatinib treatment and concluded that treatment contributed to reducing surgical morbidity. However, a multicenter phase II trial conducted in the United States has shown that complete resection was not sufficiently achieved in patients who underwent preoperative imatinib treatment: complete resection rates were 77% for primary cases and 58% for metastatic cases, whereas the treatment was not associated with severe postoperative complications. The clinical guidelines for GIST in Japan regard preoperative imatinib treatment for marginally resectable GIST as an experimental treatment. More clinical evidence is required before making preoperative imatinib treatment the standard treatment for marginally resectable GIST.
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[Sunitinib as a second-line therapy for imatinib-resistant gastrointestinal stromal tumors].
Gan To Kagaku Ryoho
PUBLISHED: 06-17-2011
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Gastrointestinal stromal tumor(GIST)is one ofthe representative diseases for which molecularly targeted therapy is very effective. Imatinib mesylate, a tyrosine kinase inhibitor of KIT and platelet-derived growth factor receptor(PDGFR), has dramatically improved the prognosis ofpatients with advanced, recurrent, and/or metastatic GISTs. Although the rate of response to imatinib therapy is high, the emergence ofimatinib -resistant tumors and the second-line therapy following imatinib therapy have become new clinical problems. Sunitinib malate, a multi-targeted tyrosine kinase inhibitor that shows activity against KIT and other receptor tyrosine kinases, including PDGFR and vascular endothelial growth factor receptor, is the only treatment for imatinib-resistant GISTs that is covered by national health insurance in Japan as ofthis writing. Several clinical trials that evaluated sunitinib as potential second-line therapy in Western countries and Japan found a clinical benefit rate of2 4 to 39% and a median time to progression of7 months. However, it is necessary to adequately manage the adverse events of sunitinib therapy in order to receive the full benefits of the therapy, because various severe adverse events, particularly thrombocytopenia and hand-foot syndrome in Japanese GIST patients, frequently lead to poor tolerability. Further investigation is required to find an appropriate regimen for Japanese GIST patients.
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Gastrectomy as a secondary surgery for stage IV gastric cancer patients who underwent S-1-based chemotherapy: a multi-institute retrospective study.
Gastric Cancer
PUBLISHED: 05-19-2011
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Current advances in chemotherapy provide opportunities for stage IV gastric cancer patients with distant metastasis to undergo potentially curable resection. There are, however, few data on gastrectomy as a secondary surgery aimed at rendering such patients cancer-free.
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[An update on surgical treatment for gastrointestinal stromal tumor].
Gan To Kagaku Ryoho
PUBLISHED: 05-14-2011
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Complete surgical resection is the treatment of choice for primary gastrointestinal stromal tumor (GIST), even with current advances in molecular targeting therapy with imatinib and sunitinib. In recent years, function-preserving and minimally invasive surgeries have also been performed as treatment strategies for submucosal tumors, including GISTs that are clinically diagnosed as low-risk. It is crucial, however, not to compromise radicality when indicating these procedures. On the other hand, a multidisciplinary treatment, including surgical resection, is necessary even for the treatment of advanced or metastatic/ recurrent GISTs in which the treatment of choice is imatinib therapy. Furthermore, surgical treatment is expected to be effective for resectable liver metastases, secondary resistance to imatinib, or residual tumors responding to imatinib. In this regard, surgical resection as a multidisciplinary treatment is considered to have gained recognition as an important option. However, sufficient evidence is lacking, and thus, the results of ongoing clinical trials are highly anticipated. For the surgical treatment of GIST, it is important to select patients carefully based on objective data to obtain maximum therapeutic effects.
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Pedunculated gastric tube interposition in an esophageal cancer patient with prepyloric adenocarcinoma.
World J Gastrointest Oncol
PUBLISHED: 04-26-2011
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Gastric carcinoma is one of the malignancies that are most frequently associated with esophageal carcinoma. We describe herein our device for advanced esophageal cancer associated with early gastric cancer in the antrum. A 57-year-old man presenting with dysphagia and upper abdominal pain was admitted to our hospital. Preoperative examinations revealed locally advanced squamous cell carcinoma (SCC) of the middle thoracic esophagus (T3N0M0 Stage IIA) and mucosal signet-ring cell carcinoma of the gastric antrum (T1N0M0 Stage?IA). Although the gastric tumor appeared to be an intramucosal carcinoma, its margin was obscure, so endoscopic en-bloc resection was considered inadequate. We chose surgical resection of the gastric tumor as well as the esophageal SCC after neoadjuvant chemotherapy with 5-fluorouracil and cisplatin for advanced esophageal cancer. Following transthoracic esophagectomy with three-field lymph node dissection, the gastric carcinoma was removed by gastric antrectomy, which preserved the right gastroepiploic vessels, and a pedunculated short gastric tube was used as the esophageal substitute. Twenty-eight months after the surgery, the patient is well with no evidence of cancer recurrence. Because it minimizes surgical stress and organ sacrifice, gastric tube interposition is a potentially useful technique for esophageal cancer associated with localized early gastric cancer.
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Risk factors that influence early death due to cancer recurrence after extended radical esophagectomy with three-field lymph node dissection.
Ann. Surg. Oncol.
PUBLISHED: 04-16-2011
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Extended radical esophagectomy with three-field lymph node dissection (3-FLD) has offered significant survival benefit, but some patients still suffer from early recurrence and die within 1 year after surgery. The purpose of this study was to identify the risk factors that influence early death due to cancer recurrence after extended radical esophagectomy with 3-FLD.
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Planning of occupational dose reduction at BWR power plant by past dose record analysis combined with on-site workers idea analysis.
Radiat Prot Dosimetry
PUBLISHED: 04-16-2011
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In order to establish a plan for occupational dose reduction at operating plants, outage inspection works that involve high-dose exposure were selected and a determination of the major causes of high-dose exposure made by plant-by-plant comparison of doses received during inspection works. The comparison was made to investigate the relationship between exposure and the volume of objects to be inspected, working time and man-hour of each work process and ambient dose rates at work areas. In parallel with this, an analysis has also been carried out on 400 data items in a questionnaire survey conducted on relevant individuals, including foremen, radiation safety personnel, on-site workers and plant designers regarding ideas for dose reduction methods. With combination of these two analyses, matters that require improvement will be highlighted, then modification of equipment or revision of work procedures necessary for occupational dose reduction will be planned by plant designers through review.
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Plasma free amino acid profiling of five types of cancer patients and its application for early detection.
PLoS ONE
PUBLISHED: 04-08-2011
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Recently, rapid advances have been made in metabolomics-based, easy-to-use early cancer detection methods using blood samples. Among metabolites, profiling of plasma free amino acids (PFAAs) is a promising approach because PFAAs link all organ systems and have important roles in metabolism. Furthermore, PFAA profiles are known to be influenced by specific diseases, including cancers. Therefore, the purpose of the present study was to determine the characteristics of the PFAA profiles in cancer patients and the possibility of using this information for early detection.
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1,6-Dihydro-2H-indeno[5,4-b]furan derivatives: design, synthesis, and pharmacological characterization of a novel class of highly potent MT?-selective agonists.
J. Med. Chem.
PUBLISHED: 04-07-2011
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A novel series of 1,6-dihydro-2H-indeno[5,4-b]furan derivatives were designed and synthesized as MT(2)-selective ligands. This scaffold was identified as a potent mimic of the 5-methoxy indole core of melatonin, and introduction of a cyclohexylmethyl group at the 7-position of this scaffold afforded an MT(2)-selective ligand 15 (K(i) = 0.012 nM) with high MT(1)/MT(2) selectivity (799). Compound 15 was identified as a potent full agonist for the MT(2) subtype and exhibited reentrainment effects to a new light/dark cycle in ICR mice at 3-30 mg/kg. This result demonstrated the involvement of the MT(2) receptors in chronobiotic activity.
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Comparison of expression patterns of shell matrix protein genes in the mantle tissues between high- and low-quality pearl-producing recipients of the pearl oyster, Pinctada fucata.
Zool. Sci.
PUBLISHED: 03-30-2011
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The production of a cultured pearl is the result of a complex interplay between the donor and recipient oysters. However, there is a paucity of information on the relationship between donor and recipient oyster gene expression patterns and pearl quality. Shell matrix proteins affect not only the formation of the shell, but also that of the pearls. We compared the gene expression patterns of five shell matrix proteins (msi60, nacrein, msi31, prismalin-14, and aspein) in the mantle edge (ME), which forms the prismatic layer, and the mantle center (MC), which forms the nacreous layer, between high- (HP) and low quality pearl- (LP) producing recipient oysters. After culturing for about two months, ME and MC tissues were collected from nine recipient oysters: four with HP, five with LP. In the ME, the average threshold cycle (?C(T)) for aspein was higher in HP than in LP (t-test, p = 0.03). Additionally, in the MC, the average ?C(T) for msi60 was lower in HP than in LP (p = 0.06). This means the relative expression level of msi60 in the mantle of HP was higher than that of LP, and expression level of aspein in the mantle of HP was lower than that of LP. Pearl quality was closely related to the expression patterns of shell matrix protein genes of recipient oysters.
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Cholesterol attenuates and prevents bilayer damage and breakdown in lipoperoxidized model membranes. A spin labeling EPR study.
Biochim. Biophys. Acta
PUBLISHED: 03-03-2011
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The stabilizing effect of cholesterol on oxidized membranes has been studied in planar phospholipid bilayers and multilamellar 1-palmitoyl-2-linoleoyl-phosphatidylcholine vesicles also containing either 1-palmitoyl-2-glutaroyl-phosphatidylcholine or 1-palmitoyl-2-(13-hydroxy-9,11-octadecanedienoyl)-phosphatidylcholine oxidized phosphatidylcholine in variable ratio. Lipid peroxidation-dependent membrane alterations in the absence and in the presence of cholesterol were analyzed using Electron Paramagnetic Resonance spectroscopy of the model membranes spin labelled with either cholestane spin label (3-DC) or phosphatidylcholine spin label (5-DSPC). Cholesterol, added to lipid mixtures up to 40% final molar ratio, decreased the inner bilayer disorder as compared to cholesterol-free membranes and strongly reduced bilayer alterations brought about by the two oxidized phosphatidylcholine species. Furthermore, Sepharose 4B gel-chromatography and cryo electron microscopy of aqueous suspensions of the lipid mixtures clearly showed that cholesterol is able to counteract the micelle forming tendency of pure 1-palmitoyl-2-glutaroyl-phosphatidylcholine and to sustain multilamellar vesicles formation. It is concluded that membrane cholesterol may exert a beneficial and protective role against bilayer damage caused by oxidized phospholipids formation following reactive oxygen species attack to biomembranes.
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Association between breast cancer risk and the wild-type allele of human ABC transporter ABCC11.
Anticancer Res.
PUBLISHED: 12-29-2010
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International mortality and frequency rates for breast cancer have been associated with the wet type of human earwax. It was recently found that earwax type is determined by a single nucleotide polymorphism (SNP), 538G>A (Gly180Arg), in ABCC11. The G allele determines the wet type of earwax as a Mendelian trait with a dominant phenotype. The present study examined the association between the frequency rate of breast cancer and the frequency of the G allele of ABCC11.
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Gene expression patterns in the outer mantle epithelial cells associated with pearl sac formation.
Mar. Biotechnol.
PUBLISHED: 09-08-2010
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For pearl culture, nucleus and mantle grafts are implanted into the gonad of the host oyster. The epithelial cells of the implanted mantle graft elongate and surround the nucleus, and a pearl sac is formed. Shell matrix proteins secreted by the pearl sac play an important role in pearl formation. We studied the gene expression patterns of six shell matrix proteins (msi60, n16, nacrein, msi31, prismalin-14, and aspein) in the epithelial cells associated with pearl sac formation. There were differences in the expression patterns of the six genes in the epithelial cells, and the relative expression levels for msi60 and aspein differed between the mantle graft and pearl sac (48 days after implantation). Therefore, the gene expression patterns of the epithelial cells were genetically undetermined, and changed between before and after pearl sac formation. The gene expression patterns of the epithelial cells of the pearl sac may be regulated by the host oysters.
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[Long-term survival of a breast cancer patient with liver metastasis treated with trastuzumab and Paclitaxel].
Gan To Kagaku Ryoho
PUBLISHED: 06-23-2010
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We report a long-term survival case of metastatic breast cancer treated with trastuzumab and paclitaxel. The patient was a 64-year-old female. She underwent right quadrantectomy with axillary lymphadenectomy for advanced breast cancer. Histological examination showed papillotubular carcinoma, f, t2, n1(6/14), ER(-), PgR(-), HER2(3+). CMF and radiation were performed as adjuvant therapy. One year after the operation she was diagnosed to have liver metastasis and initiated trastuzumab treatment. Paclitaxel was also intermittently administered when the tumor marker was elevated. Four years after the operation, she experienced obstructive jaundice and was diagnosed as hepatic portal region metastasis. Obstructive jaundice was promptly alleviated after receiving trastuzumab and vinorelbin. No adverse events were reported over sixty-eight months of trastuzumab treatment. Long-term trastuzumab and intermittent chemotherapy would be one of the optimal treatments for HER2-positive breast cancer.
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Three-dimensional structural analysis of eukaryotic flagella/cilia by electron cryo-tomography.
J Synchrotron Radiat
PUBLISHED: 05-04-2010
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Electron cryo-tomography is a potential approach to analyzing the three-dimensional conformation of frozen hydrated biological macromolecules using electron microscopy. Since projections of each individual object illuminated from different orientations are merged, electron tomography is capable of structural analysis of such heterogeneous environments as in vivo or with polymorphism, although radiation damage and the missing wedge are severe problems. Here, recent results on the structure of eukaryotic flagella, which is an ATP-driven bending organelle, from green algae Chlamydomonas are presented. Tomographic analysis reveals asymmetric molecular arrangements, especially that of the dynein motor proteins, in flagella, giving insight into the mechanism of planar asymmetric bending motion. Methodological challenges to obtaining higher-resolution structures from this technique are also discussed.
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Novel type of bicellar disks from a mixture of DMPC and DMPE-DTPA with complexed lanthanides.
Langmuir
PUBLISHED: 04-14-2010
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We report on the formation of bicelles from a mixture of dimyristoylphosphatidylcholine (DMPC) and the chelator-lipid dimyristoylphosphatidylethanolamine-diethylenetriaminepentaacetate (DMPE-DTPA) with complexed lanthanides, either thulium (Tm(3+)) or lanthanum (La(3+)). The two phospholipids used have the same acyl-chain length but differ in headgroup size and chemical structure. The total lipid concentration was 15 mM, and the molar ratio of DMPC to DMPE-DTPA was 4:1. The system was studied with small angle neutron scattering (SANS) in a magnetic field, cryo-transmission electron microscopy (cryo-TEM), and (31)P NMR spectroscopy. We found that, after appropriate preparation steps, that is, extrusion through a polycarbonate membrane followed by a cooling step, monodisperse small unilamellar disks (flat cylinders called bicelles) are formed. They have a radius of 20 nm and a bilayer thickness of about 4 nm and are stable in the investigated temperature range of 2.5-30 degrees C. Fitting of SANS data with a form factor for partly aligned flat cylinders shows that the bicelles are slightly orientable in a magnetic field of 8 T if DMPE-DTPA is complexed with Tm(3+).
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CT assessment of breast cancer for pathological involvement of four or more axillary nodes.
Breast Cancer
PUBLISHED: 04-02-2010
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To predict the likelihood of ?4 pathologically positive axillary nodes in breast cancer patients by computed tomography (CT) before neoadjuvant chemotherapy (NAC).
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[A case of recurrent breast cancer with life-threatening liver metastasis remarkably responding to classical CMF].
Gan To Kagaku Ryoho
PUBLISHED: 03-25-2010
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A 35-year-old woman with recurrent breast cancer with liver metastasis was treated with classical CMF because they had been resistant to anthracycline, taxane and vinorelbine. A remarkable response was achieved, FDG-PET demonstrated that FDG accumulation disappeared in the liver metastasis. Toxicities were tolerable and classical CMF could be continued on an outpatient basis without compromising quality of life. Our experience suggested that classical CMF was a useful regimen for recurrent metastatic breast cancer refractory to treatment with new agents.
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Nucleotide-induced global conformational changes of flagellar dynein arms revealed by in situ analysis.
Nat. Struct. Mol. Biol.
PUBLISHED: 03-24-2010
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Outer and inner dynein arms generate force for the flagellar/ciliary bending motion. Although nucleotide-induced structural change of dynein heavy chains (the ATP-driven motor) was proven in vitro, our lack of knowledge in situ has precluded an understanding of the bending mechanism. Here we reveal nucleotide-induced global structural changes of the outer and inner dynein arms of Chlamydomonas reinhardtii flagella in situ using electron cryotomography. The ATPase domains of the dynein heavy chains move toward the distal end, and the N-terminal tail bends sharply during product release. This motion could drive the adjacent microtubule to cause a sliding motion. In contrast to in vitro results, in the presence of nucleotides, outer dynein arms coexist as clusters of apo or nucleotide-bound forms in situ. This implies a cooperative switching, which may be related to the mechanism of bending.
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Can the quality of pearls from the Japanese pearl oyster (Pinctada fucata) be explained by the gene expression patterns of the major shell matrix proteins in the pearl sac?
Mar. Biotechnol.
PUBLISHED: 03-20-2010
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For pearl culture, the pearl oyster is forced open and a nucleus is implanted into the gonad with a mantle graft. The outer mantle epithelial cells of the implanted mantle graft elongate and surrounding the nucleus a pearl sac is formed. Shell matrix proteins secreted by the pearl sac play an important role in the regulation of pearl formation. Recently, seven shell matrix proteins were identified from the pearl oyster Pinctada fucata. However, there is a paucity of information on the function of these proteins and their gene expression patterns. Our study aims to elucidate the relationship between pearl type, quality, and gene expression patterns of six shell matrix proteins (msi60, n16, nacrein, msi31, prismalin-14, and aspein) in the pearl sac based on real-time PCR analysis. After culturing for about 2 months, the pearl sac tissues were collected from 22 individuals: 12 with high quality (HP), nine with low quality (LP), and one with organic (ORG) pearl formation. The surface of each of the 12 HP pearls was composed only of a nacreous layer; in contrast, that of the nine LP pearls was composed of nacreous and prismatic layers. The six target gene expressions were detected in all individuals. However, delta threshold cycle (?C(T)) for msi31 was significantly higher in the HP than in the LP individuals (Mann-Whitneys U test, p=0.02). This means that the relative expression level of msi31, which constitutes the framework of the prismatic layer, was higher in the LP than in the HP individuals.
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A human epidermal growth factor receptor 2 expression-based approach to neoadjuvant chemotherapy for operable breast cancer.
Jpn. J. Clin. Oncol.
PUBLISHED: 03-18-2010
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We investigated the pathological effects of neoadjuvant chemotherapy based on the human epidermal growth factor receptor 2 in operable breast cancer.
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Gastrointestinal stromal tumor with two genetic abnormalities on different alleles: report of a case.
Surg. Today
PUBLISHED: 02-24-2010
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We report a case of a gastrointestinal stromal tumor (GIST) with strong and faint KIT protein staining, respectively, at two different sites. A single point mutation (c1727 T>C) was detected in DNA extracted from both sites, and a further deletion mutation (c1678_1680 del GTT) was detected in DNA from the site with strong KIT protein staining. Cloning analysis indicated that the point mutation and the deletion were present on different alleles.
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Laparoscopic tailored Nissen fundoplication.
Surg Endosc
PUBLISHED: 02-23-2010
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It is difficult sometimes to determine the suture points for proper Nissen fundoplication under laparoscopy. We introduce a new procedure to define the suture points in Laparoscopic Nissen fundoplication (LNF).
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Local and global mobility in the ClpA AAA+ chaperone detected by cryo-electron microscopy: functional connotations.
Structure
PUBLISHED: 02-16-2010
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The ClpA chaperone combines with the ClpP peptidase to perform targeted proteolysis in the bacterial cytoplasm. ClpA monomer has an N-terminal substrate-binding domain and two AAA+ ATPase domains (D1 and D2). ClpA hexamers stack axially on ClpP heptamers to form the symmetry-mismatched protease. We used cryo-electron microscopy to visualize the ClpA-ATPgammaS hexamer, in the context of ClpAP complexes. Two segments lining the axial channel show anomalously low density, indicating that these motifs, which have been implicated in substrate translocation, are mobile. We infer that ATP hydrolysis is accompanied by substantial structural changes in the D2 but not the D1 tier. The entire N domain is rendered invisible by large-scale fluctuations. When deletions of 10 and 15 residues were introduced into the linker, N domain mobility was reduced but not eliminated and changes were observed in enzymatic activities. Based on these observations, we present a pseudo-atomic model of ClpAP holoenzyme, a dynamic proteolytic nanomachine.
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The topoisomerase II alpha gene status in primary breast cancer is a predictive marker of the response to anthracycline-based neoadjuvant chemotherapy.
Pathol. Res. Pract.
PUBLISHED: 01-20-2010
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This study aimed at evaluating the usefulness of topoisomerase II alpha (TOP2A) for predicting the effect of anthracycline-based neoadjuvant chemotherapy in breast cancer. The TOP2A status was examined using fluorescent in situ hybridization (FISH) in 14 pre-chemotherapeutic breast cancer tissues, and was also assessed by immunohistochemistry (IHC) in 14 pairs of pre- and post-chemotherapeutic breast cancer specimens. TOP2A gene aberration by IHC tended to show a correlation with pathological responses but this was not statistically significant (p=0.060). On the other hand, the low TOP2A/CEP17 ratio correlated with good pathological responses (p=0.012). TOP2A overexpression was not significantly associated with response (p=0.580). Our results thus suggest that the TOP2A/CEP17 ratio may be a useful predictor of the effects of anthracycline-based neoadjuvant chemotherapy in breast cancer.
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Novel L-amino acid oxidase with antibacterial activity against methicillin-resistant Staphylococcus aureus isolated from epidermal mucus of the flounder Platichthys stellatus.
FEBS J.
PUBLISHED: 12-15-2009
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Fish produce mucus substances as a defensive outer barrier against environmental xenobiotics and predators. Recently, we found a bioactive protein in the mucus layer of the flounder Platichthys stellatus, which showed antibacterial activity against Staphylococcus epidermidis, Staphylococcus aureus and methicillin-resistant S. aureus. In this study, we isolated and identified the antibacterial protein from the mucus components of P. stellatus using a series of column chromatography steps. We then performed gel electrophoresis and cDNA cloning to characterize the protein. The antibacterial protein in the mucus had a molecular mass of approximately 52 kDa with an isoelectric point of 5.3, and cDNA sequencing showed that it corresponded completely with the peptide sequence of antibacterial protein from the gill. A BLAST search suggested that the cDNA encoded an antibacterial protein sharing identity with a number of L-amino acid oxidases (LAAOs) and possessing several conserved motifs found in flavoproteins. RT-PCR using a specific primer, and immunohistochemical analysis with anti-LAAO IgG, demonstrated tissue-specific expression and localization in the gill. Moreover, the anti-LAAO IgG was able to neutralize the antibacterial activity of the protein against methicillin-resistant S. aureus. Thus, we demonstrated that this antibacterial protein, identified from P. stellatus-derived epidermal mucus, is a novel LAAO-like protein with antibacterial activity, similar to snake LAAOs.
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Molecular details of Bax activation, oligomerization, and membrane insertion.
J. Biol. Chem.
PUBLISHED: 12-12-2009
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Bax and Bid are pro-apoptotic members of the Bcl-2 protein family. Upon cleavage by caspase-8, Bid activates Bax. Activated Bax inserts into the mitochondrial outer membrane forming oligomers which lead to membrane poration, release of cytochrome c, and apoptosis. The detailed mechanism of Bax activation and the topology and composition of the oligomers are still under debate. Here molecular details of Bax activation and oligomerization were obtained by application of several biophysical techniques, including atomic force microscopy, cryoelectron microscopy, and particularly electron paramagnetic resonance (EPR) spectroscopy performed on spin-labeled Bax. Incubation with detergents, reconstitution, and Bid-triggered insertion into liposomes were found to be effective in inducing Bax oligomerization. Bid was shown to activate Bax independently of the stoichiometric ratio, suggesting that Bid has a catalytic function and that the interaction with Bax is transient. The formation of a stable dimerization interface involving two Bcl-2 homology 3 (BH3) domains was found to be the nucleation event for Bax homo-oligomerization. Based on intermolecular distance determined by EPR, a model of six adjacent Bax molecules in the oligomer is presented where the hydrophobic hairpins (helices alpha5 and alpha6) are equally spaced in the membrane and the two BH3 domains are in close vicinity in the dimer interface, separated by >5 nm from the next BH3 pairs.
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The usefulness of olfactory bulb kindling as a model for evaluation of antiepileptics.
Epilepsia
PUBLISHED: 10-20-2009
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The present study was undertaken to clarify the behavioral and electroencephalographic characteristics of olfactory bulb (OB) kindling in rats, in comparison with those of amygdala (AMG) kindling. In addition, the usefulness of OB kindling as a model to evaluate antiepileptics was studied.
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MRT letter: In situ observation method for microstructural changes of steel during hot deformation.
Microsc. Res. Tech.
PUBLISHED: 09-29-2009
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We report on the result of an in situ method for observing microstructural changes during hot deformation. The observation of microstructural changes of steel at 1,473 K under tensile strain is demonstrated using the reported method. The development of deformed structures and the formation of a new grain boundary, which subsequently moved with increased strain, were clearly observed. The effectiveness of this method was confirmed by the results of several examples.
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Vesicles as soft templates for the enzymatic polymerization of aniline.
Langmuir
PUBLISHED: 08-13-2009
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The feasibility of using surfactant vesicles as soft templates for the peroxidase-triggered polymerization of aniline was investigated. It was found that mixed anionic vesicles (diameter approximately 80 nm) composed of sodium dodecylbenzenesulfonate (SDBS) and decanoic acid (1:1, molar ratio) are promising templates. In the presence of the vesicles and horseradish peroxidase/hydrogen peroxide (H2O2) as initiator system, aniline polymerizes under optimized conditions at pH=4.3 to the desired conductive emeraldine form of polyaniline (PANI). The optimal polymerization conditions were elaborated, and some of the chemical and physicochemical aspects of the reaction system were investigated. After addition of aniline and peroxidase to the vesicles, aniline is only loosely associated with the vesicles, as shown by NOESY-NMR and zeta potential measurements. In contrast, the peroxidase strongly binds to the vesicle surface, as shown by fluorescence measurements using TNS (2-(p-toluidino)naphthalene-6-sulfonate) as vesicle membrane probe. This binding of the enzyme to the vesicle surface indicates that the polymerization reaction is initiated predominantly on the surface of the vesicles. Cryo-transmission electron microscopy indicates that the polymerization product remains associated with the vesicles on their surface. For short reaction times (30 s
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Asymmetry of inner dynein arms and inter-doublet links in Chlamydomonas flagella.
J. Cell Biol.
PUBLISHED: 08-12-2009
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Although the widely shared "9 + 2" structure of axonemes is thought to be highly symmetrical, axonemes show asymmetrical bending during planar and conical motion. In this study, using electron cryotomography and single particle averaging, we demonstrate an asymmetrical molecular arrangement of proteins binding to the nine microtubule doublets in Chlamydomonas reinhardtii flagella. The eight inner arm dynein heavy chains regulate and determine flagellar waveform. Among these, one heavy chain (dynein c) is missing on one microtubule doublet (this doublet also lacks the outer dynein arm), and another dynein heavy chain (dynein b or g) is missing on the adjacent doublet. Some dynein heavy chains either show an abnormal conformation or were replaced by other proteins, possibly minor dyneins. In addition to nexin, there are two additional linkages between specific pairs of doublets. Interestingly, all these exceptional arrangements take place on doublets on opposite sides of the axoneme, suggesting that the transverse functional asymmetry of the axoneme causes an in-plane bending motion.
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In vivo effect of imatinib on progression of cecal GIST-like tumors in exon 17-type c-kit knock-in mice.
Lab. Invest.
PUBLISHED: 07-27-2009
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Two families with a germline Asp820Tyr mutation at exon 17 of the c-kit gene and multiple gastrointestinal stromal tumors (GISTs) have been reported. Recently, we generated a knock-in mouse model of the family, and mice with KIT-Asp818Tyr corresponding to human KIT-Asp820Tyr showed a cecal GIST-like tumor. In this report, we examined the in vivo effect of imatinib on tumor progression in knock-in mice. Imatinib of 100 microg/g body weight was administered to heterozygous (KIT-Asp818Tyr/+) mice orally for 7, 14 and 28 days, and cecal tumors were dissected. Both macroscopic size and the measured volume of cecal tumors were not significantly reduced after a 7-, 14- and 28-day administration of imatinib when compared with those before imatinib administration. Cell proliferation was assessed by Ki-67 immunohistochemistry and the labeling index significantly decreased after imatinib administration, but the value of the index after imatinib was only about half compared with that before imatinib. Western blotting and real-time PCR revealed that KIT expression was almost equivalent, but KIT phosphorylation was significantly but not completely inhibited in tumor tissues after 7, 14 and 28 days of imatinib administration when compared with that before imatinib administration. Phosphorylation of Akt and Stat1 was accordingly inhibited after imatinib administration. Thus, imatinib seemed to inhibit in vivo tumor proliferation but not decrease tumor volume on this mouse model, probably because of an insufficient inhibition of phosphorylation of KIT and its downstream signaling molecules. These results suggested that progression of multiple GISTs in patients with germline Asp820Tyr might be partially controlled by imatinib and that model mice provide an opportunity to examine the effect of various other targeted drugs on in vivo tumor progression.
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Allergic reactions to oxaliplatin in a single institute in Japan.
Jpn. J. Clin. Oncol.
PUBLISHED: 06-25-2009
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Allergic reactions to oxaliplatin can be severe and are an important cause of discontinuation of treatment. A retrospective review was performed for 105 patients who received FOLFOX regimens between May 2005 and June 2007. Twenty-five cases (23.8%) of allergic reactions were identified, including 9 late onset reactions (8.6%) and 16 immediate reactions (15.2%). Severe allergy (Grades 3 and 4) occurred in seven patients (6.7%). Re-introduction of FOLFOX was attempted for seven immediate onset patients with a severity grade of 1 or 2, and three of these patients (42.9%) showed relapse of allergy. In approximately 10% of the patients, FOLFOX had to be discontinued due to allergy before the disease became refractory to the regimen. Our experience indicates that allergy to oxaliplatin may be a significant concern and that methods are required for suppression of this allergy.
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Clinical usefulness of high-dose toremifene in patients relapsed on treatment with an aromatase inhibitor.
Breast Cancer
PUBLISHED: 06-04-2009
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Aromatase inhibitors (AIs) have been employed as adjuvant therapy or as treatment for recurrent cases. However, when AI treatment fails, it is unclear which endocrine therapy is the most appropriate to introduce at this point and how effective it will be. In this study, we investigated the efficacy and safety of toremifene (TOR, Fareston(®)), a selective estrogen receptor modulator (SERM).
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Feasibility of AC/EC followed by weekly paclitaxel in node-positive breast cancer in Japan.
Anticancer Res.
PUBLISHED: 05-16-2009
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The feasibility and efficacy of adriamycin or epirubicin in combination with cyclophosphamide followed by weekly paclitaxel (AC/EC-weekly PAC) as adjuvant chemotherapy for breast cancer was investigated.
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Synchronous development of HCC and CCC in the same subsegment of the liver in a patient with type C liver cirrhosis.
World J Hepatol
PUBLISHED: 04-08-2009
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As a result of having undergone computed tomography (CT), a 75-year-old woman with type-C liver cirrhosiswas shown to have two tumors on the ventral and dorsal sides of subsegment 3 (S3). The tumor on the ventral side was diagnosed as a classic hepatocellular carcinoma (HCC), while that on the dorsal side was considered atypical for a HCC. Although the indocyanine green (ICG) findings indicated poor hepatic reserve, the prothrombin time (PT) was relatively good. An operation was performed in February 2007; however, this resulted in exploratory laparotomy. Dynamic CT performed 12 mo after the operation revealed that the tumor on the dorsal side of S3 had apparently increased. The marginal portion of the tumor was shown to be in the early and parenchymal phases, while the internal portion was found to have grown only slightly in the delayed phase. We diagnosed this tumor as a cholangiocellular carcinoma (CCC). S3 subsegmentectomy was performed in April 2008. The tumor on the ventral side was pathologically diagnosed as a moderately differentiated HCC, and that on the dorsal side was diagnosed as a CCC. We can therefore report a rare case of synchronous development of HCC and CCC in the same subsegment of the liver in a patient with type-C liver cirrhosis. We also add a literature review for all the reported cases published in Japan and around the world, and summarize the features of double cancer exhibiting both HCC and CCC.
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Effects of antiepileptics on lateral geniculate nucleus-kindled seizures in rats.
J. Pharmacol. Sci.
PUBLISHED: 04-04-2009
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The present study was undertaken to clarify the characteristics of lateral geniculate nucleus (LGN) kindling in rats, especially the efficacies of antiepileptics, in comparison with those of amygdala (AMG) kindling. Daily electrical stimulation of the LGN led to the development of a generalized convulsion (kangaroo posture and falling back) in all subjects, similar to AMG kindling. The kindling response of the LGN differed from that of the AMG in a number of respects, that is, a high after-discharge (AD) threshold, a large number of stimulations for completion of kindling, and a different pattern of electroencephalogram (EEG) development. On the other hand, the oral administration of sodium valproate, carbamazepine, clobazam, or zonisamide caused dose-dependent inhibitions of both seizure stage and AD duration of LGN-kindled seizures, whereas ethosuximide had no significant effects. In addition, seizure stage was more potently inhibited than AD duration by these antiepileptics, particularly with clobazam. In conclusion, LGN kindling possesses characteristics that are different from AMG kindling. In addition, it was demonstrated that LGN kindling is a useful model, similar to other types of limbic system kindling, for the evaluation of antiepileptics.
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Sebaceous carcinoma of the breast.
Pathol. Int.
PUBLISHED: 03-06-2009
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Sebaceous carcinoma (SC) of the breast is a rare malignant tumor and only nine cases, including the present one, have been reported in the English-language literature. The present report describes a case of mammary SC in a 50-year-old Japanese woman. The tumor was gray-white on cut surface and separate from the skin and the nipple. Microscopically, lobules encircled by a fibrous envelope and cords or small cell nests in the stroma were noted. These two types of structures were composed of dark cells and clear foamy cells. The dark cells had large nuclei and amphophilic cytoplasm. The clear foamy cells had numerous lipid vacuoles, confirmed on immunostaining with anti-adipophilin antibody and electron microscopy. In the lobules the gradual transitions from basal dark cells to central clear foamy cells and comedo-like necrosis were observed. The tumor cells were positive on immunohistochemistry for cytokeratins (CAM5.2, AE1/AE3), Her2/neu and androgen receptor but negative for estrogen and progesterone receptors. This is the first case of an androgen receptor-positive mammary SC to be reported, and therefore contributes to the understanding of the clinicopathological features of SC of the breast.
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Reexpansion Pulmonary Edema following Laparoscopy-Assisted Distal Gastrectomy for a Patient with Early Gastric Cancer: A Case Report.
Case Rep Surg
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We report here a case of reexpansion pulmonary edema following laparoscopy-assisted distal gastrectomy (LADG) for early gastric cancer. A 57-year-old Japanese woman with no preoperative comorbidity was diagnosed with early gastric cancer. The patient underwent LADG using the pneumoperitoneum method. During surgery, the patient was unintentionally subjected to single-lung ventilation for approximately 247 minutes due to intratracheal tube dislocation. One hour after surgery, she developed severe dyspnea and produced a large amount of pink frothy sputum. Chest radiography results showed diffuse ground-glass attenuation and alveolar consolidation in both lungs without cardiomegaly. A diagnosis of pulmonary edema was made, and the patient was immediately intubated and received ventilatory support with high positive end-expiratory pressure. The patient gradually recovered and was weaned from the ventilatory support on the third postoperative day. This case shows that single-lung ventilation may be a risk factor for reexpansion pulmonary edema during laparoscopic surgery with pneumoperitoneum.
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Breast cancer manifested by hematologic disorders.
J Thorac Dis
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Breast cancer is the most common type of cancer in women. However, it is very rarely manifested as hematologic disorders. A 35-year-old woman was admitted because of disseminated intravascular coagulation. Examinations revealed the presence of breast cancer in her left breast; therefore, paclitaxel was administered weekly. Although disseminated intravascular coagulation was controlled, pulmonary dysfunction due to lymphangitis carcinomatosa suddenly occurred 10 weeks after treatment. Pulmonary dysfunction was effectively treated with epirubicin and cyclophosphamide. Twenty-three weeks after treatment, the patient developed liver dysfunction accompanied with jaundice due to progressive metastatic lesions in the liver; liver dysfunction improved after the administration of vinorelbine. Subsequently, because of the recurrence of pulmonary dysfunction, rechallenge with epirubicin and cyclophosphamide was performed and was effective; however, this therapy was discontinued because of its adverse effects. She expired of liver failure 33 weeks after the occurrence of disseminated intravascular coagulation. Metastatic tumors in the bone marrow, lung, and liver showed different sensitivities to different anti-cancer agents. We report a case of breast cancer manifested by hematologic disorders which was treated by a sequential chemotherapy.
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Impacts and predictors of cytotoxic anticancer agents in different breast cancer subtypes.
Oncol. Res.
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Breast cancer is not a single entity. This study therefore aimed to identify differences in the impacts of anticancer agents and predictive factors between different breast cancer subtypes. A total of 234 patients with luminal (n = 109), luminal-HER2 (L-H, n = 29), HER-2 (n = 35), or triple negative (TN, n = 61) breast cancer subtypes were treated with standard neoadjuvant chemotherapy consisting of an anthracycline and/or taxane. Pathological response and prognosis were examined in each subtype. Expression levels of estrogen and progesterone receptors, HER-2, nuclear grade, MIB-1, p53, topoisomerase IIalpha (topoIIalpha), cytokeratin (CK) 5/6, and epidermal growth factor receptor (EGFR) were examined in association with quasipathological complete response (QpCR). QpCR rates were 9.1% (10/109) in luminal, 45% (13/29) in L-H, 37% (13/35) in HER2, and 54.1% (33/61) in TN. Non-QpCR patients showed significantly poorer 3-year disease-free survival than QpCR patients in TN, but not in patients with other subtypes. No factors were associated with QpCR in luminal patients. Patients with higher nuclear grade were more likely to achieve QpCR in L-H. The proliferative markers MIB-1 and topoIlalpha had opposite impacts on pathological response in HER-2 and TN. The QpCR rate was significantly higher in TN lacking CK5/6 and/or EGFR expression, defined as nonbasal subtype, compared with basal subtype (p = 0.049). Cytotoxic anticancer agents were associated with different responses in different breast cancer subtypes. Identifying basal-type cancer and further subdivision of nonbasal types is important for treating TN patients.
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Preoperative endocrine therapy with goserelin acetate and tamoxifen in hormone receptor-positive premenopausal breast cancer patients.
Breast Cancer
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BACKGROUND: The use of preoperative endocrine therapy for breast cancer has increased during the last decade. Although several studies have reported favorable response rates in postmenopausal women, its effectiveness in premenopausal women remains unknown. This study therefore aimed to evaluate the potential benefits of preoperative endocrine therapy in premenopausal women. METHODS: Fifty-three patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative invasive breast cancer were included in this study. Preoperative endocrine therapy with goserelin acetate and tamoxifen was administered for 3 months. Clinical evaluations were performed by ultrasonography before and after endocrine therapy. Pathological evaluations were performed using core biopsy and surgical specimens. Immunohistochemical evaluations of ER, progesterone receptor (PgR), HER2, and Ki-67 were performed before and after endocrine therapy. RESULTS: Partial response (PR) was observed in 23 % (12/53) and progressive disease (PD) in 2 % (2/53) of patients. Significant suppression of Ki-67 was observed following endocrine therapy in 90 % (47/52) of patients (P < 0.0001). Significant downregulation of PgR was observed after endocrine therapy (P = 0.0002), which tended to be correlated with clinical response (P = 0.058). CONCLUSIONS: Three months of preoperative endocrine therapy with goserelin acetate and tamoxifen was safe and effective in premenopausal patients with invasive breast cancer, with a 23 % PR rate. Changes in PgR and Ki-67 expression might be promising markers for endocrine responsiveness.
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WallFlex™ Duodenal Stent Placement in a Gastric Cancer Patient with Malignant Stenosis of a Roux-en-Y Gastrojejunostomy following Distal Gastrectomy.
Case Rep Oncol
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A 69-year-old Japanese woman with a history of distal gastrectomy with a Roux-en-Y reconstruction for advanced gastric cancer was admitted to our hospital complaining of severe dysphagia. On admission, the patient was only able to take liquids, and a firm, fist-sized tumor was palpable in her left upper abdomen. An endoscopic examination disclosed stenosis of the jejunal limb of the gastrojejunostomy. Abdominal computed tomography revealed that a recurrent tumor, 5.0 cm in diameter, was compressing the jejunal limb of the gastrojejunostomy. A knitted nitinol self-expandable metallic stent (WallFlex™ duodenal stent) was placed endoscopically at the stenotic jejunum from the gastrojejunostomy. The time required for stenting and total endoscopic manipulation was 12 and 35 minutes, respectively. No stent-related complications were observed. The patient could resume oral ingestion 1 day after endoscopic stenting and was discharged on the fifth day after treatment. She survived for 201 days after stenting. She continued oral ingestion for 194 days and stayed at home for 165 days. The WallFlex duodenal stent allows safe endoscopic stenting, even in cases of malignant stenosis of a gastrojejunostomy following distal gastrectomy. This stenting device will extend the indications for endoscopic palliation of gastric cancer patients with gastric outlet stenosis.
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Risk factors influencing the pleural drainage volume after transthoracic oesophagectomy.
Eur J Cardiothorac Surg
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The objective of this study was to clarify the factors influencing pleural drainage volume after transthoracic oesophagectomy and to determine criteria for the selection of patients who would benefit from the early removal of chest drains.
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Functionalized low-density lipoprotein nanoparticles for in vivo enhancement of atherosclerosis on magnetic resonance images.
Bioconjug. Chem.
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To allow visualization of macrophage-rich and miniature-sized atheromas by magnetic resonance (MR) imaging, we have converted low-density lipoprotein (LDL) into MR-active nanoparticles via the intercalation of a 1,4,7,10-tetraazacyclodecane-1,4,7-triacetic acid (DO3A) derivative and the subsequent coordination reaction with Gd(3+). After careful removal of nonchelated Gd(3+), an MR-active LDL (Gd(3+)-LDL) with a remarkably high payload of Gd(3+) (in excess of 200 Gd(3+) atoms per particle) and a high relaxivity (r(1) = 20.1 s(-1) mM(-1) per Gd(3+) or 4040 s(-1) mM(-1) per LDL) was obtained. Dynamic light-scattering photon correlation spectroscopy (DLS) and cryo transmission electron microscope (cryoTEM) images showed that Gd(3+)-LDL particles did not aggregate and remained of a similar size (25-30 nm) to native LDL. Intravenous injection of Gd(3+)-LDL into an atherosclerotic mouse model (ApoE(-/-)) resulted in an extremely high enhancement of the atheroma-bearing aortic walls at 48 h after injection. Free Gd(3+) dissociation from Gd(3+)-LDL was not detected over the imaging time window (96 h). Because autologous LDL can be isolated, modified, and returned to the same patient, our results suggest that MR-active LDL can potentially be used as a noninfectious and nonimmunogenic imaging probe for the enhancement of atheroplaques presumably via the uptake into macrophages inside the plaque.
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Polarity and asymmetry in the arrangement of dynein and related structures in the Chlamydomonas axoneme.
J. Cell Biol.
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Understanding the molecular architecture of the flagellum is crucial to elucidate the bending mechanism produced by this complex organelle. The current known structure of the flagellum has not yet been fully correlated with the complex composition and localization of flagellar components. Using cryoelectron tomography and subtomogram averaging while distinguishing each one of the nine outer doublet microtubules, we systematically collected and reconstructed the three-dimensional structures in different regions of the Chlamydomonas flagellum. We visualized the radial and longitudinal differences in the flagellum. One doublet showed a distinct structure, whereas the other eight were similar but not identical to each other. In the proximal region, some dyneins were missing or replaced by minor dyneins, and outer-inner arm dynein links were variable among different microtubule doublets. These findings shed light on the intricate organization of Chlamydomonas flagella, provide clues to the mechanism that produces asymmetric flagellar beating, and pose a new challenge for the functional study of the flagella.
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Revisiting the supramolecular organization of photosystem II in Chlamydomonas reinhardtii.
J. Biol. Chem.
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Photosystem II (PSII) is a multiprotein complex that splits water and initiates electron transfer in photosynthesis. The central part of PSII, the PSII core, is surrounded by light-harvesting complex II proteins (LHCIIs). In higher plants, two or three LHCII trimers are seen on each side of the PSII core whereas only one is seen in the corresponding positions in Chlamydomonas reinhardtii, probably due to the absence of CP24, a minor monomeric LHCII. Here, we re-examined the supramolecular organization of the C. reinhardtii PSII-LHCII supercomplex by determining the effect of different solubilizing detergents. When we solubilized the thylakoid membranes with n-dodecyl-?-D-maltoside (?-DM) or n-dodecyl-?-D-maltoside (?-DM) and subjected them to gel filtration, we observed a clear difference in molecular mass. The ?-DM-solubilized PSII-LHCII supercomplex bound twice more LHCII than the ?-DM-solubilized supercomplex and retained higher oxygen-evolving activity. Single-particle image analysis from electron micrographs of the ?-DM-solubilized and negatively stained supercomplex revealed that the PSII-LHCII supercomplex had a novel supramolecular organization, with three LHCII trimers attached to each side of the core.
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Cartwheel architecture of Trichonympha basal body.
Science
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Centrioles and basal bodies are essential for the formation of cilia, flagella, and centrosomes. They exhibit a characteristic ninefold symmetry imparted by a cartwheel thought to contain rings of SAS-6 proteins. We used cryoelectron tomography to investigate the architecture of the exceptionally long cartwheel of the flagellate Trichonympha. We found that the cartwheel is a stack of central rings that exhibit a vertical periodicity of 8.5 nanometers and is able to accommodate nine SAS-6 homodimers. The spokes that emanate from two such rings associate into a layer, with a vertical periodicity of 17 nanometers on the cartwheel margin. Thus, by using the power of biodiversity, we unveiled the architecture of the cartwheel at the root of the ninefold symmetry of centrioles and basal bodies.
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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.