Cortical liquefaction in severe human herpesvirus 6 encephalopathy.
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Cerebral Cortex↗
Biomedical subjects
N Takada
Publications and source records attributed to N Takada.
The cell death machinery controlled by Bax and Bcl-XL is evolutionarily conserved in Ciona intestinalis.
Bax and Bcl-XL are key regulators of apoptosis in mammals. Here we report the functional characterization of two Bcl-2 homologues, ciBax and ciBcl-XL, in a basal invertebrate-chordate ascidian Ciona intestinalis. CiBax is a Ciona homologue of the BH1-3 pro-apoptotic protein Bax, whereas ciBcl-XL is a Bcl-XL-like anti-apoptotic protein. Molecular modeling analysis showed that ciBax and ciBcl-XL share both sequence and structural similarities to human Bax and Bcl-XL, respectively. Like their human counterparts, ciBax could form a homodimer or oligomers as well as heterodimerize with ciBcl-XL, and overexpression of ciBax caused apoptosis that could be attenuated by ciBcl-XL. Mutagenesis studies showed that the BH3 domain of ciBax is critical for its cell death-inducing function and also for its interaction with ciBcl-XL. In Ciona embryos, ectopic expression of ciBax but not its BH3 deletion mutant resulted in cell dissociation and apoptosis after late gastrula stage of embryonic development. Moreover, not only wild type ciBcl-XL but also a mutant ciBcl-XL(F101V), which is unable to interact with ciBax, could block cell dissociation and developmental deficit in Ciona embryos induced by overexpression of ciBax. Taken together, these findings suggest that functional homologues of both the BH1-3 death effector Bax and the pro-survival Bcl-XL exist in sea squirt Ciona intestinalis, and they control the cell death machinery independent of their heterodimerization.
Animals↗
Evaluation of activation treatments for blastocyst production and birth of viable calves following bovine intracytoplasmic sperm injection.
The objective of this study was to compare the effectiveness of different methods of bovine oocyte activation following intracytoplasmic sperm injection (ICSI) in terms of oocyte cleavage and blastocyst rates, and calf production. Oocytes were harvested, post mortem, from the ovaries of Japanese Black heifers or cows. ICSI was carried out using a piezo-electric actuator. The injected or sham-injected oocytes that were assigned to three activation treatments, each replicated three times, were studied: (1) exposure to 5 microM ionomycin for 5 min (ionomycin); (2) exposure to 5 microM ionomycin for 5 min followed by culture in TCM199 for 3 h and a further 3h culture in 1.9 mM 6-dimethylaminopurine (DMAP-ionomycin+DMAP); (3) exposure to 7% ethanol in TCM199 for 5 min, 4 h after ICSI (ethanol). One or two blastocysts from the ionomycin+DMAP (8 recipients) and ethanol (17 recipients) oocyte activation treatments were non-surgically transferred into Holsteins for the study of calf production. The highest cleavage and blastocyst production rates were observed in the ionomycin+DMAP treatment (83.9% and 40.1%) by the ICSI. These rates were significantly (P<0.05) higher than those for the ionomycin oocyte activation treatment (57.6% and 18.2%) but did not differ from the ethanol treatment (75.6% and 29.4%). In the sham-injected, the highest blastocyst production rates were observed for the ionomycin+DMAP and ethanol treatments (10.7% and 11.3%). Pregnancy and birth rates for blastocysts derived from the ethanol oocyte activation treatment (58.8% and 47.4%) were significantly higher (P<0.05) than those of the ionomycin+DMAP treatment (12.5% and 9.2%). The results showed that post-ICSI oocyte activation with ethanol is more effective than activation with ionomycin alone or with ionomycin+DMAP for the production of viable blastocysts and calves.
Adenine↗
Selection of sexed bovine embryos using rapid fluorescence in situ hybridisation.
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Animals↗
Real-time monitoring for detecting rejection using strain gauge force transducers in porcine small bowel transplantation.
PURPOSE: The clinical results of small bowel transplantation (SBT) have not been satisfactory mainly because of the immunological barrier. It is important to detect the presence of and to perform adequate treatment of rejection as early as possible to improve graft survival. Therefore, we have established a pig model to monitor graft motility as a means to detect rejection in real time. METHODS: Orthotropic SBT was performed in 25 pigs using FK-506 (0.05 to 0.1 mg/kg/d) immunosuppression. The interdigestive motor patterns were evaluated using strain gauge force transducers (SG). Seven pigs without SBT were treated as controls (C). Animals that displayed migrating motor complex (MMC) activity as evidenced by duration, amplitude, and interval in the graft were alive more than 10 days with adequate oral feeding: the functional graft (FG) group. In contrast the rejection (R) group did not show these activities on data recorded within 10 days before death due to rejection. RESULTS: The FG group showed MMC propagated throughout the graft with all parameters almost the same as the control group except for the duration. In contrast, all parameters in the group R were significantly lower than those in group FG, suggesting that group R motility was obviously impaired by rejection. CONCLUSIONS: The SG method may afford real-time monitoring of transplanted bowel motility that could be useful to detect rejection after SBT.
Animals↗
Comparison of three-field esophagectomy for esophageal cancer incorporating open or thoracoscopic thoracotomy.
BACKGROUND: Thoracoscopic esophagectomy for esophageal cancer has been performed as an alternative to open surgery to reduce surgical trauma. However, its effect on pulmonary function, exercise tolerability, and quality of life is unknown. METHODS: Fifty-one patients with esophageal cancer underwent thoracic esophagectomy with radical lymphadenectomy by posterolateral thoracotomy (29 cases) or thoracoscopic surgery (22 cases). Patients performed spirometry and exercise tolerance testing and completed a quality-of-life questionnaire before and 3 months after surgery. RESULTS: Pre-to-postoperative change in vital capacity was 74.3 +/- 10.6% in the thoracotomy group and 84.9 +/- 10.4% in the thoracoscopy group (p = 0.021). Maximum oxygen uptake was similar, but dyspnea was the more common factor limiting exercise tolerance postoperatively in the thoracotomy group. Change in pre-to-postoperative performance status was 1.20 +/- 0.62 in the thoracotomy group and 0.55 +/- 0.51 in the thoracoscopy group (p = 0.0003). CONCLUSIONS: Thoracoscopic esophagectomy for esophageal cancer has better preservation of pulmonary function and quality-of-life.
Adult↗
A comparison of video-assisted thoracoscopic oesophagectomy and radical lymph node dissection for squamous cell cancer of the oesophagus with open operation.
BACKGROUND: A direct comparison of open operation and video-assisted thoracoscopic surgery (VATS) for radical oesophagectomy has yet to be published. METHODS: Medical records of 149 patients with oesophageal squamous cell carcinoma who underwent oesophagectomy and three-field lymphadenectomy were reviewed. Seventy-seven patients had the thoracic procedure performed via a 5-cm minithoracotomy and four ports (VATS group); the others were operated on by conventional posterolateral thoracotomy (open group). RESULTS: The mean number of retrieved mediastinal nodes, blood loss and morbidity were similar in the VATS and open groups (33.9 versus 32.8 nodes, 284 versus 310 g, and 32 versus 38 per cent respectively). The thoracic procedure took longer in patients having VATS than in the control group (227 versus 186 min; P = 0.031). Vital capacity reduction was less with VATS than in the open group (15 versus 22 per cent; P = 0.016). The 3- and 5-year survival rates were similar: 70 and 55 per cent respectively for VATS compared with 60 and 57 per cent for the open procedure. CONCLUSION: VATS provides comparable results to open radical oesophagectomy, with less surgical trauma.
Adult↗
Transfer of cholesterol and diacylglycerol from lipophorin to Bombyx mori ovarioles in vitro: role of the lipid transfer particle.
The objective of this study was to characterize the transfer of diacylglycerol (DAG) and cholesterol from larval Bombyx mori lipophorin to ovarioles. Transfer studies were carried out by incubating pupal ovarioles (5-day) with [(3)H]-cholesterol and [(3)H]-DAG-labeled lipophorin under different conditions. Transfer of both cholesterol and DAG exhibited hyperbolic dependency on lipophorin concentration with apparent Km values of 0.83 +/- 0.17 mg/ml and 0.74 +/- 0.16 mg/ml, respectively. Pretreatment of ovarioles with anti-lipid transfer particle (LTP) IgG significantly inhibited transfer of labeled DAG to ovarioles (75%) and not cholesterol. Injection of B. mori pupae (day 4) with anti-LTP IgG significantly affected the weight (65%), number of eggs (49%), amount of lipid (74%), and protein (65%) of the adult ovaries. Matured eggs had a very faint yellow color and deformed shape compared to controls. The inhibitory effect demonstrates the active role LTP plays in growth of ovaries, development, and oogenesis. The effect on vitellogenin shortage on egg development and maturation was determined by implanting ovaries in male recipients that lack vitellogenin. An 80% decline in egg production was observed. However, the mature eggs were normal in shape, color, and lipid content. Thus, restricting lipid or protein delivery to developing ovaries would dramatically affect choriogenesis.
Animals↗
Identification of candidate genes encoding the core components of the cell death machinery in the Ciona intestinalis genome.
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Animals↗
Learning curve of video-assisted thoracoscopic esophagectomy and extensive lymphadenectomy for squamous cell cancer of the thoracic esophagus and results.
BACKGROUND: The efficacy of thoracoscopic radical esophagectomy for cancer of the thoracic esophagus and the learning curve required have yet to be clearly established. METHODS: Eighty treatment-naive patients with esophageal cancer without contiguous spread underwent esophageal mobilization and extensive mediastinal lymphadenectomy through a 5-cm minithoracotomy and four trocar ports. The outcomes in the first 34 patients (group 1) and the last 46 patients (group 2) were compared. RESULTS: There were no differences in background or clinicopathologic factors between the two groups. The duration of the thoracoscopic procedure and blood loss were less (p <0.0001), the incidence of postoperative pulmonary infection was less (p = 0.0127), and the number of mediastinal nodes retrieved was greater (p = 0.0076) in group 2. Multivariate analysis demonstrated that surgical experience (number of cases performed) predicted the risk of pulmonary infection (p = 0.0331). CONCLUSION: Video-assisted thoracoscopic radical esophagectomy can be performed with safety and efficacy comparable to those of open esophagectomy. Morbidity decreases with the surgeon's experience.
Adult↗
Video-assisted thoracoscopic esophagectomy and radical lymph node dissection for esophageal cancer. A series of 75 cases.
BACKGROUND: The efficacy of thoracoscopic radical esophagectomy for cancer has yet to be established, mainly because previous reports have not included a sufficient number of cases. METHODS: Seventy-five treatment-naive patients with esophageal cancer without contiguous spread underwent esophageal mobilization and extensive mediastinal lymphadenectomy through a 5-cm mini-thoracotomy and four trocar ports. RESULTS: Video-assisted thoracoscopic surgery was performed without major intraoperative complications or emergency conversion to open surgery. We retrieved 34.1+/-13.0 mediastinal nodes, including 11.5+/-3.8 tracheobronchial nodes and 6.2+/-3.0 recurrent laryngeal nodes. Mean time of operation and blood loss were less in the last 39 patients than the first 36 (186.7+/-25.3 min and 165.4+/-101.8 g vs 270. 2+/-96.0 min and 421.5+/-31.2 g, respectively: p <0.0001 and p <0.001). Pulmonary morbidity was 5% in the later 39 patients. Survival was 90%, 80%, and 57% at 1, 2, and 5 years after surgery. CONCLUSION: Thoracoscopic radical esophagectomy has less morbidity and comparable survival to conventional surgery, after a moderate amount of experience. Mini-thoracotomy is essential to perform the procedure safely and effectively.
Adult↗
Usefulness of self-expandable metallic stent with an antireflux mechanism as a palliation for malignant strictures at the gastroesophageal junction.
BACKGROUND: Patients with unresectable malignant gastroesophageal strictures often are troubled with reflux esophagitis after stent placement. METHODS: A self-expandable metallic stent (SEMS) without an antireflux mechanism was placed in seven patients with unresectable malignant gastroesophageal strictures (group A), and SEMS with an antireflux mechanism was placed in five patients (group B). After we obtained monitoring systems, two patients in group A and all the patients in group B underwent measurement of bilirubin and pH in the esophagus using a 24-h bilirubin and pH monitor. RESULTS: The mean percentage of total time less than 0.14 for use of the bilirubin absorbance unit was 12.4% in group B and 64.0% in group A. The mean percentage of total time for a pH less than 4 was 2.9% in group B and 37.8% in group A. CONCLUSION: The placement of SEMS with the antireflux mechanism can be effective not only for palliation of gastroesophageal stricture, but also for prevention of reflux.
Adenocarcinoma↗
Differential screening-selected gene aberrative in neuroblastoma protein modulates inflammatory pain in the spinal dorsal horn.
Differential screening-selected gene aberrative in neuroblastoma (DAN) belongs to a novel gene family that includes the Xenopus head-inducing factor, Cerberus and the dorsalizing factor, Gremlin. It has been suggested that members of this family control diverse processes in growth, development and the cell cycle.Here, we demonstrate that the DAN protein is produced in the small neurons of the dorsal root ganglion and is transported to the nerve terminals in the spinal dorsal horn in adult rats. Furthermore, intrathecal injection of an antibody to the DAN protein suppressed inflammatory pain caused by the introduction of complete Freund's adjuvant or carrageenan into the rat hindpaw. The amount of mRNA for DAN in dorsal root ganglion neurons and of its expressed protein in the spinal dorsal horn were both increased in inflammatory models.Together, these data suggest that the DAN protein may be a novel neuromodulator in primary nociceptive nerve fibers.
Afferent Pathways↗
Prognostic factors after oesophagectomy and extended lymphadenectomy for squamous oesophageal cancer.
BACKGROUND: The prognosis of patients without nodal metastasis of oesophageal cancer is generally good, but recurrence develops in some cases. METHODS: Data on 88 consecutive patients with squamous oesophageal cancer who underwent three-field lymph node dissection from 1986 to September 1998 and who had no evidence of nodal disease were reviewed retrospectively. Disease status was based on histological examination of the section of each node with the largest surface area, stained with haematoxylin and eosin. RESULTS: The 3- and 5-year survival rates of patients without lymph node metastasis were 85 and 81 per cent respectively, better than in patients with metastasis. Twelve patients died from recurrence. Recurrence was haematogenous in nine patients and locoregional in three. Survival was worse in men, for patients with lesions located in the upper thoracic oesophagus, and in those with lymphatic or blood vessel invasion. Only the presence of lymphatic invasion correlated with survival on multivariate analysis (P = 0.04). CONCLUSION: Although survival was generally good in patients without nodal metastasis from oesophageal cancer following three-field lymph node dissection, patients with lymphatic invasion remained at risk for haematogenous dissemination.
Adult↗
Self-expandable metallic stents with an anti-reflux mechanism for malignant strictures of gastroesophageal junction.
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Duodenogastric Reflux↗
Functional characterization of naturally occurring mutants (P405R and P425L) of p73alpha and p73beta found in neuroblastoma and lung cancer.
The novel candidate tumor suppressor p73, a structural and functional homolog of p53, activates various p53 responsive promoters and induces tumor cell apoptosis. Although p73 is infrequently mutated in human cancers, we have previously found two types of p73 mutation with amino acid substitution (P405R and P425L) in primary neuroblastoma and lung cancer. Here we report generations of the p73 mutants with either P405R or P425L substitution and functional analysis of these naturally occurring mutants. Indirect immunofluorescence staining revealed that nuclear accumulation of p73alpha or p73beta was not affected by these mutations. The P425L substitution reduced the ability of p73alpha to transactivate various p53 responsive promoters (p21(Waf1), Mdm2, and Bax). Moreover, this down-regulation was correlated with the reduced capability of p73alpha(P425L) to suppress cell growth in p53-deficient SAOS-2 cells. In contrast, p73beta(P425L) was as effective as wild-type p73beta in transactivation and growth inhibition. On the other hand, the P405R substitution had no significant effect on both the transcriptional activity and the growth-suppressive ability of p73alpha or p73beta. These results suggested that, at least, one of the naturally occurring p73 mutants, p73alpha(P425L), was a functionally defective mutant of p73.
Amino Acid Substitution↗
Retinoic acid-induced apoptosis of the CHP134 neuroblastoma cell line is associated with nuclear accumulation of p53 and is rescued by the GDNF/Ret signal.
BACKGROUND: Neuroblastoma (NBL) is one of the most common solid malignancies in childhood and is derived from the sympathetic precursor cells. Although p53, a tumor suppressor, has been reported to be rarely mutated in NBLs, it is sequestered abnormally in the cytoplasm of the NBL cell. The mechanism and functional role of the abnormal intracellular localization of p53 remain unclear. PROCEDURE: Here, we established an in vitro system of apoptosis model using a NBL cell line CHP134 which also showed a cytoplasmic sequestration of p53. The treatment of the cells with 1 or 5 microM all-trans retinoic acid (RA) induced moderate neurite outgrowth followed by massive death of CHP134 cells by days 5 to 6. RESULTS: TUNEL staining showed that the cell death was due to apoptosis. Immunofluorescent stain demonstrated that p53 was strongly positive in the nucleus on day 5, which was accompanied with induction of p21WAF1. In addition, expression of caspase-3 was also increased during the cell death. Intriguingly, the RA treatment induced expression of Ret tyrosine kinase receptor in CHP134 cells. CONCLUSIONS: The addition of ligands, glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN), inhibited apoptosis as well as nuclear accumulation of p53 in the cell. The present results suggest that the RA-induced apoptosis of NBL cells is associated with activation of both the caspase cascade and the p53-mediated pathway with its nuclear translocation. The neurotrophic signal through the GDNF-Ret system may prevent the neuronal cell death.
Active Transport, Cell Nucleus↗
Genetic analysis of p73 localized at chromosome 1p36.3 in primary neuroblastomas.
BACKGROUND: Human p73, a novel homolog of p53, has recently been cloned and mapped at chromosome 1p36.3, the locus for putative tumor suppressor gene(s) of neuroblastoma (NBL) and other cancers. p73, like p53, inhibits growth and induces apoptosis in neuroblastoma and osteosarcoma cell lines. PROCEDURE: To test the hypothesis that p73 is a NBL suppressor gene, we examined expression, allelo-typing, and mutation of the p73 gene in primary human neuroblastomas. Loss of heterozygosity (LOH) for p73 was performed in 272 primary NBLs using a CT repeat polymorphic marker, which we found in intron 9 of the p73 gene. RESULTS: p73 LOH was observed in 28 out of 151 (19%) informative cases. The high frequency of p73 LOH was significantly associated with sporadic neuroblastomas (P< 0.001), MYCN amplification (P< 0.001), and advanced stages (P< 0.05). Mutational analyses by PCR-SSCP (single strand conformation polymorphism) revealed two mis-sense mutations in 140 NBLs, one somatic and one germline. CONCLUSION: Thus, the present results have shown that mutation of p73 is infrequent in NBLs, although the p73 locus is frequently lost in advanced stage tumors. These suggest that p73 may not be a tumor suppressor in the classic Knudson manner.
Amino Acid Substitution↗