[Computer simulation as a tool to study complex phenomena of biology].
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Animals↗
Biomedical subjects
S Kondo
Publications and source records attributed to S Kondo.
Radical distal pancreatectomy with en bloc resection of the celiac artery, plexus, and ganglions for advanced cancer of the pancreatic body: a preliminary report on perfect pain relief.
OBJECTIVE: The purpose of this study was to report the effect of radical distal pancreatectomy with en bloc resection of the celiac artery, plexus, and ganglions for locally advanced cancer of the pancreatic body on intractable abdominal and/or back pain and to explore the histopathologic mechanism of this pain. PATIENTS: Five patients with pancreatic body cancer involving the celiac and/or common hepatic artery underwent this radical surgery intended to cure the cancer. DESIGN: A retrospective analysis was performed. MAIN OUTCOME MEASURES: Surgical magnitude, postoperative pain control, postoperative outcome, and histopathologic findings were studied. RESULTS: Arterial reconstruction, gastrointestinal reconstruction, and blood transfusions were unnecessary. The organ deficit was limited to the distal pancreas, spleen and left adrenal gland. There was no postoperative mortality. Postoperative complications occurred in four patients, who were successfully managed with medical treatment. This led to prolonged hospital stays. The intractable preoperative abdominal and/or back pain was completely relieved immediately after surgery in all patients. Perfect pain control has been maintained from surgery to the last follow-up. Histopathologic examination of the surgical specimens revealed cancer invasion of the celiac plexus in all patients. CONCLUSIONS: This operation offers not only disease radicality but also perfect pain relief. The survival benefit has not yet been fully defined.
Abdominal Pain↗
A case of primary leiomyosarcoma of the chest wall successfully resected under the video-assisted thoracoscopic approach.
We report a case of a 62-year-old woman with primary leiomyosarcoma of the chest wall which was successfully resected under the video-assisted thoracoscopic approach. The disease was found during the treatment for a malignant melanoma of the left heel. On the preoperative CT images, the lesion was suspected to be a metastasis of the malignant melanoma. The thoracoscopic surgery revealed that the tumor originated from the parietal pleura, and it was resected with a 5-mm margin of normal pleura. Histopathologically, the tumor was diagnosed as low-grade leiomyosarcoma. Since no residual tumor cells were proven in the resected margins histologically, further resection was not performed. At present, she is alive and well with no sign of recurrence of leiomyosarcoma two years and one month after operation. Thoracoscopic surgery is worth trying for accurate diagnosis of and effective treatment for a chest lesion without apparent invasion of the chest wall on the preoperative CT images.
Biopsy↗
Scope and limitations of chiral B-
A new chiral oxazaborolidine catalyst was prepared in situ from 3, 5-bis(trifluoromethyl)phenylboron dichloride and N-(p-toluenesulfonyl)-(S)-tryptophan. This catalyst is much more active than Corey's original catalyst for the Mukaiyama aldol reaction of aldehydes with silyl enol ethers. The observed syn selectivities and re-face attack of silyl enol ethers on carbonyl carbon of aldehydes imply that the extended-transition state model is applicable.
Journal Article↗
Double-labeled donor probe can enhance the signal of fluorescence resonance energy transfer (FRET) in detection of nucleic acid hybridization.
A set of fluorescently-labeled DNA probes that hybridize with the target RNA and produce fluorescence resonance energy transfer (FRET) signals can be utilized for the detection of specific RNA. We have developed probe sets to detect and discriminate single-strand RNA molecules of plant viral genome, and sought a method to improve the FRET signals to handle in vivo applications. Consequently, we found that a double-labeled donor probe labeled with Bodipy dye yielded a remarkable increase in fluorescence intensity compared to a single-labeled donor probe used in an ordinary FRET. This double-labeled donor system can be easily applied to improve various FRET probes since the dependence upon sequence and label position in enhancement is not as strict. Furthermore this method could be applied to other nucleic acid substances, such as oligo RNA and phosphorothioate oligonucleotides (S-oligos) to enhance FRET signal. Although the double-labeled donor probes labeled with a variety of fluorophores had unexpected properties (strange UV-visible absorption spectra, decrease of intensity and decay of donor fluorescence) compared with single-labeled ones, they had no relation to FRET enhancement. This signal amplification mechanism cannot be explained simply based on our current results and knowledge of FRET. Yet it is possible to utilize this double-labeled donor system in various applications of FRET as a simple signal-enhancement method.
DNA Probes↗
Ab initio study of reactions between halogen atoms and various fuel molecules by Gaussian-2 theory.
Ab initio calculations by using Gaussian-2 theory have been carried out for the reactions between halogen atoms and various fuel molecules, i.e. fluorine, chlorine, and bromine atoms vs. hydrogen, methane, ethane, ethylene, acetylene, ammonia, silane, dichlorosilane and phosphine. The activation energy for the reaction between a halogen atom and a fuel molecule seems to indicate whether the reaction between the fuel gas and the corresponding halogen gas occurs spontaneously when they are brought into contact to each other at room temperature.
Explosions↗
Characterization of a mouse ctgf 3'-UTR segment that mediates repressive regulation of gene expression.
We isolated a small segment of the 3'-untranslated region (3'-UTR) in the mouse connective tissue growth factor (ctgf/fisp12) gene and evaluated its functionality. Comparison of the nucleotide sequences of human and mouse ctgf 3'-UTRs revealed a conserved small segment of 91 bases. The corresponding segments of the 3'-UTRs shared as much as 82.4% homology, whereas the overall homology between the 3'-UTRs was 71.8%. To study the functionality of the conserved segment, the corresponding region of mouse ctgf cDNA was amplified from NIH3T3 cells. When it was fused downstream of a marker gene, it showed remarkable repressive effects on gene expression. The repressive effect of the sense form was more prominent than that of the antisense form. Computer analyses of these sequence predicted stable secondary structures, suggesting that they act at the RNA level. The predicted structures of the sense and antisense forms appeared to be slightly different, which is consistent with the difference in repressive function. These findings defined the conserved small element in the mouse ctgf gene as a potent negative regulator of gene expression, which may act at a posttranscriptional level.
3' Untranslated Regions↗
Identification of an RNA element that confers post-transcriptional repression of connective tissue growth factor/hypertrophic chondrocyte specific 24 (ctgf/hcs24) gene: similarities to retroviral RNA-protein interactions.
The repressive effect of the 3'-untranslated region (3'-UTR) in human connective tissue growth factor/ hypertrophic chondrocyte specific 24 (ctgf/hcs24) mRNA on gene expression had been demonstrated in our previous study. Here, we identified a minimal RNA element in the 3'-UTR, which acts as a cis-acting element of structure-anchored repression (CAESAR). Deletion analyses of the 3'-UTR led us to minimize the element of 84 bases at the junction of the coding region and the 3'-UTR. The minimized RNA segment is predicted, and actually capable of forming a stable secondary structure in vitro. Mutational analyses disclosed a significant relationship between the predicted structure and repressive effect. The utility of CAESAR as a post-transcriptional regulatory element was represented by the fact that steady-state mRNA levels were not affected by CAESAR linked in cis, while protein levels from such a chimeric gene were markedly reduced. Of note, the CAESAR sequence exerted no effect, when it was placed upstream of the promoter. Finally, RNA gel electromobility-shift analyses demonstrated a nuclear factor that interacts with the folded CAESAR. Taken together, it was uncovered that CAESAR of ctgf is a novel post-transcriptional structured RNA regulatory element, probably acting through direct interactions with a nuclear factor as observed in retroviral RNA elements with certain proteins.
3' Untranslated Regions↗
Mutations of the bak gene in human gastric and colorectal cancers.
The Bcl-2 homologue Bak is a potent inducer of apoptosis. We performed PCR-based single-strand conformational polymorphism and sequencing analysis of the entire coding region of the bak gene (exons 2-6) in 24 primary gastric cancers (6 early-stage and 18 advanced-stage cancers) and 20 primary colorectal cancers (6 early-stage and 14 advanced-stage cancers). The data herein demonstrate, for the first time, the mutation of the bak gene in gastric and colorectal cancers. Missense bak gene mutations were observed in 3 of 24 (12.5%) gastric cancers and 2 of 20 (10.0%) colorectal cancers. Sequence alterations without amino acid alteration were observed 1 of 24 (4.2%) gastric cancers and 2 of 20 (10.0%) colorectal cancers. Mutations in the bak gene were observed only in advanced-stage gastrointestinal cancers but not in early-stage cancers. Our observations suggest that mutations in this gene predispose bearers to the development of gastrointestinal malignancies in at least a subset of the cases.
Colorectal Neoplasms↗
2-5A antisense telomerase RNA therapy for intracranial malignant gliomas.
Malignant gliomas are the most common intracranial tumors and are considered incurable. Therefore, exploration of novel therapeutic modalities is essential. Telomerase is a ribonucleoprotein enzyme that is detected in the vast majority of malignant gliomas but not in normal brain tissues. We, therefore, hypothesized that telomerase inhibition could be a very promising approach for the targeted therapy of malignant gliomas. Thus, 2-5A (5'-phosphorylated 2'-5'-linked oligoadenylate)-linked antisense against human telomerase RNA component (2-5A-anti-hTER) was investigated for its antitumor effect on an intracranial malignant glioma model. 2-5A is a mediator of one pathway of IFN actions by activating RNase L, resulting in RNA degradation. By linking 2-5A to antisense, RNase L degrades the targeted RNA specifically and effectively. Prior to the experiments using intracranial tumor models in nude mice, we modified the in vitro and in vivo treatment modality of 2-5A-anti-hTER using a cationic liposome to enhance the effect of 2-5A-anti-hTER. Here we demonstrate that 2-5A-anti-hTER complexed with a cationic liposome reduced the viability of five malignant glioma cell lines to 20-43% within 4 days but did not influence the viability of cultured astrocytes lacking telomerase. Furthermore, treatment of intracranial malignant gliomas in nude mice with 2-5A-anti-hTER was therapeutically effective compared with the control (P < 0.01). These findings clearly suggest the therapeutic potentiality of 2-5A-anti-hTER as a novel approach for the treatment of intracranial malignant gliomas.
Adenine Nucleotides↗
LiV2O4 spinel as a heavy-mass fermi liquid: anomalous transport and role of geometrical frustration
Transport and specific heat measurements on hydrothermally grown single crystals reveal the formation of a heavy-mass Fermi liquid in the LiV2O4 spinel, below a coherence temperature of T* = 20-30 K. A few observations which illustrate the uniqueness of this spinel are discussed in connection with the origin of the heavy mass, such as the anomalous absence of resistivity saturation above T* and the close proximity to a spin glass phase where the influence of the magnetic frustration is evident.
Journal Article↗
A novel telomerase-specific gene therapy: gene transfer of caspase-8 utilizing the human telomerase catalytic subunit gene promoter.
Apoptosis is a genetically encoded cell death process and is a pathway that may be disrupted in tumor cells. Therefore, therapies that restore the ability to undergo apoptosis are promising for the treatment of tumor cells. We have demonstrated that the transfer of apoptosis-inducible genes inhibits the growth of tumors in vitro and in vivo through induction of apoptosis. However, to restrict induction of apoptosis to tumor cells, we need to explore a tumor-specific expression system of these genes. In the present study, we developed the telomerase-specific transfer system of apoptosis-inducible genes, utilizing the promoter of the human telomerase catalytic subunit (hTERT) gene. Approximately 90% of tumors have telomerase activity whereas most normal cells do not express the activity. These observations indicate that telomerase is a particularly attractive target for the tumor-specific expression system of vectors. We demonstrate here that by using the hTERT promoter-driven caspase-8 expression vector (hTERT/caspase-8), apoptosis is restricted to telomerase-positive tumor cells of wide range, and is not seen in normal fibroblast cells without telomerase activity. Furthermore, treatment of subcutaneous tumors in nude mice with the hTERT/caspase-8 construct inhibited tumor growth significantly because of induction of apoptosis (p < 0.01). The telomerase-specific expression of apoptosis-inducible genes afforded by the hTERT promoter, therefore, may be a novel and promising targeting approach for the treatment of tumors with telomerase activity.
Animals↗
Real-time monitoring of in vitro transcriptional RNA synthesis using fluorescence resonance energy transfer.
We have developed a novel method for real-time monitoring of RNA synthesis in in vitro transcription reactions using fluorescence resonance energy transfer (FRET). Two 15mer DNAs, either of which was labeled with Bodipy493/503 as a donor or Cy5 as an acceptor, were prepared. When the two fluorescent DNAs hybridized to adjacent locations on Xenopus: elongation factor 1-alpha (xelf1-alpha) RNA, the distance between the two fluorophores became very close, causing FRET to occur and resulting in changes in fluorescence spectra. A high accessibility 30mer site of xelf1-alpha RNA was found and excess amounts of a pair of donor and acceptor DNA probes that were complementary to the site were added to the in vitro transcription reaction solution. Changes in fluorescence spectra were observed in response to progression of xelf1-alpha RNA synthesis that showed that the fluorescent probes hybridized to the synthesized RNA. Furthermore, when probes hybridizing to the synthesized xelf1-alpha RNA with less efficiency were used to monitor the reaction, spectral changes in response to RNA synthesis were also observed. This result suggests that the probes hybridized to synthesizing RNA molecules before they folded to form secondary structure and that there is no need to select sites on the RNA for the probes, which is required for probes hybridizing to folded RNA molecules.
Animals↗
Prevention of rat cerebral aneurysm formation by inhibition of nitric oxide synthase.
BACKGROUND: Cerebral saccular aneurysm is a major cause of subarachnoid hemorrhage, one of the cerebrovascular diseases with the highest mortality. The mechanisms underlying the development of aneurysms, however, still remain unclear. We have made a series of reports on an animal model of experimentally induced cerebral aneurysms that resemble human cerebral aneurysms in their location and morphology, suggesting that the arterial wall degeneration associated with aneurysm formation develops near the apex of arterial bifurcation as a result of an increase in wall shear stress. Using the animal model and human specimens, we examined the role of nitric oxide (NO) in the degenerative changes and cerebral aneurysm formation. METHODS AND RESULTS: Inducible NO synthase (iNOS) was immunohistochemically located at the orifice of human and rat aneurysms. Nitrotyrosine distribution was also seen in the human aneurysm. Although no iNOS immunostaining was found in normal arteries, iNOS immunoreactivity was observed in parallel with the development of early aneurysmal changes in rats. In contrast, during the early development of aneurysm, endothelial NOS immunostaining in the endothelium was weakened compared with that in the control arteries. An NOS inhibitor, aminoguanidine, attenuated both early aneurysmal changes and the incidence of induced aneurysms. A defibrinogenic agent, batroxobin, which may diminish shear stress by reduction of blood viscosity, prevented iNOS induction as well as early aneurysmal changes. CONCLUSIONS: The evidence suggests that NO, particularly that derived from iNOS, is a key requirement for the development of cerebral aneurysm. The iNOS induction may be caused by an increase in shear stress near the apex.
Animals↗
Generation of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, in picrotoxinin-administered rat brain.
The levels of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, and other molecular species of monoacylglycerols in rat brain were examined. In this study, we sacrificed the animals in liquid nitrogen to minimize postmortem changes. We found that rat brain contains 0.23 nmol/g tissue of 2-arachidonoylglycerol, which accounts for 10.5% of the total monoacylglycerol present in this tissue. We next investigated the level of 2-arachidonoylglycerol after in vivo stimulation with picrotoxinin. We found that the level of 2-arachidonoylglycerol was elevated markedly in picrotoxinin-administered rat brain (4- to 6-fold over the control level). Changes in the levels of other molecular species were relatively small or negligible. Several cannabimimetic molecules as well as Delta(9)-tetrahydrocannabinol are known to depress neurotransmission and to exert anticonvulsant activities; endogenous 2-arachidonoylglycerol produced during neural excitation may play a regulatory role in calming the enhanced synaptic transmission.
Animals↗
Treatment of prostate cancer in vitro and in vivo with 2-5A-anti-telomerase RNA component.
Prostate cancer is the most common malignancy of elderly men in the United States. Since there is no curative treatment for advanced prostate cancer, exploration of novel modalities of treatment is essential. Telomerase, a ribonucleoprotein, is detected in the vast majority of prostate cancer, but not in normal or benign prostatic hyperplasia tissues. Thus, telomerase is expected to be a very strong candidate for targeted therapy of prostate cancer. In this study, we synthesized a 19-mer antisense oligonucleotide against the RNA component of human telomerase (hTR) linked to a 2-5A molecule (2-5A-anti-hTR) and examined its cytotoxic effect on prostate cancer cells. The 2-5A antisense strategy relies on the recruitment and activation of RNase L at the site of targeted RNA sequence. We here show that treatment with 2-5A-anti-hTR in the presence of a cationic liposome reduced cell viability of tumor cell lines tested to 9-18% within 6 days. In contrast, normal fibroblast cells were resistant to the treatment. Its effect was mainly due to induction of apoptosis by activated caspase family members. Furthermore, treatment of subcutaneous tumors in nude mice with 2-5A-anti-hTR significantly suppressed the tumor growth through induction of apoptosis (P<0.001). The treatment with 2-5A-anti-hTR may be a promising strategy for the treatment modality of prostate cancer with telomerase activity.
Animals↗
Cervical myelopathy caused by C3-C4 spondylosis in elderly patients: a radiographic analysis of pathogenesis.
STUDY DESIGN: A radiographic analysis of elderly patients with cervical spondylotic myelopathy, particularly those with involvement of the C3-C4 level. OBJECTIVES: To elucidate the potential contributors to the higher incidence of pathology at C3-C4 in the elderly. SUMMARY OF BACKGROUND DATA: In this study, the elder patients showed a greater predilection for involvement of the C3-C4 lesion compared with their younger counterparts. No previous study has addressed C3-C4 pathology in elderly patients. METHODS: This study included 18 patients, 10 men and 8 women, with cervical spondylotic myelopathy caused by C3-C4 disorders (group I). For the purpose of comparison, 18 younger patients (less than 50 years of age) with myelopathy (group II) and 30 volunteers over the age of 65 (group III) were also investigated. Mean age at admission was 73.5 years for group I, 42.4 years for group II, and 73.4 years for group III. Radiographic analysis, using static and dynamic radiographs, was performed to evaluate the morphologic features. RESULTS: The mean spinal canal diameter for groups I and II was significantly smaller than that for group III. Group I exhibited greater C2-C7 lordosis. The aged population, group I and group III, showed greater C3-C4 angulation associated with C4 forward inclination in neutral standing position as compared with younger patients. Regarding dynamic factors, group I showed the largest segmental motion at C3-C4, and, conversely, the smallest mobility at the lower segments, with significant differences. CONCLUSIONS: Using radiographic analysis, morphologic features that predispose patients to disorders of the C3-C4 motion segment were evaluated. These features included 1) greater C3-C4 angulation associated with age-related postural change and 2) hypermobility at the C3-C4 segment compensating for decreased mobility at the lower segments.
Adult↗
Anti-sense oligonucleotide of p21(waf1/cip1) prevents interleukin 4-mediated elevation of p27(kip1) in low grade astrocytoma cells.
Elevation of the cyclin-dependent kinase (cdk) inhibitor, p27(kip1) is necessary for Interleukin (IL)-4-mediated growth arrest of human low grade astrocytoma (RTLGA) cells and occurs at 24 h of treatment. Pathways involved in IL4 alteration of p27(kip1) are unknown, however. Here we investigated whether other cdk inhibitors contributed to the actions of IL-4 on RTLGA cells. By 12 h of IL-4 treatment, both cdk4 and cdk2 kinase activities against the retinoblastoma protein (pRb) were reduced and nuclear entry of pRb was prohibited. Twelve-hour cdk complexes contained elevated p21(waf1/cip1) but not p27(kip1), p15(ink4B) or p16(ink4A). IL-4 increased p21(waf1/cip1) but not p27(kip1) mRNA levels, and stimulated luciferase activity of a p21(waf1/cip1) promoter-luciferase reporter. In p53-mutant WITG3 cells, IL-4 did not alter p21(waf1/cip1) mRNA and promoter-luciferase activity or p27(kipl) protein, suggesting a need for functional p53. STAT6 phosphorylation by IL-4, however, occurred in both p53-mutant WITG3 and p53-functional RTLGA cells. Pre-treatment of RTLGA with anti-sense but not missense p21(waf1/cip1) oligonucleotide prior to IL-4: (a) restored cdk activities; (b) reduced cdk4-associated p21(waf1/cip1) levels; (c) prevented p27(kipl) elevation; and (d) reversed growth arrest. These results are the first to suggest that p21(waf1/cip1) is essential for IL-4-mediated elevation of p27(kip) and growth arrest of astrocytoma cells.
Astrocytoma↗