High-dose ethosuximide for epilepsy in Angelman syndrome: implication of GABA(A) receptor subunit.
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Angelman Syndrome↗
Biomedical subjects
M Ueno
Publications and source records attributed to M Ueno.
Endomucin is expressed in embryonic dorsal aorta and is able to inhibit cell adhesion.
Recent studies have suggested the existence of progenitors common to hematopoietic and endothelial cells, called hemangioblasts, in, for instance, embryonic dorsal aorta. To identify a membrane-bound or secretory molecule regulating early hematopoiesis, we screened a cDNA library from dorsal aortas of embryonic day (E) 10.5 mice by a signal sequence trap method and obtained a clone encoding a sialoprotein, endomucin-1. Immunohistochemistry revealed that the endomucin-1 transcript was specifically expressed in the endothelial cells of dorsal aorta of E10.5 mouse embryo. Overexpression of endomucin-1 strongly inhibited adhesion and aggregation of cells, including cultured endothelial cells from E10.5 dorsal aorta. These data suggest that endomucin-1 may play a role in detachment of hematopoietic cells from endothelium during early hematopoiesis.
Amino Acid Sequence↗
Annexin II overexpression correlates with stromal tenascin-C overexpression: a prognostic marker in colorectal carcinoma.
BACKGROUND: Overexpression of annexin II, a calcium-dependent phospholipid-binding protein, has been reported in various carcinomas. One of its ligands is tenascin-C, an extracellular matrix glycoprotein with predominantly antiadhesive qualities that also has been reported to be a prognostic marker for several carcinomas. In the current study, the authors investigated the correlation between the overexpression of annexin II and tenascin-C in colorectal carcinoma. METHODS: Western blot analysis of annexin II expression was examined in four human colorectal carcinoma cell lines. Using immunohistochemical methods, the authors also examined expression of annexin II and tenascin-C in 105 primary colorectal carcinoma cases. RESULTS: Although annexin II was expressed in human colon carcinoma cell lines, there was no apparent correlation between its expression level and the metastatic potential of these cell lines. The authors observed overexpression of annexin II and tenascin-C proteins in 29.5% and 49.5%, respectively, of colorectal carcinoma cases. Overexpression of annexin II was found to be correlated significantly with histologic type, tumor size, depth of invasion, and pTNM stage, whereas tenascin-C overexpression was noted to be correlated significantly with histologic type, depth of invasion, lymphatic invasion, venous invasion, lymph node metastasis, and pTNM stage. Expression of annexin II was shown to be correlated significantly with that of tenascin-C. Multivariate analysis demonstrated that annexin II and tenascin-C cooverexpression was an independent factor of poor prognosis in patients with colorectal carcinoma. CONCLUSIONS: The data from the current study suggest that both annexin II and tenascin-C are overexpressed in advanced colorectal carcinoma and that they may be related to the progression and metastatic spread of colorectal carcinoma.
Annexin A2↗
A novel inhibitor of ceramide trafficking from the endoplasmic reticulum to the site of sphingomyelin synthesis.
Ceramide produced at the endoplasmic reticulum (ER) is transported to the lumen of the Golgi apparatus for conversion to sphingomyelin (SM). N-(3-Hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide (HPA-12) is a novel analog of ceramide. Metabolic labeling experiments showed that HPA-12 inhibits conversion of ceramide to SM, but not to glucosylceramide, in Chinese hamster ovary cells. Cultivation of cells with HPA-12 significantly reduced the content of SM. HPA-12 did not inhibit the activity of SM synthase. The inhibition of SM formation by HPA-12 was abrogated when the Golgi apparatus was made to merge with the ER by brefeldin A. Moreover, HPA-12 inhibited redistribution of a fluorescent analog of ceramide, N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pentanoyl)-d-erythro-sphingosine (C(5)-DMB-Cer), from intracellular membranes to the Golgi region. Among four stereoisomers of the drug, (1R,3S)-HPA-12, [corrected] which resembles natural ceramide stereochemically, was found to be the most active, although (1R,3S)-HPA-12 [corrected] did not affect ER-to-Golgi trafficking of protein. Interestingly, (1R,3S)-HPA-12 [corrected] inhibited conversion of ceramide to SM little in mutant cells defective in an ATP- and cytosol-dependent pathway of ceramide transport. These results indicated that (1R,3S)-HPA-12 [corrected] inhibits ceramide trafficking from the ER to the site of SM synthesis, possibly due to an antagonistic interaction with a ceramide-recognizing factor(s) involved in the ATP- and cytosol-dependent pathway.
Amides↗
Facile and stereoselective access to nonracemic tricyclic cyclobutanes by asymmetric intramolecular Michael-aldol reaction: thermodynamic equilibrium and activation by iodonium ion.
Intramolecular Michael-aldol reactions of (-)-phenylmenthyl enoates tethered to cycloalkanone affords tricyclic cyclobutanes with high degrees of diastereochemical control. Kinetic and thermodynamic studies revealed that the Michael-aldol reaction is reversible under conditions in which trimethylsilyl iodide is used in the presence of hexamethyldisilazane at ambient temperature. Different levels of diastereoselectivity are observed when this cyclization process is carried out under kinetic vs thermodynamic conditions. Finally, an influence of added iodonium donors on the reaction rate has been noted.
Journal Article↗
Structural characterization of heparan sulfate and chondroitin sulfate of syndecan-1 purified from normal murine mammary gland epithelial cells. Common phosphorylation of xylose and differential sulfation of galactose in the protein linkage region tetrasaccharide sequence.
Syndecan-1, present on the surfaces of normal murine mammary gland epithelial cells, is a transmembrane hybrid proteoglycan, which bears glycosaminoglycan (GAG) side chains of heparan sulfate (HS) and chondroitin sulfate (CS). Purified syndecan-1 ectodomains were analyzed for disaccharide composition and the GAG-protein linkage region after digestion with bacterial lyases. The HS chains contained predominantly a nonsulfated unit with smaller proportions of two monosulfated, two disulfated, and a trisulfated unit, whereas CS chains were demonstrated for the first time to bear GlcUA-GalNAc(4-O-sulfate) as a major component as well as GlcUA-GalNAc, GlcUA-GalNAc(6-O-sulfate), and an E disaccharide unit GlcUA-GalNAc(4,6-O-disulfate) as minor yet appreciable components. Two kinds of linkage region tetrasaccharides, GlcUA-Gal-Gal-Xyl and GlcUA-Gal-Gal-Xyl(2-O-phosphate), were found for the HS chains in a molar ratio of 55:45. In marked contrast, an additional sulfated tetrasaccharide, GlcUA-Gal(4-O-sulfate)-Gal-Xyl, was demonstrated only for the CS chains, and the unmodified phosphorylated and sulfated components were present at a molar ratio of 55:26:19. The present study thus provided conclusive evidence for the hypothesis that 4-O-sulfation of Gal is peculiar to CS chains in contrast to the phosphorylation of Xyl, which is common to both HS and CS chains. These modifications may be required for biosynthetic maturation of the linkage region tetrasaccharide sequence, which is a prerequisite for creating the repeating disaccharide region of GAG chains and/or biosynthetic selective chain assembly of CS and HS chains.
Animals↗
Delayed functional recovery by vincristine after sciatic nerve crush injury: a mouse model of vincristine neurotoxicity.
Neuropathy is the dose-limiting side effect of vincristine (VCR) in cancer therapy. However, no simple experimental model has yet been reported. Here, we present a simple experimental model of VCR neurotoxicity using a mouse sciatic nerve crush model, which allows evaluation within a few weeks. VCR administered intravenously once on the day after the crush lesion caused a dose-dependent delay of the recovery of motor and sensory functions. The minimal dose required to cause the delay was 0.25 mg/kg, which corresponded to five times the usual clinical dose for man and was far less than the reported doses required to cause functional impairment in intact animals. The model would be useful not only for the development of new drugs but also for the estimation of the drug interactions in combination cancer therapy.
Animals↗
Ultrastructural and permeability features of microvessels in the periventricular area of senescence-accelerated mice (SAM).
Brain transfer of intravenously injected horseradish peroxidase (HRP) and the ultrastructural features of the vessels were examined in periventricular areas in senescence-accelerated mice (SAMP8), which show age-related deficits in learning and memory, and senescence-accelerated resistant mice (SAMR1), which do not show age-related deficits. In all mice examined with light microscopy, staining reaction for HRP was seen in the periventricular area adjacent to the medial side of the lateral ventricle. Electron microscopic examination in the periventricular area of young and old mice of both strains showed that the staining reaction for HRP appeared in the vesicular profiles of the endothelial cytoplasm, the cytoplasm of the perivascular cells, the basal lamina, and the adjoining extracellular spaces of the white matter, suggesting an incomplete blood-brain barrier (BBB) in the periventricular white matter. In addition, irregularly thickened endothelial cell cytoplasm, membranous inclusions within the basal lamina, and electron-dense endothelial cell cytoplasm were occasionally seen in aged SAMP8 mice. These findings were not observed in 3-month-old SAMP8 mice and 3- and 13-month-old SAMR1 mice. Perivascular collagen deposits were also frequently seen in aged SAMP8 mice. These findings indicate that the endothelial cells and pericytes in the periventricular white matter in aged SAMP8 mice have an ultrastructure with damaged BBB function. Intravascular substances can easily penetrate the periventricular white matter and the BBB of the vessels in the area can be deteriorated with aging in SAMP8 mice.
Aging↗
Microemulsion formed by alkyl polyglucoside and an alkyl glycerol ether with weakly charged films.
We have studied the effects on phase equilibria of a nonionic surfactant mixture-water-oil system when replacing small amount of surfactant molecules by ionic surfactant, sodium dodecyl sulfate (SDS). The nonionic surfactant system contains dodecyl-beta-D-maltoside (C(12)AG2) and iso-octyl glyceryl ether (i-C(8)GE) as cosurfactant, water and cyclohexane at constant water to oil ratio of 60/40 (w/w). Adding a small amount of SDS has large impact on the phase behavior. Clear liquid crystalline phase and upper microemulsion phase are added to the phase sequence at high i-C(8)GE/(C(12)AG2+i-C(8)GE) ratio. We also compare the phase equilibria of pure dodecyl maltoside system with polyglucosides mixture system.
Journal Article↗
Bcl-X expression in esophageal squamous cell carcinoma: association with tumor progression and prognosis.
BACKGROUND AND OBJECTIVES: Bcl-2 family proteins are regulators of programmed cell death and important in the development and progression of human various tumors. The role of these proteins in the development, progression and differentiation of esophageal squamous cell carcinoma (ESCC) is unclear. METHODS: We investigated the expression of Bcl-2, Bcl-X, and Bax using immunohistochemistry in 86 ESCCs, and scored the expression by the weighted score. RESULTS: Bcl-2 expression related to pT category (P=0.043) and histological grade (P = 0.001). Bcl-X expression related to pT category (P = 0.003), pN category (P = 0.041) and the number of positive nodes (P = 0.036), and had a tendency to relate to histological grade (P = 0.086). Bax expression had a tendency to relate to pN category (P = 0.081). The inverse relationship between Bcl-2 and Bcl-X expression was detected (P = 0.001), while the positive one between Bcl-X and Bax expression was detected (P = 0.014). Patients with low Bcl-X weighted score had a significantly longer survival compared with those with high Bcl-X weighted score. Multivariate analysis revealed Bcl-X expression as the independent prognostic factors (P = 0.022). CONCLUSION: These results imply that Bcl-2 family proteins, especially Bcl-X, may contribute to the progression in ESCC.
Adult↗
Double-injection FDG method to measure cerebral glucose metabolism twice in a single procedure.
UNLABELLED: [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) may be used to examine changes in cerebral glucose metabolism in two physiological conditions. We proposed and evaluated a double injection-single session FDG method with biological constraints for this purpose. METHODS: Simulated brain time-radioactivity curves (TACs) generated by using a plasma TAC from an actual study and physiological combinations of input values in a kinetic model were analyzed to evaluate the accuracy of the proposed method. The reproducibility of the estimated values obtained by this method was tested in five normal volunteers who were studied with a dynamic PET scan and two injections of FDG in a single session while fasting. RESULTS: The simulation study showed that the estimated values obtained by the proposed method agreed well with the input values. In the human study, plasma glucose levels were 5.3 +/- 0.2 and 5.0 +/- 0.2 mM in the first and second measurements, respectively. The difference between the plasma glucose measurements was small but statistically significant (p < 0.05). Although no systematic deviations were noted in K*1 or rCMRglc, there were small deviations in K* (less than 10%) and LC (less than 5%) with a statistical significance (p < 0.01). CONCLUSION: The deviation between the measurements in K* and LC seemed to relate to the difference in the plasma glucose level. The double-injection FDG method with biological constraints can be used to estimate rCMRglc and LC sequentially in a single PET scanning session.
Blood Glucose↗
Assessment of cerebral hemodynamics before and after revascularization in patients with occlusive cerebrovascular disease by means of quantitative IMP-SPECT with double-injection protocol.
UNLABELLED: The purpose of this study was to validate a double-injection (DI) method with N-isopropyl-[123I]p-iodoamphetamine (IMP) to measure regional cerebral blood flow (rCBF) twice in a single session of dynamic SPECT and to elucidate a possible role of this method to identify patients with occlusive disease of major cerebral arteries, who might benefit from cerebral revascularization procedures (CR). MATERIALS AND METHODS: Fourteen patients with occlusion or severe stenosis of the internal carotid or middle cerebral artery were studied before and after CR to assess hemodynamic changes after revascularization treatment. We quantitatively measured rCBF before and after acetazolamide (ACZ) challenge along with cerebrovascular reserve capacity (CVR) with two injections of IMP in a single session of dynamic SPECT scans (DI method). The reliability and reproducibility of the DI method were validated by means of a simulation study and in eight patients who were examined without ACZ challenge to measure baseline rCBF twice. RESULTS: The analysis of simulated noisy data with realistic noise levels showed that the errors of the estimates for the first and the second rCBF and for the increase in rCBF were 2.6%, 8.1% and 10.4%, respectively. In the 8 patients examined by the DI method to measure baseline rCBF twice, the mean and the SD of percentage differences between the two consecutive measurements in rCBF were -1.3% and 5.5%, respectively. Eight out of 14 patients with occlusive disease had at least one region with a CVR less than 10%. They showed a significant increase in resting rCBF after CR, not only in the ipsilateral hemisphere (from 26.1 +/- 6.4 to 33.4 +/- 4.7) but also in the contralateral one (from 28.3 +/- 7.0 to 34.7 +/- 4.7) with a recovery of the ipsilateral CVR from 9.3 +/- 17.2 to 41.2 +/- 20.1%. The remaining six patients with good-moderate CVR did not show an increase in rCBF after CR (from 28.0 +/- 2.7 to 28.3 +/- 3.4). The three of them with a moderate CVR (10-25%) before CR showed normalization of CVR after CR. CONCLUSION: Patients with decreased rCBF and reduced CVR benefited from CR in terms of an increase in rCBF and recovery of CVR. The quantitative double-injection IMP-SPECT has the ability to identify those patients who may benefit from CR.
Aged↗
Schizosaccharomyces pombe taf1+ is required for nitrogen starvation-induced sexual development and for entering the dormant GO state.
Environmental change, such as nutritional starvation, induces physiological and morphological alterations that enable fission yeast cells to survive. We isolated a novel gene, taf1+, required for the response to nitrogen starvation in the fission yeast Schizosaccharomyces pombe. taf1 disruptants could not mate upon nitrogen starvation, but could upon carbon starvation. taf1 disruptants had a defect in inducing stell+ expression under nitrogen starvation conditions. Furthermore, they lost viability quickly in nitrogen-depleted medium. Unlike wild-type cells, starved taf1-cells had nuclear chromatin that were flat and adhered to the cell periphery. These results indicate that tqf1+ is required for nitrogen starvation-induced sexual development and entering the dormant G0 state.
Amino Acid Sequence↗
Fission yeast tor1 functions in response to various stresses including nitrogen starvation, high osmolarity, and high temperature.
A target of rapamycin (TOR) protein is a protein kinase that exerts cellular signal transduction to regulate cell growth in response to extracellular nutrient conditions. In the Schizosaccharomyces pombe genome database, there are two genes encoding TOR-related proteins, but their functions have not been analyzed. Here we report that one of the genes, referred to as tor1+, is required for sexual development induced by nitrogen starvation. Ste11 is a key transcription factor for the initiation of sexual development. The expression of ste11+ is normally regulated in tor1- cells; and overexpression of ste11+ hardly rescues the defect in fertility in tor1-. Upon nitrogen starvation, tor1+ cells promote two rounds of the cell cycle to become arrested at the G1 phase before initiation of sexual development. The tor1- cells do not promote such a cell cycle, suggesting that Tor1 is necessary for the response to nitrogen starvation. The tor1- cells show no growth or very slow growth under various stress conditions, including external high pH, high concentrations of salts or sorbitol, and high temperature. These results suggest that Tor1 is necessary for any response to a wide range of stresses. The vegetative growth of tor1- cells is inhibited by rapamycin, although tor1+ cells are resistant to the drug. The tor1- cells are hypersensitive to fluphenazine and cyclosporin A, which specifically inhibit calmodulin and calcineurin, respectively.
Amino Acid Sequence↗
Antiplatelet therapy for a pregnant woman with a mechanical aortic valve: report of a case.
A 24-year-old woman, who had undergone an aortic valve replacement with a 21-mm St. Jude Medical mechanical aortic valve, wished to have a child. She visited our department because she was aware of the risks associated with pregnancy while undergoing anticoagulant therapy using warfarin potassium. The patient opted to undergo the recommended alternative method involving the use of antiplatelet agents (dipyridamole, ticlopidine, and aspirin) in place of warfarin potassium. Antiplatelet agents were administered while regularly monitoring the platelet aggregability along with the coagulation and fibrinolytic activity. At the 36th week of gestation, antiplatelet agents were discontinued and instead were followed by continuous heparin infusion. A healthy baby was delivered by cesarean section without any complications at the 38th week. Antithrombotic therapy using antiplatelet agents appears to be an effective option for preventing serious problems for pregnant women with a mechanical heart valve.
Adult↗
alpha-1-Antichymotrypsin gene A1252G variant (ACT Isehara-1) is associated with a lacunar type of ischemic cerebrovascular disease.
alpha-1-Antichymotrypsin (ACT) is a plasma protease inhibitor belonging to the serpine superfamily; it has many functions. and thus qualitative change in ACT is likely to result in specific diseases. We previously reported a variant AACT (ACT Isehara-1, Met389Val, A1252G) in patients with ischemic cerebrovascular disease (CVD). The present study was designed to examine the association of the variant with ischemic CVD, in 87 patients and 397 age-matched controls. We found that the frequency of the A1252G variant (ACT Isehara-1) was higher in the group with ischemic CVD than in the control group (P = 0.0397), which appeared to be independent of known risk factors. We subdivided the CVD group into lacunar and atherothrombotic subgroups. Further analysis by subtype of ischemic CVD showed an association of ACT Isehara-1 with lacunar infarction (P = 0.0036). These results suggest that ACT lsehara-1 is a new genetic risk factor for ischemic CVD, especially lacunar-type infarction, in Japan.
Adult↗
Anatomical major resection versus nonanatomical limited resection for liver metastases from colorectal carcinoma.
BACKGROUND: Although systematic anatomical hepatic resection has been reported to improve patient survival in hepatocellular carcinoma, principles of hepatectomy procedure have not been clearly demonstrated in secondary hepatic malignancy. The purpose of the present study was to determine whether selection of surgical procedures for liver resection is associated with the pattern of tumor recurrence or patient survival. METHODS: During the period of 1980 through 1999, 174 cases underwent liver resection for hepatic metastasis from colorectal cancer. Of these, 96 underwent systematic anatomical major hepatic resection (anatomical group) and 78 cases underwent nonanatomical limited resection (nonanatomical group). Subset analysis of 115 patients with unilobar single or double tumors was also conducted. RESULTS: The overall 5-year survival rate of 174 patients was 43.2%. Univariate analysis did not show a significant difference in patient survival according to surgical procedure (anatomical group versus nonanatomical group). Operative morbidity and mortality rates were slightly higher in anatomical group. From the subset analysis in unilobar single or double tumors, anatomical major hepatectomy was unnecessary in 80.4% of the cases if the tumors were resectable by nonanatomical limited resection. Ninety percent of the ipsilateral recurrence, which could have been avoided if the first operation was anatomical hemihepatectomy, could undergo second hepatectomy with 5-year survival rate of 58.3%. CONCLUSIONS: There was not a significant difference in patient survival according to surgical procedure. To minimize surgical stress and operative risk, nonanatomical limited liver resection should be a basic surgical procedure for colorectal metastases.
Colorectal Neoplasms↗
Effects of aging and blood pressure on the structure of the thoracic aorta in SAM mice: a model of age-associated degenerative vascular changes.
The effects of aging and blood pressure on the structural alterations of the thoracic aorta were examined using male, accelerated senescence-prone, short-lived SAMP11 mice or accelerated senescence-resistant, long-lived SAMR1 mice. The aortic wall thickness increased significantly by 34% in SAMR1 and by 62% in SAMP11 with advanced age. We observed branching, breakage and disorganization of the elastic lamellae, an increase in thin collagen fibrils between the medial smooth muscle cells and hypertrophy but a significant decrease in the number of medial smooth muscle cells with aging in both strains. These alterations observed in SAMP11 occurred earlier and were more exaggerated with advanced age than in SAMR1. The aortic lumen dilated gradually in SAMR1, but narrowed significantly in SAMP11 with aging. The systolic blood pressure did not differ significantly among SAMP11s aged 3-9months, or among all ages of SAMR1. However, it was elevated in SAMP11 at the terminal stage of their life. Our results suggest that the aorta in SAMR1 might reflect the physiological process of aging, whereas SAMP11 showed earlier changes due to the senescence acceleration of the vascular cells, which were exaggerated by the elevated blood pressure.
Aging↗