Famotidine and acquired long QT syndrome.
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Electrocardiography↗
Biomedical subjects
T Endo
Publications and source records attributed to T Endo.
Microsequencing of glycans using 2-aminobenzamide and MALDI-TOF mass spectrometry: occurrence of unique linkage-dependent fragmentation.
2-Aminobenzamide-derivatized oligosaccharides were separated by three lectin column chromatographies and then subjected to matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) for structural characterization of the carbohydrates. The combination of sequential exoglycosidase digestion and MALDI-TOF MS greatly facilitates the monosaccharide sequencing and is more feasible than size-exclusion column chromatography in terms of the time consumed and the laboriousness of the procedure. By this strategy, microsequencing of 2-3 pmol of oligosaccharide derivatives could be achieved. Furthermore, spectra obtained by the post source decay (PSD) mode provide excellent sequence information. The relative intensities of metastable ions due to fragmentation at glycosidic linkages were different among linkage isomers of particular oligosaccharides. These results demonstrate that PSD analysis possesses significant potential for the estimation of glycosidic linkage in carbohydrate structures.
Carbohydrate Sequence↗
Amphidinolide T, novel 19-membered macrolide from marine dinoflagellate Amphidinium sp.
A novel 19-membered macrolide, amphidinolide T (1), has been isolated from a marine dinoflagellate Amphidinium sp., and the structure was elucidated on the basis of spectroscopic data. Relative stereochemistry at C-7, C-8, and C-10 was deduced from the NOESY correlations, while absolute configurations at C-2, C-13, C-14, and C-18 were assigned on the basis of NMR data of the MTPA esters of 1 and those of degradation products of 1.
Animals↗
Structural basis of presequence recognition by the mitochondrial protein import receptor Tom20.
Most mitochondrial proteins are synthesized in the cytosol as precursor proteins with a cleavable N-terminal presequence and are imported into mitochondria. We report here the NMR structure of a general import receptor, rat Tom20, in a complex with a presequence peptide derived from rat aldehyde dehydrogenase. The cytosolic domain of Tom20 forms an all alpha-helical structure with a groove to accommodate the presequence peptide. The bound presequence forms an amphiphilic helical structure with hydrophobic leucines aligned on one side to interact with a hydrophobic patch in the Tom20 groove. Although the positive charges of the presequence are essential for import ability, presequence binding to Tom20 is mediated mainly by hydrophobic rather than ionic interactions.
Aldehyde Dehydrogenase↗
Alterations with age of the neurons expressing P(0) in the rat spinal cord.
In mammals, P(0) expression is thought to be restricted to the peripheral nervous system (PNS), whereas in some other vertebrates it is expressed not only in the PNS but also in the central nervous system (CNS). Previously we reported that P(0) is expressed in the rat spinal cord and that its glycosylation state changes with age. In this report, we determine, by immunohistochemical and immunocytochemical analyses, that the neurons in the spinal cord express P(0). Furthermore, our data show that the number of neurons expressing P(0) decreases and their sizes become smaller with age. Thus, the results emphasize the importance of neurons expressing P(0) in the spinal cord in the formation and maintenance of the neural network.
Aging↗
Mesenchyme with fgf-10 expression is responsible for regenerative capacity in Xenopus limb buds.
A young tadpole of an anuran amphibian can completely regenerate an amputated limb, and it exhibits an ontogenetic decline in the ability to regenerate its limbs. However, whether mesenchymal or epidermal tissue is responsible for this decrease of the capacity remains unclear. Moreover, little is known about the molecular interactions between these two tissues during regeneration. The results of this study showed that fgf-10 expression in the limb mesenchymal cells clearly corresponds to the regenerative capacity and that fgf-10 and fgf-8 are synergistically reexpressed in regenerating blastemas. However, neither fgf-10 nor fgf-8 is reexpressed after amputation of a nonregenerative limb. Nevertheless, nonregenerative epidermal tissue can reexpress fgf-8 under the influence of regenerative mesenchyme, as was demonstrated by experiments using a recombinant limb composed of regenerative limb mesenchyme and nonregenerative limb epidermis. Taken together, our data demonstrate that the regenerative capacity depends on mesenchymal tissue and suggest that fgf-10 is likely to be involved in this capacity.
Amino Acid Sequence↗
Suppression of paraquat-induced wet dog shakes by nitric oxide synthase inhibitors in rats.
We have found that paraquat (PQ), a widely used herbicide, causes wet dog shakes (WDS), which involve the central opioid system, in rats. A non-selective nitric oxide (NO) synthase (NOS) inhibitor, N(omega)-nitro-L-arginine (L-NA), but not its less active enantiomer, N(omega)-nitro-D-arginine, decreased the PQ-induced WDS in a dose-related manner. A selective neuronal NOS inhibitor in vivo, 7-nitroindazole, also decreased the PQ-induced WDS. Although an opioid receptor antagonist, naloxone, reversed the suppressive effect of these NOS inhibitors on the PQ-induced WDS, L-arginine, an NO precursor, had no effect on it. These findings suggest that the suppression of the PQ-induced WDS by NOS inhibition is associated with the central opioid system and is insusceptible to exogenous L-arginine.
Animals↗
Afferents of cranial sensory ganglia pathfind to their target independent of the site of entry into the hindbrain.
In vertebrates, sensory neurons interconnect a variety of peripheral tissues and central targets, conveying sensory information from different types of sensory receptors to appropriate second-order neurons in the central nervous system (CNS). To explore the possibility that the different rhombomere environments where sensory neurons enter into the hindbrain affect the pathfinding capability of growth cones, we studied the development of the VIIIth ganglion afferent both in vivo and in vitro. We focused on the vestibular nerve because it is the only cranial nerve projecting to the cerebellum, allowing for ready identification from its pattern of projection. Embryonic rat brain was cut along the dorsal midline and, with the VIIIth and Vth ganglia still attached, flat mounted and visualized with antibodies specific for sensory ganglia. Axons reached the cerebellar primordium at embryonic day (E) 13, then splayed out towards the edges of the rhombic lip of rostral hindbrain. In vitro, the VIIIth ganglion showed development similar to that in vivo and innervated the cerebellum, an appropriate target, indicating that mechanisms for axon guidance and target recognition are preserved in vitro. When the VIIIth ganglion was transplanted to the position of the Vth ganglion, axons from the transplanted ganglion entered the cerebellar primordium with a trajectory characteristic of the VIIIth nerve. These results indicate that the central projection pattern of the VIIIth nerve is not affected by the environment of nerve entry into the brainstem, suggesting that axons of sensory cranial ganglion intrinsically possess the capacity to find their target correctly.
Afferent Pathways↗
Antibody studies of factor VIII inhibitor in a case with Waldenström's macroglobulinemia.
We report a case of Waldenström's macroglobulinemia with prominent bleeding tendency; laboratory investigation revealed an elevated activated partial thromboplastin time. Further laboratory evaluation showed circulating factor VIII anticoagulant, deemed polyclonal IgG, with a titer of 700 Bethesda Units/ml. The factor VIII inactivation kinetics of the patient plasma were identical to those of a type II inhibitor, and the inhibitor was found to recognize the A2 domain of the factor VIII heavy chain. Apparently, paraprotein is not always the cause of reduced activity of coagulation factors in neoplastic dysproteinemias.
Aged↗
Functional association between nicotinic acetylcholine receptor and sarcomeric proteins via actin and desmin filaments.
By affinity chromatography utilizing alpha-cobrotoxin from digitonin-solubilized fractions of rabbit skeletal muscle, we found that many proteins are associated with the nicotinic acetylcholine receptor (AChR). In addition to the proteins we previously reported to bind to AChR (including dystrophin-dystrophin-associated protein (DAP) complex, utrophin, rapsyn, and actin; Mitsui et al. [1996] Biochem. Biophys. Res. Commun.224:802-807), alpha-actinin, desmin, myosin, tropomyosin, troponin T, and titin are also identified to be associated with AChR. Alkaline treatment or Triton X-100 solubilization released dystrophin-DAP complex, utrophin, and rapsyn from the AChR fraction, while actin and desmin remained associated. These findings demonstrate that AChR is supported primarily by a submembranous organization of actin and desmin filaments, and is linked to sarcomeric proteins via these filaments. To further investigate whether the association has any functional role, we studied the effect of acetylcoline on ATPase activity of the AChR fraction. Acetylcholine (0.5-4 microM) significantly activated Mg(2+)-ATPase activity of digitonin-solubilized AChR fraction (P < 0.05). Furthermore, we found that desmin as well as actin activated myosin Mg(2+)-ATPase activity. From these findings, it is suggested that desmin and actin form a submembranous organization in the postsynaptic region, and function as mediators of excitation of AChR to the sarcomeric contraction system.
Acetylcholine↗
Both cell-surface carbohydrates and protein tyrosine phosphatase are involved in the differentiation of astrocytes in vitro.
Astrocytes are important in the development and maintenance of functions of the CNS, acting in cooperation with neurons and other glial cells. The glycans on astrocyte membrane are believed to play important roles in cell-cell communication. Plant lectins are useful probes, because the lectins can bind to certain cell surface receptors and elicit cellular responses that are normally activated by endogenous ligands for those receptors. In the present study, we investigated the effect of Datura stramonium agglutinin (DSA) on astrocytes and characterized several molecular events. The addition of DSA to a culture of flat, polygonal, immature astrocytes derived from the neonatal rat cerebellum caused the cells to become stellate in shape, similar to astrocytes observed in vivo, concomitant with an increase in expression of astrocyte-specific intermediate filament (glial fibrillary acidic protein [GFAP]) and inhibition of proliferation. These results indicate that DSA binds to astrocytes and triggers differentiation. We also found a decrease in the extent of tyrosine-phosphorylation of a 38-kDa protein. To elucidate the molecular events during astrocyte differentiation, we examined the effects of various signal transduction inhibitors on the transformation from the polygonal to stellate shape (stellation). Interestingly, only tyrosine phosphatase inhibitors, orthovanadate and phenylarsine oxide, showed an inhibitory effect. Our results suggest that DSA induced astrocyte differentiation acts via tyrosine dephosphorylation.
Animals↗
Expression of various matrix proteases and Ets family transcriptional factors in ovarian cancer cell lines: correlation to invasive potential.
OBJECTIVES: The aim of our study was to determine the important molecules responsible for the invasive activity of ovarian cancer cells. METHODS: We compared the biological characteristics, that is, growth rate, motility, and invasive activity, of five ovarian cancer cell lines with the gene expression of various matrix proteases (matrix metalloproteinase-1 [MMP-1], MMP-2, MMP-9, membrane-type MMP type 1 [MT1-MMP], MT2-MMP, MT3-MMP, urokinase plasminogen activator [uPA]), their inhibitors (tissue inhibitor of metalloproteinase type 1 [TIMP-1], TIMP-2, plasminogen activator inhibitor type 1, [PAI-1], and PAI-2), and the potential transcriptional regulators E1AF and Ets-1. RESULTS: There was no clear correlation in the growth rate, motility, and invasion, suggesting that there are independent properties for malignant potential in ovarian cancer cells. However, HTBOA, a poorly differentiated cancer cell line, exhibited highly invasive activity, rapid growth, and increased motility. This cell line also expressed both Ets transcriptional factors, E1AF and Ets-1, and many matrix-degrading enzymes. Three cell lines that expressed E1AF showed rapid cell growth. The highly invasive cell lines, HTBOA and HTOA (well-differentiated serous cystadenocarcinoma), produced either MMP-2 or MMP-1, and both cell lines expressed MT1-MMP and uPA. Furthermore, the active forms of pro-MMP-2 and pro-MMP-1 were detected in HTBOA and HTOA by zymography. CONCLUSION: We conclude that activated MMP-2 and MMP-1 are important in the invasive activity of these ovarian cancer cells.
Adenocarcinoma↗
Large-scale production of CMP-NeuAc and sialylated oligosaccharides through bacterial coupling.
A large-scale production system of cytidine 5'monophospho-N-acetylneuraminic acid (CMP-NeuAc) and sialyloligosaccharides was established by a whole-cell reaction through the combination of recombinant Escherichia coli strains and Corynebacterium ammonia-genes. For the production of CMP-NeuAc, two recombinant E. coli strains were generated that overexpressed the genes of CMP-NeuAc synthetase and CTP synthetase, respectively. C. ammoniagenes contributed to the formation of UTP from orotic acid. CMP-NeuAc was accumulated at 27 mM (17 g/l) after a 27-h reaction starting with orotic acid and N-acetylneuraminic acid. When E. coli cells that overexpressed the alpha-(2-->3)-sialyltransferase gene of Neisseria gonorrhoeae were put into the CMP-NeuAc production system, 3'-sialyllactose was accumulated at 52 mM (33 g/l) after an 11-h reaction starting with orotic acid, N-acetylneuraminic acid, and lactose. Almost no oligosaccharide byproducts other than 3'-sialyllactose were observed after the reaction. The production of 3'-sialyllactose at a 5-l jar fermenter scale was almost the same as that at a beaker scale, which indicated the high potential of the 3'-sialyllactose production on an industrial scale.
Biotechnology↗
Prevalence of Barrett's esophagus and expression of mucin antigens detected by a panel of monoclonal antibodies in Barrett's esophagus and esophageal adenocarcinoma in Japan.
Barrett's esophagus (BE) is an acquired disorder associated with a high incidence of adenocarcinoma of the lower esophagus. Moreover, it has been reported that short-segment BE may be associated with adenocarcinoma of the esophagogastric junction. The objective of this study was to define the prevalence of BE and the mucin profile in BE, including the short-segment type, and to compare the mucin profile in BE with the profiles of Barrett's adenocarcinoma and distal esophageal adenocarcinoma among Japanese. In total, 650 adult subjects underwent endoscopic examination for evaluation of BE. Although the prevalence of traditional (long segment) BE was 0.62%, the overall prevalence of BE including short-segment type was 15.7%. In Barrett's epithelium, the short-segment type predominantly had gastric type mucin, while the middle- and long-segment types possessed intestinal mucin, especially colonic type mucin (sulfo-Lewis(a)), with high frequency. In Barrett's epithelium with adenocarcinoma, all Barrett's epithelium adjacent to carcinomas showed a predominance of immunoreactivity to sulfo-Lewis(a). In Barrett's adenocarcinomas, colonic type mucin was detected in 100% by monoclonal antibody (MoAb) 91.9H. Small-intestinal mucin and gastric mucin were stained in 50% and 12.5% of the subjects, respectively. Colonic type mucin was also detected with high frequency (80%) in distal esophageal adenocarcinomas without Barrett's epithelium. These data suggest that the epitope, not of small-intestinal type or gastric type mucin, but of colonic type mucin (sulfo-Lewis(a)), may be associated with, at least in part, the malignant phenotype of BE.
Adenocarcinoma↗
Macrocystic serous cystadenoma of the pancreas: importance of co-existent tiny cysts depicted by EUS.
The case of a 38-year-old man with an unusual type of serous cystadenoma of the pancreas is reported. A multilocular cystic tumor in the head of the pancreas was detected on abdominal ultrasonography and computed tomography. On endoscopic ultrasonography, the major cysts ranged from 2.0 to 4.5 cm in size. In addition to these large cysts, a few small cysts were detected. Based on these findings, this tumor was diagnosed as a macrocystic type serous cystadenoma. Because endoscopic retrograde pancreatogram showed a compression of the main pancreatic duct around the tumor, and because the size of the tumor had been increasing over a 3-year period, surgical intervention was performed. The resected tumor consisted of macrocysts, with a few small cysts, and was histologically diagnosed as serous cystadenoma. Endoscopic ultrasonography appears to provide an excellent inside image of this unusual tumor, and because of its ability to detect small cystic lesions clearly, it could be useful in the diagnosis of macrocystic serous cystadenoma.
Adult↗
Molecular analysis of alpha-thalassemia in Nepal: correlation with malaria endemicity.
Thalassemia is a prevalent hereditary disorder characterized by impaired synthesis of globin chains. It has been suggested that the high frequency of thalassemia might reflect heterozygote advantage due to reduced susceptibility to malaria. In Nepal, malaria has often occurred in places below the altitude of 1,200m. We carried out a microepidemiological study on thalassemia in two neighboring populations in Nepal, the Danuwar and the Tamang. Settlements of the Danuwar are located below the limit of the malarial zone (1,200m in altitude), whereas those of the Tamang are found in malaria-free uplands. Three heterozygotes for hemoglobin E (HbE) were observed in the Danuwars. We detected one type (-alpha3.71) of alpha+-thalassemia that involves a deletion of 3.7kb, leading to a loss of one of two alpha-globin genes, in the Danuwars, at a high gene frequency of 63%, while the gene frequency in the Tamangs was only 5%. Analysis of the alpha-globin gene cluster revealed that four different haplotypes were associated with the type of alpha+-thalassemia in the Danuwars. Nucleotide sequences of the D-loop region in the mitochondrial DNA of the two populations indicated a similar nucleotide diversity in each population. The fixation index, FST, representing the degree of genetic differentiation estimated from mitochondrial DNA diversities (FST, 0.05), was smaller than that obtained from the gene frequencies of alpha-thalassemia (FST, 0.55). If we assume neutral molecular evolution in the D-loop region of mitochondrial DNA, these results suggest that the high frequency of alpha+-thalassemia may be due to biological adaptation to the malarial environment rather than to events such as a bottleneck.
DNA, Mitochondrial↗
Effect on rat kidney preservation in the cold of various sugars added to Euro-Collins solution to adjust osmolarity.
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Animals↗
Donor bone marrow cell infusion is effective in inducing tolerance in dogs treated with fractionated lymphoid irradiation and FK506.
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Animals↗