[An operative case of gastrointestinal stromal tumor (GIST) incarcerated into duodenal lumen].
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Aged↗
Biomedical subjects
T Senda
Publications and source records attributed to T Senda.
The suppression of potassium cyanide-induced mortality by the increase of extracellular acetylcholine level in the brain.
We examined whether potassium cyanide (KCN)-induced mortality in mice was regulated by acetylcholine transmission in the brain. Our novel compound, (+/-)-1-(1,2-diphenyl)ethyl-4-[2-(3,4-dimethoxyphenyl)ethyl]piperazine dihydrochloride (SA3251), suppressed KCN-induced mortality in mice. In parallel, SA3251 increased the cortical and hippocampal extracellular acetylcholine level in conscious, freely-moving rats. Interestingly, the time course patterns of these two events induced by SA3251 correlated. These results suggest that the central cholinergic system plays an important role in the suppression of KCN-induced mortality.
Acetylcholine↗
PcpA, which is involved in the degradation of pentachlorophenol in Sphingomonas chlorophenolica ATCC39723, is a novel type of ring-cleavage dioxygenase.
The pentachlorophenol (PCP) mineralizing bacterium Sphingomonas chlorophenolica ATCC39723 degrades PCP via 2,6-dichlorohydroquinone (2,6-DCHQ). The pathway converting PCP to 2,6-DCHQ has been established previously; however, the pathway beyond 2,6-DCHQ is not clear, although it has been suggested that a PcpA plays a role in 2, 6-DCHQ conversion. In this study, PcpA expressed in Escherichia coli was purified to homogeneity and shown to have novel ring-cleavage dioxygenase activity in conjunction with hydroquinone derivatives, and converting 2,6-DCHQ to 2-chloromaleylacetate.
Amino Acid Sequence↗
Crystal structure of an aromatic ring opening dioxygenase LigAB, a protocatechuate 4,5-dioxygenase, under aerobic conditions.
BACKGROUND: Sphingomonas paucimobilis SYK-6 utilizes an extradiol-type catecholic dioxygenase, the LigAB enzyme (a protocatechuate 4,5-dioxygenase), to oxidize protocatechuate (or 3,4-dihydroxybenzoic acid, PCA). The enzyme belongs to the family of class III extradiol-type catecholic dioxygenases catalyzing the ring-opening reaction of protocatechuate and related compounds. The primary structure of LigAB suggests that the enzyme has no evolutionary relationship with the family of class II extradiol-type catecholic dioxygenases. Both the class II and class III enzymes utilize a non-heme ferrous center for adding dioxygen to the substrate. By elucidating the structure of LigAB, we aimed to provide a structural basis for discussing the function of class III enzymes. RESULTS: The crystal structure of substrate-free LigAB was solved at 2.2 A resolution. The molecule is an alpha2beta2 tetramer. The active site contains a non-heme iron coordinated by His12, His61, Glu242, and a water molecule located in a deep cleft of the beta subunit, which is covered by the alpha subunit. Because of the apparent oxidation of the Fe ion into the nonphysiological Fe(III) state, we could also solve the structure of LigAB complexed with a substrate, PCA. The iron coordination sphere in this complex is a distorted tetragonal bipyramid with one ligand missing, which is presumed to be the O2-binding site. CONCLUSIONS: The structure of LigAB is completely different from those of the class II extradiol-type dioxygenases exemplified by the BphC enzyme, a 2,3-dihydroxybiphenyl 1,2-dioxygenase from a Pseudomonas species. Thus, as already implicated by the primary structures, no evolutionary relationship exists between the class II and III enzymes. However, the two classes of enzymes share many geometrical characteristics with respect to the nature of the iron coordination sphere and the position of a putative catalytic base, strongly suggesting a common catalytic mechanism.
Amino Acid Sequence↗
Effects of mitogen-activated protein kinase inhibitors or phosphodiesterase inhibitors on interleukin-1-induced cytokines production in synovium-derived cells.
The effects of mitogen-activated protein (MAP) kinase inhibitors or phosphodiesterase (PDE) inhibitors on interleukin (IL)-1-induced cytokines production in synovium-derived cells were investigated. Human synoviocyte (HS) or synovial sarcoma (SW982) stimulated by IL-1beta (100 ng/ml) produced various cytokines including IL-6, IL-8, GROalpha, VEGF, basic FGF and tumor necrosis factor alpha (TNFalpha) in vitro. SB202190 or SB203580, an inhibitor of p38 MAP kinase, inhibited all cytokines production in both cells. PD98059, an inhibitor of MAP kinase kinase (MEK), inhibited IL-6, IL-8 and basic FGF production in HS and all cytokines production except basic FGF in SW982. However, many of its effects were weaker than those of SB202190 or SB203580. Quazinone, an inhibitor of cyclic GMP-inhibited PDE, scarcely affected cytokines production in both cells. Rolipram or R0201724, an inhibitor of cyclic AMP-specific PDE, inhibited IL-8 and basic FGF production in HS and TNFalpha production in SW982, however, it enhanced the other cytokines production in SW982. These results suggest that the activation of MAP kinase cascade may be important for IL-1-induced cytokines production in synovium-derived cells. On the other hand, the role of cyclic AMP may be dependent on cell and cytokine types.
4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
Kinesin cross-bridges between neurosecretory granules and microtubules in the mouse neurohypophysis.
Neurosecretory granules are conveyed along microtubules in the neurohypophysial axon. By both quick-freeze deep-etch and thin section electron microscopies, we found cross-bridges between the granules and microtubules. The length of the cross-bridges (mean 26.6 +/- 15.2 nm) was not uniform, and its histogram was multi-phasic showing the highest peak around 20 nm and several lower peaks in the range of 40-100 nm. This implies that cross-bridges are complexes of several kinds of constituents. Immunofluorescence microscopy showed the expression of a motor protein kinesin in the mouse neurohypophysis. Immunoelectron microscopy detected kinesin at the contact sites of neurosecretory granules to microtubules. These results suggest that kinesin is a major component of the cross-bridges, and involved in the neurosecretory granule transportation.
Animals↗
Localization of MCC (mutated in colorectal cancer) in various tissues of mice and its involvement in cell differentiation.
Localization of the MCC (mutated in colorectal cancer) gene product, a cell cycle-regulating protein mutated in several colorectal tumors, in various mouse tissues was examined by immunohistochemistry and immunoelectron microscopy. MCC was localized on microvilli and in the apical cytoplasm in renal proximal tubule epithelial cells and pancreatic acinar cells. In hepatocytes, MCC was exclusively detected on microvilli. MCC was highly expressed in the cerebral cortex and the molecular layer of the cerebellar cortex and was partially associated with membrane organelles in neuronal elements. Adrenal chromaffin cells showed little expression of MCC. MCC was localized to the cell margins of ependymal cells, thyroid follicular cells, and anterior pituitary cells. In parotid acinar cells, only the apical surface was immunopositive. MCC was not expressed in skeletal and cardiac muscle. MCC was present at lateral cell borders in the duodenum and colon epithelium. In addition, the apical cytoplasm of colon epithelial cells exhibited intense immunoreactivity. The amount of MCC increased during differentiation of NGF-treated PC12 cells. In conclusion, MCC was expressed in differentiated cells and was associated with the plasma membrane and membrane organelles. In addition to the negative regulation of the cell cycle, MCC may be involved in cell differentiation.
Animals↗
Midkine is expressed during repair of bone fracture and promotes chondrogenesis.
Midkine (MK) is a heparin-binding growth/differentiation factor implicated in the control of development and repair of various tissues. Upon fracture of the murine tibia, MK was found to be transiently expressed during bone repair. MK was immunohistochemically detected in spindle-shaped mesenchymal cells at the fracture site on day 4 after fracture and in chondrocytes in the area of endochondral ossification on day 7. MK expression was decreased on day 14 and scarcely seen on day 28 when bone repair was completed. This mode of MK expression is reminiscent of MK expression during development. MK was expressed in hypertrophic chondrocytes of the prebone cartilage rudiments on embryonic day 14 in mouse embryos. MK was also strongly expressed in the epiphyseal growth plate. MK was localized intracellularly during both bone repair and development, and this localization was confirmed by immunoelectron microscopy for embryonic chondrocytes. When MK cDNA was transfected into ATDC5 chondrogenic cells and overexpressed, the majority of transfected cells with strong MK expression showed enhanced chondrogenesis as revealed by increased synthesis of sulfated glycosaminoglycans, aggrecan, and type II collagen. These results suggest that MK plays important roles in chondrogenesis and contributes to bone formation and repair.
Aggrecans↗
[Structure and function of helical cytokines and their cognate receptors].
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Cytokines↗
The carboxyl-terminal region of protein C is essential for its secretion.
We have previously reported a mutated protein C, designated protein C Nagoya (PCN), characterized by the deletion of a single guanine residue (8857G). This frameshift mutation results in the replacement of the carboxyl-terminal 39 amino acids of wild-type protein C (G381-P419) by 81 abnormal amino acids. This elongated mutant was not effectively secreted, and was retained in the endoplasmic reticulum. To determine why PCN is not secreted, we constructed a series of mutants from which some or all of the 81 amino acids were deleted. None of these shortened proteins were secreted from producing cells, indicating that the carboxyl-terminal extension is not mainly responsible for the intracellular retention of PCN, and that the 39 carboxyl-terminal amino acids of wild-type protein C are required for secretion. To determine which residues are essential for the secretion of protein C, deletion mutants of the carboxyl-terminal region (D401-P419) were prepared. Metabolic labeling showed that mutants of protein C truncated before W417, Q414, E411, or K410 were efficiently secreted. On the other hand, the mutants truncated before D409 were retained and degraded intracellularly. Immunofluorescence and immunoelectron microscopy showed that truncation before D409 blocks the movement from rough endoplasmic reticulum to the Golgi apparatus. To understand the conformational change in the carboxyl-terminal region, two models of truncated activated protein C were constructed using energy optimization and molecular dynamics with water molecules.
Amino Acid Sequence↗
Structural significance of azaheterocyclic amines related to Parkinson's disease for dopamine transporter.
We have evaluated the neuronal uptake of 12 neutral and quaternary azaheterocyclic amines that are possible candidates for idiopathic Parkinson's disease via dopamine transporter of striatal synaptosomes. The double-reciprocal plots for dopamine transporter obtained from Wistar rat and C57BL/6 mouse synaptosomes with N-methyl-4-phenylpyridinium cation (MPP+) as a substrate were identical to each other. Neutral beta-carbolines and tetrahydroisoquinolines were unfavorable substrates for dopamine transporter. The quarternization of these compounds strikingly increased the affinity for dopamine transporter with 2-10 times greater Km and 10 times smaller Vmax values than MPP+. Although catechol tetrahydroisoquinolines were weak substrates, their quarternization reduced their original properties as substrates for dopamine transporter. These results provide both topographic and electrogenic information of azaheterocyclic amines for the dopamine transporter-mediated influx. The intramolecular distance between the N-atom and the centroid of the benzene ring could be an important factor for the recognition of binding site of dopamine transporter, and an adequate net charge similar to dopamine would be further required for translocation into the cells.
1-Methyl-4-phenylpyridinium↗
Female sterility in mice lacking the basigin gene, which encodes a transmembrane glycoprotein belonging to the immunoglobulin superfamily.
Basigin (Bsg) is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. Bsg knock-out mice exhibit infertility of both sexes. Based on limited results, defective implantation has been considered to be the cause of the female infertility. We demonstrate here that disruption of the Bsg gene produces the failure of female reproductive processes including not only implantation but also fertilization. Bsg mRNA expression in cumulus cells and basolateral localization of the Bsg protein in the endometrial epithelium further support the importance of Bsg in these processes.
Animals↗
A null mutation in basigin, an immunoglobulin superfamily member, indicates its important roles in peri-implantation development and spermatogenesis.
Basigin is a highly glycosylated transmembrane protein with two immunoglobulin-like domains. We generated mutant mice lacking the basigin gene (Bsg) by gene targeting. Bsg (-/-) embryos developed normally during preimplantation stages. However, the majority of Bsg (-/-) embryos died around the time of implantation. At this time, basigin mRNA was strongly expressed in the trophectoderm, embryo proper, and uterine endometrium of Bsg (+/+) mice. These results suggest that basigin is involved in intercellular recognition during implantation. Embryos which survived the critical period yielded Bsg (-/-) mutant mice. Half of the mutant mice died before 1 month after birth, due to interstitial pneumonia. The surviving adult mutant mice were small and sterile. Spermatogenesis was arrested in the mutant mice. Most of the spermatocytes in the Bsg (-/-) mouse were arrested and degenerated at the metaphase of the first meiosis, and only a small number differentiated to step 1 spermatids. In the female mutants, the ovaries and genital tract were morphologically normal, and the defect was probably in the capability of implantation of the uterus. In conclusion, basigin is an important cell-surface molecule involved in early embryogenesis and reproduction.
Animals↗
Effect of SA4503, a novel sigma1 receptor agonist, against glutamate neurotoxicity in cultured rat retinal neurons.
We examined the effects of sigma1 receptor agonists against glutamate-induced neurotoxicity in cultured retinal neurons. Primary cultures obtained from fetal rat retinas (16-19 d gestation) were used. The neurotoxic effect of glutamate was quantitatively assessed using the trypan blue exclusion method. A brief exposure of retinal cultures to glutamate (500 microM) led to delayed neuronal cell death. The glutamate-induced neurotoxicity was inhibited by (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,b]-cyclohepten-5 ,10-imine hydrogen maleate (MK-801). The sigma1 receptor agonists, 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)-piperazine dihydrochloride (SA4503) and (+)-pentazocine at a concentration range of 0.1 approximately 100 microM reduced the glutamate-induced neurotoxicity in a dose-dependent manner. In addition, the neuroprotective effects of both SA4503 and (+)-pentazocine were antagonized by co-treatment with N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine monohydrochloride (NE-100), a putative sigma1 receptor antagonist. These findings suggest that sigma1 receptor agonists protect retinal cells against glutamate-induced neurotoxicity.
Analgesics, Opioid↗
Intermembrane bridges within membrane organelles revealed by quick-freeze deep-etch electron microscopy.
Intracellular membrane-bounded organelles, such as the endoplasmic reticulum, Golgi apparatus, and mitochondrion, possess and maintain their shape and intrinsic relationship due to the nature of their membrane organization. To reveal the membranous attachments that support these shapes and relationships, we examined various kinds of cells by quick-freeze deep-etch electron microscopy. In the cisternae of the endoplasmic reticula, we found intermembrane bridges linking opposite membranes of the cisternae. Membranes of adjoining rough endoplasmic reticulum cisternae were linked by intermembrane bridges crossing a narrow cytoplasmic gap between cisternae. Intermembrane bridges were also found in and between the Golgi cisternae and in nuclear envelopes. Three kinds of intermembrane bridges were found within mitochondria: one linking between outer and inner mitochondrial membranes and the other two spanning the intracristal space and intercristal matrix space. The presence of intermembrane bridges within membrane organelles, except for those between rough endoplasmic reticulum cisternae, was seen in all cell types examined. Intermembrane bridges within membrane organelles provide a structural basis for the membrane organization of the organelles and thus may contribute to the functional integrity of the organelles.
Animals↗
Effect of alignment of the transplanted graft extracellular matrix on cellular repopulation and newly synthesized collagen.
This study examines the effect of alignment of the transplanted graft extracellular matrix on cellular repopulation and new collagen synthesis. The lateral half of the patellar tendon was harvested as a tendon graft from Lewis rats and frozen at -80 degrees C. In order to maintain the original alignment of the graft extracellular matrix, the graft was transplanted to a same size defect in the patellar tendon of other Lewis rats (group I). For controls, the graft was transplanted in a lax condition after excision of only the distal half of the lateral side of a patellar tendon (group II). After transplantation, six animals in each group were killed at 3, 7, 14, and 28 days. Cellular repopulation was assessed by using fibrillar-actin (F-actin) labeling with rhodamine-phalloidin, and new collagen synthesis was detected by means of a polyclonal antibody against type III collagen aminopropeptide (pN collagen III). Collagen fibril profiles were observed under the transmission electron microscope. On the 3rd day after transplantation, no specific fluorescence was detected in either group. Specific labeling for F-actin and pN collagen III, however, was observed at both ends of the graft in both groups at 1 week and throughout the graft at 2 weeks after transplantation. Consistent with the actin bundles' orientation, pN collagen III was aligned parallel to the longitudinal axis of the graft in group I. Collagen fibrils with a smaller diameter, mixed evenly and everywhere with a larger diameter, increased gradually in group I. However, smaller collagen fibrils in group II increased more slowly and were distributed unevenly. In summary, the dense collagen arrangement in the native patellar tendon determined the alignment of the repopulating cells, and the distribution of newly synthesized collagen might be affected by the actin cytoskeleton within the repopulating cells.
Actins↗
Intergranular bridges in the anterior pituitary cell and their possible involvement in Ca2+-induced granule-granule fusion.
Quick-freeze deep-etch electron microscopy showed the presence of bridge-like structures between adjacent secretory granules in rat anterior pituitary secretory cells. These intergranular bridges were variable in length and thickness. The finest bridges were 7-8 nm in length, while the longest ones were as long as 80 nm. Annexin II, one of the Ca2+-dependent phospholipid-binding proteins, is known to interlink between two membranes and induce aggregation of liposomes and chromaffin granules under the presence of Ca2+. In anterior pituitary cells, annexin II was detected by immunoelectron microscopy at the contact sites of secretory granules with other granules. The anterior pituitary cells treated under the presence of extracellular Ca2+ with Clostridium perfringens enterotoxin which induces Ca2+ influx showed multigranular exocytosis, i.e., multiple fusions of secretory granules with each other and with the plasma membrane. The granule-granule fusion in progress could be captured by the quick-freeze deep-etch technique. The membranes of adjacent secretory granules were partially fused at their contact sites where intergranular strands were no longer seen, while there existed intergranular strands between unfused portions of the granule membranes. From these results, we consider that the intergranular bridges, some of which may be composed of annexin II, are involved in Ca2+-induced granule-granule fusion in anterior pituitary cells.
Animals↗
Special smooth muscle cells along the submucosal surface of the guinea pig colon with reference to its spontaneous contractions.
Antiperistalses occur from the flexure region of the guinea pig colon. We previously demonstrated that the circular muscle at the mesenteric border of the flexure region produced spontaneous regular contractions and found special smooth muscle cells believed to be pacemakers along the submucosal surface of the circular muscle layer. In this study, we revealed bipolar- and multipolar-type special smooth muscle cells along the submucosal surface of the muscle layer. Their slender cell processes contacted each other and formed a cellular network. Caveolae, filament structures expressing smooth muscle actin, vimentin, some desmin, and basal lamina were prominent features. The special smooth muscle cells corresponded to c-Kit-immunopositive cells and so-called interstitial cells or interstitial cells of Cajal in other reports. Their population was larger in the flexure region and the proximal colon than in the distal colon. The circular muscle layer at the flexure region was thicker than in other regions. The contraction in the flexure region showed the highest frequency and regularity. The dense population of special smooth muscle cells at the flexure region and thicker muscle layer may make the mechanical contraction more regular. The antiperistalsis from the flexure region could be explained in relation to the highest frequency of the pulsating contraction.
Actins↗