[Pheochromocytoma with severe paralytic ileus occurred from acute pulmonary edema caused by metoclopramide].
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Adrenal Gland Neoplasms↗
Biomedical subjects
K Matsubara
Publications and source records attributed to K Matsubara.
Construction of preferential cDNA microarray specialized for human colorectal carcinoma: molecular sketch of colorectal cancer.
cDNA microarray analyses can be used to identify candidate genes that play important roles in human carcinogenesis. To gain insight into the molecular sketch of colorectal cancer, we have constructed cDNA microarrays specialized for colorectal cancer, which we named "Colonochip" by selecting genes that are expressed in colorectal cancer, normal colonic mucosa, and liver metastatic cancer tissues. This microarray contained 4608 nonredundant cDNA clones from over 30,000 cDNA clones derived from the three types of human cDNA libraries, as well as clones from 170 additional conventional major genes suspected to be involved in colorectal carcinogenesis, according to literatures. Using this "Colonochip," we were able to identify 59 genes showing twofold or more differential expression between primary cancer and normal colonic mucosa, potent candidates for diagnosis, and therapy of colorectal cancer for further studies.
Amphiregulin↗
Carrier-mediated processes in blood--brain barrier penetration and neural uptake of paraquat.
Due to the structural similarity to N-methyl-4-phenyl pyridinium (MPP(+)), paraquat might induce dopaminergic toxicity in the brain. However, its blood--brain barrier (BBB) penetration has not been well documented. We studied the manner of BBB penetration and neural cell uptake of paraquat using a brain microdialysis technique with HPLC/UV detection in rats. After subcutaneous administration, paraquat appeared dose-dependently in the dialysate. In contrast, MPP(+) could not penetrate the BBB in either control or paraquat pre-treated rats. These data indicated that the penetration of paraquat into the brain would be mediated by a specific carrier process, not resulting from the destruction of BBB function by paraquat itself or a paraquat radical. To examine whether paraquat was carried across the BBB by a certain amino acid transporter, L-valine or L-lysine was pre-administered as a co-substrate. The pre-treatment of L-valine, which is a high affinity substrate for the neutral amino acid transporter, markedly reduced the BBB penetration of paraquat. When paraquat was administered to the striatum through a microdialysis probe, a significant amount of paraquat was detected in the striatal cells after a sequential 180-min washout with Ringer's solution. This uptake was significantly inhibited by a low Na(+) condition, but not by treatment with putrescine, a potent uptake inhibitor of paraquat into lung tissue. These findings indicated that paraquat is possibly taken up into the brain by the neutral amino acid transport system, then transported into striatal, possibly neuronal, cells in a Na(+)-dependent manner.
1-Methyl-4-phenylpyridinium↗
Anticoagulant properties of a sulfated galactan preparation from a marine green alga, Codium cylindricum.
An anticoagulant was isolated from a marine green alga, Codium cylindricum. The anticoagulant was composed mainly of galactose with a small amount of glucose, and was highly sulfated (13.1% as SO3Na). The anticoagulant properties of the purified anticoagulant were compared with that of heparin by assays of activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using normal human plasma. The anticoagulant showed similar activities with heparin, however, weaker than heparin. On the other hand, the anticoagulant did not affect PT even at the concentration at which APTT and TT were strongly prolonged. The anticoagulant did not potentiate antithrombin III (AT III) and heparin cofactor II (HC II), thus the anticoagulant mechanism would be different from that of other anticoagulants isolated so far from the genus Codium.
Anticoagulants↗
L-Deprenyl prevents the cell hypoxia induced by dopaminergic neurotoxins, MPP(+) and beta-carbolinium: a microdialysis study in rats.
N-Methyl-4-phenylpyridinium (MPP(+)) and 2,9-di-methyl-norharmanium (2,9-Me2NH(+)), which is a beta-carbolinium proposed as an endogenous MPP(+)-like toxin underlying Parkinson's disease, are strong mitochondrial toxins. We have measured the extracellular lactate levels as a marker for the in vivo cell hypoxia in the striatum of freely moving rats. The perfusions with MPP(+) and 2,9-Me2NH(+) increased extracellular lactate levels in a dose-dependent manner. These increases in lactate levels were significantly prevented by the co-perfusion with 10 microM L-deprenyl, a selective monoamine oxidase (MAO)-B inhibitor, but not by pargyline, a non-specific MAO inhibitor. The increase in extracellular lactate levels was considered to be the reflection of the cell damage resulted from the impairment of mitochondrial function. The present results suggested that L-deprenyl would rescue nerve cells from these toxins through the direct influence on the mitochondrial electron transport.
1-Methyl-4-phenylpyridinium↗
Nicotinamide-N-methyltransferase is higher in the lumbar cerebrospinal fluid of patients with Parkinson's disease.
Parkinson's disease (PD) may be initiated or precipitated by endogenous toxins with a structure similar to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in genetically-predisposed individuals. Nicotinamide N-methyltransferase (NNMT) catalyzes N-methylation of nicotinamide and other pyridines to form pyridinium ions. The protein amount of NNMT was measured in the lumbar cerebrospinal fluid of PD patients by immunoblot analysis using anti-human NNMT antibody. In younger (65 years old or younger) PD patients, the relative level of NNMT protein was significantly higher than that in younger controls. The NNMT protein was significantly affected by aging: the amount decreased along with aging in PD patients. These findings suggested that excess NNMT in the central nervous system might be implicated in the PD pathogenesis.
Aging↗
Molecular cloning and characterization of DEC2, a new member of basic helix-loop-helix proteins.
DEC1 is a basic helix-loop-helix (bHLH) protein related to Drosophila Hairy, Enhancer of split and HES, and involved in the control of proliferation and/or differentiation of chondrocytes, neurons, etc. We report here the identification and characterization of human, mouse and rat DEC2, a novel member of the DEC subfamily. DEC2 had high (97%) and moderate (52%) similarities in the bHLH region and the Orange domain with DEC1, respectively. However, DEC2, but not DEC1, had alanine and glycine-rich regions in the C-terminal half. Unlike Hairy, Enhancer of split and HES, DEC2 lacked the WRPW motif for interaction with the corepressor Groucho. The DEC2 gene was mapped to human chromosome 12p11.23-p12.1, mouse chromosome 6 G2-G3 and rat chromosome 4q43 distal-q4, where the conserved linkage homology has been identified among these species. Unlike DEC1, which was broadly expressed in many tissues, DEC2 showed a more restricted pattern of mRNA expression. The DEC subfamily proteins may play an important role in tissue development.
Amino Acid Sequence↗
Usefulness of dual-head coincidence gamma camera with thick NaI crystals for nuclear oncology: comparison with dedicated PET camera and conventional gamma camera with thin NaI crystals.
AIM: A comparative study of the images obtained with a dual-head coincidence gamma camera with thick NaI crystals (19 mm), a dedicated PET camera with BGO crystals and a conventional gamma camera with thin NaI crystals (9.5 mm) was conducted to clarify the clinical feasibility of a dual-head coincidence gamma camera with thick NaI crystals. METHODS: FDG images of 27 patients with malignant tumors were obtained by means of a dual-head coincidence gamma camera with thick NaI crystal and a dedicated PET camera with BGO crystals. The images of bone scintigraphy in 10 cancer patients obtained with the dual-head coincidence gamma camera were compared with those taken by a conventional dual-head gamma camera with thin NaI crystals. RESULTS: Patient-basis sensitivity in 27 patients with neoplasms and lesion-basis sensitivity of the dual-head coincidence gamma camera and the dedicated PET camera were 74.1% and 85.2% (n.s.), 66.7% and 72.2% (n.s.), respectively. The tumor to background FDG uptake ratio derived from the coincidence gamma camera was significantly lower than that derived from the dedicated PET camera (mean +/- s.d.; 3.48 +/- 3.77 vs. 8.12 +/- 8.92, p < 0.0001), but the tumor to background FDG uptake ratio obtained with both methods correlated well (r = 0.84, p < 0.001). Similar whole body bone scans were obtained with the dual-head coincidence gamma camera and the conventional dual-head gamma camera in all 10 patients. CONCLUSION: These results suggest that the dual-head coincidence gamma camera with thick NaI crystals has potentially high clinical applicability for community hospitals.
Adult↗
Glutamate is not involved in the MPP+-induced dopamine overflow in the striatum of freely moving C57BL/6 mice.
The role of glutamate in the N-methyl-4-phenyldihydropyridinium (MPP+) toxicity has been argued in the past decade. However, the effects of glutamate efflux and NMDA antagonist on MPP+-induced dopamine overflow have not been documented. To clarify this, we perfused MPP+ through a microdialysis probe in the striatum of freely moving mature C57BL/6 mice. The 60-min perfusion of 10 and 100 microM MPP+ strikingly increased dopamine levels to 28- and 93-fold of the basal values, respectively. In contrast, an administration of MPP+ did not induce marked glutamate release: the MPP+-perfusion slightly increased the glutamate level at 100 microM, but not at 10 microM. The addition of 100 microM (+)-MK-801 or 200 microM (+/-)-AP-7 to the perfusate did not attenuate MPP+-induced dopamine overflow. The extent of dopamine release only depended on the amount of MPP+ accumulation into the cells. These results indicated that, at least in the striatum, neither glutamate release nor the NMDA antagonist, including (+)-MK-801, could regulate MPP+-evoked dopamine overflow.
1-Methyl-4-phenylpyridinium↗
Norharman, an indoleamine-derived beta-carboline, but not Trp-P-2, a gamma-carboline, induces apoptotic cell death in human neuroblastoma SH-SY5Y cells.
Carbolines, azaheterocyclic amines derived from indoleamines, have various biological activities, such as neurotoxicity of beta-carbolines and potent mutagenicity of gamma-carbolines. In this study, structural significance among these carbolines was investigated in relation to the types of cell death, apoptosis and necrosis, using human neuroblastoma SH-SY5Y cells. DNA damage was quantitatively analyzed by a single-cell gel electrophoresis assay. DNA damage was induced by both beta-carbolines, harman and norharman, and gamma-carbolines, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-4-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), in a dose dependent manner. Gamma-carbolines were more potent to damage DNA than beta-carbolines. Alkaline lysis of the cells prevented DNA damage induced by beta-carboline, and pre-treatment of the cells with cycloheximide, an inhibitor of protein synthesis, reduced DNA damage caused by norharman. Morphological observation showed condensed and fragmented nuclei typical for apoptosis, in the cells treated with norharman. Thus, DNA damage induced by norharman was proved to be apoptotic. However, harman, which had a methyl substitution at the position 1, might induce necrosis in the cells. On the other hand, gamma-carbolines, Trp-P-1 and Trp-P-2, directly damaged DNA. Thus, the nitrogen atom at the gamma-position and/or an amino group in carboline structure would be required to induce the direct DNA cleavage.
Apoptosis↗
Inactivation of SSI-1, a JAK/STAT inhibitor, in human hepatocellular carcinomas, as revealed by two-dimensional electrophoresis.
BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is one of the most common human cancers, and many efforts have been paid to discover aberrant expression control in HCC, however the specific molecular mechanisms involved in hepatocarcinogenesis remain to be determined. METHODS: To investigate genomic changes that occur in human primary hepatocellular carcinomas (HCC), we carried out restriction landmark genomic scanning. This two-dimensional electrophoretic system displays 2000-3000 NotI-landmark sites in a single gel. RESULTS: We detected one landmark spot that showed diminished signal intensities in a majority of the HCCs we examined. Cloning revealed that this spot represented a NotI-cluster sequence that was enriched with CpG dinucleotides in the promoter region of a gene encoding Janus kinase (JAK)-binding protein, SSI-1 (also known as JAB1 or SOCS-1). Expression of the SSI-1 gene was markedly reduced in half of eight HCCs analyzed. CONCLUSIONS: This protein regulates the Janus kinase signal transducers and activators of transcription signal transduction pathway, which transmits signals from cytokines to the intracellular apparatus. These data suggest that dysregulation of the pathway relate with progression of HCC.
Carcinoma, Hepatocellular↗
Construction of comparative cytogenetic maps of the Chinese hamster to mouse, rat and human.
We constructed comparative cytogenetic maps of the Chinese hamster to mouse, rat and human by fluorescence in-situ hybridization using 36 cDNA clones of mouse, rat, Syrian hamster, Chinese hamster and human functional genes. In this study, 30 out of the 36 genes were newly mapped to Chinese hamster chromosomes. The chromosomal homology of the Chinese hamster was identified and arranged in 19, 19 and 18 segments of conserved synteny in mouse, rat and human, respectively. Additionally, two of the 19 segments homologous to mouse chromosomes were initially identified in this study.
Animals↗
SOCS-1, a negative regulator of the JAK/STAT pathway, is silenced by methylation in human hepatocellular carcinoma and shows growth-suppression activity.
Hepatocellular carcinoma (HCC) is a major cause of cancer death, but the molecular mechanism for its development beyond its initiation has not been well characterized. Suppressor of cytokine signaling (SOCS-1; also known as JAB and SSI-1) switches cytokine signaling 'off' by means of its direct interaction with Janus kinase (JAK). We identified aberrant methylation in the CpG island of SOCS-1 that correlated with its transcription silencing in HCC cell lines. The incidence of aberrant methylation was 65% in the 26 human primary HCC tumor samples analyzed. Moreover, the restoration of SOCS-1 suppressed both growth rate and anchorage-independent growth of cells in which SOCS-1 was methylation-silenced and JAK2 was constitutively activated. This growth suppression was caused by apoptosis and was reproduced by AG490, a specific, chemical JAK2 inhibitor that reversed constitutive phosphorylation of STAT3 in SOCS-1 inactivated cells. The high prevalence of the aberrant SOCS-1 methylation and its growth suppression activity demonstrated the importance of the constitutive activation of the JAK/STAT pathway in the development of HCC. Our results also indicate therapeutic strategies for the treatment of HCC including use of SOCS-1 in gene therapy and inhibition of JAK2 by small molecules, such as AG490.
Antineoplastic Agents↗
Early elevation of serum thrombopoietin levels and subsequent thrombocytosis in healthy preterm infants.
To verify pathophysiological mechanisms underlying thrombocytosis in low-birth-weight (LBW) preterm babies, we evaluated kinetic changes in platelet counts and thrombopoietic cytokines including thrombopoietin (TPO), interleukin 6 (IL-6) and IL-11 in 24 uncomplicated preterm infants. Platelet counts in cord blood (CB) (265 +/- 64 x 10(9)/l) were similar to adult levels, increased by d 14 (473 +/- 140 x 10(9)/l), and then remained fairly constant. Thrombocytosis (> 500 x 10(9)/l) was observed in 9/24 (38%) subjects. Mean TPO level in CB was 5.11 +/- 1.51 fmol/ml, peaked at d 2 (7.64 +/- 3.28 fmol/ml), decreased at d 5 (3.93 +/- 1.67 fmol/ml), and thereafter kept fairly constant during the remaining neonatal period. Compared with term infants, mean TPO levels of preterm infants in CB and at d 2 were significantly higher (P < 0.01). There was an inverse correlation between platelet counts and TPO levels (r = 0.45, P < 0.001, n = 88). Preterm neonates with thrombocytosis had significantly higher TPO values in CB than those without thrombocytosis (P < 0.05). There was no significant relationship between platelet counts and IL-6. IL-11 was not detectable. These results suggest that an early elevation of serum TPO levels is related to the subsequent thrombocytosis in LBW preterm infants.
Biomarkers↗
Prenatal sonographic diagnosis of Pena-Shokeir syndrome type I.
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Abnormalities, Multiple↗
Spiral computed tomography and three-dimensional image reconstruction of an aberrant innominate artery.
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Brachiocephalic Trunk↗
The preparation of rapidly disintegrating tablets in the mouth.
Elderly people, children and patients sometimes have difficulties swallowing tablets. To solve this problem, a novel method of preparing tablets that disintegrate rapidly in the mouth was developed. A tablet with high porosity is required for rapid disintegration, but such a tablet is generally fragile. To make a tablet having both high porosity and practical strength, amorphous sucrose, which has good compactability, was used. Mannitol powder with freeze-dried amorphous sucrose was tableted at low compression and stored under certain conditions. The tablet disintegrated rapidly in the mouth, because of its high porosity. The tensile strength of the tablet increased remarkably during storage, while the porosity of the tablet seemed almost unchanged. The results of thermal analysis and powder x-ray diffraction measurement showed that the amorphous sucrose in tablet crystallized during storage. The increase in the tensile strength of the tablet was due to crystallization of the amorphous sucrose and formation of new internal contact points in the tablet. It was concluded that this crystalline transition method is a very useful method to prepare a rapidly disintegrating tablet.
Administration, Oral↗
Role of Rab3 GDP/GTP exchange protein in synaptic vesicle trafficking at the mouse neuromuscular junction.
The Rab3 small G protein family consists of four members, Rab3A, -3B, -3C, and -3D. Of these members, Rab3A regulates Ca(2+)-dependent neurotransmitter release. These small G proteins are activated by Rab3 GDP/GTP exchange protein (Rab3 GEP). To determine the function of Rab3 GEP during neurotransmitter release, we have knocked out Rab3 GEP in mice. Rab3 GEP-/- mice developed normally but died immediately after birth. Embryos at E18.5 showed no evoked action potentials of the diaphragm and gastrocnemius muscles in response to electrical stimulation of the phrenic and sciatic nerves, respectively. In contrast, axonal conduction of the spinal cord and the phrenic nerve was not impaired. Total numbers of synaptic vesicles, especially those docked at the presynaptic plasma membrane, were reduced at the neuromuscular junction approximately 10-fold compared with controls, whereas postsynaptic structures and functions appeared normal. Thus, Rab3 GEP is essential for neurotransmitter release and probably for formation and trafficking of the synaptic vesicles.
Action Potentials↗