Gastric inflammatory polyposis after long-term intermittent use of nonsteroidal anti-inflammatory drugs and histamine2-receptor antagonists.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to T Takeya.
Explore the source record for details and available documents.
Osteoclast differentiation factor (ODF) induces differentiation of mouse RAW264 cells to mature osteoclasts. To understand the mechanism controlling a coupling between withdrawal from the cell cycle and differentiation, we examined cell cycle progression and expression profiles of cell cycle regulatory genes at the initial phase in committed cells. ODF rapidly converted the hyperphosphorylated form of the retinoblastoma protein (pRb) into the hypophosphorylated form. The p21 protein was induced by ODF treatment in the same time course with that of dephosphorylation of pRb, followed by a sharp decline. After this period, a delayed entry of the S phase started accompanying the induction of CycD3 and cdk6 in differentiating cells. Hydroxyurea treatment indicated that the S phase entry was a prerequisite for osteoclast formation. Thus, ODF induces pleiotropic effects on cell cycle regulatory genes in RAW264 cells during the initial phase of the differentiation process to osteoclasts.
Murine CD46 (mCD46) is a type 1 membrane protein expressed predominantly in testicular germ cells, the distribution profile of which is in contrast to that of human CD46 showing a ubiquitous tissue distribution. We have identified an additional message of mCD46 that encodes a putative secretory form [Nomura et al. (1999) Immunogenetics 50, 245-254]. Here, we cloned three cDNAs encoding putative soluble CD46 from murine testis. These soluble form messages were yielded on insertion of unidentified nucleotide sequences, 77, 179, and 73 ntds, into the junctions between the SCR3 and SCR4 (variant 2), ST(c) and UK (variant 3), and SCR4 and ST(c) (variant 1) domains, respectively, the last one corresponding to the reported soluble form. The exons corresponding to these three inserts were identified in the murine CD46 genome, indicating that the alternative splicing of mRNA participates in the generation of these various CD46 messages. In normal mouse sera and cell lines, however, virtually no soluble CD46 was detected on immunoblotting. On Northern blotting analysis with specific probes, on the other hand, variant 1 was found to be predominantly expressed in the liver and heart. In addition, all variant messages were detected on PCR in all organs examined. When a rabbit cell line, RK13 cells, was transfected with cDNA of variant 1, protein synthesis was detected on immunoblotting. Although the mCD46 protein production was inefficient, this variant 1 exhibited factor I-cofactor activity as to inhibition of the complement cascade. Since the mCD46 protein was reported to be markedly up-regulated on infection of murine cells with mCMV, the soluble mCD46 proteins may act as a complement regulator that controls the systemic complement system under the conditions of a viral infection.
The membrane filter hybridization technique has been widely used for gene expression profiling. The preparation of sensitive and reliable probes is critical for quantitative analysis in this technique. We report a method in which fluorescently labeled poly(dU) is used to detect poly(A)-containing mRNA that hybridizes to specific gene targets. The probe can be used commonly for every sample, alleviating problems encountered in preparing cDNA probes by reverse transcription, particularly when many samples are to be analyzed. Moreover, the sensitivity is at least comparable to cDNA probes prepared by conventional protocols, and intensities of signals after hybridization are independent of mRNA sizes and solely dependent on copy numbers. This method was also shown to be applicable to DNA chip technology.
Carbonic anhydrase II (CAII) catalyzes the reversible hydration of carbon dioxide and plays key roles in acid base homeostasis in mammals. We found that human CAII gene promoter could be activated in human cells such as HeLa and T47D cells when the CAII promoter-luciferase gene was transfected with v-Src and assayed as a reporter of the promoter activity. Kinase negative mutants of Src, in contrast, showed little activation. The activation was completely suppressed with the introduction of a dominant-negative Ras in T47D cells, while no suppression was observed in HeLa cells. Introduction of various kinds of deletions into the CAII promoter revealed two essential regions responsible for this activation. No activation, however, was observed in activated Fyn-transfected human cells or in v-Src-transfected rodent cells. These findings suggest that Src can modulate the human CAII promoter by exerting its tyrosine kinase activity in certain human cells, and that two types of Src signaling pathways, Ras-dependent and -independent, exist in a cell type dependent manner.
The reaction of oleanane triterpenoid 1b with a FeIII(PA; picolinate)3/H2O2/MeCN system (reagent system A), a simple model system for mono-oxygenase, gave the 11 alpha-hydroxyl derivative 3 as major product, along with 11-oxo derivative 4 and 12-oxo derivative 6. The reaction of lupane triterpenoid 2b with reagent system A gave only oxidative rearrangement compounds, (20R)-aldehyde 8 and (20S)-aldehyde 9 were epimeric isomers. Then, we have found that iron(III) picolinate complex, FeIII(PA)3 is efficient in effecting the rearrangement of triterpenoid epoxides 5 and 7 into the corresponding carbonyl compounds, 6, 8 and 9 with 1,2-shift of the hydride.
The temporal changes in intensity of myelination of the nervous pathways in 0 to 42-day-old Wistar rats were quantitatively analyzed by immunohistochemistry with anti-proteolipid protein and compared with that obtained by immunohistochemistry with anti-myelin basic protein. Immunohistochemistry was performed on paraffin-embedded tissue according to the standard ABC technique. Intensity of myelination was examined by an image analyzing system. We analyzed nine nervous pathways: corpus callosum, optic tract, internal capsule, spinal tract of the trigeminal nerve, inferior cerebellar peduncle, cerebellar white matter, pyramidal tract, medial longitudinal fasciculus, and cuneate fasciculus. The presence of immunoreactive fibers for proteolipid protein (PLP) in the spinal tract of the trigeminal nerve, medial longitudinal fasciculus and cuneate fasciculus was noted on postnatal day 0. Those of the corpus callosum, inferior cerebellar peduncle, cerebellar white matter, pyramidal tract and internal capsule were noted on day 7, and that of optic tract on day 14. The time required to reach the intensity of myelination of day 42 was day 14 for the cuneate fasciculus, day 21 for the spinal tract of the trigeminal nerve, inferior cerebellar peduncle and medial longitudinal fasciculus, day 28 for the optic and pyramidal tracts, day 35 for the corpus callosum and day 42 for the internal capsule and cerebellar white matter. The appearance of immunoreactive fibers for PLP was usually earlier than that for myelin basic protein (MBP) and the pattern of difference between PLP and MBP can be classified into three groups: (1) their time of appearance and progress are almost the same, as in the optic tract; (2) the appearance and progress of PLP occurs earlier than those of MBP, as in the pyramidal tract; (3) the appearance of PLP occurs earlier than that of MBP, but their progress is the same. Our findings revealed that the time of appearance and progress of myelination as measured by PLP are different among the nervous pathways, and that there is also a difference between PLP and MBP. This difference between PLP and MBP may indicate a functional difference between them.
A new member of the connexin family was isolated from the porcine ovary. The amino acid sequence deduced from the nucleotide sequence of genomic as well as complementary DNA clones predicted the reading frame encoding the 60-kDa protein product, indicating the largest molecular mass among the connexin family genes analyzed to date; we named this gene Cx-60 based on its predicted molecular mass. The features of its primary structure were compared with those of other connexin genes, and the characteristics of its expression profile were examined in mammalian ovarian follicles. Cx-60 shares significant similarities with other connexins in the transmembrane and extracellular domains, but showed a highly unique primary structure in the cytoplasmic and carboxyl-terminal domains. The Cx-60 gene was unique in that its messenger RNA was detected in both the theca interna compartment and cumulus cells in the ovary; of other tissues, Cx-60 expression was relatively evident in the colon, thymus, and spleen. Cx-60, in contrast to Cx-43, was expressed constitutively upon gonadotropin stimulation when examined in hypophysectomized rats. Taken together, these results indicate that at least the connexin genes Cx-60, Cx-43, Cx-32, Cx-30.3, and Cx-26 are expressed in porcine ovarian follicles with differing expression profiles, including cell specificity.
We devised a three-dimensional method for estimation of cerebral development and myelination which measures cerebral volume using MRI. Accuracy of the system was estimated using cadaver brains. The mean percentage error in the calculated volumes compared with the real volumes was 2.33%, range 0.00-5.33%. We applied the method to the volume of both cerebral hemispheres (CH), basal ganglia, thalamus and internal capsule (BT), and myelinated white matter (WM) in 44 neurologically normal individuals (4 months to 28 years of age), 13 patients with spastic motor disturbances (2-25 years of age), and 9 patients with athetotic motor disturbances (2-23 years of age). In the neurologically normal cases, the volumes of CH, BT and WM increased with age; the volume of MW more slowly than that of CH. In cases with spastic motor disturbances, the volumes of CH, BT and WM were between -1.4 and 3.5 SD, -1.0 and -3.5 SD, and 0.0 and -5.2 SD respectively, of those of neurologically-normal cases. On the other hand, 7 of the 9 cases with athetotic motor disturbances were within 2 SD of the volume of CH in neurologically normal cases. Our method for direct measurement of cerebral volume based on serial MRI should be useful for the accurate assessment of brain development and quantitative analysis of delayed myelination.
Non-enzymic oxygenation reaction of methyl valproate (2) utilizing a simple model system for mono-oxygenases, Fe(MeCN)2(6+)-H2O2-Ac2O in MeCN, was investigated in connection with stereochemical analyses of the mammalian metabolites of 1. This oxygenation reaction of methyl valproate (2) gave a 92:8 mixture of the anti-isomer 4a and the syn-isomer 4b, together with 5a, and 5b corresponding to the mammalian metabolites of 1. The stereochemistry of 4a, 5a, and 5b was elucidated by spectral analyses of the corresponding beta-lactone 6a, gamma-lactone 7a and 7b prepared from the oxygenation products. The asymmetric synthesis of (+)-7a was also achieved.
A stable cation radical Weitz' aminium salt, tris(4-bromophenyl)aminium hexachloroantimonate (BAHA) initiated electron transfer has been found to efficiently promote a great variety of reactions on electron-rich substrates: e.g. the cation radical pericyclic reactions, the chain-induced cation radical oxygenation of strained olefines and dienes, and several other intriguing reactions on a great variety of electron-rich substrate. The discovery of the Weitz' aminium salt catalysed Diels-Alder reaction has stimulated interest in cation radical chemistry and facilitated the development of a wide range of cation radical pericyclic chemistry. Applications of the method to the synthesis of natural products utilizing BAHA are also presented. Reaction of a lignan precursor, cinnamyl alcohols with BAHA in tetrahydrofuran (THF) gave a furofuran lignan, (+/-)-sesamin in one step. Podophyllum lignans, (+/-)-isopodophyllotoxin and (+/-)-isopicropodophyllin were synthesized by a biomimetic procedure from the doubly unsaturated esters by means of the BAHA induced cation-radical cycloaddition reaction. A new general synthesis for (+/-)-dibenzocyclooctadiene lignans was established utilizing novel synthetic method for quinone derivatives by oxidation with BAHA. Reactions of phenol derivatives using BAHA gave the corresponding quinone derivatives, which may be useful synthon for obtaining quassinoids such as quassin.
The temporal order of the myelination of the nervous pathways in 0-42-day-old Wistar rats was quantitatively analyzed using immunohistochemistry with anti-myelin basic protein (MBP) antibody. Immunohistochemistry was performed on paraffin-embedded tissue according to the standard ABC technique. For the objective evaluation of myelination, we converted the level stained with the immunohistochemical method into continuous numbers of 0-256 giving the intensity of myelination, using an image analyzing system. We analyzed nine nervous pathways: corpus callosum, optic tract, internal capsule, spinal tract of trigeminal nerve, inferior cerebellar peduncle, cerebellar white matter, pyramidal tract, medial longitudinal fasciculus, and cuneate fasciculus. The onset of the myelination of the spinal tract of the trigeminal nerve, inferior cerebellar peduncle, medial longitudinal fasciculus and cuneate fasciculus was day 7 (postnatal). That of the corpus callosum, optic tract, internal capsule and cerebellar white matter was day 14, and that of the pyramidal tract was day 21. The time required to reach the level of myelination of day 42 was day 21 for the spinal tract of the trigeminal nerve and the inferior cerebellar peduncle, day 28 for the internal capsule, day 35 for the corpus callosum, optic tract, cerebellar white matter and pyramidal tract, and day 42 for the medial longitudinal fasciculus. Our method using immunohistochemistry with anti-MBP antibody provided a highly sensitive and objective criterion for judging precisely the time and the progress of myelination in each nervous pathway and compare one nervous pathway with another.
Connexin genes expressed in porcine ovaries were isolated by reverse transcription-PCR, and the expression of four connexin genes (Cx-43, -32, -30.3, and -26) was detected by in situ hybridization in internal and surrounding compartments of large antral follicles. Cx-43 and Cx-30.3 were expressed in the theca interna as well as in the granulosa cell compartment. However, two zones were observed in the theca interna by probing with Cx-43; about a quarter of the region close to the lamina basalis appeared devoid of Cx-43 messenger RNA (mRNA) and protein as well. Cx-30.3, in contrast, seemed to be expressed ubiquitously in these two compartments. Cx-26 and Cx-32 were expressed only in the thecal cells. Both Cx-43 and -30.3 also gave positive signals in the cumulus cells to the same extent as obtained in the granulosa cells with the respective probes, whereas the expression of Cx-32 and -26 was undetectable. Cx-43 mRNA drastically decreased in the functioning stage of the corpus luteum, whereas Cx-30.3 mRNA increased significantly in the early stage of luteinization in the estrus cycles. These results suggest that Cx-43 is not the only gap junction protein to be expressed in the ovarian follicle; other proteins, such as Cx-32, -30.3, and -26 seem to be expressed, and their expressions are regulated differently.
We analyzed dystrophin in case of normal control, Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD) and infectious muscular disease using two-dimensional gel electrophoresis and immunoblotting with 3 monoclonal dystrophin antibodies: Dys 1, a mid-rod-domain antibody; Dys 2, a C-terminal-domain antibody; and Dys 3, an N-terminal-domain antibody. In cases of normal control, a clearly separated doublet of bands was observed for Dys 1 and 3 at molecular weights 400 and 420 kDa. The isoelectric point was between pH approximately 5.7-approximately 5.9, similar to that for the myosin heavy chain. In one DMD case, a single faint band was observed for Dys 2. BMD presented a single-band pattern for each antibody. Infectious diseases cases showed 3- to 5-band patterns for Dys 1 and single or no bands for Dys 2 and 3. The pI of the Dys 1 band was almost identical. These results suggest coexistence of normal dystrophin and its proteolytic products, both containing triple helical segment, and show that two-dimensional gel electrophoresis may be applicable in the analysis of dystrophin in muscular disease.
cDNA clones encoding stage-and/or space-specific genes in porcine ovarian follicles have been investigated by differential screening of cDNA libraries of granulosa cells and corpus luteum. A clone corresponding to mRNA preferentially expressed in the functional stage of corpus luteum was found to encode a protein similar to the human prostatic secretory protein, PSP94, which had been originally identified in male genital organs. The expression was detected widely in the functional corpora lutea by in situ hybridization histochemistry, but the signal was most prominent in the luteal cells surrounding blood vessels. In contrast, despite the structural similarity in their products, the expression of this newly identified gene was not detected in porcine prostate, suggesting that these structurally related proteins play different roles in mammalian genital organs.
Six children with acute cerebral insult, ranging in age from 3 days to 8 years, revealed periodic lateralized epileptiform discharges in their electroencephalographic recordings. Their etiologic factors were cerebral infarction, intracranial bleeding, purulent meningitis, acute infantile hemiplegia, and encephalitis. Each patient exhibited a different type of convulsive seizure. Computer tomography or magnetic resonance imaging revealed diffuse lesions covering the cerebral cortex and subcortical white matter in 2 patients, a lesion of the subcortical white matter in 1 patient, a linear lesion in the cortex and along the borderline between the cortex and the subcortical white matter in 1 patient, and localized lesions in the cortex and basal ganglia in 1 patient. There were findings indicating the disconnection of the cerebral cortex with deeper structures in 3 patients. The appearance rate of periodic lateralized epileptiform discharges increased at levels of consciousness from 5 to 7 on a pediatric modification of the Glasgow Coma Scale. At levels of consciousness from 8 to 14 and below 4, the rate was very low.
Parameters of linear measurement were compared with actual brain volume to assess the significance of linear measurements as indices of atrophy in 31 neurologically normal children and 22 neurologically abnormal children. Brain volume was established by means of an image-analyzing system using contiguous CT scans. The parameters or indices estimated were: (1) the maximum transverse width of both hemispheres, (2) the maximum longitudinal length of both hemispheres, (3) the maximum frontal subarachnoid space, (4) the maximum width of the interhemispheric fissure, (5) the maximum width of the Sylvian fissure, (6) Evans' ratio, (7) the maximum width of the third ventricle, (8) the cella media index, (9) the maximum width of the fourth ventricle. In neurologically normal children, the maximum transverse width of both hemispheres, the maximum longitudinal length of both hemispheres, the maximum width of the interhemispheric fissure and the maximum width of the Sylvian fissure correlated significantly with the combined volume (CV) of both hemispheres and basal ganglia. In particular, the maximum transverse width of both hemispheres and the maximum longitudinal length of both hemispheres had a high correlation. In neurologically abnormal children the maximum transverse width of both hemispheres and the maximum width of the interhemispheric fissure were significantly correlated with the CV of both hemispheres and basal ganglia.
Two antipeptide antibodies, one against the peptide corresponding to residues 307-327 (alpha Y91) and one against the peptide corresponding to the C-terminal portion (alpha C92) of the deduced amino acid sequence of the extracellular signal-regulated kinase 1 (ERK1), precipitated two 41-kDa and/or two 43-kDa phospho-proteins from mitogen-stimulated Swiss 3T3 cells. Electrophoretic mobilities on two-dimensional gels of the immunoprecipitated 41- and 43-kDa phosphoproteins were similar to those of the 41- and 43-kDa cytosol proteins, whose increased tyrosine phosphorylation we and others had originally identified in various mitogen-stimulated cells (Cooper, J. A., Sefton, B. M., and Hunter, T. (1984) Mol. Cell. Biol. 4, 30-37; Kohno, M. (1985) J. Biol. Chem. 260, 1771-1779); phosphopeptide map analysis revealed that they were respectively identical molecules. All those phosphoproteins contained phosphotyrosine, and the more acidic forms contained additional phosphothreonine. Immunoprecipitated 41- and 43-kDa phosphoproteins had serine/threonine kinase activity toward myelin basic protein (MBP) and microtuble-associated protein 2 (MAP2). With the combination of two-dimensional gel electrophoresis and the kinase assay in MBP-containing polyacrylamide gels of the alpha Y91 immunoprecipitates, with or without phosphatase 2A treatment, we showed that only their acidic forms were active. These results clearly indicate that 41- and 43-kDa proteins, the increased tyrosine phosphorylation of which is rapidly and commonly induced by mitogen stimulation of fibroblasts, are family members of ERKs/MAP2 kinases and that phosphorylation both on tyrosine and threonine residues is necessary for their activation.