[Expression of COX-1 and COX-2 and gastrointestinal diseases].
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Animals↗
Biomedical subjects
Y Takei
Publications and source records attributed to Y Takei.
A novel hepatic stellate (Ito) cell-derived protein, epimorphin, plays a key role in the late stages of liver regeneration.
Limited data exist regarding morphogenesis and differentiation during liver regeneration. We examined the role of epimorphin on liver regeneration. After 70% partial hepatectomy, mouse liver was collected on days 1, 3, 7, and 14 for immunohistochemistry and the detection of epimorphin mRNA and connexin 32. Using primary cultured rat hepatocytes, morphogenesis and differentiation of cells were tested with or without epimorphin. Seven days after cell inoculation, the expression of connexin 32 and the cell-cell communication was tested as a marker of differentiation. Epimorphin was detected exclusively in hepatic stellate cells. Connexin 32 was detected only in hepatocytes. After partial hepatectomy, epimorphin mRNA was detected on day 3 and peaked at day 7, followed by protein expression. Connexin 32 expression showed a similar time course. Cultured hepatocytes formed multicellular spheroids in an active epimorphin-coated culture dish and showed positive dye coupling, whereas the cell-cell communication was lost without active epimorphin. Because epimorphin was expressed late in liver regeneration, it might play a role in morphogenesis and differentiation.
Animals↗
Identification of a novel MCM3-associated protein that facilitates MCM3 nuclear localization.
MCM3 is essential for the initiation of DNA replication and also participates in controls that ensure DNA replication is initiated once per cell cycle. In a two-hybrid screen for proteins that interact with human MCM3, we identified and cloned a novel protein of which the calculated molecular weight is 80,291. A specific antibody against the protein identified a 80-kDa protein in HeLa cell extract, indicating the protein actually expressed in cells. The interaction of these proteins was confirmed by immunoprecipitation assay. Moreover, we clarified a nuclear localization signal of human MCM3, and we find that mutagenesis on the nuclear localization signal of MCM3 affected the binding of newly isolated MCM3-assosiated protein, Map80. Map80 was expressed in Escherichia coli as a fusion with His6 tag and purified with sequential column chromatographies. The addition of recombinant Map80 stimulated the amount of nuclear localized MCM3. These results suggest that Map80 is involved in the nuclear localization pathway of MCM3.
Acetyltransferases↗
Usefulness of nested PCR and sequence analysis in a nosocomial outbreak of neonatal enterovirus infection.
BACKGROUND: Non-polio enterovirus infections are recognized in children during summer-fall seasons and they sometimes cause large outbreaks. We experienced a nosocomial infection in the neonatal nursery and echovirus type 7 was isolated from samples of four patients. OBJECTIVES: We diagnosed the horizontal infection of four neonates by reverse transcriptase-nested polymerase chain reaction (RT-nested PCR) and the nucleotide sequence. STUDY DESIGN: Total RNA was extracted from clinical isolates, serum samples and cerebrospinal fluid (CSF). We amplified enterovirus genome in the 5'-noncoding region by nested PCR and determined the nucleotide sequences. RESULTS: Enterovirus genome was detected in all isolates, in the acute-phase sera in all four patients and in the CSF in one patient by the first PCR. By using nested PCR, the genome was detected from convalescent-phase sera in two patients. All enterovirus genome obtained from the nursery outbreak showed the same sequences with 100% homology. CONCLUSION: We demonstrated the clinical advantages of RT-nested PCR from serum samples and the analysis of nucleotide sequencing gave the supportive evidence of identification of transmission pathway.
5' Untranslated Regions↗
Defect in synaptic vesicle precursor transport and neuronal cell death in KIF1A motor protein-deficient mice.
The nerve axon is a good model system for studying the molecular mechanism of organelle transport in cells. Recently, the new kinesin superfamily proteins (KIFs) have been identified as candidate motor proteins involved in organelle transport. Among them KIF1A, a murine homologue of unc-104 gene of Caenorhabditis elegans, is a unique monomeric neuron- specific microtubule plus end-directed motor and has been proposed as a transporter of synaptic vesicle precursors (Okada, Y., H. Yamazaki, Y. Sekine-Aizawa, and N. Hirokawa. 1995. Cell. 81:769-780). To elucidate the function of KIF1A in vivo, we disrupted the KIF1A gene in mice. KIF1A mutants died mostly within a day after birth showing motor and sensory disturbances. In the nervous systems of these mutants, the transport of synaptic vesicle precursors showed a specific and significant decrease. Consequently, synaptic vesicle density decreased dramatically, and clusters of clear small vesicles accumulated in the cell bodies. Furthermore, marked neuronal degeneration and death occurred both in KIF1A mutant mice and in cultures of mutant neurons. The neuronal death in cultures was blocked by coculture with wild-type neurons or exposure to a low concentration of glutamate. These results in cultures suggested that the mutant neurons might not sufficiently receive afferent stimulation, such as neuronal contacts or neurotransmission, resulting in cell death. Thus, our results demonstrate that KIF1A transports a synaptic vesicle precursor and that KIF1A-mediated axonal transport plays a critical role in viability, maintenance, and function of neurons, particularly mature neurons.
Animals↗
Golgi vesiculation and lysosome dispersion in cells lacking cytoplasmic dynein.
Cytoplasmic dynein, a minus end-directed, microtubule-based motor protein, is thought to drive the movement of membranous organelles and chromosomes. It is a massive complex that consists of multiple polypeptides. Among these polypeptides, the cytoplasmic dynein heavy chain (cDHC) constitutes the major part of this complex. To elucidate the function of cytoplasmic dynein, we have produced mice lacking cDHC by gene targeting. cDHC-/- embryos were indistinguishable from cDHC+/-or cDHC+/+ littermates at the blastocyst stage. However, no cDHC-/- embryos were found at 8.5 d postcoitum. When cDHC-/- blastocysts were cultured in vitro, they showed interesting phenotypes. First, the Golgi complex became highly vesiculated and distributed throughout the cytoplasm. Second, endosomes and lysosomes were not concentrated near the nucleus but were distributed evenly throughout the cytoplasm. Interestingly, the Golgi "fragments" and lysosomes were still found to be attached to microtubules. These results show that cDHC is essential for the formation and positioning of the Golgi complex. Moreover, cDHC is required for cell proliferation and proper distribution of endosomes and lysosomes. However, molecules other than cDHC might mediate attachment of the Golgi complex and endosomes/lysosomes to microtubules.
Animals↗
Tetrapod-type [Asp1] angiotensin is present in a holostean fish, Amia calva.
The renin-angiotensin system has been identified in various vertebrates, from elasmobranchs to mammals. Tetrapod (amphibians to mammals) angiotensin (ANG) has Asp at the N-terminus, but Asp is replaced by Asn in elasmobranch and teleost fish. ANG I has been isolated from incubates of plasma and kidney extracts of the bowfin Amia calva, a holostean fish, using the eel vasopressor activity as an assay system; its sequence was found to be H-Asp-Arg-Val-Tyr-Val-His-Pro-Phe-Asn-Leu-OH after sequence analysis, mass spectrometry, and comparison with the synthetic peptide. This sequence is identical to bullfrog ANG I. [Asn1] ANG I was not detected. Thus the bowfin is the first fish species which contains only [Asp1] ANG I. The bowfin ANG I and II were no more vasopressor than eel peptides in the bowfin, indicating that bowfin ANG II receptors do not distinguish between [Asp1] and [Asn1] peptides. In the rat, bowfin ANG I and rat [Ile5, His9] ANG I have equipressor activities when examined in different animals, but the vasopressor activity of bowfin ANG I decreased following rat ANG I in the same animals, although the activity of rat ANG I was unaffected after bowfin ANG I. The present study directly demonstrates the presence of the renin-angiotensin system in a holostean fish and showed that its ANG II receptors have not yet fully coevolved with the homologous [Asp1] peptide.
Angiotensin I↗
A radioimmunoassay for the determination of angiotensin II in elasmobranch fish.
A homologous radioimmunoassay was developed to determine the concentration of angiotensin II (Asn1, Pro3, Ile5)-Ang II) in elasmobranchs. Cross-reactivity with elasmobranch angiotensin I and other heterologous angiotensins was high and therefore all potentially cross-reacting angiotensins were separated by high performance liquid chromatography after prior extraction with Sep-Pak C18 cartridges. The validity of the assay for the determination of elasmobranch Ang II was demonstrated by parallelism with a series of Ang II standards with serially diluted elasmobranch plasma extracts. Overall recovery of elasmobranch Ang II added to a plasma pool was 75.1 +/- 5.2%. Plasma Ang II concentrations measured by our RIA were similar in fish adapted to 70, 100, or 120% SW at 139 +/- 20.1, 109 +/- 15.3, and 119 +/- 16.3 fmol . ml-1, respectively.
Adaptation, Physiological↗
Development of glycosylated human interleukin-1alpha, neoglyco IL-1alpha, by coupling with D-galactose monosaccharide: biological activities in vitro.
In the previous study, galactose with C9 spacer was chemically coupled to human recombinant (rh) IL-1alpha in order to study the effect of glycosylation on its activities, and to develop IL-1 with less deleterious effects. In this study we examined a variety of IL-1 activities in vitro, including proliferative effect on T cells, antiproliferative effect on myeloid leukemic cells and melanoma cells, stimulatory effects on IL-6 synthesis by melanoma cells and PGE2 synthesis by fibroblast cells Galactose-introduced IL-1alpha (Gal-IL-1alpha) exhibited reduced activities from 10 to 10000 times compared with unmodified IL-1alpha in all the activities performed in vitro. The competitive binding of 125I-IL-1alpha to mouse T cells and pre-B cells with unlabeled IL-1alpha s suggests a decrease in binding affinities of Gal-IL-1alpha to both type I and type II IL-1 receptors. Therefore, reduced activities of Gal-IL-1alpha are due, at least partially, to the decrease in their receptor binding affinities.
Animals↗
Development of glycosylated human interleukin-1alpha, neoglyco IL-1alpha, coupled with D-galactose monosaccharide: biological activities in vivo.
In our previous study, a galactose monosaccharide with C9 spacer was chemically coupled to recombinant human interleukin 1alpha (rhIL-1alpha) in order to study the effect of glycosylation on its activities, and to develop IL-1 with less deleterious effects. The glycosylated IL-la exhibited reduced activities in vitro by 10 to 10000-fold depending upon different aspects of activities addressed. The affinity to type I and II IL-1 receptors were also reduced. In this study we examined a variety of IL-1 activities in vivo, including upregulation of serum levels of IL-6, alpha1-acid glycoprotein, NOx, corticosterone, downregulation of serum level of glucose, and recovery of peripheral white blood cells (WBCs) from myelosuppression in 5-fluorouracil-treated mice. In contrast to the biological activities in vitro, these activities in vivo were uniformly reduced by only about 10 to 20-fold compared to untreated IL-1alpha.
Animals↗
Development of glycosylated human interleukin-1alpha, neoglyco IL-1alpha, by coupling with D-galactose monosaccharide: synthesis and purification.
In order to develop glycosylated cytokine, recombinant human IL-1alpha was chemically modified with galactose monosaccharide. Galactose with C9 spacer, 8-(hydrazinocarbonyl)octyl beta-D-galactopyranoside (3), was synthesized by glycosylation of C9 spacer, methyl 9-hydroxynonanoate, with acetobromogalactose, followed by deacetylation and hydrazidation. Total yield of 3 was 43.6% in three steps. Compound 3 was coupled to IL-1alpha by the acyl azide method. The glycosylated IL-1 was purified by anion-exchange chromatography, and galactose coupled to IL-1 was confirmed by R. communis lectin blotting. Based on the molecular weight, the average number of carbohydrate molecules introduced per molecule of IL-1alpha was estimated to be 9.1.
Galactose↗
Event-related potentials in patients with obsessive-compulsive disorder.
Twenty-three unmedicated patients with obsessive-compulsive disorder (OCD) were compared with 12 unmedicated patients with social phobia (SP) and 18 age-matched normal controls (C) using a two-tone auditory oddball event-related potentials (ERP) paradigm. The OCD group showed significantly shorter P300 latencies and shorter N200 latencies for target stimuli than the SP and the C groups. The OCD patients also tended to have greater N200 negativity compared with normal controls. However, there were no significant relationships between these ERP abnormalities in OCD patients and the type or severity of their OCD symptoms. In the mean ERP waveforms, increased N200 negativity for target stimuli, as well as the provocation in the later part of N200 for non-target stimuli, were more commonly observed in the OCD and the SP groups compared with the C group. These results raise the possibility that the shorter N200 and P300 latencies in OCD patients may be an OCD-specific phenomenon that is more closely related to the biological basis for OCD, rather than the characteristics of their OCD symptoms. On the other hand, increased negativity in the N200 region, even for non-target stimuli, may represent the common abnormalities among anxiety disorders.
Adolescent↗
Awareness of and attitude of elderly subjects regarding health care and welfare in rapidly ageing population in Japan.
OBJECTIVES: We aimed to obtain information on the degree of knowledge and understanding about the current systems of health care and welfare held by the elderly, in order to achieve comprehensiveness in family practice. METHOD: We conducted a study on the awareness of healthy elderly persons by direct interview. The study was carried out in Kuni Village in a remote mountainous region in Japan, where the elderly population accounts for 24.8% of the total population. The subjects were self-dependent in their daily living activities and were aged 65 years and older. RESULTS: The subjects' knowledge of health care and welfare systems was generally good, and the degree of their utilization of these systems was also good. But 83.3% of those who did not want to utilize the welfare system indicated their preference to depend on their family for support. CONCLUSION: Family physicians must endeavour to offer comprehensive care to their patients by including these systems for rapidly ageing communities.
Aged↗
Personality disorders in patients with obsessive-compulsive disorder in Japan.
A total of 75 patients with obsessive-compulsive disorder (OCD) were studied in order to investigate the characteristics of OCD symptoms and the comorbidity of personality disorders (PD). Contamination obsessions and checking compulsions were most commonly found in patients, of whom 53% met the criteria for at least one PD. Among comorbid PD, the anxious-fearful (cluster C) PDs, such as avoidant, obsessive-compulsive and dependent PD, were most prevalent, followed by the odd-eccentric (cluster A) PDs, such as paranoid and schizotypal PD. The patients with PD had more severe social maladaptation and concurrent depressive and anxious symptoms than the patients without any PD, despite the similar severity of OCD symptoms. These results are consistent with those reported in the Western world, and are considered to be relatively stable cross-culturally.
Adolescent↗
Cyclooxygenase-2 inhibitors suppress the growth of gastric cancer xenografts via induction of apoptosis in nude mice.
To clarify the role of mitogen-inducible cyclooxygenase (COX-2) in the development of malignant tumors, we investigated the effects of COX-2 inhibitors on the growth of gastric cancer xenografts in nude mice in vivo. MKN45 gastric cancer cells (5 x 10(6) cells/animal) that overexpress COX-2 were inoculated subcutaneously into athymic mice. NS-398, a specific COX-2 inhibitor, or indomethacin, a nonspecific COX-2 inhibitor, was administered orally to animals every day for 20 days. These drugs reduced the tumor volume significantly. Immunohistochemistry using bromodeoxyuridine, nick end labeling, and electron microscopy showed that NS-398 induced apoptosis in cancer cells in a dose-dependent manner and inhibited cancer cell replication slightly. Indomethacin also induced apoptosis and suppressed replication of tumor cells. There was a significant negative correlation between tumor volume and apoptotic cell number within the tumor. These results are consistent with the hypothesis that COX-2 inhibitors suppress growth of gastric cancer xenografts mainly by inducing apoptosis and suppressing replication of the neoplastic cells. It follows that COX-2 plays an important role in the development of gastric cancer.
6-Ketoprostaglandin F1 alpha↗
Effects of homologous atrial natriuretic peptide on drinking and plasma ANG II level in eels.
The effects of eel atrial natriuretic peptide (ANP) on drinking were investigated in eels adapted to freshwater (FW) or seawater (SW) or in FW eels whose drinking was stimulated by a 2-ml hemorrhage. An intra-arterial infusion of ANP (0.3-3.0 pmol . kg-1 . min-1), which increased plasma ANP level 1.5- to 20-fold, inhibited drinking dose dependently in all groups of eels. The drinking rate recovered to the level before ANP infusion within 2 h after infusate was replaced by saline. The inhibition at 3.0 pmol . kg-1 . min-1 was profound in FW eels and hemorrhaged FW eels, whereas significant drinking still remained after inhibition in SW eels. Plasma ANG II concentration also decreased dose dependently during ANP infusion and recovered to the initial level after saline infusion in all groups of eels. The decrease at 3.0 pmol . kg-1 . min-1 was large in FW eels and hemorrhaged FW eels compared with that of SW eels. Thus the changes in drinking rate and plasma ANG II level were parallel during ANP infusion. Plasma sodium concentration and osmolality decreased during ANP infusion in SW and FW eels, and they were restored after saline infusion. In hemorrhaged FW eels, however, ANP infusion did not alter plasma sodium concentration and osmolality. Hematocrit did not change during ANP infusion in any group of eels. Collectively, ANP infusion at physiological doses decreased drinking rate and plasma ANG II concentration in parallel in both FW and SW eels. It remains undetermined whether the inhibition of drinking is caused by direct action of ANP or through inhibition of ANG II, which is known as a potent dipsogen in all vertebrate species, including eels.
Angiotensin II↗
Role of daunorubicin in the induction therapy for adult acute myeloid leukemia.
PURPOSE: To evaluate the relationship of total-dose of daunorubicin (DNR) to the induction therapy and treatment outcome, we have administered individualized doses of DNR during induction treatment to patients with acute myelogenous leukemia (AML). PATIENTS AND METHODS: Ninety-two previously untreated adult patients with AML who entered our hospital were analyzed for the dose of DNR required to achieve complete remission (CR), the CR rate, disease-free survival (DFS), and overall survival (OS). Induction therapy consisted of DNR 40 mg/m2 daily intravenously from day 1 until the marrow was hypoplastic, cytarabine (Ara-C), prednisolone (PRD), and/or 6-thioguanine (6-TG). RESULTS: Eighty-three of 92 patients with adult AML were assessable for this study. Sixty-three (76%) patients achieved CR. Fifty-two of 63 CR patients achieved the CR in the first course of induction therapy, and 11 patients required the second course of induction therapy. The 5-year and 10-year DFS rates were 31.2% and 5-year and 10-year OS rates were 45.1% and 42.3%, respectively. The median total dose of DNR in the induction therapy was 280 mg/m2 (120 to 480 mg/m2). DNR dose did not influence the response to therapy and was not influenced by the initial WBC count or French-American-British (FAB) system classification. CONCLUSION: These results indicated that when the dose was linked to observed tumor response, the optimal dose of DNR in the induction therapy was approximately 280 mg/m2 (40 mg/m2 for 7 days), which is greater than the conventional dose of 40 to 60 mg/m2 for 3 days.
Adolescent↗
beta-Glucosidase activity in the rat small intestine toward quercetin monoglucosides.
In order to evaluate the positional specificity for a glucoside group in the hydrolysis of flavonoid glucosides in the rat small intestine, beta-glucosidase activity was measured with the quercetin monoglucosides, quercetin-3-O-beta-D-glucopyranoside (Q3G), quercetin-4'-O-beta-D-glucopyranoside (Q4'G) and quercetin-7-O-beta-D-glucopyranoside (Q7G), as well as with quercetin-3-O-rutinoside (rutin) and p-nitrophenyl-beta-D-glucopyranoside (NPG) by using the HPLC technique. Enzymes were prepared from rat small intestinal mucosa of the duodenum, jejunum and ileum, among which the enzyme activity of the jejunum was highest for all the glycosides tested. Q4'G was the richest substrate for a beta-glucosidase solution among these glycosides, while rutin and NPG were both poor substrates. This suggests that dietary flavonoid glucosides are primarily hydrolyzed and liberated aglycones in the jejunum.
Animals↗