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Biomedical subjects

K Noguchi

Publications and source records attributed to K Noguchi.

At least 19 recordsLinked to original sources
PubMed1999

Molecular cloning and chromosomal mapping of mouse intronless myc gene acting as a potent apoptosis inducer.

Our previous findings suggest that the activation of the rat intronless myc gene provides a selective advantage in tumor suppression through apoptosis induction. In the present study, to examine whether intronless myc gene acting as an apoptosis inducer is evolutionarily conserved in mammalian cells, we isolated the mouse intronless myc gene and characterized it. A sequence analysis demonstrated that mouse intronless myc gene, ms-myc, has a linearly opened translatable frame consisting of 1293bp with 90% homology with that of rat s-myc. The chromosomal locus of ms-myc was identified on chromosome 19B by a fluorescent in situ hybridization (FISH) analysis. Gene transfection experiments showed that the transient overexpression of ms-Myc with transactivation activity effectively induces cell death in a wild-type p53-independent manner. In addition, cells stably expressing transfected ms-myc became more susceptible to apoptosis induced by genotoxic stress such as UV-irradiation and hydrogen peroxide compared with untransfected control cells. These observations suggest that the rodents commonly contain an s-myc-type of intronless myc gene with apoptosis-inducing activity.

Amino Acid Sequence↗
PubMed1999

Differential regulation of alpha- and beta-CGRP mRNAs within oculomotor, trochlear, abducens, and trigeminal motoneurons in response to axotomy.

Spinal and cranial motoneurons express alpha- and beta-calcitonin gene-related peptide (CGRP) mRNAs constitutively at variable ratios, and these two mRNAs are differentially regulated following axotomy in spinal, facial, and hypoglossal motoneurons. The purpose of this study was to investigate the change in CGRP mRNA expression following nerve injury in oculomotor, trochlear, abducens, and trigeminal motor nuclei in which beta-CGRP mRNA is predominantly expressed under normal conditions. Using male Sprague-Dawley rats, either the left eyeball and the orbital contents including the bulbar muscles were removed, or the left masseter nerve was ligated and transected. The rats were allowed to survive for 1, 3, 7, 14, 28, 56 days following these procedures. The levels of mRNAs for alpha- and beta-CGRP and growth-associated protein (GAP)-43 were analyzed by in situ hybridization histochemistry using 35S-labeled oligonucleotide probes. Following nerve injury, the expression of alpha-CGRP mRNA rapidly increased on the directly-injured side in all of these nuclei. Thereafter, it gradually decreased and returned to about the control level at postoperative day 56 within oculomotor, trochlear, and abducens motoneurons, but it sustained at a high level within trigeminal motoneurons. The expression of beta-CGRP was quite variable among these nuclei, and significant changes were also seen on the side contralateral to the directly-injured side. These data indicate that the up-regulation of alpha-CGRP mRNA may be a common response of cranial motor neurons following axotomy even if the constitutive expression of beta-CGRP mRNA exceeds that of alpha-CGRP mRNA in these neurons.

Abducens Nerve↗
PubMed1999

Role of diffusion-weighted echo-planar MRI in distinguishing between brain brain abscess and tumour: a preliminary report.

Our purpose was to evaluate diffusion-weighted (DW) echo-planar MRI in differentiating between brain abscess and tumour. We examined two patients with surgically confirmed pyogenic brain abscess and 18 with metastatic brain tumours or high-grade glioma, using a 1.5 T system. The apparent diffusion coefficient (ADC) of each necrotic or solid contrast-enhancing lesion was measured with two different b values (20 and 1200 s/mm2). All capsule-stage brain abscesses (4 lesions) and zones of cerebritis (2 lesions) were identified on high-b-value DWI as markedly high-signal areas of decreased ADC (range, 0.58-0.70 [(10-3 mm2/s; mean, 0.63)]). All cystic or necrotic portions of brain tumours (14 lesions) were identified on high-b-value DWI as low-signal areas of increased ADC (range, 2.20-3.20 [(10-3 mm2/s; mean, 2.70)]). Solid, contrast-enhancing portions of brain tumours (19 lesions) were identified on high-b-value DWI as high-signal areas of sightly decreased or increased ADC (range, 0.77-1.29 [(10-3 mm2/s; mean, 0.94)]). Our preliminary results indicate that DW echo-planar MRI be used for distinguishing between brain abscess and tumour.

Aged↗
PubMed1999

Interleukin-4 and interferon-gamma inhibit prostaglandin production by interleukin-1beta-stimulated human periodontal ligament fibroblasts.

The purpose of the present study was to investigate the involvement of cyclooxygease-1 (COX-1) and cyclooxygenase-2 (COX-2) in prostaglandin (PG) production by human periodontal ligament (PDL) fibroblasts stimulated with a proinflammatory cytokine, inerleukin-1beta (IL-1beta), and to examine the effect of interleukin-4 (IL-4), a Th2 cytokine, and interferon-gamma (IFN-gamma), a Th1 cytokine, on PG production by the cells. IL-1beta-stimulated PDL fibroblasts produced prostaglandin E2 (PGE2) in a time-dependent manner. Indomethacin, a non-selective COX-1/COX-2 inhibitor, and NS-398, a selective COX-2 inhibitor, completely inhibited PGE2 production by IL-1beta-stimulated cells. Northern blot analysis showed that COX-2 mRNA was detected in IL-1beta-stimulated PDL cells, although not detected in unstimulated cells, while expression of COX-1 mRNA was in the same extent in both the cells. Dexamethasone inhibited COX-2 mRNA expression, COX activity and PGE2 production in IL-1beta-stimulated cells. IL-4 and IFN-gamma suppressed PGE2 production by IL-1beta-stimulated PDL fibroblasts, but COX activity enhanced by IL-1beta treatment was significantly inhibited by IL-4, not by IFN-gamma. Northern blot analysis showed that IL-4 depressed COX-2 mRNA expression with no effect on COX-1 mRNA expression. On the other hand, IFN-gamma had no effect on expression of COX-1 and -2 mRNA. These data suggest that COX-2 is primarily responsible for PGE2 production by IL-1beta-stimulated human PDL fibroblasts and that IL-4 inhibited PGE2 production by IL-1beta-stimulated PDL fibroblasts through down-regulation of COX-2 expression, while IFN-gamma suppressed the PGE2 production with no effect on COX-2 expression.

Cells, Cultured↗
PubMed1999

Prostaglandin E2 and I2 regulate intercellular adhesion molecule-1 expression in interleukin-1 beta-stimulated human gingival fibroblasts.

The present study investigated the effect of prostaglandin (PG) E2 and PGI2 on intercellular adhesion molecule-1 (ICAM-1) expression in interleukin-1 beta (IL-1 beta)-stimulated human gingival fibroblasts (HGF). IL-1 beta potently induced ICAM-1 expression in HGF and indomethacin, a cyclooxygenase inhibitor, enhanced ICAM-1 expression in the cells. These data showed that endogenous PGs generated by HGF stimulated with IL-1 beta downregulated ICAM-1 expression. IL-1 beta significantly increased the levels of PGE2 and, to a lesser extent, those of 6-keto-PGF1 alpha (a stable metabolite of PGI2) in the culture media of HGF. Indomethacin completely inhibited the production of PGE2 and 6-keto-PGF1 alpha in IL-1 beta-stimulated HGF. Exogenous PGE2 and carbacyclin (a stable derivative of PGI2) in the presence of indomethacin dose-dependently suppressed ICAM-1 expression in IL-1 beta-challenged HGF. Since PGE2 and PGI2 are known to elevate intracellular cyclic AMP (cAMP) levels, we examined the effect of dibutyryl cAMP, a cAMP analogue, and isobutylmethylxanthine, a phosphodiesterase inhibitor, on ICAM-1 expression. Both agents downregulated ICAM-1 expression in IL-1 beta-stimulated HGF. These results suggest that PGE2 and PGI2 downregulate ICAM-1 expression in IL-1 beta-stimulated HGF through a cAMP-dependent mechanism and that intracellular cAMP elevation in HGF may control inflammatory and immune responses in periodontal disease.

Cells, Cultured↗
PubMed1999

Long-term changes in brain following continuous phencyclidine administration: an autoradiographic study using flunitrazepam, ketanserin, mazindol, quinuclidinyl benzilate, piperidyl-3,4-3H(N)-TCP, and AMPA receptor ligands.

Phencyclidine induces a model psychosis which can persist for prolonged periods and presents a strong drug model of schizophrenia. When given continuously for several days to rats, phencyclidine and other N-methyl-D-aspartate (NMDA) antagonists induce neural degeneration in a variety of limbic structures, including retrosplenial cortex, hippocampus, septohippocampal projections, and piriform cortex. In an attempt to further clarify the mechanisms underlying these degeneration patterns, autoradiographic studies using a variety of receptor ligands were conducted in animals 21 days after an identical dosage of the continuous phencyclidine administration employed in the previous degeneration studies. The results indicated enduring alterations in a number of receptors: these included decreased piperidyl-3,4-3H(N)-TCP (TCP), flunitrazepam, and mazindol binding in many of the limbic regions in which degeneration has been reported previously. Quinuclidinyl benzilate and (AMPA) binding were decreased in anterior cingulate and piriform cortex, and in accumbens and striatum. Piperidyl-3,4-3H(N)-TCP binding was decreased in most hippocampal regions. Many of these long-term alterations would not have been predicted by prior studies of the neurotoxic effects of continuous phencyclidine, and these results do not suggest a unitary source for the neurotoxicity. Whereas retrosplenial cortex, the structure which degenerates earliest, showed minimal alterations, some of the most consistent, long term alterations were in structures which evidence no immediate signs of neural degeneration, such as anterior cingulate cortex and caudate nucleus. In these structures, some of the receptor changes appeared to develop gradually (they were not present immediately after cessation of drug administration), and thus were perhaps due to changed input from regions evidencing neurotoxicity. Some of these findings, particularly in anterior cingulate, may have implications for models of schizophrenia.

Animals↗
PubMed1999

Profile of urinary bile acids in infants and children: developmental pattern of excretion of unsaturated ketonic bile acids and 7beta-hydroxylated bile acids.

Unusual bile acids, such as unsaturated ketonic and 7beta-hydroxylated bile acids, have been detected in urine early in life. To elucidate the normal profiles of usual and unusual urinary bile acids in the neonatal and pediatric periods, we measured the concentrations of 28 kinds in urine from normal newborns, infants, and children by gas chromatography-mass spectrometry. The mean total bile acid/Cr ratio in 7-d-old infants was significantly higher than in subjects of other age groups (birth, 2-4 mo, 5-7 mo, 11-12 mo, 2-3 y, 9-14 y, and adult) (p < 0.05). Relatively large amounts of unusual bile acids were detected during infancy, especially during the period up to 1 mo of age. At that time, 1beta,3alpha,7alpha,12alpha-tetrahydroxy-5bet a-cholan-24-oic, 7alpha, 12alpha-dihydroxy-3-oxo-5beta-chol-1-en-24-oic, and 7alpha,12alpha-dihydroxy-3-oxo-4-cholen-24-oic acids were predominant among the unusual urinary bile acids present. Moreover, the levels of 3alpha,7beta,12alpha-trihydroxy-5beta-cholan+ ++-24-oic acid increased significantly after 2-4 mo of age. These results indicate that bile acid synthesis and metabolism in the liver of developing infants are significantly different from that occurring in the liver of adults. Significant amounts of urinary isomerized 7beta-hydroxylated bile acids were detected after late infancy, probably because of changes in the intestinal bacterial flora response to a change in nutrition. We describe, for the first time, evidence of the epimerization of the 7alpha-hydroxyl group of cholic acid, which may be unique to human development.

Adolescent↗
PubMed1999

The novel analgesic compound OT-7100 (5-n-butyl-7-(3,4,5-trimethoxybenzoylamino)pyrazolo[1,5-a]pyrimid ine) attenuates mechanical nociceptive responses in animal models of acute and peripheral neuropathic hyperalgesia.

We investigated the effects of OT-7100, a novel analgesic compound (5-n-butyl-7-(3,4,5-trimethoxybenzoylamino)pyrazolo[1,5-a]pyrimidi ne), on prostaglandin E2 biosynthesis in vitro, acute hyperalgesia induced by yeast and substance P in rats and hyperalgesia in rats with a chronic constriction injury to the sciatic nerve (Bennett model), which is a model for peripheral neuropathic pain. OT-7100 did not inhibit prostaglandin E2 biosynthesis at 10(-8)-10(-4) M. Single oral doses of 3 and 10 mg/kg OT-7100 were effective on the hyperalgesia induced by yeast. Single oral doses of 0.1, 0.3, 1 and 3 mg/kg OT-7100 were effective on the hyperalgesia induced by substance P in which indomethacin had no effect. Repeated oral administration of OT-7100 (10 and 30 mg/kg) was effective in normalizing the mechanical nociceptive threshold in the injured paw without affecting the nociceptive threshold in the uninjured paw in the Bennett model. Indomethacin had no effect in this model. While amitriptyline (10 and 30 mg/kg) and clonazepam (3 and 10 mg/kg) significantly normalized the nociceptive threshold in the injured paw, they also increased the nociceptive threshold in the uninjured paw. These results suggest that OT-7100 is a new type of analgesic with the effect of normalizing the nociceptive threshold in peripheral neuropathic hyperalgesia.

Amitriptyline↗
PubMed1998

Effects of halothane, ketamine and nitrous oxide on dynorphin mRNA expression in dorsal horn neurons after peripheral tissue injury.

Peripheral tissue injury is known to induce changes in gene expression in spinal neurons and result in a prolonged alteration of neuronal excitability. The purpose of this study was to examine the effect of halothane on the dynorphin mRNA expression in spinal dorsal horn neurons after peripheral tissue injury by formalin injection and compare the effect to that of ketamine and nitrous oxide. Male Sprague-Dawley rats were anesthetized with 1.3% halothane, ketamine, or 67% nitrous oxide. Fifteen minutes after induction of anesthesia, rats received an intraplantar injection of 150 microliter 5% formalin into the unilateral hindpaw. General anesthesia was maintained for 8 h, and the expression of preprodynorphin (PPD) and preproenkephalin (PPE) mRNAs in the spinal cord (L4-5) was examined by in situ hybridization. The degree of edema of the inflamed foot was not different among the three anesthesia groups and the control (no anesthesia) group. The number of neurons expressing PPD mRNA dramatically increased in the superficial dorsal horn ipsilateral to the formalin injection in the control group compared to the contralateral side. The number of neurons labeled for PPD mRNA in the halothane group was significantly less than the control group. However, the number of PPD mRNA-expressing neurons in both the ketamine and nitrous oxide groups was significantly less than the halothane group. The expression of PPE mRNA was not influenced by these anesthetics. These data indicate that the suppressive effect of halothane anesthesia on the induction of PPD mRNA in dorsal horn neurons was smaller than those of ketamine and nitrous oxide, suggesting an important supplemental way to control the alteration of gene expression in spinal neurons for clinical settings.

Anesthetics, General↗
PubMed1998

Male-to-female sex reversal in M33 mutant mice.

Polycomb genes in Drosophila maintain the repressed state of homeotic and other developmentally regulated genes by mediating changes in higher-order chromatin structure. M33, a mouse homologue of Polycomb, was isolated by means of the structural similarity of its chromodomain. The fifth exon of M33 contains a region of homology shared by Drosophila and Xenopus. In Drosophila, its deletion results in the loss of Polycomb function. Here we have disrupted M33 in mice by inserting a poly(A) capture-type neo(r) targeting vector into its fifth exon. More than half of the resultant M33cterm/M33cterm mutant mice died before weaning, and survivors showed male-to-female sex reversal. Formation of genital ridges was retarded in both XX and XY M33cterm/M33cterm embryos. Gonadal growth defects appeared near the time of expression of the Y-chromosome-specific Sry gene, suggesting that M33 deficiency may cause sex reversal by interfering with steps upstream of Sry. M33cterm/M33cterm mice may be a valuable model in which to test opposing views regarding sex determination.

Animals↗
PubMed1998

The RIIbeta regulatory subunit of protein kinase A binds to cAMP response element: an alternative cAMP signaling pathway.

cAMP, through the activation of cAMP-dependent protein kinase (PKA), is involved in transcriptional regulation. In eukaryotic cells, cAMP is not considered to alter the binding affinity of CREB/ATF to cAMP-responsive element (CRE) but to induce serine phosphorylation and consequent increase in transcriptional activity. In contrast, in prokaryotic cells, cAMP enhances the DNA binding of the catabolite repressor protein to regulate the transcription of several operons. The structural similarity of the cAMP binding sites in catabolite repressor protein and regulatory subunit of PKA type II (RII) suggested the possibility of a similar role for RII in eukaryotic gene regulation. Herein we report that RIIbeta subunit of PKA is a transcription factor capable of interacting physically and functionally with a CRE. In contrast to CREB/ATF, the binding of RIIbeta to a CRE was enhanced by cAMP, and in addition, RIIbeta exhibited transcriptional activity as a Gal4-RIIbeta fusion protein. These experiments identify RIIbeta as a component of an alternative pathway for regulation of CRE-directed transcription in eukaryotic cells.

3T3 Cells↗
PubMed1998

Medial amygdala stimulation produces a long-lasting excitatory postsynaptic potential/spike dissociation in the dentate gyrus in vivo.

We have previously found that high-frequency stimulation of the medial amygdala (MeA) induces long-term potentiation (LTP) of the population spike in the perforant path-dentate granule cell synapses of anesthetized rats. In the present study, we investigated the influence of MeA stimulation on the relationship between the population excitatory postsynaptic potential (pEPSP) and population spike in the dentate gyrus. High-frequency stimulation of the MeA produced a leftward shift of the E-S curve, in which population spike amplitude was plotted against pEPSP slope at various stimulus intensities. MeA-induced population spike LTP was also observed under blockade of GABAergic inhibition with picrotoxin. These results suggests that MeA stimulation leads to a long-lasting change in the internal firing characteristics of the dentate granule cells.

Action Potentials↗
PubMed1998

Functional modulation of human recombinant gamma-aminobutyric acid type A receptor by docosahexaenoic acid.

Human gamma-aminobutyric acid type A (GABAA) receptors were expressed in the baculovirus/Sf-9 insect cell expression system using recombinant cDNA of alpha1beta2gamma2s subunits. The effect of unsaturated fatty acids on GABAA receptor complexes was investigated electrophysiologically using conventional whole cell recording under voltage clamp. Three distinct effects of docosahexaenoic acid (DHA) on the GABA responses were observed. First, DHA, at a concentration of 10(-7) M or greater, accelerated the desensitization after the peak of the GABA-induced current. Second, DHA (10(-6) M) potentiated the peak amplitude of GABA response. This potentiation by DHA was inhibited in the presence of Zn2+ (10(-5) M); Cu2+ and Ni2+ mimicked the action of Zn2+. Zn2+ (10(-5) M) did not block the GABA response on alpha1beta2gamma2s receptor complexes. Third, DHA, at a concentration of 3 x 10(-6) M or higher, gradually suppressed the peak amplitude of GABA response. A protein kinase A inhibitor, a protein kinase C inhibitor, and a Ca2+ chelator did not modify the effects of DHA on GABA-induced chloride ion current. Six unsaturated fatty acids other than DHA were examined. Arachidonic acid mimicked the effect of DHA while e.g. oleic acid had no effect. The inhibition of the GABA response in the presence of DHA was also observed in cells expressing GABAA receptors of alpha1 and beta2 subunit combinations. The data show that the gamma subunit is essential for DHA and arachidonic acid to potentiate the GABA-induced Cl- channel activity and to affect the desensitization kinetics of the GABAA receptor.

Animals↗
PubMed1998

Medical amygdala-induced spike potentiation in the rat dentate gyrus is dependent on N-methyl-D-aspartate receptors and subcortical afferents.

We have previously found that high-frequency stimulation of the medial amygdala (MeA) produces a long-lasting potentiation of the population spike at medial perforant path-granule cell synapses in the dentate gyrus of anesthetized rats. The present study was performed to determine whether this novel form of potentiation requires activation of N-methyl-D-aspartate (NMDA) receptors and subcortical afferents. The MeA-induced spike potentiation was completely blocked by the NMDA receptor antagonist 3-((R,S)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (3.5 mg/kg, i.p). When the fimbria-fornix, a major pathway of subcortical afferents, was lesioned, the early phase of MeA-induced spike potentiation remained intact, but the late phase of potentiation was abolished. These results suggest that the NMDA receptor is essentially required for the induction of MeA-induced spike potentiation, while subcortical afferents contribute to the establishment of potentiation.

Afferent Pathways↗
PubMed1998

Characterization of tau phosphorylation in glycogen synthase kinase-3beta and cyclin dependent kinase-5 activator (p23) transfected cells.

One of the histopathological markers in Alzheimer's disease is the accumulation of hyperphosphorylated tau in neurons called neurofibrillary tangles (NFT) composing paired helical filaments (PHF). Combined tau protein kinase II (TPK II), which consists of CDK5 and its activator (p23), and glycogen synthase kinase-3beta (GSK-3beta) phosphorylate tau to the PHF-form in vitro. To investigate tau phosphorylation by these kinases in intact cells, the phosphorylation sites were examined in detail using well-characterized phosphorylation-dependent anti-tau antibodies after overexpressing the kinases in COS-7 cells with a human tau isoform. The overexpression of tau in COS-7 cells showed extensive phosphorylation at Ser-202 and Ser-404. The p23 overexpression induced a mobility shift of tau, but most of the phosphorylation sites overlapped the endogenous phosphorylation sites. GSK-3beta transfection showed the phosphorylation at Ser-199, Thr-231, Ser-396, and Ser-413. Triplicated transfection resulted in phosphorylation of tau at 8 observed sites (Ser-199, Ser-202, Thr-205, Thr-231, Ser-235, Ser-396, Ser-404, and Ser-413).

Animals↗
PubMed1998

New stacking variant of Laves phase found in (Ti0.95 V0.05) Co2 alloy.

Microstructures of the Laves phase alloy, (Ti0.95 V0.05) Co2, were studied by high resolution electron microscopy and electron diffraction. In this alloy system, coexistence of several kinds of layered structures was observed. Among these structures, a new stacking variant was found and was analyzed to be ABCAB'A'C'BCA'C'B'. This structure belongs to the trigonal system of the space group P3m1 (no. 164). The lattice parameters presented in the hexagonal system are a = 0.4727 +/- 0.0009 nm and c = 4.628 +/- 0.008 nm. This structure is called 12T in the Ramsdell notation and 4323 in the Zhdanov symbol, and is classified into hP3m1-(6i)5(3f)(3e)(2d)12(2c)6 using the Wyckoff notation.

Alloys↗
PubMed1998

Cocaine-induced changes in glutamate and GABA immunolabeling within rat habenula and nucleus accumbens.

We previously reported that subchronic administration of cocaine for 5 days via slow-release pellets results in pronounced degeneration in the lateral habenula (LHB) and its primary efferent tract, the fasciculus retroflexus [Ellison (1992): Brain Res 598:353-356; Ellison and Switzer (1993): Neuroreport 5:17-20]. The lateral habenula receives both GABA and glutamate afferents. In order to test the hypothesis that the cocaine-induced degeneration of the fasciculus retroflexus may be related to changes in synaptic activity of either GABA or glutamate nerve terminals within the LHB, the density of nerve terminal immunolabeling of either neurotransmitter was quantified after 5 days of chronic drug administration followed by either 1 or 14 days off the drug. The shell of the nucleus accumbens (NACs) was also analyzed, since this area is thought to be associated with the reward aspects of addictive stimulant drug administration and was previously shown not to be associated with fiber degeneration. We found that cocaine treatment resulted in a significant decrease in the density of nerve-terminal GABA immunolabeling located within the LHB in animals taken off the drug for either 1 or 14 days, while there was no change in the density of glutamate immunolabeling. In the NACs, there was a decrease in the density of glutamate immunolabeling within nerve terminals 1 day but not 14 days after cocaine administration. There was no change in the density of GABA immunolabeling within the NACs following the 1 or 14 day-off period. These results suggest that there are long-term changes in the density of GABA immunolabeling within the LHB and that the effects seen in glutamate synapses within the NACs are transitory. The long-term decrease in GABA immunolabeling within the LHB is consistent with the hypothesis that a decrease in inhibitory synaptic activity, leading to increased excitatory influence on LHB neurons, may result in neurotoxicity and the subsequent degeneration of the fasciculus retroflexus.

Animals↗