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Biomedical subjects

K Noguchi

Publications and source records attributed to K Noguchi.

At least 55 records · Page 3Linked to original sources
PubMed2001

Change in gene expression in facial nerve nuclei and the effect of superoxide dismutase in a rat model of ischemic facial paralysis.

Peripheral nerve injury induces changes in gene expressions of a variety of neuroactive substances in cell somata, which may have roles in the adaptive response to the injury, neuronal survival, growth and regeneration. In this study, we designed a rat model of ischemic peripheral facial paralysis with a selective embolization technique, and observed mRNA expression of calcitonin gene-related peptide (CGRP), c-jun, and growth associated protein (GAP)-43 in facial nerve nuclei using in situ hybridization histochemistry. The rats were demonstrated to have a transient facial paralysis consistently, and thus this method was regarded as a model of minor peripheral nerve injury. The mRNA of CGRP, c-jun and GAP-43 showed a distinct pattern of induction and time course of increase after the ischemic nerve injury. The results suggest that the small injury to the peripheral nerve was able to induce changes in mRNA expression in the cell body of motoneurons. We also investigated the protective effect of superoxide dismutase (SOD), which is a free radical-scavenging enzyme involved in cellular antioxidant defenses. The SOD treatment clearly alleviated the behavioral impairment and decreased the CGRP mRNA expression at 3rd day after injury. These data suggest that a free radical generated by the ischemia may be partially responsible for ischemic nerve damage and the change in gene expression in motoneurons.

Animals↗
PubMed2001

Expression of TMEFF1 mRNA in the mouse central nervous system: precise examination and comparative studies of TMEFF1 and TMEFF2.

TMEFF1 and TMEFF2 are putative transmembrane proteins comprised of one epidermal growth factor (EGF)-like domain and two follistatin-like domains. Both TMEFF1 and TMEFF2 are predominantly expressed in the brain. We previously demonstrated that recombinant TMEFF2 protein can promote survival of neurons in primary culture and determined expression sites of TMEFF2 mRNA in the mouse central nervous system. To extend our understanding of TMEFF protein functions, we compared precise sites of expression of TMEFF1 and TMEFF2 mRNA using in situ hybridization analysis. Although both TMEFF genes are widely expressed in the brain, they exhibit different patterns of expression. TMEFF1 showed comparatively higher signals in the pyramidal cells of fifth layer of the cerebral neocortex, CA3, CA1 and subiculum regions of the hippocampus, locus coeruleus, and dentate cerebellar nucleus. In contrast, TMEFF2 is highly expressed in the medial habenular, CA2, CA3 and dentate gyrus region of the hippocampus, corpus callosum, cerebellar cortex and cranial nerve nuclei (III, IV, VII, X, XII). The results presented here indicate that expression of TMEFF1 and TMEFF2 are regulated differently and that they play region-specific roles in the central nervous system.

Animals↗
PubMed2001

ASK1-signaling promotes c-Myc protein stability during apoptosis.

We previously reported that JNK is involved in the regulation of c-Myc-mediated apoptosis triggered by UV irradiation and anticancer drug treatment. Here we show that ASK1 is an upstream regulator for c-Myc-mediated apoptosis triggered by UV, and we found a direct role for Ser-62 and Ser-71 in the regulation of protein stability and function of c-Myc. The ASK1-JNK pathway enhanced the protein stability of c-Myc through phosphorylation at Ser-62 and Ser-71, which was required for c-Myc-dependent apoptosis by ASK1-signaling. Interestingly, ASK1-signaling attenuated the degradation of ubiquitinated c-Myc without affecting the ubiquitination process. Together, these findings indicate that the ASK1-JNK pathway promotes the proapoptotic activity of c-Myc by modulating c-Myc protein stability through phosphorylation at Ser-62 and Ser-71.

3T3 Cells↗
PubMed2001

Tumor necrosis factor alpha (TNFalpha)-like factor produced by macrophages in rainbow trout, Oncorhynchus mykiss.

The presence of a Tumor Necrosis Factor alpha (TNFalpha)-like molecule has been suggested in fish by biological assays and biological and antigenic cross-reactivities with human TNFalpha. In the present study, whether rainbow trout macrophages produce TNFalpha was examined. Murine recombinant TNFalpha (m-rTNFalpha) was used as the standard mammalian TNFalpha. The supernatants were harvested from trout macrophage culture stimulated with lipopolysaccharide (LPS) and then passed through a Polymyxin B column to remove LPS. Results show that trout macrophage culture supernatants exhibit TNF-like activities. The supernatants significantly enhanced neutrophil migration and macrophage respiratory burst activity as assessed by NBT reduction test. The supernatants were also highly cytotoxic to murine L929 cells, which are known to be sensitive to mammalian TNFalpha. The biological activities of TNF in the trout macrophage culture supernatant was determined as 2.6 U ml(-1) in the presence of actinomycin D. This indicates biological cross-reactivity of trout TNFalpha-like factor on mammalian cells. Moreover, these activities were inhibited by a rabbit anti-mTNFalpha antibody. These results suggest that rainbow trout macrophages produce a TNFalpha-like factor that is similar to the mammalian TNFalpha in functions.

Animals↗
PubMed2001

Inhibition of PSA flare in prostate cancer patients by administration of flutamide for 2 weeks before initiation of treatment with slow-releasing LH-RH agonist.

BACKGROUND: A prospective randomized study was designed to determine whether flutamide (FLU) administered before treatment with a luteinizing hormone-releasing hormone agonist (LH-RHa) prevented prostate-specific antigen (PSA) flare in prostate cancer patients. METHODS: Prostate cancer patients were randomized into two groups and received either FLU (n = 11) or no pretreatment (n = 13) for 2 weeks before the initial injection of LH-RHa. LH-RHa (every 4 weeks) and FLU (every day) were administered throughout the period of this study. Blood samples, for the determination of PSA, testosterone (T), and luteinizing hormone levels, were collected before FLU administration, and before and 2, 7, 14, 28, 56, and 84 days after the first administration of LH-RHa. RESULTS: Treatment with FLU prior to LH-RHa induced an early decline in PSA level. The mean PSA level showed no significant secondary rise after LH-RHa administration in those patients with FLU pretreatment. Patients in both groups showed T flare after the first LH-RHa administration. However, the number of patients with PSA flare was significantly lower in patients with prior FLU administration than in those with LH-RHa alone. CONCLUSION: These results clearly demonstrate that, in patients with prostatic cancer, the administration of FLU for 2 weeks prior to the first LH-RHa administration is effective in preventing PSA flare, as well as in inducing an early decline in PSA levels.

Administration, Oral↗
PubMed2001

HNS-32, a novel azulene-1-carboxamidine derivative, inhibits nifedipine-sensitive and -insensitive contraction of the isolated rabbit aorta.

The vasorelaxant profile of a novel azulene-1-carboxamidine derivative, HNS-32 [N1,N1-dimethyl-N2-(2-pyridylmethyl)-5-isopropyl-3,8-dimethyl-azulene-1-carboxamidine, CAS 186086-10-2], was investigated in the isolated rabbit aorta precontracted with high KCl, noradrenaline (NA) or phorbol 12, 13-dibutyrate (PDBu) and compared with those of nifedipine and nitroglycerin. In preparations without endothelium, HNS-32 elicited concentration-dependent, full inhibition of contractions elicited by high KCI (80 mM), NA (3x10(-6) M) or PDBu (10(-6) M). In contrast, nifedipine inhibited only the contraction elicited by membrane depolarization with high KCl. Nitroglycerin also attenuated high-KCl-, NA- and PDBu-elicited contractions effectively, although full suppression was obtained only for NA-elicited contraction. Whilst the relaxant effect of HNS-32 was not affected by the presence of endothelium, the relaxant response to acetylcholine was endothelium dependent. Addition of excess Ca2+ restored both the HNS-32-reduced tension in muscle precontracted with high KCI and the nifedipine-mediated tension decrease. Relaxation elicited by HNS-32 was not affected by the adenylate cyclase inhibitor, 9-(tetrahydro-2'-furyl)adenine (SQ 22,536, 10(-4) M), the soluble guanylate cyclase inhibitor, 1H-(1,2,4)-oxadiazolo-(4,3-a)-quinoxalin-1-one (ODQ, 10(-5) M) or a cocktail of K+ channel blockers (glybenclamide 10(-6) M, tetraethylammonium 2x10(-3) M, apamin 10(-7) M, 4-aminopyridine 10(-4) M and Ba2+ 10(-5) M). These findings indicate that HNS-32 inhibits both L-type Ca2+ channel-dependent and -independent vascular contraction. Blockade of Ca2+ entry through L-type Ca2+ channels may be involved in the inhibitory effect of HNS-32 on the contraction due to membrane depolarization with high KCl. On the other hand, HNS-32 seems to inhibit Ca2+ channel-independent contraction via mechanism(s) other than elevation of cyclic nucleotides (cAMP and cGMP) and opening of K+ channels.

Animals↗
PubMed2001

Adult T-cell leukemia associated with gastric carcinoma: report of a case.

A 67-year-old man was admitted to our hospital with nausea and epigastralgia, and a diagnosis of smoldering type adult T-cell leukemia (ATL) associated with advanced gastric carcinoma was made. The gastric carcinoma had caused pyloric stenosis, and investigations revealed regional lymph node metastasis. The patient underwent total gastrectomy, splenectomy, cholecystectomy, and lymph node dissection with a Roux-en-Y anastomosis. Histological examination of the regional lymph nodes revealed not only metastases of gastric carcinoma, but also of ATL lymphoma, indicating a final diagnosis of advanced gastric carcinoma with locoregional lymph node due to both metastasis of the gastric carcinoma and the ATL lymphoma. Despite the administration of postoperative adjuvant chemotherapy comprised of cisplatin/adriamycin/5-fluorouracil in combination with oral etoposide and immunotherapy using ubenimex, paraplegia suddenly developed caused by the metastasis of ATL to the epidural space. Resection of this metastatic tumor for decompression of the spinal cord resulted in resolution of the paraplegia; however, the patient died about 1 month later from rapid systemic tumor growth.

Adenocarcinoma↗
PubMed2001

Downregulation of lipopolysaccharide-induced intercellular adhesion molecule-1 expression via EP2/EP4 receptors by prostaglandin E2 in human fibroblasts.

In the present study, the effect of prostaglandin E2 (PGE2) on intercellular adhesion molecule-1 (ICAM-1) expression in human gingival fibroblasts (HGF) stimulated with lipopolysaccharides (LPS) was investigated. LPS were isolated from periodontopathic bacteria, Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) and Porphyromonas gingivalis (P. gingivalis), by the phenol-water method and Escherichia coli (E. coli) LPS was used as a control. PGE2 significantly inhibited A. actinomycetemcomitans-, P. gingivalis- and E. coli-LPS-induced ICAM-1 expression. Next, of four PGE2 receptor subtypes (EP1, EP2, EP3 and EP4), we examined which subtype(s) was involved in inhibition of LPS-elicited ICAM-1 expression by PGE2. Eleven-deoxy-PGE1, a selective EP2/EP4 agonist, and butaprost, a selective EP2 agonist, attenuated A. actinomycetemcomitans-, P. gingivalis- and E. coli-LPS-elicited ICAM-1 expression, although butaprost was less potent than PGE2 and 11-deoxy-PGE1. Sulprostone, an EP1/EP3 agonist, and ONO-AP-324, an EP3 agonist, was inert to the LPS-elicited ICAM-1 expression. Furthermore, dibutyryl cAMP, a cAMP analogue, and forskolin, an adenylate cyclase activator, downregulated A. actinomycetemcomitans-, P. gingivalis- and E. coli-LPS-elicited ICAM-1 expression in HGF. Our data suggest that PGE2 downregulates A. actinomycetemcomitans- and P. gingivalis-LPS-induced ICAM-1 expression in HGF, via EP2/EP4 receptors by cAMP-dependent signaling pathways. The cAMP-elevating agents such as EP2/EP4 receptor activators may serve to control inflammatory and immune responses in periodontal disease.

Aggregatibacter actinomycetemcomitans↗
PubMed2001

Prostaglandin F2alpha upregulates interleukin-6 production in human gingival fibroblasts.

Prostaglandin F2alpha (PGF2alpha) is a bioactive lipid mediator which has been suggested to be involved in the pathogenesis of periodontal disease. However, the roles of PGF2alpha in periodontal lesions are poorly understood. In the present study, we investigated the effect of PGF2alpha on interleukin (IL)-6 production in human gingival fibroblasts (HGF). PGF2alpha stimulated IL-6 production in a time- and concentration-dependent fashion. IL-1beta and tumor necrosis factor alpha (TNFalpha), proinflammatory cytokines, induced IL-6 production in a time-dependent manner, and PGF2alpha synergistically enhanced IL-6 production induced by IL-1beta and TNFalpha. IL-6 mRNA was expressed in PGF2alpha-stimulated HGF, and PGF2alpha increased IL-6 mRNA levels induced by IL-1beta and TNFalpha. Fluprostenol, a selective FP receptor agonist, could mimic PGF2alpha-induced IL-6 production. Since FP receptors are coupled to elevation of intracellular calcium and activation of protein kinase C (PKC), the mechanism of IL-6 production by PGF2alpha was investigated using TMB-8, an inhibitor of Ca2+ mobilization from intracellular stores, and calphostin C, an inhibitor of PKC. TMB-8 significantly suppressed PGF2alpha-induced IL-6 production, whereas calphostin C showed a stimulatory effect on PGF2alpha-induced IL-6 production. From these data, we suggest that PGF2alpha upregulates IL-6 production through FP receptors in HGF, that PGF2alpha synergistically enhances IL-6 production in IL-1beta- and TNFalpha-stimulated HGF, and that PGF2alpha-induced IL-6 production may be dependent on intracellular Ca2+ mobilization and be downregulated by PKC activation. PGF2alpha may be involved in the pathogenesis of periodontal disease by enhancing IL-6 levels in periodontal lesions.

Calcium↗
PubMed2001

Involvement of cyclooxygenase-2 in serum-induced prostaglandin production by human oral gingival epithelial cells.

The purpose of the present study was to investigate the involvement of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in prostaglandin (PG) production by human oral gingival epithelial (OGE) cells stimulated with proinflammatory cytokines including interleukin(IL)-1alpha, IL-1alpha and tumor necrosis factor alpha (TNFalpha), and serum. Fetal bovine serum (FBS)-stimulated OGE cells produced significant levels of PGE2, whereas IL-1alpha, IL-1beta and TNFalpha could not induce significant PGE2 production. FBS induced PGE2 production in a dose- and time-dependent manner. NS-398, a selective COX-2 inhibitor, inhibited PGE2 production by FBS-stimulated cells as completely as indomethacin, a non-selective COX-1/COX-2 inhibitor. Expression of COX-2 protein in FBS-stimulated cells was increased, compared with that in unstimulated cells, whereas COX-1 protein expression was similar both in unstimulated and in FBS-stimulated cells. COX-2 mRNA was detected in FBS-stimulated cells, but not in unstimulated cells. We suggest that COX-2 is responsible for PG production by human OGE cells stimulated with serum and that OGE cells may be involved in PG production in periodontal lesions. Selective COX-2 inhibitors, which have the advantage of reduced gastric toxicity, may provide a useful approach to treatment of periodontal disease.

Analysis of Variance↗
PubMed2001

Upregulation of matrix metalloproteinase-1 production by prostaglandin F2alpha in human gingival fibroblasts.

In the present study, we investigated the effect of prostglandin F2alpha (PGF2alpha) and combination of PGF2alpha and interleukin(IL)-1beta on matrix metalloproteinase (MMP)-1 production in human gingival fibroblasts (HGF). PGF2alpha enhanced MMP-1 production in a dose-dependent manner in HGF. Combination of PGF2alpha and IL-1beta induced a synergistic increase of MMP-1 production in HGF. Furthermore, fluprostenol, a specific FP receptor agonist, increased MMP-1 production and induced a synergistic enhancement of IL-1beta-induced MMP-1 production in HGF, similar to PGF2alpha. FP receptor mRNA expression was detected in HGF, by reverse transcription-polymerase chain reaction. Northern blot analysis revealed that PGF2alpha enhanced MMP-1 mRNA expression in HGF and that PGF2alpha increased MMP-1 mRNA levels induced by IL-1beta. In conclusion, we suggest that PGF2alpha increases MMP-1 production in HGF and synergistically enhances MMP-1 production in IL-1beta-stimulated HGF. PGF2alpha may be involved in degradation of connective tissue in periodontal lesions.

Blotting, Northern↗
PubMed2001

Effect of 1-week treatment with erythropoietin on the vascular endothelial function in anaesthetized rabbits.

Chronic administration of erythropoietin (EPO) is often associated with hypertension in animals and humans. The aim of this study was to estimate whether 1-week treatment with EPO can affect the vascular endothelial function. Rabbits were given with EPO (400 iu kg(-1) s.c.) or saline each other day for 1 week. Hypotensive responses to intravenously given acetylcholine (ACh), endothelium-independent nitric oxide donors (NOC7, nitroprusside and nitroglycerin) and prostaglandin I2 were tested before and after administration of N(G)-nitro-L-arginine methyl ester (L-NAME), a specific nitric oxide synthase inhibitor, under pentobarbitone anaesthesia. Blood haemoglobin concentration in EPO group was significantly higher than that in control group, whereas baseline values of aortic pressure, heart rate and femoral vascular resistance were similar. The dose of ACh (172 ng kg(-1)) requiring for a 15 mmHg hypotension from the baseline in EPO group was apparently higher than that (55 ng kg(-1)) in control group. On the contrary, hypotensive responses to NOC7, nitroprusside, nitroglycerin and prostaglandin I2 were comparable between two groups. The extent of ACh-induced hypotension did not correlate with haemoglobin concentration. L-NAME significantly inhibited the ACh-induced vasodilating response in control group but did not in EPO group. In another set of rabbits, the same treatment with EPO also decreased vasodilating responses to carbachol, bradykinin and substance P besides ACh as compared with control group. These results indicate that 1-week treatment with EPO selectively attenuates depressor responses to endothelium-dependent vasodilators in anaesthetized rabbits, most likely due to inhibition of endothelial nitric oxide synthase.

Acetylcholine↗
PubMed2001

Increased expression of cyclooxygenase-2 in human salivary gland tumors.

We examined the immunohistochemical localization of cyclooxygenase (COX)-2 in human salivary gland tumors. Thirty salivary gland adenomas (SGA), 40 salivary gland carcinomas (SGC) and 15 normal salivary glands (NSG) were studied. NSG showed restricted COX-2 staining only in the epithelial cells of salivary ducts. In contrast, COX-2 protein was detected in 27 cases of SGA (90%), except for three myoepitheliomas, and in all cases of SGC (100%) at various intensities and in various fashions. Thirteen SGA (43%) and 36 SGC (90%) cases showed strong COX-2 staining predominantly in tumor cells containing ductal components, as did serous and mucous acinic components of acinic cell carcinomas, mucoepidermoid carcinomas and mucinous carcinomas. These findings may suggest that COX-2 in salivary gland tumors is expressed in tumor cells derived from pluripotential ductal epithelium that can histologically develop into either serous or mucinous acinar cells.

Adenoma↗
PubMed2001

The effect of electroacupuncture on pain behaviors and noxious stimulus-evoked Fos expression in a rat model of neuropathic pain.

Chronic-constriction injury (CCI) of the sciatic nerve causes mechanical and heat hyperalgesia and mechanical allodynia in the plantar surface of the hindpaw. The underlying mechanism thought to account for these phenomena include central sensitization induced by peripheral nerve injury, ie, the increase in neuronal activity of spinal dorsal horn neurons. As a marker of neuronal activation of the central nervous system, Fos expression has been used widely to monitor the change in neuronal activity evoked by peripheral input. In this study, we examined the antinociceptive effect of electroacupuncture (EA) on pain behavior and noxious stimulus-evoked Fos expression in dorsal horn neurons of the spinal cord in CCI rats 14 days after injury. Male Sprague-Dawley rats (180 to 200 g) received loose ligation of the left sciatic nerve. Heat and mechanical hyperalgesia and mechanical allodynia were examined by the plantar foot test, the pin-prick test, and the von Frey test before and after the EA treatment (100 Hz, 0.3 millisecond, 3 or 1 mA, 20 minutes) into the Zusanli point (S36). When EA stimulation to the Zusanli point was applied, the mechanical and heat hyperalgesia were significantly suppressed; however, mechanical allodynia was not affected. The EA stimulation to nonacupuncture point did not show any significant effect. Next, pinch stimulation was applied to the plantar surface of the operated hindpaw of the CCI rats for 10 minutes, and the stimulus-evoked Fos expression in dorsal horn neurons in L4-L6 spinal cord levels was then examined by using immunohistochemistry. The number of noxious stimulus-evoked Fos-labeled neurons in both the superficial and deep laminae of the dorsal horn in the CCI rats was increased significantly compared with those in sham-operated rats, suggesting an increased excitability of dorsal horn neurons to noxious stimuli. Concurrent EA treatment to the Zusanli point with the pinch stimulus suppressed the increase in the number of Fos-labeled cells in the spinal dorsal horn in the CCI rats. The present results show that EA treatment has antinociceptive effects on both pain behavior and neuronal activation of the spinal dorsal horn neurons in CCI rats.

Journal Article↗