Biomedical subjects

N Ogata

Publications and source records attributed to N Ogata.

At least 55 records · Page 3Linked to original sources

PubMed2000

Spinal intradural perimedullary arteriovenous fistula with varix in infant.

A rare occurrence of type IV spinal arteriovenous malformation (intradural perimedullary arteriovenous fistula) is described in an 18-month-old boy initially misdiagnosed with Guillain-Barré syndrome. An intramedullary mixed-intensity mass lesion at Th1 was demonstrated by magnetic resonance imaging together with flow voids over the dorsal aspect of the swollen spinal cord. Angiography demonstrated an intradural perimedullary arteriovenous fistula including an intraparenchymal vascular pocket. After partial embolisation of the posterior spinal arteries through the left intercostal-radicular artery, the arteriovenous fistula was removed completely together with an organised haematoma. The fistula directly opened into a vascular pocket, which was confirmed pathologically to be a varix. The postoperative course was uneventful, and the patient resumed ambulation within 4 months. The case, subclassifiable as a type IVb spinal perimedullary AVF, was unique given its location and the patient's age at presentation.

Central Nervous System Vascular Malformations↗

PubMed2000

Insulin receptor substrate-1 in osteoblast is indispensable for maintaining bone turnover.

Insulin receptor substrates (IRS-1 and -2) are essential for intracellular signaling by insulin and IGF-I, anabolic regulators of bone metabolism. Mice lacking the IRS-1 gene IRS-1(-/-) showed severe osteopenia with low bone turnover. IRS-1 was expressed in osteoblasts, but not in osteoclasts, of wild-type (WT) mice. IRS-1(-/-) osteoblasts treated with insulin or IGF-I failed to induce tyrosine phosphorylation of cellular proteins, and they showed reduced proliferation and differentiation. Osteoclastogenesis in the coculture of hemopoietic cells and osteoblasts depended on IRS-1 expression in osteoblasts and could not be rescued by IRS-1 expression in hemopoietic cells in the presence of not only IGF-I but also 1,25(OH)(2)D(3). In addition, osteoclast differentiation factor (RANKL/ODF) was not induced by these factors in IRS-1(-/-) osteoblasts. We conclude that IRS-1 deficiency in osteoblasts impairs osteoblast proliferation, differentiation, and support of osteoclastogenesis, resulting in low-turnover osteopenia. Osteoblastic IRS-1 is essential for maintaining bone turnover, because it mediates signaling by IGF-I and insulin and, we propose, also by other factors, such as 1,25(OH)(2)D(3).

Animals↗

PubMed2000

Binding of alkyl- and alkoxy-substituted simple phenolic compounds to human serum proteins.

Wood creosote, primarily a mixture of simple alkyl- and/or alkoxy-substituted phenolic compounds with closely related structures, has long been used as an oral antidiarrheal agent. The use of wood creosote as a parenteral antidiarrheal agent was investigated, and for basic pharmacokinetic data we measured the extent of equilibrium binding of its six major constituent phenolic compounds to human serum proteins using an ultrafiltration method. The percent binding of these major constituent phenolic compounds, namely phenol, guaiacol, p-cresol, o-cresol, creosol and 4-ethylguaiacol, bound to 40-mg/ml human serum albumin was 15.5+/-0.9, 28.0+/-1.5, 37.2+/-0.7, 52.3+/-5.3, 36.8+/-2.0 and 56.7+/-2.4%, respectively, while percent binding to human serum (68 mg protein/ml) was 41.3+/-0.7, 42.6+/-0.5, 64.8+/-0.4, 70.1+/-1.6, 65.7+/-0.2 and 83.1+/-0.1% (mean +/- standard deviation, n = 4), respectively, when tested individually at a concentration of 500 micromol/l. Saturation of binding was not observed for the phenolic compounds up to a concentration of 50 mmol/l. Phenolic compounds with a lipophilic substituent showed higher percent binding to proteins than those without it. We conclude that simple phenolic compounds having alkyl- and/or alkoxy-substituents bind to serum proteins to a considerable extent and that the binding is hydrophobic and nonspecific.

Blood Proteins↗

PubMed1999

Suppression of atherosclerotic development in Watanabe heritable hyperlipidemic rabbits treated with an oral antiallergic drug, tranilast.

BACKGROUND: Inflammatory and immunological responses of vascular cells have been shown to play a significant role in the progression of atheromatous formation. Tranilast [N-(3,4-dimethoxycinnamoyl) anthranillic acid] inhibits release of cytokines and chemical mediators from various cells, including macrophages, leading to suppression of inflammatory and immunological responses. This study tested whether tranilast may suppress atheromatous formation in Watanabe heritable hyperlipidemic (WHHL) rabbits. METHODS AND RESULTS: WHHL rabbits (2 months old) were given either 300 mg x kg-1 x d-1 of tranilast (Tranilast, n=12) or vehicle (Control, n=13) PO for 6 months. Tranilast treatment was found to suppress the aortic area covered with plaque. Immunohistochemical analysis showed that there was no difference in the percentage of the RAM11-positive macrophage area and the frequency of CD5-positive cells (T cells) in intimal plaques between Tranilast and Control. Major histocompatibility complex (MHC) class II expression in macrophages and interleukin-2 (IL-2) receptor expression in T cells, as markers of the immunological activation in these cells, was suppressed in atheromatous plaque by tranilast treatment. Flow cytometry analysis of isolated human and rabbit peripheral blood mononuclear cells showed that an increase in expression both of MHC class II antigen on monocytes by incubation with interferon-gamma and of IL-2 receptor on T cells by IL-2 was suppressed by the combined incubation with tranilast. CONCLUSIONS: The results indicate that tranilast suppresses atherosclerotic development partly through direct inhibition of immunological activation of monocytes/macrophages and T cells in the atheromatous plaque.

Administration, Oral↗

PubMed1999

Trans-splicing of a voltage-gated sodium channel is regulated by nerve growth factor.

Mammalian sensory neurons express a voltage-gated sodium channel named SNS. Here we report the identification of an SNS transcript (SNS-A) that contains an exact repeat of exons 12, 13 and 14 encoding a partial repeat of domain II. Because the exons 12-14 are present in single copies in genomic DNA, the SNS-A transcript must arise by trans-splicing. Nerve growth factor, which regulates pain thresholds, and the functional expression of voltage-gated sodium channels increases the levels of the SNS-A transcript several-fold both in vivo and in vitro as measured by RNase protection methods, as well as RT-PCR. These data demonstrate a novel regulatory role for the nerve growth factor and are the first example of trans-splicing in the vertebrate nervous system.

Alternative Splicing↗

PubMed1999

Licensed recombinant hepatitis B vaccines protect chimpanzees against infection with the prototype surface gene mutant of hepatitis B virus.

The emergence in vaccinated individuals of hepatitis B virus (HBV) mutants with amino acid substitutions within the a determinant of the surface protein has raised the possibility that such variants represent neutralization escape mutants. We previously demonstrated that one such mutant HBV, strain AS, with an arginine substituted for glycine at surface gene codon 145, was infectious and pathogenic in seronegative chimpanzees. In the present study, the protective efficacy of licensed hepatitis B vaccines was evaluated against challenge with this mutant virus. Four chimpanzees were immunized with 1 of 2 licensed recombinant hepatitis B vaccines. Shortly after the chimpanzees developed antibodies to hepatitis B surface antigen (anti-HBs), they were challenged intravenously with mutant HBV strain AS. Two unvaccinated chimpanzees served as positive controls. The 4 vaccinated chimpanzees did not develop evidence of HBV infection or hepatitis during 2 years following virus challenge. In contrast, the 2 unvaccinated chimpanzees developed HBV infection and hepatitis. Serum anti-HBs in the vaccinated chimpanzees reacted not only with wild-type surface antigen, but also with mutant surface antigen by competition enzyme-linked immunosorbent assay (ELISA). Thus, immunization of chimpanzees with licensed recombinant hepatitis B vaccines stimulates anti-HBs that is broadly reactive and affords protection against infection with a surface gene mutant of HBV, suggesting that properly immunized individuals are not at significant risk of infection with this prototype variant strain of HBV.

Animals↗

PubMed1999

Transfection of basic fibroblast growth factor (bFGF) gene or bFGF antisense fene into human retinal pigment epithelial cells.

BACKGROUND: Transplantation of RPE cells offers a potential of restoring retinal pigment epithelium (RPE) function and has been shown to be effective in the dystrophic RCS rat model. Recently, RPE transplantation was attempted in patients with age-related macular degeneration. Basic fibroblast growth factor (bFGF) plays important roles in maintaining normal retinal function. The purpose of this study was to introduce bFGF sense or antisense cDNA into human RPE cells to alter the expression of bFGF. METHODS: Human bFGF sense cDNA or antisense cDNA was inserted into the pBK-CMV vector. For stable gene expression, we introduced the plasmids into RPE cells using the electroporation method. Following electroporation, transfected RPE cells were cultured and resistant cells were selected in the presence of antibiotic G418. We analyzed the expression of the transfected genes in the cloned RPE cells by polymerase chain reaction (PCR) and by reverse transcription (RT)-PCR. RESULTS: Cloned RPE cells in which the bFGF sense or antisense cDNA had been efficiently transfected were established. PCR and RT-PCR analysis demonstrated not only the presence but also the expression of bFGF sense or antisense cDNA in the transfected RPE cells. CONCLUSIONS: Human bFGF sense cDNA or antisense cDNA can be efficiently introduced into cultured RPE cells by the electroporation method. The successful expression of the genes into RPE cells demonstrated that this technique can be used to regulate bFGF expression and thus increase the scope of RPE transplantation for the treatment of retinal diseases.

Cells, Cultured↗

PubMed1999

Burst production of superoxide anion in human endothelial cells by lysophosphatidylcholine.

This study examined whether lysophosphatidylcholine (lysoPC), an atherogenic lipid, may stimulate production of O2*-, in cultured human endothelial cells. Production of O2*- was detected by bis-N-methylacridinium nitrate (lucigenin)-elicited chemiluminescence. LysoPC was found to induce burst production of O2*-, peaked at 2-4 min after the stimulation, in intact endothelial cells. LysoPC also stimulated NADH-dependent production of O2*- in particulate fraction of the cells, and the action of lysoPC was inhibited by diphenyliodonium. The results suggested that lysoPC stimulated production of O2*- partly through membrane-associated NADH-dependent O2*- production systems.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗

PubMed1999

Vertebral arteriovenous fistula that developed in the same place as a previous ruptured aneurysm: a case report.

BACKGROUND: Aneurysms of the extracranial vertebral artery (VA) and vertebral arteriovenous fistulas (VAVFs) are relatively rare diseases. The most frequent cause of both diseases is trauma. Atraumatic lesions are less common. Presented here is a case of atraumatic AVF of the extracranial VA that developed in the same location as a previous ruptured aneurysm of the ipsilateral VA that was originally treated by proximal occlusion 11 years earlier. METHODS: A 40-year-old woman presented with a massive hematoma in the upper posterior neck region caused by the rupture of an extracranial VA aneurysm. Proximal occlusion of the VA was performed by use of a detachable balloon. She enjoyed good health for 11 years, then she noticed a pulsatile bruit. Angiograms revealed an AVF between the left VA that was fed by collateral circulation and the paravertebral venous plexus. Incidentally found were soft tissue masses in the left retroauricular and the right suboccipital regions. Also, skull X-ray films showed multiple bony defects. Biopsy of the subcutaneous mass was performed in the hope of obtaining clues as to which pathological processes had weakened the artery. RESULTS: As direct transarterial access to the fistula was out of the question, the fistulous compartment of the paravertebral venous plexus was tightly packed with multiple platinum coils effected by the transfemoral approach. A histological examination of the specimen revealed features of a neurofibroma, and a diagnosis of neurofibromatosis Type 1 was established. CONCLUSIONS: In this case, transvenous embolization of the VAVF was successfully performed. The fragility of the arterial wall, related to neurofibromatosis Type 1, was considered to contribute to the development of the aneurysm and AVF.

Adult↗

PubMed1999

The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways.

Many damage-sensing neurons express tetrodotoxin (TTX)-resistant voltage-gated sodium channels. Here we examined the role of the sensory-neuron-specific (SNS) TTX-resistant sodium channel alpha subunit in nociception and pain by constructing sns-null mutant mice. These mice expressed only TTX-sensitive sodium currents on step depolarizations from normal resting potentials, showing that all slow TTX-resistant currents are encoded by the sns gene. Null mutants were viable, fertile and apparently normal, although lowered thresholds of electrical activation of C-fibers and increased current densities of TTX-sensitive channels demonstrated compensatory upregulation of TTX-sensitive currents in sensory neurons. Behavioral studies demonstrated a pronounced analgesia to noxious mechanical stimuli, small deficits in noxious thermoreception and delayed development of inflammatory hyperalgesia. These data show that SNS is involved in pain pathways and suggest that blockade of SNS expression or function may produce analgesia without side effects.

Afferent Pathways↗

PubMed1999

Down-regulation of TGF-beta receptors in human colorectal cancer: implications for cancer development.

Many colorectal cancer cells are resistant to the anti-proliferative effects of transforming growth factor-beta (TGF-beta). TGF-beta also acts as paracrine factor from cancer cells on their mesenchymal cells. The aim of this study was to examine the expression of TGF-beta and its receptors in human colorectal cancer tissue and determine any relationship with cancer growth. In situ hybridization and Northern blot hybridization detection of TGF-beta1, type I and type II receptor mRNA and immunohistochemical staining of TGF-beta1 were performed using 11 human colorectal adenomas, 22 colorectal cancers and ten normal colorectal mucosas as control. TGF-beta receptor mRNAs were expressed mainly by normal colorectal epithelial cells and adenoma. However, mRNAs for TGF-beta receptors were only faintly, if at all, expressed in eight of 22 human colorectal cancers. In addition, intense signals of TGF-beta1 mRNA and the protein were detected in all colorectal cancers. TGF-beta receptor mRNAs and TGF-beta1 protein were also distributed in fibroblasts and endothelial cells in the interstitium. Moreover, Smad 4 protein was translocated to nucleus in primarily cultured adenoma cells, but not in cancer cells after TGF-beta stimulation. The escape of human colon cancer from TGF-beta-mediated growth inhibition by down-regulation of TGF-beta receptors as well as the effects of TGF-beta on stroma formation and angiogenesis indicate a possible role for TGF-beta in the progression of colon cancer in an intact host.

Adenoma↗

PubMed1999

Anti-diarrhoeal effects of seirogan in the rat small intestine and colon examined in vitro.

BACKGROUND: Seirogan is a beechwood extract composed of guaiacol, creosol and other related phenolic compounds which is widely used as an anti-diarrhoeal agent in Asia. Abnormalities in water and electrolyte transport are often the cause of diarrhoea, but the mechanism of action of seirogan on small intestinal and colonic mucosal ion transport is unknown. AIM: To examine the effect of seirogan on electrogenic ion transport in vitro. METHODS: Sheets of rat jejunum and colon were mounted in Ussing chambers, and transmural potential difference (PD) was used as an electrical marker of changes in mucosal ion transport. Hypersecretory conditions were induced by acetylcholine (ACh). RESULTS: Serosal or mucosal application of seirogan (0.1-100 microg/mL) decreased basal jejunal transmural PD. Pre-treatment of the tissue with the neurotoxin, tetrodotoxin, did not inhibit the seirogan-induced changes in basal electrical activity. Seirogan had no effect on basal transmural PD in the ileum and colon. Under ACh-induced hypersecretory conditions in the small intestine and colon, addition of serosal or mucosal seirogan produced antisecretory effects determined indirectly by measurement of transmural PD. CONCLUSION: The ability of seirogan to decrease basal transmural PD in the jejunum, and inhibit the ACh-induced electrical responses, may contribute to its anti-diarrhoeal action.

Animals↗

PubMed1999

Expression of vascular endothelial growth factor and its receptor (KDR/flk-1) mRNA in experimental choroidal neovascularization.

PURPOSE: Vascular endothelial growth factor (VEGF) is an angiogenic peptide that has been suggested to be important in the pathogenesis of choroidal neovascularization. We investigated the transcription of VEGF and its receptor KDR/flk-1 genes during the development of experimentally induced choroidal neovascularization. METHODS: Rat VEGF or KDR cDNA was inserted in PGEM or pBluescript to prepare antisense or sense riboprobes. Multiple krypton laser burns were applied to the posterior pole of pigmented rat eyes according to a previously described protocol which produces choroidal neovascularization. At intervals of up to 4 weeks after photocoagulation, the eyes were removed and cut into thin sections. The sections were subjected to in situ hybridization with digoxigenin (DIG)-labeled single-strand rat VEGF and KDR cDNA riboprobes. RESULTS: In normal adult rat retinas, VEGF and KDR mRNA expression was mainly observed in the ganglion cell and the inner nuclear layers. During the development of neovascularization, VEGF and KDR mRNAs were detected in retinal pigment epithelial-like cells, fibroblast-like cells and endothelial cells in neovascular lesions. The level of expression was strongest at 1 week after photocoagulation in lasered lesions, and decreased by 4 weeks after photocoagulation. CONCLUSIONS: Our findings demonstrate that expression of VEGF and its receptor KDR may play a role in the formation of experimentally induced choroidal neovascularization. In this study, VEGF and its receptor were co-localized, suggesting that an autocrine and/or paracrine mechanism may be operative.

Animals↗

PubMed1999

Phosphorothioate oligonucleotides induction into experimental choroidal neovascularization by HVJ-liposome system.

PURPOSE: The purpose of this study was to determine whether the inactivated hemagglutinating virus of Japan (HVJ)-liposome method can induce phosphorothioate oligonucleotides effectively into an experimentally-induced choroidal neovascularization of rats. We also examined whether antisense phosphorothioate oligonucleotides against VEGF could be induced into choroidal neovascularization as a therapeutic agent by the HVJ-liposome method. METHODS: The experiments were conducted on a rat model of choroidal neovascularization. FITC-labeled phosphorothioate oligonucleotides were coencapsulated in liposomes. The liposomes were coated with the envelope of inactivated HVJ and injected into the vitreous cavity following photocoagulation of pigmented rat eyes. The eyes were removed following injection, fixed, frozen and cut into thin sections. Induction of oligonucleotides was observed under a laser confocal scanning microscope for fluorescence and the development of choroidal neovascularization was evaluated histopathologically. RESULTS: Phosphorothioate oligonucleotides were effectively induced into ganglion cells and into the cells of the choroidal neovascularization induced by laser photocoagulation. Highly effective induction of oligos was observed 3 to 14 days after intravitreal injection of HVJ-liposomes after which the level decreased. Antisense oligonucleotides against VEGF were induced specifically into cells in the choroidal neovascularization, however neovascularization was still observed. CONCLUSIONS: Phosphorothioate oligonucleotides can be effectively induced into ganglion cells, and specifically into cells in choroidal neovascularization. Although antisense oligonucleotides against VEGF failed to prevent choroidal neovascularization, the HVJ-liposome method provided a highly effective means of inducing antisense oligos for in vivo antisense therapy.

Animals↗

PubMed1999

Effects of atrial and brain natriuretic peptides on lysophosphatidylcholine-mediated endothelial dysfunction.

Lysophosphatidylcholine (LPC), a major atherogenic lysophospholipid contained in oxidized low-density lipoprotein (ox-LDL), induces endothelial dysfunction. Recent studies showed that natriuretic peptides (NPs) have antiatherogenic properties by inhibiting vascular smooth-muscle cell proliferation, but their effects on endothelial cells are little known. We examined whether atrial and brain NPs (ANP and BNP) have a protecting action against LPC-induced endothelial dysfunction. LPC (10 microM) significantly inhibited thrombin (0.001-1 U/ml)-induced endothelium-dependent relaxation without affecting endothelium-independent relaxation to sodium nitroprusside in isolated porcine coronary arteries. The impaired endothelium-dependent relaxation induced by LPC was prevented by treatment with ANP or BNP (i microM). In cultured bovine aortic endothelial cells (BAECs), LPC (10 microM) significantly attenuated bradykinin (1 microM)-stimulated nitric oxide (NO) release; however, this was prevented by ANP and BNP. Because LPC-induced endothelial dysfunction has been shown to be mediated at least in part by activation of the protein kinase C (PKC)-dependent signaling pathway, we also examined the effects of ANP and BNP on LPC-induced modulation of PKC activities in BAECs. LPC (10 microM) significantly stimulated PKC activity in BAECs. However, ANP or BNP significantly inhibited LPC (10 microM)-induced PKC activation. In conclusion, ANP and BNP protected endothelial cells from LPC-induced dysfunction in both isolated coronary arteries and cultured ECs. The mechanism appears to be at least in part related to the inhibition of LPC-induced PKC activation by NPs. These new actions of ANP and BNP against lysolipid-induced endothelial cytotoxicity may partly account for antiatherogenic properties of NPs.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1999

Effect of wood creosote and loperamide on propulsive motility of mouse colon and small intestine.

To elucidate a mechanism of the antidiarrheal activity of wood creosote, its effect on the propulsive motility of mouse colon and small intestine was studied using a charcoal meal test and a colonic bead expulsion test. The effect was compared with that of loperamide. At an ordinary therapeutic dose, wood creosote inhibited the propulsive motility of colon, but not of small intestine. On the other hand, loperamide inhibited the propulsive motility of small intestine, but not of colon. The results indicate that at least a part of the antidiarrheal activity of wood creosote and loperamide is attributable to their antikinetic effect predominantly on colon of the former and predominantly on small intestine of the latter.

Animals↗

PubMed1999

Membrane active lipids in remnant lipoproteins cause impairment of endothelium-dependent vasorelaxation.

We have recently found that remnant lipoproteins (RLPs) and their lipid fractions impair endothelium-dependent vasorelaxation (EDR). This study was aimed at clarifying mechanisms responsible for RLP-induced endothelial dysfunction in isolated rabbit aortas. RLPs were isolated from plasma in hyperlipidemic subjects by use of the immunoaffinity gel mixture of anti-ApoA1 and anti-ApoB100 monoclonal antibodies and ultracentrifugation. Organ chamber experiments showed that EDR impairment was restored by addition of reduced glutathione (GSH) or N-acetylcysteine, antioxidants, into the incubation buffer containing isolated rabbit aortas and RLPs (0.75 mg of triglyceride/mL). Furthermore, the incubation of isolated human red blood cells (RBCs) with RLP and its lipids converted the normal shape of RBCs to echinocytes, but coincubation with antioxidants suppressed the RLP-induced RBC transformation, suggesting that they exerted oxidative damage on RBC surface membranes. Studies with HPLC and the postcolumn chemiluminescence method showed that RLPs contain a substantial amount of phosphatidylcholine hydroperoxides. Peroxidized phosphatidylcholine also impaired EDR and had echinocytogenic action, both of which were suppressed by N-acetylcysteine. RLPs isolated from the plasma of patients under treatment with alpha-tocopherol, an antioxidant, had a lower level of phosphatidylcholine hydroperoxides (15% of the amount in nontreated patients), which was associated with a lack of the inhibitory action on EDR and with lesser effect on RBC transformation. Oxidative damage caused by lipid components in RLPs, especially peroxidized phospholipids, deteriorates cell surface membrane and may be at least partly responsible for RLP-induced impairment of EDR.

Animals↗

PubMed1999

Combining endovascular and neurosurgical treatments of high-risk dural arteriovenous fistulas in the lateral sinus and the confluence of the sinuses.

OBJECT: The authors describe the use of a systemic approach to treat dural arteriovenous fistulas (DAVFs) in the lateral sinus and the confluence of sinuses in 17 patients who presented with signs and symptoms related to intracranial hemorrhage, infarction, and diffuse brain swelling. METHODS: Angiographic examination revealed three different types of DAVFs in these high-risk patients: 1) extremely high flow DAVF not associated with sinus occlusion or leptomeningeal retrograde venous drainage (LRVD); 2) localized DAVF with exclusive LRVD and without sinus occlusion; and 3) diffuse DAVF with sinus occlusion and LRVD. Because of the complex nature of these lesions, the authors adopted a staged protocol in which they combined endovascular and surgical treatments. CONCLUSIONS: The authors believe that by close collaboration between endovascular therapists and vascular neurosurgeons, high-risk DAVFs in the lateral sinus and the confluence of sinuses can be successfully managed without treatment-related morbidity and mortality.

Adult↗