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Biomedical subjects

H Utsumi

Publications and source records attributed to H Utsumi.

At least 73 records · Page 4Linked to original sources
PubMed1998

Presence of emerinopathy in cases of rigid spine syndrome.

Rigid spine syndrome (RSS) shows clinical similarities to Emery-Dreifuss muscular dystrophy (EDMD). Differential diagnosis between EDMD and RSS is essential because EDMD is often associated with life-threatening cardiomyopathy that can be cured by an implantation of a cardiac pacemaker. To determine if any of the patients with RSS had mutations of the emerin gene (responsible gene for X-linked EDMD or emerinopathy), we screened the patients for mutations. We found seven patients with a clinical picture consistent with RSS in the 6500 diagnostic muscle biopsies in our National Center over the last 19 years. We identified a novel mutation in the gene (1-bp frame-shift deletion in the exon 1) in one of the seven patients with RSS. This mutation created a premature termination at codon 12 and was expected to produce a severely truncated emerin. Emerin was not detected in the skeletal muscle. The unaffected mother of the patient was a heterozygous carrier for the mutation. The remaining six patients with RSS had no mutation in the gene and showed normal expression of emerin in the skeletal muscle. Our results emphasize the presence of clinical overlap between possible RSS and EDMD, and reinforce the necessity of molecular genetic diagnosis of emerin to exclude emerinopathy in a patient population that has a clinical diagnosis of RSS.

Adolescent↗
PubMed1998

Characterization of transgenic tobacco with an increased alpha-linolenic acid level

Microsomal omega-3 fatty acid desaturase catalyzes the conversion of 18:2 (linoleic acid) to 18:3 (alpha-linolenic acid) in phospholipids, which are the main constituents of extrachloroplast membranes. Transgenic tobacco (Nicotiana tabacum) plants with increased 18:3 contents (designated SIIn plants) were produced through the introduction of a construct with the tobacco microsomal omega-3 fatty acid desaturase gene under the control of the highly efficient promoter containing the E12Omega sequence. 18:3 contents in the SIIn plants were increased by about 40% in roots and by about 10% in leaves compared with the control plants. With regard to growth at 15 degreesC and 25 degreesC and the ability to tolerate chilling at 1 degreesC and 5 degreesC, there were no discernible differences between the SIIn and the control plants. Freezing tolerance in leaves and roots, which was assessed by electrolyte leakage, was almost the same between the SIIn and the control plants. The fluidity of plasma membrane from the SIIn plants was almost the same as that of the control plants. These results indicate that an increase in the 18:3 level in phospholipids is not directly involved in compensation for the diminishment in growth or membrane properties observed under low temperatures.

Journal Article↗
PubMed1998

Establishment and characterization of a hypocatalasemic mouse cell strain.

Contact-inhibited catalase-deficient fibroblast cell strain has been established from the homozygous hypocatalasemic C3H/Csb mutant mouse. This cell strain has low level of catalase enzyme activity and has normal level of enzyme activities of both glutathione peroxidase and superoxide dismutase. Catalase-deficient C3H/Csb mutant cell strain is markedly more sensitive to the toxicity of hydrogen peroxide compared to wild-type C3H/Csa cell strain. In addition, mutant cell strain is sensitive to X-rays and near-UV compared to wild-type cell strain, but shows the same sensitivities to topoisomerase II inhibitors, adriamycin and 4'-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA), and the DNA cross-linking agents, cisdiamminedichloroplatinum (II) (cis-Pt) and trans-diamminedichloroplatinum (II) (trans-Pt). These cell strains will be of use in the study of the roles which catalase plays in the intracellular prevention of DNA damage induced by oxidative stress.

Acatalasia↗
PubMed1998

[Clinical features and treatment of sarcoidosis involving the central nervous system].

PURPOSE: The purpose of this study was to investigate the clinical features, diagnosis, and treatment modalities of three cases with neurosarcoidosis, which involved the central nervous system (CNS). CASES: Three men with neurosarcoidosis, aged 27, 29 and 60 years, are presented. Two of them had previously been given a diagnosis of sarcoidosis. The clinical symptoms of these cases included diabetes insipidus, pituitary dysfunction, seizure, mental disorder, visual field disturbance and pyramidal tract signs. In these cases, CT scan and MRI showed the presence of a tumor near the pituitary gland, diffuse nodules in the subarachnoid space or meningoencephalitis associated with angitis. The level of angiotensin converting enzyme (ACE) in the sera and in the cerebrospinal fluid, were elevated in the two cases who had no brain biopsy. All three cases were treated with steroids; two of them received pulse steroid therapy. RESULTS: The two cases who received pulse steroid therapy responded quickly, with improvement in clinical features, serum ACE levels and neuroradiological findings. Under oral administration of steroids, all three cases recovered with complete remission of neurosarcoidosis except for endocrinological symptoms. DISCUSSION: The main pathological changes of neurosarcoidosis are granulomatous angitis of the venular walls and occasionally, of the capillaries near the meninx and Virchow-Robin space. The patients also had symptoms of secondary meningoencephalitis. These changes were mainly located in the hypothalamus and pituitary gland. The patients had complex symptoms resulting from endocrine system granuloma, as well as from cerebral ischemia. The severity of the disease and effectiveness of treatment, can be evaluated by measuring ACE levels in the cerebrospinal fluid (over 1. 0 IU/l), and by Gd-enhanced MRI. Early pulse steroid therapy with subsequent oral steroid administration is thought to be important for neurosarcoidosis treatment, in order to prevent irreversible damage in the CNS.

Adult↗
PubMed1997

Synthesis and imaging of blood-brain-barrier permeable nitroxyl-probes for free radical reactions in brain of living mice.

Three different lipophilic nitroxyl-probes having capability to pass the blood-brain barrier were, for the first time, synthesized to estimate free radical reactions in brain of living animals. Two of the three were designed to be hydrolyzed by esterase and remain in cell. All 3 probes had high n-octanol/buffer partition coefficients and gave 2 signal components in in vivo ESR spectra at head of living mice after intravenous injection. The ESR parameters of 2 components agreed with those of probes dissolved in water and lipidic phases. ESR-CT imaging on the nitroxyl-proves after intravenous injection revealed that all probes presented in both encephalon and extracranial region of head. Tissue distribution of the nitroxyl-probes demonstrated that the newly synthesized lipophilic nitroxyl-probes had capability to pass the blood-brain barrier and accumulated in brain than that of hydrophilic probe.

Animals↗
PubMed1997

Mutational specificity of the ferrous ion in a supF gene of endonuclease III/VIII deficient Escherichia coli.

When 125 microM Fe2+/EDTA treated plasmid pUB3 was used to transfect an Escherichia coli NKJ2004 (nth nei) host, which is totally defective in glycosylases for thymine glycol and 5-hydroxycytosine, a 3.7 fold increase in mutation frequency was observed. Among 46 supF mutants sequenced, 28 had base substitutions, with G:C-->C:G transversion predominant (14 cases), followed by G:C-->T:A transversion (6 cases) and G:C-->A:T transition (6 cases). The results are consistent with our previous Fe2+ mutagenesis results where, in the wild type host, 78% were base substitutions, with G:C-->C:G transversion (59%) predominant, followed by G:C-->T:A transversion (28%) and G:C-->A:T transition (11%). Treatment of pUB3 DNA with Fe2+/EDTA did not yield formation of Endonuclease III sensitive sites. The possibility of 5-hydroxycytosine as the causative lesion for Fe2+ induced G:C-->C:G transversion is discussed.

DNA Repair↗
PubMed1997

[Effect of nicotine-administration on tyrosine hydroxylase-containing neuron in the rat forebrain; immunohistochemical study with semiquantitative morphometric analysis].

Nicotine is toxic substance that is absorbed by cigarette smoking and easily causes dependence. It is clear that smoking is bad for health, however, the effects of nicotine itself on the central nervous system have not been elucidated. We studied the effects of nicotine-administration (5 mg/kg x 2/day, 7 days) on immunoreactivity for tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine synthesis, in the rat forebrain including the cerebral cortex, hippocampus, striatum and hypothalamus to investigate the influence on catecholaminergic neurons. In the nicotine-administration group, both the number and intensity of TH-immunoreactive fibers and terminals increased in the fronto-parietal cortex, anterior cingulate cortex and hippocampus in comparison with those of the control group, and a significant difference was demonstrated by computer assisted morphometric analysis. These findings suggest that nicotine-administration influences catecholaminergic neural systems in the forebrain, especially in the cerebral cortex and hippocampus and that these effects might be related to developing the dependence on smoking.

Animals↗
PubMed1996

In vivo detection of mouse liver nitric oxide generation by spin trapping electron paramagnetic resonance spectroscopy.

Nitric oxide, a paramagnetic molecule synthesized in biological systems, plays an important role in many pathophysiological processes. In vivo electron paramagnetic resonance spectroscopy/imaging could be a useful tool to study, in situ and in real time, nitric oxide generation. In this study the intracellular production of nitric oxide in tissues of living septic-shock mouse was detected by the spin trapping technique in combination with electron paramagnetic resonance spectroscopy. A lipophilic spin trap agent was used and nitric oxide formation was determined by the intensity of its iron-mononitrosyl complex. Among all examined tissues at 20 degrees C, the highest signal intensity of the trapped nitric oxide was found in the liver homogenates (n = 5). The amount of complex found in the kidneys was about 40% of that found in the liver. In the brain and lung, around 10% was found. This study reports, for the first time, the in vivo detection of nitric oxide generation in the upper abdomen of septic-shock mice (n = 3). Within 1 h after the trap injection, the signal was stable, indicating that the formation had reached a steady state.

Animals↗
PubMed1996

Selective increase in astrocytic elements in the rat dentate gyrus after chronic toluene exposure studied by GFAP immunocytochemistry and electron microscopy.

Using glial fibrillary acidic protein (GFAP) immunohistochemistry, and electron microscopy, we examined changes in the features of astrocytes in the dentate gyrus of the hippocampal formation after high-dose chronic toluene inhalation (2000 ppm, 4 h/day) for 1 month. In toluene-treated rats, the numbers of GFAP-immunoreactive (IR) astrocytes were not changed, whereas the area and intensity of GFAP-IR processes were increased markedly in the dentate gyrus. In addition, dense, thick and highly-stained GFAP-IR processes appeared entering into the granular cell layer, compared with those of controls. At the electron microscopic level, numerous astrocytic processes with high electron density intervened between the granular cells. These results suggest that high-dose of chronic toluene exposure induces morphological changes in astrocytes in the dentate gyrus of the hippocampal formation.

Administration, Inhalation↗
PubMed1996

The effects of acute phencyclidine treatment on neuropeptide Y (NPY) neuronal system in the rat arcuate nucleus studied by immunocytochemistry and in situ hybridization.

Phencyclidine (PCP) is a dissociative drug and an antagonist of N-methyl-D-aspartate (NMDA) receptor. The effects of PCP treatment on neuropeptide Y (NPY) system in the arcuate nucleus of the rat hypothalamus were examined both by immunocytochemistry and in situ hybridization. In acute PCP-treated rats, the NPY-immunoreactive perikarya appeared in the arcuate nucleus but no perikarya were detected in controls, without colchicine pretreatment. The signals of NPY mRNA by in situ hybridization increased in the PCP-treated rats than those of controls. These results suggest that the NPY system in the arcuate nucleus might be partly controlled by glutamatergic neurons.

Animals↗
PubMed1996

In vivo ESR studies on pharmacokinetics and metabolism of parenteral lipid emulsion in living mice.

PURPOSE: We applied non-invasive and real-time method with in vivo ESR spectroscopy to determining pharmacokinetics and metabolism of lipid emulsion as a drug carrier in living mice. METHODS: A spin-labeled triglyceride (SL-TG) was newly synthesized and lipid emulsion containing SL-TG was prepared. In vivo ESR spectra in mice were observed after intravenous administration of the lipid emulsion. RESULTS: In vivo ESR spectra consisted of three components, coinciding with the in vitro spectra of SL-TG particles, free and immobilized fatty acids. The amount of the components depended on both the observing domain and the period after administration. In the chest, all three components were observed, while SL-TG particle was lacking in the abdomen. The half-life of the lipid particles in the chest was 2 hr. CONCLUSIONS: Non-invasive and real-time analysis of drug carriers in living animal is successfully accomplished using an in vivo ESR method.

Animals↗
PubMed1996

Free radicals from 1-palmitoyl-2-arachidonoylphosphatidylcholine liposomes in Fe2+/ascorbic acid solution.

The generation of free radicals during the lipid peroxidation of liposomes composed of 1-palmitoyl-2-arachidonoylphosphatidylcholine (PAPC-liposome) in Fe2+/ascorbic acid (AsA) solution was studied by the ESR spin trapping technique. A carbon-centered radical adduct was observed using alpha-(4-pyridyl-1-oxide)-N-tert-butyl-nitorone (4-POBN) and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), but no oxygen-centered radicals such as .OH, LO., and LOO. were observed. The lipid peroxidation evaluated as 2-thiobarbituric acid reactive substances was inhibited by the addition of 4-POBN. The intensity of this inhibitory effect was dependent on the time when 4-POBN was added to the mixture of PAPC-liposomes and Fe2+/AsA solution, and no inhibitory effect could be observed after 4 min. The signal intensity of the carbon-centered radical adduct was dependent on the lipid concentration of PAPC-liposomes. These results suggest that the alkyl radicals generated from PAPC-liposome peroxidation induced by Fe2+/AsA were trapped by DMPO or 4-POBN at an earlier stage of lipid peroxidation.

Ascorbic Acid↗
PubMed1996

Cellular effect of thermal neutron capture treatment using 10B1-para-boronophenylalanine: lethal effect on melanoma cells with different degrees of X-ray sensitivity.

We studied the effect of neutron capture treatment using 10B-compound on X-ray sensitive P-39 and X-ray resistant G-361 human melanoma cell lines, and found a high lethal effect of boron neutron capture therapy in comparison with conventional ionizing radiation. The P-39 line was sensitive to thermal neutron radiation, and extremely sensitive to bleomycin treatment, whereas the G-361 line was resistant to both forms of treatment; however, the two cell lines had similar sensitivity to thermal neutron radiation after pretreatment with 10B1-para-boronophenylalanine (10B1-BPA, 200 micrograms/ml medium). These results show that the thermal neutron capture products (a 7Li nucleus and alpha particle) are highly damaging and short range in tumor cells and thus more efficiently inactivate melanoma cells irrespective of x-ray sensitivity, than conventional X-ray-irradiation.

Antibiotics, Antineoplastic↗
PubMed1995

Effect of chronic toluene exposure on tyrosine hydroxylase-positive nerve elements in the rat forebrain: an immunohistochemical study combined with semiquantitative morphometric analysis.

The effects of chronic toluene exposure [3000 p.p.m. for 4 h (09:00-11:00, 13:00-15:00)] every day for 3 weeks on immunoreactivity for tyrosine hydroxylase (TH), the rate limiting enzyme of catecholamine synthesis, in the rat forebrain were studied. In toluene-exposed rats, increases in both number and intensity of TH-immunoreactive fibres and terminals were observed in most parts of the forebrain including the cerebral cortex, hippocampus, lateral septal nucleus and hypothalamus, compared with control rats. These findings suggest that chronic toluene exposure might influence catecholaminergic neural systems.

Animals↗
PubMed1995

Immunohistochemical alterations in neuropeptide Y-positive nerve elements in rat cerebral cortex following acute phencyclidine treatment.

Phencyclidine (PCP) is a dissociative drug and has been known to be an antagonist of N-methyl-D-aspartate (NMDA) receptor. We examined possible effects of acute treatment with PCP on neuropeptide Y (NPY) immunoreactive nerve fibres and cell bodies in rat forebrain by immunocytochemistry combined with morphometric analysis. Following the treatment, significant alterations were observed throughout the cerebral cortex, compared with controls. NPY-positive perikarya were increased in number (178%) whereas NPY-positive fibres and terminals were decreased in area (38%). The result suggests that the cortical NPY neuronal system is controlled, at least partly, by glutamatergic inputs via NMDA receptor-mediated mechanisms.

Animals↗
PubMed1995

In vivo ESR measurements of free radical reactions in living mice.

In vivo ESR measurements were carried out to estimate free radical reactions in living mice using nitroxyl radicals as probes. The ESR signal of nitroxyl radical which was intravenously or intramuscularly injected to living female ddY mice decreased gradually by reducing to the corresponding hydroxylamine. The reduction rate was enhanced by oxidative stress, and pre-treatment of antioxidants suppressed the enhancement of signal decay. Oral administration of carbon tetrachloride enhanced signal decay in upper abdomen but not in thorax. These results indicated that free radicals, which can reduce nitroxyl radical, were produced in the upper abdomen by oral administration of carbon tetrachloride.

Animals↗