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Biomedical subjects

T Sugimori

Publications and source records attributed to T Sugimori.

At least 19 recordsLinked to original sources
PubMed2004

DNA oxidation injury in bone early after steroid administration is involved in the pathogenesis of steroid-induced osteonecrosis.

OBJECTIVE: Using a rabbit model, we investigated the DNA oxidation injury occurring in bone following steroid administration and focused on the relation between DNA oxidation injury and osteonecrosis. METHODS: Japanese white rabbits weighing about 3.5 kg were injected with a single intramuscular dose of methylprednisolone 4 mg/kg and divided into groups consisting of 10 rabbits each, which were killed after 3, 5 and 14 days (groups A, B and C respectively). As a control, five untreated rabbits (group N) were also studied. An immunohistochemical study of the diaphysis of the proximal femur was conducted using the monoclonal antibody N45.1, which is a highly specific antibody against 8-hydroxy-2'-deoxyguanosine, an index of DNA oxidation injury. Also, using NIH Image freeware, the positive area (8-OHdG %PA) of each group was calculated and the four groups were compared. RESULTS: Osteonecrosis was detected only in group C (70%). N45.1 positivity was noted in bone marrow haematopoietic cells and was particularly marked in groups B and C. 8-OHdG %PA was 1.6 +/- 0.2% in group N, 2.2 +/- 0.4% in group A, 4.8 +/- 0.4% in group B and 5.1 +/- 0.5% in group C, with significantly greater oxidation injury found in groups B and C (P < 0.001). CONCLUSION: Oxidative injury was demonstrated soon after the administration of methylprednisolone in a rabbit model prior to the development of osteonecrosis. This finding may suggest new strategies to prevent steroid-induced osteonecrosis, such as the optimally timed (early) administration of antioxidant agents.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

Three-dimensional morphological analysis of the proximal femoral canal, using computer-aided design system, in Japanese patients with osteoarthrosis of the hip.

An accurate three-dimensional morphological analysis of the femur is required to produce well fitting uncemented femoral implants. A computer-aided design system made it possible to produce three-dimensional femoral models and to accurately measure certain parameters with planes standardized for all subjects. The study subjects were Japanese; there were 89 patients (113 hips) with osteoarthrosis (OA) and 18 volunteers (36 hips) free of hip joint complaints and with no abnormal radiological findings (normal; N). The femoral canal was classified into three types, A-I, A-II, and B-II, based on the shape in the frontal and sagittal planes. Either triangular (type T) or circular (type C) shapes were identified at the proximal cross section. Type A-II, which is considered the standard type, accounted for 89% of the N hips, and 42% of the OA hips. Type A-I, with a posterior canal plane strongly inclined toward the anterior, accounted for 26% of the OA hips and 6% of the N hips; 96% of type A-I hips were triangular. Type B-II, which had a steep medial canal plane, accounted for 29% of the OA hips and 6% of the N hips; 63% of type B-II hips were circular.

Adult↗
PubMed1998

A new technique for morphologic measurement of the femur. Its application for Japanese patients with osteoarthrosis of the hip.

The cementless femoral prostheses developed in Western countries have commonly been used for Japanese patients, but it has been noted that it is difficult to achieve a good fit between the cementless femoral prostheses and some femora. In Japan, there are many patients with secondary osteoarthrosis (OA) of the hip, but Western designed femoral prostheses seem to be mainly for use with primary OA of the hip. To design femoral prostheses better suited to Japanese patients, a new method to study the morphometry of the femur is required--one which can determine the particular features of the femur in Japanese patients. In this study, a new morphologic measurement technique of the femur is proposed and applied to a number of Japanese OA patients in order to demonstrate its efficacy. In this technique, a three-dimensional solid model based on the outer and inner borders of the femoral cortex is constructed from 3-D CT images and computer-aided design (CAD) software. The bone axis is defined as the line of best fit to the centers of gravity of the femur cross sections in each CT plane by using the least square method. A new femur coordinate system is considered based on this bone axis. The corrected outer borders of the cortex are reconstructed in sections perpendicular to the bone axis. The angle between the principal axis of inertia of the sections and a plane defined by the femur coordinate system is selected as providing a good measurement of the torsion value to characterize the femur morphology. The angles of principal axis were measured in 110 OA and 36 normal hips, and then compared with each other. A significant difference between the OA and normal group was observed especially in the proximal region above the section 6 mm below the level of the lesser trochanter. It is suggested that the anteversion of the femoral neck influences the torsion of the parts below the lesser trochanter. From the results, it is demonstrated that the proposed measurement technique is a reliable and efficient means of determining femur morphology.

Adult↗
PubMed1997

Emerging paradigms of integrin ligand binding and activation.

Adhesion of cells to each other or to the extracellular matrix provides essential signals that regulate many cellular functions including cell migration, proliferation, differentiation and apoptosis. The integrin superfamily orchestrates many of these complex adhesive events through regulated interactions with a large variety of ligands. Crystallization of some ligands and of a ligand-binding integrin domain, reviewed here, together with extensive mutagenesis studies are beginning to shed light on the inner workings of these receptors.

Animals↗
PubMed1996

Solvent-accessible residues on the metal ion-dependent adhesion site face of integrin CR3 mediate its binding to the neutrophil inhibitory factor.

Neutrophil adhesion-dependent functions such as chemotaxis, spreading, and phagocytosis are inhibited by neutrophil inhibitory factor (NIF), a glycoprotein produced by the hookworm Ancylostoma caninum. The NIF binding site has been localized to the A-domain of integrin CR3 (CD11b/CD18) and shown to be metal-dependent. The recently solved crystal structure of the A-domain from CD11b revealed a putative metal ion-dependent adhesion site (MIDAS) on the top of the structure. To determine if NIF binds to the A-domain at its MIDAS face, amino acid substitutions involving 24 residues present in surface loops and adjacent helices in the structure were created. The expressed CD11b A-domain and CR3 heterodimers were then tested in a blinded manner for their ability to bind to biotinylated NIF. The solvent-exposed Gly143, Asp149, Glu178-Glu179, and Arg208, all located on the MIDAS face, in close proximity to the metal ion, were involved in CR3-NIF interaction. These data show that the natural integrin antagonist, NIF, binds to CR3 through the MIDAS region and identify putative contact residues in this region that could be targeted therapeutically.

Amino Acid Sequence↗
PubMed1995

Inhibitory properties of recombinant human monocyte/neutrophil elastase inhibitor.

Human monocyte/neutrophil elastase inhibitor (HEI) is a serpin superfamily protein that rapidly and irreversibly inhibits neutrophil and pancreatic elastase. We generated a recombinant baculovirus that supports production of HEI in insect cells at approximately 400 times the level in monocytes. Recombinant HEI was found to be indistinguishable from monocyte HEI in its physicochemical properties and ability to inhibit neutrophil elastase and pancreatic elastase. The recombinant protein was used to test for additional functions. HEI was shown to inhibit proteinase 3, an important neutrophil inflammatory protease, by the classical serpin mechanism of forming a covalent protease-protease inhibitor complex. Preliminary evidence suggests that HEI also inhibits neutrophil cathepsin G. On the other hand, HEI does not inhibit u-plasminogen activator (urokinase). These findings suggest that HEI functions as a class-specific regulator of the neutrophil serine proteases characteristically found at inflammatory sites.

Animals↗
PubMed1990

[Experimental head injury of rabbits using pendulum impactor. An electron microscopic study].

Brain damage in the early stage of experimental head injury was studied under electron microscope, especially with respect to the permeability of the blood brain barrier and damage to nerve fibers. Lightly anesthetized rabbits were treated by intravenous injection of horseradish peroxidase (150-250 mg/kg) and were subjected to occipital impacts with a pendulum impactor. The animals were then perfused with a 2.5% glutaraldehyde mixture. Small blocks of the brain were sampled, incubated, postfixed, and embedded in Epon. These sections were observed under an electron microscope without staining. The authors' criteria of concussion have been previously published. There were three nonconcussion, 11 nonlethal concussion and seven lethal concussion animals. All cases of lethal concussion showed subarachnoid hemorrhage (SAH) in the brainstem and 57% of them showed microscopic parenchymal perivascular hemorrhages in the brainstem. Fifty-five percent of the nonlethal concussion cases showed SAH in the brainstem with a little parenchymal hemorrhage. The nonconcussion cases showed no hemorrhagic change except contusions and/or SAH of the cerebellum. Hemorrhagic changes were frequently seen in the cerebrum and cerebellum of nonlethal and lethal concussion cases without correlation to the severity of concussion. Under electron microscope, nonconcussion cases showed mild splitting of myelins. In nonlethal concussion cases, swelling of perivascular astrocytic feet was seen to a moderate degree in the cerebrum, pons, and medulla oblongata and damage to axons and myelins were mainly seen in the pons and medulla oblongata. Many cored dense bodies containing peroxidase were diffusely recognized in vascular endothelial cells. In lethal concussion cases, beside findings seen in nonlethal concussion, intravascular peroxidase was seen to leak from the intravascular space through an opened tight junction to the extracellular space, axons and neurophils.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effect of low molecular weight heparin preparations on the inhibition of thrombin by heparin cofactor II.

1. Heparin molecules approximately 24 to 30 residues in length are required to catalyze the thrombin-HC II reaction. The requirement for heparin molecules of this length is consistent with a model for catalysis in which heparin binds HC II and thrombin simultaneously to form a ternary complex in a manner similar to that proposed for the thrombin-AT III reaction. Smaller molecules (18 or more monosaccharide units in length) are required to catalyze the thrombin-AT III reaction. 2. The specific AT III-binding pentasaccharide containing 3-O-sulfated glucosamine is not required for activity with HC II. 3. Some low molecular weight heparin preparations have significant activity with HC II (approximately 10 to 20% that of standard heparin). This is probably related to the presence of species with molecular weights greater than 6000 to 7500 (24 to 30 monosaccharide units) in these preparations.

Antithrombin III↗
PubMed1989

Purification and properties of neuraminidase isozymes in Arthrobacter ureafaciens mutant.

An Arthrobacter ureafaciens mutant (M1057) capable of producing neuraminidase constitutively was isolated by NTG mutagenesis from A. ureafaciens KMS 3663. Four molecular species (L, M1, M2, and S) of neuraminidase isozymes were homogeneously purified from the mutant and parent strains by means of DEAE-cellulose, affinity chromatography, ammonium sulfate precipitation, chromatofocusing, and Ultrogel AcA44 gel filtration. The molecular weights of L, M1, M2, and S isozymes were shown to be approximately 88,000, 66,000, 66,000, and 52,000, respectively. The optimal pHs and Km values of these isozymes for N-acetylneuraminosyl-alpha,(2-6)-lactose were 4.5-5.5 and 0.6-0.8 mM. Neuraminidase L, M1, M2, and S were able to hydrolyze oligosaccharides, glycoproteins and gangliosides containing alpha,(2-3)-, alpha,(2-6)-, and alpha,(2-8)-linked N-acetylneuraminic acid. Among these isozymes isolated, isozyme S was most active on colominic acid.

Arthrobacter↗
PubMed1989

[Early pathophysiological findings in experimental concussion in rabbits].

Early neurophysiological changes and pathological findings were studied following experimental cerebral concussion in rabbits. The animals were lightly anesthetized and subjected to occipital trauma with a pendulum impactor. Experimental concussion was defined as fulfillment of at least two of the three following criteria: apnea for more than 10 seconds, absence of the light reflex for more than 10 seconds, and bradycardia or tachycardia (less than 50% or more than 10% of the preimpact rate, respectively). There were 13 cases of lethal concussion, 16 of nonlethal concussion, and 15 of nonconcussion. The resultant head acceleration ranged from 250 to 1660 G and its duration was 0.8 to 5.5 msec. During the first 30 seconds after impact, electroencephalographic activity showed little change even in cases of lethal concussion, but slowed over the next several minutes due to respiratory suppression. The duration of apnea in cases of nonconcussion was under 9 seconds and, in cases of nonlethal concussion, averaged 21 seconds. Five of the rabbits with lethal concussion were apneic throughout the observation period, and the remaining eight exhibited apnea for an average of 46 seconds after impact. The light reflex was absent for less than 9 seconds in nonconcussion cases and for an average of 71 seconds in cases of nonlethal concussion. One animal with lethal concussion exhibited absence of the light reflex throughout, and the remaining 12 animals for an average of 39 seconds. Bradycardia was seen in 15 cases of nonlethal and two cases of lethal concussion. Six rabbits with lethal concussion had tachycardia. Two animals without concussion showed bradycardia and the remainder showed no change.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Effect of mono- and diaminopyridines on release of [3H]norepinephrine from isolated guinea-pig atrium.

Neurochemical evidence has been obtained that 4-aminopyridine, 3,4-diaminopyridine and 3,3-dimethyl-1-(4-amino-3-pyridyl)urea HBr (LF-14), concentration-dependently enhanced the stimulation-evoked release of [3H]norepinephrine ([3H]NE) from isolated guinea-pig atrium. The effects of aminopyridines, compounds known to inhibit potassium channels, were Ca0-dependent. High pressure liquid chromatography, combined with radiochemical detection, indicated that the increased stimulated release of radioactivity was due to [3H]NE. Since the aminopyridines studied also enhanced the release of [3H]NE from atrium treated with cocaine, a blocker of uptake1, it seems likely that the increased release of NE caused by the aminopyridines is due to the enhanced release of NE from sympathetic axon terminals and not to the inhibition of reuptake. It is probable that the sympathomimetic cardiac effects (positive inotropic and chronotropic effect) of aminopyridines observed in animal experiments is due to the increased release of NE, caused by these compounds.

4-Aminopyridine↗
PubMed1986

Shortened action of succinylcholine in individuals with cholinesterase C5 isozyme.

To test the possibility that individuals with and without plasma cholinesterase C5 isozyme have differences in neuromuscular sensitivity to succinylcholine chloride, we examined the effects of succinylcholine in these two groups of patients. Sera from 491 adult patients were examined for presence of the plasma cholinesterase C5 isozyme by use of electrophoresis with polyacrylamide; 24 were positive for the C5 isozyme. Plasma cholinesterase activity and duration of action of succinylcholine were measured in 12 C5 positive patients and 18 C5 negative patients, all of whom had the normal cholinesterase genotype. C5 positive patients had 30.1 per cent higher mean plasma cholinesterase activity than C5 negative patients. The duration of neuromuscular blockade, measured by the first twitch height evoked by train-of-four stimulation, was significantly shorter in C5 positive patients than C5 negative patients. The C5 positive individuals had shorter duration of action of succinylcholine than C5 negative individuals.

Adult↗
PubMed1984

Purification and properties of N-acetylneuraminate lyase from Escherichia coli.

N-Acetylneuraminate lyase [N-acetylneuraminic acid aldolase EC 4.1.3.3] from Escherichia coli was purified by protamine sulfate treatment, fractionation with ammonium sulfate, column chromatography on DEAE-Sephacel, gel filtration on Ultrogel AcA 44, and preparative polyacrylamide gel electrophoresis. The purified enzyme preparation was homogeneous on analytical polyacrylamide gel electrophoresis, and was free from contaminating enzymes including NADH oxidase and NADH dehydrogenase. The enzyme catalyzed the cleavage of N-acetylneuraminic acid to N-acetylmannosamine and pyruvate in a reversible reaction. Both cleavage and synthesis of N-acetylneuraminic acid had the same pH optimum around 7.7. The enzyme was stable between pH 6.0 to 9.0, and was thermostable up to 60 degrees C. The thermal stability increased up to 75 degrees C in the presence of pyruvate. No metal ion was required for the enzyme activity, but heavy metal ions such as Ag+ and Hg2+ were potent inhibitors. Oxidizing agents such as N-bromosuccinimide, iodine, and hydrogen peroxide, and SH-inhibitors such as p-chloromercuribenzoic acid and mercuric chloride were also potent inhibitors. The Km values for N-acetylneuraminic acid and N-glycolylneuraminic acid were 3.6 mM and 4.3 mM, respectively. Pyruvate inhibited the cleavage reaction competitively; Ki was calculated to be 1.0 mM. In the condensation reaction, N-acetylglucosamine, N-acetylgalactosamine, glucosamine, and galactosamine could not replace N-acetylmannosamine as substrate, and phosphoenolpyruvate, lactate, beta-hydroxypyruvate, and other pyruvate derivatives could not replace pyruvate as substrate. The molecular weight of the native enzyme was estimated to be 98,000 by gel filtration methods. After denaturation in sodium dodecyl sulfate or in 6 M guanidine-HCl, the molecular weight was reduced to 33,000, indicating the existence of 3 identical subunits. The enzyme could be used for the enzymatic determination of sialic acid; reaction conditions were devised for determining the bound form of sialic acid by coupling neuraminidase from Arthrobacter ureafaciens, lactate dehydrogenase, and NADH.

Escherichia coli↗
PubMed1983

Immobilization of proteins on partially hydrolyzed agarose beads.

Treatment of agarose beads with mild acid (0.2 M HCl, 55 degrees C, several hours) hydrolyzes some of the glycosidic bonds between D-galactosyl residues and 3,6-anhydro-L-galactosyl residues, and thus produces aldehydo-groups useful for immobilization of amino compounds by reductive amination with NaCNBH3. More than 20 mg (0.3 mumol) of bovine serum albumin could be coupled per gram of partially hydrolyzed agarose beads. Arthrobacter neuraminidase immobilized by this method was useful for desialylation of sialyl glycoconjugates, and was found not to leach from the gel and to be much more thermostable than the free enzyme.

Animals↗
PubMed1983

Experimental studies on vertical infection of mice with Japanese encephalitis virus. IV. Effect of virus strain on placental and fetal infection.

An experiment was carried out to examine the effect of an inoculated strain of Japanese encephalitis virus on the establishment of experimental vertical infection of mice with this virus. In it, closed-colony mice of the CFW strain were inoculated intravenously with seven strains of the virus at 7 days of pregnancy. After that, an attempt was made to recover the virus from placenta and fetus, so that the infection rate of each strain might be determined. As a result, the infection rate was high for both placenta and fetus in the case of the AS-6 and Sagara strains both of which had undergone three passages in the mouse brain. The placental infection rate was high and the fetal infection rate relatively low in the case of the JaGAr01 and Fuji strains which had undergone 7 and 150 passages, respectively, in the mouse brain. The infection rate was very low for both placenta and fetus in the case of the Nakayama-Yakken strain which had undergone more than 100 passages in the mouse brain. There was no difference in the severity of viremia after inoculation between the AS-6 and Fuji strains. Both placental and fetal infection rates were low in the case of the JaTH160 strain which had undergone passages in mice by intraperitoneal inoculation and which presented a strong peripheral infectivity and induced a severe viremia after inoculation. Neither placental nor fetal infection occurred in the case of the S- strain used as live virus vaccine. These results indicated that placental and fetal infection rates varied from one virus strain to another.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Experimental studies on vertical infection of mice with Japanese encephalitis virus III. Effect of gestation days at the time of inoculation on placental and fetal infection.

An experiment was carried out on the effect of gestation days at the time of inoculation on the establishment of experimental vertical infection with Japanese encephalitis virus in mice. In it, mice of the CFW strain in a closed colony were inoculated intravenously with a field strain at different times over a period from 3 to 12 days of gestation. After that, an attempt was made to recover the virus from the placenta and fetus to estimate the rate of infection. As a result, placental infection was established not when the virus was inoculated at 3 days of gestation, but when it was inoculated at 4 days of gestation or later. The rate of infection was relatively high when the virus was inoculated at 6 days of gestation or later. Fetal infection was established relatively frequently when the virus was inoculated some time between 7 and 10 days of gestation, but quite infrequently when the virus was inoculated at any other time than this. There was a difference in rate between placental and fetal infection at a given time of inoculation in days of gestation. This difference seemed to have been induced not by a difference in intensity of viremia appearing after inoculation, but by a difference in degree of development between placental and fetal tissues at the time of inoculation.

Animals↗