Biomedical subjects

N Yagi

Publications and source records attributed to N Yagi.

At least 73 records · Page 4Linked to original sources

PubMed1996

Role of base-backbone and base-base interactions in alternating DNA conformations.

Sequence-specific conformational differences between dinucleotide steps are characterised using published crystal coordinates with special attention to steric hindrance of the methyl group of a T base to the neighbouring base, and, more importantly, to the sugar-phosphate backbone. The TT step is inflexible and B-like, as it has two methyl groups which interlock with each other and with the sugar-phosphate backbones. AT slides, or overtwists, so that the methyl groups move away from the backbones, both lead the step towards the A-conformation. TA is most flexible as it does not have such restriction. These characteristics are observed with other pyrimidine-pyrimidine, pyrimidine-purine, purine-pyrimidine steps, respectively, but to less extent, depending on the number of non-A:T basepairs in the steps.

Base Sequence↗

PubMed1996

Surgical implication of aortic dissection on long-term outcome in Marfan patients.

We herein review our 17-year surgical experience for the treatment of ascending aortic aneurysm in patients with Marfan syndrome to clarify the risks of increased mortality and reoperation. The subjects consisted of 15 patients who had all undergone surgery for the aortic root and ascending aorta at Niigata University Hospital between July 1978 and January 1995. Aortic valve replacement and ascending aortic wrapping were performed in 5 patients, Bentall or Cabrol operation in 6, and combined aortic arch reconstruction and Cabrol operation in 2, as the initial surgery. Patients who had an aortic dissection (Stanford type A) at initial surgery were assigned to group I (n = 7), while those with an aortic root aneurysm were assigned to group II (n = 8). In group I, 3 patients required a second operation for the remaining aortic arch aneurysm, and 1 died due to a late rupture of the distal aneurysm. In group II, no patient needed a reoperation; however, 1 died due to an intracranial hemorrhage and another due to composite valve graft failure and distal dissection. The results thus indicate that aortic dissection seems to affect long-term outcome, and therefore the combined repair of the aortic root and transverse arch is recommended in Marfan patients with aortic dissection involving the transverse aortic arch.

Adolescent↗

PubMed1996

Rebamipide protects against activation of neutrophils by Helicobacter pylori.

Our objectives were to determine whether rebamipide, a unique antiulcer agent, would inhibit adhesive reactions between neutrophils and endothelial cells as well as the production of active oxygen species from neutrophils elicited by an extract of H. pylori. A water extract of H. pylori that was prepared from biopsy materials obtained from a patient with gastric ulcer increased the surface expression of CD18 on human neutrophils isolated from peripheral blood, the adhesion of neutrophil-endothelial cells, and the production of active oxygen species by neutrophils. Rebamipide, at concentrations of 10(-5) and 10(-6) M, reduced the adherence of neutrophils to endothelial cells as well as the CD18 expression on neutrophils induced by this bacterial extract. Rebamipide also inhibited the production of active oxygen species from neutrophils stimulated by H. pylori extract. These results suggest that rebamipide protects against the gastric mucosal inflammation associated with H. pylori by inhibiting neutrophil function.

Alanine↗

PubMed1996

Cross-bridge movement in rat slow skeletal muscle as a function of calcium concentration.

A single fibre bundle from rat soleus muscle was chemically skinned with saponin and the transfer of myosin heads from the thick filaments to the thin filaments at a sarcomere length of 2.4 microm was measured as a function of Ca2+ concentration using an x-ray diffraction method at 4-7 degrees C. In the relaxed state, the 1,0 spacing was 42.08 nm. The spacing showed no significant decrease when the Ca2+ concentration was below the threshold (-log10 [Ca2+] or pCa 5.8). No significant transfer of the myosin heads occurred when the Ca2+concentration was below the threshold (pCa 5.8). When the muscle was maximally activated at pCa 4.4, the spacing decreased to 40.35 nm. During the maximum isometric contraction at pCa 4.4, 54. 9 +/- 6.5% (+/-SE of the mean) of the myosin heads were transferred to the thin filaments. The transfer of the myosin heads was approximately proportional to relative tension. These results suggest that myosin heads of both fast-twitch and slow-twitch skeletal muscles transferred on the common movement as a function of Ca2+ concentration.

Actins↗

PubMed1996

Modulation of vascular calcium channel activity in response to acute volume expansion in rats.

The mechanisms of the increased resistance in hypertension are still unclear. Several studies have indicated that the potential-sensitive Ca2+ channels (PSC) are altered in arteries isolated from hypertensive patients or animals. An expansion of body fluid volume may trigger local autoregulatory responses or may induce the release of humoral factors, either of which could increase systemic vascular resistance and cause volume-dependent forms of hypertension. We tested the hypothesis that volume expansion per se may cause the alterations of PSC similar to those seen in hypertension. For this, we examined the alterations of PSC in aortas from volume-expanded rats with the use of dihydropyridine-type Ca2+ channel activator, BayK 8644, in parallel with the changes in endothelium-dependent relaxation. Volume expansion was produced by a rapid intravenous infusion of saline (10% of body weight) over 30 min in rats. At the end of infusion, rats were killed and aorta removed for in vitro measurement of isometric tension. Relaxation to acetylcholine (10(-7)-10(-5) mol/L, % relaxation to 10(-7) mmol/L norepinephrine contraction) was not significantly changed. In contrast, contractile response to BayK 8644 (10(-9)-10(-6) mol/L, % response to 50 mmol/L KCl) was significantly enhanced in rats with volume expansion (12 control rats: 11.6 +/- 4.9%; 18 volume-expanded rats: 40.9 +/- 10.4% at 10(-6) mol/L, p < 0.05). These findings suggest that acute volume expansion could induce a similar enhanced vascular Ca2+ channel activity to that seen in hypertension in rats.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1996

DNA conformation and its changes upon binding transcription factors.

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Base Sequence↗

PubMed1996

Bioavailability and diuretic effect of furosemide following administration of tablets and retarded capsules to human subjects.

Two kinds of dosage forms (tablets and retarded capsules) of furosemide (F) were compared in vitro dissolution profile and in vivo absorption studies. The dissolution of F from retarded capsules was extremely restricted in the first fluid of the JP XII disintegration test (within 0.8%), while the dissolution of F from tablets and retarded capsules in the second fluid of JP XII disintegration test were both complete. Metabolite specific assay of F showed F, conjugation of F with glucuronic acid (FG) and acyl migration isomers of FG (FG-iso) in urine or plasma. The mean cumulative urinary excretion of F following administration of the tablets during 24 h was twice that of retarded capsules. The mean area under the plasma concentration-time curve (AUC) of F following administration of tablets was 1.5 times that of retarded capsules. The mean cumulative urine volume during 24 h, however, was not significantly different between the two dosage forms. Clockwise hysteresis relationships between the diuretic response and the urinary excretion rate of F was observed after administration of retarded capsules. A straight relation between logarithm of the diuresis and logarithm of the urinary excretion of F was observed after maximum excretion rate of F following administration of both dosage forms.

Absorption↗

PubMed1996

Development of bioactive functions in Hydrangeae dulcis folium. VI. Syntheses of thunberginols A and F and their 3'-deoxy-derivatives using regiospecific lactonization of stilbene carboxylic acid: structures and inhibitory activity on histamine release of hydramacrophyllols A and B.

Lactonization reaction of 2-carboxystilbene mediated by copper(II) chloride proceeded regiospecifically to give the five-membered lactone, while the bromolactonizations using N-bromosuccinimide and anodic oxidation were found to furnish the six-membered lactone. Using these regiospecific lactonization reactions as a key step, antiallergic and antimicrobial isocoumarins and the benzylidenephthalides thunberginols A and F and their 3'-deoxyanalogs were synthesized from phyllodulcin and hydrangenol. Two phthalides called hydramacrophyllols A and B were isolated from Hydrangeae Dulcis Folium and their stereostructures were determined on the basis of physicochemical and chemical evidence, which included the syntheses of hydramacrophyllols A and B from hydrangenol by the application of the lactonization method using copper(II) chloride. In addition, hydramacrophyllols A and B were found to exhibit an inhibitory effect on the histamine release from rat peritoneal exudate cells induced by antigen-antibody reaction.

Animals↗

PubMed1996

The role of DNase and EDTA on DNA degradation in formaldehyde fixed tissues.

Degradation and extraction of high molecular weight DNA from formaldehyde fixed tissues suitable for gene analysis are presented. We previously reported that DNase might play an important role in the degradation of DNA extracted from formaldehyde fixed tissues (Tokuda et al. 1990). In the present study, DNase activity of the supernatant from rat tissues fixed in buffered formaldehyde at room temperature was negligible within 3 hr. Analysis of DNA extracted from reconstituted chromatin revealed that the degradation increased in the absence of DNase depending on the duration of the formaldehyde fixation. Furthermore, high molecular weight DNA could be extracted from tissues devoid of DNase activity fixed in buffered formaldehyde containing EDTA. These results demonstrated that DNA degradation was due mainly to a mechanism other than DNAse which was inhibited by EDTA. For clinical application, v-H-ras gene was successfully detected by Southern blotting from rat spleen tissues fixed in buffered formaldehyde especially at 4 C. Fixation at low temperature is useful for gene analysis.

Animals↗

PubMed1996

Local gastric and serum concentrations of rebamipide following oral administration to patients with chronic gastritis.

The potential anti-ulcer action of rebamipide (CAS 11911-87-6, OPC-12759) on experimental and clinical injury to the gastric mucosa depends on its presence in sufficient concentration in the gastric mucosa. To investigate its local penetration, rebamipide levels in the gastric mucosa and serum were measured. A dose of 100 mg of rebamipide was given orally (tablet) to patients with chronic gastritis (n = 32). Gastroscopy was performed between 22 and 353 min after drug ingestion. Venous blood was sampled for determination of serum concentrations. Samples were analyzed by high-performance liquid chromatography (HPLC). The maximal concentration in the gastric mucosa was reached after 30-60 min, and the concentration remained elevated for about 120 min thereafter. The mean mucosal concentration of rebamipide between 30 and 120 min after ingestion was 60.0 +/- 109.8 micrograms/g of tissue, which was higher than 0.1 mmol/l (37 micrograms/g of tissue). The serum concentration of rebamipide peaked about 30-60 min after drug ingestion and remained elevated for about 5 h thereafter. The mean serum concentration of rebamipide between 30 and 120 min after ingestion was 0.25 +/- 0.23 microgram/ml, being below the level of 1.0 mumol/l (0.37 microgram/ml). Data indicate that the concentration of rebamipide in the gastric mucosa resulted from local penetration, and suggest that the blood level and systemic distribution of rebamipide have little effect on its antioxidative and anti-neutrophilic activities.

Adult↗

PubMed1996

[Colonic stricture due to acute pancreatitis--the examination of our cases and the past reports in Japan].

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Acute Disease↗

PubMed1995

Effect of a novel histamine H2 receptor antagonist, IT-066, on acute gastric injury induced by ischemia-reperfusion in rats, and its antioxidative properties.

The effect of a novel histamine H2 receptor antagonist IT-066 (3-amino-4-[4-[4-(1-piperidinomethyl)-2-pyridyloxy]-cis-2-++ +butenylamino]- 3-cyclobutene-1,2-dione hydrochloride), on acute gastric mucosal injury induced by ischemia-reperfusion was investigated from the standpoint of oxygen radical-mediated lipid peroxidation in rats. Ischemia-reperfusion injury was produced in the rat stomach by applying a small vascular clamp to the celiac artery for 30 min and subsequent removal of the clamp for 60 min. The decrease in gastric mucosal blood flow was not influenced by treatment with IT-066. The antiulcer activity of IT-066 was demonstrated in this injury after intragastric ingestion as well as after intravenous injection. IT-066 significantly inhibited this injury in the presence of exogenous HCl. The mucosal protection by IT-066 was not reversed by pretreatment with indomethacin or nitric oxide synthase inhibitor. The increase in lipid peroxides in the gastric mucosa after ischemia-reperfusion was significantly inhibited by the intragastric treatment with IT-066 at doses of 1.0 and 3.0 mg/kg. The total area of erosions closely paralleled the accumulation of lipid peroxide with a significant correlation. A spin trapping method using 5,5-dimethyl-1-pyrroline-N-oxide showed that IT-066 scavenged superoxide radical and hydroxyl radical generated by the hypoxanthine-xanthine oxidase system and the hydrogen peroxide-ferrous iron system, respectively. IT-066 also significantly inhibited the in vitro increase of lipid peroxide in the gastric mucosal homogenates induced by a free radical initiator. These results suggest that the protective effect of IT-066 against ischemia/reperfusion-induced gastric mucosal injury may result in part from its antioxidative properties.

Animals↗

PubMed1995

Administration of monoclonal antibodies against vascular cell adhesion molecule-1/very late antigen-4 abrogates predisposing autoimmune diabetes in NOD mice.

The interaction of vascular cell adhesion molecule-1 and very late antigen-4 (alpha 4 beta 1-integrin) has been recently known to be profoundly involved in the trafficking of lymphocytes from the circulation into the inflammatory tissues. To elucidate the role of these molecules in the development of autoimmune diabetes, the expression of these adhesion molecules on inflamed islets and the effects of administration of monoclonal antibodies to these molecules on insulitis and overt diabetes were evaluated in nonobese diabetic (NOD) mice. Immunohistochemical study revealed the overexpression of vascular cell adhesion molecule-1 on vascular endothelium near or within inflamed islets and alpha 4-integrin on islet-infiltrating mononuclear cells. Either anti-vascular cell adhesion molecule-1 or anti-alpha 4-integrin monoclonal antibody prevented the transfer of diabetes in irradiated NOD mice which received spleen cells from acutely diabetic NOD mice. When both monoclonal antibodies were administrated to NOD mice during 2-30 weeks of age, neither lymphocytic infiltration to islets nor overt diabetes was observed. Furthermore, administration of these antibodies even from 10 weeks of age could inhibit the development of insulitis and diabetes, whereas administration during 2-5 weeks of age could not. Splenocytes obtained from these treated mice showed no significant change of cytokine production and preserved the ability to transfer diabetes into NOD scid/scid mice. This suggests that treatment with antibodies against these adhesion molecules can inhibit insulitis and diabetes without affecting the Th1/Th2 balance or effector T cells. The blockade of vascular cell adhesion molecule-1/very late antigen-4 interaction would be suitable for therapeutical treatment of the predisposing and latent type I (insulin-dependent) diabetic subjects.

Animals↗

PubMed1995

Structural changes in actin-tropomyosin during muscle regulation: computer modelling of low-angle X-ray diffraction data.

The crystal structure of G-actin monomer has been used together with tropomyosin in a filament model to explain the low-angle X-ray diffraction data from relaxed and activated actin filaments. The four-subdomain actin monomer can be approximated quite well by a four-sphere unit. Orienting this unit and tropomyosin into a filament by searching for the best fit between the computed Fourier transform and the observed vertebrate skeletal muscle low-angle actin layer-lines from muscles at non-overlap sarcomere lengths produced models for the structural changes within the thin filaments (actin plus tropomyosin) between the resting state and the active states, which occur as a result of calcium-activation and independent of myosin interaction with actin. The models are very sensitive to changes in the positions of the centres of mass of the subdomains, but not to the exact shape of the objects used to represent them (e.g. spheres, ellipsoids etc.), as long as the volume is fixed, at the resolution here considered. It is concluded that, even with a four-subdomain structure for the actin molecules, the observed low-angle X-ray diffraction patterns cannot be explained without a substantial azimuthal swing of the tropomyosin strands when resting filaments are calcium-activated. The direction of this swing upon calcium-activation is away from a position close to the proposed major binding site of the myosin head on actin; a result consistent with the original "steric blocking model" of thin filament-based regulation in which the tropomyosin position on actin is crucial for regulation of the myosin crossbridge cycle on actin. Tropomyosin sterically hindering myosin attachment in the "off" state remains a possibility. However, even in the "on" state, the tropomyosin position is close enough to the myosin-binding site to have an effect, where it could regulate the transition of the head from a weak to a strong state. In addition to this tropomyosin movement there are small, but plausible, actin subdomain movements. A tropomyosin shift on its own will not explain the data. Allowance for possible movement of actin subdomain 2 along with the tropomyosin shift still does not explain the data. An additional small movement of subdomain 1; the main myosin-binding subdomain, is postulated.

Actin Cytoskeleton↗

PubMed1995

Stereochemical basis of DNA bending by transcription factors.

Superstructure-formation of DNA plays an important role in transcription regulation as well as in chromatin formation. To understand the stereochemical basis of DNA bending by proteins we analysed the structural characteristics of dinucleotide steps which occur at the site where DNA is bent upon binding a transcription factor. When DNA is considerably bent in a crystal structure the bending is not spread smoothly over a length, but the DNA is kinked at a pair of crucial steps which are highly rolled and untwisted. These rolled steps are spaced 6-10 bp apart and are predominantly occupied by pyrimidine-purine sequences. In association with another dinucleotide step at the centre, which combines 6 bp-spaced rolled steps towards the same side of the DNA, these produce two essentially different types of DNA bending.

Base Composition↗

PubMed1995

Structural changes in myosin cross-bridges during shortening of frog skeletal muscle.

X-ray diffraction patterns from frog sartorius muscle were recorded during steady shortening with various loads. The intensity of the third meridional reflection from the thick filament decreased on shortening to an extent proportional to the drop in tension. The intensity correlated more closely with the tension than with the shortening velocity. The Bragg spacing of the third meridional reflection decreased in proportion to the decrease in tension. The intensity decrease of the actin layer lines at 1/5.1 and 1/5.9 nm-1 was roughly proportional to the decrease in the load, indicating that the number of cross-bridges decreases similarly. The intensity of the (1,1) equatorial reflection showed a significant decrease only with low loads. Assuming that a steady structural state is attained during steady shortening, the results are consistent with the cross-bridge model in which the number of myosin cross-bridges decreases during shortening.

Actins↗

PubMed1995

Effects of adenosine diphosphate on the structure of myosin cross-bridges: an X-ray diffraction study on a single skinned frog muscle fibre.

Using a technique to obtain a detailed X-ray diffraction pattern from a single skinned frog muscle fibre, we studied the effects of ADP on the structure and arrangement of myosin heads. An imaging plate and a cooled-CCD X-ray detector were used to record the diffraction patterns. Addition of 1 mM ADP to a rigor fibre increased the intensity of the third-order meridional reflection of the myosin repeat by 50-85%. The intensity of the sixth-order meridional reflection also increased. After removing the ADP, these intensities decreased but did not return to the level before the ADP was added. No significant changes were observed in the intensities of the equatorial reflections and the actin layer-lines. These results suggest that, upon ADP binding, the conformation of a myosin head changes without detaching from actin. The structural change may involve a relative motion between domains of the myosin head by the closure of the cleft to which an ADP molecule binds.

Adenosine Diphosphate↗

PubMed1995

Role of neutrophil-mediated inflammation in aspirin-induced gastric mucosal injury.

The objectives of this study were to determine the roles of neutrophil-endothelial cell interactions and oxygen-derived free radicals in the pathogenesis of aspirin-induced gastric mucosal injury in rats. Oral administration of acidified aspirin (200 mg/kg) resulted in linear hemorrhagic erosions and an increase in myeloperoxidase activity, an index of neutrophil infiltration, in the gastric mucosa. Aspirin-induced gastric damage and the increase in myeloperoxidase activity were significantly inhibited by the injection of anti-CD11a, anti-CD11b, anti-intercellular adhesion molecule-1 monoclonal antibodies, and the combination of superoxide dismutase and catalase, which are scavengers of active oxygen species. These results suggest that neutrophil-endothelial adhesive interactions, which occur via CD11a/ CD18- and CD11b/CD18-dependent interactions with intercellular adhesion molecule-1, and oxygen-derived free radicals produced by neutrophils are implicated in the production of aspirin-induced gastric mucosal injury.

Animals↗