Biomedical subjects

N Yagi

Publications and source records attributed to N Yagi.

At least 55 records · Page 3Linked to original sources

PubMed1998

A pre-active attached state of myosin heads in rat skeletal muscles.

X-ray diffraction experiments were performed on rat soleus and psoas muscles using synchrotron radiation from a multipole wiggler. The X-ray diffraction patterns were recorded at a time resolution of 16.7 ms with an X-ray image intensifier and a CCD video camera. A bundle of 10-15 muscle fibres was activated by photorelease of 2.2 mM ATP from 7 mM caged-ATP at 15 degrees C. In soleus muscle fibres in the presence of 40 microns Ca2+, the tension developed with a half-time of 0.13 s. The intensities of the (1,1) equatorial reflection and the actin layer-lines at 1/36 nm-1 and 1/5.9 nm-1 decreased from their rigor values in the first 16.7 ms frame to a level higher than in the resting state, and then remained unchanged during the tension development. The intensity of the 14.5 nm meridional reflection increased as the tension developed. These results show that after the ATP release some myosin heads are stereospecifically attached to actin well before tension development, and suggest that their number does not change markedly on contraction.

Actins↗

PubMed1998

Rebamipide protects against indomethacin-induced gastric mucosal injury in healthy volunteers in a double-blind, placebo-controlled study.

The aim of the present study was to evaluate rebamipide in the prevention of indomethacin-induced gastric mucosal injury in healthy volunteers. Twenty healthy males (mean age 21.8 years, range 20-26) participated. This is a randomized, double-blind, placebo-controlled study. The 20 subjects were randomized to either indomethacin 25 mg three times a day and placebo three times a day or indomethacin and rebamipide 100 mg three times a day for seven days. Endoscopy was performed at baseline and again after the treatment. In the placebo group, eight of 10 subjects (80%) developed symptoms compared to three of seven (43%) in the rebamipide group. The incidence of gastric lesions was 70% in the placebo group, which was significantly higher than that in the rebamipide group (14%). The lipid peroxide levels in the mucosa of the gastric body significantly increased in the placebo group. This increase was not inhibited by rebamipide. Myeloperoxidase activity in the gastric mucosa tended to increase in the placebo group, but tended to decrease in the rebamipide group. These results indicate that rebamipide may be an effective prophylaxis against indomethacin-induced gastropathy in humans.

Adult↗

PubMed1997

Mechanical study of rat soleus muscle using caged ATP and X-ray diffraction: high ADP affinity of slow cross-bridges.

1. The cross-bridges in slow- and fast-twitch fibres (taken, respectively, from soleus and psoas muscles of rats) were examined in mechanical experiments using caged ATP and X-ray diffraction, to compare their binding of ATP and ADP. 2. Caged ATP was photolysed in rigor fibres. When ADP was removed from pre-photolysis fibres, the initial relaxation (+/- Ca2+) in soleus was as fast as that in psoas fibres, whereas the subsequent contraction (+Ca2+) was slower in soleus than in psoas. The ATPase rate during the steady-state contraction was also slower in soleus fibres. 3. When ADP was added to pre-photolysis fibres (+/- Ca2+), tension developed even in the initial phase, the overall tension development being biphasic. Both initial and late components of the Ca(2+)-free contraction were enhanced when ADP was added before photolysis, although pre-photolysis ADP was not a prerequisite for the late component. The effect of ADP was greater in soleus than in psoas fibres. Static experiments on rigor fibres revealed a higher ADP affinity in soleus fibres. 4. The intensity of the actin layer-line from ADP rigor soleus fibres decreased rapidly on photorelease of ATP. We conclude that, despite the tight ADP binding of the soleus cross-bridge, its isometric reaction is not rate limited by the 'off' rate of ADP.

Adenosine Diphosphate↗

PubMed1997

High prevalence of GAD65 (and IA-2) antibodies in Japanese IDDM patients by a new immunoprecipitation assay based on recombinant human GAD65.

Marked differences have been reported in the prevalence of glutamic acid decarboxylase (GAD) antibodies between Caucasian (63-84%) and Japanese (30-50%) or Asian (5-50%) IDDM patients. Using a new immunoprecipitation assay based on 125I-labelled recombinant human GAD65 we have reassessed prevalence of GAD65 antibodies in Japanese patients. We also assessed prevalence of IA-2 antibodies. GAD65 antibodies were detected in 83.3% of sera taken within 1 year of onset, comparable to the prevalence reported in Caucasian patients. Positivity decreased to 66.7% after 2 to 3 years and to 54.3% after 3 years from onset, still higher than previously reported Asian prevalence. Except in one patient, high antibody levels persisted chronically, up to 12 years. There was no difference in the prevalence of GAD65 antibodies between Japanese IDDM patients with and without autoimmune thyroid disease (AITD). IA-2 antibodies were detected in 64.7% of sera taken within 1 year of onset. Prevalence of IA-2 antibodies was lower than that of GAD65 antibodies. The difference in positivity in Asian IDDM patients between present and previous reports arose from the sensitivity of our assay for GAD65 antibodies. Additionally, the patients we studied had classic IDDM with a well-defined onset. We conclude that prevalence of GAD65 antibodies in Japanese IDDM patients is comparable to that in Western studies. There was no relationship of GAD65 antibody positivity to coexistence of AITD. Our results suggest that autoimmunity is the most significant cause of Japanese IDDM.

Adolescent↗

PubMed1997

Prognostic significance of argyrophilic nucleolar organizer region (AgNOR) in resected non-small cell lung cancer (NSCLC).

The expression of the nucleolar organizer regions (NORs) was quantified in paraffin sections of tumors and lymph node metastasis, by means of digital image analysis, in 75 patients with resected non-small cell lung cancer (NSCLC). Patients were divided in two groups: early stage (stages I and II) and advanced stage (stages IIIa, IIIb and IV). The prognostic significance of AgNOR expression was tested by Cox regression analysis in models controlled for age, sex, vital status, stage and histological type. Tumors at early stages had a lower expression of AgNOR than those at more advanced diseases. The mean values obtained for NORs in advanced disease were almost the same as those in the primary tumors when compared with the corresponding lymph node metastasis (r = 0.90; p < 0.01; linear regression). The prognostic role of AgNOR was significant only for tumors at stages I and II and not for advanced neoplasms (stages IIIa, IIIb and IV). These results encourage the inclusion of AgNOR quantitation in routine material, especially in early lung cancer.

Adult↗

PubMed1997

Monochloramine-induced cell growth inhibition and apoptosis in a rat gastric mucosal cell line.

Recent studies have indicated that monochloramine (NH2Cl), a reaction product of NH3 and hypochlorous acid, is involved in the pathogenesis of Helicobacter pylori-associated gastric mucosal damage, but how NH2Cl contributes to lesions is unclear. In the present study, the effects of NH2Cl on mucosal cell growth and the cell cycle were evaluated in vitro using a normal rat gastric mucosal cell line RGM-1. Cell viability was assessed by the Trypan Blue dye exclusion test and cell cycle patterns were determined by DNA labeling with propidium iodide and flow cytometric quantification. NH2Cl inhibited the growth of RGM-1 cells in a concentration-dependent manner. Exposure of cells to NH2Cl caused a time- and dose-dependent loss of G1-phase cells with accumulation of G2/M-phase cells, and produced a fraction of subdiploid cells with oligonucleosomal DNA degradation characteristic of apoptosis. NH2Cl-induced apoptosis was confirmed by fluorescent microscopy with Hoechst 33342 and propidium iodide. These results suggest that NH2Cl inhibits gastric mucosal cell growth and induces apoptosis in RGM-1 cells, events that may be important in gastric mucosal damage or atrophy induced by H. pylori infection.

Animals↗

PubMed1997

An abnormal sodium metabolism in Japanese patients with essential hypertension, judged by serum sodium distribution, renal function and the renin-aldosterone system.

OBJECTIVE: The role of the renin-aldosterone system and the ability of renal sodium reabsorption to facilitate pressure natriuresis were analyzed by using a sufficient number of Japanese patients with essential hypertension. METHODS: We studied 3222 normal Japanese subjects (610 in Kashiwa City Hospital and 2612 in Shinshu University Hospital), 741 Japanese patients with essential hypertension (256 in Kashiwa City Hospital and 485 in Shinshu University Hospital), 20 patients with aldosterone-producing adenomas and 11 patients with idiopathic hyperaldosteronism to determine the possible roles of sodium, renal function, and plasma aldosterone concentration (PAC) on blood pressure elevation. Inappropriate elevation of aldosterone levels [elevation of the aldosterone:plasma renin activity (PRA) ratio] was used to assess aldosterone action. RESULTS: The peak of the serum sodium distribution curve was approximately 2 mmol/l higher in the patients with essential hypertension than it was in controls. The prevalence of higher serum sodium concentrations (> or = 147 mmol/l) also was increased significantly hypertensive patients. Age-related deterioration of renal function did not explain the hypertension and abnormal sodium metabolism in the hypertensive patients. In stepwise regression analysis, the serum sodium concentration was related inversely to the PRA and positively to the PAC:PRA ratio. Although there was an inverse relationship between urinary sodium excretion (representing sodium intake) and the PRA, urinary sodium excretion proved not to be significant as a source of variation in the PAC or in the PAC:PRA ratio in the hypertensive patients. Although the PAC was within the normal range in patients with serum sodium concentrations of 147 mmol/l or more and an elevated PAC:PRA ratio, it was inappropriately high for the stimulus applied, as indicated by the PRA; this is similar to the situation with aldosterone-producing adenomas or idiopathic hyperaldosteronism. CONCLUSION: Serum sodium distribution patterns differed between normal subjects and patients with essential hypertension in this Japanese population. The deterioration of renal function and increased sodium intake did not explain this abnormal sodium metabolism. A higher serum sodium concentration is related to an elevated blood pressure, and, in some patients, an inappropriate elevation of plasma aldosterone levels. Of the Japanese hypertensive patients, 10-14% exhibited serum sodium concentrations of 147 mmol/l or more and inappropriate elevations of aldosterone level (suppressed PRA and normal aldosterone level). The defect in these patients presumably lies in the inappropriately high secretion of aldosterone.

Adult↗

PubMed1997

[Preparation and evaluation of solid dispersions of pilocarpine hydrochloride for alleviation of xerostomia].

This investigation was carried out to try the application of pilocarpine hydrochloride (PC) solid dispersion as sustained release dosage form. Four preparations of PC with ethylcellulose and/or hydroxypropylmethylcellulose phthalate were prepared by the organic solvent method. The preparation D including PC: ethylcellulose: hydroxypropylmethylcellulose phthalate (1:9:10 at weight ratio) showed the best sustained release behavior in dissolution test among four preparations. The preparation D was examined by powder X-ray diffractometry and differential scanning calorimetry, and confirmed to be solid dispersion. Saliva secretory effect of preparation D was examined in healthy male volunteers, and its effect for Xerostomia was showed.

Cellulose↗

PubMed1997

Morphometric evaluation of argyrophilic nucleolar organizer region is useful in predicting long-term survival in squamous cell carcinoma of the lung.

Nucleolar organizer regions identified by means of an argyrophilic technique (AgNOR) were quantified by digital image analysis in 81 patients with squamous cell carcinoma of the lung. Survival rate was modeled as function of AgNOR expression by Cox regression models controlled for staging, histologic grade, age, and sex. Our results indicate that AgNOR expression has a significant prognostic role. Tumors at lower stages have a lower expression of AgNOR than those with more advanced disease. Tumors with high histopathologic grade have a higher expression of AgNOR. Patients with low AgNOR expression presented a higher survival rate than those with higher amounts of AgNOR. The foregoing results strongly encourage the development of prospective trials to assess the real role of AgNOR in determining prognosis in squamous cell carcinoma of the lung.

Aged↗

PubMed1997

[Long-term clinical results with a new surgical method for the fragile valvular annulus].

We performed prosthetic valve replacement with skirt in 11 patients for the fragile valvular annulus. Subjects included 6 patients with active infective endocarditis involving aortic root abscess, 2 patients with systemic disease requiring steroid treatment, and 3 patients with hemolysis or perivalvular leakage. Operative procedure in 11 patients was performed aortic valve replacement with Dacron or Xenomedica skirt attached to the prosthetic ring. One patient died of heart failure during perioperative period. 2 patients died of arrhythmia, heart failure in late postoperative period. The event free rate was 77.1% since 5 years after operation. We conclude that prosthetic valve replacement with skirt is useful to tha fragile valvular annulus.

Adult↗

PubMed1997

[Ascending aortic aneurysms operated through redo median sternotomy under selective cerebral perfusion].

Case 1: A 34-year-old man who had received ventricular septal closure at 4 years old was found to suffer from annuloaortic ectasia with severe aortic regurgitation and giant ascending aortic aneurysm accompanying with dissection. Median sternotomy was performed under selective cerebral perfusion to control bleeding when the aorta was injured. He was successfully replaced the ascending aorta and the aortic valve with the composite graft including an aortic prosthetic valve by modified Piehler's procedure. Case 2: A 44-year-old man received mitral valve replacement and tricuspid annuloplasty due to mitral regurgitation with tricuspid regurgitation. After surgery, he suffered from mediastinitis. Three months later, he was found to have pseudoaneurysm of the ascending aorta. During the sternotomy done under selective cerebral perfusion, the pseudoaneurysm was injured but bleeding was controlled easily. The defect of the aorta was closed successfully using a Dacron patch and covered with the right sternocleidomastoid muscle flap. Sternotomy under selective cerebral perfusion is very useful and safe for such patients as to have risks to injure the aorta or the heart during the sternotomy.

Adult↗

PubMed1997

Acute dialysis and continuous renal replacement: the emergence of new technology involving the nephrologist in the intensive care setting.

The emergence of dialytic support for patients with reversible renal failure was one of the most significant advances in critical care medicine. Supporting a patient with a failed organ till organ recovery has not had the same success with other organ failures. Despite the indispensable nature of the support, dialysis was intermittent at best, and carried its own morbidity. The emergence of a "continuous" dialysis delivery system, originally through an arteriovenous access and later through veno-venous methodology, began to simulate the continuity of the natural kidney, and lifted much of the fluid and drug restrictions imposed by the intermittent nature of standard dialytic therapies. Components of the system were next reviewed for improvement and biocompatability. Differences in patient outcome were documented with various component comparisons, and disparate patient tolerance of delivery modality was also clearly proven. The hemodynamic stability of continuous treatment created utilization to be focused on the more unstable, the more severely compromised patient group. In this context, comparative studies with intermittent delivery methods showed improved hemodynamic stability among patients treated with continuous renal replacement therapies (CRRT), but no clear difference in patient mortality. Patient characteristics and severity scoring have recently been undertaken to better describe the population, and attempts at dialysis dosing is currently being developed for ARF dialysis recipients. Early results seem to point toward a dialysis dose effect on mortality in certain groups of ICU acute renal failure patients. However, the dialytic process is only depurative and artificial. Plastic membrane bio-incompatibility, human physiological responses to foreign material exposure, either in the circuit material itself or introduced from therapy methodology, pose practical and theoretical problems. Recent advances in the field of bio-artificial technology have allowed the development of functioning hybrid "blood processors," which function as a renal tubule and may be able to not only "clean" blood, but also allow for other cellular functions not currently possible with dead membrane technology. Combining living cells with a continuous delivery method may be the next significant step toward a fully functional renal replacement therapy.

Hemofiltration↗

PubMed1997

Effect of the histamine H2-receptor antagonist (+/-)-(E)-1-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-3'-[2-[[[5-methylamino ) methyl-2-furyl] methyl]thio]ethyl]-2"-(methylsulfonyl)guanidine on acute gastric mucosal injury in rats and its free-radical scavenging activities.

The protective effect of T-593 ((+/-)-(E)-1-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-3'-[2-[[[5-(methylamino) methyl-2-furyl]methyl]thio]ethyl]-2"-(methylsulfonyl)guanidine, CAS 140695-21-2), a new histamine H2-receptor antagonist, was investigated in rats with acute gastric mucosal injury. An ischemic injury followed by reperfusion was produced by applying a small vascular clamp to the celiac artery for 30 min and then removing it for 60 min. T-593 significantly reduced the area of the lesion in the stomach in a dose-dependent manner, and doses of 0.3 and 3.0 mg/kg inhibited the increase of lipid peroxides in the gastric mucosa after ischemia-reperfusion. A spin-trapping method using 5,5-dimethyl-1-pyrroline-N-oxide showed that T-593 scavenged hydroxyl radicals generated by the hydrogen peroxide-ferrous iron sulfate system. T-593 also significantly inhibited the increase of lipid peroxides induced by free-radical initiators in gastric mucosal homogenates. Thus, the protective effect of T-593 against acute gastric mucosal injury induced by ischemia and followed by reperfusion may result, in part, from its antioxidant properties.

Animals↗

PubMed1996

Labelling of thin filaments by Myosin heads in contracting and rigor vertebrate skeletal muscles.

A method of crystallographic analysis to identify myosin heads interacting with specific actin sites in vertebrate striated muscles is described. It is based on a Fourier transform of a helix in which probability of occurrence of subunits varies periodically. It predicts the presence of layer-lines at 1/24 and 1/10.4 nm(-1) which are experimentally observed in contracting and rigor vertebrate striated muscles, showing that the myosin heads are interacting with specific sites on actin but are still maintaining their average 14.5 nm axial periodicity.

Journal Article↗

PubMed1996

Small-Angle X-ray Diffraction of Muscle Using Undulator Radiation from the Tristan Main Ring at KEK.

Time-resolved X-ray diffraction of muscle has demanded ever-increasing flux into small sample volumes with low beam divergence. Results are reported of static and time-resolved small-angle X-ray diffraction studies on muscle fibers using a hard X-ray undulator installed in the Tristan main ring at KEK, Tsukuba, Japan, as an innovative source of synchrotron radiation more intense and better collimated than that available with the Photon Factory bending-magnet beamline. Static studies used the low divergence of the source to obtain detailed high-quality diffraction patterns of stable muscle states. The diffraction patterns from live skeletal muscles showed the numerous (over 100) meridional reflections. The well collimated beam from the undulator made it possible to clearly resolve, with an angular resolution of ca 700 nm, the closely spaced diffraction peaks arising from the two halves of the thick filaments centred on the M lines in a sarcomere, in addition, the diffraction peaks from the thin filaments on opposite sides of the Z bands could be resolved with an angular resolution of ca 1000 nm. The detailed structure of the meridional pattern defines the nature of the molecular packing in the thick and thin filaments. Time-resolved experiments using a focusing mirror aimed to prove cross-bridge states in striated muscle fibers by collecting X-ray diffraction data at a 0.185 ms time resolution from sinusoidally oscillating chemically skinned rabbit muscle fibers during active contraction and in rigor. When sinusoidal length changes at 500 Hz with a peak-to-peak amplitude of 0.6% of the muscle length were applied to a small fiber bundle, the tension showed a simple elastic response during the length oscillation. In the active muscle the intensity of the 14.5 nm myosin-based meridional reflection changed out of phase with the tension change during the oscillating length change. In contrast, in the rigor muscle it occurred in phase with the tension change. The high time-resolved experiments provide an insight into the coupling between conformational changes and force generation of the actomyosin cross-bridges. These studies provide a preview of the expected gains for muscle studies from the more widespread use of undulator radiation at third-generation synchrotron sources.

Journal Article↗

PubMed1996

Induction of tolerance in murine autoimmune diabetes by transient blockade of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 pathway.

The present study demonstrated that a short-term administration of mAbs against leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) at critical periods resulted in complete protection of autoimmune diabetes in non-obese diabetic (NOD) mice. When these mAbs were administered for only 6 days at 2 wk of age, neither diabetes nor insulitis was observed at 30 wk of age. It appears that the tolerance against beta cell Ag(s) was induced by this transient blockade of the LFA-1/ICAM-1 pathway. Protective suppressor activity was not enough to prevent diabetes because co-transfer of splenocytes from female NOD mice, which had received these mAbs at 2 wk of age, resulted in only a short delay of the diabetic onset caused by adoptive transfer of splenocytes from acutely diabetic NOD mice. Transfer of these splenocytes to young NOD mice could not also abrogate the spontaneous diabetes and insulitis. Furthermore, cyclophosphamide treatment could not abrogate the protection. When splenocytes from the treated NOD mice were transferred to NOD-SCID mice, none of the recipient mice developed significant insulitis and subsequent overt diabetes, suggesting the absence or the inactivation of diabetogenic effector T cells. However, splenic T cells from the insulitis-free NOD mice that had received the mAb treatment preserved proliferative responses to both islet cells and 65-kDa glutamic acid decarboxylase (GAD65) in vitro. These results suggest that a unique peripheral tolerance was induced by the transient blockade of the LFA-1/ICAM-1 pathway in an early age of NOD mice.

Adoptive Transfer↗

PubMed1996

Analysis of co-crystal structures to identify the stereochemical determinants of the orientation of TBP on the TATA box.

Possible stereochemical determinants of the orientation of TBP on the TATA box are discussed using the crystal coordinates of TBP-TATA complexes, which have been determined by other groups. The C-terminal half of the TBP beta-sheet interacts with the TATA site of the DNA, and the N-terminal half with the A-rich site, so that the two sites with distinct curvatures produce a unique fit. Although chemical contacts take place between one side of the beta-sheet and the DNA minor groove, the interaction seems to be facilitated indirectly by the characteristics of the other side of the beta-sheet and the DNA major groove. Thus, Ala71, Leu162 and Pro190 differentiate the curvature of the beta-sheet in the N- and C-halves. The methyl positions in the DNA major groove modulate the bendability of the two DNA sites by using differences in the rolling capacity of TA and AT compared with PyT, and in the shifting capacity of AT compared with TT. The deformations of the first steps (TA and PyT) in the two sites are the largest and thus are important for the overall bending of the DNA. The differences between the two DNA sites are greatest at the second steps (AT and TT) and so these are important for determining the orientation of TBP.

Amino Acid Sequence↗

PubMed1996

An in-the-groove view of DNA structures in complexes with proteins.

DNA structures bound to transcription factors are studied by using the crystal coordinates of complexes. Structural characteristics which are found at the sites where a protein secondary structure, an alpha-helix or a beta-sheet binds, can be understood in terms of fitting of the concave surface of the DNA major groove and the convex surface of the protein secondary structure; the former changes, becoming narrower or wider so that it fits the latter. An alpha-helix, independent of which groove it binds to, tends to produce a narrow major groove and a wide minor groove. When the major groove becomes narrower, the DNA helix axis bends around the major groove. Bending of DNA, which is overall structural change, is achieved by changes in local parameters (in particular, the roll parameter) so that an intermediate feature, the groove, fits the protein surface.

Base Composition↗