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S Ono

Publications and source records attributed to S Ono.

At least 397 records · Page 22Linked to original sources
PubMed1995

[Leukocyte-mediated production of eicosanoids in rat lungs: modulation by a calcium antagonist].

Formyl peptide (fMLP) by itself does not increase eicosanoid levels in rat lungs, but eicosanoid levels and edema do increase if endotoxin (ETX) is given before an fMLP challenge. The role of pulmonary intravascular leukocytes in fMLP-induced eicosanoid production in rat lungs was studied, as was the effect of a calcium antagonist (Ro 40-5967). ETX increased the levels of 6-keto PGF1 alpha, but not the levels of TXB2 or LTB4. A second challenge with fMLP in ETX-primed rats resulted in increased production of these three eicosanoids, and increased neutrophil accumulation, as assessed by myeloperoxidase assay. The calcium antagonist attenuated both the production of eicosanoids and the accumulation of neutrophils in the lung. The levels of both 6-keto PGF1 alpha and TXB2 correlated well with lung neutrophil accumulation. Leukocytes isolated from the pulmonary vasculature released TXB2 and LTB4 when stimulated with fMLP in vitro. The amount of these eicosanoids released from pulmonary intravascular leukocyte suspension was well correlated with neutrophil counts in a leukocyte suspension. These data indicate that fMLP-induced production of eicosanoids in the lung, especially production of TXB2, is mediated by pulmonary intravascular neutrophils, and that calcium antagonists can attenuate eicosanoid production by decreasing the accumulation of neutrophils in the lung.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

[A true aneurysm of the right internal mammary artery, accompanied by diminished grasping power of the right hand].

A 69-year-old man was admitted to our hospital after an abnormal shadow was found on a chest radiograph. The preoperative diagnosis was right subclavian aneurysm. Loss of grip in the right hand developed, and the patient underwent surgery. During surgery, the aneurysm was found to have originated from the right internal mammary artery. The root of the right internal mammary artery was tied and the right subclavian artery, which had been compressed and displaced by the aneurysm, was replaced. A chest radiograph obtained 6 months after surgery showed that the trachea was no longer displaced. However, the gripping force of the right hand had not recovered.

Aged↗
PubMed1995

[An experience of surgery for thymolipoma in a patient with amyotrophic lateral sclerosis].

A 48-year-old male with amyotrophic lateral sclerosis (ALS) was revealed to have an anterior mediastinal tumor, occupying left hemithorax on a chest CT. The tumor compressed the left lower lobe, resulting in a hypoventilation, which required a continuous ventilatory support. Although ALS has poor prognosis in general, we decided to remove the tumor surgically. Because the symptoms related to ALS was limited to his extremities, indicating he could potentially reestablish his life under ventilator-free condition, when a remove of the tumor improved a hypoventilation. A remove of the tumor was performed via antero-axillar thoracotomy, and reexpansion of the left lower lobe was achieved, followed by improvement of lung function and of respiratory symptoms. Histological examination revealed that the tumor was composed of mature adipose tissue and thymic tissue, diagnosed as thymolipoma. Postoperative course was uneventful.

Amyotrophic Lateral Sclerosis↗
PubMed1995

[Role of peptide leukotrienes in monocrotaline-induced lung disease].

Monocrotaline (MCT) causes lung inflammation and right ventricular hypertrophy associated with lung vascular thickening in rats. We hypothesized that peptide leukotrienes play a role in MCT-induced lung disease, and examined the effect of ONO 1078, a specific antagonist of LTC4, D4 and E4 receptors on MCT-induced right ventricular hypertrophy and on lung vascular thickening. Next, we measured leukotriene C4 (LTC4) levels in the lung tissue of MCT-treated rats. Within 3 weeks after the injection MCT had caused an increase in the ratio of right ventricular weight to left ventricle+septum weight (RV/(LV+S)) and an increase in media wall thickness of the muscular arteries of the lung. In rats given both ONO 1078 and MCT, these changes were significantly less severe than in rats given MCT only. The LTC4 levels in MCT-treated rats were significantly higher than in saline-treated control rats. These results indicate that this antagonist of peptide leukotriene receptors inhibits right ventricular hypertrophy induced by MCT, and suggest a role for peptide leukotrienes in the inflammatory process that contributes to lung vascular remodeling in MCT-treated rats.

Animals↗
PubMed1994

Subtype- and species-selectivity of a tachykinin receptor antagonist, FK888, for cloned rat and human tachykinin receptors.

We investigated the receptor-binding properties and potencies of FK888 (N2-[(4R)-4-hydroxy-1-(1-methyl-1H-indol-3-yl)carbonyl-L-prolyl]-N- phenylmethyl-3-(2-naphthyl)-L-alaninamide), a tachykinin receptor antagonist, for the rat and human tachykinin receptor subtypes (NK1, NK2 and NK3) expressed in transfected mammalian cells. In displacement analyses, using membrane preparations derived from monkey kidney COS-7 cells transiently expressing tachykinin receptor subtypes, FK888 showed a subtype selectivity for NK1 receptor and its affinity for the human NK1 receptor was 320-fold higher than that for the rat NK1 receptor, demonstrating species difference in its binding affinity. This was in marked contrast to FK224 (N-[N2-[N-[N-[N-[2,3-didehydro-N-methyl-N-[N-[3-(2-pentylphenyl )- propionyl]-L-threonyl]tyrosyl-L-leucynyl]-D-phenylalanyl]-L- allothreonyl]-L-asparaginyl]-L-serine-n-lactone) that was selective for NK1 and NK2 receptors with similar affinities for the rat and human receptors. In Chinese hamster ovary cells permanently expressing the human NK1 receptor, FK888 inhibited the substance P-induced phosphatidylinositol hydrolysis and produced a parallel shift in the dose-response curve for substance P. Schild analysis of the antagonism of phosphatidylinositol hydrolysis by FK888 yielded a pA2 value of 8.9 and a slope of 0.97 of the regression line. FK888 itself showed no stimulatory effect on phosphatidylinositol hydrolysis in Chinese hamster ovary cells expressing the human NK1 receptor. Thus, FK888 is a potent, competitive and selective antagonist for human NK1 receptor.

Animals↗
PubMed1994

Functional anatomy of taste perception in the human brain studied with positron emission tomography.

Regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) in 10 normal volunteers with the purpose of measuring rCBF changes related to taste physiology. Discrimination of 0.18% saline from pure water was associated with significantly increased rCBF values in the thalamus, the insular cortex, the anterior cingulate gyrus, the parahippocampal gyrus, the lingual gyrus, the caudate nucleus, and the temporal gyri. The results indicate that rCBF changes in these structures may reflect oral exposure to salt.

Adolescent↗
PubMed1994

Novel potassium-channel openers: preparation and pharmacological evaluation of racemic and optically active N-(6-amino-3-pyridyl)-N'-bicycloalkyl-N"-cyanoguanidine derivatives.

The previous paper reported on the synthesis and pharmacological evaluation of N-(6-amino-3-pyridyl)-N'-bicycloalkyl-N"-cyanoguanidine derivatives, from among which three compounds were selected as potent potassium-channel openers. In the present study, selected compounds were tested for antagonism of potassium-induced contraction of rat aorta, hypotensive activity in normotensive rats, and diuretic activity in spontaneously hypertensive rats. This led to further evaluation of compound (+/-)-10 and selection of (+)-N-(6-amino-3-pyridyl)-N'- [(1S,2R,4R)-bicyclo- [2.2.1]hept-2-yl]-N"-cyanoguanidine ((+)-10) (AL0670) for development as an antihypertensive agent. Although AL0670 is regarded as a pinacidil-type K(+)-channel opener, it showed different pharmacological and conformational profiles from pinacidil.

Animals↗
PubMed1994

Characterization of a novel cofilin isoform that is predominantly expressed in mammalian skeletal muscle.

Cofilin is an actin-modulating protein of 20 kDa, which is widely distributed throughout muscle and non-muscle cells. By means of immunoblotting combined with two-dimensional gel electrophoresis, we found that two cofilin variants, muscle type (M-type) and non-muscle type (NM-type), exist in mammals, while a single isoform exists in chickens. During in vitro myogenesis of mouse C2 cells, expression of the M-type cofilin was upregulated. To better understand the nature of the M-type cofilin, we cloned cDNAs encoding M-type cofilin from the cDNA library of C2 myotubes and determined the entire sequence. The deduced peptide sequence contained a nuclear localization signal and a putative actin-binding sequence as reported in NM-type cofilin. The sequence showed 81% identity in the amino acid residues with the mouse NM-type cofilin sequence and, interestingly, higher homology (96% identity) with that of chicken cofilin. The mRNA encoding M-type cofilin, though it contains two variants that differ in the size of their 3'-non-coding sequences, was detected predominantly in heart, skeletal muscle, C2 myotubes, and testis by Northern blotting, while the mRNA for NM-type cofilin was seen in a variety of non-muscle tissues. The presence of the muscle type isoform of cofilin strongly suggests that cofilin is deeply involved in the regulation of actin function not only in non-muscle cells but also in muscle cells.

3T3 Cells↗
PubMed1994

Molecular and physiological alterations in murine ventricular dysfunction.

The present study reports the development and characterization of a murine model of right ventricular dysfunction following graded constriction in the pulmonary artery via microsurgical approaches. To analyze in vivo ventricular function, a technique of x-ray contrast microangiography was developed to allow the quantitative analysis of ventricular volumes and of ejection fraction in normal and pressure-overloaded right ventricle. Severe, chronic pulmonary arterial banding for 14 days resulted in right ventricular dilatation and dysfunction, associated with right atrial enlargement, and angiographic evidence of tricuspid regurgitation. These effects were dependent on the extent of hemodynamic overload, since more moderate pulmonary arterial constriction resulted in hypertrophy with maintenance of right ventricular function. With severe pulmonary artery constriction, the murine right ventricle displays a failing heart phenotype including chamber dilation with reduced function that resembles right ventricular dysfunction in man during chronic pulmonary arterial hypertension. Northern and immunoblot analyses demonstrate a marked down-regulation of phospholamban mRNA and its corresponding protein with both levels of constriction, while a less pronounced but significant depression of sarcoplasmic reticulum Ca(2+)-ATPase protein was observed with severe overload, suggesting that this pattern is an early genetic marker of ventricular dysfunction. By coupling mouse genetics with this murine model and the ability to assess cardiac function in vivo, one should be able to test the role of the down-regulation of phospholamban and other defined alterations in the cardiac muscle gene program in the onset of the failing heart phenotype.

Adenosine Triphosphatases↗
PubMed1994

Preferential usage of the Fc receptor gamma chain in the T cell antigen receptor complex by gamma/delta T cells localized in epithelia.

zeta and eta chains of the T cell antigen receptor (TCR) complex and the gamma chain of Fc receptors (FcR gamma) constitute a family of proteins important for the expression of, and signal transduction through, these receptors in hematopoietic cells. In zeta-deficient mice, TCR expression was reduced in most T cells. By contrast, CD8 alpha alpha + TCR-gamma/delta + intestinal intraepithelial lymphocytes in these mice expressed a normal level of TCR. Biochemical analysis of the TCR complex in these cells from zeta-deficient as well as normal mice revealed the predominant usage of FcR gamma. Furthermore, gamma/delta + T cells in epithelia of the skin and female reproductive organs from zeta-deficient mice also showed relatively high TCR expression, indicating the usage of FcR gamma. These observations demonstrate the preferential usage of FcR gamma by gamma/delta + T cells localized in epithelia of normal mice.

Animals↗
PubMed1994

Immobilized anti-TCR mAb induces split functions in a CD8+ CTL clone.

A signal through the T cell receptor (TCR) without a second costimulatory signal provided by antigen-presenting cell (APC) generally causes a state of anergy in CD4+ T helper (Th) 1 cells, but not in CD4+ Th2 cells. In contrast, less is known about anergic CD8+ T cells. We have examined whether a CD8+ cytotoxic T lymphocyte (CTL) clone incapable of producing IL-2 could be rendered into a state of unresponsiveness by treatment with immobilized anti-TCR mAb in the absence of a secondary stimulation. The CD8+ CTL clone was induced into nonproliferative response to subsequent antigen stimulation while it was bound to immobilized anti-TCR mAb. The immobilized anti-TCR mAb-treated CTL clone also failed to significantly produce cytokine with antigen stimulation. In contrast, the ability of the CTL clone to specifically lyse target cells was apparently retained. The results suggest that there might be intracellular signal pathways via the TCR for CTL functions such as proliferative response, cytokine production, and CTL killing.

Animals↗
PubMed1994

Recovery of antitumor CD4+ T cell responsiveness, suppressed in the tumor-bearing state, by release from tumor burden.

The present study investigates the recovery of antitumor CD4+ T cell responsiveness, suppressed in the tumor-bearing state, following release of tumor burden. Spleen cells from BALB/c mice bearing a syngeneic tumor (CSA1M) 1-3 weeks after the inoculation with CSA1M cells produced interleukin-2 (IL-2) and IL-4 upon in vitro cultures without addition of exogenous tumor antigens. This lymphokine production was achieved through collaboration between anti-CSA1M CD4+ T cells and antigen-presenting cells (APC) that has been pulsed with CSA1M tumor antigens in vivo in the tumor-bearing state. The lymphokine-producing capacity gradually decreased as the tumor-bearing period increased, and spleen cells from mice at late (8-10 week) tumor-bearing stages produced reduced levels of lymphokines. Because APC in these cells exhibited enhanced capacities to present tumor antigens, the reduced responsiveness was ascribed to the dysfunction of CD4+ T cells themselves. However, removal of a tumor after 8 weeks resulted in a remarkable recovery of the lymphokine-producing capacities of whole spleen cells. In contrast to the reduction in CSA1M-antigen-presenting activity of APC following tumor resection, CD4+ T cells exhibited a reciprocal increase in their responsiveness to CSA1M antigens. The recovery of antitumor responsiveness was also observed in the in vitro cultures free from tumor burden; when spleen cells from mice at late tumor-bearing stages were pre-incubated for 1-2 days and re-cultured in fresh medium, they produced potent amounts of IL-2 and IL-4. These results indicate that the immunodysfunction of antitumor CD4+ T cells induced in the tumor-bearing state is not irreversible, and release from tumor burden results in almost complete recovery of the potent antitumor responsiveness they previously expressed.

Animals↗
PubMed1994

Cardiac involvement of progressive muscular dystrophy (Becker type, Limb-girdle type and Fukuyama type) evaluated by radionuclide method.

Tl-201 SPECT and Tc-99m-Human serum albumin (HSA) multigated radionuclide ventriculography were performed on 11 patients with progressive muscular dystrophy (Becker type 2, Fukuyama type 2, Limb-girdle type 7) to evaluate myocardial involvement. Hypoperfusion was detected in 8 patients on Tl-201 SPECT. Decreases in both systolic function (left ventricular ejection fraction; LVEF) and diastolic function (peak filling rate; PFR) were also seen in these patients. A high incidence of myocardial involvement of these kinds of progressive muscular dystrophy was suggested.

Adolescent↗
PubMed1994

In vivo assessment of left ventricular remodelling after myocardial infarction by digital video contrast angiography in the rat.

OBJECTIVE: The aim was to develop a digital video contrast angiographic method for assessing global left ventricular function and volume in vivo in the rat and then to apply it to a study of ventricular remodelling after coronary occlusion, with and without reperfusion. METHODS: Digital contrast angiography was performed on 29 rats, including the following groups: sham operated (n = 11), non-transmural myocardial infarction produced by reperfusion (n = 8), and transmural infarction produced by permanent occlusion (n = 10). Under anaesthesia three weeks later, biplane fluoroscopic images were acquired following venous contrast injection. Levophase images were digitised, and left ventricular end diastolic and end systolic volumes and ejection fractions were obtained using an area-length method. Left ventricular ejection fraction data also were calculated by videodensitometry from video density curves. RESULTS: Compared to the sham operated group, the reperfused group showed a significant decrease in left ventricular ejection fraction, at 53(SD 7) v 70(5)% (p < 0.01), and an increase in end diastolic volume. The permanent occlusion group showed a further decrease in the ejection fraction [40(8)%] and a further significant increase in end diastolic volume compared to the reperfused group (p < 0.01). Left ventricular ejection fraction correlated inversely with percent infarct size (r = 0.882) and showed a positive correlation with the spared epicardial area (r = 0.721). Most haemodynamic variables, including maximum left ventricular dP/dt, failed to discriminate between the groups. The methods showed reasonable accuracy when tested in vitro using contrast filled balloons. In vivo, the left ventricular ejection fraction calculated by densitometry showed adequate interobserver variability (2 SD +/- 8.5 percentage points), but the area-length method showed somewhat more scatter. CONCLUSIONS: Digital video contrast angiography is a feasible method for the assessing global left ventricular function in the rat and should be useful in other small animal models. Significant differences in left ventricular volumes and ejection fractions were detected between reperfused and permanent occlusion groups, whereas haemodynamic variables showed non-significant trends. Reperfusion after 45 min of occlusion caused sparing of the epicardium, prevented unfavourable remodelling, and improved the ejection fraction compared to permanent occlusion.

Angiography, Digital Subtraction↗
PubMed1994

Regional cerebral blood flow in diabetic patients: evaluation by N-isopropyl-123I-IMP with SPECT.

Regional cerebral blood flow (rCBF) was measured using N-isopropyl-123I-iodoamphetamine (123I-IMP) with single photon emission computed tomography (SPECT) in 27 patients with diabetes mellitus with an average age of 64.1 years and with an average fasting plasma glucose of 145 mg dl-1. Their data were compared with those of 12 non-diabetic subjects with an average age of 64.6 years. None had cerebral infarction on computed tomographic (CT) studies. There were no significant differences in the physiological or laboratory data between the diabetic and non-diabetic groups except for their fasting plasma glucose and HbA1c levels. A reference sampling method using continuous arterial blood sampling was employed to quantify the rCBF. The average rCBF in each region of the cerebrum and cerebellum was significantly lower in the diabetic group than in the non-diabetic group (P < 0.01). Although a definite cause was obscure, the rCBF of the diabetic patients was reduced even in the absence of findings indicative of cerebral infarction on a CT study.

Amphetamines↗
PubMed1994

Elastin cross-linking in the skin from patients with amyotrophic lateral sclerosis.

Two cross-links unique to elastin, desmosine and isodesmosine were measured and compared in skin tissue (left upper arm) from 10 patients with amyotrophic lateral sclerosis (ALS) and from seven age-matched controls. The contents of desmosine and isodesmosine were significantly decreased (p < 0.01 and p < 0.01, respectively) in patients with ALS compared with those of controls, and were negatively and significantly associated with duration of illness in ALS patients (r = -0.77, p < 0.01 and r = -0.65, p < 0.05, respectively). The decline in skin desmosine and isodesmosine is more rapid in ALS than in normal ageing. Thus cross-linking of skin elastin is affected in ALS.

Aged↗