Search PubMed⌕ Search

Biomedical subjects

H Kubo

Publications and source records attributed to H Kubo.

At least 91 records · Page 5Linked to original sources
PubMed1999

Effects of sarpogrelate hydrochloride on platelet aggregation, and its relation to the release of serotonin and P-selectin.

Inhibitory effects of sarpogrelate hydrochloride (sarpogrelate), a 5-HT2 receptor antagonist, on platelet aggregation was examined as well as the relationship to serotonin and P-selectin, a platelet alpha-granule membrane glycoprotein. Platelet aggregation was induced by simultaneous addition of collagen (0.06-0.12 microg/ml), which did not induce aggregation alone, and serotonin (0.88 micromol/1) to platelet-rich plasma (PRP). The PRP was obtained from healthy volunteers and percentage maximum aggregation (MA) was measured. Serotonin levels and P-selectin levels in the supernatant of PRP after aggregation were determined. When vehicle-treated PRP was stimulated in the aforementioned manner, platelet aggregation dependent on collagen concentration was induced. Serotonin levels and P-selectin levels were also dependent on collagen concentration. Sarpogrelate (10(-6) to 10(-4) mol/l) inhibited such aggregation dose-dependently, and decreased serotonin levels and P-selectin levels in a dose-dependent manner. There were close correlations between MA and serotonin levels, MA and P-selectin levels, as well as serotonin and P-selectin levels. These results suggest that extracellular release of serotonin and P-selectin from platelets was caused by induction of aggregation, and these responses were suppressed by sarpogrelate.

Adult↗
PubMed1999

ANTHOCYANINLESS2, a homeobox gene affecting anthocyanin distribution and root development in Arabidopsis.

The ANTHOCYANINLESS2 (ANL2) gene was isolated from Arabidopsis by using the maize Enhancer-Inhibitor transposon tagging system. Sequencing of the ANL2 gene showed that it encodes a homeodomain protein belonging to the HD-GLABRA2 group. As we report here, this homeobox gene is involved in the accumulation of anthocyanin and in root development. Histological observations of the anl2 mutant revealed that the accumulation of anthocyanin was greatly suppressed in subepidermal cells but only slightly reduced in epidermal cells. Furthermore, the primary roots of the anl2 mutant showed an aberrant cellular organization. We discuss a possible role of ANL2 in the accumulation of anthocyanin and cellular organization of the primary root.

Amino Acid Sequence↗
PubMed1999

Sodium/calcium exchange contributes to contraction and relaxation in failed human ventricular myocytes.

Defects in myocyte contraction and relaxation are key features of human heart failure. Sodium/calcium exchanger-mediated contribution to contraction and relaxation were separated from other mechanisms [L-type calcium current, sarco(endo)plasmic reticulum (SR) Ca(2+)-ATPase] based on voltage, temperature, and selective blockers. Rod-shaped left ventricular myocytes were isolated from failed human explants (n = 29) via perfusion with collagenase-containing Krebs solution. Action potentials using perforated patch and contractions using an edge detector were recorded at 0.5-1.5 Hz in Tyrode solution at 25 degrees C and 37 degrees C. Contraction duration was dependent on action potential (AP) duration at 37 degrees C but not at 25 degrees C, suggesting the role of the exchanger in relaxation and linking myocyte relaxation to the repolarization phase of the AP. Voltage-clamp experiments from -50 to +10 mV for 1,500 ms in Tyrode or Na(+)- and K(+)-free solutions after conditioning pulses triggered biphasic contractions that included a rapid SR-mediated component and a slower voltage-dependent exchanger-mediated component. We used thapsigargin to block the SR, which eliminated the rapid component, and we used an exchanger blocker, Kanebo 7943, which eliminated the slow component. The exchanger was shown to contribute to contraction through reverse-mode exchange, as well as to play a key role in relaxation of human ventricular myocytes.

Action Potentials↗
PubMed1999

L- and P-selectin and CD11/CD18 in intracapillary neutrophil sequestration in rabbit lungs.

Infusion of complement fragments induces rapid sequestration of neutrophils within pulmonary capillaries. This study examined the mechanisms through which this sequestration occurs, as well as the effect of complement fragments on the expression of L-selectin and CD11/CD18 using ultrastructural immunohistochemistry. Studies using anti-P-selectin antibodies, fucoidin, L-selectin-depleted neutrophils, and anti-CD18 antibodies showed that selectins and CD18 were not required for neutrophil sequestration. However, maintaining the sequestered neutrophils within the pulmonary capillaries required both L-selectin and CD11/CD18. Neutrophils in the pulmonary capillaries of rabbits given complement fragments expressed 72% less L-selectin and 98% more CD11/CD18 than did those in rabbits given saline. Shedding of L-selectin occurred preferentially from the microvillar processes of the plasma membrane rather than from the flat intervening regions. About 28% of L-selectin still remained on intracapillary neutrophil membranes after 15 min and was likely available for binding. Shedding of L-selectin appeared slower in vivo than in vitro. These studies indicate that neutrophil sequestration induced by complement fragments requires at least two sequential steps, one that does not require recognized adhesion molecules followed by a second that requires L-selectin and CD11/ CD18.

Animals↗
PubMed1999

Evaluation of bile acids and fusidate derivative as nasal absorption enhancers using an electrophysiological technique.

The present study was carried out to investigate the reversibility of the action of two nasal absorption enhancers, bile acids and fusidate derivative, on nasal membrane resistance. The nasal mucosa was isolated from rabbit nasal septum and mounted in a Ussing-type chamber to allow the monitoring of the membrane resistance and flux of fluorescein isothiocyanate-labeled dextran (FD10, M.W. 9400). Membrane resistance was reduced by 46% following treatment with 0.5% (w/v) sodium taurodihydrofusidate (STDHF) for 10 min and then gradually returned to the control level after being wash. The resistance was restored to 76% of the control level following a 30 min treatment with 0.5% (w/v) STDHF. However, there was no recovery of resistance following treatment with 0.5% (w/v) STDHF for 120 min or 1% (w/v) STDHF for 10in. Concurrently, FD10 transport was enhanced while membrane resistance was reduced. Treatment with 0.5% (w/v) sodium deoxycholate (DC) for more than 10 min showed no reversible action and marked FD10 transport enhancement, whereas a 10-30 min treatment with 0.5% (w/v) sodium glycocholate (GC) or sodium taurocholate (TC) resulted in the rapid recovery of membrane resistance without any enhancement of FD10 permeation. STDHF transport across the nasal mucosa was approximately 2-fold faster than that of DC, GC, and TC. The accumulation of STDHF in the nasal mucosa was 2-fold lower than that of DC and 1.7-fold higher than that of GC and TC after a 30 min treatment. The rank order of hydrophobicity determined by reverse-phase HPLC was: DC>STDHF>GC>TC. These results suggest that the reduction in membrane resistance and its reversibility appear to be due to a balance between the accumulation and clearance of STDHF.

Absorption↗
PubMed1999

Pre-operative staging of ampullary tumours by endoscopic ultrasound.

Ampullary carcinomas have a significantly higher resectability rate and better prognosis than other periampullary carcinomas, although the prognosis is poor with advanced disease. Accurate tumour staging is therefore important in surgical planning. Our objective was to evaluate the usefulness of, and problems associated with, endoscopic ultrasound (EUS) in the pre-operative staging of ampullary tumours. 35 patients with ampullary tumours were pre-operatively examined with EUS. The imaging results were compared with histopathological findings of the resected specimen according to the TNM staging classification. The overall accuracy of tumour (T) staging was 74% (26/35) for all tumours, and 67% (6/9), 71% (10/14) and 83% (10/12) respectively for T1, T2 and T3 tumours. The overall accuracy of nodal (N) staging was 63%. In diagnosing pancreatic invasion, EUS had an accuracy of 86% (30/35), a sensitivity of 83% (10/12), and a specificity of 87% (20/23). In conclusion, EUS provides an accurate method of evaluating the stage of ampullary tumours, especially infiltration into the pancreas. This modality is useful to surgeons in deciding on an appropriate therapeutic approach and in giving a prognosis.

Aged↗
PubMed1999

Effects of saiboku-to on the survival of human eosinophils.

In recent years, bronchial asthma has come to be regarded as a chronic inflammatory disease of the respiratory tract, with mast cells, lymphocytes and eosinophils playing important roles in its pathogenesis. Proteins contained in eosinophil granules, especially major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN) and eosinophil peroxidase (EPO), can cause tissue injury. When stimulated, eosinophils release mediators such as leukotriene C4 (LTC4) and platelet activating factors (PAF). Thus, they are recognized as effector cells that are actively involved in the development of allergic inflammation. In this study, eosinophils from healthy volunteers were used to investigate the effects of Saiboku-to on eosinophils whose survival had been prolonged through stimulation with eosinophil-activating cytokines such as interleukin (IL)-3, IL-5 and granulocyte macrophage colony stimulating factors (GM-CSF). As a result, the cytokine-enhanced survival of eosinophils was significantly shortened by the addition of Saiboku-to. These findings suggest that Saiboku-to has the potential to inhibit allergic responses by directly affecting eosinophils which are related to allergic inflammation.

Cell Survival↗
PubMed1999

Effect of anti-ICAM-1 on bronchial response: bronchoalveolar lavage fluid (BALF) and ultrastructural changes of bronchial epithelium in guinea pigs with dual phase bronchial response.

Eosinophils play an important role in the development of bronchial asthma, and the association between ICAM-1 and activation and migration of local eosinophils is attracting attention. Using an asthmatic model of dual phase bronchial response, the effects of anti-ICAM-1 antibody on the airway resistance, cell composition in the bronchoalveolar lavage fluid (BALF) and ultrastructure of bronchial ciliated epithelium were examined under the provoked response by inhalation of the antigen. By administration of anti-ICAM-1 antibody, the late asthmatic response (LAR) was suppressed. In the examination of bronchoalveolar lavage fluid, a significant decrease in eosinophils was found in LAR. In examining transmission and scanning electron microscopies, no difference was found in the immediate asthmatic response, but marked suppression of deciduation of bronchial ciliated epithelium was observed in LAR. These results indicated that anti-ICAM-1 antibody suppressed bronchial asthmatic attack, mainly in LAR, by controlling differentiation and migration of eosinophils.

Administration, Inhalation↗
PubMed1999

Stimulated neutrophils evoke signal transduction to increase vascular permeability in rat lungs.

The mechanisms by which stimulated neutrophils (PMNs) damage pulmonary vascular endothelium were investigated using twenty-four perfused lung preparations isolated from rats. We tested the ability of unstimulated and mechanically stimulated PMNs to adhere to pulmonary endothelial cells and, thereby, alter pulmonary vascular permeability (measured as the pulmonary filtration coefficient) and hemodynamics. To stimulate PMNs, they were gently agitated in a glass vial for 10 seconds. Perfusing lungs with the stimulated PMNs (stimulated group) elicited a 3-fold increase in the filtration coefficient as compared to lungs perfused with unstimulated cells (unstimulated group). This increase in filtration was completely blocked by preincubation of stimulated PMNs with CD18 monoclonal antibody (MoAb group). This increase in filtration coefficient was also completely blocked by GF109203X, a protein kinase C inhibitor (GF group). Pulmonary vascular resistance increased when the stimulated PMNs were injected to the isolated lungs. Although, preincubation of stimulated PMNs with CD18 MoAb successfully blocked and GF109203X partly blocked this increase in pulmonary vascular resistance. The accumulation of stimulated PMNs within the lungs, as assessed by myeloperoxidase (MPO) levels, was blocked by preincubation of stimulated PMNs with CD18 MoAb. However, GF109203X did not decrease MPO levels. These findings suggest that stimulated PMN-induced increases in pulmonary vascular filtration, resulted from endothelial cell injury caused by adhesion to the endothelial cells, evoke intracellular signaling within the endothelial cells.

Animals↗
PubMed1999

[Brain computerized tomographic and ultrasonographic findings in patients with asymptomatic carotid bruits].

This study was conducted to clarify brain and carotid lesions in patients with asymptomatic carotid bruits and their characteristics. We studied 37 patients with carotid bruits, who had various diseases other than stroke and were all neurologically normal, using by brain computerized tomography (CT) and ultrasonography (US). On CT, localized low density areas (LDAs) and their distribution were assessed, as well as the grade of periventricular lucency (PVL). Carotid lesions on US were classified into 3 categories: plaque (locally thickened intima-media complex of 2.1 mm or more in thickness), stenosis (narrowed lumen between 50% and 90% of the linearly measured diameter), and occlusion (severely narrowed lumen more than 90%). Ankle pressure index (API) less than 0.9 was defined as low. Mean age was 73.2 years-old and 28 of them were men. Bruits were heard bilaterally in 15 patients. CT findings showed LDA in 13 patients (35%) and severe PVL in 12 patients (32%). Twenty-three LDAs (13 in the left hemisphere and 10 in the right hemisphere) were seen and all were considered to be infarctions. Nineteen LDAs, 13 of them seen in the basal ganglia, were lacunae. Another 3 LDAs were seen in the watershed zone between the middle and posterior cerebral arteries, whereas the remaining one was a small cortical infarction in the left premotor area in the middle cerebral artery territory. Ultrasonography showed carotid lesions in 65 of 74 carotid arteries (plaque in 28, stenosis in 26, and occlusion in 11) and low API in 18 of 37 patients. Compared with patients with normal CT finding, the frequency of hypertension (92% vs 50%) and ischemic heart disease (69% vs 29%) was significantly high in 13 patients with silent infarction, although there was no difference in US findings. In the hemisphere ipsilateral to the carotid with bruits, which was frequently stenotic, the frequency of infarction was similar to that in the hemisphere ipsilateral to the carotid with no bruit. Regression analysis revealed that hypertension significantly correlated with the presence of cerebral infarction. These findings indicated that incidence of infarction in the elderly patients with asymptomatic carotid bruits was high and was associated with hypertension and advanced atherosclerosis in many organs, including the carotid and peripheral arteries. The reason for the lack of symptoms was considered to be that most of the infarctions were lacunae and located in the basal ganglia, although infarction did not significantly correlate with bruits or carotid lesions.

Aged↗
PubMed1999

[A study of association between lean body mass and serum insulin-like growth factor-1 in continuous ambulatory peritoneal dialysis patients].

Malnutrition is one of the major issues associated with high mortality and morbidity in chronic dialysis patients. Several methods to evaluate the nutritional status of these patients have been attempted for example anthropometric measurement and biochemical parameters. Recently, it was reported that insulin-like growth factor-1 (IGF-1) has been valuable for estimating nutritional status. In this study, we measured lean body mass (LBM) by dual energy X-ray absorptiometry (DXA), IGF-1 and other biochemical parameters in 35 patients on CAPD. Two years later, the second measurement of LBM was performed, and we assessed the percent changes of LBM and biochemical parameters. There was negative correlation between the percent changes of LBM and the duration of CAPD. In patients treated with CAPD for less than 36 months (group I) LBM increased, however, it decreased significantly in those treated for more than 36 months (group II). On the other hand, in group I there was a positive correlation between the percent changes of LBM and IGF-1. In group II there was no correlation between the percent changes of LBM and any other biochemical parameters. It could be concluded that IGF-1 is one of the predisposing factors for improving LBM of patients on CAPD for a limited duration.

Absorptiometry, Photon↗
PubMed1999

[Phase 1 clinical study of 123I-FP-CIT, a new radioligand for evaluating dopamine transporter with SPECT (I): Biodistribution and absorbed dose].

A Phase 1 clinical study of 123I-FP-CIT, N-(3-fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane (123I), developed for evaluation of dopamine transporter (DA-T) by single photon emission computed tomography (SPECT), was performed in 12 healthy male volunteers. No adverse reactions to 123I-FP-CIT (167 MBq) injection were observed. In sequential whole-body images after intravenous injection, the radioactivity was distributed mainly in the liver, abdomen, lungs and brain, and it decreased gradually with time. The radioactivity was excreted mainly in the urine and no prolonged retention of radioactivity was observed in any organs at 2 days post-injection. The radiation absorbed dose of 123I-FP-CIT, calculated on the basis of the pharmacokinetics, was equal to or less than those of other brain diagnostic imaging agents. These results suggest that i.v. injection of 123I-FP-CIT causes no significant problems in terms of its safety, biodistribution or absorbed dose.

Adult↗
PubMed1999

[Practical compensation method of downscattered component due to high energy photon in 123I imaging].

We looked into the problem that the quantitative values of 123I data vary according to collimator type. First, we made the assumption that the quantitative values of 123I data are degraded by the scattered photons from the 529 keV component which contaminate the 159 keV imaging data. Then, the 123I Dual Window (IDW) method was proposed to improve the quantitative values of the 123I data. The IDW method uses the energy window on the high-energy side to estimate the amount of scattered 529 keV photons which contaminate the 159 keV data. Since only a dual-energy window acquisition and a simple image processing are needed, the IDW method can be performed in most conventional gamma camera systems. In the torso phantom studies, the IDW method reduced the error in the semi-quantitative value 'heart/mediastinum (H/M) ratio' in 123I-MIBG myocardial scintigraphy from 22% to 1%. The results of the phantom studies indicate that the IDW method can improve the quantitative values of 123I data.

3-Iodobenzylguanidine↗
PubMed1999

[Phase 1 clinical study of 123I-FP-CIT, a new radioligand for evaluating dopamine transporter by SPECT (II): Tracer kinetics in the brain].

The kinetics of 123I-FP-CIT in the brain for healthy subjects were studied. Twelve dynamic SPECT data sets (0- to 6-hr after an intravenous injection) from a Phase 1 clinical trial of 123I-FP-CIT were analyzed. Tracer concentrations in the striatum, midbrain, cerebellum and cerebral cortex were measured on the SPECT images co-registered with the corresponding MR images. High tracer accumulation was observed in the striatum, which peaked at 60 min post-injection, followed by slow elimination (3%/hr). The kinetics were similar both in the cerebellum and in the cerebral cortex, which peaked at 15 min post-injection, followed by rapid elimination. Tracer accumulation in the midbrain was higher than in the cerebellum and cerebral cortex. The striatal specific/nonspecific binding ratio ((striatal-occipital)/occipital concentration ratio) was stable at 3-hr post-injection and later at a value of 3, suggesting that the specific binding of 123I-FP-CIT could be evaluated from a single SPECT image at 3- to 6-hr post-injection. The specific/nonspecific binding ratio at 4-hr post-injection showed a negative correlation with aging (r = -0.70, p = 0.01), with a decrease rate of 11%/decade (95% confidence interval: 3%-19%/decade).

Adult↗
PubMed1998

Complement fragment-induced release of neutrophils from bone marrow and sequestration within pulmonary capillaries in rabbits.

Infusion of complement fragments induces rapid sequestration of neutrophils within the pulmonary capillaries. This study examined the contributions of the bone marrow (BM) and the liver to the accumulation of neutrophils within the lungs. Complement fragments induced the release of neutrophils from the BM within 7 minutes of infusion, and these neutrophils sequestered in the lungs immediately upon reaching the pulmonary capillaries. Neutrophils expressing high levels of L-selectin were preferentially retained within the pulmonary microvasculature. By 30 minutes after the infusion was stopped, the circulating neutrophil counts had increased, primarily because of release from the BM. The number of neutrophils sequestered in the lung had decreased by only 27%, and the number of neutrophils in the liver increased by 223%. These studies indicate that complement fragments induce the release of neutrophils from the BM far more rapidly than previously described. These newly released neutrophils immediately sequester within the lung, increasing the number of neutrophils available to injure the lung many fold beyond the number that were circulating before infusion. The preferential retention of L-selectin-expressing neutrophils likely reflects the requirement for L-selectin-mediated adhesion in maintaining sequestered neutrophils within the pulmonary microvasculature. The number of circulating neutrophils reflects a balance between pulmonary sequestration, rapid release from the BM, and uptake by the liver and other organs.

Animals↗