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Biomedical subjects

S Kawano

Publications and source records attributed to S Kawano.

At least 181 records · Page 10Linked to original sources
PubMed1996

Functions of cardiac ion channels under normal and pathological conditions.

Using the patch clamp technique, normal and abnormal functions of cardiac ion channels were studied. The transient outward K+ current contributes to the early repolarization phase of the action potential as well as to the plateau height and total duration. The latter role is observed in at premature excitations due to slow recovery from inactivation of this current compared to that of the Ca2+ current. Early and delayed afterdepolarizations are produced by multiple components of ionic currents, especially in the former case. Transient inward current is mainly involved in the formation of delayed afterdepolarizations, but the activities can be produced by a different ionic mechanism in rare occasions. Barium-induced automaticity can be brought about by blocking and unblocking of the inward rectifier K+ channels. The ATP-sensitive K+ channels are assumed to play important roles in myocardial ischemia and related conditions. The channels are a target of the K+ channel openers and their functions are modulated by various intracellular factors. While the channel activity is strongly inhibited by intracellular ATP, ATP is necessary for the channel in an operative state. The former effect by ATP is produced by its ligand action, but the latter may be brought about by hydrolysis of MgATP, which may be regulated by the assembly and disassembly of the actin cytoskeleton.

Action Potentials↗
PubMed1996

Blood pressure and urinary C-peptide excretion in subjects with varying degrees of glucose tolerance.

To determine whether blood pressure is associated with 24-h urinary C-peptide excretion in subjects with varying degrees of glucose tolerance, we studied 247 Japanese men aged 30-69 who had never been treated with antihypertensive medications or with insulin. Plasma glucose and insulin responses during a 75-g oral glucose tolerance test, blood pressure and body mass index were obtained and urinary C-peptide excretion, in total and per kg body weight, were examined by 24-h urine collection. In monovariate analyses, urinary C-peptide excretion per kg body weight increased significantly as the blood pressure level rose (p < 0.05). After adjustment for age and body mass index by analysis of covariance, this relationship remained significant (p < 0.05), where adjusted mean values (+/- SEM) of urinary C-peptide per kg body weight were 1.56 +/- 0.05 microgram/24h/kg in the normotensive group and 2.04 +/- 0.17 microgram/24h/kg in the hypertensive (stage 2-4) group. When stratified simultaneously by glucose tolerance status and blood pressure level, adjusted mean values of urinary C-peptide per kg body weight were significantly higher in diabetic hypertensives than in diabetic normotensives. These results suggest that increase in 24-h urinary C-peptide excretion, i.e. 24-h insulin secretion, might contribute to an elevation of blood pressure both in normal and diabetic individuals.

Adult↗
PubMed1996

[Comparison of biochemical properties of human airway tryptase isolated from mucoid sputum with those of lung mast cell tryptase].

We found a novel trypsin-like enzyme (tryptase) in sputum from patients with chronic airway diseases, and named this enzyme human airway tryptase (HAT). To clarify its physiological significance in the airway, we compared biochemical properties of purified HAT with those of purified lung mast cell tryptase (MCT). Studies with model peptide substrates showed that both the HAT and MCT preferentially cleaved the COOH-terminal side of arginine residues of certain peptides, but substrate specificities to nine synthetic model substrates of HAT differed from those of MCT. Effects of protease inhibitors on the two enzymes were examined at a concentration of 10 microM. Both the HAT and MCT were strongly inhibited by the trypsin inhibitors leupeptin, antipain, and aprotinin. An alpha-1-protease inhibitor inhibited HAT by 50%, but it did not inhibit MCT. In contrast, a secretory leukocyte protease inhibitor strongly inhibited MCT, but not HAT. Mucoid sputum from patients with chronic bronchitis contained much more HAT than MCT. These differences in biochemical properties between HAT and MCT indicate that they play different physiological roles in the airways.

Asthma↗
PubMed1996

[Usefulness of 123I-BMIPP scanning for distinction of ischemic from nonischemic dilated cardiomyopathy].

To determine if imaging of blood flow (using 201Tl) and fatty acid (using 123-I-BMIPP) with SPECT can distinguish cardiomyopathy of coronary artery disease from nonischemic dilated cardiomyopathy, 24 patients with severe left ventricular dysfunction were evaluated. The origin of left ventricular dysfunction had been previously determined by coronary angiography to be ischemic (9 patients) or nonischemic (15 patients). Images were visually analyzed by three observers on a graded scale (score 0; normal, 1; mild uptake reduction, 2; severe uptake reduction, and 3; defect) in 20 left ventricular segments revealed higher defect score in ICM compared with NCM for 123I-BMIPP (35.5 +/- 14.4 versus 14.1 +/- 9.3, p <0.0005) and 201Tl (27.6 +/- 14.6 versus 12.1 +/- 7.4, p <0.005). The defect score/segment ratio also revealed higher value in ICM compared with NCM for 123I-BMIPP (2.25 +/- 0.52 versus 1.36 +/- 0.36, p <0.0001) and 201Tl (1.92 +/- 0.51 versus 1.24 +/- 0.42, p <0.005). Myocardium of ICM is more severely damaged than that of NCM. Thus, noninvasive SPECT imaging with 123I-BMIPP is helpful in distinguishing patients with severe left ventricular dysfunction secondary to coronary artery disease from those with nonischemic cardiomyopathy.

Adult↗
PubMed1996

[Significance of 123I-metaiodobenzylguanidine SPECT for detecting left ventricular involvement in patients with arrhythmogenic right ventricular dysplasia].

The right ventricle being primarily involved in ARVD, recent reports indicate the presence of histological and functional abnormalities in the left ventricle for some patients with ARVD. The aim of this study was to evaluate the significance of myocardial sympathetic dysfunction as an early sign of left ventricular (LV) involvement by 123I-MIBG (MIBG) SPECT and to compare the findings with those of 201TlCl (Tl) SPECT, radionuclide left ventriculography, ultrafast computed tomography (UFCT), magnetic resonance imaging (MRI) and echo-cardiography in 10 patients (pts) with ARVD. MIBG defects in LV regions were detected in 9 pts. Seven of the 9 pts showed MIBG defects in LV regions adjacent to RV. The subjects were divided into 2 groups based on left ventriculography, 5 with normal LVEF (> 55%) and 5 with reduced LVEF. In the normal LVEF group, 4 pts showed MIBG defects and 2 pts showed TI defects, and MIBG defects were larger than TI defects (ES: 14 +/- 6 vs. 5 +/- 7, p <0.05). In reduced LVEF group, all of 5 pts showed MIBG and TI defects, and MIBG defects were larger than TI defects (ES: 42 +/- 12 vs. 25 +/- 3, p <0.05). In comparison with normal LVEF group, reduced LVEF group showed larger and more severe MIBG defects (ES: 42 +/- 12 vs. 14 +/- 6, p <0.01, SS: 44 +/- 31 vs. 8 +/- 7, p <0.05). UFCT and MRI showed abnormal findings indicating LV fatty infiltration in only 3 of reduced LVEF group. Thus, MIBG showed abnormal distributions in the left ventricle with the highest frequency in all these modalities. These results suggest that MIBG SPECT provides a sensitive marker for detecting LV involvement in ARVD. Also, the extent of MIBG distribution abnormalities is helpful in assessing the severity of left ventricular involvement in patients with ARVD.

3-Iodobenzylguanidine↗
PubMed1996

A method of evaluating drug efficacy by statistical analysis of healing speed of peptic ulcer.

At present, the evaluation of anti-ulcer drugs is generally accomplished simply by calculating the cumulative healing rate at a certain point of time during treatment, which does not implicate any analysis of the healing speed of the ulcer. If the cumulative healing rate of an ulcer is expressed as a function of drug administration time, t, then it will be possible to calculate parameters concerning the healing speed of ulcers and thus evaluate drug efficacy as the time series analysis of the cumulative healing rate. A new method of evaluating anti-ulcer drugs by a statistical analysis of healing speed is proposed. A non-linear regression analysis was performed between two variables, t (time of drug administration: week) and y (non-healing rate: %), to obtain the exponential function y = Ae-kt. The theoretical values calculated from the exponential equation were in close proximity to the observed values. With this analysis, four parameters concerning the healing speed were defined, namely the healing rate constant, the initiation time of healing, the half-life of non-healing rate and the time necessary for 50% healing. With this method, the efficacy of drugs on peptic ulcer healing was dynamically analysed, the non-healing rate (y) being expressed as an exponential function of length of time (t) of treatment, thus obtaining digital parameters for healing speed.

Anti-Ulcer Agents↗
PubMed1996

Cerebral hypoperfusion in orthostatic hypotension with globally denervated myocardium.

A 57-yr-old woman had frequent syncope when rising from a seated position. Her blood pressure fell from 140/80 mmHg to 60-70/40 mmHg while changing positions. Iodine-123-metaiodobenzylguanidine ([123I]MIBG) did not accumulate in the heart, whereas 201Tl-Cl (201Tl) did. Raise-up 99mTc-hexamethyl-propyleneamine oxime (99mTc-HMPAO) brain SPECT revealed decreased activity in the bilateral frontal areas, and subsequent supine 99mTc-HMPAO brain SPECT revealed filling in these areas, indicating that the cerebral blood flow (CBF) was transiently decreased in the frontal areas more than others in a standing position. The plasma norepinephrine (NE) level of this patient was normal during supine rest, but when she stood up, failure to increase the plasma level of NE uncovered a sympathetic nervous dysfunction. The CBF abnormality in patients with orthostatic hypotension may be due to a "functional" hemodynamic mechanism that induces orthostatic stress. This patient had transient hypoperfusion in the frontal areas when standing, without organic cerebral arterial stenosis. Only CBF in the frontal areas revealed relative hypoperfusion. These regions might be highly susceptible to a change in blood flow. The causes of orthostatic hypotension of this patient were autonomic failure with a disturbance of the sympathetic nerve endings, which was revealed by 99mTc-HMPAO brain SPECT and cardiac [123l]MIBG imaging.

3-Iodobenzylguanidine↗
PubMed1996

[Molecular approach for analyses of gut function: an overview].

This paper reviewed recent progress in analyses of gut function by the aid of molecular biology. Particularly noted were 1) involvement of immediate early genes in mucosal epithelial proliferation in vitro and in ulcer healing in rat stomach in vivo; and 2) possible involvement of c-kit/stem cell factor, endothelin-receptor B, endothelin-3 and ret in regulation of gut motility and Hirschsprung's disease. These cases show that molecular biology, together with novel approaches through medical engineering, significantly expands our knowledge on regulation of gut functions.

Animals↗
PubMed1996

Effect of lansoprazole in mono-, dual-, or triple therapy on Helicobacter pylori eradication.

The effect of lansoprazole, in mono, dual, or triple therapy, on the eradication of Helicobacter pylori was reviewed. Lansoprazole has a cytotoxic action against this organism, the MIC being 2.56-5.25 micrograms/ml. In in vitro experiments, lansoprazole exerts direct action, i.e., antibacterial activity of lansoprazole against H. pylori and also inhibits urease activity. With antibiotics, this drug has a synergistic effect against H. pylori. In clinical studies, the eradication rate of H. pylori with lansoprazole is 0%-25% with monotherapy, 22%-33% with dual therapy (of AMPC), and 75%-82.4% with triple therapy with metronidazole and antibiotics. We inves-tigated the effect of lansoprazole on the eradication of H. pylori with dual therapy, the other agent being amoxicillin (AMPC). The eradication rate was 0% when 30 mg lansoprazole was employed as monotherapy, 33% for dual therapy with 30 mg lansoprazole and 1 g AMPC, and 71% for dual therapy with 60 mg lansoprazole and 1 g AMPC, the eradication rate with 60 mg lansoprazole and 1 g AMPC being significantly higher than that with the lower dose of lansoprazole. This result suggested that the greater acid suppression brought about by lansoprazole 60 mg enhances the action of AMPC, indicating that lansoprazole, when used with AMPC, is effective for eradication of H. pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

[Preclinical and clinical studies on the efficacy of bifonazole in patients with tinea pedis at 10 years after approval. Part 1. Susceptibility to bifonazole of clinical isolates of dermatophytes].

An investigation was carried out to determine whether or not here had been any changes in the susceptibility of clinically isolated strains of Trichophyton metagrophytes and Trichophyton rubrum (both leading causes of tinea) to bifonazole, an imidazole derivative and antifungal for topical use. Susceptibility was measured in 107 strains of these fungi isolated from clinical samples during a study on the treatment of tinea pedis with Mycospor cream in 1995, 42 strains isolated and stored in 1990, and 39 strains isolated and stored prior to development of the drug. The results are as follows: (1) There was no distinct difference in the susceptibility to bifonazole of T. mentagrophytes strains isolated before 1986 and those isolated in 1990 or 1995. (2) T. rubrum strains isolated before 1986 were slightly more susceptible to bifonazole than those isolated in 1995, while the 1990 strains were slightly less susceptible than the 1995 strains, but the difference was not significant. (3) The highest MICs of bifonazole for all the T. mentagrophytes and T. rubrum strains isolated from before 1986 and those in 1995 were relatively low, being 2.5 micrograms/ml and 1.25 micrograms/ml, respectively. These results suggest that no resistance or reduced susceptibility to bifonazole has emerged among clinical isolates of dermatophytes since the development of the drug.

Antifungal Agents↗
PubMed1996

[Fundamental and clinical studies on the efficacy of bifonazole in patients with tinea pedis at 10 years after approval. Part 2. Clinical evaluation].

The usefulness of bifonazole (Mycospor), a topical imidazole antifungal agent approved 10 years ago, was evaluated for the treatment of tinea pedis. Mycospor cream was applied by 141 patients with tinea pedis once daily for 4 233ks, and the clinical efficacy and adverse reactions (as well as any correlations with susceptibility of isolates and the mycological activity of the agent against these isolates) were studied. The results were then compared to those of a previous study. The following results were obtained. 1. Mycological activity Mycological examination results became negative in 63.2% (36/57) of the patients with plantar tinea pedis, in 94.1% (32/34) of those with interdigital tinea pedis, and in 74.7% (68/91) of all tinea pedis patients. 2. Mycological activity and MIC No correlation was found between the MICs of bifonazole against the pathogenic fungi and the rate of eradication on mycological examination. 3. Improvement of symptoms The improvement rates for local symptoms were 82.5% for plantar tinea pedis, 85.7% for interdigital tinea pedis, and 83.7% for all tinea pedis. 4. Clinical efficacy Good clinical efficacies were found in 61.4% of the patients with plantar tinea pedis, in 88.6% of those with interdigital tinea pedis, and in 71.7% of all patients. 5. Safety Regarding adverse reactions, what seemed to be contact dermatitis was reported in 5 out of 127 cases (3.9%). The reaction decreased or disappeared in all cases. 6. Usefulness Mycospor was found to be useful in 64.9% of patients with plantar tinea pedis, in 88.6% of those with interdigital tinea pedis, and in 73.9% of all tinea pedis patients. 7. Comparison with former results The results obtained in the present clinical study were comparable to those obtained in patients with tinea pedis treated in a double-blind comparative study conducted during the development of as a new topical antifungal agent. From the above results, Mycospor cream was confirmed to be still useful, although it has been used widely for the topical treatment of cutaneous mycoses in the past 10 years since its approval.

Adult↗
PubMed1995

Activation mechanism of Ca(2+)-sensitive transient outward current in rabbit ventricular myocytes.

1. The mechanism of activation of the Ca(2+)-sensitive and 4-aminopyridine (4-AP)-insensitive transient outward current, I(to)(Ca), was examined in single rabbit ventricular myocytes using the whole-cell patch-clamp technique. 2. When the steady-state intracellular Ca2+ (Ca2+i) concentration ([Ca2+]i) was < 1 nM, I(to)(Ca) could not be activated by applying pulses at 0.1 Hz. When [Ca2+]i was increased to > or = 10 nM, I(to)(Ca) was activated by 0.1 Hz depolarizing pulses in all control experiments. 3. I(to)(Ca) was completely blocked by an anion transport blocker, DIDS, or by replacement of NaCl with sodium aspartate. Upon changing extracellular [Cl-], the reversal potential was shifted as predicted for a chloride-selective conductance. When intracellular K+ was replaced with Cs+, I(to)(Ca) was also observed. From these results it was concluded that I(to)(Ca) was carried by Cl-. 4. Anion selectivity of I(to)(Ca) was investigated by the replacement of C.- with various anions. The sequence of permeability was SCN- > I- > Br- > Cl-. 5. The amplitude of I(to)(Ca) was enhanced in a [Ca2+]i-dependent manner between 10 nM and 1 microM Ca2+i, while steady-state inactivation curves and the voltage-dependent activation curves were unchanged. The half-inactivation and half-activation potentials were -35 mV and +37 mV, respectively, at all [Ca2+]i. 6. I(to)(Ca) was inhibited by blocking Ca2+ influx or Ca2+ release from sarcoplasmic reticulum, suggesting that a 'Ca(2+)-induced Ca(2+)-release' mechanism is essential for the activation of I(to)(Ca). 7. A steady-state Ca(2+)-activated Cl- current with a linear I-V relationship was observed at 1 microM Ca2+, while the current activated by depolarization was strictly dependent on Ca2+ entry or Ca2+ release from the sarcoplasmic reticulum. These results suggest that the I(to)(Ca) channel is purely ligand (Ca2+) gated and its time course reflects the concentration of Ca2+i.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1995

Response to isoproterenol as a prognostic indicator of evolution from hypertrophic cardiomyopathy to a phase resembling dilated cardiomyopathy.

OBJECTIVES: We sought to assess whether isoproterenol stress echocardiography could detect in advance in which patients hypertrophic cardiomyopathy would progress to a phase resembling dilated cardiomyopathy. BACKGROUND: In a few patients, hypertrophic cardiomyopathy has been reported to progress to a phase characterized by systolic dysfunction and left ventricular dilation, resembling dilated cardiomyopathy. METHODS: Echocardiograms were recorded before and immediately after intravenous infusion of isoproterenol (0.02 microgram/kg body weight per min) for 5 min in 18 patients with typical hypertrophic cardiomyopathy (i.e., hypertrophied, hyperdynamic and nondilated) to determine the difference in fractional shortening. The patients were categorized into those with a good response (difference in fractional shortening > 7%, 14 patients) and those with a poor response (difference < or = 7%, 4 patients). Changes in left ventricular end-diastolic diameter and fractional shortening were evaluated by using serial echocardiography over an average follow-up period of 5.4 years. RESULTS: In the good response group, neither end-diastolic diameter nor fractional shortening changed significantly during the follow-up period. In the poor response group, end-diastolic diameter significantly increased from a mean +/- SD of 41 +/- 5 to 53 +/- 5 mm (p < 0.05), and fractional shortening significantly decreased from 40 +/- 12% to 29 +/- 10% (p < 0.05). All patients in the poor response group showed a substantial decrease (> or = 5%) in fractional shortening and an increase (> or = 5 mm) in end-diastolic diameter. One patient developed congestive heart failure due to systolic dysfunction during the observation period. CONCLUSIONS: The present study confirmed that impaired responses to isoproterenol infusion are related to future deterioration of left ventricular performance in patients with typical hypertrophic cardiomyopathy.

Cardiomyopathy, Dilated↗
PubMed1995

Expression pattern of CD45 RA/RO isoformic antigens in T-lineage neoplasms.

The expression of CD45 RA/RO antigen was investigated in neoplasms including cases expressing CD7 antigen as the sole pan-T antigen (n = 8), T-lineage acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL) at various stages of differentiation (n = 32), peripheral stage T-lineage leukemia (n = 10) and adult T-cell leukemia (ATL) (n = 14). The p56lck gene expression was also investigated in selected cases. The expression pattern of CD45 RA/RO antigen was defined as of RA, mixed, or RO type. All but one CD7+ CD5- CD2- case were of the RA type. The CD7+ CD5+ CD2- prothymic stage included seven RA and one mixed type cases. One CD7+ CD5- CD2+ case was of the RA type, but the other was of the RO type. The CD7+ CD5+ CD2+ prothymic stage included three RA and four mixed type cases. All seven CD3- CD4+ CD8+ (double-positive) thymic cases were of the RO type. The CD3+ CD4+ CD8+ (triple-positive) stage included two RO and three mixed-type cases. One CD3+ CD4+ CD8- late thymic case was of the mixed type. The peripheral stage cases included five RA, three RO, and two mixed type cases. All ATL cases were of the RO type. The expression of p56lck gene in the prothymic stage was less marked than that in the thymic stage. On the basis of these results, the following sequence of pattern of the CD45 RA/RO antigen expression along with T-lineage differentiation was reconstructed: prothymic stage [RA and mixed type]-->double-positive thymic stage [RO type]-->triple-positive thymic stage [RO and mixed type]-->peripheral stage [RA, mixed, and RO type]. While one RO-type CD7+ CD5- CD2- and one RO-type CD7+ CD5- CD2+ cases were not in accord with this sequence, the pattern of CD45 RA/RO antigen expression in most of T-lineage neoplasms could be determined by the respective stage of differentiation. The poor expression of the p56lck gene by the prothymic blasts compared with the thymic blasts may be related to the expression pattern of the CD45 RA/RO molecules, which exhibits phosphatase activity. The consistent RO-type expression in the ATL cases may reflect the activated status of the neoplastic T cells due to the presence of the HTLV-I gene. Alternatively, the target cells for HTLV-I-induced neoplastic transformation may possible be of the RO type.

Adolescent↗
PubMed1995

Molecular systematics of the Trilliaceae sensu lato as inferred from rbcL sequence data.

In this paper, we examine the phylogenetic affinities of Trilliaceae sensu lato. DNA sequences of the rbcL gene were analyzed for 8 species from Trilliaceae sensu lato (Trillium kamtschaticum, T. sessile, Daiswa polyphylla, Kinugasa japonica, Paris tetraphylla, Scoliopus bigelovii, S. hallii, and Medeola virginiana) and 10 other species from Liliaceae sensu lato. The analysis indicates that Trilliaceae sensu stricto (Trillium, Daiswa, Kinugasa, and Paris) is monophyletic and that Trilliaceae sensu lato is not monophyletic. Scoliopus and Medeola do not form a clade with Trilliaceae sensu stricto. Instead, they form a clade with Uvulariaceae and Liliaceae sensu stricto, respectively. Relative to the rbcL genes of Trilliaceae sensu stricto, Scoliopus and Medeola displayed approximately 14-24 synonymous substitutions per 100 sites. In similar comparisons with Streptopus and Clintonia (Uvulariaceae), these displayed approximately 1-4 synonymous substitutions per 100 sites. The rbcL gene analysis supports the previous suggestion that Scoliopus and Medeola should be moved from Trilliaceae to Liliaceae sensu stricto. The analysis also indicated that Veratrum (Melanthiaceae) may be related to Trilliaceae sensu stricto. For reconstructing the phylogeny of lower taxonomic level as such, it was found that data on nonsynonymous base substitution as well as weighting in the first and second positions of codons are not useful.

Base Sequence↗