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Biomedical subjects

H Kai

Publications and source records attributed to H Kai.

At least 55 records · Page 3Linked to original sources
PubMed1998

Expression of proto-oncogenes and gene mutation of sarcomeric proteins in patients with hypertrophic cardiomyopathy.

Several mutations of cardiac beta-myosin heavy chain (beta-MHC) gene were reported in patients with hypertrophic cardiomyopathy (HCM). Involvement of proto-oncogenes has been shown in the mechanism of experimental cardiac hypertrophy. This study sought to examine the effects of c-H-ras and c-myc expression in the steady-state myocardium on hypertrophic changes and to evaluate the possible interaction between beta-MHC mutation and proto-oncogene expression in HCM. Endomyocardial biopsy was performed in 17 HCM patients (5 beta-MHC mutations and 1 troponin T mutation) and 7 control subjects (no mutation). Reverse transcription-polymerase chain reaction analysis revealed c-H-ras expression in all members of both groups. Cardiomyocyte size was correlated with the expression level of c-H-ras (P<0.001), and c-H-ras expression was upregulated in HCM patients (P<0.01). HCM patients with a beta-MHC mutation had the higher c-H-ras expression than did control subjects or patients without a mutation (P<0.01). c-myc mRNA was expressed in 7 of 17 HCM patients but not in control subjects. Myocyte size was greater in c-myc-positive HCM patients than in control subjects and c-myc-negative HCM patients (P<0.001 and P<0.05, respectively). The proto-oncogene expression did not affect clinical findings, myocardial fibrosis, or disarray. In conclusion, c-H-ras and c-myc expression in the steady-state myocardium may play a role in the hypertrophic mechanism in HCM. It is possible that ss-MHC gene mutation has some effect on the regulation of proto-oncogene expression in HCM.

Adolescent↗
PubMed1998

G-Protein binding domains of the angiotensin II AT1A receptors mapped with synthetic peptides selected from the receptor sequence.

The vascular angiotensin II type 1 receptor (AT1AR) is a member of the G-protein-coupled receptor superfamily. We mapped the G-protein binding domains of the AT1AR using synthetic peptides selected from the receptor sequence, which interfere with AT1AR-G-protein coupling. Membrane GTPase activity was used as a measure of the functional coupling in rat vascular smooth muscle cells. Peptides corresponding to the N-terminal region of the second intracellular loop (residues 125-137), the N-terminal region of the third intracellular loop (217-227) and the juxtamembranous region of the C-terminal tail (304-316) inhibited angiotensin II-induced GTPase activation by 30%, 30%, and 70%, respectively. The latter two domains (217-227 and 304-316) are predicted to form amphiphilic alpha-helices. Only the peptide representing residues 217-227 stimulated basal activity (45%). No synthetic peptide had a significant effect on either the number or the affinity of the AT1AR binding. These observations indicate that domains of the second and third regions and the cytoplasmic tail of the AT1AR interact with G-proteins, and that multiple contacts with these receptor domains may be important for binding and activation of the G-proteins.

Amino Acid Sequence↗
PubMed1998

Myocardial DNA strand breaks are detected in biopsy tissues from patients with dilated cardiomyopathy.

BACKGROUND: Progressive damage of cardiomyocytes with interstitial and replacement fibrosis accompanied by less inflammatory cell infiltration is observed in patients with dilated cardiomyopathy (DCM), suggesting some other mechanisms rather than necrotic cell death. HYPOTHESIS: The aim of this study was to assess the possible involvement of apoptotic process in the pathogenesis of DCM and myocarditis. METHODS: Endomyocardial biopsy was performed in patients with DCM (n = 9), myocarditis (n = 4), or atypical chest pain syndrome (as controls; n = 5). The TUNEL method was used for in situ detection of oligonucleosomal DNA strand breaks. RESULTS: The TUNEL-positive cells were observed in three of nine patients with DCM and in all four with myocarditis, but in none of the controls. The TUNEL-positive nuclei were observed exclusively in cardiomyocytes in DCM, whereas in myocarditis they were detected mainly in interstitial cells and in a few myocytes. In DCM, interstitial fibrosis was greater in the TUNEL-positive than in TUNEL-negative patients (p < 0.05). In either DCM or myocarditis, electron microscopic examination could not reveal morphologic features of apoptosis of cardiomyocytes. CONCLUSION: The DNA strand breaks were detected in cardiomyocytes in patients with DCM and mainly in interstitial cells in myocarditis. It is possible that the DNA strand breaks can be involved in mechanisms of progressive loss of functional cardiac units in these myocardial diseases.

Adult↗
PubMed1998

Development of a new method for simultaneously evaluating mucociliary clearance and pulmonary epithelial permeability in rabbit experiments by means of 18FDG, three-dimensional positron emission tomography and rectilinear scan.

We tried to simultaneously obtain the elimination constant of mucociliary clearance and the pulmonary epithelial permeability constant after inhalation of 2-[18F]fluoro-2-deoxy-D-glucose (18FDG) solution by carrying out whole lung positron emission tomography and a rectilinear scan in rabbit experiments. The elimination constant of pulmonary epithelial permeability was obtained from the decrease in the amount of the radioactivity with time in the region of interest (ROI) confined to the lungs, trachea and tracheal cannula in the rectilinear scan. The total elimination constant of the radioactivity in the lungs was obtained from the ROI confined to the lungs in the tomography. The mucociliary clearance rate constant in the lungs was then obtained after subtracting the elimination constant of the pulmonary epithelial permeability from the total elimination constant of the 18FDG in the lungs. The mucociliary clearance constant in the trachea was calculated from the residual radioactivity in the trachea and the mucociliary clearance constant in the lungs. The mean pulmonary epithelial permeability constant was 0.0020% min(-1) obtained from the rectilinear scan. The mean mucociliary clearance constants of the lungs and the trachea were 0.0006 and 0.025% min(-1), respectively. These results indicated that the pulmonary epithelial permeability and mucociliary clearance could be evaluated simultaneously with 18FDG by using three-dimensional positron emission tomography and a rectilinear scan.

Administration, Inhalation↗
PubMed1998

Regioselective syntheses of sulfated polysaccharides: specific anti-HIV-1 activity of novel chitin sulfates.

A novel and convenient method for the regioselective syntheses of sulfated analogs of chitin and chitosan is described in relation to studies on structure-biological activity. Fully protected, soluble derivatives of chitosan were found to be useful intermediates for the syntheses of a novel class of sulfated polysaccharides, 2-acetamido-2-deoxy-3-O-sulfo-(1-->4)-beta-D-glucopyranan (3-sulfate, 3S, 4) and (1-->4)-2-deoxy-2-sulfoamido-3-O-sulfo-(1-->4)-beta-D-glucopyranan (2,3-disulfate, 23-S, 3). These compounds were tested for their activities in (i) inhibiting HIV-1 replication in vitro and (ii) inhibiting blood coagulation. The results reveal that the selective sulfation at O-2 and/or O-3 affords potent antiretroviral agents showing a much higher inhibitory effect on the infection of AIDS virus in vitro than that by the known 6-O-sulfated derivative (6-sulfate, 6S). Moreover, the 23-S product completely inhibited the infection of AIDS virus to T lymphocytes at concentrations as low as 0.28 microgram/mL without significant cytotoxicity. The regioselective introduction of sulfate group(s) at O-2 and/or O-3 had little effect on generating anticoagulant activity, whereas 6-O-sulfated chitin strongly inhibits blood coagulation. These results suggest that the specific interaction of these new types of chitin sulfates with gp 120 of the AIDS virus depends significantly on the sites of sulfation rather than on the total degree of substitution on sugar residues.

Animals↗
PubMed1998

Peripheral blood levels of matrix metalloproteases-2 and -9 are elevated in patients with acute coronary syndromes.

OBJECTIVES: This study was sought to investigate whether peripheral blood levels of matrix metalloproteases (MMPs) are affected in patients with acute coronary syndromes (ACS). BACKGROUND: Synthesis of MMPs has been reported in coronary atherosclerotic lesions in patients with unstable angina (UA), suggesting a pathogenic role of MMPs in the development of ACS. METHODS: Using sandwich enzyme immunoassay, serum MMP-2 and plasma MMP-9 were measured in 33 patients with ACS (22 with acute myocardial infarction [AMI], 11 with UA), 17 with stable effort angina (EA) and 17 normal control subjects. RESULTS: Serum MMP-2 in patients with UA and AMI on day 0 was two times greater than that in control subjects, and patients with EA showed higher MMP-2 levels than those in control subjects. Plasma MMP-9 in patients with UA and AMI on day 0 was elevated by threefold and twofold versus that in control subjects, respectively. In patients with UA and AMI who underwent medical treatment (n = 11 and 13, respectively), MMP-2 elevation was sustained until day 7. In patients with UA, MMP-9 elevation on day 0 was followed by a gradual decrease toward the control range up to day 7. Some patients with AMI showed a transient MMP-9 elevation with a peak on day 3, whereas in others, MMP-9 levels were significantly elevated on day 0 and remained higher than those in control subjects up to day 3. CONCLUSIONS: Serial changes in serum MMP-2 and plasma MMP-9 were documented in patients with ACS. These findings provide an insight into the molecular mechanism of plaque destabilization.

Angina Pectoris↗
PubMed1998

Long-term outcomes of nonsurgical treatment in nonreducing anteriorly displaced disk of the temporomandibular joint.

OBJECTIVES: The aim of this study was to evaluate long-term outcomes of nonsurgical treatment in patients with persistent anterior disk displacement without reduction of the temporomandibular joint. STUDY DESIGN: Thirty-five patients were treated with occlusal splints, and 12 patients underwent additional occlusal treatments after splint treatment. These patients were evaluated clinically and radiographically. At least 2 years after the treatment, the 34 patients' symptoms were assessed with the use of a questionnaire. RESULTS: The mean maximal interincisal distance (MID) was 27.6 mm before treatment and 44.4 mm at the end of treatment (p < 0.001). Before the treatment, all 35 patients had complained of pain, and mild pain persisted in 9 patients at the end of treatment. Flattening of the condylar head and of the articular eminence increased in prevalence from 12.1% and 9.1%, respectively, before treatment to 54.5% and 51.5%, respectively, at the time of follow-up observation. At the time of the survey, the mean self-reported MID was 46.8 mm (p < 0.01). CONCLUSIONS: After the nonsurgical treatment, the clinical signs and symptoms improved significantly, although the prevalence of osteoarthrotic findings increased.

Adolescent↗
PubMed1998

Current opinion of muco-active drug research: strategies and problems.

In general, mucoactive drugs are classified into several groups. However, since many drugs have overlapping effects, it is difficult to classify the drugs into groups based on their major actions. It has been reported that many mucoactive drugs have antioxidant effects. It is reasonable to suggest that an anti-inflammatory property is crucial to demonstrate effectiveness in a clinical context. From this point of view, we have evaluated several mucoactive drugs over two decades. Of these, we will consider the following drugs with anti-inflammatory properties: sodium aceneuramate; glucocorticoids; traditional Chinese medicines; and new cysteine derivatives. On the basis of these findings, we believe that the efforts to seek for compatible actions between glucocorticoids and oriental medicines may provide new opportunities for development of ideal mucoactive drugs with specified actions, i.e. suppression of gene expression.

Anti-Inflammatory Agents↗
PubMed1998

Effects of SS320A, a new cysteine derivative, on the change in the number of goblet cells induced by isoproterenol in rat tracheal epithelium.

We examined the effects of SS320A ((-)-(R)-2-amino-3-(3-hydroxypropylthio)propionic acid), a new cysteine derivative, on the change in the number of goblet cells induced by isoproterenol in rat tracheal epithelium. Four types of goblet cells were characterized in tracheal epithelium according to their size and staining affinity with Alcian blue (AB) / periodic acid Schiff (PAS). When each rat was given a single daily injection of isoproterenol (0.05 mg/kg, i.p.) for 14 days, a significant increase was observed in AB/PAS-positive cells that were recognizable as goblet cells in tracheal epithelium. When SS320A (10-100 mg/kg, p.o.) or propranolol (1 mg/kg, s.c.) was administered before each injection of isoproterenol, the increase in the number of goblet cells induced by isoproterenol was significantly inhibited. There was no difference between male and female rats with regard to this inhibitory action. On the other hand, ambroxol, bromhexine, L-cysteine ethyl ester and S-carboxymethylcysteine (100 mg/kg, p.o., respectively), which are used as expectorants, had no inhibitory effects on the isoproterenol-induced change in the number of goblet cells. Four metabolites (M1-M4) of SS320A in rats also failed to inhibit the change induced by isoproterenol. These data suggest that SS320A itself may have a beneficial effect against mucus hypersecretion in chronic respiratory diseases.

Animals↗
PubMed1998

Local anti-inflammatory activity and systemic side effects of NM-135, a new prodrug glucocorticoid, in an experimental inflammatory rat model.

The local anti-inflammatory activity and systemic side effects of NM-135 (6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-21[[2 ,3,4,6-tetrakis-O-(4-methylbenzoyl)-beta-D-glucopyranosyl]oxy]-pregna-1, 4-diene-3,20-dione) in croton oil-induced granuloma pouches and ear edema in rats were studied. The local anti-inflammatory activity of NM-135 was stronger than that of betamethasone 17-valerate (BV). As to systemic side effects, BV and diflucortolon valerate (DFV) caused thymolysis at the doses required for the anti-inflammatory activity. In contrast, no clear systemic side effect was observed in rats administered NM-135 at the dose producing the anti-inflammatory activity. These results suggest that NM-135 is a drug exhibiting a high degree of dissociation between the local anti-inflammatory activity and systemic side effects.

Animals↗
PubMed1998

Inhibition of glycine-induced current by morphine in nucleus tractus solitarii neurones of guinea pigs.

We studied the effect of morphine on the current induced by glycine in acutely dissociated nucleus tractus solitarii (NTS) neurones of guinea pigs, by use of the whole-cell patch clamp technique. Morphine inhibited 30 microM glycine-induced current (Igly), without affecting the current caused by 30 microM GABA. The effect of morphine was concentration-dependent, with a maximal effect at 1 mM, and reversible. The half-maximum inhibitory concentration of morphine was 30 microM. The effect of morphine was not depressed by naloxone, an opioid antagonist. Furthermore, the effect was not substantially affected by methiothepin, a 5-HT1 antagonist, ketanserin, a 5-HT2 antagonist and MDL-72222, a 5-HT3 antagonist. Morphine at 30 microM shifted the concentration-response curve for Igly to the right without affecting the maximum value. The effect of morphine on Igly showed no use-dependence. The results indicate that morphine inhibits Igly in the NTS neurones, and further suggest that morphine at the concentration used may act on the glycine receptor-ionophore complex, but not on the Cl-channel of the complex.

Animals↗
PubMed1998

Problems of various fixation methods for open tibia fractures: experience in a Japanese level I trauma center.

Two hundred thirty-seven patients with open tibial fractures (245 fractures) were treated as follows: nonoperative stabilization alone (Nonop group, n = 54); immediate open reduction and internal fixation (ORIF group, n = 47); delayed ORIF (D-ORIF group, n = 109); or external fixation (EF group, n = 35). The D-ORIF group was further divided into ORIF after nonoperative treatment (Nonop/ORIF, n = 86), and ORIF after external fixation (EF/ORIF, n = 23). The open tibial fractures were classified as follows: 42 type I (no infections), 107 type II (4 infections), 43 type IIIA (3 infections), 42 type IIIB (12 infections), and 11 type IIIC (2 infections), with significant differences in infection rate between type IIIB and type I, type II, or type IIIA. The deep infection rates in Nonop, ORIF, Nonop/ORIF, EF/ORIF, and EF groups were 3.7%, 12.8%, 5.8%, 30.4%, and 2.9%, respectively. There were significant differences in deep infection rates between the EF/ORIF and Nonop/ORIF, and the EF group. The mean period of fracture healing for type IIIB fractures was delayed. The mean time to union of the EF/ORIF was significantly longer than that of the ORIF, Nonop/ORIF, and EF groups, respectively. Complete and consecutive debridement procedures and early soft-tissue coverage should be done to avoid wound infection, especially in type IIIB fractures. Delayed internal fixation after external fixation had the highest risk of infection, mandating meticulous wound management in such patients.

Adolescent↗
PubMed1997

G protein-coupled receptor kinase 5 in cultured vascular smooth muscle cells and rat aorta. Regulation by angiotensin II and hypertension.

GRK5, a recently cloned member of the G protein-coupled receptor kinase family, has been shown to phosphorylate and participate in the desensitization of angiotensin II (Ang II) type 1A (AT1A) receptors. In this study, the effect of angiotensin II on GRK5 expression was examined in cultured vascular smooth muscle cells and aortas of Ang II-infused hypertensive rats. In vascular smooth muscle cells, Ang II (100 nM) up-regulated GRK5 mRNA as early as 1 h, with a peak at 16 h. This up-regulation was dose- and calcium-dependent. The increase in GRK5 mRNA was reflected in a smaller increase in protein expression, which nonetheless had functional significance since AT1 receptor phosphorylation was increased and phospholipase C activation was decreased following prolonged incubation with Ang II. In aortas of Ang II-infused hypertensive rats, both GRK5 mRNA and protein levels increased approximately 3-fold compared with sham-operated rats at 5 and 7 days, respectively. This up-regulation was blocked either by losartan or by the nonspecific vasodilator hydralazine. Since a subpressor dose of Ang II did not increase GRK5 mRNA levels and norepinephrine infusion also increased GRK5 mRNA expression, we conclude that Ang II-induced GRK5 up-regulation in rat aortas may be due to hypertension per se. Hormone- and hemodynamic stress-induced GRK5 regulation may provide a novel molecular basis for long-term regulation of agonist sensitivity of vascular cells.

Angiotensin II↗
PubMed1997

Differential effect of codeine on coughs caused by mechanical stimulation of two different sites in the airway of guinea pigs.

We studied the difference in the effects of codeine on coughs caused by mechanical stimulation to the larynx and to the bifurcation of the trachea in lightly anaesthetized guinea pigs. Mechanical stimulation to the larynx or the bifurcation of trachea caused a stable cough response. The response was reproducible over 60 min, when stimulation was repeatedly applied at 20-min intervals. No significant difference was found between the amplitudes of the responses to mechanical stimulation of the larynx and of the tracheal bifurcation. Codeine, 10, 20 and 50 mg/kg, dose dependently depressed the coughs caused by larynx stimulation. The antitussive, however, failed to depress the cough caused by stimulation to the tracheal bifurcation, although a large dose, 50 mg/kg, significantly depressed the cough. In capsaicin-treated guinea pigs, codeine at 20 mg/kg significantly depressed the cough caused by stimulation to the tracheal bifurcation. The present results suggest that cough caused by mechanical stimulation to the larynx might be more sensitive to codeine treatment than cough caused by stimulation to the bifurcation of trachea. Furthermore, it is suggested that coughs caused by mechanical stimulation to both sites might consist of at least two components as regards their pharmacological nature.

Animals↗
PubMed1997

Vasospastic angina induced by nonsteroidal anti-inflammatory drugs.

We report two cases of vasospastic angina associated with anaphylactic reaction caused by nonsteroidal anti-inflammatory drugs (NSAIDs). Both patients exhibited anaphylactic manifestations, such as general rash and urticaria, along with angina pectoris with electrocardiographic ST-segment elevations after suppository administration of diclofenac sodium or indomethacin, the most commonly used NSAIDs. Although these patients had normal coronary arteriograms, intracoronary administration of ergonovine or acetylcholine provoked diffuse coronary artery spasms accompanied by chest pain and ischemic ST-segment changes. It is therefore suggested that an allergic mechanism may be involved as a causative factor of the coronary artery spasm induced by NSAIDs.

Aged↗
PubMed1997

Inhibition of glycine currents by dextromethorphan in neurones dissociated from the guinea-pig nucleus tractus solitarii.

1. The effect of dextromethorphan (DM) on the current induced by glycine in acutely dissociated nucleus tractus solitarii (NTS) neurones of guinea-pigs was studied by use of the whole-cell patch clamp technique. The effect of DM on gamma-aminobutyric acid (GABA)-induced currents (IGABA) was also examined. 2. DM inhibited 30 microM glycine-induced current (IGly), without affecting the current caused by 30 microM GABA. The action of DM was concentration-dependent, with a maximum effect at 100 microM, and reversible. The half-maximum inhibitory concentration (IC50) of DM was 3.3 microM, about 85 times higher than that of strychnine. 3. DM 3 microM shifted the concentration-response curve for glycine to the right without affecting the maximum value. DM 10 microM shifted the curve even more to the right, although it was not a parallel shift. Strychnine at a concentration of 0.1 microM shifted the curve for glycine in a nearly parallel fashion. 4. The effect of 10 microM DM was slightly weak voltage-dependency, but the lower concentration of DM, 3 microM, inhibited IGly equally at -50 mV and +50 mV. The effect of 3 microM DM on IGly showed no use-dependence. Blockade by strychnine 0.1 microM showed no voltage- or use-dependence. 5. The results indicate that DM inhibits IGly in single neurones of NTS, and further suggest that DM at a low concentration may act on the glycine receptor-ionophore complex, but not on the Cl channel of the complex. However, a relatively high concentration of DM may at least partly affect the Cl- channel of the complex.

Animals↗