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Biomedical subjects

M Kubo

Publications and source records attributed to M Kubo.

At least 523 records · Page 29Linked to original sources
PubMed1987

Diethylaminoethoxyhexestrol inhibition of purified rat liver lysosomal phospholipase A1: role of drug binding to substrate.

In this report, the inhibition of purified rat liver phospholipase A1 by diethylaminoethoxyhexestrol (DH) has been evaluated and the results correlated with DH binding to sonicated vesicles of di[1-14C]oleoylphosphatidylcholine. The drug bound in a positive cooperative manner to two classes of binding sites on phosphatidylcholine small unilamellar vesicles, one having an apparent high affinity and low capacity and another having a low affinity and high capacity. The observed data were shown to fit to a mixed type of inhibition when the free DH concentration (determined independently in the binding experiments) was used instead of the total drug concentration. Hydrolysis of enzyme-substrate-drug complexes was estimated to occur at a rate only half that of the enzyme-substrate complex. Results with DH suggest that both drug-enzyme and drug-substrate interactions may be important factors in the inhibition of lysosomal phospholipase A1.

Animals↗
PubMed1987

[Pathogenesis of dilated cardiomyopathy: a study based on comparison of the clinical features with other related conditions].

To investigate the pathogenesis and pathophysiology of dilated cardiomyopathy (DCM), we studied 28 patients with DCM by echocardiography and endomyocardial biopsy, and compared their findings with those of 34 patients including eight with myocarditis, seven with alcoholics, 12 with hypertensives and seven patients with hypertrophic cardiomyopathy. All 12 patients in the hypertensive group had congestive heart failure without accompanying high blood pressure, and prominent dilatation and uniform wall motion abnormality of the left ventricle observed echocardiographically on admission. After medical management, both heart failure and the echocardiographic abnormalities gradually resolved. Those in the alcoholic group had larger left ventricles and uniform wall motion abnormality compared to those in the other groups. The myocarditis and hypertrophic cardiomyopathy groups had smaller left ventricles, non-uniform wall motion and larger % myocardial fibrosis. Both ventricles in the hypertrophic cardiomyopathy group were thicker than those of the other three groups. Each patient with DCM had individual echocardiographic abnormalities, which could be categorized as two subsets depending on the degree of left ventricular dilatation and uniformity of the wall motion. The one was characterized by a prominently dilated left ventricle and uniform wall motion abnormality similar to the alcoholic group, and the other had less marked left ventricular dilatation and heterogeneous wall motion abnormality similar to the myocarditis group. From these findings, it was suggested that there are common factors to specific myocardial disease in the pathogenesis and pathophysiology of DCM, and thus, DCM might include many subsets of different etiologies.

Adult↗
PubMed1987

[Relationships between segmental left ventricular wall motion abnormalities and pathological findings in patients with dilated cardiomyopathy].

Relationships between segmental left ventricular wall motion abnormalities and myocardial fibrosis at autopsy were examined in 12 patients who died of dilated cardiomyopathy. In each case, wall motion abnormalities were assessed by two-dimensional echocardiograms for 11 segments, and semiquantitatively evaluated as normokinesis (N) to hypokinesis (H), severe hypokinesis (SH) or akinesis (A). From the necropsy specimens, the myocardial fibrosis ratio was histologically quantitated using a point-counting method in each segment corresponding to the echocardiographic segment. Wall motion abnormalities and the fibrosis ratio correlated significantly in a total of 132 segments of the 12 patients, but there were some discordances. The cases were then categorized in uniform and non-uniform groups based on the patterns of myocardial fibrosis. Wall motion abnormalities correlated much better with the fibrosis ratio in a total of 44 segments among four cases with non-uniform fibrosis, whereas no significant correlation was found in a total of 88 segments in eight cases with uniform fibrosis. The latter group had more severe segmental wall motion abnormalities in the interventricular septum than in the left ventricular free wall; and in the apical portion rather than in the basal portion, although no significant difference was observed in the fibrosis ratio among these regions. Patients with non-uniform fibrosis had higher incidences of chest pain and sudden deaths and a significantly larger left ventricular end-diastolic dimension on M-mode echocardiogram as compared to those with uniform fibrosis. Pathologically, in the former group, the heart was heavier, the mean left ventricular fibrosis ratio was significantly higher, and there was a greater incidence of infiltration of the myocardium by mononuclear cells, but there was no difference in the mean left ventricular wall thickness. These results suggest that myocardial fibrosis mainly contributes to the wall motion abnormalities in cases with non-uniform fibrosis which may be caused by chronic myocarditis, but not in cases with uniform fibrosis. In the latter group, other factors such as reduced contractility of the myocardial cells or lack of a compensatory mechanism for wall stress seem to play important roles in causing left ventricular wall motion abnormalities.

Adult↗
PubMed1987

Increased compliance of niceritrol treatment by addition of aspirin: relationship between changes in prostaglandins and skin flushing.

The relation of plasma levels of prostaglandins to the occurrence of flushing induced by niceritrol was investigated. Niceritrol increased plasma levels of PGE2 (p less than 0.01) and 6 keto-PGF1 alpha (p less than 0.05) in 10 male subjects and aspirin reduced the level of PGE2 (p less than 0.01). Five of 10 subjects had flushing, and aspirin reduced flushing in 4 subjects. On the basis of the above study, we treated 35 hyperlipidemic patients with niceritrol in combination with aspirin, investigating the effect of the treatment of serum lipids and postheparin lipolytic activity. None of the 12 cases given aspirin from the start of the treatment experienced flushing, whereas 9 of the 23 cases not given aspirin experienced flushing, which was suppressed by adding aspirin in prescription in all cases except one. Niceritrol decreased serum cholesterol, triglyceride and atherogenic index. It also increased HDL2 cholesterol and decreased HDL3 cholesterol. The LPL activity in postheparin plasma increased in all cases after niceritrol treatment. In conclusion, aspirin increased compliance of niceritrol by reducing the occurrence of flushing probably due to the decreased levels of prostaglandins, yielding favorable results for the long-term treatment of hyperlipidemia with a sufficient doses of niceritrol.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

[Pulsed Doppler echocardiographic findings in 117 professional cyclists].

To investigate the effect of long-term athletic training on the heart, pulsed Doppler echocardiography was performed in 117 male professional cyclists (Group C: 20-59 years of age), and 40 age- and sex-matched untrained normal controls (Group N). According to age, the subjects in each group were categorized in two subgroups: 74 cyclists (Group CI), 20-39 years of age and 43 cyclists (Group CII), 40-59 years of age; 24 control subjects (Group NI), 20-39 years of age and 16 control subjects (Group NII), 40-59 years of age. The average durations as professional cyclists were eight years in Group CI and 29 years in Group CII. The ratios of pre-ejection period to ejection time (LV-PEP/ET, RV-PEP/ET) as obtained from Doppler flow velocity patterns of the left and right ventricles (LV, RV) were used as parameters of systolic function. The peak flow velocities during rapid filling (LV-R, RV-R) and atrial systole (LV-A, RV-A), and the ratio of A to R (LV-A/R, RV-A/R) were used as parameters of diastolic filling dynamics. The parameters of systolic function of both ventricles and those of diastolic filling dynamics of the RV did not differ between Group C and Group N, Group CI and Group NI, and Group CII and Group NII. Study of the diastolic filling dynamics of the LV disclosed that Group C had a significantly higher LV-A/R (p less than 0.05) than did Group N; therefore, no significant differences between Group CI and Group NI, and Group CII had a significantly lower LV-R (p less than 0.005) and a higher LV-A/R (p less than 0.005) than did Group NII. Twenty-four hour ambulatory ECG monitoring was performed for 49 cyclists. Thirty cyclists aged 20-39 years were categorized in two groups according to their LV-A/R values: eight cyclists (Group A) with the LV-A/R greater than the mean + SD value (0.69) in Group NI and 22 cyclists (Group B) with the LV-A/R lower than or equal to 0.69. Nineteen cyclists aged 40-59 years were separated into two groups according to the LV-A/R value: 11 cyclists (Group A) with the LV-A/R values greater than the mean + SD value (0.89) in Group NII, and eight cyclists (Group B) with the LV-A/R equal to or less than 0.89.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

[A trial diagnosis of latent dilated cardiomyopathy].

To diagnose latent dilated cardiomyopathy (latent DCM), we performed loading echocardiography with Angiotensin II and ergometer exercise in 41 patients. Twenty-one patients were suspected of having latent DCM because of histories, of heart failure of myocarditis; 10 patients had DCM; and 10 normal persons served as controls. On angiotensin II loading, cardiac function deteriorated in the DCM group, but it was maintained in the normal controls. Nine patients in the latent DCM group showed the same pattern as normals (L1-group), and 12 did as the DCM group (L2-group). Although % fractional shortening, end-diastolic and end-systolic dimensions of the left ventricle did not differ between the L1 and L2-groups, the A/R, the ratio of the pulsed Doppler echocardiogram at the left ventricular inflow tract, was larger and the exercise change of the % fractional shortening and exercise tolerance were less in the L2-group than in the L1-group. Furthermore, the biopsy findings of the L2-group were similar to those of the DCM group in terms of myocardial degeneration, myocardial hypertrophy and interstitial fibrosis. Thus, patients in the L2-group were thought to have a risk for DCM, and were cases of latent DCM. Angiotensin II loading is thought to be useful for diagnosing such cases.

Angiotensin II↗
PubMed1986

Binding of propranolol and gentamicin to small unilamellar phospholipid vesicles. Contribution of ionic and hydrophobic forces.

Binding of propranolol and gentamicin to small unilamellar phospholipid vesicles having different surface charges was studied at pH 4.4 using an ultra-centrifugation method, and the results were analyzed by an equation describing the Langmuir adsorption isotherms. Gentamicin, a polycationic drug, bound to negatively-charged small unilamellar vesicles composed of 60% phosphatidylcholine and 40% of either phosphatidylinositol, phosphatidylglycerol or phosphatidylserine in a manner consistent with a single class of binding sites but did not bind at all to small unilamellar vesicles of phosphatidylcholine alone. In contrast, propranolol bound readily to both neutral and negatively-charged liposomes in a manner consistent with two types of binding sites. Based on the binding parameters calculated from replots, it is suggested that the high-affinity site is probably at the surface of the liposome and that ionic forces are primarily responsible for this binding. The low-affinity, high-capacity binding site for propranolol was demonstrated with both neutral and negatively-charged liposomes and appeared to be independent of the surface charge. Gentamicin, which is not hydrophobic, did not bind to the low-affinity site. It is hypothesized that hydrophobic interactions are the driving force for propranolol binding to the low-affinity site which may be the interior of the lipid bilayer.

Binding Sites↗
PubMed1986

Influence of endogenous hyperinsulinism on high density lipoprotein2 level in type 2 (non-insulin-dependent) diabetes mellitus and impaired glucose tolerance.

We determined the insulin response to an oral glucose ingestion and levels of serum lipoproteins in 25 untreated patients with type 2 diabetes mellitus, in 26 subjects with impaired glucose tolerance (IGT), and in 35 non-diabetic control subjects. The three groups had similar compositions with respect to age and sex distribution. The levels of VLDL triglyceride in the subjects with type 2 diabetes or IGT were higher than those in controls. Serum HDL- and HDL2 cholesterol were significantly decreased in type 2 diabetics, and the subjects with IGT showed a similar tendency. Serum apolipoprotein A-II levels were lower in the male subjects with type 2 diabetes or IGT than in controls. Insulin response, i.e., sum of immunoreactive insulin (IRI) levels at basal, 30, 60, 90 and 120 min after a 75-g oral glucose load, negatively correlated to HDL- and HDL2 cholesterol levels (r = -0.396, P less than 0.05; r = -0.482, P less than 0.001, respectively), and positively correlated to VLDL triglyceride values (r = 0.485, P less than 0.001) in the male subjects with type 2 diabetes or IGT. In the female subjects, fasting plasma IRI values significantly correlated to HDL cholesterol (r = -0.496, P less than 0.05). There was a significant negative correlation between the concentrations of HDL2 cholesterol and VLDL triglyceride. These data show that lipoprotein metabolism, not only in type 2 diabetics, but also in IGT tends to show changes such as decreased HDL2 cholesterol and increased VLDL triglyceride levels, and which might be related to the hypersecretion of endogenous insulin.

Adult↗
PubMed1986

The role of hepatic triglyceride lipase in the metabolism of intermediate-density lipoprotein--postheparin lipolytic activities determined by a sensitive, nonradioisotopic method in hyperlipidemic patients and normals.

With a view to elucidating the physiologic role of hepatic triglyceride lipase (H-TGL), we studied the relationship between the activity of H-TGL and the concentrations of the lipids of ultracentrifugally separated lipoprotein fractions in sera from 81 cases of primary hyperlipidemia, 5 of hypothyroidism, and 31 normal subjects. The activity of H-TGL in postheparin plasma was determined by the sensitive, nonradioisotopic method that was recently developed by us. In the entire group of subjects including the normals, the activity of H-TGL had a significant inverse correlation with the concentration of the cholesterol (r = -0.443, P less than 0.001) and phospholipid (r = -0.433, P less than 0.001) of intermediate density lipoprotein (IDL). When the patients were divided into subgroups according to the phenotype of hyperlipidemia, it was found that the correlation was more significant in type IIb (r = 0.695, P less than 0.001) or type IV + V (r = -0.664, P less than 0.0001). In the five cases of hypothyroidism, the mean IDL cholesterol level was high (28.3 +/- 12.3 mg/dL) and the H-TGL activity was very low (4.6 +/- 4.5 mumol/h/mL). The H-TGL activity was also significantly correlated with the ratio of high density lipoprotein-2 to high density lipoprotein-3 cholesterol (r = 0.351, P less than 0.001) in the entire group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Intraindividual changes in theophylline clearance during constant aminophylline infusion in children with acute asthma.

Intraindividual changes in theophylline clearance were examined in 13 children with acute exacerbation of asthma receiving a 72-hour constant intravenous infusion of aminophylline. The mean (+/- SD) first, second, and third clearances measured at 24, 48, and 72 hours after the infusion increased from 58.1 +/- 13.8 to 69.7 +/- 28.0 to 84.1 +/- 36.3 ml/hr/kg, respectively (P less than 0.02 from the first and P less than 0.05 from the second). Our results suggest that substantial intraindividual changes in theophylline clearance can occur over a rather short time during intravenously administered aminophylline therapy for acute asthma in children. We recommend that plasma theophylline concentrations be monitored frequently and that aminophylline infusion rate be adjusted on the basis of the measured theophylline concentration data during an acute episode of asthma in the pediatric patient.

Acute Disease↗