Search PubMed⌕ Search

Biomedical subjects

T Oki

Publications and source records attributed to T Oki.

At least 307 records · Page 17Linked to original sources

Chemical modification of the antitumor antibiotic glidobactin.

A variety of glidobactin analogs modified at the fatty acid, L-threonine and nucleus moieties of the molecule were synthesized and their structure-activity relationships examined. The antitumor and antifungal activity was greatly influenced by modification of the fatty acid glidobactin, with the dodecanoyl and tetradecanoyl analogs exhibiting better antitumor activity than the parent antibiotics. Replacement of the L-threonine with other amino acids greatly reduced the activity and reduction of the double bond of the nucleus completely eliminated the biological activity of glidobactin.

Antibiotics, Antineoplastic↗

BMY-28190, a novel antiviral antibiotic complex.

BMY-28190, an antibiotic complex active against herpes simplex virus type 1 (HSV-1) was produced by the cultured broth of Streptoalloteichus hindustanus sp. nov., a producing strain of tallysomycins A and B. The antibiotic complex was recovered from the broth with Amberlite IRC-50 resin and separated from the coproduced tallysomycins and nebramycins by a series of chromatographies. BMY-28190 exhibited weak inhibitory activity toward Gram-positive and Gram-negative bacteria and strong inhibitory activity toward HSV-1. Structural studies disclosed that BMY-28190 is a novel complex of gamma-poly-D-alpha, gamma-diaminobutyric acids with an average MW of 5,130.

Actinomycetales↗

BMY-28438 (3,7-dihydroxytropolone), a new antitumor antibiotic active against B16 melanoma. I. Production, isolation, structure and biological activity.

A new antitumor antibiotic BMY-28438 was isolated from the cultured broth of Streptomyces tropolofaciens No. K611-97. The antibiotic showed potent cytotoxicity against cultured B16 melanoma cells and remarkable prolongation of life span of mice bearing B16 melanoma. The structure of BMY-28438 was determined as 3,7-dihydroxytropolone on the basis of spectral analyses and direct comparison with the authentic compound synthesized.

Animals↗

[Genesis and clinical significance of the "low-pitched" aortic ejection sound].

The genesis and clinical significance of the aortic ejection sound with a low-frequency predominance and delayed appearance were studied. This is recorded on the phonocardiogram in some patients with left ventricular dysfunction. Subjects studied consisted of 10 patients with a low-pitched ejection sound and seven patients with an ordinary high-pitched aortic ejection sound. No patients had echocardiographic findings suggestive of organic lesions of the aortic valve. Time relationships among the ejection sounds, aortic valve echograms and carotid artery pulses, and then movements of the aortic valve cusps and non-invasively estimated left ventricular systolic function were compared between the two groups. Results were as follows: 1. The low-pitched ejection sound: 1) The beginning of the sound was nearly coincident with the onset of the upstroke of the carotid artery pulse and the initial full opening of the aortic valve cusps. 2) The beginning of the ejection systolic murmur followed immediately after the ejection sound. 3) The amplitude of the sound was closely related to the height of the carotid artery pulse in a case of atrial fibrillation. 2. The low-pitched ejection sound vs the high-pitched ejection sound: 1) The onset of the low-pitched ejection sound was significantly delayed. 2) The amplitude and the velocity of the initial opening of the aortic valve cusps were significantly decreased. 3) The preejection period (PEP) was significantly prolonged; the ejection time (ET) was significantly shortened; and the PEP/ET ratio was significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta↗

[Systolic clicks in mitral valve prolapse: their pathophysiological relationship to the grade and causes of prolapse].

To re-evaluate the clinical significance of non-ejection systolic clicks in mitral valve prolapse (MVP), 154 patients with idiopathic MVP (idiopathic group) and 54 patients with secondary MVP associated with atrial septal defect (secondary group) were studied using phonocardiography and two-dimensional echocardiography. There was no significant difference in the incidence of systolic clicks between the idiopathic (30%) and secondary (24%) groups. The severer the degree of prolapse, the higher the incidence of systolic clicks in both the groups. A systolic click was observed independently of age in the idiopathic group. In the secondary group, however, a systolic click was not observed in patients under 30 years old and increased with advancing age in frequency. The intensity of systolic click tended to increase in proportion to the increase of severity of prolapse in both the groups. These results suggested that systolic clicks may appear irrespective of the causes of prolapse and that the production and the intensity of systolic clicks may be related to the degree of changes in the mitral valve-chordal system and the degree of prolapse.

Adolescent↗

[Diurnal variation of the QT intervals in idiopathic mitral valve prolapse].

Diurnal variation of QT intervals was analyzed using Holter monitoring for 44 patients with mitral valve prolapse (MVP), and the relationship between ECG changes and autonomic nervous dysfunction was assessed by measuring blood catecholamine during bicycle ergometer exercise and various autonomic functional tests. The following results were obtained. 1. The QT intervals in MVP patients had greater diurnal variations and the averaged QTc was in a high level all the time. 2. Positivity of the autonomic functional tests and the catecholamine level after exercise were significantly high in patients of MVP. 3. After catecholamine depletion by beta-blocking agent (carteolol: 15 mg a day, 5 to 12 months' duration), the variation of QTc became less marked. These data indicate the presence of autonomic dysfunction in patients of MVP.

Adolescent↗

[Diastolic right ventricular hemodynamics in right ventricular overloads assessed by pulsed Doppler echocardiography].

To assess right ventricular (RV) filling dynamics, RV inflow velocity patterns of pulsed Doppler echocardiograms and jugular pulse tracings were analyzed in 59 patients with various types of RV overloads and in 20 normal subjects. The patients were classified as (1) RV volume overload group (RVVO) consisting of 25 patients with atrial septal defect (ASD) without pulmonary hypertension (PH), (2) RV pressure overload group consisting of 26 patients including 12 with primary pulmonary hypertension (PPH), eight with mitral stenosis, three with pulmonary stenosis and three with cor pulmonale, and (3) RV volume and pressure overload group consisting of eight patients with ASD and PH. The acceleration time (AT), deceleration time (DT) and the A/D ratio were measured from the RV inflow velocity patterns, and v-y interval and the y/H ratio were measured from jugular pulse tracings. The results were as follows: 1. AT was significantly prolonged in groups with pressure overload as well as pressure and volume overload compared with that of the normal controls. 2. DT was significantly prolonged in all overload groups compared with that of the normal controls except for PPH, and was particularly prolonged in the group with pressure overload. 3. The A/D ratio was significantly increased in all overload groups, particularly in the groups with pressure overload. 4. In patients with volume overloads, the v-y interval was longer and the y/H ratio was higher than in the normal controls. RVVO shifted to the right and superiorly. The reverse was true in the pressure overload group, and the high ratios were observed in the remainder. 5. In 12 patients with ASD evaluated pre- and postoperatively, AT, DT and the A/D ratio were restored to normal after surgery. These findings suggest that RV volume overload was characterized not only by increased inflow velocity during the rapid filling period, but prolongation of this period and compensatory increase of atrial inflow velocity. However, the pressure overload group had disturbed rapid filling and a decrease in end-diastolic RV compliance. The group with both pressure and volume overloads was between the two. In conclusion, the mode of RV filling in patients with RV overload showed various patterns depending on the type of overload. The RV inflow velocity pattern recorded by pulsed Doppler echocardiography is of use in discriminating these varieties.

Adult↗

[Van der Hoeve's syndrome with Ebstein's anomaly, and prolapse of the mitral and aortic valves: a case report].

A hitherto unrecognized case of van der Hoeve's syndrome complicated by Ebstein's anomaly, and prolapse of the mitral and aortic valves was reported. A 46-year-old woman presented with blue sclera, osteogenesis imperfecta and a hearing loss, which are typical symptoms of this syndrome. The electrocardiogram showed a type B WPW syndrome. The phonocardiogram showed a loud and widely split first heart sound, an accentuated protodiastolic extrasound, a decrescendo regurgitant systolic murmur, and a presystolic murmur. The x descent of the jugular phlebogram was obliterated by a markedly increased c wave. Based on M-mode and two-dimensional echocardiograms, 1) the interventricular septal motion was paradoxical and the closure of the tricuspid valve was delayed, 2) the septal tricuspid leaflet was displaced toward the apex from its normal annular insertion on the apical four-chamber view, 3) the three leaflets of the tricuspid valve were abnormally elongated, 4) the anterior mitral leaflet and the non-coronary cusp of the aortic valve were elongated and prolapsed. Doppler echocardiography detected severe tricuspid and mild mitral regurgitations. We suggest that the development of Ebstein's anomaly is possibly related to that of osteogenesis imperfecta genetically and that not only Ebstein's anomaly but a connective tissue disorder contributes to the elongated and prolapsed leaflets.

Abnormalities, Multiple↗

Deficiency of density-dependent regulation of cell growth in the culture of skin fibroblasts from patients with mucolipidosis III.

Cultured skin fibroblast cells were prepared from two patients with mucolipidosis III (ML III), which is a genetic disorder characterized by low activities of multiple lysosomal enzymes in fibroblasts. Genetic complementation analysis of fused fibroblast hybrids revealed that the patients were classified in different complementation groups. Growth curves of fibroblasts of ML III patients in culture were compared with those of fibroblasts of Sanfilippo's syndrome patients as well as of the normal fibroblasts. Normal and Sanfilippo fibroblasts gave essentially the same sigmoid curve of cell growth. However, although both ML III cell lines grew at the normal rate in the initial logarithmic phase, they continued to proliferate actively even after the cultures reached confluency. This is the first report to demonstrate the deficiency of density-dependent regulation of cell growth in the culture of nontransformed cell types. Therefore, the culture of skin fibroblasts of ML III patients may serve as a useful experimental model for investigating the regulation of cell proliferation in vitro.

Adult↗

[Correlations between the features of first heart sound and opening snap and the shape and motion of the anterior mitral leaflet in patients with mitral stenosis].

To evaluate the relationship between the motion pattern and degree of organic change of the anterior mitral leaflet (AML) and the features of the mitral component of the first heart sound (M1) or the opening snap (OS), 37 patients with mitral stenosis (MS) were studied by auscultation, phonocardiography and echocardiography. Based on the features of M1 and OS according to auscultation and phonocardiography, the patients were categorized as group I, 18 patients with loud and snappy M1 and OS; group II, 12 patients with snappy M1 but small and dull OS; and group III, seven patients with small and dull M1 and OS. Intensities of M1 and OS were calculated by the ratios of their amplitudes to the aortic component of the second heart sound on the high frequency phonocardiograms recorded at points of the maximum intensities, respectively. Echocardiographic parameters related to productions of M1 and OS were obtained from M-mode and two-dimensional echograms of the AML; they were amplitudes and velocities on closing and opening, M1 area defined as that between end-diastolic and systolic echoes, OS area between systolic and early diastolic echoes, the doming area between the trailing edge of an early diastolic echo and a line projected from the anterior annulus to the tip of the leaflet, and the degree of systolic ballooning. Results were as follows: 1. Significant differences in the area of the mitral valve orifice were found among three groups. The area was maximum in group II, minimum in group III and intermediate in group I. 2. In group I, the body of the AML was pliable, resulting in a ballooning into the left atrium in systole and a marked doming toward the left ventricle in early diastole. Various parameters related to the production of M1 and OS in group I were significantly increased as compared with those of the other two groups. 3. In group II, the body of the AML was not pliable in spite of mild organic changes in the valve. The degree of early diastolic doming was mild. Compared to group III, the intensity of M1 in group II was significantly larger, but no significant difference was observed in the parameters related to the production of M1 between the two groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

[Musical systolic murmur produced by oscillation of the systolic anterior motion of the mitral apparatus: relation to the genesis of Still's murmur].

The genesis of a musical systolic murmur produced by systolic anterior motion (SAM) of the mitral apparatus was investigated in four patients using phonocardiography and echocardiography. Two patients (Case 1 and 3) had hypertrophic cardiomyopathy (one, the obstructive type; the other, the nonobstructive type) and the remaining two (Case 2 and 4) had redundant chordae tendineae. 1. In every patient, regular oscillation of the SAM was observed, coinciding in time with the musical systolic murmur, which was simultaneously recorded. The fundamental frequency of the musical systolic murmur was recorded as integrally multiplied numbers of the SAM. Such regular oscillation was not observed in the echograms of other cardiac structures. In a patient with hypertrophic obstructive cardiomyopathy (Case 1), both the amplitude and oscillation of the SAM were increased by amyl nitrite inhalation, and were decreased by angiotensin II infusion. Correspondingly, the intensity of the musical murmur showed similar reaction. No findings suggestive of mitral valve prolapse or mitral regurgitation were found in any patients. Therefore, the oscillation of the SAM produced by blood ejected from the left ventricle was considered the source of the musical systolic murmur in these patients. 2. Two patients with redundant chordae tendineae had no clinical abnormalities except for chordal redundancy; therefore, the musical murmur in these cases was considered to be functional. Particularly, one of them was compatible in character with the so-called Still's murmur. In conclusion, the regular oscillation of the SAM may be the source of the musical systolic murmur, and they must be taken into consideration as part of the genesis of Still's murmur.

Adolescent↗

[Mitral regurgitation in mitral valve prolapse: its mechanisms and time course].

To clarify the mechanisms and time course of mitral regurgitation (MR) in mitral valve prolapse (MVP), the relationship between the timing of MR flow patterns on pulsed Doppler echocardiography and phase of mitral valve prolapse on two-dimensional echocardiography was investigated. 1. Thirty-seven patients with MVP were followed by pulsed Doppler echocardiography for one to six years with an average of 2.5 years. At the initial examination, the patients were classified in five subsets on the basis of the presence or timing of MR: 10 without MR, five with early systolic MR, one with mid-systolic MR, 15 with late systolic MR and six with pansystolic MR. During the follow-up period, the timing of MR did not change in 21 patients (three with no MR, five with early systolic MR, seven with late systolic MR and six with pansystolic MR). Various changes were observed in 16 patients, i.e., developments of late systolic MR from no MR in four, of pansystolic from no MR in three, from late systolic MR in five and from mid-systolic MR in one, and disappearing late systolic MR in three. 2. Mitral annular diameter and the prolapsing phase of 118 patients with MVP (44 without MR, eight with early systolic MR, 30 with late systolic MR and 36 with pansystolic MR) were examined by long-axis two-dimensional echocardiography. The mitral annular diameter in patients with early systolic MR was significantly less than that of other MR groups, and the diameter in patients with pansystolic MR was markedly increased. The timing of MR was determined according to the prolapsing phase and the grade of the prolapse and the systolic size of the mitral annulus. Six of the eight patients with early systolic MR first had early systolic prolapse of either mitral leaflet, and then the regurgitant gap of the mitral valve orifice was plugged by the prolapsing leaflet and/or the narrowed mitral annulus during mid-to-late systole. In 18 of the 30 patients with late systolic MR, the grade of prolapse of the mitral valve during mid-to-late systole was more severe, compared with that of early systole. The results of the present study indicated that the occurrence of MR in MVP is various in timing (early, mid-, late or pansystole) and shows various changes the during follow-up study, and that pulsed Doppler echocardiography allows phase analysis of MR in MVP.

Adult↗

[Mitral component of the first heart sound in complete left bundle branch block: the mechanism of the decreased intensity].

To clarify the mechanism of the reduced intensity of the mitral component of the first heart sound (IM) in complete left bundle branch block (LBBB), electrocardiograms, phonocardiograms, apexcardiograms and mitral valve echograms of 12 patients with LBBB (LBBB group) and 13 normal subjects (normal group) were simultaneously recorded. The first derivative of the apexcardiogram was also studied. One of the 12 patients had an intermittent LBBB. There was no significant difference in the P-Q interval between the two groups. The following results were obtained: 1. In the LBBB group; 1) The intensity of the IM, expressed as a ratio of the amplitude of the IM to that of the aortic component of the second heart sound (IIA) on the apical phonocardiograms, was significantly reduced except in one patient who had a relatively short P-Q interval. 2) The timings of the onset of the upstroke of the apexcardiogram and mitral valve closure were significantly and equally delayed. 3) The amplitude of the mitral valve echogram at the onset of the upstroke of the apexcardiogram (end-diastolic amplitude of the mitral valve) was significantly decreased. The closing velocity of the mitral valve was also decreased. 4) The amplitude ratio (H2/H1) and the rate of rise (A) of the apexcardiogram at the onset of the IM were significantly decreased. 2. The intensity of the IM, H2/H1 and A of the apexcardiogram at the onset of the IM were compared for three cases with nearly equal end-diastolic mitral valve amplitudes in each group. The intensity of the IM was apparently reduced in the LBBB group, compared with that of the normal group, and its intensity correlated inversely with H2/H1 and A. These results indicate that the reduced intensity of the IM in LBBB is caused mainly by the decreased amplitude of the mitral valve excursion at the onset of left ventricular contraction. An additional cause is the decreased tension on the closed mitral valve resulting from the slow rate of left ventricular pressure rise at the onset of the IM.

Adult↗