Biomedical subjects
Publications and source records attributed to M Hamada.
In vitro activities of benanomicins and their analogues against human immunodeficiency virus and fungi including Candida, Cryptococcus and Aspergillus, were examined. The free carboxyl group and at least one sugar moiety in the benanomicins were essential for their activities. Benanomicin A was most active and had low toxicity, and was selected as the best candidate for chemotherapy.
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A new antibiotic, dioxamycin (1) was isolated from the culture broth of the strain MH406-SF1, which was closely related to Streptomyces xantholiticus. This antibiotic was purified by countercurrent chromatography, column chromatography and preparative HPLC. The molecular formula of 1 was determined to be C38H40O15 by HRFAB-MS. The structure was determined by spectral analysis of 2D NMR; 1H-1H COSY, 13C-1H COSY, long range 13C-1H COSY (HMBC) and NOESY. The antibiotic is active in vitro against Gram-positive bacteria and some tumor cells. Dioxamycin is a benz[a]anthraquinone antibiotic related to capoamycin.
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Leuhistin has been isolated from the culture broth of Bacillus laterosporus BMI156-14F1 as part of a program designed to find microorganism-produced inhibitors of aminopeptidase M (AP-M). It was purified by use of column chromatography on Sepabeads SP206, Amberlite IRC-50, MCI gel CHP-20P and Sephadex G-10 and then isolated as colorless needles. Leuhistin inhibits AP-M strongly and it also inhibits AP-A and AP-B weakly. It is competitive with the substrate, and the inhibition constant (Ki) was 2.3 x 10(-7) M.
Poststatin, a new inhibitor of prolyl endopeptidase (PEP) was discovered in the fermentation broth of Streptomyces viridochromogenes MH534-30F3. It was purified by Diaion HP-20, Sephadex LH-20 and YMC-gel (ODS-A) column chromatography and then isolated as a colorless powder. Poststatin has the molecular formula C26H47N5O7. The IC50 value of poststatin against the PEP of partially purified porcine kidney was 0.03 microgram/ml. It has low acute toxicity. No deaths occured after iv injection of 250 mg/kg of this agent to mice.
MICs of 14 aminoglycoside antibiotics including 10 of those used clinically were determined against 50 strains of methicillin-resistant Staphylococcus aureus (MRSA) which had been isolated at a hospital in Osaka between 1986 and 1990. Arbekacin (ABK) inhibited the growth of all strains at less than or equal to 0.20-6.25 micrograms/ml, showing the most potent activities. Streptomycin showed good activities (1.56-6.25 micrograms/ml) against all strains except one resistant strain (greater than 100 micrograms/ml). Based on susceptibilities to kanamycin (98% resistant), tobramycin (84%), gentamicin (62%), amikacin (36%) and ABK (0%), MRSA strains were classified into 5 types; type 0 producing no aminoglycoside-modifying enzyme, type 1a producing APH(3'), type 1b producing AAD(4', 4''), type 2a producing APH (2'')/AAC(6') and APH(3'), and type 2b producing APH(2'')/AAC(6') and AAD(4', 4''). In addition to the aminoglycoside antibiotics, 13 known antibiotics including vancomycin (VCM) were found active against MRSA upon random screening. Taitomycin (0.013-0.050 micrograms/ml) was the most potent, and griseoluteins A and B (each 0.10-0.39 micrograms/ml), and macarbomycin (0.05-0.20 micrograms/ml) were more active than VCM (0.39-1.56 micrograms/ml). Novobiocin (less than or equal to 0.20-0.78 micrograms/ml) also showed good activities.
A 54 year-old female who had a history of hemoptysis was admitted to our hospital because of dyspnea on effort. Pulmonary arterial pressure was elevated and pulmonary arteriography showed multiple pulmonary arterial aneurysms and occlusion of the left upper lobe pulmonary artery. Systolic pulmonary arterial pressure was 110 mmHg when measured by continuous wave Doppler echocardiography. From the clinical and angiographical findings, we diagnosed this patient as having Hughes-Stovin's syndrome (forme fruste). 30 mg of diltiazem per day was initially used, and 80 mg was used thereafter. After 2 months follow up of the medication with diltiazem, systolic pulmonary arterial pressure decreased from 110 mmHg to 61 mmHg and clinical symptoms improved dramatically.
The influence of age and severity of hypertension on the blood pressure response to isometric handgrip exercise (IHG) was studied in essential hypertensive patients (n = 122). The change in blood pressure during IHG in elderly patients with isolated systolic hypertension (ISH) (n = 12) was also studied. Left ventricular hypertrophy due to hypertension was used as an index of the severity of hypertension. The change in systolic blood pressure (SBP) during IHG was markedly greater in essential hypertensives than in normotensive subjects (n = 36). Among hypertensive patients, the change in SBP increased with increasing severity of hypertension. This change in SBP was not influenced by age. The change in SBP during IHG in patients with ISH was significantly smaller than that in essential hypertensive patients and was similar to that in normotensive subjects in the elderly. These results demonstrate that age does not affect the increased blood pressure response to IHG in essential hypertensive patients but the greater the severity of hypertension, the greater the increase in SBP during IHG. Elderly patients with ISH do not have an enhanced blood pressure response to IHG.
To assess the difference between cardiovascular responses to treadmill exercise (TM) and those to bicycle ergometer exercise (EM) in provoking coronary spasm, we compared the ST segment shifts (elevation or depression) during TM and EM in 67 patients with vasospastic angina. Coronary artery spasm was demonstrated on angiography. Both TM and EM were performed on the same day during a medication-free period. For both tests, multistage, symptom-limited exercise protocols were used; EM in the morning and TM in the afternoon. The results obtained were as follows: 1. Rate-pressure products at peak exercise during TM and EM were similar. Systolic blood pressure levels at peak exercise were higher during EM than during TM (p < 0.01). The patients' heart rates at peak exercise were higher during TM than during EM (p < 0.01). Diastolic blood pressure levels at peak exercise were higher during EM than during TM (p < 0.05). 2. Exercise-induced ST elevation occurred more frequently with TM than with EM (19% vs 9%, p < 0.05). 3. Exercise-induced ST depression was provided in 27 patients during TM and in 13 during EM (40% vs 19%, p < 0.01). Among 45 patients without significant lesions, ST depression occurred in 19 during TM, but in only 7 during EM (42% vs 16%, p < 0.01). In conclusion, coronary spasm seemed to occur more frequently with TM than with EM. The mechanism causing such difference remains to be elucidated, however, we speculate that the difference between TM and EM as to enhanced autonomous nervous system activity and coronary perfusion exercise may be related to the difference in the incidence of coronary spasm.
To assess left ventricular (LV) diastolic function in patients with LV dysfunction, LV pressures (manometer tip) and biplane angiograms were analyzed for 27 patients with LV systolic dysfunction (EF < or = 0.45) (dilated cardiomyopathy or coronary artery disease) and 18 normal controls. LV volumes were obtained from frame-by-frame analyses of angiograms. LV relaxation was assessed by the time constant (T) of LV pressure decay. LV relaxation was impaired in patients with LV dysfunction, however, early diastolic filling assessed by the peak filling rate (PFR) and mean filling rate (MFR) during the rapid filling phase was maintained. Compared to the control group, early diastolic filling was significantly decreased in patients with LV dysfunction without mitral regurgitation (MR), but not in those with LV dysfunction with MR. In conclusion, although diastolic filling may be modified by MR, LV relaxation and early diastolic filling are essentially impaired in patients with LV dysfunction.
A patient with a mycotic aneurysm of the sinus of Valsalva and heart block secondary to infectious endocarditis was described. This 46-year-old man was admitted to our hospital on May 9, 1990, because of fever and progressive general malaise after extraction of a tooth. Physical examination on admission revealed blood pressure of 98/62 mmHg, pulse rate 96 per min, temperature 37.7 degrees C and respiration 35 per min. Auscultation of the heart revealed a grade 3/6 systolic murmur and a grade 2/6 diastolic murmur at the third left intercostal space. Chest radiograph showed mild cardiomegaly with moderate lung congestion. Electrocardiography revealed the first grade atrioventricular block. Echocardiography demonstrated vegetations on the aortic valve, and perforation of the non-coronary sinus of Valsalva. The prolapsed non-coronary sinus of Valsalva extended into the right atrium. Doppler echocardiography revealed a severe aortic regurgitant jet in the diastolic phase. We diagnosed the patient as having aortic regurgitation with a mycotic aneurysm of the non-coronary sinus of Valsalva due to infectious endocarditis. His condition remained severely ill despite intensive medical treatment. On May 14, 1990, aortic valve replacement and excision of the mycotic aneurysm were performed. The commissural portions of the aortic cusps were heavily thickened and calcified. The mycotic aneurysm was very fragile. During manipulating the mycotic aneurysm, the sinus accidentally perforated into the right atrium. The cardioaortic fistula was closed with a goretex patch. A demand pacemaker was implanted because of postoperative complete atrioventricular block.(ABSTRACT TRUNCATED AT 250 WORDS)
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Although X-ray crystallographic and NMR studies have been made on the adenylate kinases, the substrate-binding sites are not unequivocally established. In an attempt to shed light on the binding sites for MgATP2- and for AMP2- in human cytosolic adenylate kinase (EC 2.7.4.3, hAK1), we have investigated the enzymic effects of replacement of the arginine residues (R44, R132, R138, and R149), which had been assumed by Pai et al. [Pai, E. F., Sachsenheimer, W., Schirmer, R. H., & Schulz, G. E. (1977) J. Mol. Biol. 114, 37-45] to interact with the phosphoryl groups of AMP2- and MgATP2-. With use of the site-directed mutagenesis method, point mutations were made in the artificial gene for hAK1 [Kim, H. J., Nishikawa, S., Tanaka, T., Uesugi, S., Takenaka, H., Hamada, M., & Kuby, S. A. (1989) Protein Eng. 2, 379-386] to replace these arginine residues with alanyl residues and yield the mutants R44A hAK1, R132A hAK1, R138A hAK1, and R149A hAK1. The resulting large increases in the Km,app values for AMP2- of the mutant enzymes, the relatively small increases in the Km,app values for MgATP2-, and the fact that the R132A, R138A, and R149A mutant enzymes proved to be very poor catalysts are consistent with the idea that the assigned substrate binding sites of Pai et al. (1977) have been reversed and that their ATP-binding site may be assigned as the AMP site.
Serious complications such as angina pectoris and myocardial infarction in patients with anomalous origin of a coronary artery have been documented. However, this anomaly with dilated cardiomyopathy is very rare. We present the first case of anomalous origin of the left anterior descending coronary artery with dilated cardiomyopathy.
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