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Biomedical subjects

M Hamada

Publications and source records attributed to M Hamada.

At least 37 records · Page 2Linked to original sources

Nagstatin, a new inhibitor of N-acetyl-beta-D-glucosaminidase, produced by Streptomyces amakusaensis MG846-fF3. Taxonomy, production, isolation, physico-chemical properties and biological activities.

Nagstatin, a new inhibitor of N-acetyl-beta-D-glucosaminidase (NAG-ase) was discovered in the fermentation broth of Streptomyces amakusaensis MG846-fF3. It was purified by chromatography on Dowex 50W, Avicel and Sephadex LH-20 followed by the treatment of active carbon and then isolated as colorless powder. Nagstatin has the molecular formula of C12H17N3O6. It is competitive with the substrate, and the inhibition constant (Ki) was 1.7 x 10(-8) M.

Acetylglucosaminidase

Cyclooctatin, a new inhibitor of lysophospholipase, produced by Streptomyces melanosporofaciens MI614-43F2. Taxonomy, production, isolation, physico-chemical properties and biological activities.

Cyclooctatin has been isolated from Streptomyces melanosporofaciens MI614-43F2 as part of a program designed to find microorganism-produced inhibitors of lysophospholipase. It was purified by chromatography on silica gel, Capcell Pak C18 (HPLC) and Sephadex LH-20 followed by solvent extraction and then isolated as a colorless powder. Cyclooctatin has the molecular formula of C20H34O3. It is competitive with the substrate, and the inhibition constant (Ki) was 4.8 x 10(-6) M.

Animals

Production of bellenamine and new metabolites in a synthetic medium.

A streptomyces antibiotic, bellenamine has been produced in a simple synthetic medium consisting of D-galactose, dextrin, ammonium sulfate and calcium carbonate. Three new minor metabolites, N-(aminomethyl)succinamic acid, 1'-N-acetylbellenamine and D-beta-lysinamide have been isolated from the synthetic medium culture. They showed no antibiotic activity.

Ammonium Sulfate

Dethymicin, a novel immunosuppressant isolated from an Amycolatopsis. Fermentation, isolation, physico-chemical properties and biological activities.

In the course of screening for immunomodulators inhibiting the mixed lymphocyte culture reaction (MLCR), we found a novel immunosuppressant, dethymicin in mycelium of Amycolatopsis mediterranei MI710-51F6. From physico-chemical properties and biological activity it is different from immunosuppressants produced by microorganisms such as cyclosporins, FK506 and rapamycin. It inhibited immune responses in vitro and in vivo, and prolonged skin allograft in rats.

Actinomycetales

[Left ventricular diastolic function in apical hypertrophic cardiomyopathy].

To investigate left ventricular (LV) diastolic function in patients with apical hypertrophic cardiomyopathy (AHCM), we analyzed the LV cineangiograms (RAO 30 degrees) and pressures (tip manometer) in 11 patients with AHCM who had giant negative T waves on their electrocardiograms and "ace of spades" configurations on the LV angiograms. Ten patients with non-obstructive HCM (HNCM) and 10 normal subjects served as controls. LV volumes and instantaneous rates of LV volume changes were derived from frame-by-frame analyses of their LV angiograms. LV isovolumic relaxation was assessed according to the time constant (T) of LV pressure decay. LV diastolic distensibility was evaluated by plotting diastolic pressure-volume curves. There was no significant change in the LV systolic functions among these 3 groups. Compared with normals, LV end-diastolic pressure was equally elevated in AHCM and HNCM. The T of isovolumic pressure decay was significantly prolonged in AHCM and HNCM. LV early diastolic filling was maintained at the normal level in AHCM as assessed by the peak filling rate (PFR) during the rapid filling period and the time from end-systole to PFR. The LV diastolic pressure-volume relation shifted upwards in both AHCM and HNCM. In conclusion, impaired LV isovolumic relaxation and decreased diastolic distensibility, which are associated with HNCM, may also be present in AHCM.

Adult

[Clinical evaluation of myocardial protection by oxygenated crystalloid cardioplegic solutions with DBcAMP].

Possible enhancement of myocardial protection by adding DBcAMP and oxygenation of a crystalloid cardioplegic solution (CCS) was evaluated in a three group study. The patients having coronary bypass operation or valvular operation were divided into three groups, each consisting of 15 patients, and differing only in the type of CCS employed. Group I was protected by nonoxygenated CCS (PO2 190 mmHg, PCO2, 32 mmHg, pH 7.78, K 30 mmEq/L), Group II by adding DBcAMP to nonoxygenated CCS and Group III by adding DBcAMP to oxygenated CCS (PO2 790 mmHg, PCO2 26 mmHg, pH 7.87). Group III had significantly improved CI and double product (p less than 0.05) compared with Group II. However, CPK, CPK-MB, and myoglobin in the serum were similar in each group. Lactate and pyruvate ratio (L/P) in the coronary sinus bloods were improved to lower value after the pump than before the pump only in Group III. Base excess in the coronary sinus held on alkalosis after aortic declamp only in Group III. The refunction time was significantly shortest with Group III than with other groups (p less than 0.01, 0.05) and Group II was significantly shorter than Group I (p less than 0.05). It is concluded that oxygenation and adding DBcAMP to CCS are effectual for the myocardial metabolism and protect the myocardial damage during cardiac arrest.

Adult

[Tl-201 myocardial scintigraphic findings in patients with aortic regurgitation].

To evaluate the myocardial damage associated with aortic regurgitation, thallium-201 myocardial scintigraphy was performed in 13 patients with aortic regurgitation. The data obtained by thallium-201 single photon emission computed tomography were expressed as the extent score, and were compared with data by echocardiography. The results were as follows: 1. In 11 of 13 patients, there were moderate Tl defects in the distribution of bull's eye map, 80% in the apex, 50% in the inferior and lateral regions, 30% in the anterior region and 10% in the septal region. The mean extent score was 22.3 +/- 11.0%. 2. The extent score correlated with the increase in aortic regurgitant flow volume. The extent score according to the Sellers' classifications II, III, and IV was 13.8 +/- 3.7%, 20.1 +/- 9.8% and 31.9 +/- 10.2%, respectively. 3. There was a good negative correlation between the extent score and fractional shortening (r = -0.66, p < 0.01), however, no significant correlation was observed between the extent score and the left ventricular end-diastolic volume. These results suggest that Tl defects in patients with aortic regurgitation are mainly due to myocardial ischemia associated with a decrease in coronary perfusion pressure and that the extent score may sensitively reflect the severity of myocardial damage in cases with aortic regurgitation.

Adult

[A case of middle aged women with isolated left coronary ostial stenosis].

A-50-year-old woman was admitted to our hospital for the examination of exertional chest pain. She had no coronary risk factors. No hormonal disorders were observed. Physical and laboratory examinations revealed that she had not suffered from syphilis or aortitis syndrome or any other inflammatory diseases. An exercise electrocardiogram (Master's test) demonstrated ST segment depression in V3-6, II, III and a VF. On coronary angiography, a 75% stenosis of the left coronary ostial stenosis was found, but no abnormality was found in other arterial trees. The patient was diagnosed as having isolated coronary ostial stenosis. She underwent coronary bypass surgery from the aorta to the circumflex artery and the anterior descending coronary artery. She is now completely asymptomatic. A review of the literature together with this patient reveals the following characteristics of patients with isolated coronary ostial stenosis. Firstly, the patients are almost always middle aged woman with no coronary risk factors. Secondly, the involved coronary artery is the left main coronary artery, so its obstruction results in a serious condition. Therefore, though its pathogenesis remains to be determined, isolated left coronary ostial stenosis seems to be a distinct clinical entity.

Age Factors

Ectopic ACTH-producing adenocarcinoma of the stomach.

A 73-year-old female was admitted to our hospital because of weight loss and pretibial edema. Plasma levels of adenocorticotropic hormone (ACTH) and cortisol were elevated, and neither hormone showed circadian rhythm. Dexamethasone (2 mg for 2 days) failed to reduce the urinary excretion of 17-hydroxycorticosteroids and the plasma cortisol level. The stomach biopsy specimens showed a moderately-differentiated papillo-tubular adenocarcinoma. Computed tomography of the abdomen showed multiple metastases to the liver. Immunohistochemical staining of the autopsy specimens showed immunoreactive ACTH in the primary tumor cells of the stomach as well as the metastatic tumor cells of the liver. On the basis of the clinical, histological and immunohistochemical findings, we diagnosed this patient as having ectopic ACTH syndrome caused by adenocarcinoma of the stomach.

ACTH Syndrome, Ectopic

Low toxic derivatives of istamycin B: synthesis and preliminary evaluation.

3-O-Demethylistamycin B derived from istamycin B was one of the most potent aminoglycoside antibiotics against various bacteria. 3-O-Demethylistamycin B, however, showed considerable acute toxicity in mice. The authors attempted to prepare the derivatives of istamycin B having high potency and low toxicity. The selective N-acylation or N-amidination at the C-2 position of istamycin B could not improve the acute toxicity. The replacement of the amino group at the C-2 position of istamycin B by a hydroxyl group markedly decreased the acute toxicity. Among 2'-deamino-2'-hydroxyistamycins, 4-N-(beta-alanyl)-2'-deamino-3-O-demethyl-2'-hydroxyistamycin B0 (9d) showed good antibacterial activity against Gram-positive and Gram-negative bacteria and a low acute toxicity in mice.

Aminoglycosides

[Effect of enkephalinase inhibitor on endothelin-1 induced bronchoconstriction in guinea pigs].

Endothelin-1 (ET-1) is one of the most potent bronchoconstrictors in the guinea pig. The mechanism of its metabolism is still unclear. Phosphoramidon is known to be an enkephalinase inhibitor. We studied the effect of phosphoramidon on bronchoconstriction induced by ET-1. In the first in vitro study, a tracheal preparation was mounted in oxygenated Krebs-Ringer solution. The response was monitored by isometric transducer. Dose-response curves to ET-1 with or without phosphoramidon were obtained. Phosphoramidon potentiated ET-1 induced bronchoconstriction significantly. Next, the specific airway conductance (sGaw) was measured in conscious guinea pigs exposed to an aerosol of phosphoramidon or saline, followed by ET-1 aerosol inhalation. The ET-1 dose was increased by successively doubling the concentration. sGaw, after inhalation of phosphoramidon, was significantly reduced when exposed to ET-1. Phosphoramidon also potentiated ET-1 induced bronchoconstriction in vivo. Next, lung parenchymal tissues were prepared and placed in oxygenated Krebs-Ringer solution with or without phosphoramidon. ET-1 was added and incubated, and samples were injected into a high performance liquid chromatography column. Phosphoramidon inhibited an analysis of ET-1. These data suggest that enkephalinase plays a role in the break down of ET-1 in the airway of the guinea pig. Under the condition of decreased enkephalinase, ET-1 would potentiate bronchoconstriction.

Animals

New role of nerve growth factor--an inhibitory neuromodulator of adrenergic transmission.

In the present study, we investigated the effects of nerve growth factor (NGF) on norepinephrine (NE) release from peripheral sympathetic nerve endings of rat mesenteric artery. We made isolated mesenteric artery-intestinal loop preparations, by the modified method of Castelluci et al., from 4- and 8-week-old Wistar rats. NGF produced a dose-dependent inhibition of NE overflow from sympathetic nerve endings evoked by electrical nerve stimulation in the range of 0.1-10 ng/ml. Inhibition of NE overflow also occurred in the presence of a neuronal uptake blocker, desipramine (5 x 10(-8) M). NGF showed no effect on pressor response to exogenous NE (1 micrograms). These results suggest that NGF inhibits NE release from sympathetic nerve endings, in other words, NGF acts as an inhibitory neuromodulator of adrenergic transmission. This function of NGF might be considered as an inhibitory feedback mechanism against catecholamine-stimulated NGF synthesis.

Animals

Effect of disopyramide on systolic and early diastolic time intervals in patients with hypertrophic cardiomyopathy.

The present study clarified the effect of disopyramide on left-ventricular function in patients with hypertrophic cardiomyopathy (5 obstructive type: HOCM, 21 non-obstructive type: HNCM). The systolic and early diastolic time intervals were assessed 3 hours after a single oral administration of 100-mg disopyramide. The following parameters were evaluated at rest and after administration of disopyramide: 1) left-ventricular ejection time index (LVETI), 2) pre-ejection period index (PEPI), 3) the interval from aortic component of the second heart sound to mitral valve opening (IIA-MVO), and 4) the interval from MVO to O point of apexcardiogram (MVO-O). LVETI in HNCM did not change after disopyramide but that in HOCM was significantly shortened (P less than .05). PEPI in both HOCM and HNCM was significantly prolonged after administration of disopyramide. IIA-MVO time in both HOCM and HNCM was not influenced by disopyramide. MVO-O time in both HOCM and HNCM was significantly shortened after disopyramide. These results suggest that 1) shortening of LVETI in HOCM after disopyramide seemed to be due to the decrease in pressure gradient, 2) PEPI prolongation after disopyramide reflected the decrease in myocardial contractility, and 3) shortening of MVO-O time after disopyramide indicated the improvement of left-ventricular filling. The authors conclude that disopyramide may be an important new therapeutic agent in the treatment of patients with hypertrophic cardiomyopathy.

Adult

Abnormal development of cardiovascular systems in rat embryos treated with bisdiamine.

Administration of N,N'-bis(dichloroacetyl)-1,8-octamethylenediamine, bisdiamine, in pregnant Donryu rats on day 10 of gestation induces a high incidence of cardiovascular anomalies in fetuses. Bisdiamine administration induced aplasia of the sixth aortic arch artery, with both the right and left primitive pulmonary arteries being directly linked to the truncus, and resulting in four types of malformation of pulmonary arteries (PAs). When two primitive PAs shared a single root, the consequence was either pulmonary trunk hypoplasia, as is seen in tetralogy of Fallot, or type I persistent truncus arteriosus (PTA) as classified by Collet and Edwards. When root portions of two PAs did not fuse, either type II or type III PTA resulted. In controls, the right dorsal aorta (DA) between the right seventh intersegmental artery (IA) and the site where both DAs fuse degenerated and the left aortic arch (AA) and the right subclavian artery (SA) were formed. Bisdiamine administration induced two additional types of vascular anomalies. In one of these, the right DA between the right 4AA and the right 7IA degenerated and a left AA accompanied by an aberrant right SA resulted. In the other type, the left DA between the left 4AA and the left 7IA degenerated and a right AA accompanied by an aberrant left SA resulted. These results indicate that administration of bisdiamine induces malformation in the great blood vessels by disturbing persistency and degeneration of aortic arch arteries and DAs.

Abnormalities, Drug-Induced

Effect of hypothermic ischemia and reperfusion on calcium transport by myocardial sarcolemma and sarcoplasmic reticulum.

The effects of hypothermic ischemia and reperfusion on sarcolemma and sarcoplasmic reticulum Ca2+ transport were studied in vesicles isolated from rabbit hearts. Hypothermic global ischemia was produced by immersing hearts in saline at 4 degrees C for 3 h. Following hypothermic ischemia, reperfusion was carried out for 40 min using a Langendorff perfusion system for the working heart. Na+,K(+)-ATPase activity of sarcolemmal vesicles (SL), was not depressed by hypothermic ischemia nor by ischemia and reperfusion. The initial rate of Na(+)-Ca2+ exchange in SL vesicles was not depressed, but the maximum amount of Ca2+ uptake was increased both after hypothermic ischemia and after reperfusion. Ca2+ uptake activity of sarcoplasmic reticulum vesicles (SR) isolated from hearts subjected to hypothermic ischemia was slightly lower than that of control, and was further reduced following reperfusion. Ca(2+)-ATPase activity of SR was unaffected by hypothermic ischemia, while it was markedly lowered after reperfusion. Although the phosphoenzyme level in SR vesicles was slightly decreased, the turnover rate was reduced after reperfusion. Reperfusion injury thus took place mainly in SR while SL appeared to be tolerant to ischemia and reperfusion.

Adenosine Triphosphatases

Serum creatine kinase MM isoforms in hypertrophic cardiomyopathy.

1. To determine whether a persistent release of creatine kinase from the myocardium occurs in patients with hypertrophic cardiomyopathy, the activities of serum creatine kinase MM isoforms were measured in 22 patients with hypertrophic cardiomyopathy and in 14 normal control subjects. 2. Serum creatine kinase MB activity was significantly higher in patients with hypertrophic cardiomyopathy (7.8 +/- 3.8 i.u./l) than in normal control subjects (0.4 +/- 0.8 i.u./l; P less than 0.01). 3. Serum MMa, MMb and MMc activities in patients with hypertrophic cardiomyopathy were 19.4 +/- 4.1%, 26.7 +/- 2.5% and 33.5 +/- 7.0% of the total creatine kinase MM activity, respectively. These values for each isoform were significantly different from those in normal control subjects (11.3 +/- 3.0%, 21.5 +/- 4.4% and 40.7 +/- 7.0%, respectively). The MMa/MMc activity ratio was significantly higher in patients with hypertrophic cardiomyopathy (0.61 +/- 0.25) than in normal control subjects (0.30 +/- 0.10; P less than 0.01). 4. Our results indicate that a small amount of the myocardial tissue isoform of creatine kinase MM (MMa) is constantly released in many patients with hypertrophic cardiomyopathy.

Cardiomyopathy, Hypertrophic

Scintigraphic assessment of cardiac adrenergic innervation in patients with essential hypertension.

To assess the regional cardiac adrenergic innervation in patients with essential hypertension (EHT), simultaneous iodine-123 metaiodobenzylguanidine ([123I]MIBG) and thallium-201 (201Tl) myocardial imagings were performed in five patients with EHT, seven patients with hypertrophic cardiomyopathy (HCM), and seven normal subjects. Short axial images at rest were divided into five segments: anterior, septal, posterior, lateral, and apical segments. Percent regional uptake (%RU) of 201Tl except the septal segment in patients with EHT showed no significant difference. However, the %RU of [123I]MIBG at posterior, lateral, and apical segments was significantly lower than that at anterior and septal segments in EHT. This intraimage heterogeneity of [123I]MIBG was also observed in HCM. These results suggest that there is a difference in regional adrenergic innervation of the left ventricle with myocardial hypertrophy.

3-Iodobenzylguanidine