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Biomedical subjects

M Hamada

Publications and source records attributed to M Hamada.

At least 325 records · Page 18Linked to original sources

IC101, extracellular matrix antagonist produced by Streptomyces sp. MJ202-72F3. Production, isolation, structure determination and biological activity.

In our search for inhibitors of cell adhesion to components of extracellular matrix (ECM), fibronectin, laminin and collagen type IV, we succeeded in finding a novel cyclic hexadepsipeptide antibiotic, named IC101, which was isolated from cultured mycelium of Streptomyces albulus MJ202-72F3. It was purified by centrifugal partition chromatography, preparative reverse phase HPLC and Sephadex LH-20 and was obtained as a white powder. IC101 strongly inhibited cell adhesion to ECM components, suppressed immune responses in vitro and in vivo, and exhibited antimicrobial activity on Gram-positive bacteria.

Animals↗

Isolation and structure determination of novel phosphatidylinositol turnover inhibitors, piericidin B5 and B5 N-oxide, from Streptomyces sp.

In the course of a screening program for inhibitors of epidermal growth factor (EGF)-induced phosphatidylinositol turnover in human epidermoid carcinoma cell line A431, we discovered two novel compounds of the piericidin family from the culture broth and mycelia of a Streptomyces strain MJ288-OF3. We named them piericidin B5 and B5 N-oxide. By NMR and mass spectrometric analyses, the molecular formulas of piericidin B5 and B5 N-oxide were determined to be C27H41NO4 (MW 443) and C27H41NO5 (MW 459), respectively. Piericidin B5 and B5 N-oxide inhibited phosphatidylinositol turnover of A431 cells with IC50S of 10.0 micrograms/ml and 1.1 micrograms/ml, respectively.

Anti-Bacterial Agents↗

Delaminomycins, novel nonpeptide extracellular matrix receptor antagonist and a new class of potent immunomodulator. I. Taxonomy, fermentation, isolation and biological activity.

In order to develop a new class of immunomodulator we have searched for a low molecular weight inhibitors of cell adhesion to components of extracellular matrix (ECM), fibronectin (FN), laminin (LM) and collagen type IV (CL), and succeeded to find a group of novel antibiotics, named delaminomycins. Delaminomycins were isolated from the mycelium and cultured broth of Streptomyces albulus MJ202-72F3. It was purified by use of centrifugal partition chromatography (CPC), preparative reverse phase HPLC and Sephadex LH-20 and was obtained as a white powder. Delaminomycins with inhibitory activity for cell adhesion to ECM components suppressed immune responses in vitro and in vivo and exhibited antimicrobial activity on Gram-positive bacteria.

Adjuvants, Immunologic↗

[Antigen-induced dynamic alterations of endothelin receptors--guinea pig lung tissues].

Endothelins (ETs) are a family of peptides with potent constrictive activity in vascular and treacheal smooth muscle. The lung tissues are abundant in these peptides and their receptors; the peptides are produced by endothelial cells and airway epithelial cells, while its receptor is mainly located on smooth muscle. Therefore, it has been proposed that endothelins act in a paracrine fashion on nearby smooth muscle, thus regulating its tone. However, little is known about its physiological and pathological roles in pulmonary functions. We hypothesized that ET plays an important role in bronchoconstriction elicited by antigen challenge. In order to test this hypothesis, we investigated tracheal contractile activities and ET-receptors by employing an animal model in guinea pigs. Here, we report that guinea pigs who were sensitized followed by multiple challenges with the antigens had alterations of ET receptor(s) with respect to number and affinity.

Animals↗

Is left ventricular systolic dysfunction in hypertensive patients with heart failure normalized by long-term antihypertensive therapy?

The critical left ventricular (LV) mass when hypertensive heart failure appears, and whether LV dysfunction in hypertensives with heart failure is normalized by long-term antihypertensive therapy were investigated. LV dimension, LV mass, LV mass index, LV ejection time (LVET) and pre-ejection period (PEP) were measured in 27 normal subjects and 56 essential hypertensives, the latter divided into three groups: group I, without LV hypertrophy; group II, with LV hypertrophy; and group III, with hypertensive heart failure. LV mass and LV mass index were 135.0 +/- 23.8 g and 85.8 +/- 11.7 g/m2, respectively, in normal controls, 133.0 +/- 30.8 g and 82.0 +/- 18.4 g/m2 in group I, 222.3 +/- 38.0 g and 136.1 +/- 19.9 g/m2 in group II, and 422.0 +/- 30.3 g and 235.7 +/- 19.6 g/m2 in group III of essential hypertensives. The upper limits of LV mass and LV mass index in group II (mean + 2SD) were about 300 g and 180 g/m2, respectively. Significant shortening of LVET was observed only in group III, but PEP was prolonged with an increase in LV mass. LV diastolic dimension and PEP were not normalized by long-term antihypertensive therapy (mean: 16 months). These results indicate that the critical LV mass marking the transition from non-failing hypertrophied left ventricle to failing ventricle associated with essential hypertension is about 300 g, or LV mass index of 180 g/m2, and that LV dilatation and depressed myocardial contractility in essential hypertensives with a past history of congestive heart failure were not normalized by chronic antihypertensive therapy.

Adult↗

Ewing's sarcoma: evaluation of chemotherapy in 17 cases.

Seventeen patients with Ewing's sarcoma were divided into 3 groups according to treatment. Ten patients were treated with complete chemotherapy; 9 with VACA protocol, composed of vincristine, actinomycin-D, cyclophosphamide and doxorubicin, and the remaining 1 with T-11 protocol. Four were given incomplete VACA protocol, and another 3 received no chemotherapy. Clinical results were evaluated in the three treatment subgroups described above. All patients without systematic chemotherapy died from lung metastasis within 1 year of the initial treatment. Three of 4 patients who were given incomplete chemotherapy died after a mean survival period of 17.7 months, and one developed cancerous pleuritis after 38 months. In the group receiving complete systematic chemotherapy, 5 of 10 patients are alive, and 2 have been disease-free for more than 3 years. Distant metastasis is likely when viable cells persist at the site of the primary tumor, even if the tumor size has been considerably reduced by preoperative chemotherapy. Therefore, immediate initiation of intensive chemotherapy and maintenance for the full course of therapy can improve the prognosis of Ewing's sarcoma.

Adolescent↗

Adjuvant chemotherapy for patients with soft tissue sarcoma.

Forty patients with soft tissue sarcoma (Enneking's stage I and II) were treated in our department between 1965 and 1992. We administered VACA regimen (composed of vincristine, actinomycin-D, cyclophosphamide, and doxorubicin) to 14 of 40 patients. Among 40 patients, the 5-year survival rate was 56% in 14 patients with chemotherapy and 39% in 26 without chemotherapy (p < 0.02). In 32 patients of Stage II, the 5-year survival rate was 40% in 11 patients with chemotherapy and 31% without chemotherapy (p < 0.05). The improvement of the survival rate was due to delay in the development of lung metastases (chemotherapy group: 21.2 months after first visit, non-chemotherapy group: 9.4 months) and prolongation of the survival period after metastases (chemotherapy group: 26 months, non-chemotherapy group: 7.4 months).

Adolescent↗

Cardioplegic effect of University of Wisconsin solution on hypothermic ischemia of rat myocardium assessed by mitochondrial oxidative phosphorylation.

The effectiveness of the University of Wisconsin solution and the Collins' M solution for preservation of rat hearts was compared by examining histologic appearance, tissue water content, and mitochondrial respiratory functions after prolonged hypothermic storage and subsequent heterotopic transplantation. Survival of transplanted hearts after 5 days of reperfusion was markedly lowered by storage in Collins' M solution for 15 hours. Hearts stored in University of Wisconsin solution for 10 hours showed no increase in myocardial necrosis after 5 days of reperfusion, whereas hearts stored in University of Wisconsin solution for 15 hours and Collins' M solution for 10 and 15 hours showed a significant increase in tissue necrosis. University of Wisconsin solution reduced tissue swelling during hypothermic storage, whereas Collins' M solution did not cause such reduction. The yield of mitochondrial protein after reperfusion was significantly decreased by storage in either solution, especially after 15 hours in Collins' M solution. Mitochondrial oxidative phosphorylation was significantly inhibited by storage, especially by storage in Collins' M solution and subsequent reperfusion. These results indicate that myocardial injury, after prolonged ischemia and reperfusion, results in a decrease in functionally and structurally intact mitochondria that is dependent on preservation conditions. University of Wisconsin solution protects isolated hearts against ischemia and reperfusion injury possibly by preventing cellular and mitochondrial deterioration.

Adenosine↗

[Effect of Na-L-glutamate on mitochondrial function of ATP synthesis after prolonged preservation in rat heart].

We studied the effect of Na-L-glutamate (Glu) on mitochondrial functions of ATP synthesis after prolonged hypothermic preservation of rat hearts. We divided isolated rat hearts into the following three groups: group A, hearts without immersion as control; group B, hearts immersed in Euro-Collins solution (E-C) without Glu for 24 h at 4 degrees C; group C, hearts immersed in E-C with 10mM Glu for 24 h at 4 degrees C. Number of each group used was 6. Mitochondrial functions of ATP production were determined by measuring respiratory control index (RCI). P/O ratio and state III respiration rate. The ability of ATP production (oxidative phosphorylation rate, OPR) was calculated. RCI and P/O ratio of groups B and C were significantly lower than those of group A. RCI and P/O ratio of group C were significantly higher than that of group B. S3 rates of groups B and C were significantly lower than those of group A. S4 rate of group B was significantly higher than those of groups A and C. OPRs of groups B and C were significantly lower than that of group A. OPR of group C was significantly higher than that of group B. We concluded that Na-L-glutamate effectively protected mitochondrial functions to synthesize ATP during prolonged hypothermic preservation.

Adenosine Triphosphate↗

[A case of intrapulmonary lymph node with silicotic nodules in a patient with idiopathic interstitial pneumonia].

A 61-year-old man was admitted to our hospital on October 8, 1991 because of abnormal shadows on chest X-ray at annual checkup at his company. Chest X-ray and CT on admission showed diffuse reticular shadows in bilateral lower lung fields and a nodular opacity approximately 10 mm in diameter in the right lower lung. Since transbronchial lung biopsy was not diagnostic, an open lung biopsy was performed on October 28, 1991. The lung specimens showed diffuse pulmonary fibrosis compatible with usual interstitial pneumonia and an intrapulmonary lymph node containing silicotic nodules. Only 29 cases (including the present case) of intrapulmonary lymph nodes have been reported. Although the causes of intrapulmonary lymph nodes are not clear, smoking is considered to play an important role in the development of pulmonary lymphoid tissue. In our case, the intrapulmonary lymph node contained silicotic nodules. Only several case have been reported to have silicotic nodules in the lymph nodes. As suggested by Kradin, they may be induced by relatively low levels of exposure to dust. Our case also had pulmonary fibrosis (IIP), and is the first reported case of intrapulmonary lymph node associated with IIP. Although it is difficult to determine these two diseases occurred coincidently or not, it is possible that a low level of dust exposure may have contributed to both silicotic nodules in the lymph node and IIP.

Adult↗

ET-1 induced bronchoconstriction in the early phase but not late phase of anesthetized dogs is inhibited by indomethacin and ICI 198615.

Intratracheally injected or aerosolized ET-1 induced quick and long-lasting bronchoconstriction of anesthetized mongrel dogs, thus increasing respiratory resistance(Rrs) with concomitantly decreasing dynamic compliance(Cdyn). As collateral resistance(Rcs) was measured postexposure to aerosolized ET-1 using wedged bronchoscope technique, ET-1 increased Rcs in a dose and time dependent manner. The increase attained maximal in 2 min and then, gradually declined. When the dogs were pretreated with the intravenous injection of 0.1 micrograms/kg ICI 198615, an inhibitor of lipoxygenase, the constrictive response was slowed down. Essentially similar results were also observed with the intravenous injection of 5 mg/kg indomethacin. Our observations suggest that the early phase of the ET-1 induced bronchoconstriction is mediated by eicosanoid metabolites.

Anesthesia, Intravenous↗

Effect of disopyramide on left ventricular diastolic function in patients with hypertrophic cardiomyopathy: comparison with diltiazem.

Left ventricular diastolic function before and after the administration of disopyramide (100 mg) or diltiazem (30 mg) was assessed in 10 patients with nonobstructive type hypertrophic cardiomyopathy. Left ventricular diastolic function was assessed by Doppler echocardiography. The peak early (E) and late (A) diastolic flow velocities and E/A ratio (E/A) were measured. Three hours after the administration of disopyramide, blood pressure did not significantly change, but heart rate was decreased significantly (p less than 0.01). Disopyramide increased the E velocity and E/A ratio from 43.8 +/- 15.0 cm/sec to 51.3 +/- 16.1 cm/sec and from 0.71 +/- 0.20 to 1.00 +/- 0.24 (each p less than 0.01), respectively, and decreased the A velocity from 63.9 +/- 18.5 cm/sec to 52.1 +/- 14.9 cm/sec (p less than 0.01). Diltiazem increased the E velocity and E/A ratio from 42.8 +/- 12.5 cm/sec to 46.4 +/- 13.4 cm/sec (p less than 0.05) and from 0.74 +/- 0.21 to 0.96 +/- 0.28 (p less than 0.01), respectively, and decreased the A velocity from 60.6 +/- 16.4 cm/sec to 50.2 +/- 15.6 cm/sec (p less than 0.01). These results indicate that disopyramide improved left ventricular diastolic filling in hypertrophic cardiomyopathy, and its effect was similar to that of diltiazem.

Adult↗

Serial change of iodine-123 metaiodobenzylguanidine (MIBG) myocardial concentration in patients with dilated cardiomyopathy.

Serial change of the metaiodobenzylguanidine iodine-123 (123I-MIBG) myocardial concentration was investigated in patients with dilated cardiomyopathy (DCM). Eight DCM patients and 6 control subjects were examined. After the injection of thallium-201 and 123I-MIBG, planar chest images were obtained simultaneously for both tracers in every 30-60 min over 5 h. Serial changes of myocardial uptake ratio (MUR) were compared for both tracers. In DCM, the initial MUR of 123I-MIBG did not differ significantly from that of the controls. The washout of 123I-MIBG from the myocardium, however, was significantly increased in DCM. In particular, the decrease in the early phase (15-45 min) was significantly larger in DCM than in the controls (21.2% +/- 7.5% vs. 5.3% +/- 4.0%, P less than 0.01), showing a significant negative correlation with the left ventricular ejection fraction (r = -0.72 P less than 0.05). For 201Tl, neither the initial MUR nor the washout rate different significantly between the two. Thus, an early rapid decrease of the 123I-MIBG myocardial concentration might characterize DCM and reflect the severity of this disease.

3-Iodobenzylguanidine↗

A large conus artery in patients with hypertrophic cardiomyopathy.

We retrospectively analyzed coronary arteriograms in 66 patients with hypertrophic cardiomyopathy (HCM) who underwent coronary arteriography. Four of these patients showed a large conus artery supplying the interventricular septum, and the characteristics of their echocardiograms revealed a marked interventricular septal hypertrophy. It is suggested that in some patients with HCM, the conus artery may develop in compensation for the relatively reduced coronary blood flow which is due to the hypertrophied myocardium.

Adult↗

Effects of sublingually administered nifedipine on left ventricular isovolumic relaxation, diastolic filling, and distensibility in patients with chronic coronary artery disease.

The acute effects of nifedipine (20 mg) on left ventricular diastolic function were investigated in 16 patients with chronic coronary artery disease by measuring left ventricular pressure with a manometer-tipped catheter and by measuring volume with cineangiography. Heart rates were maintained by right atrial pacing. Left ventricular peak systolic pressure (-15%; p less than 0.01 vs control) decreased significantly. With afterload reduction, left ventricular ejection fraction (+11%; p less than 0.01) increased. There was no significant change in left ventricular end-diastolic pressure. The diastolic peak filling rate of left ventricular volume significantly increased (+36%; p less than 0.05), whereas the time from end-systole to the peak filling rate remained unchanged. Administration of nifedipine did not improve left ventricular relaxation as assessed by the isovolumic pressure decay. There was also no significant change in the left ventricular diastolic pressure-volume relationship. We conclude that nifedipine improves left ventricular systolic function with afterload reduction but has little or no effect on left ventricular diastolic properties in patients with chronic coronary artery disease.

Administration, Sublingual↗

Osteochondritis dissecans of the humeral head.

A rare case of osteochondritis dissecans (OCD) occurring in the humeral head is presented. As there are only six available records in the literature concerning OCD in the humeral head, clinical features, treatment, and etiology of OCD involvement of this anatomical part remains unclear. These points are discussed on the basis of the previous cases and ours. Osteochondritis dissecans of the humeral head commonly affects middle-aged and young males rather than females. The prevalent location of involvement is the anterosuperior aspect of the humeral head. We propose that repetitive microtrauma is one of the important causes of OCD in the humeral head. Moreover, we suggest that the most authentic treatment for OCD with a partial detached osteochondral fragment is removal of this fragment and drilling.

Arthroscopy↗