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Biomedical subjects

M Hamada

Publications and source records attributed to M Hamada.

At least 73 records · Page 4Linked to original sources

A 25-year-old patient with low cardiac risk factors having a combination of variant angina and severe coronary arterial lesions--a case report.

A 25-year-old man with low cardiac risks underwent coronary arteriography because of chest pain at rest. His only risk factors for coronary artery disease was smoking. Both right and left coronary arteries were ectatic and the left anterior descending artery was obstructed. In the acetylcholine provocation test, the left circumflex coronary artery showed severe constriction. Thus, this patient was diagnosed as having a combination of variant angina and occlusive coronary artery disease.

Adult↗

Aortic distensibility is closely related to the progression of left ventricular hypertrophy in patients receiving hemodialysis.

Aortic stiffening and left ventricular hypertrophy are believed to be major determinants for the prognosis of patients with end-stage renal disease. However, the relationship between left ventricular hypertrophy and aortic stiffness remains to be determined. Echocardiographically determined parameters and aortic distensibility determined with cine magnetic resonance were evaluated in 21 patients undergoing chronic hemodialysis. Hemodynamic variables measured at the beginning of the study were compared with those measured after 28 months. Aortic distensibility determined at the descending aorta was markedly lower in patients undergoing hemodialysis than in healthy control subjects. During the follow-up period, blood pressure and hemodynamic variables, including left ventricular mass index, remained unchanged. However, multiple regression analysis indicated that aortic distensibility independently contributed to the left ventricular mass index and to the change in left ventricular mass index between baseline and after 28 months. Baseline left ventricular mass index negatively correlated to aortic distensibility (r = -0.74, p < 0.0001), and the changes in left ventricular mass index positively correlated to aortic distensibility (r = 0.52, p < 0.05). Our study demonstrates that aortic distensibility at the descending aorta is a predictable marker for the development or regression of left ventricular hypertrophy. Therefore, patients with end-stage renal disease must be treated with appropriate drugs to improve aortic distensibility.

Aged↗

Coronary spastic angina induced by anticholinesterase medication for myasthenia gravis--a case report.

Myasthenia gravis (MG) is characterized by weakness of skeletal muscles because of a decrease in the number of available acetylcholine receptors at neuromuscular junctions. Anticholinesterase medication is widely used to treat MG, but muscarinic side effects sometimes appear and limit the drug usage. To their knowledge, the authors present the first case of coronary spastic angina quite possibly induced by anticholinesterase medication to treat MG. The appearance of coronary spastic angina in the present case is likely mediated through the increase of acethylcholine by anticholinesterase medication.

Aged↗

Apical hypertrophic cardiomyopathy associated with life-threatening paroxysmal atrial flutter with a slow ventricular response: a case report.

A 58-year-old male patient had apical hypertrophic cardiomyopathy (HCM) associated with a life-threatening tachycardia due to atrial flutter. Following palpitation and dyspnea for 2-3 h, he became unconscious because of circulatory catastrophe, but was fully resuscitated. An electrocardiogram recorded just before the loss of consciousness revealed atrial flutter at a rate of 260 beats/min with a 2:1 ventricular response. He was diagnosed as having apical HCM based on the echocardiographic and left ventriculographic findings. Atrial stimulation at a rate of 150 pacings/min for 1 min caused a marked drop in systemic systolic blood pressure from 170 to 120 mmHg. The patient was treated with 150 mg of cibenzoline per day to prevent supraventricular tachyarrhythmias and to improve left ventricular diastolic function. At the time of the recent follow-up at 2 and a half years, he felt quite well.

Atrial Flutter↗

Effect of beta-blocker on left ventricular function and natriuretic peptides in patients with chronic heart failure treated with angiotensin-converting enzyme inhibitor.

To evaluate whether or not beta-blockers can improve the condition of patients with heart failure treated with a combination of diuretics, digitalis and angiotensin-converting enzyme inhibitor (ACEI), 52 patients with chronic heart failure who have been treated with ACEI for more than 6 months were enrolled. They were divided into 2 groups: 26 patients continued the same therapy another 6 months or more (group A), and 26 patients were given oral metoprolol for 6 months or more, in addition to the ACEI (group B). Echocardiographic parameters and atrial and brain natriuretic peptides (ANP, BNP) were measured. The left ventricular dimensions at end-diastole and end-systole were significantly decreased and fractional shortening was significantly increased in group B after 6 months' treatment with the beta-blocker, but these parameters remained unchanged in group A. Plasma levels of both ANP and BNP were significantly decreased in group B, but remained unchanged in group A. These results indicate that concomitant beta-blocker therapy can improve left ventricular function and attenuate plasma ANP and BNP levels in patients with chronic heart failure treated with ACEI.

Adrenergic beta-Antagonists↗

Effects of coronary blood flow on left ventricular function in essential hypertensive patients.

To elucidate the mechanism of left ventricular dysfunction associated with left ventricular hypertrophy in hypertension, coronary blood flow (CBF) and left ventricular mass (LVM) were measured in 62 patients with essential hypertension (mean age, 54 +/- 13 years) and 22 normotensive control subjects (mean age, 57 +/- 13 years). According to the indicator fractionation principle, CBF/cardiac output (CO), estimated on the basis of the ratio of myocardial uptake/total injected dose of thallium-201 (% cardiac uptake), was measured. CBF and CBF per 100 g of myocardium (unit CBF) were calculated according to the following formulas: CBF=% cardiac uptake x CO, and unit CBF=(CBF/LVM) x 100, where CO and LVM are echocardiographically determined. Midwall fractional shortening (FS) and isovolumic relaxation time (IRT) were calculated as the indices of systolic and diastolic functions. CBF was greater in hypertensives than in controls (218.2 +/- 74.0 vs. 187.4 +/- 40.4 ml/min, p < 0.05), though unit CBF was smaller in hypertensives than in controls (99.1 +/- 22.0 vs. 141.2 +/- 31.6 ml/min/100 g, p < 0.0001). Multiple regression analyses showed that unit CBF was the most potent predictor of both midwall FS and IRT. A positive correlation was found between midwall FS and unit CBF (r=0.669, p < 0.0001), and a negative correlation between IRT and unit CBF (r=-0.579, p < 0.0001). In conclusion, myocardial ischemia reflected by the decrease in unit CBF may be closely related to left ventricular dysfunction in patients with essential hypertension.

Adult↗

Cardiomyocyte functions couple with left ventricular geometric patterns in hypertension.

Previous studies have suggested the prognostic significance of left ventricular (LV) geometric patterns in essential hypertension. However, the relation between cardiomyocyte functional changes and LV geometric patterns has not been clarified. This study was designed to assess the morphological and functional changes in isolated myocytes derived from different LV geometric patterns in hypertension. After 2-3 weeks of a high-salt (8%) diet from the age of 6 weeks, 20 Dahl salt-sensitive (DS) rats were classified into the following three groups on the basis of an echocardiographically determined LV mass index and the relative wall thickness: concentric hypertrophy (11), eccentric hypertrophy (4), and concentric remodeling (5). Ten Dahl salt-resistant (DR) rats served as controls. In vivo LV functions were assessed based on echocardiographic measurements. We examined ventricular myocytes isolated from all groups. To evaluate the force-frequency relation, cardiomyocytes isolated from all groups were paced at stimulation rates of 0.3, 0.5, 1.0, 2.0, and 3.0 Hz. Concentric hypertrophy and eccentric hypertrophy groups exhibited an increase in myocyte width but no changes in the length. Concentric hypertrophy and concentric remodeling groups demonstrated in vivo LV dysfunction. In addition, DS rats, especially these with concentric hypertrophy, demonstrated impaired frequency responses in terms of both myocyte contraction and relaxation compared with DR rats. This impaired force-frequency relationship was especially remarkable at high frequencies. These findings suggest that the structural and functional changes in cardiomyocytes are closely related to the LV geometric pattern and may contribute to a different prognosis according to different geometric patterns.

Animals↗

Time-course changes in left ventricular geometry and function during the development of hypertension in Dahl salt-sensitive rats.

Serial changes of left ventricular (LV) geometry and function during the development of hypertension were studied in 50 Dahl salt-resistant (DR) and 88 Dahl salt-sensitive (DS) rats fed an 8% NaCl diet beginning at the age of 6 weeks. Echocardiography at 6, 8, 11, 13, 14, 15, and 18 weeks and in vivo invasive hemodynamic determination at 6, 8, 11, 14, and 18 weeks were performed. After 11 weeks, 33 DS rats were observed for survival analysis. The survival analyses showed that the incidence of death was 57.6% due to heart failure, 27.3% due to stroke, and 15.2% due to sudden death. However, death in the early stages of hypertension was due almost entirely to sudden death or stroke. A high value of relative wall thickness (RWT) and a small end-diastolic dimension were predictive of sudden death and stroke, but LV mass (LVM) was not. Concerning the change in LV geometric patterns, LVM continued to increase to 18 weeks. The RWT increased or remained at a plateau up to 13 weeks, and then progressively decreased after 13 weeks. In contrast, LV function was hyperdynamic between 8 and 11 weeks when compared to DR rats. However, after 13 weeks, all hemodynamic variables of DS rats deteriorated progressively, and all DS rats died of heart failure. Thus, our study indicates that the cardiovascular events associated with the progression of hypertension vary widely according to the stage of hypertension and that RWT is more sensitive in predicting LV conditions than LVM in hypertension.

Animals↗

The effect of coronary vasospasm on the direction of ST-segment deviation in patients with both hypertrophic cardiomyopathy and vasospastic angina.

BACKGROUND: There has been no report of ECG changes during anginal attacks in patients with coexistent hypertrophic cardiomyopathy (HCM) and vasospastic angina. STUDY OBJECTIVES: To elucidate the change in ST-segment during anginal attacks in patients with coexistent HCM and vasospastic angina (the HCM group) in comparison with that of patients with vasospastic angina and no left ventricular hypertrophy (the non-HCM group). DESIGN: Retrospective study. PATIENTS: Twelve patients in the HCM group, and 28 patients in the non-HCM group. MEASUREMENTS: The direction of ST segment shift, either ST-segment elevation or depression, on the ECGs recorded during vasospastic anginal attacks with severe vasoconstriction in the epicardial coronary artery after intracoronary injection of acetylcholine. RESULTS: Age, male gender, and distribution of coronary arteries in which the vasospasm occurred were similar between the two groups. Collateral circulation to the affected arteries was absent in all the study patients. The prevalence of anginal attacks associated with ST-segment elevation was 2.7 times higher in the non-HCM group than in the HCM group (51. 5% [17 of 33 attacks] vs 18.8% [3 of 16 attacks], respectively; p = 0.03). CONCLUSIONS: In the HCM group, myocardial ischemia associated with a transmural injury pattern seen on the ECG, which is represented as ST-segment elevation, seldom develops during vasospastic anginal attacks because of marked left ventricular hypertrophy.

Acetylcholine↗

Gastrointestinal stromal tumors of the small intestine that expressed c-kit protein.

We report two patients with gastrointestinal stromal tumors (GISTs) of the small intestine that expressed c-kit protein (CD117). One was a 68-year-old woman with epigastralgia and vomiting. A submucosal tumor of the upper jejunum was detected, and partial resection was carried out. The histology revealed a GIST negative for CD34 but positive for CD117. The other was a 42-year-old woman with progressive anemia, melena and lower abdominal pain. Intussusception was detected, and a partial resection was carried out. A submucosal tumor of the lower jejunum was noted. The histology revealed a GIST positive for both CD34 and CD117.

Adult↗

Tubelactomicin A, a novel 16-membered lactone antibiotic, from Nocardia sp. I. Taxonomy, production, isolation and biological properties.

A novel 16-membered lactone antibiotic named tubelactomicin A was isolated from the culture broth of an actinomycete strain. The producing organism, designated MK703-102F1, was identified as a member of Nocardia. Tubelactomicin A was isolated from the culture broth by Diaion HP20 absorption, ethyl acetate extraction, silica gel and Sephadex LH-20 column chromatographies and centrifugal liquid-liquid partition chromatography (CPC). Tubelactomicin A showed strong activity against acid-fast bacteria including the drug-resistant strains.

Anti-Bacterial Agents↗

Migrastatin, a new inhibitor of tumor cell migration from Streptomyces sp. MK929-43F1. Taxonomy, fermentation, isolation and biological activities.

A new compound, migrastatin, was isolated from a cultured broth of Streptomyces sp. MK929-43F1, as an inhibitor of tumor cell migration. It was purified by column chromatographies on silica gel and Sephadex LH-20 and HPLC. Migrastatin has the molecular formula of C27H39NO7 consisting of 14-membered macrolide and glutarimide moiety. It inhibited spontaneous migration of human esophageal cancer EC17 cells. Migration inhibitory activity of migrastatin was not dependent on cytotoxicity or inhibition of protein synthesis.

Animals↗

Melleolides K, L and M, new melleolides from Armillariella mellea.

Three new sesquiterpenoid aromatic esters designated melleolides K (1), L (2) and M (3) were isolated from the cultured mycelia of Armillariella mellea (Vahl. ex Fr.) Karst. Structures of these compounds were determined on the basis of various NMR spectral data, chemical transformations and X-ray analysis. Compounds 1, 2 and 3 showed antimicrobial activities.

Agaricales↗

ABC transporter genes, kasKLM, responsible for self-resistance of a kasugamycin producer strain.

We previously reported that a 7.6-kb DNA fragment from Streptomyces kasugaensis M338-M1, a kasugamycin (KSM) producer, included KSM acetyltransferase gene (kac338) and some other genes possibly involved in KSM biosynthesis. As an extension of that study, a 10-kb SacI-KpnI DNA fragment, located approximately 5-15-kb upstream of kac33, was cloned and a 4.2-kb SacI-EcoRI fragment therefrom was sequenced, revealing one incomplete (designated ORF J) and three complete open reading frames (designated kasK, kasL and kasM). The coding frames of kasK, L and M overlap one another with terminator/initiator ATGA sequence. RT-PCR analysis of a DNA region including kasKLM indicated the presence of one transcript that is long enough to span the three genes. The kasK gene potentially encodes an ATP-binding protein of the ATP-binding cassette (ABC) transporter superfamily. Homology search for the deduced KasK protein shows similarity to other ABC transporters involved in self-resistance of a mithramycin and possibly doxorubicin producer strain. The kasL and kasM genes encode different integral membrane proteins, both having six putative transmembrane helices. An expression plasmid for kasKLM (pTV-KLM) was constructed and these genes were expressed in E. coli JM 109, which had been sensitive to KSM. The transformant acquired resistance to KSM, suggesting that KasK, L and M proteins as a set in S. kasugaensis M338-M1 pump out KSM to protect the producer from its toxic metabolite.

ATP-Binding Cassette Transporters↗

MK800-62F1, a new inhibitor of apoptotic cell death, from Streptomyces diastatochromogenes MK800-62F1. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activity.

A new compound, MK800-62F1, was isolated from a cultured broth of Streptomyces diastatochromogenes MK800-62F1. It inhibited H2O2-induced apoptosis in human small cell lung carcinoma Ms-1 cells as well as in human T-cell leukemia Jurkat cells. In addition, MK800-62F1 also inhibited camptothecin-induced apoptosis in Jurkat cells, which was mediated by intracellular H2O2 generation. MK800-62F1 did not exhibit antioxidative activity in vitro, suggesting that inhibition of apoptosis by MK800-62F1 was not due to the scavenging of H2O2, rather it was due to the modulation of the downstream event of H2O2 generation.

Antineoplastic Agents, Phytogenic↗

New triene-ansamycins, thiazinotrienomycins F and G and a diene-ansamycin, benzoxazomycin.

New triene-ansamycins designated thiazinotrienomycins F (TT-F) and G (TT-G) and a new diene-ansamycin, benzoxazomycin, were isolated from a culture broth of Streptomyces sp. MJ672-m3 and their structures were elucidated by spectroscopic analyses. The Mean Graphs of TT-G suggests that the tumor growth inhibitory activities are almost as strong as TT-B, in respect of GI50 and TGI against several human cancer cell lines.

Alanine↗

Topological analysis of p21WAF1/CIP1 expression in esophageal squamous dysplasia.

In the normal stratified squamous epithelium of the esophagus, only the third to the fifth layers of cells express the cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21). Using immunohistochemical staining, we examined the topological distribution of cells expressing p21, p53, Ki67, and cytokeratin 10 (CK10), a differentiation marker of esophageal squamous cell carcinoma (SCC), in 25 superficial SCCs and 72 dysplastic lesions of the esophagus. Image analysis of p21, p53, and Ki67 expression was also performed in 48 dysplastic lesions. In superficial SCCs, although Ki67- and p53-expressing cells were mainly distributed in the deep layers of tumors despite tumor differentiation, the distribution of p21 correlated with tumor differentiation. In dysplastic lesions, p53- and Ki67-coexpressing cells tended to locate in the same layers and expand in the lower layers of epithelium with the progression of dysplasia. p21-expressing cells shifted to the upper layers of the epithelium with the progression of dysplasia. However, this change was heterogeneous; in some lesions, p21-expressing cells were confined to the superficial layers of atypical cells (confined type), whereas in others, p21-overexpressing cells were scattered among atypical cells (scattered type). CK10 expression was observed in 25% of dysplastic lesions, and the frequency of CK10 expression was significantly higher in the scattered than in the confined type. Our results suggest that esophageal squamous dysplasia represents the earliest pathological process in esophageal squamous carcinogenesis. Our results also suggest that differentiation of esophageal SCC is determined at the stage of dysplasia, and that p21 plays a critical role in the differentiation process.

Adult↗

Specificity of novel allosterically trans- and cis-activated connected maxizymes that are designed to suppress BCR-ABL expression.

Chronic myelogenous leukemia (CML) is associated with the presence of the Philadelphia chromosome, which is generated by the reciprocal translocation of chromosomes 9 and 22. In the case of L6 (b2a2) mRNA, it is difficult to cleave the abnormal mRNA specifically because the mRNA includes no sequences that can be cleaved efficiently by conventional hammerhead ribozymes near the BCR-ABL junction. We recently succeeded in designing a novel maxizyme, which specifically cleaves BCR-ABL fusion mRNA, as a result of the formation of a dimeric structure. As an extension of our molecular engineering of maxizymes, as well as to improve their potential utility, we examined whether an analogous conformational change could be induced within a single molecule when two maxizymes were connected via a linker sequence. An active conformation was achieved by binding of the construct to the BCR-ABL junction in trans, with part of the linker sequence then acting as an antisense modulator in cis (within the complex) to adjust the overall structure. Results of studies in vitro in the presence of cetyltrimethylammonium bromide (CTAB) (but not in its absence) suggested that a certain kind of connected maxizyme (cMzB) might be able to undergo a desired conformational change and, indeed, studies in vivo confirmed this prediction. Therefore, we successfully created a fully functional, connected maxizyme and, moreover, we found that the activity and specificity of catalytic RNAs in vivo might be better estimated if their reactions are monitored in vitro in the presence of CTAB.

Allosteric Regulation↗