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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
PubMed2001

Identification of the HLA-A24 peptide epitope within cytomegalovirus protein pp65 recognized by CMV-specific cytotoxic T lymphocytes.

Among cytomegalovirus (CMV) tegument proteins, phosphoprotein 65 (pp65) has been identified as the important target antigen of the cytotoxic T lymphocyte (CTL) response against the virus. We synthesized seven CMV-pp65-derived peptides carrying an HLA-A24-binding motif, and investigated the ability of these peptides to induce CMV-specific CTL. We identified one nonamer peptide (pp65113-121; VYALPLKML) able to bind HLA-A24 and induce CTL responses in vitro in peripheral blood mononuclear cells (PBMC) from CMV-seropositive individuals. The peptide-specific CTLs generated were capable of recognizing pp65 expressed on CMV-infected fibroblasts as well as pp65113-121 peptide bound to the surface of C1R-A*2402 cells in an HLA-A24-restricted manner. The pp65113-121 peptide thus might be considered a synthetic peptide vaccine in HLA-A24-positive individuals.

Antigens, Viral↗
PubMed2001

Neurally mediated syncope and cardiac beta-adrenergic receptor function.

To evaluate the mechanism of neurally mediated syncope (NMS), we investigated basal autonomic nerve function using a conventional pharmacological method and [123I]-metaiodobenzyl-guanidine (MIBG) single photon emission computed tomography (SPECT). Nine patients with NMS, whose syncope was induced by head-up tilt test with or without isoproterenol, underwent [123I]-MIBG SPECT. Eight of nine NMS patients showed reduced myocardial uptake (two patients, diffuse; four patients, anteroseptal and inferior; one patient, anteroseptal; one patient, inferior). In the study of pharmacological autonomic nervous function test, atropine sulfate (atr.) (0.04 mg/kg), isoproterenol (isp.) (5 x 10(-3) microg/kg/min), propranolol (prop.) (0.2 mg/kg), phenylephrine (phenyl.) (0.4 microg/kg/min), and phentolamine (phent.) (0.2 mg/kg) were successively administered to patients with NMS (n = 5) and control subjects (n = 5). The heart rate (HR) after atr. and prop., and systolic blood pressure (SBP) after phent. were defined as intrinsic HR (IHR) and intrinsic SBP (ISBP). Parasympathetic activity (increase in HR by atr.), beta-sympathetic tone (HR after atr. minus IHR), beta-sensitivity (change in HR by 1 microg isp./kg/min), beta-secretion (beta-tone/beta-sensitivity), alpha-sympathetic tone (SBP before phenyl. minus ISBP), alpha-sensitivity (change in SBP by 1 microg phenyl./kg/min) and alpha-secretion (alpha-tone/alpha-sensitivity) were also calculated. The beta-secretion was decreased (0.0027+/-0.0008 versus 0.0060+/-0.0004 microg/kg/min/isp.; p < 0.05), while the beta-sensitivity was increased (5850+/-947 versus 3150+/-292 beats/microg/kg/min isp.; p < 0.05) in NMS compared with control subjects. In the other indexes, there were no significant differences between two groups. The results of the present study suggest that increased beta-sensitivity may contribute hypercontraction of left ventricles, which might partially explain the mechanism of NMS.

3-Iodobenzylguanidine↗
PubMed2001

Widespread use of TATA elements in the core promoters for RNA polymerases III, II, and I in fission yeast.

In addition to directing transcription initiation, core promoters integrate input from distal regulatory elements. Except for rare exceptions, it has been generally found that eukaryotic tRNA and rRNA genes do not contain TATA promoter elements and instead use protein-protein interactions to bring the TATA-binding protein (TBP), to the core promoter. Genomewide analysis revealed TATA elements in the core promoters of tRNA and 5S rRNA (Pol III), U1 to U5 snRNA (Pol II), and 37S rRNA (Pol I) genes in Schizosaccharomyces pombe. Using tRNA-dependent suppression and other in vivo assays, as well as in vitro transcription, we demonstrated an obligatory requirement for upstream TATA elements for tRNA and 5S rRNA expression in S. pombe. The Pol III initiation factor Brf is found in complexes with TFIIIC and Pol III in S. pombe, while TBP is not, consistent with independent recruitment of TBP by TATA. Template commitment assays are consistent with this and confirm that the mechanisms of transcription complex assembly and initiation by Pol III in S. pombe differ substantially from those in other model organisms. The results were extended to large-rRNA synthesis, as mutation of the TATA element in the Pol I promoter also abolishes rRNA expression in fission yeast. A survey of other organisms' genomes reveals that a substantial number of eukaryotes may use widespread TATAs for transcription. These results indicate the presence of TATA-unified transcription systems in contemporary eukaryotes and provide insight into the residual need for TBP by all three Pols in other eukaryotes despite a lack of TATA elements in their promoters.

Amino Acid Motifs↗
PubMed2001

Effect of weekly or successive iron supplementation on erythropoietin doses in patients receiving hemodialysis.

AIMS: To conduct a 3-month prospective study to determine the optimal way for intravenous iron supplementation in hemodialysis (HD) patients with resistance to recombinant human erythropoietin (rHuEPO) therapy due to deficient iron storage. METHODS: Thirty-five HD patients with iron deficiency were divided into three groups: (1) patients receiving an intravenous infusion of 40 mg of iron during the first ten HD sessions (n = 12); (2) patients receiving 40 mg of iron injected once a week for 10 weeks (n = 12), and (3) patients without any iron supplementation (n = 11). The rHuEPO dosage was adjusted to maintain hemoglobin levels >10.0 g/dl, and the degree of anemia was assessed 3 months later. RESULTS: In group 1, the hemoglobin levels were significantly increased after 4 weeks and remained increased until the end of the study (p < 0.01). In group 2, the hemoglobin levels were gradually increased until the end of the study (p < 0.01). There was no difference in the final hemoglobin values between both groups. The rHuEPO dosage was significantly decreased from 131 +/- 18 to 90 +/- 17 U/kg/week in group 1 (p < 0.01), but could not be changed in group 2 during the observation period despite a similar elevation of the serum ferritin level. In group 3, the rHuEPO doses were rather increased at the end of the study (p < 0.05). CONCLUSION: Aggressive iron supplementation for the short term may be effective to restore rHuEPO hyporesponsiveness in HD patients with functional iron deficiency.

Aged↗
PubMed2001

Antiarrhythmic drug, cibenzoline, can directly improve the left ventricular diastolic function in patients with hypertrophic cardiomyopathy.

The effect of cibenzoline on left ventricular diastolic function was investigated in patients with hypertrophic cardiomyopathy (HCM). Before and 2 h after an oral administration of 200 mg of cibenzoline, echocardiographic, apexcardiographic and gated radionuclide angiographic studies were performed in 12 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 7 with hypertrophic nonobstructive cardiomyopathy (HNCM). After administration of cibenzoline, the left ventricular pressure gradient decreased from 96+/-33 mmHg to 29+/-22 mmHg (<0.0001). Fractional shortening decreased from 53.3+/-7.5 to 45.4+/-6.2% (p=0.0008) in patients with HOCM and from 49.9+/-8.7 to 40.9+/-7.5% (p=0.0039) in patients with HNCM. On the other hand, E-wave velocity increased and A-wave velocity decreased in both groups. The time between the second heart sound and O point was shortened from 253+/-53 to 176+/-21 ms (p<0.0001) in patients with HOCM and from 245+/-54 to 185+/-44 ms (p=0.0050) in patients with HNCM. The time to peak filling rate was shortened from 248+/-79 to 190+/-40 ms (p=0.0072) in patients with HOCM and from 218+/-33 to 163+/-26 ms (p=0.0052) in patients with HNCM. These results indicate that in patients with HCM, cibenzoline suppresses left ventricular systolic function, but can markedly improve left ventricular diastolic dysfunction through its direct action.

Adult↗
PubMed2001

Ischemic preconditioning and lipopolysaccharide attenuate nuclear factor-kappaB activation and gene expression of inflammatory cytokines in the ischemia-reperfused rat heart.

Ischemic preconditioning (IP) and pretreatment with lipopolysaccharide (LPS) reduce myocardial infarct size, but the precise mechanisms remain unknown. Rats were divided into 3 groups: the Control (C) group was subjected to 30 min ischemia followed by 3 h reperfusion; the IP and LPS groups had the same ischemia-reperfusion (I-R) insult with either preconditioning stimuli or pretreatment with LPS, respectively. Infarct size was smaller in the IP (23.4+/-2.3% of risk zone size) and LPS groups (28.5+/-2.0% of risk zone size) than in the C group (52.3+/-3.4% of risk zone size). Nuclear factor kappa-B (NF-kappaB) binding activity increased at 30 min reperfusion and declined thereafter, then rose again at 3 h reperfusion in the C group. The values in the IP (362% of control) and LPS (324% of control) groups were higher before I-R, and then decreased from 30 min (46% and 64% of control, respectively) until 3 h reperfusion (22% and 36% of control, respectively). Nuclear staining of NF-kappaB after reperfusion was less in the IP and LPS groups than in the C group. Expressions of cytokine mRNAs (interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha) were detected 30 min after the onset of reperfusion and their levels remained high after 3 h of reperfusion. These expressions of cytokine mRNAs after I-R were substantially suppressed by IP and LPS, although IP and LPS alone induced modest expressions of these cytokine mRNAs. These data suggest that IP and LPS contribute to infarct size reduction via the downregulation of NF-kappaB and the attenuation of cytokine gene expression.

Animals↗
PubMed2001

Lack of effect of the abnormal fatty acid metabolism in NC/Nga mice on their atopic dermatitis.

Although clinical evidence has suggested that dysregulated fatty acid metabolism is associated with atopic disorders, the molecular basis for such a correlation remains to be demonstrated. In the present study, we analyzed the fatty acid composition in peripheral blood cells of NC/Nga mice, a model for atopic dermatitis (AD). We found that arachidonic acid significantly accumulated in mice with the AD manifestation. In addition, the leucotriene B4-releasing ability upon calcium ionophore A23187 stimulation was potentiated in blood cells. An arachidonic acid accumulation was not apparent in the non-atopic BALB/c strain, but was still observed in healthy NC/Nga mice fed under specific pathogen-free conditions. These results indicate that a disturbed fatty acid metabolism in NC/Nga mice was not a trigger factor for their dermatitis development.

Animals↗
PubMed2001

An angiotensin II type 1 receptor blocker, candesartan, increases myocardial apoptosis in rats with acute ischemia-reperfusion.

Angiotensin II (Ang II) and apoptosis contribute significantly to myocardial ischemia-reperfusion (I-R) injury. Evidence indicates that Ang II may activate apoptosis in myocytes. The present study was undertaken to investigate the effects of angiotensin receptor blockers (ARBs), candesartan, on the apoptosis of cardiac myocytes in rats after I-R. Rats were divided into a control group, a candesartan group I (0.015 mg/kg), and a candesartan group II (0.03 mg/kg). Candesartan was intravenously administered 30 min before ischemia. All rats were subjected to 30 min of coronary occlusion followed by 3 h of reperfusion. The data showed that left ventricular (LV) systolic pressure and LV +dp/dt was decreased after administration of candesartan, but increased after reperfusion in the candesartan group II, compared with those in the candesartan group I and control group. LV -dp/dt was decreased after candesartan administration in candesartan group II. The number of apoptotic cells in the candesartan groups (497+/-204 and 543+/-254, respectively) was higher than that in the control group (287+/-166; p<0.05). There was no significant difference in infarct size among the three groups. However, plasma CPK was lower in the candesartan groups than in the control group. Northern blot analysis showed that p53 mRNA was upregulated in the candesartan groups, in association with increased expression of bax mRNA. Immunohistochemical analysis showed that p53 and bax immunoreactivity were increased in both of the candesartan groups. In conclusion, candesartan increased apoptosis in the rat hearts after acute I-R, and this increase was possibly mediated by upregulation of p53 and bax gene expressions. In addition, candesartan was shown to improve LV function, in association with reduction of CPK release.

Acute Disease↗
PubMed2001

Relative wall thickness is an independent predictor of left ventricular systolic and diastolic dysfunctions in essential hypertension.

The objective of this study was to elucidate the relationship between left ventricular geometry and left ventricular (LV) function in patients with untreated essential hypertension. We evaluated LV systolic and diastolic functions by M-mode echocardiography in 24 normotensive control subjects (NC) and 129 patients with essential hypertension. Patients were divided into four groups according to the relative wall thickness and LV mass index: a normal left ventricle (n=57), a concentric remodeling (n=7), a concentric hypertrophy (n=31), and an eccentric hypertrophy (n=34) group. LV systolic function as measured by midwall fractional shortening (FS) was significantly decreased in both the concentric remodeling and concentric hypertrophy groups; no differences were observed for endocardial FS. LV diastolic function as measured by isovolumic relaxation time (IRT) was also decreased in both the concentric remodeling and concentric hypertrophy groups. In multivariate analysis, relative wall thickness (p<0.0001), end-systolic wall stress (p<0.0001), and systolic blood pressure (p=0.002) were independently associated (r2=0.72) with midwall FS in a model including age, LV mass index, body mass index, diastolic blood pressure and IRT. In addition, relative wall thickness (p=0.0008) and age (p<0.0001) were independently associated (r2=0.31) with IRT in a model including LV mass index, end-systolic wall stress, body mass index, systolic and diastolic blood pressures and midwall FS. We conclude that LV geometry as evaluated by relative wall thickness may provide a further independent stratification of LV systolic and diastolic functions in essential hypertension.

Adult↗
PubMed2001

Hypoglycemic syncope induced by a combination of cibenzoline and angiotensin converting enzyme inhibitor.

A 65-year-old Japanese woman with dilated cardiomyopathy, hypothyroidism and refractory sustained ventricular tachycardia experienced a near-death hypoglycemic syncope. The attack seemed to be induced by a high level of serum insulin, probably due to cibenzoline and by concomitant use of an angiotensin converting enzyme inhibitor (ACEI). Additionally, decreased food intake because of a severe toothache may have contributed to the deterioration of her condition. This case warns cardiologists that a combined cibenzoline and ACEI therapy can provoke serious adverse effects such as hypoglycemic syncope in the elderly. Therefore, the possibility of a hypoglycemic attack associated with these drugs should be explained to patients who are in poor condition.

Aged↗
PubMed2001

Myocardial ischemia induced by anomalous aortic origin of the right coronary artery in a patient with atrial septal defect.

A 27-year-old woman with atrial septal defect (ASD) and a sensation of squeezing in the anterior chest by effort was admitted to our hospital. In addition to the ASD, the coronary angiogram showed an abnormal anomalous position of the right coronary artery. Exercise thallium (Tl)-201 cardiac scintigram with an electrocardiogram clearly detected myocardial ischemia in the inferior area. In the operative findings, the orifice of the right coronary artery was positioned high above the commissure between the right and left sinuses of Valsalva, and it ran between the aorta and pulmonary trunk. Considering myocardial ischemia possibly caused by the anomalous origin of the right coronary artery, a coronary artery bypass graft (CABG) was simultaneously performed to the right coronary artery with direct closure of ASD. The myocardial ischemic finding in the inferior area disappeared after the operation, and she was also relieved from the chest pain. In view of these findings, we suggest that an active combination treatment such as CABG and ASD closure is highly successful in a patient with a threatening coronary anomaly and congenital heart disease.

Adult↗
PubMed2001

Congenitally corrected transposition of the great arteries in a 65-year-old woman.

A 65-year-old Japanese woman was admitted to hospital because of exertional dyspnea. Transthoracic echocardiography showed diffuse hypokinesis of the left-sided ventricular wall, but was not clear enough to provide useful information because of the rotation of the cardiac apex and the presence of lung tissue. Systemic ventriculography showed that the left-sided ventricle with heavy trabeculations was morphologically similar to a normal right ventricle. Magnetic resonance imaging (MRI) clearly revealed corrected transposition of the great arteries. Because this patient had no severe associated cardiac anomalies, systemic ventricular dysfunction is thought to be the major cause of exertional dyspnea. MRI is a useful non-invasive method for the rapid evaluation of cardiac morphology.

Aged↗
PubMed2001

In vitro transmission of HCMV between fibroblasts and peripheral blood leukocytes in the presence of IL-4.

We demonstrated transmission of human cytomegalovirus (HCMV) from the human lung fibroblast MRC-5 to peripheral blood leukocytes (PBLs). mRNA of the HCMV immediately-early (IE) antigen was detected in PBLs cultured with IL-2 or IL-2 + IL-4 that made direct contact with HCMV-infected MRC-5, whereas it was not detected in PBLs prevented from making cell-to-cell contact. However, mRNA of HCMV IE was not detected in PBLs cultured with IL-2 and IFN-gamma that made direct contact with HCMV-infected MRC-5. Transmission of the pp65 antigen was increased in culture medium containing IL-4. At a higher viral infection titer, cell-free HCMV infected adherent PBLs cells. The subset, which did not adhere, did not infect cell-free viruses even at a very high multiplicity of infection. Moreover, the adhered subset of PBLs infected with HCMV was able to transmit HCMV to non-infected fibroblasts. Our results suggest that cell-to-cell contact (when PBLs make direct contact with HCMV-infected cells) is important in the mechanism of HCMV transmission and that the adherent cells of PBLs are one of the most important vehicles for HCMV infection. Moreover, we suggest that type 2 cytokines such as IL-4 enhance the transmission of HCMV to PBLs.

Antigens, Viral↗
PubMed2001

Tripropeptins, novel antimicrobial agents produced by Lysobacter sp. I. Taxonomy, isolation and biological activities.

Peptide antibiotics tripropeptins A, B, C, D and Z were isolated from cultured cells and broth of Lysobacter sp. The differences among these components are in the lengths of the alkyl side chain. Tripropeptins are active against Gram-positive bacteria including MRSA in vitro. Bactericidal activity of tripropeptin C disappeared in the simultaneous presence of chloramphenicol, a bacteriostatic agent.

Anti-Bacterial Agents↗
PubMed2001

Some biological and biochemical activities of resormycin, a novel herbicidal antibiotic.

Biological and biochemical activities of resormycin were studied using unicellular green algae, Selenastrum capricornutum (abbreviated as Selena.), as a test organism. Resormycin inhibited the growth in vitro of Selena. more strongly in the dark than in the light. A weaker but more photo-stable derivative, (+/-)-2,3-dihydro-resormycin, showed more long-lasting activity against Selena. in the light. Resormycin started killing Selena. only after exposure for 2 days and longer, even at high concentrations. Resormycin at concentrations near IC50 rapidly inhibited incorporation of 3H-leu, but not 3H-UR or 3H-TdR, into the TCA insoluble fraction of Selena. Herbicidal activity of resormycin was confirmed using some crops and weeds.

Antifungal Agents↗
PubMed2001

Phagocytosis of alveolar macrophages after conagenin injection to rats.

Phagocytic functions of rat alveolar macrophages (AM) following intraperitoneal injection of conagenin (CNG) and of AM sub-populations fractionated by Percoll discontinuous gradient centrifugation were investigated. Phagocytosis of opsonized-sheep red blood cells (SRBC) following in vitro incubation with CNG showed a significant increase in a higher density of AM (fraction IV). In addition, phagocytosis was also increased in lower density ones (fractions I and II) by macrophage-activating factor (MAF) co-cultivation. CNG-injected rats for 5 consecutive days showed a dose-dependent increase in phagocytosis of AM compared to the control rats. Although the distribution of AM sub-population in rats injected CNG was not significantly different compared to the control rats, phagocytosis was significantly increased in AM of a lower density fraction (fraction II). These results suggest that CNG directly increases phagocytosis of AM in a higher density fraction, and indirectly enhances phagocytosis in AM of a lower density fraction via increasing MAF-like material production.

Adjuvants, Immunologic↗
PubMed2001

Isolation and structural determination of phepropeptins A, B, C, and D, new proteasome inhibitors, produced by Streptomyces sp.

We have isolated four related compounds named phepropeptins A, B, C, and D, as inhibitors of proteasome proposed to regulate many cellular functions. From an NMR analysis, the phepropeptins appeared as cyclic hexapeptides, differing in the two residues of the constituent amino acids from one another, with four conserved amino acid moieties. Based on an amino acid analysis, we synthesized two possible cyclic peptides to phepropeptin B that differ in the configurations. A comparison of the properties between the natural and synthesized compounds revealed that the structure of phepropeptin B was cyclo(-L-Leu-D-Phe-L-Pro-L-Phe-D-Leu-L-Val-). The phepropeptins showed inhibition to the proteasomal chymotrypsin-like activity but not to alpha-chymotrypsin.

Amino Acids↗