Biomedical subjects

T Yamagata

Publications and source records attributed to T Yamagata.

At least 73 records · Page 4Linked to original sources

PubMed1999

Transcriptional inhibition of p53 by the MLL/MEN chimeric protein found in myeloid leukemia.

The t(11;19)(q23;p13.1) translocation is frequently found in adult myeloid leukemia. In the MLL/MEN fusion protein generated by this translocation, most of the coding region of the MEN protein, an RNA polymerase II elongation factor, is fused to the N-terminal third of the MLL protein, a possible transcriptional regulator. However, the molecular mechanism of leukemogenesis by the fusion protein remains unclear. We investigated the effects of the fusion protein on p53 function using luciferase assays. Overexpression of the fusion protein suppressed the transactivation ability of p53. This negative effect of the fusion protein on p53 function was dependent on the region derived from MEN. Moreover, p53 coimmunoprecipitated with MLL/MEN as well as MEN, suggesting that the fusion protein binds to p53 through the MEN region. We found that MEN binding to p53 was mediated by its N-terminal region and repression of p53 transcriptional activity was mediated by its C-terminal region. We also found that these two functional regions were essential for the transformation of Rat1 cells mediated by MEN. Although we could not demonstrate a functional difference between MLL/MEN and MEN in this study, these data suggest that the MLL/MEN chimeric transcriptional regulator may exert its oncogenic activity by inhibiting the function of the p53 tumor-suppressor protein by binding to it. Our findings provide a novel insight into the leukemogenic mechanism exerted by the t(11;19)(q23;p13.1) translocation.

Adult↗

PubMed1999

Relation between QT dispersion and adenosine triphosphate stress thallium-201 single-photon emission computed tomographic imaging for detecting myocardial ischemia and scar.

It is not known if QT dispersion is useful for detecting coronary artery disease. We investigated whether QT dispersion at baseline and during adenosine triphosphate (ATP) infusion correlate with the imaging patterns obtained from ATP stress thallium-201 single-photon emission computed tomography (ATP-SPECT). QT dispersion was determined in 169 patients who underwent ATP-SPECT from 12-lead electrocardiograms obtained at baseline and 3 minutes after the beginning of ATP infusion. Based on the results of ATP-SPECT, patients were divided into 4 groups: normal (n = 55), ischemia (n = 38), ischemia and scar (n = 42), and scar (n = 34). Baseline QT dispersions (mean +/- SD) in the normal, ischemia, ischemia and scar, and scar groups were 48 +/- 15, 50 +/- 17, 69 +/- 25, and 70 +/- 24 ms, respectively. Baseline QT dispersion was significantly greater in the groups with myocardial scar. QT dispersions during ATP infusion were 43 +/- 16, 63 +/- 20, 76 +/- 20, and 62 +/- 25 ms in the normal, ischemia, ischemia and scar, and scar groups, respectively. QT dispersion increased with ATP infusion in patients with myocardial ischemia. QT dispersion at baseline and during ATP infusion correlated with the ATP-SPECT imaging pattern. These findings suggest that baseline QT dispersion and ATP-induced changes in QT dispersion may help detect the presence of myocardial ischemia and scar.

Adenosine Triphosphate↗

PubMed1999

Prenatal diagnosis of Lowe syndrome by OCRL1 messenger RNA analysis.

Prenatal screening of oculo-cerebro-renal syndrome of Lowe (OCRL; McKusick 309000) was performed using cultured amniocytes. Following identification of defective mRNA expression in the OCRL; gene of the proband's fibroblasts, the mRNA size and quantity of the cultured amniocytes were compared. Based on this analysis, the fetus was diagnosed as being normal and was subsequently delivered as a healthy boy. This is the first reported successful prenatal screening of OCRL using a comparison with defective mRNA of OCRL1 from affected subjects.

Adolescent↗

PubMed1999

Magnetic resonance imaging of meniscal degeneration in torn menisci: a comparison between anterior cruciate ligament deficient knees and stable knees.

Signal anomalies observed in magnetic resonance imaging of the intrameniscal tissue adjacent to the tear were compared between stable knees (group 1, 54 menisci) and anterior cruciate ligament (ACL) deficient knees (group 2, 98 menisci). The histological significance of these signal anomalies was also studied (n = 25). The frequency of intrameniscal signal anomalies adjacent to the tear was significantly lower in ACL-deficient knees than in ACL-stable knees (P = 0.0022). There was a close correlation between the imaging anomalies and the presence of histological lesions (fissures, degeneration) within meniscal tissues adjacent to the tear (sensitivity: 0.95, specificity: 0.60). Our results suggest that the severity of intrameniscal degenerative changes adjacent to the tear are lower in ACL-deficient knees than in ACL-stable knees.

Adolescent↗

PubMed1999

Paradoxical effects of pirenzepine on parasympathetic activity in chronic heart failure and control.

We studied the effect of intravenous pirenzepine (3 mg) in normal subjects (n=15, 43+/-16 years old) and in patients with chronic heart failure (n=15, 61+/-12 years old) to assess the effect of low-dose pirenzepine on vagal activity. R-R intervals and the standard deviations, low-frequency power (LF: ln ms2, 0.04-0.15 Hz), high-frequency power (HF: ln ms2, 0.15-0.40 Hz) and the ratio of low- to high-frequency power (LF/HF ratio) were measured 10 min before and after pirenzepine using a Holter analysis system. Pirenzepine was found to cause a significant increase in the R-R interval from 903+/-112 to 956+/-129 ms in the control group (P<0.0001) and from 927+/-141 to 958+/-168 ms in patients with chronic heart failure (P<0.01). Pirenzepine also increased HF significantly from 4.29+/-0.32 to 5.16+/-0.38 ln ms2 in the control group (P<0.0001) and from 4.04+/-0.16 to 4.48+/-0.24 ln ms2 in the chronic heart failure group (P<0.05). Pirenzepine did not significantly alter the LF/HF ratio in either group. We emphasize that pirenzepine appears to have a vagoinimetic effect in patients with chronic heart failure and that it may be useful for augmenting vagal control of the heart in some patients with chronic heart failure.

Adult↗

PubMed1999

Brain-derived neurotropic factor prevents superoxide anion-induced death of PC12h cells stably expressing TrkB receptor via modulation of reactive oxygen species.

In our previous report (Satoh et al., 1999. Regulation of reactive oxygen species by nerve growth factor but not by Bcl-2 as a novel mechanism of protection of PC12 cells from superoxide anion-induced death. J. Biochem. 125, 952-959), we reported that nerve growth factor (NGF) protected PC12 cells from superoxide anion (O2-)-induced cell death through a novel regulation of reactive oxygen species (ROS) which increased O2- and decreased hydrogen peroxide (H2O2), indicating that decreasing conversion from O2- to H2O2 is a critical process for the protection by NGF. In the present study, we performed a comparative study on protective mechanisms between NGF and brain-derived neurotrophic factor (BDNF) using TrkB-expressing PC12h cells. When compared with NGF, BDNF induced a weaker but significant protective effect on the cells from O2- induced death. BDNF did not seem to change the total amount of ROS in the cells treated with xanthine and xanthine oxidase. On the other hand, BDNF increased O2- and decreased H2O2- levels in the same cells, although not so strongly as NGF. These results suggest that decreasing conversion from O2- to H2O2 is also critical for the protection by BDNF, which is considered to play a central role in survival and differentiation of CNS neurons.

Animals↗

PubMed1999

Acute relapsing encephalopathy mimicking acute necrotizing encephalopathy in a 4-year-old boy.

A 4-year-old boy showed two episodes of encephalitis/encephalopathy involving disturbed consciousness, convulsion, and paresis associated with the elevated levels of protein and myelin basic protein of the cerebrospinal fluid. MRI studies of the brain revealed symmetrical lesions in the brain stem and thalami at the first episode, and additional lesions were found in the cerebellum involving both the gray and white matter in the second episode. The intensities of MRI lesions were low in T I and high in T2. These episodes were followed by an elevation of the anti-viral antibody titers, for influenza A virus during the first episode and for adenovirus during the second. In the second episode, intravenous methylprednisolone therapy resulted in rapid improvement of his neurological signs.

Brain↗

PubMed1999

Single-cell analysis of mitochondrial DNA in patients and a carrier of the tRNA(Leu)(UUR) gene mutation.

We examined heteroplasmy of mutated mitochondrial DNA in single peripheral lymphocytes derived from 4 individuals carrying the nt 3243 A-to-G mutation, including two patients with MELAS, a patient with cardiomyopathy, deafness and diabetes mellitus, and the asymptomatic mother of one of the MELAS patients. In these subjects, all lymphocytes examined were heteroplasmic to different degrees, with a wider range of heteroplasmy evident in the symptomatic patients than in the healthy carrier.

Abnormalities, Multiple↗

PubMed1999

Postnatal changes in the types of muscle fibre in the canine inferior pharyngeal constrictor.

Deglutition is considered to be immature in infants and to mature postnatally. We evaluated postnatal changes in muscle fibre type composition in the canine inferior pharyngeal constrictor muscle, which consists of the thyropharyngeal (TP) and cricopharyngeal (CP) muscles, using ATPase staining with respect to the maturation of deglutition. In the TP muscle type IIA and type IIB fibres, the main components in the adult, were already predominant at 1 week postnatally. The percentage of primitive type IIC fibre showed a rapid reduction and reached the adult level within 6 weeks. In the CP muscle, the majority of fibres were type IIC at 2 weeks. At 2 months, more than 20% of the fibres were still type IIC and the proportion of type I fibres as a main component in the adult was smaller than that of the adult. None of the puppies younger than 9 weeks old had a fibre type composition similar to that of the adult. In the extensor digitorum longus and flexor digitorum superficialis, the compositions of muscle fibre types became similar to that of the adult at 6 and 9 weeks of age, respectively. Thus, the TP muscle matured more rapidly than the limb muscles, while the CP muscle matured more slowly. We speculated that the TP and CP muscles have specific individual differentiation patterns associated with their functional roles before and after birth, compared with the limb muscles.

Aging↗

PubMed1999

Requirement for a different hydrophobic moiety and reliable chromogenic substrate for endo-type glycosylceramidases.

A series of synthetic lactosides with aglycones that differed in length and structure were used to determine the substrate specificity of endo-type glycosylceramidases. Endoglycoceramidases (EGCase) from bacteria preferred lactosides with an acylamide structure over simple n-alkyl lactosides. While ceramide glycanase (CGase) from leech did not show preference. N -Acylaminoethyl beta-lactosides and n -alkyl lactosides were substrates for both EGCase and CGase, but N-acylaminobutyl beta-lactosides, whose acylamide residue differs from that in ceramide, were not hydrolyzed by EGCases. Thus, EGCases, but not CGase, appear to require an N-acyl group at the same position as that of intact glycosphingolipid for substrate recognition. A p-nitrophenyl lactoside derivative possessing an N-acyl chain was degraded by both EGCases and CGase and this chromogenic substrate may be an alternative substrate for endo-type glycosylceramidase activity. Km of the chromogenic lactoside for CGase and Rhodococcus EGCase were 28 microM and 2.9 mM, respectively.

Chromogenic Compounds↗

PubMed1999

Regulation of reactive oxygen species by nerve growth factor but not Bcl-2 as a novel mechanism of protection of PC12 cells from superoxide anion-induced death.

Although neurotrophins protect PC12 cells and neurons from oxidative stress-induced death, the molecular mechanism of this effect is largely unknown. Xanthine (XA)+xanthine oxidase (XO) increased the production of the superoxide anion (O2-) and hydrogen peroxide (H2O2), and the death of PC12 cells. Catalase but not superoxide dismutase (SOD) nor a NO scavenger protected PC12 cells from death, indicating that H2O2 is the main effector responsible for this cell death. Both nerve growth factor (NGF) and Bcl-2 protected PC12 cells from O2--induced toxicity. NGF enhanced the production of O2- and suppressed that of H2O2, suggesting that it inhibits the conversion of O2- to H2O2, while Bcl-2 had no such effect. These results suggested that NGF protected the cells from oxidative stress by altering the composition of the reactive oxygen species (ROS) without affecting their total level.

Animals↗

PubMed1999

Sequence variation and evolution of the mitochondrial DNA control region in the musk shrew, Suncus murinus.

The complete mitochondrial DNA (mtDNA) control region was cloned and sequenced in the musk shrew, Suncus murinus, Insectivora. The general aspect was similar to that found in other mammals. We have found in two locations of this region the presence of arrays of tandem repeats like those in other shrew species. One array was located in the left domain containing the termination-associated sequences (TAS) and the length of a copy was 77 bp. The other repeats were situated upstream from the recognition site for the end of H-strand replication in the right domain and were 20 bp long. The left halves of the control region containing the former repeats were sequenced and compared in several laboratory lines and wild animals from different localities, variations in copy number of repeated sequences were found both among individuals and within an individual. A comparative study of repeated sequences provides useful indication for the origin and evolution of tandem repeated sequences. Strand slippage and mispairing during replication of mtDNA with concerted manner is currently regarded as a dominant theory to account molecular mechanism for tandemly repeated sequences, and the pattern of sequence and length variation in our study supports this theory. Our results, however, suggest that the evolution of the repeated sequences containing the TAS in the musk shrew might go through the process of two steps; at the first step one complete repeated and several incomplete repeated sequences had reproduced in common ancestor of the shrew, and the second stage step-up of complete repeated sequences occurred with concerted evolution after differentiation into continental and insular groups.

Animals↗

PubMed1999

Adenosine 5'-triphosphate induced dilation of human coronary microvessels in vivo.

OBJECT: This study was performed to compare the coronary microvascular response to adenosine 5'-triphosphate (ATP) with the response to adenosine in humans. METHODS: Coronary blood flow velocity was determined using a Doppler flow wire. After intracoronary nitroglycerin infusion, intracoronary bolus injections of adenosine (20 microg) and ATP (20 microg) were performed to induce reactive hyperemia. PATIENTS: Twenty-nine patients (23 men and 6 women, mean age: 63+/-9 years) with coronary artery disease and risk factors for coronary atherosclerosis were studied. RESULTS: Coronary flow reserve in response to ATP was similar to that for adenosine (2.7+/-0.7 vs. 2.7+/-0.7). However, the duration of ATP-induced vasodilation was longer than that of adenosine-induced dilation (39+/-25 seconds vs. 26+/-12 seconds, p<0.0001). The coronary flow reserve obtained with either ATP or adenosine was significantly reduced in the interventioned arteries compared with non-stenosed arteries. The coronary flow reserve obtained with ATP was similar to that obtained with adenosine in both artery groups. The duration of the vasodilator effect of ATP was significantly greater than that of adenosine in both artery groups. CONCLUSION: These results suggest that ATP induces maximal dilation of coronary microvessels, most likely through an endothelium-independent mechanism. The degradation of ATP to adenosine 5'-monophosphate (AMP) and adenosine, as well as the direct action of ATP on A2-adenosine receptors may be responsible for the dilation. We conclude that coronary flow reserve can be determined safely with intracoronary ATP administration.

Adenosine↗

PubMed1999

Idiopathic verapamil-sensitive left ventricular tachycardia complicated by right ventricular outflow tract ventricular tachycardia and ventricular fibrillation.

Idiopathic ventricular tachycardias (VTs) are generally divided into those arising from the right ventricle and those arising from the left ventricle. There has been few reports of two morphologically distinct VT occurring in patients with no apparent structural heart disease. We report a patient with verapamil-sensitive left VT with a right bundle branch block pattern that spontaneously changed to VT with a left bundle branch block pattern. Ventricular fibrillation was induced by the application of programmed stimulation. Although it is unclear if our patient with pleomorphic VT has ventricular vulnerability, it is necessary to investigate further and follow him carefully.

Adult↗

PubMed1999

The role of nitric oxide in bradykinin-induced dilation of coronary resistance vessels in patients with hypercholesterolemia.

OBJECT: In hypercholesterolemic patients, acetylcholine- and substance P-mediated endothelium-dependent dilation of the coronary resistance vessels is impaired due to decreased nitric oxide production. However, it is not clear if bradykinin-induced coronary vasodilation is impaired in these patients. We investigated whether the endothelium-dependent dilation of coronary resistance vessels mediated by bradykinin is impaired in patients with hypercholesterolemia and, if so, whether this impairment is caused by a decreased production of nitric oxide. METHODS: We examined the coronary vascular responses to acetylcholine and bradykinin. The vascular responses to bradykinin were also assessed after N(G)-monomethyl-L-arginine was infused to inhibit nitric oxide production. Drugs were infused into the left coronary ostium and coronary blood flow (CBF) and coronary vascular resistance were evaluated by quantitative angiography and Doppler flow velocity measurements. PATIENTS: Twelve hypercholesterolemic patients and 11 control patients with angiographically normal coronary arteries were studied. RESULTS: The vasodilator responses to acetylcholine and bradykinin were reduced in hypercholesterolemic patients compared with control patients (p<0.005 and p<0.04, respectively, by two-way analysis of variance (ANOVA)). The CBF responses to acetylcholine and bradykinin were significantly correlated (r=0.56; p<0.01). Bradykinin-induced dilation was similar in hypercholesterolemic patients and control patients after inhibition of nitric oxide. CONCLUSION: These results suggest that the bradykinin-mediated endothelium-dependent dilation of coronary resistance vessels may be impaired due to depressed nitric oxide production in patients with hypercholesterolemia.

Acetylcholine↗

PubMed1999

[FRAXE mental retardation].

The folate sensitive fragile site FRAXE is located in Xq28, 600 kb distal to the fragile X syndrome (FRAXA) fragile site. An unstable GCC triplet repeat responsible for FRAXE exists in the 5' untranslated region of FMR2 gene. Normal alleles range from 10-35 repeats and more frequently 15-20 GCCs. An expanded GCC repeat over 200 is methylated, inactivates FMR2, and results in FRAXE mental retardation. Affected individuals show mild mental retardation and/or autistic symptoms FMR2 is a large gene consisting of 21 exons spanning about 600 kb. FMR2 mRNA is about 9.5 kb and is expressed in the brain(especially in the hippocampus and the amygdala) in adults and also in placenta. The FMR2 protein is 1311 amino acids, contains nuclear localization signals, and is a putative transcription factor.

Chromosome Fragile Sites↗

PubMed1999

Assessment of right artrial mapping and P wave-triggered signal-average in patients with paroxysmal atrial fibrillation.

To assess right atrial mapping and P wave-triggered signal-averaged electrocardiogram (ECG) in patients with paroxysmal atrial fibrillation (PAF), this study examined right atrial electrograms using atrial mapping and parameters by P wave-triggered signal-averaged ECG in 39 patients without sick sinus syndrome. Subjects were divided into those with PAF (n = 13; 60+/-13 years old) and a control group (n = 26; 49+/-19 years old). The total number of abnormal right atrial electrograms per patient was significantly greater in the PAF group (3.2+/-1.9) than in the control group (1.1+/-0.9; P < .001). The longest duration of right atrial electrogram in the PAF group tended to be greater than that in the control group (P = .06). The filtered P wave duration was significantly longer in the PAF group than in the control group (144+/-21 vs 125+/-14 ms [P < .002]). The values of the root mean square of P wave-triggered signal-averaged ECG 15 ms from the onset (RMSi 15) and 20 ms from the offset (RMSe 20) were significantly lower in the PAF group (1.1+/-0.4 microV, 1.4+/-0.5 microV) than in the control group (1.9+/-1.1 microV [P < .02], 2.1+/-0.9 microV [P < .01]). The total number of right atrial electrograms in patients with RMSi 15 of < or =1.5 microV was significantly greater than in patients with RMSi 15 of >1.5 microV (2.2+/-1.8 vs 1.3+/-1.3 [P < .05]). Thus, the total number of abnormal right atrial electrograms per patient, the total filtered P wave duration, RMSi 15, and RMSe 20 may be good indices of PAF in patients without sick sinus syndrome. RMSi 15 may reflect the total number of the abnormal right atrial electrograms per patient.

Atrial Fibrillation↗

PubMed1998

Effects of endoglycoceramidase or D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol on glucose uptake, glycolysis, and mitochondrial respiration in HL60 cells.

The glycosphingolipid content of HL60 cells was reduced by endoglycoceramidase, an enzyme which specifically hydrolyzes glycosphingolipids on the cell surface, or by D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, an inhibitor which specifically reduces the activity of UDP-glucose:ceramide glucosyltransferase. Reduction of the glycosphingolipid content by both reagents resulted in enhancement of glucose uptake and glycolysis. Neither of these effects was observed in the presence of cytochalasin B, an inhibitor of facilitated glucose transport. The uptake of radiolabeled 3-O-methylglucose by the cells was not affected by treatment with either of the reagents, indicating no activation of the glucose transporter. On the other hand, both reagents decreased the level of ATP and CO2 production. The molecule mediating these effects appeared to be ceramide, since both treatments actually increased the intracellular ceramide content, and the cell-permeable short-chain ceramide N-acetylsphingosine, but not sphingosine, sphinganine, or palmitic acid, mimicked the effects of both reagents to comparable extents. Finally, the function of electron transport in isolated mitochondria fractions was found to be reduced by treatment of the cells with N-acetylsphingosine. These results strongly suggest that ceramide may affect mitochondrial respiration.

Cell Membrane Permeability↗