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Biomedical subjects

T Kunieda

Publications and source records attributed to T Kunieda.

At least 73 records · Page 4Linked to original sources
PubMed1999

Increased plasma levels of adrenomedullin in patients with pulmonary hypertension.

Adrenomedullin, a potent hypotensive peptide, reduces blood pressure and pulmonary vascular resistance, and increases pulmonary blood flow. The mRNA for adrenomedullin and its receptor is highly expressed in the lung, suggesting a regulatory role for adrenomedullin in the pulmonary circulation. To investigate the clinical significance of adrenomedullin in patients with pulmonary hypertension, we studied the relationship between plasma levels of adrenomedullin and pulmonary haemodynamics. Venous, arterial and pulmonary arterial blood samples were obtained during cardiac catheterization and plasma levels of adrenomedullin were measured by specific radioimmunoassay in 33 consecutive patients with severe pulmonary hypertension (12 cases of primary pulmonary hypertension, 21 with chronic thromboembolic pulmonary hypertension; age 49+/-16 years, mean pulmonary arterial pressure 50+/-15mmHg). In addition, plasma levels of adrenomedullin were measured before and after acute nitric oxide inhalation. The changes in plasma adrenomedullin during the follow-up period of 10.3+/-4.3 months were also evaluated (n=5). Sixty-two healthy subjects served as the control group. Adrenomedullin was measured in an antecubital vein in the controls. Plasma levels of adrenomedullin were significantly higher in the patients with pulmonary hypertension than in the control subjects (10.1+/-8.7 versus 4.9+/-1.1pmol/l, P<0.01). Plasma levels of adrenomedullin, expressed as their natural logarithm, were significantly correlated with mean right atrial pressure (r=0.71, P<0.01), stroke volume (r=-0.63, P<0.01), total pulmonary resistance (r=0.60, P<0.01), mean pulmonary arterial pressure (r=0.37, P<0.05), and the natural logarithm of plasma atrial natriuretic peptide (r=0. 63, P<0.01). Plasma levels of adrenomedullin did not change significantly after nitric oxide inhalation, but significantly increased in association with the elevation of the total pulmonary resistance during the long-term follow-up period. These results suggest that plasma levels of adrenomedullin increase in proportion to the extent of pulmonary hypertension.

Administration, Inhalation↗
PubMed1998

Transgene expression in malignant glioma using a replication-defective adenoviral vector containing the Egr-1 promoter: activation by ionizing radiation or uptake of radioactive iododeoxyuridine.

One approach to improving the specificity of gene therapy involves using radiosensitive promoters to activate gene expression selectively in the radiation field. In this study, we evaluated the ability of irradiation to regulate the transcription of a recombinant replication-defective adenovirus vector, Ad.Egr-1/lacZ, containing the radiation-inducible Egr-1 promoter driving the beta-galactosidase reporter gene in glioma cells. Transcripts of the Egr-1 gene in human and rat glioma cells were induced following irradiation with as little as 2 Gy. This dose was 10-fold less than previously reported, and comparable to doses of irradiation used clinically in standard fractionated radiotherapy for brain tumors. When 9L rat gliosarcoma cells were infected with Ad.Egr-1/lacZ in vitro and exposed to 2 Gy of external beam irradiation, there was a threefold increase in beta-galactosidase expression. Irradiation of intracerebral 9L tumors infected with the Ad.Egr-1/lacZ virus, using either external beam radiotherapy (2 Gy) or the thymidine analog 5-iodo-2'-deoxyuridine radiolabeled with the Auger electron emitter iodine-125 ([125I]IdUrd), also resulted in increased beta-galactosidase activity of the tumor cells. These results indicate that the use of viral vectors containing radiation-inducible promoters represents a novel therapeutic approach that enables gene therapy to be spatially and temporally regulated by ionizing radiation. These findings also support a potential role for radiation-inducible promoters in the treatment of malignant brain tumors.

Animals↗
PubMed1998

Human supplementary motor area is active in preparation for both voluntary muscle relaxation and contraction: subdural recording of Bereitschaftspotential.

Bereitschaftspotentials (BPs) preceding muscle relaxation and contraction were compared by using subdural electrodes which were implanted onto the right medial frontal surface in two patients with supplementary motor area (SMA) seizure. The applied movement paradigm (muscle relaxation and contraction tasks) was completely the same as employed in our previous study [Terada, K., Ikeda, A., Nagamine, T. and Shibasaki, H., Electroenceph. clin. Neurophysiol., 95 (1995) 335-345]. In both patients, either negative or positive BPs were observed in the SMA-proper and supplementary negative motor area (SNMA) starting at 1.2-1.8 prior to both movements. In one patient, BP was more widespread in the relaxation task whereas more restricted to the hand area in the contraction task. In the other patient, the BPs were observed in the cortical area rostral to SNMA (pre-SMA), in addition to the SMA-proper, in both tasks. It is concluded that SMA-proper and SNMA, and probably pre-SMA as well, in humans are similarly active in preparation for both voluntary muscle contraction and relaxation.

Adult↗
PubMed1998

Antioxidant activity of a novel vitamin E derivative, 2-(alpha-D glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol.

A novel vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG), has excellent water-solubility (> 1 x 10[3] mg/ml). The antioxidant activity of TMG was investigated. Kinetic studies of the inhibition of radical-chain reaction of methyl linoleate in solution demonstrated that the peroxyl radical-scavenging activity was not changed by the replacement of phytiyl side chain of vitamin E to glucosyl group. TMG acted as an effective inhibitor on lipid peroxidation of egg yolk phosphatidylcholine (PC)-liposomal suspension induced by a water-soluble and a lipid-soluble radical generator, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) and 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN). Its effectiveness was higher than that of ascorbic acid (AsA) when liposomal suspension was exposed to a lipid-soluble radical generator, AMVN. TMG also showed an excellent antioxidant activity on cupric ion-induced lipid peroxidation of PC-liposomal suspension, and suppressed the oxidation of rat brain homogenate which contained trace level of iron ion. On the other hand, AsA acted as a prooxidant on both the cupric ion-induced liposomal peroxidation and the oxidation of rat brain homogenate. When human plasma was exposed to either AAPH or AMVN, the accumulation of cholesteryl ester hydroperoxides was retarded by the addition of TMG.

Adult↗
PubMed1998

Plasma brain natriuretic peptide levels increase in proportion to the extent of right ventricular dysfunction in pulmonary hypertension.

OBJECTIVES: This study sought to investigate the influence of right ventricular (RV) hemodynamic variables and function on the secretion of brain natriuretic peptide (BNP) in patients with isolated RV overload. BACKGROUND: Plasma BNP is known to increase in proportion to the degree of left ventricular (LV) overload. However, whether BNP secretion is also regulated in the presence of RV overload remains unknown. METHODS: Plasma BNP and atrial natriuretic peptide (ANP) levels in the pulmonary artery were measured in 44 patients with RV overload: 18 with RV volume overload (RVVO) due to atrial septal defect and 26 with RV pressure overload (RVPO) due to primary or thromboembolic pulmonary hypertension. Right heart catheterization was performed in all patients. RV and LV ejection fraction, myocardial mass and volume of the four chambers were determined by using electron beam computed tomography. RESULTS: Although both plasma BNP and ANP levels were significantly elevated in patients with RV overload compared with values in control subjects, plasma BNP and the BNP/ANP ratio were significantly higher in patients with RVPO than with RVVO (BNP 294 +/- 72 vs. 48 +/- 14 pg/ml; BNP/ANP 1.6 +/- 0.2 vs. 0.8 +/- 0.2, both p < 0.05). Plasma BNP correlated positively with mean pulmonary artery pressure (r = 0.73), total pulmonary resistance (r = 0.79), mean right atrial pressure (r = 0.79), RV end-diastolic pressure (r = 0.76) and RV myocardial mass (r = 0.71); it correlated negatively with cardiac output (r = -0.33) and RV ejection fraction (r = -0.71). Plasma BNP significantly decreased from 315 +/- 120 to 144 +/- 54 pg/ml with long-term vasodilator therapy (total pulmonary resistance decreased from 23 +/- 4 to 15 +/- 3 Wood U). CONCLUSIONS: Plasma BNP increases in proportion to the extent of RV dysfunction in pulmonary hypertension.

Adult↗
PubMed1998

Cortical activation during fast repetitive finger movements in humans: steady-state movement-related magnetic fields and their cortical generators.

OBJECTIVE: To study the cortical physiology of fast repetitive finger movements. METHODS: We recorded steady-state movement-related magnetic fields (ssMRMFs) associated with self-paced, repetitive, 2-Hz finger movements in a 122-channel whole-head magnetometer. The ssMRMF generators were determined by equivalent current dipole (ECD) modeling and co-registered with anatomical magnetic resonance images (MRIs). RESULTS: Two major ssMRMF components occurred in proximity to EMG onset: a motor field (MF) peaking at 37+/-11 ms after EMG onset, and a postmovement field (post-MF), with inverse polarity, peaking at 102+/-13 ms after EMG onset. The ECD for the MF was located in the primary motor cortex (M1), and the ECD for the post-MF in the primary somatosensory cortex (S1). The MF was probably closely related to the generation of corticospinal volleys, whereas the post-MF most likely represented reafferent feedback processing. CONCLUSIONS: The present data offer further evidence that the main phasic changes of cortical activity occur in direct proximity to repetitive EMG bursts in the contralateral M1 and S1. They complement previous electroencephalography (EEG) findings on steady-state movement-related cortical potentials (ssMRCPs) by providing more precise anatomical information, and thereby enhance the potential value of ssMRCPs and ssMRMFs for studying human sensorimotor cortex activation non-invasively and with high temporal resolution.

Adult↗
PubMed1998

Cloning and mapping of the mouse Gpx2 gene encoding gastrointestinal glutathione peroxidase.

Gastrointestinal glutathione peroxidase (GSHPx-GI) is an enzyme expressed in intestinal epithelial cells and may reduce hydroperoxides generated from the ingested diet. We isolated a genomic clone containing the mouse Gpx2 gene encoding 190 amino acids of GSHPx-GI. This gene is composed of two exons and an intron. The nucleotide sequence of the coding region was 89.9% identical with that of the human GPX2 gene. A TGA opal codon predicted to encode a selenocysteine was identified at codon 40. A genomic clone containing a pseudogene for the Gpx2 gene was also isolated. The nucleotide sequence of the pseudogene was 98.3% identical with that of the mouse Gpx2 gene and showed characteristics of a processed pseudogene. Linkage analysis using backcross mouse progeny indicated the mouse Cpx2 gene and its pseudogene to be located on mouse chromosomes 12 and 7, respectively.

Amino Acid Sequence↗
PubMed1998

Nucleotide sequence of endothelin-B receptor gene reveals origin of piebald mutation in laboratory mouse.

Piebald (Ednrbs) is a coat color mutation of laboratory mice caused by a decreased expression of endothelin-B receptor gene (Ednrb). The IITES and JF1 mouse strains, whose origins are believed to be different from those of the common laboratory inbred strains, also show a phenotype similar to Ednrbs. In the present study, we found that the nucleotide sequence of the Ednrb gene of the IITES and JF1 mice is identical to that of the Ednrbs allele, Ednrbs allele has an RFLP of the Ednrb gene identical with that of M. m. molossinus but different from other subspecies, and at least particular regions of chromosome 14 proximal to the Ednrb locus of the IITES and JF1 strains are derived from M. m. molossinus. These findings clearly indicate that the Ednrbs allele of the laboratory mice has its origin in M. m. molossinus.

Alleles↗
PubMed1998

[Effectiveness of continuous intravenous prostaglandin E 1 against pulmonary hypertension].

Pulmonary hypertension is a progressive disease for which no effective therapy has been found. Short-team treatment with alprostadil alfadex (PGE 1) can improve hemodynamics but the effects of long-term treatment have not been reported. We administered intravenous PGE 1 to 16 patients with pulmonary hypertension for 4 weeks in addition to conventional therapy. Hemodynamic and symptomatic effects were evaluated. The infusion was interrupted in 7 patients (44%) because of fever and an increase in levels of C-reactive protein in serum. In the remaining 9 patients, the drug lowered pulmonary artery pressure and resistance, and imareased cardiac output significantly in 7 patients. PGE 1 can improve hemodynamics and relieve symptoms in patients with pulmonary hypertension, barring severe side effects.

Adult↗
PubMed1997

Shortening of Doppler-derived deceleration time of early diastolic transmitral flow in the presence of pulmonary hypertension through ventricular interaction.

Deceleration time (DT) of the early transmitral flow velocity has recently been highlighted as a simple, noninvasive indicator of pulmonary arterial wedge pressure. In patients with pulmonary hypertension without left-sided heart disease, however, increased right ventricular pressure may result in an abnormal ventricular septal motion, which may impact on left ventricular (LV) early diastolic filling. We sought to determine if DT may be influenced by the severity of pulmonary hypertension in patients without left-sided heart disease. Doppler-derived transmitral flow and hemodynamic parameters were simultaneously assessed in 26 patients with pulmonary hypertension (primary pulmonary hypertension = 11; chronic thromboembolism = 15). Transmitral Doppler variables including DT were correlated with hemodynamics and LV deformity index measured in early diastole with 2-dimensional echocardiography. DT significantly correlated with the total pulmonary resistance (r = -0.70, p <0.001). Multivariate analysis revealed that DT was independently determined by total pulmonary resistance, but not by pulmonary arterial wedge pressure, heart rate, or patient's age in our study population. DT showed a correlation with LV deformity index (r = -0.74, p <0.001). These results indicate that DT may shorten in association with the severity of pulmonary hypertension and that the shortened DT in pulmonary hypertension may be attributable to right ventricular pressure overload which causes geometric changes.

Adult↗
PubMed1997

Bone marrow transplantation in newborn rats with mucopolysaccharidosis type VI: biochemical, pathological, and clinical findings.

BACKGROUND: Mucopolysaccharidosis type VI (MPS VI) is the lysosomal storage disorder caused by the deficient activity of arylsulfatase B (ASB). In this study, we evaluated bone marrow transplantation (BMT) for the treatment of MPS VI and the effects of irradiation on the survival and engraftment of bone marrow-transplanted neonatal rats. METHODS: One- to 2-day-old MPS VI rats were injected with normal bone marrow after irradiation with 200, 400, or 800 cGy. Ninety percent of the animals receiving a single dose of 200 cGy (n=30) survived the procedure, whereas irradiation with 400 cGy (n=23) or 800 cGy (n=12) resulted in significant mortality (78% and 100%, respectively). Engraftment was monitored by determining ASB activities in peripheral white blood cells and by Y chromosome in situ hybridization analysis. Fifty-two percent of the animals from the 200-cGy group engrafted for up to 8 months after BMT; among the five animals that survived the 400-cGy dose, all engrafted. In comparison, only 20% of nonirradiated animals engrafted at low levels. Of the 24 engrafted animals that were monitored for 8 months after BMT, clinical and/or radiographic improvements were noted in only one (BMT animal 3). Enzymatic analysis revealed that the ASB activities in the reticuloendothelial organs of this animal, as well as two other engrafted but clinically unimproved animals (BMT animals 1 and 2), were normal or near normal; correspondingly, the glycosaminoglycan levels in these organs were significantly reduced. Consistent with the clinical and biochemical observations, light and electron microscopic findings were more improved in BMT animal 3 as compared with BMT animals 1 and 2, although a reduction of storage was evident in each of these transplant recipients, particularly in the trachea and aorta, two tissues that are characteristic sites of pathology in human patients. CONCLUSIONS: These results indicate that BMT in newborn MPS VI patients may prevent many of the pathological and clinical findings in this disorder, but is likely to have very limited and unpredictable effects on the skeletal abnormalities.

Animals↗
PubMed1997

Regeneration of Sarcophaga imaginal discs in vitro: implication of 20-hydroxyecdysone.

When the 3/4 sectors of leg imaginal discs of Sarcophaga were cultured in vitro in the presence of 2.5 x 10(-8) M 20-hydroxyecdysone, wound healing and restoration of their morphology occurred. This concentration of ecdysone was critical for wound healing and was 40 times lower than that necessary for inducing differentiation of imaginal discs in vitro. Lost positional values revealed by expression of the wingless gene were found to show partial recovery under these conditions. These results suggest that a low titer of ecdysone is essential for the regeneration of imaginal discs.

Amino Acid Sequence↗
PubMed1997

Synthesis of a novel vitamin E derivative, 2-(alpha-D-glucopyranosyl) methyl-2,5,7,8-tetramethylchroman-6-ol, by alpha-glucosidase-catalyzed transglycosylation.

A novel derivative of vitamin E, vitamin E glucoside, was synthesized from 2-hydroxymethyl-2,5,7,8-tetramethylchroman-6-ol and maltose in a solution containing DMSO by transglycosylation with alpha-glucosidase from Saccharomyces species. The glycosylated product was identified as 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG) by mass spectrometry and nuclear magnetic resonance spectroscopy. The optimal pH of transglycosylation was 5.5, and the yield of TMG increased as the concentration of maltose increased. TMG has high solubility in water (> 1 x 10(3) mg/mL). The 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity of TMG was found to be nearly the same as those of alpha-tocopherol, Trolox (2-carboxy-2,5,7,8-tetramethylchroman-6-ol), and ascorbic acid.

Antioxidants↗
PubMed1997

Modality-specific organization for cutaneous and proprioceptive sense in human primary sensory cortex studied by chronic epicortical recording.

Modality specificity of human primary somatosensory cortex was studied by recording somatosensory evoked potentials (SEPs) from subdural electrodes in a patient with intractable focal motor seizure. A newly developed device was used for selectively activating proprioception. The spatial and temporal distributions of proprioception-related SEPs elicited by brisk passive flexion movement at the proximal interphalangeal (PIP) joint of the middle finger (4 degrees in 25 ms) were quite different from those to cutaneous sense evoked by electric stimulation of the digital nerve at the same site. It was for the first time demonstrated that proprioception-related SEPs following passive finger movement do not originate in area 3b, which was clearly activated by cutaneous stimulation, and that other sites at the sensorimotor cortex such as areas 2, 3a and 4 possibly contribute to the cortical processing of proprioception.

Adult↗
PubMed1997

Characteristics of pulmonary artery pressure waveform for differential diagnosis of chronic pulmonary thromboembolism and primary pulmonary hypertension.

OBJECTIVES: The accurate diagnosis of chronic pulmonary thromboembolism (CPTE) is a prerequisite for life-saving surgical interventions. To help in the differential diagnosis of CPTE and primary pulmonary hypertension (PPH), we characterized the configuration of the pulmonary artery pressure waveform. BACKGROUND: Because CPTE predominantly involves the proximal arteries, whereas PPH involves the peripheral arteries, we hypothesized that patients with CPTE would have stiff or high resistance proximal arteries, whereas those affected by PPH would have high resistance peripheral arteries. These differences in the primary lesions would make arterial pulsatility relative to mean pressure larger in CPTE than in PPH. METHODS: In 34 patients with either CPTE (n = 22) or PPH (n = 12) whose pulmonary systolic pressure was > or = 50 mm Hg, we measured pulmonary artery pressure using a fluid-filled system that included a balloon-tipped flow-directed catheter. RESULTS: To quantify the magnitude of pulsatility relative to mean pressure, we normalized pulse pressure by mean pressure, hereinafter referred to as fractional pulse pressure (PPf). PPf was markedly higher in CPTE than in PPH (mean [+/-SD] 1.41 +/- 0.20 and 0.80 +/- 0.18, respectively, p < 0.001) and was diagnostic in separating the two groups without overlap. Similarly, the coefficient of variation of pulmonary artery pressure also separated the two groups without overlap (0.45 +/- 0.06 and 0.25 +/- 0.06, respectively, p < 0.001). Fractional time to half the area under the pressure curve separated the two groups reasonably well (0.35 +/- 0.02 and 0.43 +/- 0.03, respectively, p < 0.001). CONCLUSIONS: The analysis of pulsatility of pulmonary artery pressure is useful in the differential diagnosis of CPTE and PPH.

Adult↗
PubMed1997

Impaired left ventricular myocardial metabolism in patients with pulmonary hypertension detected by radionuclide imaging.

To assess whether left ventricular myocardial metabolism is affected by the presence of right ventricular pressure overload, we performed 123I-beta-methyl-iodophenyl pentadecanoic acid (123I-BMIPP) and 99Tc(m)-sestamibi (99Tc(m)-MIBI) single photon emission tomography in 24 patients with pulmonary hypertension and in 10 control subjects. The left ventricle was divided into six regions using a short-axis tomogram at the mid-ventricular level. The relative regional uptake (RRU, %) was determined for each region as the ratio of the regional uptake per pixel to the maximum uptake in the six regions. Right heart catheterization was performed to obtain mean pulmonary arterial pressure. 123I-BMIPP uptake in the septum and the adjacent myocardium of the left ventricle was lower in patients with pulmonary hypertension than in control subjects (septal RRU, 75 +/- 6 vs 85 +/- 4%; anteroseptal RRU, 76 +/- 6 vs 86 +/- 3%; posteroseptal RRU, 75 +/- 4 vs 84 +/- 4%; P < 0.001). The reduction in 99Tc(m)-MIBI uptake was confined to the septum in patients with pulmonary hypertension (79 +/- 5 vs 85 +/- 5%; P < 0.05). Interestingly, the septal RRU of 123I-BMIPP and the sum of the septal, anteroseptal and posteroseptal RRUs of 123I-BMIPP were negatively correlated with mean pulmonary arterial pressure (r = -0.70 and -0.55, respectively; P < 0.01). In conclusion, myocardial metabolism in the interventricular septum and the adjacent regions of the left ventricle may be impaired in proportion to the degree of pulmonary hypertension.

Adult↗