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Biomedical subjects

M Takano

Publications and source records attributed to M Takano.

At least 163 records · Page 9Linked to original sources

Evaluation of left ventricular wall motion and function in patients with previous myocardial infarction by three-dimensional 99mTc-HSAD multigated cardiac pool imaging.

To evaluate left ventricular (LV) wall motion stereoscopically from all directions and to calculate the LV volume by three-dimensional (3D) imaging. 99mTc-DTPA human serum albumin-multigated cardiac pool-single photon emission computed tomography (99mTc-MUGA-SPECT) was performed. A new data processing program was developed with the Application Visualization System-Medical Viewer (AVS-MV) based on images obtained from 99mTc-MUGA-SPECT. In patients with previous myocardial infarction, LV function and LV wall motion were evaluated by 3D-99mTc-MUGA imaging. The LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were obtained from 3D-99mTc-MUGA images by the surface rendering method, and the left ventricular ejection fraction (LVEF) was calculated at thresholds of 35% (T1), 40% (T2), 45% (T3), and 50% (T4). There was a strong correlation between the LV volume calculated by 3D-99mTc-MUGA imaging at a threshold of 40% and that determined by contrast left ventriculography (LVEDV: 194.7 +/- 36.0 ml vs. 198.7 +/- 39.1 ml, r = 0.791, p < 0.001; LVESV: 91.6 +/- 44.5 ml vs. 93.3 +/- 41.3 ml, r = 0.953, p < 0.001), respectively. When compared with the LVEF data obtained by left ventriculography, significant correlations were found for 3D images reconstructed at each threshold (T1: r = 0.966; T2: r = 0.962; T3: r = 0.958; and T4: r = 0.955). In addition, when LV wall motion obtained by 3D-99mTc-MUGA imaging (LAT and LAO views) was compared with the results obtained by left ventriculography (RAO and LAO views), there was good agreement. 3D-99mTc-MUGA imaging was superior in allowing evaluation of LV wall motion in all directions and in assessment of LV function, since data acquisition and image reconstruction could be done within a short time with the three-detector imaging system and AVS-MV. This method appears to be very useful for the observation of both LV wall motion and LV function in patients with ischemic heart disease, because it is a noninvasive examination.

Adult↗

Evaluation of renal tubular secretion and reabsorption of levofloxacin in rats.

PURPOSE: Levofloxacin, a quinolone antibacterial drug, is a zwitterion at physiological pH. We examined the effect of cationic and anionic drugs on renal excretion of levofloxacin by means of in vivo clearance to characterize the mechanisms of renal excretion of this drug. METHODS: In vivo clearance was studied in male Wistar albino rats. A bolus dose of 2.85 mg/kg of levofloxacin was administered, followed by a constant infusion of 7.08 micrograms/min. Cimetidine, tetraethylammonium, or p-aminohippurate was administered as a bolus and incorporated into the infusion solution. After reaching steady state, urine and blood concentrations were measured, and pharmacokinetic parameters were calculated. RESULTS: Renal clearance was 2.56 +/- 0.42 ml/min in control, which accounted for 34% of the total body clearance. Renal clearance was significantly decreased to 0.83 +/- 0.25 ml/min by cimetidine (p < .05), corresponding to 32% of the control value. The cationic drug, tetraethyl-ammonium also reduced the renal clearance of levofloxacin, but the effect of the anionic drug, p-aminohippurate, was slight. The clearance ratio of levofloxacin, which was calculated by renal clearance divided by the plasma unbound fraction and the glomerular filtration rate, was 1.60 +/- 0.38 in the control and it was decreased to 0.68 +/- 0.17 and 1.11 +/- 0.22 by cimetidine and tetraethylammonium, respectively. CONCLUSIONS: The present results suggest that the renal excretion of levofloxacin in rats involves tubular secretion and reabsorption, in addition to glomerular filtration, and that tubular secretion is inhibited by cimetidine.

Animals↗

The structures of integration sites in transgenic rice.

Extensive genomic sequencing and sequence motif analysis have been conducted over the integration sites of two transgenic rice plants, #478 and #559, carrying the luciferase gene and/or hygromycin phosphotransferase gene. The transgenes reside in a region with inverted structure and a large duplication of rice genome over 2 kb. Integration was found at the AT-rich region and/or at the repetitive sequence region, including a SAR-like structure, retrotransposon and telomere repeats. The presence of a patch of sequence homology between plasmid and target DNA, and a small region of duplication involving the target DNA around the recombination site, implicated illegitimate recombination in the process of gene integration. Massive rearrangement of genomic DNA including deletion or translocation was also observed at the integration site and the flanking region of the transgene. The recognition sites of DNA topoisomerases I or II were observed in the rearranged sequences. Since only three junctions of transgenic rice were implicated in the illegitimate recombination and extensive rearrangement of the rice genome, rice protoplasts may be active in this process.

Amino Acid Sequence↗

Mutational analysis of BRCA1 gene in ovarian and breast-ovarian cancer families in Japan.

We analyzed the alteration of BRCA1 in DNA obtained from 83 individuals of 13 Japanese site-specific ovarian cancer families and 6 breast-ovarian cancer families. Six germline mutations were detected in 7 families, which consisted of 4 breast-ovarian cancer and 3 site-specific ovarian cancer families, by single-strand conformation polymorphism analysis, followed by direct sequence determination. The mutations included three frameshifts, two nonsense mutations, and one missense mutation causing loss of a zinc-binding motif. The frequency of loss of heterozygosity at the microsatellite markers on the BRCA1 gene was 57% (8 of 14 cases) in site-specific ovarian cancer families, and 100% (6 of 6 cases) in breast-ovarian cancer families. All tumors of the patients carrying a mutation of BRCA1 showed deletion of wild-type alleles, implicating BRCA1 as a tumor suppressor gene. These results suggest that germline mutations of the BRCA1 gene play an important role in the carcinogenesis of breast and/or ovarian cancer in a majority of breast-ovarian cancer families and in some site-specific ovarian cancer families.

Adult↗

Renal excretion of vancomycin in rats with acute renal failure.

We have investigated the renal excretion of vancomycin in rats with acute renal failure (ARF) induced by uranyl nitrate or cisplatin. The renal clearance of the antibiotic after uranyl nitrate or cisplatin injection was separately evaluated by calculating the glomerular filtration rate (GFR) and secretory clearance. The reduced renal clearance of vancomycin in these ARF rats was a result of a decrease in both GFR and secretory clearance. The extents of the decreases in GFR and in secretory clearance were not, however, proportional, the extent of the decrease in secretory clearance being more pronounced. These results suggest that the renal tubular secretion of vancomycin was reduced more predominantly than glomerular filtration in these ARF models.

Acute Kidney Injury↗

Development of muscarinic potassium current in fetal and neonatal rat heart.

Single atrial myocytes were isolated from fetal, neonatal, and adult rat hearts. The muscarinic K+ current activated by rapid application of acetylcholine (ACh) and adenosine (Ado) was recorded under the whole cell voltage clamp. The current density (pA/pF) of ACh-induced K+ current increased from gestation day 12 to the maximum on neonatal day 20 and decreased in the adult myocytes due to greater increase of the membrane capacitance. The development of Ado-induced K+ current followed a similar time course except for a remarkable decrease after neonatal day 10. No significant change was found in single-channel properties during the development. Receptor subtypes were M2 and A1 receptors for ACh and Ado, respectively. In the dose-response relationship, the half-maximal concentration for ACh-induced current markedly decreased with age, from 1.44 (fetus) to 0.17 microM (adult), whereas that for Ado increased from 0.45 (fetus) to 0.99 microM (adult). These changes of the muscarinic K+ current were discussed in relation to the functional development of cardiac myocytes and underlying mechanisms.

Acetylcholine↗

Development of inwardly rectifying K+ channel family in rat ventricular myocytes.

The ATP-sensitive K+ current (I(K,ATP)), the inward rectifier K+ current (I(K1)), and the acetylcholine-activated K+ current (I(K,ACh)) were recorded in fetal, neonatal, and adult rat ventricular myocytes using the patch-clamp technique. The density (pA/pF) of I(K1) increased from gestation day 10 through neonatal day 1 and then decreased after neonatal day 30. The density of I(K,ATP) activated maximally by metabolic inhibition changed in parallel with the I(K1) density, and the density of I(K,ATP) channel distribution was 1.3 times higher than that of I(K1) throughout the development. We failed to observe developmental changes in the single-channel conductance and the mean open time of I(K1) and I(K,ATP) channels. However, the open probability of the I(K,ATP) channel was lower in fetuses, and the sensitivity to ATP was highest in 1-day neonates. I(K,ACh) were present in the ventricle at all stages of development but at a much lower density than in atrium. The relationship between the resting membrane potential and the development of the inwardly rectifying K-channel family is discussed.

Adenosine Triphosphate↗

Inhibition of PAH transport by parathyroid hormone in OK cells: involvement of protein kinase C pathway.

We have previously shown that the p-aminohippurate (PAH) transport system in OK kidney epithelial cell line is under the regulatory control of protein kinase C. Parathyroid hormone (PTH) could activate protein kinase C, as well as protein kinase A, in OK cells. In the present study, the effect of PTH on PAH transport was studied in OK cells. PTH inhibited the transcellular transport of PAH from the basal to the apical side, as well as the accumulation of PAH in OK cells. Basolateral PAH uptake was inhibited by PTH in a dose- and time-dependent manner. Protein kinase A activators did not affect the transcellular transport or the accumulation of PAH. The PTH-induced inhibition of the accumulation of PAH was blocked by a protein kinase C inhibitor staurosporine. These results suggest that PTH inhibits the PAH transport in OK cells and that the messenger system mediated by protein kinase C, not protein kinase A, plays an important role in the regulation of PAH transport by PTH.

1-Methyl-3-isobutylxanthine↗

Renal hemodynamic changes induced by captopril and angiotensin-converting enzyme gene polymorphism.

We studied the relationship between renal hemodynamic changes induced by a single acute administration of captopril (50 mg p.o.) and angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in 27 healthy human volunteers, 7 with DD genotype, 10 with ID, and 10 with II genotype. The increase in effective renal plasma flow (p < 0.02) and the fall in renal vascular resistance (p < 0.01) in response to captopril were significantly less in subjects with the DD genotype than in subjects with the other genotypes. These data suggest that intrarenal ACE inhibition by captopril differs according to ACE gene ID polymorphism in healthy humans.

Adult↗

[Causative factors resulting in intractability of congenital hydrocephalus--analysis of psychomotor development and MRI findings of the brain in sixteen congenitally hydrocephalic patients].

Sixteen patients out of 58 children with congenital hydrocephalus were retrospectively investigated in terms of their psychomotor development and morphological findings of the brain by magnetic resonance imaging (MRI), and morphological backgrounds of the brain in patients affected by "intractable hydrocephalus" were intended to be clarified. The 16 patients were primarily diagnosed as having aqueductal stenosis or communicating hydrocephalus during the era before introduction of MRI. On the basis of the rate of head growth, sixteen patients were divided into three groups; group-1: overt neonatal hydrocephalus (5 cases) ; group-2: rapidly progressive hydrocephalus with normal head circumference at birth (5 cases); and group-3: slowly progressive hydrocephalus with its onset after the neonatal period (6 cases). Psychomotor development of the 16 cases was analyzed by using various methods including the Tanaka-Binet intelligence test and WISC-R. Four cases in group-1 and all cases in group-2 were found to have IQ or DQ below 50, while the other remaining cases were found to have IQ of 82 in group-1 (one case) and IQ ranging from 67 to 113 in group-3. MRI performed in those 9 cases with IQ below 50 revealed various morphological abnormalities of the brain. Those abnormalities were characterized by disturbance of organogenesis and/or histogenesis of the brain dating from the first 20 weeks of fetal life. It is strongly suggested that in the pathogenesis of intractable hydrocephalus developmental malformation of the brain occurring during the first 20 weeks of gestation are involved. Functional and morphological impairments of the brain possibly caused by progression of fetal hydrocephalus and delay of CSF diversion before and after birth seem important in the pathogenesis of intractable hydrocephalus.

Adolescent↗

[Genetic testing of BRCA1 for familial ovarian cancers].

Ovarian cancer is the most lethal kind of gynecological malignancy. Though combination therapy has improved, the prognosis is still poor. It is a risk factor to have a member affected with breast or ovarian cancer in one's family or to have been affected with these diseases. Genetic testing will more effectively enable earlier diagnosis and cure of such diseases. Including the selected results of familial ovarian cancers, we discuss the effectiveness and difficulty of genetic testing of BRCA1 in Japan.

BRCA1 Protein↗

[Correlation of semiquantitative analysis of the distribution of pulmonary perfusion with pulmonary function in chronic obstructive pulmonary disease].

We carried out ventilation-perfusion scintigraphy and pulmonary function tests in 56 patients with chronic obstructive pulmonary disease (COPD) and 19 healthy volunteers. We used 99mTc-macroaggregated albumin for the perfusion scintigraphy and 33Xe gas for the ventilation scintigraphy. The lung volume image was created by computerized summation of the radioactivity in the rebreathing phase. Regions of interest (ROIs) were set automatically on lung volume image, which included each whole lung, and on perfusion image, including areas with relatively high radioactivity, with cut-off levels of 50%, 70%, and 90%. The number of pixels in each RO1 was used as an index of lung volume (L) or perfusion (P). Perfusion per unit of lung volume (P/L) was also used as an index of perfusion. P70 and P70/L showed the better correlations than the other parameters, including significant correlations with vital capacity, FEV1.0, peak flow rate, RV/ TLC, diffusing capacity and arterial oxygen partial pressure. The significant difference in P70 and P70/L between patients with hypoxemia and those without hypoxemia suggested that P70 and P70/L are useful indicators of the severity of COPD. We conclude that semiquantified values of pulmonary perfusion scintigraphy are significantly correlated with pulmonary function and the severity of COPD.

Aged↗

[Changes in metabolism and peritumoral circulation after radiosurgery of metastatic brain tumors: evaluation by three dimensional dual isotope SPECT].

Concurrent use of two different isotopes, 201T1C1 and 123I-IMP, in SPECT is useful in separative evaluation of tumor metabolism and peritumoral circulation. Three dimensional SPECT employed in our study has an obvious advantage over two dimensional SPECT for its accurate imaging of tumors and peritumoural areas. Changes of tumor metabolism and regional circulation in peritumoral edematous tissues were investigated by fused 3-D SPECT images using 201T1C1 and 123I-IMP. In this study, the volume of isotope accumulative and isotope defective regions were measured. Fusion of SPECT images was performed by the use of panning visualization software; Application Visualization System Medical View (K.G.T.). The threshold of 3-D rendering was determined by conforming the volume of the hemisphere and of the tumor estimated on CT to the volume of 123I-IMP and 201T1C1 accumulating area respectively. Accumulative volume of 201T1C1 in the tumor decreased remarkably at 7 days after radiosurgery (p < 0.01). Defective volume of peritumoral hypoperfusion was measured on 3-D SPECT. The average volume was 80.5 + 32.5cm3 before radiosurgery. It decreased by approximately 60% at 7 days after radiosurgery (p < 0.05). Analysis of 3-D SPECT images using two different isotope tracers is reliable and useful to evaluate early the changes of metabolism and peritumoral circulation in or around intracerebral tumors.

Aged↗

[Quantitative evaluation of pulmonary perfusion volume using 99mTc-MAA SPECT: a comparison of COPD patients and healthy volunteers].

99mTc-MAA pulmonary perfusion single-photon emission computed tomography was performed on 18 patients with chronic obstructive pulmonary disease (COPD) and 41 healthy male volunteers. We quantified the extent of pulmonary perfusion with the Application Visualization System. We measured the pulmonary perfusion volume (PV) at 8 threshold levels encompassing 10 percentage points each from 21-100%. We also calculated the ratio of perfusion volume to total perfusion volume (TPV) at each threshold. Pulmonary perfusion volume in healthy volunteers remained relatively constant at levels of 31-70% and decreased gradually at levels of 71-100%. There was no significant difference in perfusion volume between smokers and non-smokers. Perfusion volume in COPD patients gradually decreased at levels of 31-60% and markedly decreased at levels greater than 60%. Perfusion volume differed significantly between COPD patients and healthy volunteers at levels of 41-100%. The mean PV/TPV value of COPD patients was significantly higher than that of healthy volunteers at levels of 21-40% and significantly lower than that of healthy volunteers at levels of more than 50%. This finding demonstrates that lung volume at high levels of pulmonary perfusion is decreased in COPD patients. The pulmonary perfusion volume at levels of more than 60% is an efficient means of distinguishing COPD patients from healthy subjects.

Adult↗

[Hyperalgesia induced by intrathecal administration of nitroglycerin involves NMDA receptor activation in the spinal cord].

Spinal NMDA receptors are involved in hyperalgesia and chronic pain. The activation of spinal NMDA receptor results in the production of nitric oxide in the second order neurons in the spinal cord dorsal horn. We investigated the effects of intrathecally administered nitroglycerin (NTG) which releases nitric oxide in the cell. Formalin test which reflects phasic and tonic nociception was used as a nociceptive measure in rats with chronically implanted intrathecal catheters. Intrathecal injection of NTG resulted in the increase of flinching behavior induced by formalin injection to one paw in phase 1 (phasic) and phase 2 (tonic) responses in a dose-dependent manner. Intrathecally administered NMDA antagonist, MK-801 (MK) dose-dependently inhibited the effect of NTG but the effect was significant only in the phase 2 of the formalin test. MK given after formalin injection had significantly less effect on the phase 2 response. L-NAME (NOS inhibitor), MB (guanylate cyclase inhibitor) and HB (nitric oxide scavenger) significantly antagonized the hyperalgesic effect of NTG in the phase 2 of the formalin test. These results show that nitric oxide plays an important role in producing hyperalgesia in the spinal cord acting postsynaptically as well as pre-synaptically.

Animals↗

Cholesterol modulates organic cation transport activity and lipid fluidity in rat renal brush-border membranes.

The role of cholesterol in organic cation transport was studied in rat renal brush-border membranes. H+ gradient-dependent uptake of the organic cation tetraethylammonium in brush-border membrane vesicles was stimulated by cholesterol enrichment in a dose-dependent manner. The dissipation rate of the H+ gradient, a driving force for organic cation transport in brush-border membranes, was reduced by cholesterol enrichment. Tetraethylammonium uptake in the absence of H+ gradient was also stimulated by cholesterol enrichment. These findings indicate that cholesterol modulates tetraethylammonium uptake by affecting the intrinsic activity of the organic cation transporter and the H+ gradient dissipation rate. Therefore, cholesterol content should be an important determinant for organic cation transport in renal brush-border membranes.

Animals↗

cDNA cloning and functional expression of a novel rat kidney organic cation transporter, OCT2.

A cDNA encoding a novel organic cation transporter, designated as OCT2 was isolated from the rat kidney. The rat OCT2 cDNA (2,205 bp) had an open reading frame encoding for a 593-amino acid protein (calculated molecular mass of 66 kDa) which shows 67% identity with the rat OCT1. Northern hybridization and reverse transcription-PCR analyses revealed that the rat OCT2 mRNA transcript was expressed predominantly in the kidney, at higher level in the medulla than in the cortex, but this transcript was not detected in the brain, heart, lung, liver, small intestine or spleen. When expressed in Xenopus oocytes, rat OCT2 stimulated the uptake of tetraethylammonium, and the uptake was markedly inhibited by the presence of cimetidine, procainamide and quinidine. These findings suggest that OCT2 is responsible for the transport of cationic drugs in the kidney.

Amino Acid Sequence↗