Three dimensional segmented myocardial perfusion images by selective intracoronary injection of contrast using 256 slice cone beam computed tomography.
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Biomedical subjects
Publications and source records attributed to K Odaka.
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A recombinant adenovirus (rAd) expressing Cre recombinase derived from bacteriophage P1 has already been extensively used for the conditional gene activation and inactivation strategies in mammalian systems. In this study, we generated AxCAFLP, a rAd expressing FLP recombinase derived from Saccharomyces cerevisiae and carried out quantitative comparisons with Cre-expressing rAd in both in vitro and in cultured cells to provide another efficient gene regulation system in mammalian cells. In the in vitro experiments, the relative recombination efficiency of FLP expressed in 293 cells infected with FLP-expressing rAd was approximately one-thirtieth that of Cre even at 30 degrees C, the optimum temperature for FLP activity, and was approximately one-ninetieth at 37 degrees C. Co-infection experiments in HeLa cells using a target rAd conditionally expressing LacZ under the control of FLP showed that an FLP-expressing rAd, infected at a multiplicity of infection (MOI) of 5, was able to activate the transgene in almost 100% of HeLa cells whereas the Cre-expressing rAd was sufficient at an MOI of 0.2. Since an MOI of 5 is ordinarily used in rAd experiments, these results showed that the FLP-expressing rAd is useful for gene activation strategies and is probably applicable to a sequential gene regulation system in combination with Cre-expressing rAd in mammalian cells.
The purpose of this study was to validate the measurement of global and regional left ventricular cardiac function with ECG-gated fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) by comparison with the corresponding indices from X-ray left ventriculography (LVG). Twenty-six patients (23 men, 3 women, mean age 60.4 years) underwent LVG and ECG-gated (eight frames/cycle) FDG-PET within an interval of 10.2+/-6.8 days. A volumetric sampling approach was used to obtain both global (EF: ejection fraction) and regional [%WT: relative regional count increase from end-diastolic (ED) to end-systolic (ES) phase] functional parameters. The gated PET parameters were compared with the corresponding findings of LVG in seven myocardial segments. EF(gated PET) and EF(LVG) did not differ significantly (30%+/-10% vs 32%+/-10%, P=NS). The two EF values correlated significantly, showing no significant systematic measurement bias [EF(gated PET) = 2.61+0.86 x EF(LVG), R=0.84, P<0.0001]. Inter- and intra-observer reproducibility for EF were R=0.95, P<0.0001 and R=0.92, P<0.0001, respectively. Regional function was evaluated with LVG in 144 myocardial segments comprising 35 normokinetic, 70 hypokinetic and 39 a/dyskinetic segments. Visual analysis of LVG and gated PET correlated significantly (P<0.001), with an overall concordance ratio of 58% (83/144, kappa=0.35). Gated PET overestimated the regional function in 27% (39/144) and underestimated it in 15% (22/144). %WT showed significant differences between each pair of groups (a/dyskinesis, 13.2%+/-9.3%; hypokinesis, 17.1%+/-8.8%; normokinesis, 21.8%+/-10.9%). Inter- and intra-observer reproducibility was significant for %WT (R=0.77, P<0.0001 and R=0.79, P<0.0001, respectively). In conclusion, gated FDG PET permits assessment of global left ventricular cardiac function. In addition, assessment of regional function is feasible using the visual or the quantitative parameters.
A statistically significant correlation was observed between the severity of anatomic stenosis and coronary flow reserve in experimental animals. A similar correlation in human coronary artery disease (CAD) was shown using positron emission tomography (PET) and pharmacologic vasodilator stress. The present study tested whether the concept of relative myocardial perfusion reserve (MPR) might be superior to absolute MPR in correlating coronary stenosis determined by quantitative coronary arteriography in patients with single vessel CAD using [13N]ammonia and PET. The study group comprised 21 patients (62 +/-10 years old; 15 men, 6 women) with normal left ventricular function who underwent angioplasty for isolated left anterior descending coronary artery stenosis. Absolute MPR, the ratio of dipyridamole-induced hyperemic blood flow to baseline blood flow by [13N]ammonia PET, and relative MPR, the ratio of MPR in regions supplied by stenosed coronary arteries to MPR in remote regions, were measured before and 3 months after angioplasty. The percent diameter stenosis was also quantified on coronary arteriograms just before the angioplasty and again at 3 months after. The study found that absolute MPR (r=0.755; p<0.0001) and relative MPR (r=0.814; p<0.0001) were inversely and nonlinearly correlated with the percent stenosis on angiography. The fitting curve of the correlation between relative MPR and coronary stenosis on angiography was identical to that observed in animal models. Therefore, relative MPR measured by [13N]ammonia PET more accurately and specifically describes stenosis severity in patients with CAD compared with absolute MPR, probably because of its independence from hemodynamic variations and the effects of coronary risk factors.
UNLABELLED: Previously, sympathetic reinnervation of the transplanted heart has been described using invasive catheterization techniques and noninvasive radionuclide imaging techniques. However, little is known about the agreement between these 2 methods. Thus, correlation between (11)C-hydroxyephedrine (HED) PET and invasively measured norepinephrine (NE) release was investigated in transplant recipients in this study. METHODS: Using PET and the catecholamine analog HED, 17 patients were studied between 2 mo and 13.6 y after transplantation. Based on results in completely denervated hearts, areas with HED retention >7%/min were defined as reinnervated. Additionally, transcardiac NE release induced by intravenous tyramine (55 microg/kg) was measured by coronary sinus and aortic catheterization within 1 wk of the PET study. NE levels between coronary sinus and aortic root, DeltaNE(CS-AO), were calculated at baseline and after tyramine administration. Differences of more than 3 SD of baseline (>163 pg/mL) were interpreted as reinnervation. RESULTS: HED retention indicated reinnervation in 10 patients. Maximal HED retention ranged from 4.3%/min to 16.4%/min. DeltaNE(CS-AO) 1 min after tyramine administration ranged between -10 pg/mL and 1157 pg/mL, and 8 patients were above the reinnervation threshold. Fisher's exact test demonstrated good agreement between results of PET and DeltaNE(CS-AO) measurements (P = 0.002). Maximal HED retention was also significantly correlated with NE release (r = 0.69; P = 0.001). CONCLUSION: Results of invasively measured NE release and noninvasive (11)C-HED PET are well correlated. This study further supports the usefulness of PET as a noninvasive approach for detection of reappearance of catecholamine uptake sites after heart transplantation.
The role of cardiac sympathetic nerves in the regulation of myocardial metabolism is not well defined. Owing to the presence of incomplete reinnervation, heart transplant recipients provide a unique model to study the effects of efferent sympathetic innervation. Using this model, we sought to determine the influence of cardiac sympathetic signals on substrate utilisation and overall oxidative metabolism. In 21 transplant recipients, positron emission tomography was applied to determine sympathetic innervation with the noradrenaline analogue carbon11 hydroxyephedrine, oxidative metabolism with carbon11 acetate (n=14), and glucose utilisation with fluorine-18 fluorodeoxyglucose (n=7). The reinnervated area comprised 22% +/- 20% of the left ventricle. Oxidative metabolism was similar in denervated and reinnervated myocardium [0.06 +/- 0.01 vs 0.06 +/- 0.01/min for k(mono)], while glucose uptake was significantly higher in denervated myocardium (6.9 +/- 6.6 vs 6.0 +/- 6.2 micromol/min/100 g; P=0.03). Reinnervation mainly occurred in the territory of the left anterior descending artery, where retention of 11C-hydroxyephedrine (6.8 +/- 2.7%/min) was higher compared with territories of the left circumflex (4.1 +/- 1.7%/min; P<0.01) and right coronary (3.8 +/- 1.1%/min; P<0.01) arteries. Oxidative metabolism was similar in all three territories, but compared with the reinnervated territory of the left anterior descending artery (53% +/- 16% of maximum), relative FDG uptake was higher in territories of the left circumflex (76% +/- 6%, P<0.01) and right coronary (67% +/- 10%, P<0.05) arteries. Similar degrees of regional heterogeneity were not observed in normals. Thus, while overall energy production through oxidative metabolism remains unaffected, cardiac utilisation of glucose in the fasting state is increased in the absence of catecholamine uptake sites. Innervated myocardium, however, may preferentially utilise free fatty acids, suggesting a role for sympathetic tone in substrate utilisation.
PURPOSE: The purpose of this study was to determine the effects of disopyramide and verapamil on the renal handling of cisplatin (CDDP) and nephrotoxicity in rats. The stereoselective effect of verapamil was also studied. METHODS: CDDP was administered to rats by i.v. bolus injection or by infusion at a constant rate with or without concomitant administration of racemic disopyramide, racemic verapamil, or each verapamil enantiomer. The concentrations of CDDP in plasma and in the kidney and liver were determined by HPLC. In separate experiments, CDDP was administered as described above, and blood urea nitrogen (BUN) was monitored for 7 days. RESULTS: The BUN level after administration of CDDP was significantly reduced by coadministration of either disopyramide or verapamil. Renal accumulation of CDDP was significantly reduced by these drugs, whereas accumulation into the liver was not significantly changed. The relationship between the BUN levels and the area under the curve of CDDP concentration in the kidney versus time (AUCk) was analyzed using a sigmoid Emax model; this showed that the reduced BUN levels were explained by the AUCk. Furthermore, verapamil showed stereoselective inhibition of the renal accumulation of CDDP. CONCLUSIONS: The renal accumulation of CDDP was inhibited by disopyramide and verapamil, and this inhibition resulted in the amelioration of nephrotoxicity.
A conventional equivalent current dipole estimation provides one of the quantitative measures to evaluate the discrepancy between two single-dipole-like magnetic field patterns, though there is one problem; all stimulus positions in the visual field do not necessarily contribute to the generation of a single-dipole-like magnetic field. Another important problem occurs when the field pattern is complex and cannot be approximated by a dipole. This makes it difficult to evaluate the discrepancy between two magnetic field patterns by the dipole parameters. In this paper, we determined the stimulus positions adequate for generating single-dipole-like magnetic field patterns by evaluating the magnetic field's goodness-of-fit to the field generated by a single dipole. We propose to use a similarity (SIM) as a quantitative measure of the discrepancy between two complex magnetic field patterns. The SIM is defined as an angle between two magnetic field vectors. We evaluated the discrepancy between the 100 ms post-stimulus responses to pattern-reversal (Rv) stimulus, pattern-onset (Pat) stimulus, and luminance-onset (Lumi) stimulus. The following results were obtained: (1) Stimulation of some of the octants in the fovea, far from the vertical meridian, elicited a single-dipole-like magnetic field pattern at a latency of 100 ms, though stimulation of the central part of the fovea, and stimulation of the octants along the vertical meridian, did not elicit a single-dipole-like magnetic field pattern; (2) The discrepancy between responses was quantitatively evaluated by the SIM even if the field patterns were complex; (3) The SIM analysis showed that the discrepancy between the responses to the Rv and the Lumi stimuli, as well as that between the responses to the Pat and the Lumi stimuli, were greater than that between the responses to the Rv and the Pat stimuli.
The effects of epidermal growth factor (EGF) on neonatal intestines were examined in the rat. In 5-day-old rats, sucrase, trehalase, alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (gamma-GTP) activities in the small intestines were significantly increased after subcutaneous injection of EGF for 3 days (1 microgram/rat/day). gamma-GTP activity was also accelerated after oral EGF administration (2 micrograms/rat/day). Small intestines of 12-day-old rats injected with EGF for 10 days (1 microgram/rat/day) were significantly heavier than those of controls. These results suggest that EGF influences neonatal growth improving enlargement and functional development of their intestines.
The effects of epidermal growth factor (EGF) on fetal growth were examined in mice. EGF is synthesized in large amounts by the mouse submandibular glands. On the 18th day of gestation, the body weight of fetuses whose mothers had undergone sialoadenectomy (excision of the submandibular glands) was significantly lower than that of controls. However, the maternal-plasma EGF concentration was not significantly affected by sialoadenectomy. The body weight of fetuses whose mothers were injected with EGF for 7 days during pregnancy was significantly higher than that of controls. Sialoadenectomy altered the blood amino acid concentrations in adult female animals, especially the levels of leucine and isoleucine. These results suggest that EGF influences fetal growth mainly by regulating maternal nutrition.
Magnetic compound action fields (CAFs) evoked by electrical stimulation of the median nerve at the wrist were recorded with 7-channel 2nd-order SQUID gradiometers. CAFs measured over the elbow and upper arm were biphasic with field patterns and polarities corresponding to the depolarization and repolarization fronts of the action potential volley.
Surface harmonic expansions are used to represent boundaries between regions of different conductivity in the human head. This facilitates calculation of the electric potential and magnetic field generated by neural current sources using discretized integral equations.
Chemotherapy for liver metastasis of breast cancer has rarely been found effective. We devised a new regimen of chemotherapy for recurrent breast cancer mainly using ifosfamide. It was found clinically applicable and particularly effective for liver metastasis. The tumor decreased in size and the levels of various tumor-markers markedly decreased following drug administration. This treatment has made for longer survival for some patients. Side effects could be well controlled with steroid hormones and Na-bicarbonate.
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Decreased reactivity in mixed lymphocyte culture (MLC) was observed in patients within 1 yr after allogeneic and autologous bone marrow transplantation. Suppressor activity of peripheral blood mononuclear cells (PBMC) from transplant patients was studied by adding these cells as modulator cells to a bidirectional MLC with cells from normal individuals. PBMC from transplant patients markedly suppressed MLC reactivity in a dose-dependent manner. Suppressor activity was present in cells forming rosettes with sheep erythrocytes. Treatment of modulator cells with monoclonal antibodies against T cell differentiation antigens (OKT8, OKIa1) and complement completely abolished suppression of MLC. Suppressor activity was unaffected by 30 Gy irradiation. Suppressor activity declined gradually after transplantation and was inversely correlated with MLC reactivity of each patient at a significant level (p less than 0.01). These observations suggest that OKT8+ Ia+ radioresistant suppressor T cells play a role in the development of decreased MLC reactivity observed during the early post-transplant period.
The effect of peripheral blood mononuclear cells (PBMCs) from bone marrow recipients on in vitro growth of erythroid burst-forming units (BFU-E) was studied. PBMCs were obtained from 5 allogeneic, 1 syngeneic and 1 autologous bone marrow recipient(s) at different intervals after transplantation. The number of BFU-E was significantly increased when donor bone marrow cells were co-cultured with PBMCs obtained from allogeneic marrow recipients in the early post-transplant period. No effect was observed using PBMCs obtained in the later post-transplant period, PBMCs from a syngeneic marrow recipient, or PBMCs from an autologous marrow recipient. The BFU-E enhancing activity was present among T cells and was abolished by treating them with OKT3 or OKT4 antibody and complement. These observations suggest that chimeric T lymphocytes, probably of the helper/inducer subset, from allogeneic marrow recipients in the early post-transplant period have a potent enhancing effect on in vitro erythropoiesis.
Autologous mixed lymphocyte culture (AMLR) is an immunologic response with memory and specificity and plays a role in immune regulation. Effects of T cells activated by AMLR were studied in the regulation of in vitro erythropoiesis. AMLR-activated T cells were cocultured with autologous non-T, nonphagocytic peripheral blood mononuclear cells for assaying erythroid progenitor cells (BFU-E). T cells activated for 3 days in AMLR showed significant enhancement of in vitro colony growth by BFU-E. In contrast, activated T cells from day 7 AMLR caused significant suppression of BFU-E growth. Both enhancing and suppressing activities of AMLR-activated T cells were mediated by an la-positive and radiosensitive population within the OKT4+ subset. These observations suggest that AMLR-activated T cells may play a role in the immune-mediated regulation of in vitro erythropoiesis. It is also suggested that heterogeneous T-cell subsets may exert regulatory functions in the regulation of in vitro hematopoiesis.
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