Biomedical subjects

J Konishi

Publications and source records attributed to J Konishi.

At least 19 recordsLinked to original sources

PubMed2005

MR tractography for the evaluation of functional recovery from lenticulostriate infarcts.

OBJECTIVE: To evaluate the anatomic and clinical relationship between the lenticulostriate artery (LSA) territory and the corticospinal tract (CST) in patients with acute infarcts in this territory using MR tractography. METHODS: Thirteen consecutive patients who presented with acute infarcts in the LSA territory and who also had undergone an MRI study within 3 days after symptom onset were studied. Visualization of the CST was achieved by postprocessing the acquired diffusion tensor imaging data. To classify lesion location, the LSA territory was divided into four subsegments, the boundaries of which were drawn by axial and coronal planes crossing through the foramen of Monro. Infarct volume and extent of CST involvement were measured and compared with neurologic findings. RESULTS: All of the infarcts were located in the posterior segment. All of the depicted CSTs crossed the LSA territory only at the posterosuperior quadrant. The extent of CST involvement within the infarcts was correlated with the severity of the patient's motor deficit (p < 0.01) and with the clinical outcome (p < 0.05). CONCLUSIONS: The corticospinal tracts (CSTs) crossed the lenticulostriate artery territory exclusively at the posterosuperior quadrant, and the degree of CST involvement within the infarcts was directly related to stroke severity and functional recovery.

Adult↗

PubMed2004

Decrease in cortical benzodiazepine receptors in symptomatic patients with leukoaraiosis: a positron emission tomography study.

BACKGROUND AND PURPOSE: [11C]flumazenil (FMZ), a ligand that selectively binds to the central benzodiazepine receptor in the neuronal membrane, is useful for evaluating neuronal viability in a positron emission tomography (PET) scan. Using this ligand, we investigated whether there was a correlation between neuronal integrity in various brain structures and dementia in patients with leukoaraiosis. METHODS: Twelve patients with extensive leukoaraiosis on magnetic resonance imaging were divided into groups of patients with or without dementia. Based on a 2-compartment, 2-parameter model that included metabolite-corrected arterial input and PET-measured cerebral radioactivity, the distribution volume of FMZ (FMZ-V(d)) was calculated in various regions of interest by nonlinear curve fitting. Additionally, tracer kinetic analysis was applied for voxel-by-voxel quantification of FMZ-V(d), and data analysis was performed by statistical parametric mapping. RESULTS: The presence of dementia was associated with a reduced FMZ-V(d) in widespread areas of the cerebral cortex, including the bilateral frontopolar and frontal/insular areas, the left temporo-occipital border areas, and the left marginal cortical areas. CONCLUSIONS: Differences in neuronal integrity in the cerebral cortex might determine whether patients with leukoaraiosis become symptomatic or not.

Aged↗

PubMed2003

2-(2'-Hydroxyphenyl)benzene sulfinate desulfinase from the thermophilic desulfurizing bacterium Paenibacillus sp. strain A11-2: purification and characterization.

2-(2'-Hydroxyphenyl)benzene sulfinate (HPBSi) desulfinase (TdsB), which catalyzes the final step of desulfurization of dibenzothiophene (DBT), was purified from a thermophilic DBT- and benzothiophene (BT)-desulfurizing bacterium: Paenibacillus sp. strain A11-2. The molecular mass of the purified enzyme was 31 kDa and 39 kDa by gel filtration and sodium dodecyl sulfate polyacrylamide gel electrophoresis, respectively, suggesting a monomeric structure. The optimal temperature and pH for the reaction involving TdsB was 55 degrees C and the enzyme was more resistant to heat treatment than DszB, a counterpart purified from Rhodococcus erythropolis. The optimum pH for TdsB activity was pH 8. TdsB converted HPBSi to 2-hydroxybiphenyl (2-HBP) and sulfite stoichiometrically. The Km and kcat values for HPBSi were 0.33 mM and 0.32 s(-1), respectively. TdsB was inactivated by SH reagents such as p-chloromercuribenzoic acid and 5,5'-dithio-bis-2-nitrobenzoic acid, but was not inhibited by chelating reagents such as EDTA and o-phenanthroline. TdsB was also inhibited by o-hydroxystyrene, the final desulfurized product of BT. However, 2-HBP and its derivatives showed only a weak inhibitory effect. TdsB desulfurized 2-(2'-hydroxyphenyl)ethen-1-sulfinate to yield o-hydroxystyrene, but DszB could not. A site-directed mutagenesis study revealed the cysteine residue at position 17 to be essential to the catalytic activity of TdsB.

Bacillaceae↗

PubMed2002

Purification and characterization of the monooxygenase catalyzing sulfur-atom specific oxidation of dibenzothiophene and benzothiophene from the thermophilic bacterium Paenibacillus sp. strain A11-2.

A benzothiophene (BT) and dibenzothiophene (DBT) monooxygenase (TdsC), which catalyzes the oxidation of the sulfur atoms in BT and DBT molecules, was purified from Paenibacillus sp. strain A11-2. The molecular mass of the purified enzyme and its subunit were determined to be 200 kDa and 43 kDa by gel filtration and sodium dodecyl sulfate polyacrylamide gel electrophoresis, respectively, indicating a tetrameric structure. The N-terminal amino acid sequence of the purified TdsC completely matched the amino acid sequence deduced from the nucleotide sequence of the tdsC gene reported previously [Ishii et al. (2000) Biophys Biochem Res Commun 270:81-88]. The optimal temperature and pH for the TdsC reaction were 65 degrees C and pH 9, respectively. TdsC required NADH, FMN and TdsD, a NADH-dependent FMN oxidoreductase, for its activity, as was observed for TdsA. FAD, lumiflavin and/or NADPH had some effect on the maintenance of TdsC activity. A comparison of the substrate specificity of TdsC and DszC, the homologous monooxygenase purified from Rhodococcus erythropolis strain KA2-5-1, demonstrated a contrasting pattern towards alkylated DBTs and BTs.

Alkylation↗

PubMed2002

Biodesulfurization of benzothiophene and dibenzothiophene by a newly isolated Rhodococcus strain.

Rhodococcus sp. KT462, which can grow on either benzothiophene (BT) or dibenzothiophene (DBT) as the sole source of sulfur, was newly isolated and characterized. GC and GC-MS analyses revealed that strain KT462 has the same BT desulfurization pathway as that reported for Paenibacillus sp. A11-2 and Sinorhizobium sp. KT55. The desulfurized product of DBT produced by this strain, as well as other DBT-desulfurizing bacteria such as R. erythropolis KA2-5-1 and R. erythropolis IGTS8, was 2-hydroxybiphenyl. A resting cells study indicated that this strain was also able to degrade various alkyl derivatives of BT and DBT.

Biodegradation, Environmental↗

PubMed2002

Abnormal cortical mechanisms of voluntary muscle relaxation in patients with writer's cramp: an fMRI study.

Although it is hypothesized that there is abnormal motor inhibition in patients with dystonia, the question remains as to whether the mechanism related to motor inhibition is specifically impaired. The objective of the present study was to clarify the possible abnormalities of the mechanisms underlying voluntary muscle relaxation during motor preparation and execution in patients with writer's cramp, using event-related functional MRI. Eight patients with writer's cramp and 12 age-matched control subjects participated in the study. Two motor tasks were employed as an experimental paradigm. In the relaxation task, subjects were asked to hold their right wrist in the horizontal plane by maintaining moderate contraction of wrist extensor muscles in the premotor phase; they relaxed those muscles voluntarily just once during each fMRI scanning session. In the contraction task, subjects extended the right wrist voluntarily from the same premotor state as for the relaxation task. Five axial images covering the primary sensorimotor cortex (SMC) and supplementary motor area (SMA) were obtained once every second. Activated volumes in the left SMC and the SMA were significantly reduced in patients for both muscle relaxation and contraction tasks. These data suggest that there is impaired activation in both SMC and SMA in voluntary muscle relaxation and contraction in patients with writer's cramp. This implies that abnormalities of both inhibitory and excitatory mechanisms in motor cortices might play a role in the pathophysiology of focal dystonia.

Adult↗

PubMed2001

Dynamic micro-magnetic resonance imaging of liver micrometastasis in mice with a novel liver macromolecular magnetic resonance contrast agent DAB-Am64-(1B4M-Gd)(64).

DAB-Am64-(1B4M-Gd)(64) is a newly synthesized macromolecular liver magnetic resonance imaging (MRI) contrast agent with a polypropylenimine diaminobutane (DAB) dendrimer conjugated with a bifunctional diethylenetriaminepentaacetic acid (DTPA) derivative for complexing Gd(III) atoms. The characteristics of DAB-Am64-(1B4M-Gd)(64), which quickly accumulated in the liver, have been reported recently. In the present study, the dynamic micro-MRI with DAB-Am64-(1B4M-Gd)(64) was obtained in the mouse liver metastasis model using colon carcinoma cells to evaluate the ability to visualize the micrometastatic tumors compared with that using Gd-DTPA. The dynamic micro-MRI with DAB-Am64-(1B4M-Gd)(64) was able to homogeneously enhance the normal liver parenchyma and visualize micrometastatic tumors of 0.3-mm diameter in the liver of the mice with better contrast than that with Gd-DTPA. In conclusion, DAB-Am64-(1B4M-Gd)(64) is a new liver MRI contrast agent potentially useful for diagnosis of micrometastasis in the liver.

Animals↗

PubMed2001

Neural substrates involved in imitating finger configurations: an fMRI study.

Imitation plays a very important role in human cognition. Because previous neuroimaging studies on human imitation used rather simple actions as target stimuli, some aspects of imitation such as perceiving target actions or manipulating one's own mental image could not be studied. We used complicated non-symbolic (S-) and symbolic (S+) finger configurations as target stimuli in order to study the neural substrates involved in the perception of target actions and mental image manipulation during imitation. Bilateral supramarginal gyrus activation was detected when the S- condition was compared with the S+ condition. Our result suggests the involvement of the supramarginal gyrus especially for the imitation of novel actions.

Adult↗

PubMed2001

3D-micro-MR angiography of mice using macromolecular MR contrast agents with polyamidoamine dendrimer core with reference to their pharmacokinetic properties.

Four novel macromolecular MRI contrast agents, all of which had the same chemical composition but different molecular weights, were prepared using generation-3, -4, -5, and -6 polyamidoamine (PAMAM) dendrimers conjugated with a bifunctional diethylenetriaminepentaacetic acid derivative to change the blood retention, tissue perfusion, and excretion. Size-dependent changes in the pharmacokinetics were observed in the biodistribution study. (153)Gd-labeled generation-6 PAMAM-conjugates remained in the blood significantly longer than all of the other preparations (P < 0.001). The increase in blood-to-organ ratio of the preparations was found to correlate with increasing molecular size (P < 0.001). Additionally, 3D-micro MR images and angiography of mice of high quality and detail were obtained using PAMAM-(1B4M-Gd)x as a macro-molecular MRI contrast agent with a 1.5-T clinical MRI instrument. Numerous fine vessels of approximately 200 microm diameter were visualized on subtracted 3D-MR angiographms with G6D-(1B4M-Gd)(192). The quality of the images was sufficient to estimate the microvasculature of cancerous tissue for anti-angiogenesis therapy and to investigate knockout mice. Magn Reson Med 45:454-460, 2001.

Animals↗

PubMed2001

Micro-MR angiography of normal and intratumoral vessels in mice using dedicated intravascular MR contrast agents with high generation of polyamidoamine dendrimer core: reference to pharmacokinetic properties of dendrimer-based MR contrast agents.

Pharmacokinetic characteristics of intravascular macromolecular magnetic resonance imaging (MRI) contrast agents with polyamidoamine dendrimer cores smaller than generation-7 were previously studied in the literature. To evaluate the effects of greater hepatic uptake on the pharmacokinetics of the larger generation dendrimers, the MRI contrast agents GxD-(1B4M-Gd)(2(x+2)) were synthesized with generation-7, -8, and -9 polyamidoamine dendrimers and 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid (1B4M). Their pharmacokinetic characteristics in mice were compared with that of G6D-(1B4M-Gd)(256). In biodistribution and dynamic micro-MRI studies, significantly less renal accumulation of G7D-(1B4M-Gd)(512), G8D-(1B4M-Gd)(1024), and G9D-(1B4M-Gd)(2048) was shown compared to G6D-(1B4M-Gd)(256) (P < 0.01). There was a significantly greater accumulation of G8D-(1B4M-Gd)(1024) and G9D-(1B4M-Gd)(2048) in the liver compared to G6D-(1B4M-Gd)(256) and G7D-(1B4M-Gd)(512) (P < 0.01). The highest blood retention of all dendrimer-based MRI contrast agents was exhibited by G7D-(1B4M-Gd)(512) (P < 0.01). The normal and intratumoral fine vessels of approximately 100 microm diameter were visualized in normal or tumor-bearing mice by high resolution three-dimensional-micro-MR angiographs with G7D-(1B4M-Gd)(512) and G8D-(1B4M-Gd)(1024) with good vessel-to-soft tissue contrast. In summary, increased accumulation in the liver with concomitant decreased uptake in the kidney was caused by increased molecular sizes of the dendrimer-based MRI contrast agents.

Analysis of Variance↗

PubMed2001

Novel intravascular macromolecular MRI contrast agent with generation-4 polyamidoamine dendrimer core: accelerated renal excretion with coinjection of lysine.

One of the major limitations to macromolecular MRI contrast agents (MRI-CAs) is their slow clearance and associated decreased excretion of gadolinium (Gd(III)). The effect of coinjecting lysine to accelerate renal excretion of a macromolecular MRI-CA (generation-4 PAMAM dendrimer (G4D-(1B4M-Gd)64)) was investigated. The biodistribution and urine and fecal excretion in athymic mice was evaluated with and without lysine coinjection. 3D-dynamic-micro-MRI with G4D-(1B4M-Gd)64 was obtained with and without lysine coinjection, and the serial signal intensity (SI) change in the blood and organs was evaluated. When lysine was coinjected, urinary excretion of G4D-(1B4M-Gd)64 increased 5.4-fold compared to that without lysine, resulting in decreased renal accumulation of G4D-(1B4M-Gd)64 from 150% to 40% injected dose per gram (P < 0.001). On dynamic MRI with G4D-(1B4M-Gd)64, when lysine was coinjected, the kidney-to-blood SI ratio was significantly lower than that obtained without lysine (P < 0.001). When lysine was coinjected, the G4D-(1B4M-Gd)64 was excreted from the kidney intact.

Animals↗

PubMed2001

3D MR angiography of intratumoral vasculature using a novel macromolecular MR contrast agent.

Noninvasive methods to visualize blood flow in the intratumoral vasculature have not previously been studied. In the present study, the use of a novel intravascular MR contrast agent with a generation-6 polyamidoamine dendrimer core (G6-(1B4M-Gd)192; MW: 175kD) was investigated, and the vasculature in experimental tumors was visualized using 3D MR angiography (MRA). Xenografted tumors in nude mice of two different histologies-KT005 (human osteogenic sarcoma) and LS180 (human colon carcinoma)-were used to obtain 3D MRA using G6-(1B4M-Gd)192 and Gd-DTPA. The contrast MR sectional images were correlated with the corresponding histological sections. The intratumoral vasculature in the KT005 tumor was clearly visualized by 3D MRA, which became more evident with the growth of the tumor xenograft. In contrast, the intratumoral vasculature in the LS180 tumor was sparser and much less developed than that in KT005 tumors. Blood vessels with a diameter as small as 100 microm based on histology were visualized using 0.033 mmol Gd/kg of G6-(1B4M-Gd)192. In conclusion, intratumoral vasculature with a 100-microm diameter was visualized better using 3D MRA with G6-(1B4M-Gd)192 than with Gd-DTPA.

Animals↗

PubMed2001

Positive effects of polyethylene glycol conjugation to generation-4 polyamidoamine dendrimers as macromolecular MR contrast agents.

Macromolecules conjugated with polyethylene glycol (PEG) acquire more hydrophilicity, resulting in a longer half-life in circulation and lower immunogenicity. Two novel conjugates for MRI contrast agents were synthesized from a generation-4 polyamidoamine dendrimer (G4D), 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid (1B4M), and one or two PEG molecules with a molecular weight of 20000 Da (PEG(2)-G4D-(1B4M-Gd)(62) (MW: 96 kD), PEG(1)-G4D-(1B4M-Gd)(63) (MW: 77 kD)). Their pharmacokinetics, excretion, and properties as vascular MRI contrast agents were evaluated and compared with those of G4D-(1B4M-Gd)(64) (MW: 57 kD). PEG(2)-G4D-(1B4M-Gd)(62) remained in the blood significantly longer and accumulated significantly less in the liver and kidney than the other two preparations (P < 0.01). Although the blood clearance was slower, PEG(2)-G4D-(1B4M-Gd)(62) was excreted more readily without renal retention than the other two preparations. In conclusion, the positive effects of PEG conjugation on a macromolecular MRI contrast agent were found to be prolonged retention in the circulation, increased excretion, and decreased accumulation in the organs.

Animals↗

PubMed2001

Novel liver macromolecular MR contrast agent with a polypropylenimine diaminobutyl dendrimer core: comparison to the vascular MR contrast agent with the polyamidoamine dendrimer core.

As MRI contrast agents, more hydrophobic molecules reportedly accumulate in the liver and thus are potentially useful as liver MRI contrast agents. In this study, a generation-4 polypropylenimine diaminobutane dendrimer (DAB-Am64), which is expected to be more hydrophobic than the generation-4 polyamidoamine dendrimer (PAMAM-G4D), was used to synthesize a conjugate with 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid (1B4M) [DAB-Am64-(1B4M-Gd)(64)] for complexing Gd(III) ions. This DAB conjugate quickly accumulated in the liver and its characteristics were studied and compared with those of a PAMAM conjugate [PAMAM-G4D-(1B4M-Gd)(64)], which is known to be a useful vascular MRI contrast agent, in regard to its availability as a liver MRI contrast agent. DAB-Am64-(1B4M-Gd)(64) accumulated significantly more in the liver and less in blood than PAMAM-G4D-(1B4M-Gd)(64) (P < 0.001). Contrast-enhanced MRI with DAB-Am64-(1B4M-Gd)(64) was able to homogeneously enhance liver parenchyma and visualize both portal and hepatic veins of 0.5 mm diameter in mice. In conclusion, DAB-Am64-(1B4M-Gd)(64) is a good candidate for a liver MRI contrast agent.

Animals↗

PubMed2001

Pharmacokinetics and enhancement patterns of macromolecular MR contrast agents with various sizes of polyamidoamine dendrimer cores.

Four macromolecular contrast agents are synthesized to visualize small vessels by MRI using generation-3 (G3D), -4 (G4D), -5 (G5D), and -6 (G6D) polyamidoamine dendrimers conjugated to chelated gadolinium (Gd). The pharmacokinetics, enhancement patterns, and the ability of these constructs to visualize fine vessels is evaluated by dynamic MRI in relationship to their size. Gd-G6D and -G5D exhibit a prolonged high vascular (ventricular) signal intensity (SI) with high ventricle-to-organ SI ratios. The initial high vascular SI with Gd-G4D decreases to a value as low as that obtained with Gd-G3D and Gd-dimeglumine-diethylenetriaminepentaacetic acid (Gd-DTPA). Gd-G5D, -G4D, and -G3D show high renal SIs, and Gd-DTPA prominently enhances the skin. Gd-G6D and -G5D present fine vasculature significantly more clearly than Gd-G3D and -DTPA (P < 0.005). As the molecular size increases, the excretion of the 153Gd-conjugates is retarded. In conclusion, Gd-G6D and -G5D are retained in the blood and present fine vessels with high quality and detail, and should be adequate for visualizing small tumor vasculature.

Animals↗

PubMed2001

Double-injection FDG method to measure cerebral glucose metabolism twice in a single procedure.

UNLABELLED: [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) may be used to examine changes in cerebral glucose metabolism in two physiological conditions. We proposed and evaluated a double injection-single session FDG method with biological constraints for this purpose. METHODS: Simulated brain time-radioactivity curves (TACs) generated by using a plasma TAC from an actual study and physiological combinations of input values in a kinetic model were analyzed to evaluate the accuracy of the proposed method. The reproducibility of the estimated values obtained by this method was tested in five normal volunteers who were studied with a dynamic PET scan and two injections of FDG in a single session while fasting. RESULTS: The simulation study showed that the estimated values obtained by the proposed method agreed well with the input values. In the human study, plasma glucose levels were 5.3 +/- 0.2 and 5.0 +/- 0.2 mM in the first and second measurements, respectively. The difference between the plasma glucose measurements was small but statistically significant (p < 0.05). Although no systematic deviations were noted in K*1 or rCMRglc, there were small deviations in K* (less than 10%) and LC (less than 5%) with a statistical significance (p < 0.01). CONCLUSION: The deviation between the measurements in K* and LC seemed to relate to the difference in the plasma glucose level. The double-injection FDG method with biological constraints can be used to estimate rCMRglc and LC sequentially in a single PET scanning session.

Blood Glucose↗

PubMed2001

Assessment of cerebral hemodynamics before and after revascularization in patients with occlusive cerebrovascular disease by means of quantitative IMP-SPECT with double-injection protocol.

UNLABELLED: The purpose of this study was to validate a double-injection (DI) method with N-isopropyl-[123I]p-iodoamphetamine (IMP) to measure regional cerebral blood flow (rCBF) twice in a single session of dynamic SPECT and to elucidate a possible role of this method to identify patients with occlusive disease of major cerebral arteries, who might benefit from cerebral revascularization procedures (CR). MATERIALS AND METHODS: Fourteen patients with occlusion or severe stenosis of the internal carotid or middle cerebral artery were studied before and after CR to assess hemodynamic changes after revascularization treatment. We quantitatively measured rCBF before and after acetazolamide (ACZ) challenge along with cerebrovascular reserve capacity (CVR) with two injections of IMP in a single session of dynamic SPECT scans (DI method). The reliability and reproducibility of the DI method were validated by means of a simulation study and in eight patients who were examined without ACZ challenge to measure baseline rCBF twice. RESULTS: The analysis of simulated noisy data with realistic noise levels showed that the errors of the estimates for the first and the second rCBF and for the increase in rCBF were 2.6%, 8.1% and 10.4%, respectively. In the 8 patients examined by the DI method to measure baseline rCBF twice, the mean and the SD of percentage differences between the two consecutive measurements in rCBF were -1.3% and 5.5%, respectively. Eight out of 14 patients with occlusive disease had at least one region with a CVR less than 10%. They showed a significant increase in resting rCBF after CR, not only in the ipsilateral hemisphere (from 26.1 +/- 6.4 to 33.4 +/- 4.7) but also in the contralateral one (from 28.3 +/- 7.0 to 34.7 +/- 4.7) with a recovery of the ipsilateral CVR from 9.3 +/- 17.2 to 41.2 +/- 20.1%. The remaining six patients with good-moderate CVR did not show an increase in rCBF after CR (from 28.0 +/- 2.7 to 28.3 +/- 3.4). The three of them with a moderate CVR (10-25%) before CR showed normalization of CVR after CR. CONCLUSION: Patients with decreased rCBF and reduced CVR benefited from CR in terms of an increase in rCBF and recovery of CVR. The quantitative double-injection IMP-SPECT has the ability to identify those patients who may benefit from CR.

Aged↗

PubMed2001

Performance assessment of O-18 water purifier.

In the synthesis of 18F-FDG by the nucleophilic substitution method, 18O-H2O is usually used as target water. The target water should be recovered after synthesis and reused, because it is expensive, but recovered water contains impurities such as organic substances, and it must be purified before reuse. For this reason Sumitomo Heavy Industries, Ltd. developed an O-18 water purifier for elimination of organic substances in recovered water. This instrument consists of a UV irradiation unit and low-temperature distillation unit. Our institution had an opportunity to test use this instrument and evaluated its performance. The concentrations of organic substances after UV irradiation was greatly reduced, and recovery efficiency after distillation by the low-temperature distillation unit was very satisfactory at 99.3 +/- 0.5%. Furthermore, the yield of 18F-FDG from 18O-H20 purified with this instrument was sufficient for the clinical use.

Fluorodeoxyglucose F18↗