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K Ishizu

Publications and source records attributed to K Ishizu.

At least 19 recordsLinked to original sources
PubMed2007

Association of vascular parkinsonism with impaired neuronal integrity in the striatum.

The purpose of this study is to identify the underlying differences between patients with white matter lesions (WMLs) who manifested gait disturbance suggestive of vascular parkinsonism (VaP) and those who did not, using the PET scan. Fourteen patients with extensive WMLs, as determined by MRI, were divided into two groups - 7 with gait disturbance and 7 without it. Neuronal integrity was evaluated with a PET scan using [(11)C]flumazenil (FMZ) by calculating the distribution volume of FMZ (FMZ-V(d)) in various regions of interest by non-linear curve fitting. Additionally, tracer kinetic analysis was applied for voxel-by-voxel quantification of FMZ-V(d) and data analysis was performed using statistical parametric mapping. The striatal FMZ-V(d) values were inversely correlated with the motor UPDRS scores (r = 0.70, p < 0.005), and their reductions were associated with the presence of gait disturbance. Therefore, differences in neuronal integrity in the striatum may determine whether patients with WMLs develop VaP or not.

Aged↗
PubMed2006

Prefrontal hypofunction in patients with intractable mesial temporal lobe epilepsy.

We compared the cognitive functions and interictal cerebral glucose metabolism of 11 patients with mesial temporal lobe epilepsy (MTLE) with frequent seizures to those of 10 patients with MTLE with rare seizures; the groups were matched for age, sex, education, IQ, and focus side. The frequent-seizure group had more set-shifting impairment that correlated with glucose hypometabolism in the prefrontal cortices. Our results suggest that frequent seizures in MTLE are associated with hypofunction of the prefrontal cortex.

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↗
PubMed2001

[14C]Serotonin uptake and [O-methyl-11C]venlafaxine kinetics in porcine brain.

As part of our program of developing PET tracers for neuroimaging of psychotropic compounds, venlafaxine, an antidepressant drug, was evaluated. First, we measured in vitro rates of serotonin uptake in synaptosomes prepared from selected regions of porcine brain. Then, we determined the pharmacokinetics of venlafaxine, [O-methyl-11C]-labeled for PET. Synaptosomal studies showed that the active uptake of [14C]5-HT differed markedly between brain regions, with highest rates in hypothalamus, raphé region, and thalamus, and lowest rates in cortex and cerebellum. PET studies showed that the unidirectional rate of uptake of [O-methyl-11C]venlafaxine from blood to brain was highest in the hypothalamus, raphé region, thalamus and basal ganglia and lowest in the cortex and cerebellum. Under normal physiological conditions, the capillary permeability-surface area (PS) product for [O-methyl-11C]venlafaxine could not be estimated, because of complete flow-limitation of the cerebral uptake. Nevertheless, a correlation occurred between the apparent partition volume of the radiotracer and the rate of active uptake of 5-HT in selected regions of the porcine brain. During hypercapnia, limitations of blood-brain transfer were observed, giving PS-products for water that were only ca. 50% higher than those of venlafaxine. Thus, under normal physiological conditions, the rate of uptake of venlafaxine from blood into brain is completely flow-limited.

Animals↗
PubMed2001

[A case of infected urachal cyst successfully drained by a catheter perforating the bladder].

A 42-year-old man complained of lower abdominal pain. Computed tomographic scan and magnetic resonance imaging revealed an infected urachal cyst. A drainage catheter, which had multiple holes over a 10 cm length from the catheter tip, was placed in the urachal cyst. The catheter was inserted from the subumbilicus region and the catheter tip was intended to be situated at the caudal end of the urachal cyst. However, the catheter tip accidentally perforated the bladder and urine flowed out of the bladder through the catheter. Because the urine diluted and washed out the pus in the urachal cyst, the infected urachal cyst was successfully drained. Percutaneous drainage and antibiotics allowed resolution of the inflammatory process. On the twenty-third day after catheter placement, excision of the urachal cyst and partial cystectomy were performed with relative ease and without any complications.

Adult↗
PubMed2000

Solution Properties of Star-Shaped Polystyrenes Having Peripheral Charged Ions.

Functionalized polystyrene stars were prepared by copolymerization of polystyryl lithium with divinylbenzene in a mixture of benzene/tetrahydropyran, where the polystyrene arms were prepared by anionic polymerization using [2-[(N,N-dimethylamino)-methyl]phenyl]lithium as the initiator. These functional stars were converted by quaternization with methyl iodide into polystyrene stars having peripheral positive charges. We studied the charge effects on the solution properties of such stars. The hydrodynamic dimension of peripheral charged polystyrene (PS) stars depended strongly on the solubility parameter between PS segments and solvent. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Positron emission tomography of radioligand binding in porcine striatum in vivo: haloperidol inhibition linked to endogenous ligand release.

The ligands N-methylspiperone and haloperidol both bind to D(2)-like dopamine receptors. The competitive nature of the binding over a wide range of haloperidol concentrations and the effect on dopamine release have never been tested in vivo. We determined the competitive interaction between 3-N-[(11)C]methylspiperone ([(11)C]NMSP) and haloperidol binding to striatal dopamine D(2)-like receptors with positron emission tomography (PET) of pig brain. [(11)C]NMSP tomography was performed with haloperidol at five different plasma concentrations maintained constant by programmed infusion. Kinetic parameters of ligand competition for binding in the striatum were determined by deconvolving time-activity curves of the striatum and cerebellum from metabolite-corrected arterial plasma [(11)C]NMSP and haloperidol concentrations. Two types of [(11)C]NMSP-binding sites were evident in the striatum, both saturable by haloperidol administration. The preponderant or primary sites bound [(11)C]NMSP irreversibly, as dopamine D2-like receptors, while the secondary sites bound [(11)C]NMSP reversibly, as do serotonin S2 receptors. Woolf-Hanes plots revealed the predicted approximately linear relationships between the binding indices and the haloperidol plasma concentration. For the irreversible binding sites, this relationship indicated a 50% inhibitory concentration of haloperidol of 2 nM in plasma and a maximum binding capacity of 64 pmol cm(-3) in striatum. For the reversible binding sites, the relationship indicated a 50% inhibitory plasma concentration of haloperidol of 1 nM and a maximum binding capacity of 4.5 pmol cm(-3). Second-order polynomial Eadie-Hofstee-Scatchard plots were consistent with increased competition from an endogenous ligand of the irreversibly binding sites only with increasing doses of haloperidol. At the highest haloperidol dose, this hypothetical endogenous ligand had risen 6-7-fold. We contend that this reveals the release of dopamine by high concentrations of haloperidol.

Animals↗
PubMed2000

Increased cortical activation during hearing of speech in cochlear implant users.

To investigate the cortical activities while listening to noise and speech in cochlear implant (CI) users, we compared cerebral blood flow in postlingually deafened CI users with that in normal hearing subjects using positron emission tomography. While noise activation in CI users did not significantly differ from that in normal subjects, hearing speech activated more cortical areas in CI users than in normal subjects. A comparison of speech activation in these two groups revealed higher activation in CI users not only in the temporal cortices but also in Broca's area and its right hemisphere homologue, the supplementary motor area and the anterior cingulate gyrus. In postlingually deafened subjects, the hearing of speech coded by CI may be accompanied by increased activation of both the temporal and frontal cortices.

Adult↗
PubMed2000

Detection and a possible mechanism of magnetic field effect on the crystal growth of sedimentary calcium carbonate.

Sedimentary calcium carbonate was grown at a physiological pH6.8 from a mixture of equivolume of 70 mM Ca(NO(3))(2) and 70 mM NaHCO(3) aqueous solution. The kinetics of the crystal growth was monitored by means of turbidity measurement. The apparent absorption is gradually increased with the elapsed time after the mixing and reaches its maximum at t(max). The average t(max) is significantly decreased from =467 s (for n=13 runs) to 408 s (n=13) by application of the static magnetic field (SMF) of H=400 mT to the precipitating solution. The application of SMF at 120 s later the mixing shows the same =396 s (n=9) as that of 408 s. It has been thus detected that the application of SMF is ineffective in the stage of the nucleation or the earlier stage of the crystal growth but effective in the Ostwald ripening stage of the growth nucleus or the later stage of the crystal growth where large numbers of the growing crystalline particles seem greater than a few hundred nanometers. A possible mechanism for the SMF effect is as follows. An ion escaping from the growing crystal surface with a certain 'migration velocity' due to a random walk process has significant probability to drift onto the identical surface or at least the identical crystal by means of Lorentz force, because the translational displacement of the crystal during a cycle of the cyclotron motion of the ion is smaller than the size of the growing crystal. This type of drift results in the suppression of re-dissolution of the ions on the growing surface and in the acceleration of the growth in the later stage of the crystal growth. The undetected SMF effect in the earlier stage of the crystal growth can be partly attributed to the re-dissolution due to the thermodynamic instability of the small nuclei which predominates over the presumable SMF effect. This can be partly ascribed to the large translational displacement of the small particle. The application of this mechanism to an oscillating magnetic field will predict the presence of a window for the frequency of the oscillating magnetic field.

Journal Article↗
PubMed2000

The magnetic field effect affecting on the metallic chemical components of egg shell as demonstrated for breeding chicken.

The chickens were raised under fixation of the permanent magnet (80 mT) and the effect of extra magnetic field, which affects on the content of the several inorganic chemical elements of egg shell, was investigated by X-ray fluorescence spectroscopy. From 3 days after fixing the magnet, the relative concentration of Ca begun to increase. After 10 days, the relative contents of Ca were decreased, while conversely the contents of K were increased. Though there was a linear relationship between Ca content and P content in inner layer of chicken egg shell, the relationship was greatly hindered by applying the static magnetic field. The experimental result suggests that both Ca and K ion transport can be perturbed by addition of extra magnetic field in the incubation processes of chicken egg, and that Ca, P and K ions play the important role in egg shell formation.

Journal Article↗
PubMed2000

Cortical networks subserving the perception of tinnitus--a PET study.

Subjective tinnitus is an auditory phantom perception that may arise from any aberrant signal within the auditory system. Further processing of this signal and the conscious perception of tinnitus takes place in the cerebral cortex. A few functional brain-imaging studies have been performed to elucidate the underlying cerebral mechanisms of this perception. These studies mostly concern rare types of tinnitus (e.g. tinnitus changeable by oral-facial movements), or compared tinnitus patients with healthy volunteers. These studies attributed variable activation of the primary auditory cortices, associative auditory cortices and the left hippocampus to the perception of tinnitus. Based on these heterogeneous results, no consensus on the underlying mechanisms has been reached. The aim of the present study was to obtain further details of the central perception and processing of the tinnitus signal. Positron emission tomography (PET) was used to map the tinnitus-specific central activity. By contrasting PET-images of suppressed tinnitus with PET-images of the habitual tinnitus sensation, we were able to identify a right prefrontal-temporal network associated with the perception of tinnitus. Besides the evidence of activation of associative auditory sensory regions, the results indicated that activation of cortical centres subserving attention and emotion may underlie the continuous irritability associated with severe tinnitus.

Adult↗
PubMed2000

A novel weekday-on/weekend-off UFT schedule.

In a step toward a clinical trial, the tumor response and survival of a weekday-on/weekend-off schedule of UFT was compared with its conventional daily schedule in a cancer-bearing rat model. The dose-intensive schedule--600 mg of UFT for 5 days followed by 2 drug-free days--amounts to a weekly dose similar to the conventional schedule of 400 mg/day. The weekday-on/weekend-off schedule provided increased survival and significantly greater antitumor activity than the conventional daily schedule, with no difference in adverse reactions. A study was also conducted in human subjects to measure fluorouracil (5-FU) concentrations that identified the pharmacokinetic activity during the 2 drug-free days of the weekday-on/weekend-off schedule. The plasma 5-FU concentration declined markedly after 24 hours, but the concentration in the tumor remained at a relatively high level after 2 days off the drug. A one-year clinical study evaluated the compliance and toxicity of the weekday-on/weekend-off UFT schedule as adjuvant chemotherapy for colorectal cancer. Based on the findings of all these studies, the weekday-on/weekend-off schedule for UFT as adjuvant chemotherapy for colorectal cancer can be recommended for a clinical trial.

Administration, Oral↗
PubMed1999

Potent antitumor activity of MS-247, a novel DNA minor groove binder, evaluated by an in vitro and in vivo human cancer cell line panel.

We synthesized a novel anticancer agent MS-247 (2-[[N-[1-methyl-2-[5-[N-[4-[N,N-bis(2-chloroethyl) amino] phenyl]] carbamoyl]-1H-benzimidazol-2-yl] pyrrol-4-yl] carbamoyl] ethyldimethylsulfonium di-p-toluenesulfonate) that has a netropsin-like moiety and an alkylating residue in the structure. We evaluated antitumor activity of MS-247 using a human cancer cell line panel coupled with a drug sensitivity database and subsequently using human cancer xenografts. The average MS-247 concentration required for 50% growth inhibition against a panel of 39 cell lines was 0.71 microM. The COMPARE analysis revealed that the differential growth inhibition pattern of MS-247 significantly correlated with those of camptothecin analogues and anthracyclins, indicating that MS-247 and the two drug groups might have similar modes of action. MS-247 exhibited remarkable antitumor activity against various xenografts. A single i.v. injection of MS-247 significantly inhibited the growth of all 17 xenografts tested, which included lung, colon, stomach, breast, and ovarian cancers. In many cases, MS-247 was more efficacious than cisplatin, Adriamycin, 5-fluorouracil, cyclophosphamide, VP-16, and vincristine and was almost comparable with paclitaxel and CPT-11; these are the most clinically promising drugs at present. MS-247 was noticeably more effective than paclitaxel (in HCT-15) and CPT-11 (in A549, HBC-4, and SK-OV-3). The toxicity of MS-247, indicated by body weight loss, was reversible within 10 days after administration. The MS-247 mode of action showed DNA binding activity at the site where Hoechst 33342 bound, inhibited topoisomerases I and II (as expected by the COMPARE analysis) blocked the cell cycle at the G2-M phase, and induced apoptosis. These results indicate that MS-247 is a promising new anticancer drug candidate to be developed further toward clinical trials.

Animals↗
PubMed1999

Synthesis and Structural Ordering of Gradient-Modulus Star Copolymers.

Gradient-modulus star copolymers were synthesized by crosslinking of polystyrene/isoprene tapered anions with divinylbenzene in benzene. The styrene content in the tapered arm was determined by 1H-nuclear magnetic resonance as a parameter of conversion. The composition of the arm showed the gradient structure and was in good agreement with that calculated by reactivity ratios. The solution properties of gradient-modulus star copolymers were examined by static and dynamic light scatterings. The structural ordering of gradient-modulus star copolymers were investigated by means of small-angle X-ray scattering. Gradient-modulus star copolymers formed a body-centered cubic (BCC) structure near the overlap threshold (C*). Above C*, this structure changed to the mixed lattice of BCC and face-centered cubic (FCC) structures. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Positron emission tomography of cortical centers of tinnitus.

Tinnitus is associated with a wide variety of disorders in the auditory system. Whether generated peripherally or centrally, tinnitus is believed to be associated with activity in specific cortical regions. The present study tested the hypothesis that these cortical centers subserve the generation, perception and processing of the tinnitus stimulus and that these processes are suppressed by lidocaine and masking. Positron emission tomography was used to map the tinnitus-specific central activity. By subtracting positron emission tomography images of regional cerebral blood flow distribution obtained during suppression of the tinnitus from positron emission tomography images obtained during the habitual tinnitus sensation, we were able to identify brain areas concerned with the cerebral representation of tinnitus. Increased neuronal activity caused by tinnitus occurred predominantly in the right hemisphere with significant foci in the middle frontal and middle temporal gyri, in addition to lateral and mesial posterior sites. The results are consistent with the hypothesis that the sensation of tinnitus is associated with activity in cortical regions functionally linked to subserve attention, emotion and memory. For the first time, the functional anatomy of conditions with and without the habitual tinnitus sensation was obtained and compared in the same subjects.

Adult↗
PubMed1999

Stimulus-dependent central processing of auditory stimuli: a PET study.

Positron emission tomography (PET) was used to investigate the neural systems involved in the central processing of different auditory stimuli. Noise, pure tone and pure-tone pulses, music and speech were presented monaurally. O-15-water PET scans were obtained in relation to these stimulations presented to five normal hearing and healthy subjects. All stimuli were related to a basic scan in silence. Processing of simple auditory stimuli, such as pure tones and noise, predominantly activate the left transverse temporal gyrus (Brodmann area [BA] 41), whereas sounds with discontinued acoustic patterns, such as pure-tone pulse trains, activated parts of the auditory association area in the superior temporal gyri (BA 42) in both hemispheres. Moreover, sounds with complex spectral, intensity, and temporal structures (words, speech, music) activated spatially even more extensive associative auditory areas in both hemispheres (BA 21, 22). PET has revealed a remarkable potential to investigate early central auditory processing, and has provided evidence of the coexistence of functionally linked, but individually active parallel and serial auditory networks.

Acoustic Impedance Tests↗