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Biomedical subjects

I Yamada

Publications and source records attributed to I Yamada.

At least 19 recordsLinked to original sources

Ex vivo measurement of brain tissue viscoelasticity in postischemic brain edema.

Knowledge of the biomechanical properties of postischemic brain tissue is important for understanding the mechanisms of postischemic secondary brain tissue injury. We describe the method and results of biomechanical property measurement in ex vivo postischemic brain tissue by applying an indentation method. Mongolian gerbils were subjected to a transient unilateral hemispheric ischemia. At day 1 after ischemia, multi-parametric MRI was performed, the brain was removed under anesthesia, sliced, and kept in a container with silicone oil for the measurement. A compression probe attached to a pressure transducer was inserted to a pre-determined depth at the regions of interest and maintained at a constant speed. A pressure relaxation curve was recorded for the calculation of elasticity modulus (E) and viscosity modulus (eta) according to Maxwell-Voigt's 3-element model. One day after ischemia, E and eta decreased to 78.7% and 73.1% of the control level, respectively. This decrease corresponded to a mild decrease in apparent diffusion coefficient (ADC) and magnetization transfer ratio, and an increase in T2 value. Tissue water content increased to 105.1% of control. Microvacuolation with demyelination and axonal disruption was evident in the postischemic brain tissue.

Animals↗

Neurological dysfunctions versus apparent diffusion coefficient and T2 abnormality after transient focal cerebral ischemia in Mongolian gerbils.

We examined temporal profiles of neurological dysfunctions and compared them with apparent diffusion coefficient (ADC) and T2 changes in ischemic cortical regions after transient focal cerebral ischemia in Mongolian gerbils. Mongolian gerbils (n = 7) underwent right common carotid artery occlusion for 20 minutes. Asymmetric motor behavior and unilateral somatosensory dysfunction were quantified by the elevated body swing test and the bilateral asymmetry test at 0, 2, 3, and 8 days after ischemia. The results were compared to the ADC and T2 changes in the primary motor cortex and the somatosensory cortex. Transient motor dysfunction was observed at day 2 after ischemia. MRI revealed transient and mild ADC decrease without T2 increase at day 2 after ischemia in the primary motor cortex. Persistent somatosensory dysfunction was observed at 2, 3, and 8 days after ischemia, which corresponded to a moderate ADC decrease, and a mild T2 increase in the primary somatosensory cortex at days 2 and 3 after ischemia. Time profiles of neurological deficits concurred with ADC changes of the post-ischemic cortex responsible for the deficits. The post-ischemic lesions responsible for the neurological deficits were detectable by using ADC mapping in the acute phase after transient focal cerebral ischemia.

Animals↗

A potential pitfall of MR imaging for assessing mandibular invasion of squamous cell carcinoma in the oral cavity.

BACKGROUND AND PURPOSE: Whether MR imaging is superior to CT in evaluating the presence and extent of mandibular invasion by squamous cell carcinoma remains controversial. The purpose of this study was to directly compare the diagnostic accuracy of MR imaging and that of CT. METHODS: MR and CT images in 51 patients with squamous cell carcinoma of the oral cavity were evaluated for the presence and extent of mandibular invasion. The results were correlated with histopathologic findings. RESULTS: Twenty-five of 51 patients had histopathologic evidence of mandibular cortical invasion. The tumor involved both the cortex and the bone marrow in all 25 patients and involved the inferior alveolar canal in 5 patients. The sensitivity and specificity for mandibular cortical invasion were 96% and 54% for MR imaging and 100% and 88% for CT, respectively. Those for inferior alveolar canal involvement were 100% and 70% for MR imaging and 100% and 96% for CT, respectively. In both evaluations, the specificity of MR imaging was significantly lower than that of CT (McNemar test, P = .004 in the former and P = .002 in the latter). Chemical shift artifact by bone marrow fat was postulated to be the source of most false-positive cases on MR imaging findings for mandibular cortical invasion. Those for inferior alveolar canal involvement were due to MR imaging visualization of the tumor and surrounding inflammation with similar signal intensity. CONCLUSION: In assessing the presence and extent of mandibular invasion by squamous cell carcinoma, the specificity of MR imaging was significantly lower than that of CT.

Adult↗

Approaches to syndromic surveillance when data consist of small regional counts.

INTRODUCTION: Statistical systems designed for syndromic surveillance often must be able to monitor data received simultaneously from multiple regions. Such data might be of limited size, which would eliminate the possibility of using more common surveillance methods that assume data from a normal distribution. OBJECTIVES: The objectives of this study were to design and illustrate a multiregional surveillance system based on data inputs consisting of small regional counts, where frequencies are typically on the order of </=5. METHODS: Cumulative sum (CUSUM) methods designed for cumulating the sum of the deviations between observed and expected Poisson-distributed data were modified to account for changing expectations over time, including weekly and monthly effects. Data on lower respiratory tract infections during 1996-1999 at multiple Boston clinics among residents from 287 census tracts were used to illustrate the approach. RESULTS: When each region was monitored, 19% of the census tracts signaled a departure during 1999 from the base period (1996-1998) rates. When local statistics were used to monitor tracts and neighborhoods consisting of surrounding tracts, 60% of tracts experienced departures during 1999 from the base period. These results imply that the increases in lower respiratory tract infection that occurred during 1999 were geographically pervasive. CONCLUSIONS: Poisson CUSUM methods are useful for monitoring small regional counts over time. The methods can be generalized to account for time-varying expectations in the counts.

Epidemiologic Measurements↗

Pharmacokinetics/pharmacodynamics of Y-700, a novel xanthine oxidase inhibitor, in rats and man.

The pharmacokinetics and pharmacodynamics of a novel xanthine oxidase (XO) inhibitor, Y-700, were evaluated in rats and healthy male volunteers. In a rat model of hyperuricemia, oral Y-700 (0.3-10 mg/kg) showed a more potent and a longer-lasting hypouricemic action than allopurinol. A single oral dosing of Y-700 (5, 20 or 80 mg) to volunteers caused a dose-dependent reduction of serum uric acid levels indicating close relationship to plasma concentrations of the compound. In addition, Y-700 was hardly excreted in urine but mainly excreted in feces in rats and volunteers. These results suggested that Y-700 is a new effective inhibitor of XO in rats and humans with high oral bioavailability being predominantly eliminated via the liver unlikely to allopurinol.

Administration, Oral↗

Observation of helicity-induced Alfvén eigenmodes in large-helical-device plasmas heated by neutral-beam injection.

The helicity-induced Alfvén eigenmodes (HAEs) with the toroidal mode number n=2 and 3 are observed for the first time in the Large Helical Device plasmas heated by neutral beam injection. The observed mode frequency is about 8 times higher than that of the observed toroidicity-induced Alfvén eigenmodes, and is proportional to the Alfvén velocity. The modes are excited when the ratio of the beam velocity to the Alfvén velocity exceeds about unity. The frequency lies just above the lower bound of the HAE gap in the plasma edge region of rho>0.7 (rho: normalized minor radius).

Journal Article↗

Sawtooth oscillation in current-carrying plasma in the large helical device.

Sawtooth oscillations have been observed in current-carrying helical plasmas by using electron-cyclotron-emission diagnostics in the Large Helical Device. The plasma current, which is driven by neutral beam injection, reduces the beta threshold of the sawtooth oscillation. When the central q value is increased due to the plasma current, the core region crashes, and, when it is decreased, the edge region crashes annularly. Observed rapid mixture of the plasma in the limited region suggests that these sawtooth crashes are reconnection phenomena. Unlike previous experiments, no precursor oscillation has been observed.

Journal Article↗

Temporal evolution of apparent diffusion coefficient and T2 value following transient focal cerebral ischemia in gerbils.

We examined the time course of apparent diffusion coefficient (ADC) and T2 values in gerbils subjected to transient focal cerebral ischemia and compared them with histopathologic changes. Ten gerbils were subjected to two times 10-min occlusions of the left common carotid artery and examined with diffusion-weighted and T2-weighted MR imaging, at the interocclusion period and 1 hour, 2 hours. 1 day, 2 days, 4 days, and 7 days after the second occlusion. Immediately after the last MR imaging, their brains were examined histopathologically. ADC values decreased 1 hour after the second occlusion and continued to decrease up to 1 or 2 days later. ADC values remained lowered up to 4 days and slightly recovered at 7 days. T2 values were normal at 1 and 2 hours and began to increase at 1 day. T2 values began to recover at 4 days. Histopathologically, infarction was confined in the fronto-parietal cortex, dorsolateral caudate nucleus and dorsolateral thalamus, and neuronal necrosis was found in the pyramidal cell layer of the hippocampus. This study indicates that sequential ADC and T2 studies of gerbils subjected to transient focal cerebral ischemia provide a useful tool for evaluating temporal evolution of ischemic brain injury and edema, including cytotoxic and vasogenic edema.

Animals↗

Tissue distribution of a new photosensitizer ATX-S10Na(II) and effect of a diode laser (670 nm) in photodynamic therapy.

The aims of the present study were to analyse the quantitative tissue distribution of ATX-S10Na(II) and to investigate the maximal effect of a diode laser and the irradiation conditions required to obtain this effect in photodynamic therapy (PDT) with ATX-S10Na(II). Spectrofluorometry was used to obtain quantitative tissue distribution of ATX-S10Na(II) in Colon 26 carcinoma-bearing mice as a function of time following administration. Next, transplanted tumours of mice with or without ATX-S10Na(II) were treated with the diode laser under conditions in which power density and irradiation time were varied. Tumour tissue concentrations of ATX-S10Na(II) were higher than in all tissues at all intervals following administration. The uptake of ATX-S10Na(II) by most tissues was rapid, with maximal concentrations occurring 1 h after i.v. injection, and ATX-S10Na(II) was almost excreted within 24 h after administration. The maximal depth of necrosis induced by PDT in the treated tumour was 7.9 mm under conditions in which power density was 160 mW/cm2 and total dose was above 100 J/cm2. PDT with ATX-S10Na(II) and the diode laser is useful for the treatment of superficial cancers.

Animals↗

Metabolic fate of pitavastatin, a new inhibitor of HMG-CoA reductase: human UDP-glucuronosyltransferase enzymes involved in lactonization.

1. Pitavastatin is a potent competitive inhibitor of HMG-CoA reductase little metabolized in hepatic microsomes. Pitavastatin lactone, which can be converted back to the unchanged form, is the major metabolite of pitavastatin in humans. To clarify the mechanism of the lactonization of pitavastatin and the metabolic properties of the lactone, we performed experiments in vitro. 2. On addition of UDP-glucuronic acid, human hepatic microsomes produced pitavastatin lactone and an unknown metabolite (UM-2). UM-2 was converted to its unchanged form by enzymatic hydrolysis and to a lactone form non-enzymatically. Using several human UGT-expressing microsomes, UGT1A3 and UGT2B7 were principally responsible for glucuronidation of pitavastatin leading to lactonization. 3. No marked difference in intrinsic clearance between pitavastatin and its lactone form was detected in human hepatic microsomes. 4. Pitavastatin lactone showed no inhibitory effects on CYP2C9- and CYP3A4-mediated metabolism of model substrates in contrast to other HMG-CoA reductase inhibitors. 5. The mechanism of pitavastatin lactone formation has been clarified, in that glucuronidation by UGT occurs first followed by lactonization via an elimination reaction. It was also found that pitavastatin lactone demonstrates no drug-drug interactions.

Biotransformation↗

Metabolic fate of pitavastatin, a new inhibitor of HMG-CoA reductase: similarities and difference in the metabolism of pitavastatin in monkeys and humans.

1. To elucidate any potential species differences, the in vitro metabolism of pitavastatin and its lactone was studied with hepatic and renal microsomes from rats, dogs, rabbits, monkeys and humans. 2. With the addition of UDP-glucuronic acid to hepatic microsomes, pitavastatin lactone was identified as the main metabolite in several animals, including humans. 3. Metabolic clearances of pitavastatin and its lactone in monkey hepatic microsome were much greater than in humans. 4. M4, a metabolite of pitavastatin with a 3-dehydroxy structure, was converted to its lactone form in monkey hepatic microsomes in the presence of UDP-glucuronic acid as well as to pitavastatin. These results implied that lactonization is a common pathway for drugs such as 5-hydroxy pentanoic acid derivatives. 5. The acid forms were metabolized to their lactone forms because of their structural characteristics. 6. UDP-glucuronosyltransferase is the key enzyme responsible for the lactonization of pitavastatin, and overall metabolism is different compared with humans owing to the extensive oxidative metabolism of pitavastatin and its lactone in monkey.

Animals↗

Island dynamics in the large-helical-device plasmas.

In the Large Helical Device plasma discharges, the size of an externally imposed island with mode number ( n/m = 1/1) decreases substantially when the plasma is collisionless ( nu(*)< approximately 1) and the beta is finite ( > approximately 0.1%) at the island location. For the collisional plasmas with finite beta, on the other hand, the size of the island increases. However, there is a threshold in terms of the vacuum island size below which the island enlargement is not seen.

Journal Article↗

Observation of the "self-healing" of an error field island in the large helical device.

It was observed that the vacuum magnetic island produced by an external error magnetic field in the large helical device shrank in the presence of plasma. This was evidenced by the disappearance of flat regions in the electron temperature profile obtained by Thomson scattering. This island behavior depended on the magnetic configuration in which the plasmas were produced.

Journal Article↗

Simultaneous determination of taxol and its metabolites in microsomal samples by a simple thin-layer chromatography radioactivity assay--inhibitory effect of NK-104, a new inhibitor of HMG-CoA reductase.

The inhibitory effect of NK-104, a potent inhibitor of HMG-CoA reductase, on taxol metabolism was examined using radio-TLC. This method is described for in vitro measurement of taxol metabolites as an alternative to the commonly used HPLC assay. After incubation of 14C-taxol with human liver microsomes, the supernatants were developed using a solvent system consisting of toluene-acetone-formic acid (60:39:1, v/v) and quantified with a bioimaging analyzer. The described method provides a valuable tool for the simultaneous determination of unchanged taxol and its major metabolites. There was no inhibitory effect of NK-104 on CYP-mediated metabolism of taxol in human liver microsomes.

Antineoplastic Agents, Phytogenic↗

Reduction of ion thermal diffusivity associated with the transition of the radial electric field in neutral-beam-heated plasmas in the large helical device.

Recent large helical device experiments revealed that the transition from ion root to electron root occurred for the first time in neutral-beam-heated discharges, where no nonthermal electrons exist. The measured values of the radial electric field were found to be in qualitative agreement with those estimated by neoclassical theory. A clear reduction of ion thermal diffusivity was observed after the mode transition from ion root to electron root as predicted by neoclassical theory when the neoclassical ion loss is more dominant than the anomalous ion loss.

Journal Article↗

Interstitial photodynamic therapy with rotating and reciprocating optical fibers.

BACKGROUND: Photodynamic therapy (PDT) is an effective treatment modality that allows selective destruction of malignant tumor cells. However, because of the difficulty in exposing deeper areas of tumors, the modality has strictly limited indications. In this study, the authors introduce a new method for delivering laser light to a three-dimensional, wide area with the purpose of improving the therapeutic value of PDT. METHODS: Three patients with squamous cell carcinoma of the tongue were treated with the present course. After administering porfimer sodium, laser-proof tubes were inserted through the tumor, and optical fibers were passed through the tubes. Pulse laser was emitted from the obliquely prepared fiber tip and distributed toward the target area while rotating and reciprocating the optical fiber. RESULTS: Two patients achieved a complete response without any complications or functional disabilities. The third patient, however, had a partial response and required surgery. CONCLUSIONS: The results indicate the capability of distributing laser light to an entire area of solid tumor. However, the ideal dose of laser light for the treatment of tumors remains unknown. Interstitial PDT will be more efficacious and reliable after the dosimetry is established.

Aged↗

Synthesis and structure-activity relationships of 1-phenylpyrazoles as xanthine oxidase inhibitors.

A series of 1-phenylpyrazoles was evaluated for inhibitory activity against xanthine oxidase in vitro. Of the compounds prepared, 1-(3-cyano-4-neopentyloxyphenyl)pyrazole-4-carboxylic acid (Y-700) had the most potent enzyme inhibition and displayed longer-lasting hypouricemic action than did allopurinol in a rat model of hyperuricemia induced by the uricase inhibitor potassium oxonate.

Allopurinol↗