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Biomedical subjects

Nobuyuki Kawai

Publications and source records attributed to Nobuyuki Kawai.

At least 19 recordsLinked to original sources
PubMed2006

Inhibition of transcellular tumor cell migration and metastasis by novel carba-derivatives of cyclic phosphatidic acid.

Cyclic phosphatidic acid (1-acyl-sn-glycerol-2,3-cyclic phosphate; cPA) is a naturally occurring analog of lysophosphatidic acid (LPA) with a variety of distinctly different biological activities from those of LPA. In contrast to LPA, a potent inducer of tumor cell invasion, palmitoyl-cPA inhibits FBS- and LPA-induced transcellular migration and metastasis. To prevent the conversion of cPA to LPA we synthesized cPA derivatives by stabilizing the cyclic phosphate ring; to prevent the cleavage of the fatty acid we generated alkyl ether analogs of cPA. Both sets of compounds were tested for inhibitory activity on transcellular tumor cell migration. Carba derivatives, in which the phosphate oxygen was replaced with a methylene group at either the sn-2 or the sn-3 position, showed much more potent inhibitory effects on MM1 tumor cell transcellular migration and the pulmonary metastasis of B16-F0 melanoma than the natural pal-cPA. The antimetastatic effect of carba-cPA was accompanied by the inhibition of RhoA activation and was not due to inhibition of the activation of LPA receptors.

Animals↗
PubMed2006

Ruptured high flow gastric varices with an intratumoral arterioportal shunt treated with balloon-occluded retrograde transvenous obliteration during temporary balloon occlusion of a hepatic artery.

A patient presented with hematemesis due to gastric variceal bleeding with an intratumoral arterioportal shunt. Contrast-enhanced CT revealed gastric varices and hepatocellular carcinoma with tumor thrombi in the right portal vein. Angiography and angio-CT revealed a marked intratumoral arterioportal shunt accompanied with reflux into the main portal vein and gastric varices. Balloon-occluded retrograde venography from the gastro-renal shunt showed no visualization of gastric varices due to rapid blood flow through the intratumoral arterioportal shunt. The hepatic artery was temporarily occluded with a balloon catheter to reduce the blood flow through the arterioportal shunt, and then concurrent balloon-occluded retrograde transvenous obliteration (BRTO) was achieved. Vital signs stabilized immediately thereafter, and contrast-enhanced CT revealed thrombosed gastric varices. Worsening of hepatic function was not recognized. BRTO combined with temporary occlusion of the hepatic artery is a feasible interventional procedure for ruptured high flow gastric varices with an intratumoral arterioportal shunt.

Aged↗
PubMed2006

Transhepatic catheter-directed thrombolysis for portal vein thrombosis after partial splenic embolization in combination with balloon-occluded retrograde transvenous obliteration of splenorenal shunt.

A 66-year-old woman underwent partial splenic embolization (PSE) for hypersplenism with idiopathic portal hypertension (IPH). One week later, contrast-enhanced CT revealed extensive portal vein thrombosis (PVT) and dilated portosystemic shunts. The PVT was not dissolved by the intravenous administration of urokinase. The right portal vein was canulated via the percutaneous transhepatic route under ultrasonic guidance and a 4 Fr. straight catheter was advanced into the portal vein through the thrombus. Transhepatic catheter-directed thrombolysis was performed to dissolve the PVT and a splenorenal shunt was concurrently occluded to increase portal blood flow, using balloon-occluded retrograde transvenous obliteration (BRTO) technique. Subsequent contrast-enhanced CT showed good patency of the portal vein and thrombosed splenorenal shunt. Transhepatic catheter-directed thrombolysis combined with BRTO is feasible and effective for PVT with portosystemic shunts.

Aged↗
PubMed2006

Diagnostic value of kinetic analysis using dynamic FDG PET in immunocompetent patients with primary CNS lymphoma.

PURPOSE: The purpose of this study was to investigate the accumulation of FDG in immunocompetent patients with primary central nervous system (CNS) lymphoma using qualitative and quantitative PET images and to compare baseline with follow-up PET after therapy. METHODS: Twelve immunocompetent patients with CNS lymphoma were examined. Dynamic emission data were acquired for 60 min immediately following injection of FDG. In seven patients, repeated PET studies were performed after treatment. Applying a three-compartment five-parameter model, K (1), k (2), k (3), k (4), vascular fraction (V ( B )) and cerebral metabolic rate of glucose (CMR(Glc)) were obtained. We evaluated the FDG uptake visually using qualitative and parametric images and quantitatively using parametric images. RESULTS: A total of 12 lesions were identified in ten patients with newly diagnosed CNS lymphoma. On visual analysis, ten lesions showed an increase on qualitative images, eight showed an increase on K (1) images, 12 showed an increase on k (3) images and ten showed an increase on CMR(Glc) images. On quantitative analysis, k (2), k (3) and CMR(Glc) values of the lesion were significantly different from those of the normal grey matter (p<0.02-0.0005). A total of three lesions were identified in two patients with recurrent tumour. All three lesions showed an increase on qualitative, k (3) and CMR(Glc) images. The K (1), k (2), k (3) and CMR(Glc) values after treatment were significantly different from those obtained before treatment (p<0.04-0.008). CONCLUSION: Kinetic analysis, especially with respect to k (3), using dynamic FDG PET might be helpful for diagnosis of CNS lymphoma and for monitoring therapeutic assessment.

Adult↗
PubMed2006

Palladium-catalyzed stereospecific synthesis of 2,6-disubstituted tetrahydropyrans: 1,3-chirality transfer by an intramolecular oxypalladation reaction.

PdCl2(CH3CN)2 (10 mol %) catalyzed reactions of non-3-ene-2,8-diols 1 and 2 gave 2,6-disubstituted tetrahydropyrans 3 and 4 in excellent yields with high diastereoselectivities (>20:1). Intramolecular cyclizations of the hydroxy nucleophile to the chiral allylic alcohol take place efficiently under mild conditions. A new stereogenic center is generated on the tetrahydropyran ring by 1,3-chirality transfer from the chiral allylic alcohol via a syn-SN2' type process. Cis tetrahydropyran 3E was formed from syn-2,8-diols 1a and 2a, and trans tetrahydropyran 4E was formed from anti-2,8-diol 1b, stereospecifically. Cis tetrahydropyran bearing a cis alkene 3Z was obtained from 2b at -40 degrees C, while 4E was formed from 2b in the presence of catalytic amount of water at -40 degrees C. The face selectivity of these cyclizations can be rationalized by taking a favorable conformation of the intermediary Pd pi-complex with allylic alcohols, escaping the allylic strain and 1,3-diaxial interactions. A stereocontrolled synthesis of optically pure 2-alkenyl-6-methyltetrahydropyran 17 was achieved efficiently in four steps from 6-silyloxy-1-heptyne 13 with an aldehyde and included asymmetric alkynylation, partial reduction of alkyne, deprotection of the silyl group, and the stereospecific cyclization.

Catalysis↗
PubMed2006

Magnetic resonance imaging and positron emission tomography findings in status epilepticus following severe hypoglycemia.

We recently experienced a case with asymmetrical cortical abnormality on MRI with focal status epilepticus following severe hypoglycemia. The cerebral blood flow and metabolisms for oxygen and glucose were determined using positron emission tomography (PET) during focal status epilepticus following severe hypoglycemia and at the follow-up period. Prolonged seizure activity produced profound glucose hypermetabolism and mild hyperemia in the region of the presumed cortical focus of epilepsy and in structures anatomically remote from the focus, corresponding to the areas of abnormal signal intensity on the MRI. The patient remained comatose and exhibited a diffuse hypoperfusion/hypometabolism and symmetrical brain atrophy on the follow-up PET and MRI, respectively. Cytotoxic brain edema due to profound glucose metabolism without compensatory increase of the blood flow during status epilepticus may account for the brain abnormality observed on the early MRI. Simultaneous examination of the cerebral blood flow and metabolism using PET can provide useful information about the pathology in patients with status epilepticus.

Aged↗
PubMed2006

Chiari I malformation accompanied by assimilation of the atlas, Klippel-Feil syndrome, and syringomyelia: case report.

BACKGROUND: Chiari I malformation, accompanied by superposed bony anomaly of the craniovertebral junction, is comparatively rare. We report a case of Chiari I malformation accompanied by assimilation of the atlas, Klippel-Feil syndrome, and syringomyelia. CASE DESCRIPTION: The patient was a 61-year-old woman demonstrating numbness of the extremities, sensory impairment, muscular weakness, and tendon hyper-reflexia. X-ray images and CT scans demonstrated assimilation of the atlas to the occipital bone, C2 and C3 fusion, abnormal passage of the vertebral arteries, and an anomalous bony mass on the right lateral mass of the atlas protruding into the spinal column. The odontoid process was also deviated to the left. Magnetic resonance images demonstrated bilateral descent of the cerebellar tonsils and syringomyelia extending from C6 to T8. Computed tomographic scans with the head rotated to the right demonstrated increased narrowing of the vertebral column caused by the right lateral mass of the atlas, and MR images confirmed exaggerated deformation of the spinal cord at the same region. This deformation manifested no neurologic symptoms, and we therefore performed foramen magnum decompression and duraplasty using Gore-Tex (W.L. Gore & Associates, Inc., Flagstaff, AZ). In the early postoperative period, neurologic symptoms improved. CONCLUSION: We believe it is important that a treatment plan for Chiari I malformation accompanied by bony anomaly of the craniovertebral junction be determined based on morphologic investigation of the region supplemented by dynamic imaging-based evaluation of instability, or a careful inspection for atypical passage of the vertebral arteries, a frequent site of complication.

Arnold-Chiari Malformation↗
PubMed2006

Differences in the neuronal stem cells survival, neuronal differentiation and neurological improvement after transplantation of neural stem cells between mild and severe experimental traumatic brain injury.

We developed a novel protocol for generation and selective amplification of neural progenitor cells regionally specified to the rostral brain but not the spinal cord from mouse embryonic stem cells (ESCs). The neural progenitors could differentiate in vitro and in vivo into many cholinergic and a few GABAergic neurons but rarely into astrocytes. The transplanted neurospheres could survive in the hippocampus (CA3) of animals with mild traumatic brain injury (TBI). Twelve weeks after transplantation (a week after the behavioral test), we found significant cholinergic differentiation recognized as ChAT immunoreactivity in the eGFP+transplanted cells. Moreover, the grafts contained a few GAD67+cells. However, we barely found GFAP+astrocytes within the grafts. Furthermore, presynaptic formations of graft-derived neurons were recognized by immunohistochemistry of near the grafts around CA3. However, these findings were not observed in severe TBI group. So, we examined NGF, BDNF, and FGF-2 mRNA by RT-PCR in 12 mice including normal, mild TBI and severe TBI group. Increases in the neurotrophic factors' mRNA were evident in the hippocampus on the ipsilateral side in the mild TBI group. Statistical analysis revealed significant differences between the mild and severe TBI groups. The data also revealed significant differences between the mild TBI and normal groups. The transplanted neurospheres could survive in the mild TBI animals, but not in the severe TBI group.

Animals↗
PubMed2006

Neural stem cells transplantation in cortex in a mouse model of Alzheimer's disease.

OBJECTIVE: The goal of this study was to elucidate the effect of neurospheres (NS) on dementia in the mouse model of nucleus basalis of Meynert (NBM) lesion. METHODS: Mouse embryonic stem cell (ES) derived neurospheres were transplanted into the frontal association cortex and barrel field of S1 cortex of C57BL/6 mice 4 weeks after including a lesion of NBM by ibotenic acid, while other healthy mice that received ES cells served as control. Behavioral tests by 8-arm radial maze were conducted 8 weeks after transplantation, and double staining of choline acetyltransferase (ChAT), serotonin, amyloid-beta protein (AP) and green fluorescent protein (GFP) 12 weeks after transplantation. We found that the neurospheres transplanted into the mouse cortex survived and produced many ChAT-positive neurons and a few serotonin-positive neurons in and around the grafts. The working memory error decreased significantly in the mice grafted with neurospheres. In contrast, the ES cells developed into teratomas in all of the control mice and expressed no neurons, and the working memory deteriorated remarkably. CONCLUSIONS: Transplantation of neurospheres, but not ES cells, into the prefrontal and parietal cortices, dramatically alleviated the cholinergic deficits and recent memory disruption in the NBM lesioned mice.

Alzheimer Disease↗
PubMed2005

The role of attention in the facilitation effect and another "inhibition of return".

The present study investigated how anticipation of a target's appearance affects human attention to gaze cues provided by a schematic face. Subjects in a 'catch' group received a high number of 'catch' trials, in which no target stimulus appeared. Subjects in the control group did not receive any catch trials. As in previous studies, both groups showed a facilitation effect to the cued location during shorter stimulus onset asynchrony (SOA). In both groups, an analysis of eye movements confirmed that subjects' eyes remained on the fixation point, ruling out the possibility that the facilitation effect was due to shifting eye movements (saccades) as opposed to a shift in covert attention. But while the control group's response time (RT) decreased as SOA increased, the catch group's RT had a U-shaped pattern and the facilitation effect to the cued location was reversed at the longest SOA (1005 ms). These results suggest that subjects in the catch group disengaged their attention during long SOAs because they expected the trial to be a catch trial. This disengagement of attention during long SOAs results in a delay before attention could be re-focused to the previous location regardless of the cue validity ["IOR (inhibition of return)"-like-phenomenon]. Unlike the conventional IOR, we suggest that this "IOR"-like phenomenon caused by an unpredictive central gaze cue is likely to be mediated by an endogenous mechanism.

Adult↗
PubMed2005

Repeated injections of energy in the first 600 ms of the giant flare of SGR 1806-20.

The massive flare of 27 December 2004 from the soft gamma-ray repeater SGR 1806-20, a possible magnetar, saturated almost all gamma-ray detectors, meaning that the profile of the pulse was poorly characterized. An accurate profile is essential to determine physically what was happening at the source. Here we report the unsaturated gamma-ray profile for the first 600 ms of the flare, with a time resolution of 5.48 ms. The peak of the profile (of the order of 10(7) photons cm(-2) s(-1)) was reached approximately 50 ms after the onset of the flare, and was then followed by a gradual decrease with superposed oscillatory modulations possibly representing repeated energy injections with approximately 60-ms intervals. The implied total energy is comparable to the stored magnetic energy in a magnetar (approximately 10(47) erg) based on the dipole magnetic field intensity (approximately 10(15) G), suggesting either that the energy release mechanism was extremely efficient or that the interior magnetic field is much stronger than the external dipole field.

Journal Article↗
PubMed2005

Crossed cerebellar glucose hypermetabolism demonstrated using PET in symptomatic epilepsy--case report.

A 65-year-old male with an old cerebral contusion in the frontal lobes had suffered from status complex partial seizures. Ictal positron emission tomography with an F-18 fluorodeoxyglucose ([18F]FDG-PET) scan revealed hypermetabolism in the frontal, temporal and parietal lobes and the contralateral cerebellar hemisphere. The patient underwent a next-day PET scan with the 15O-labeled gas inhalation technique, which showed mild hyperperfusion and oxygen hypermetabolism in these areas. An interictal [18F]FDG-PET scan 17 days after the initial epilepsy demonstrated glucose hypometabolism of the frontal, temporal and parietal lobes and the contralateral cerebellar hemisphere. Increased glucose metabolism on the interictal PET scan and decreased glucose metabolism on an interictal PET scan in the epileptogenic supratentorial zones and the contralateral cerebellar hemisphere are interesting observations for understanding the pathophysiology in long-standing partial seizures.

Aged↗
PubMed2005

Evaluation of tumor FDG transport and metabolism in primary central nervous system lymphoma using [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) kinetic analysis.

OBJECTIVE: Although 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been used as a promising tool to diagnose primary central nervous system lymphoma (PCNSL) because the tumor shows very high FDG accumulation, no data exist evaluating the extent of tumor FDG transport and metabolism. The aim of this study was to evaluate the feasibility of FDG-PET kinetic analysis in measurement of uptake parameters of FDG in the lymphoma tissues and in the assessment of treatment effects in patients with PCNSL. METHODS: Dynamic FDG-PET examination was performed in 7 histologically proven PCNSL patients before and after methotrexate-based chemotherapy. RESULTS: Before the chemotherapy, the highest CMRglc in the tumor for all 7 patients was 79.4 +/- 27.2 micromol/100 g/min. This value was significantly higher than that observed in the normal cortex in 14 control patients (44.3 +/- 6.0 micromol/100 g/min, p < 0.001). The phosphorylation (k3) activity was also significantly higher in the tumor (0.093 +/- 0.026 min(-1)) compared with the normal cortex (0.064 +/- 0.014 min(-1), p < 0.05). On the other hand, the transporter (K1) activity in the tumor (0.079 +/- 0.016 ml/min) was similar to that observed in the normal cortex (0.082 +/- 0.012 ml/min). The chemotherapy significantly reduced the volume of the tumor in 6 of 7 patients and the highest CMRglc in the tumor examined 18.0 +/- 5.5 days after the chemotherapy (34.0 +/- 21.8 micromol/100 g/min) was significantly lower than that observed before the chemotherapy (p < 0.01). This reduction in FDG uptake was concomitant with a significant reduction in both the K1 and k3 values (p < 0.05). The reduction in the k3 value after the chemotherapy was marked in 6 of 7 patients in whom the tumor responded to the first chemotherapy. CONCLUSIONS: Dynamic image acquisition can separate regional FDG uptake into FDG transport and phosphorylation activity in the lymphoma tissues. Tumor FDG uptake was significantly higher with accelerated phosphorylation activity compared with that observed in the normal cortex.

Aged↗
PubMed2005

Usefulness of [18F]FDG-PET kinetic analysis in non-enhancing primary central nervous system lymphoma: case report.

A 62-year-old woman experienced headache and rapidly progressive left hemiparesis over 2 weeks. Diffusion-weighted and fluid-attenuated inversion recovery MR images of the head showed increased signal intensity in the right basal ganglia, periventricular white matter and the brain stem. Enhancement was not observed on a T1-weighted spin-echo MR image after the administration of a contrast material. An 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) study with kinetic analysis showed decreased FDG transport and increased hexokinase activity in the lesions compared with the contralateral hemisphere. The diagnosis was made by biopsy of the right caudate head and pathologic specimens were positive for malignant large-cell lymphoma, B-cell phenotype. The patient received high-dose methotrexate with CHOP chemotherapy, and an [18F]FDG-PET study with kinetic analysis showed decreased hexokinase activity after the first chemotherapy. Kinetic [18F]FDG-PET analysis may be useful to diagnose and monitor the treatment effect in non-enhancing primary central nervous system lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Hemodynamic and metabolic changes in a patient with cerebral venous sinus thrombosis: evaluation using O-15 positron emission tomography.

The cerebral hemodynamics and oxygen metabolism before and after the recanalization of the occluded sinus were evaluated using O-15 positron emission tomography (PET) scanning in a 21-year-old woman with superior sagittal sinus thrombosis. During the initial presentation, there was increased regional cerebral blood volume (rCBV) in the left frontal and parietal lobes with moderately increased rCBV in the right parietal lobe. Recanalization of the occluded sinus resulted in a normalization of elevated rCBV in the frontal and parietal lobes and improvements of rCBF and regional cerebral metabolic rate for oxygen in the occipital lobe. Clinical improvement after recombinant tissue plasminogen activator therapy was accompanied by restoration of cerebral hemodynamics and oxygen metabolism, although magnetic resonance venography showed only partial recanalization of the occluded sinus. PET evaluation of the cerebral hemodynamics and oxygen metabolism may be of value in gaining further insight into pathophysiological characteristics of human cerebral venous sinus thrombosis.

Adult↗
PubMed2005

Matrix metalloproteinase 2 and 9 expression correlated with cavernous sinus invasion of pituitary adenomas.

OBJECT: Matrix metalloproteinase (MMP) 2 and 9 are important for tissue breakdown in the process of tumor invasion. The aim of this study is to evaluate the relationship between the expression of MMP-2, MMP-9, MIB-1 LI and cavernous sinus invasion in pituitary adenomas. METHODS: Tissue samples from 54 patients with pituitary adenomas were studied. Expression of MMP-2, MMP-9, and MIB-1 labeling index (LI) were evaluated by immunohistochemical method. In sixteen cases, the expression of MMP-2 and MMP-9 mRNA was also examined by RT-PCR assay. RESULTS: Thirty-four patients were women and 20 were men, with a mean age of 49.9 years old (range 18-76 years). There were 12 cases with cavernous sinus invasion, and 42 were noninvasive cases. MMP-2 and MMP-9 score of invasive case (3.9 +/- 0.5,4.1 +/- 0.4) were significantly higher than those (2.3 +/- 0.2; p < 0.01; 2.6 +/- 0.2; p < 0.01) without invasion. The MIB-1 LI of this study presented no significantly difference between the invasive and noninvasive pituitary adenomas. The percentage of MMP-2 mRNA/beta-actin mRNA and MMP-9 mRNA/beta-actin mRNA were also observed significantly higher in invasive pituitary adenomas (68.2 +/- 15.3%; 59.7 +/- 12.5%) than noninvasive pituitary adenomas (21.8 +/- 8.2%, p < 0.05; 33.3 +/- 5.4%, p < 0.05). CONCLUSIONS: Our study suggests that the expression of MMP-2 and MMP-9 may have a value to assess the invasive pituitary adenomas, and proliferation and invasion of pituitary adenomas may present a different mechanism.

Adenoma↗
PubMed2004

Fetal habituation correlates with functional brain development.

In this study, we divided 26 fetuses at 32-37 weeks of gestation into three groups using combined criteria of gestational age and behavioral indicators. We investigated fetal habituation to vibroacoustic stimulation (VAS). Fetuses showed habituation from at least 32 weeks of gestation. Furthermore, fetuses less developed from behavioral standpoint took significantly more trials to achieve habituation than developed fetuses even in the same gestational age. Taken together with these data, it was proved that there was a relationship between aspects of behavioral development and habituation.

Acoustic Stimulation↗