Biomedical subjects

H Okazawa

Publications and source records attributed to H Okazawa.

At least 91 records · Page 5Linked to original sources

PubMed1995

[Phase 1 clinical study of 123I-iomazenil: a new probe to evaluate central-type benzodiazepine receptor with SPECT].

A Phase 1 clinical study of 123I-iomazenil (IMZ), a new radiopharmaceutical developed for evaluation of central-type benzodiazepine receptor (BZR) with SPECT, was performed to examine its safety and biodistribution in six healthy volunteers. The brain uptake of 123I-IMZ reached a maximum value of 11.7 +/- 1.6% of the injected dose at 10-20 min after i.v. administration, and then decreased slowly. The regional tracer distribution immediately after injection (0-10 min) was considered to be a reflection of the cerebral blood flow. From 2 to 3 hours post-injection, washout of the radioactivity from the deep gray matter was observed, resulting in the distribution reflecting the reported distribution of BZR. No significant accumulation was seen in any organ other than the brain. The estimated absorbed dose of 123I-IMZ calculated by the MIRD method was comparable to that of 123I-N-isopropyl-p-iodoamphetamine. Neither adverse reactions nor abnormal clinical laboratory findings due to the drug administration were observed. These results suggest that 123I-IMZ is a safe and promising agent for evaluating the function of central-type BZR.

Adult↗

PubMed1995

Delayed data acquisition for optimal PET activation studies with oxygen-15-water in cerebral arteriovenous malformation.

UNLABELLED: In the clinical application of activation PET studies with 15O-water, optimal PET images are required when the high activity of a nearby lesion might affect the activated area. METHODS: To determine the optimal time for data acquisition of PET images, we performed serial dynamic PET measurements in five patients with cerebral arteriovenous malformation (AVM). All AVMs were closest to the motor cortices, and the activation task was opponent finger movement contralateral to the AVM. Activation PET and MR images were coregisterated for localization of activated foci. RESULTS: Time-activity curves of the nidus and normal cortex from the dynamic PET data demonstrated a discrepancy in peak time and significant radioactivity increase in the nidus during the early phase. Elimination of the initial PET data provided better contrast in activated foci without affecting the calculated cerebral blood flow of other areas. CONCLUSION: Delayed data acquisition can avoid interference of the AVM nidus with the activated area.

Adult↗

PubMed1994

Molecular control of neuronal survival in the chick embryo.

Neurotrophins are structurally related proteins which promote the survival and differentiation of specific neuronal populations during the development of vertebrate embryos. Like many growth factors, the neurotrophins mediate their actions by binding to membrane proteins that have a ligand-activated tyrosine kinase activity. The interactions of the neurophins with their neuronal receptors have been mostly studied using chick embryonic neurons. These neurons are also extensively used to characterise biological responses to neurotrophins in physiologically relevant systems. We have recently cloned and expressed the chick homologue of trkB (ctrkB), thought to be a receptor for BDNF, and examined by in situ hybridisation the pattern of expression of the ctrkB gene during development of the chick embryo. We found that whereas the sequence of ctrkB shows a high degree of conservation with the mammalian homologues in the intracellular tyrosine kinase domain, the extracellular binding domain is less well conserved. As in mammals, ctrkB mRNAs appear to exist in differentially spliced forms that result in a full length and a truncated receptor lacking the tyrosine kinase domain. These two forms are differentially expressed in neurons and non-neuronal cells respectively. The binding characteristics of ctrkB expressed in a transfected cell line are similar, but not identical to those of the BDNF binding sites on primary chick neurons, specially with regard to the affinity of BDNF.

Animals↗

PubMed1994

Optimal dose of injection in activation study with O-15 water and PET.

In activation studies with the bolus method for O-15 water and PET, the radiotracer concentration may reach the limits of the system in terms of dead time correction and accidental coincidence. To obtain the optimal injection dose of O-15 water, we performed a normal volunteer study to evaluate the relationship between the injected dose and the radioactivity concentration in the brain and a phantom study to evaluate the performance of the PET scanner (PCT3600W) under high count rate conditions and the effect of averaging on the signal to noise ratio for the PET images. A linear relationship was noted between the injected dose (normalized for each body weight: x) and the mean radiotracer concentration in the brain measured by PET (y) (y = 2.52 + 30.1 x, n = 64, r = 0.87, p < 0.001). The percent error in the measurement of radioactivity with PET was within +/- 5% in the 100 to 2000 nCi/ml (3.7-74 KBq/ml) range. Below 100 nCi/ml (3.7 KBq/ml), the percent error increased due to the rapid increase in noise in the reconstructed images. Over 1000 nCi/ml (37 KBq/ml), on the other hand, the noise was almost unchanged. With our PET scanner, the optimal range of the radiotracer concentration in the brain is below 1000 nCi/ml (37 KBq/ml), corresponding to an injection dose of 33 mCi (1.22 GBq)/60 kg body weight. With the same total dose, the increment of number of repeated measurements for averaging provided the better signal to noise ratio. In designing a paradigm for an activation PET study, the injection dose and the number of repeated measurements for averaging should be considered.

Adult↗

PubMed1994

Clinical application and quantitative evaluation of generator-produced copper-62-PTSM as a brain perfusion tracer for PET.

UNLABELLED: Copper-62-pyruvaldehyde bis(N4-methylthiosemicarbazone) copper II (62Cu-PTSM) has been proposed as a generator-produced positron-emitting tracer for perfusion imaging. To evaluate the characteristics of 62Cu-PTSM as a cerebral perfusion tracer, brain PET images of 62Cu-PTSM were compared with cerebral blood flow (CBF). METHODS: Following an intravenous injection of 62Cu-PTSM, a serial dynamic PET scan was performed for 10 min with arterial sampling in 10 subjects. CBF was measured by 15O-labeled water before the 62Cu-PTSM study. RESULTS: Dynamic PET scan with octanol-extracted arterial input function indicated the presence of significant back-diffusion of 62Cu-PTSM from the brain within 3 min after injection, followed by stable activity from 3 to 10 min. Comparison with 15O-water PET demonstrated less contrast between high- and low-flow regions in 62Cu-PTSM image and a nonlinear relationship of flow and 62Cu-PTSM uptake, which suggests the underestimation of CBF in high-flow regions due to the existence of back-diffusion. CONCLUSION: Although 62Cu-PTSM can be used widely for evaluation of brain perfusion with PET, kinetic analysis and correction may be needed to quantify regional CBF.

Adolescent↗

PubMed1994

Effects of hyperglycemia on FDG uptake in human brain and glioma.

UNLABELLED: This study evaluates the effects of hyperglycemia on fluorodeoxyglucose (FDG) uptake in the human brain and in brain tumors. METHODS: We performed glucose loading during FDG PET studies in nine patients with brain tumors (eight gliomas and one brain metastasis) and one with resected glioma. Two FDG PET scans were obtained in all cases within 1 wk in a control state and with glucose loading by intravenous infusion of 10% glucose solution. Serial arterial blood sampling was performed in all cases to obtain fractional uptake of FDG normalized by the plasma integral uptake of radioactivity (FU). RESULTS: In all nine patients with brain tumors, the tumor was depicted more clearly with glucose loading than in the control state. Glucose loading decreased FU in the cerebral cortex (54.2% +/- 13.8%) nearly in inverse proportion to the plasma glucose level, while the tumors showed a decrease (42.5% +/- 15.6%), resulting in an increased tumor-to-cortex ratio by 26.0% +/- 5.7%. Fractional uptake in the cerebellum, white matter and the edematous area also decreased by glucose loading (53.9% +/- 13.2%, 49.6% +/- 10.3% and 34.9% +/- 9.6%, respectively). CONCLUSION: These results demonstrate the different effects of hyperglycemia on normal brain tissue and on tumor, suggesting that glucose loading may be a valuable adjunct to FDG PET to enhance detection of recurrent or residual brain tumors.

Adult↗

PubMed1994

Gene regulation of trkB and trkC in the chick retina by light/darkness exposure.

The trk gene family members; the neurotrophic receptors for neurotrophins, are implicated in the survival and the differentiation of neurons. The roles of these protooncogenes have been argued in the pathological conditions and in the specific developmental stage when the programmed cell death occurs to neurons. Here we studied a physiological role of the trk family members in the retina through observations of their gene regulation by light/darkness exposure. Northern blot analysis and immunohistochemistry demonstrate that trkB and trkC are up-regulated by light exposure and down-regulated by darkness in the rod/cone layer, the outer nuclear layer, and the ganglion cell layer. This physiological regulation suggests that these trk family members play a protective role from the damaging effect of light exposure in the retinal neurons.

Animals↗

PubMed1993

Molecular cloning and expression of a novel truncated form of chicken trkC.

The trk family of tyrosine protein kinase genes serves crucial roles for the development of the nervous system and the survival of neurons. The members of this gene family, trk, trkB and trkC, bind a distinct neurotrophin of the nerve growth factor (NGF) gene family, and trigger the intracellular signals which elicit trophic and differentiating effects on neurons. Adding to these neurotrophic receptor kinases, the truncated forms without the tyrosine kinase domain have been cloned and characterized. It has been thought that the existence of truncated forms is limited to trkB; however, very recently the truncated trkC has been cloned in rat [(1993) Neuron 10, 963-974; (1993) Neuron 10, 975-990]. We independently approached and molecularly cloned a truncated form which belongs to the chicken trkC. The truncated trkC possesses the binding and the transmembrane domains but not the tyrosine kinase domain. Northern blot analysis shows that the truncated form is preferentially expressed in the adult central nervous system. The truncated form is scarcely expressed during the embryonic stages. The conservation of the truncated trkC beyond species suggests they have specific functions.

Amino Acid Sequence↗

PubMed1993

trk immunoreactivity at neuronal dendrite and cell body.

Neurotrophins homologous to the nerve growth factor (NGF) bind the neurotrophic receptors of the trk gene family. Since the target tissues release these neurotrophic factors to the neuron, it has been believed that their trophic effects are mediated by the retrograde axonal transport. However it remains an open question whether the neurotrophins act through the autocrine or the paracrine mechanisms, since the protein-level expression of trk has not been studied so far. We have made polyclonal antibodies against the recombinant proteins of chicken trkC and rat trkB. These antibodies showed immunoreactivity at the dendrite and the cell body of neuron. This subcellular localization strongly suggests the autocrine or the paracrine mechanism of the neurotrophic factors. At the same time, our data provide basic knowledge to decide where to deliver these neurotrophic factors in the therapy of neurodegenerative diseases.

Amino Acid Sequence↗

PubMed1993

Hybrid cell extinction and re-expression of Oct-3 function correlates with differentiation potential.

The Oct-3 gene is expressed in highly undifferentiated cells and is implicated in mammalian early embryogenesis. We have generated a series of hybrid cells between pluripotent embryonal carcinoma cells (Oct-3+) and fibroblasts (Oct-3-), and have studied the regulation and function of Oct-3. Upon fusion, the hybrid cells differentiated to nestin+/Brn-2+ cells resembling neuroepithelial stem cells. Expression of Oct-3 was extinguished at the transcriptional level in all the hybrid cells examined. The Oct-3 modulating activity required for the Oct-3-mediated enhancer activation was also extinguished. When the Oct-3 transactivating function was introduced into the hybrid cells, they transformed into morphologically distinct nestin-/Brn-2- cells ('revertants'). When the 'revertant' cells subsequently lost Oct-3 expression, they differentiated back to nestin+/Brn-2+ cells. The close correlation between the phenotypic changes and the gain/loss of Oct-3 function indicates that Oct-3 can induce dedifferentiation of the neural cells.

Animals↗

PubMed1993

Expression and binding characteristics of the BDNF receptor chick trkB.

Previous studies using transfected cells have indicated that the mammalian receptor tyrosine kinase trkB binds the neurotrophins brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4. However, most studies demonstrating that these neurotrophins prevent the death of embryonic neurons and have specific neuronal receptors have been performed with chick neurons. In order to explore the possibility that trkB is the molecular entity representing the high-affinity receptor for brain-derived neurotrophic factor on embryonic chick neurons, we cloned and expressed a chick trkB cDNA. In situ hybridisation results indicate that the distribution of trkB mRNA in the peripheral nervous system of the developing chick embryo correlates well with the structures known to respond to brain-derived neurotrophic factor. Binding studies performed with a cell line stably transfected with the ctrkB cDNA indicate a dissociation constant for brain-derived neurotrophic factor of 9.9 x 10(-10) M, which is distinctly higher than that found on primary chick sensory neurons (1.5 x 10(-11) M). When binding of brain-derived neurotrophic factor was determined in the presence of other neurotrophins, neurotrophin-3 was found efficiently to prevent the binding of brain-derived neurotrophic factor to both the ctrkB cell line and embryonic sensory neurons. In vitro, neurotrophin-3 at high concentrations completely blocked the survival normally seen with brain-derived neurotrophic factor. Thus, unlike previous cases of receptor occupancy by heterologous neurotrophins (which resulted in agonistic effects), the interaction between the brain-derived neurotrophic factor receptor and neurotrophin-3 on sensory neurons is antagonistic.

Amino Acid Sequence↗

PubMed1992

Dopaminergic stimulation up-regulates the in vivo expression of brain-derived neurotrophic factor (BDNF) in the striatum.

We investigated the effect of dopamine on the in vivo expression of brain-derived neurotrophic factor (BDNF) in the striatum of mouse. BDNF mRNA expression in the striatum, which was quantified with the reverse transcriptase polymerase chain reaction, was up-regulated from 2 h after oral administration of levodopa, a precursor of dopamine. The increase was sustained for 16 h. Co-administration of haloperidol partially inhibited dopamine-induced BDNF enhancement. These data suggest that dopaminergic stimulation directly promotes the expression of BDNF in the striatum in vivo.

Amino Acid Sequence↗

PubMed1992

[XYY syndrome associated with motor neuropathy].

We described a case of XYY syndrome associated with motor neuropathy. The case was a 27-year-old male, who had 47-XYY chromosome karyotype. His symptoms were distal dominant muscle weakness and muscle atrophy in his lower extremities without objective sensory disturbance. He had no mental retardation or family history of neurologic diseases. The electrophysiological and pathological examinations revealed that his symptoms were due to peripheral motor neuropathy (neuronal type). His motor neuropathy may be of sporadic type. There may be some relation in the pathogenesis between XYY syndrome and motor neuropathy, although in the literature, XYY syndrome with motor neuropathy had not been reported so far.

Adult↗

PubMed1991

The oct3 gene, a gene for an embryonic transcription factor, is controlled by a retinoic acid repressible enhancer.

Oct3 is an embryonic octamer-binding transcription factor, whose expression is rapidly repressed by retinoic acid (RA). In this report, we have determined the transcriptional control region of the oct3 gene and studied the mechanism of the RA-mediated repression. The chromosomal oct3 gene consists of five exons. Three subdomains of the POU region and transactivating domain are located in separate exons. Transcription initiates at multiple sites in the GC-rich region lacking a typical TATA box. The upstream 2 kb region can confer the cell type-specific expression and RA-mediated repression. Analysis of the upstream region by deletion mutagenesis locates a cis element (RARE1) which functions as a stem cell-specific, yet RA-repressible, enhancer. Footprint and gel-retardation assays show that RARE1 is composed of two domains, each of which is recognized by distinct factors. Microinjection of oct3-lacZ constructs into fertilized eggs indicates that RARE1 can function in early embryos. We suggest that RARE1 is a critical cis element for oct3 gene expression in embryonic stem cells and for the RA-mediated repression.

Amino Acid Sequence↗

PubMed1991

[A case of Crow-Fukase syndrome with increased serum interleukin-6].

We experienced a 47-year-old Japanese female with polyneuropathy, edema, hypertrichosis, hyperpigmentation, and white nail, which were diagnostic as having Crow-Fukase syndrome. Laboratory and radiological evaluation showed neither plasma cell dyscrasia nor monoclonal gammopathy. Increased factor VIII activity and thrombocytosis, which suggested thrombotic tendency, were observed at the exacerbation of clinical symptoms. In her third exacerbation, she presented marked cyanosis in her right foot, and angiography confirmed narrowing of arteries at the ankle. Increased serum interleukin-6 was also observed, and the production of interleukin-6 by endothelial cells of cutaneous angioma was shown. Possible role of interleukin-6 in Crow-Fukase syndrome was discussed.

Factor VIII↗

PubMed1990

[Therapy of malignant pheochromocytoma using I-131 metaiodobenzylguanidine--report of a case].

A 67 year-old-female had multiple metastases to her lung, liver and paraaortic lymph nodes from a post-operative malignant pheochromocytoma. She was treated with 3.7 GBq (100 mCi) of I-131 metaiodobenzylguanidine (MIBG). Metastatic nodules in lung and liver almost disappeared and the secretion of catecholamines decreased than baseline rates. However, major but temporary untoward response, such as hypertension and hyperglycemia, was seen after the I-131 MIBG administration.

3-Iodobenzylguanidine↗

PubMed1990

A novel octamer binding transcription factor is differentially expressed in mouse embryonic cells.

We have identified a novel octamer binding factor (Oct-3) in P19 embryonal carcinoma cells. Oct-3, which recognizes the typical octamer motif (ATTTGCAT) as well as the AT-rich sequence TTAAAATTCA, is present in P19 stem cells but disappears when the cells are induced to differentiate by retinoic acid (RA). Cloned cDNA corresponding to Oct-3 encodes a protein of 377 amino acids. Oct-3 has a conserved POU domain, but the remaining part is distinct from other POU domain-containing proteins such as Oct-1 and Oct-2. mRNA of 1.5 kb coding for Oct-3 is abundant in P19 stem cells but is dramatically repressed during RA-induced differentiation. Repression of the 1.5 kb mRNA is rapid and specific to RA. In mouse, oct-3 mRNA is undetectable in all the adult organs examined. The N-terminal proline-rich region of Oct-3, when fused to the DNA binding domain of c-Jun, functions as a transcriptional activating domain. We suggest that Oct-3 is a novel octamer binding transcription factor that is developmentally regulated during mouse embryogenesis.

Amino Acid Sequence↗

PubMed1989

[31P-NMR spectroscopy of mitochondrial myopathies: the relation between abnormal energy metabolism and muscle biopsy findings].

31P-NMR spectra were obtained from the quadriceps femoris muscle (at rest and after aerobic exercise) of the 7 cases of mitochondrial myopathies (2 cases of mitochondrial encephalomyopathy and lactic acidosis(MELA), 1 case of myoclonus epilepsy with regged red fiber, 1 case of Kearns-Sayre syndrome, 3 cases of progressive external ophthalmoplegia), using superconducting whole body MR (Magnetom, Siemens). One case showed abnormally low Pcr/Pi ratio in the resting state. An aerobic exercise using ergometer was performed on the other 6 patients. Three of them demonstrated significant reduction and delayed recovery of the Pcr/Pi ratio after exercise. This reduction was not detected in the control subjects. Histological studies of biopsied muscles revealed ragged red fibers in all the cases, the number varies, however, from 0.5 to 15.3 per cent of the total fibers. Abnormalities in the Pcr/Pi ratio of phosphorus spectra, in resting state or after exercise, tend to be observed in patients showing abundant ragged red fibers. Focal cytochrome c oxidase deficiency with relatively small amount of ragged red fibers (less than 10 per cent of the total fibers) was histologically noted in five of our patients, excluding 2 MELA patients. Biochemical assay of mitochondria enzyme was normal. It has been assumed that these patients have no primary defect in energy metabolism and the occasionally observed cytochrome c oxidase deficient fibers are non-specific findings probably caused by some devastating process occurring in these fibers. However, our present studies revealed abnormal reduction and delayed restoration of the Pcr/Pi ratio in 2 out of 5 focal cytochrome c oxidase deficiency cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Lactic↗