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Biomedical subjects

Y Okubo

Publications and source records attributed to Y Okubo.

At least 37 records · Page 2Linked to original sources
PubMed2001

Visualization of IP(3) dynamics reveals a novel AMPA receptor-triggered IP(3) production pathway mediated by voltage-dependent Ca(2+) influx in Purkinje cells.

IP(3) signaling in Purkinje cells is involved in the regulation of cell functions including LTD. We have used a GFP-tagged pleckstrin homology domain to visualize IP(3) dynamics in Purkinje cells. Surprisingly, IP(3) production was observed in response not only to mGluR activation, but also to AMPA receptor activation in Purkinje cells in culture. AMPA-induced IP(3) production was mediated by depolarization-induced Ca(2+) influx because it was mimicked by depolarization and was blocked by inhibition of the P-type Ca(2+) channel. Furthermore, trains of complex spikes, elicited by climbing fiber stimulation (1 Hz), induced IP(3) production in Purkinje cells in cerebellar slices. These results revealed a novel IP(3) signaling pathway in Purkinje cells that can be elicited by synaptic inputs from climbing fibers.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2001

Infrared spectroscopic study on the properties of the anhydrous form II of trehalose. Implications for the functional mechanism of trehalose as a biostabilizer.

FTIR spectra were obtained for several different states of trehalose including dihydrate crystal, anhydrous form II (designated by Gil, A. M.; Belton, P. S.; Felix V. Spectrochim. Acta 1996, A52, 1649-1659), anhydrate crystal, dried melt, amorphous solid and aqueous solution. From the observation of the symmetric and antisymmetric stretch vibrations of the glycosidic linkage, it is found that this sugar assumes at least three types of backbone conformations. Among them, the conformation with C(2) symmetry is characterized as 'open state', which means that the sugar easily absorbs water molecules. The conformation of the sugars in anhydrous form II and in freeze-dried trehalose is shown to be in the open state. Next, the hygroscopic properties of the anhydrate, form II and the amorphous solid are compared based on their IR spectra. Interestingly, form II alone is converted to the original dihydrate in a week under mild environmental-like conditions: relative humidity of 40% and room temperature. These results suggest the possibility that form II plays a role in avoiding the devitrification of the sugar glass. Finally, we discuss the role of form II in preserving freeze-dried biomaterials.

Animals↗
PubMed2001

Overexpression of homeobox gene HOXD3 induces coordinate expression of metastasis-related genes in human lung cancer cells.

Homeobox-containing genes are expressed in spatiotemporal fashion during embryogenesis and act as master transcription-regulating factors which control the expression of a variety of genes involved in morphogenesis. They are also expressed in a tissue-specific manner in normal adult tissues and appear to give cells spatial information in the maintenance of their architectural integrity. We transfected a HOXD3 class I homeobox-containing gene into human lung cancer A549 cells and investigated alterations in gene expressions and phenotypes related to the maintenance of tissue architecture in HOXD3-overexpressing A549 cells. In the HOXD3-overexpressing cell lines, expression of E-cadherin was lost and plakoglobin was strongly repressed, whereas integrin alpha3 and beta3 were up-regulated and N-cadherin and integrin alpha4 were newly expressed. Compared with parental and control transfectant lines, the HOXD3-overexpressing cell lines showed highly motile and invasive activity. Blocking experiments using anti-integrin beta1 and beta3 suggested that the increased haptotaxis of the HOXD3-overexpressing cells to vitronectin resulted from increased expression and activation of integrin alphavbeta3, and that overexpression of the HOXD3 gene converted the integrin beta1-dependent haptotaxis to fibronectin into both integrin beta1- and beta3-dependent one. HOXD3 overexpression increased production of matrix-degrative enzymes including matrix metalloproteinase-2 and urokinase-plasminogen activator. When the tumor cells were intravenously injected into the tail veins of nude mice, HOXD3 transfectants formed a significantly large number of metastatic foci in lungs compared with the control transfectants. These findings suggest that HOXD3 can act as a metastasis-promoting gene in human lung cancer A549 cells.

Antigens, CD↗
PubMed2001

Age-related reduction of extrastriatal dopamine D2 receptor measured by PET.

Although the aging effect of dopamine D2 receptor in the striatum is well-documented, the effect of age on the extrastriatal dopamine D2 receptor has not been fully examined. Since the density of extrastriatal dopamine D2 receptor is very low, suitable ligands are limited. In this study, we used [11C]FLB 457 to quantify the extrastriatal dopamine D2 receptor in the living human brain. Twenty-seven healthy male subjects aged from 21 to 82 years participated in the positron emission tomography study. Extrastriatal [11C]FLB 457 binding was quantified with a reference tissue model using cerebellum as a reference region. Binding potentials corresponding to Bmax/Kd were used to evaluate age-related change. We found age-related decreases of D2 receptor binding in all measured extrastriatal regions. The decrease of D2 receptor binding was 13.8% per decade in frontal cortex, 12.0% in temporal cortex, 13.4% in parietal cortex, 12.4% in occipital cortex, 12.2% in hippocampus, and 4.8% in thalamus. These findings suggest that the amounts of D2 receptor declines in all brain regions as part of the normal aging process.

Adult↗
PubMed2001

Association between cadmium concentration in rice and mortality in the Jinzu River basin, Japan.

A follow-up survey on 2101 inhabitants (1566 men, 535 women), who participated in a 1967 health survey and had resided in their present rural community since birth was conducted to determine the influence of environmental cadmium exposure on the mortality of the general population in the Jinzu River basin. The survey was conducted over 6128 days from August 1, 1967 to May 10, 1984. The rural communities were divided into two groups, one with a cadmium concentration in rice of < 0.30 ppm and the other > or = 0.30 ppm. The influence of cadmium concentration in rice on mortality was analyzed using SMRs and a Cox's proportional hazards model. In both sexes, SMRs tended to be greater in the > or = 0.3 ppm group as compared to < 0.3 ppm group. The Cox hazard ratios for males and females in the > or = 0.30 ppm group, to those in the < 0.30 ppm group, were 1.42 and 1.10, respectively (significant in the men). Since the mean cadmium concentration in rice in each rural community was closely related to the development of renal injury, in regions with high cadmium concentrations in rice, the development of renal injury induced by cadmium is believed to be the factor underlying the increased mortality observed.

Adult↗
PubMed2001

Relation among dopamine D(2) receptor binding, obesity and personality in normal human subjects.

Personality is a behavioral pattern, which differs among individuals. Kretschmer (Kretschmer, E., Physique and Character: an Investigation of the Nature of Constitution and the Theory of Temperament, New York, 1921) categorized personality variants according to the concept of fundamental body types. Recently, several lines of evidence suggest that the central dopamine system may underlie the regulation of weight and the personality trait. In this study, we examined the dopamine D2 receptor (D2R) binding using positron emission tomography with [11C]FLB 457 [(s)-N-[(1-ethyl-2-pyrrolidinyl) methyl]-5-bromo-2,3-dimethyloxybenzamide] together with body mass index (BMI) and personality trait on the temperament and character inventory (TCI) in 16 normal subjects. Our data demonstrate that there was a significant relation among D2R binding in the amygdala, BMI and personality trait of harm avoidance. It can be assumed that variation of dopaminergic activity in the amygdala underlies the personality variants related to the concept of fundamental body type.

Adult↗
PubMed2001

Cortical oscillations in human medial temporal lobe during wakefulness and all-night sleep.

We have recorded human medial temporal lobe electrocorticogram during wakefulness and natural sleep in epileptic patients with subdural electrodes. From these recordings, we have found gamma (30-150 Hz) [Neuroscience 90 (1999) 1149] and beta-1 (10-20 Hz) [NeuroReport 10 (1999) 3055] activities during wakefulness in human medial temporal lobe. In this paper, we will report changes of these frequencies across wake and natural sleep. Electrocorticograms during wake, slow wave sleep and rapid eye movement (REM) sleep were subjected to fast Fourier transformation analysis. During wake two spectral enhancements, beta-1 and gamma, were consistently observed across subjects. In the raw signal, beta-1 was observed as a regular rhythmic oscillation. In slow wave sleep, the beta-1 peak disappeared but gamma remained, although slightly reduced in power. During REM sleep, beta-1 appeared again, but the peak frequency was significantly lower than during wake (mean frequency: wake=16.6, REM=12.8 Hz). The gamma peak was also present in REM sleep. It has been known that the rhythmic slow activity (RSA) or theta is observed in some animals. However, it is unclear whether the human hippocampus displays similar activity. Since human beta-1 appears during wake and REM sleep when RSA is observed in other species, and since beta-1 is also a regular rhythmic oscillation, we propose that beta-1 may be the functional equivalent of hippocampal RSA (theta) observed in some animals. Functional significances of the gamma activity should be further investigated.

Adult↗
PubMed2001

Reduced volume of the cerebellar vermis in neuroleptic-naive schizophrenia.

BACKGROUND: Neuroimaging studies have suggested the possible role of the cerebellum in the pathophysiology of schizophrenia. However, no study has investigated the detailed structures of the cerebellum in patients without a history of neuroleptic medication. The objective of this study is to examine the volume of detailed structures of the cerebellum in neuroleptic-naive schizophrenic patients and to examine the relationship between cerebellar morphology and clinical symptoms. METHODS: Magnetic resonance imaging scans were acquired from 20 male neuroleptic-naive schizophrenic patients and 20 healthy control subjects. We measured the volumes of the cerebrum, cerebellar hemisphere, cerebellar gray and white matter, and vermis. Symptoms were assessed with the Brief Psychiatric Rating Scale. Total Brief Psychiatric Rating Scale scores and subscale scores were used for analysis. RESULTS: The volume of the vermis was significantly reduced in the schizophrenic group relative to the control group, whereas no significant differences were found in the volumes of other cerebellar structures and the cerebrum. Reduction in the vermal volume correlated with the total Brief Psychiatric Rating Scale Depression subscore and Paranoia subscore. CONCLUSIONS: This study indicates that the volume of the vermis is reduced in patients with schizophrenia, and reduction in vermal volume is suggested to be related to the pathophysiology of the disease.

Adult↗
PubMed2001

Mechanism of hypergammaglobulinemia by HIV infection: circulating memory B-cell reduction with plasmacytosis.

The mechanism of hypergammaglobulinemia in patients infected with HIV has remained unclear in spite of the identification of a reduction of CD4+ T cells. The amounts of CD27+ memory B cells were remarkably reduced in the peripheral blood and immunoglobulin (Ig) production was diminished in HIV-infected patients. Some of the freshly isolated patients' T cells expressed the CD70 (CD27 ligand) on the surface and the CD70 expression on both of the CD4+ and CD8+ T cells was greatly enhanced by various stimuli. It was also striking that plasmacytosis was observed in patients' bone marrow. Thus, our findings suggest that CD70 expressed spontaneously or by activation on T cells of HIV-infected patients stimulates memory B cells via CD27 and promotes their differentiation into plasma cells, resulting in the elevation of serum Ig levels and the elimination of circulating memory B cells in HIV-infected patients.

Adult↗
PubMed2001

A retrospective study on the relation between renal dysfunction and cadmium concentration in rice in individual hamlets in the Jinzu River basin, Toyama Prefecture, Japan.

Using as an index of exposure the Cd concentration in rice and as an index of health effect the urinary abnormality rate (proteinuria, glycosuria, and proteinuria with glycosuria) in the most systematic and extensive health screening examination conducted in 1967 and 1968 in the Jinzu River basin, Japan (a total of 13,183 subjects), we investigated whether a dose-response relationship exists between the two indices. For subjects that lived in the same hamlet since birth, with low Cd concentrations in rice it was confirmed that renal dysfunction does not develop unless the length of residence is prolonged, whereas with high Cd concentrations in rice renal dysfunction develops even when the length of residence is short. For subjects that lived in the same hamlet for over 30 years and that were aged over 50 years, the urinary abnormality rate in individual hamlets showed significant increases with increases in the mean Cd concentration in rice, demonstrating that a dose-response relationship existed. The allowable values of Cd concentration in rice were estimated to be in the range of 0.05-0.20 ppm, representing values lower than the 0.4 ppm provisionally adopted by the Japanese government.

Adult↗
PubMed2001

Error analysis for quantification of [(11)C]FLB 457 binding to extrastriatal D(2) dopamine receptors in the human brain.

To estimate receptor binding of ligand by positron emission tomography (PET) without an arterial input function, several quantitative approaches based on the use of a reference region have been proposed. We compared three approaches for quantifying extrastriatal D(2) dopamine receptors using [(11)C]FLB 457. The PET measurements were performed on seven healthy men. Binding potential (BP) of [(11)C]FLB 457 was calculated by the reference tissue model method, transient equilibrium method, and late time method. The reference tissue model describes the time-activity curve in a brain region in terms of that in the reference region, assuming that the levels of nondisplaceable radioligand binding in both regions are the same. The transient equilibrium theoretically occurs when the derivative for specific binding is zero. With the late time method, BP is calculated by integrating a late part of the time-activity curve. BP values obtained by all methods were in good agreement with those obtained by the kinetic approach, and the highest coefficient of correlation was observed in the reference tissue model method. In the simulation study, the error of BP calculated by the reference tissue model method was smallest. Moreover, the effect of the difference in the influx rate constant K(1) between the brain and the reference regions on BP was nearly avoided as theoretically predicted. We concluded that the reference tissue model method is most suitable for calculating BP of extrastriatal D(2) dopamine receptors with [(11)C]FLB 457.

Adult↗
PubMed2001

Dopamine D2 receptors in the insular cortex and the personality trait of novelty seeking.

Human personality has been considered to have a neurochemical background. We examined the relation between extrastriatal dopamine D2 receptor binding in living human brain and the personality trait of novelty seeking that has been proposed to be related to dopaminergic function in the brain. We measured extrastriatal dopamine D2 receptors of 24 healthy young male subjects using [(11)C]FLB 457 positron emission tomography. The personality trait of each subject was assessed by the Temperament and Character Inventory (TCI). Correlation of dopamine D2 receptor binding with novelty seeking was calculated using region-of-interest analysis and statistical parametric mapping based on the binding potential images generated using a reference tissue model. A significant negative correlation was observed between binding potential values and the novelty seeking scores on TCI in the right insular cortex. No significant correlation was observed in any other region. Our result indicates that there is a significant association between dopamine D2 receptor binding and the human novelty seeking trait in the right insular cortex.

Adult↗
PubMed2001

7Li 2D CSI of human brain on a clinical scanner.

Lithium salts have been widely used in the treatment of mood disorders, but the mechanism of action is still not clear. In this work, a methodology for two-dimensional Lithium-7 imaging on clinical systems is presented. The data were acquired using a phosphorus volume head coil that was re-tuned for the Lithium-7 frequency. A spectroscopic sequence was used to acquire the free induction decay (FID) after volume excitation using a hard pulse. The results obtained on the head of patients undergoing lithium treatment (n = 7, 0.6 mEq/l average serum level) demonstrate that images of adequate signal to noise ratio (100:1) can be obtained in acceptable imaging times (55 min) using the proposed methodology. The distribution of 7Li appears uniform in the brains of the patients studied.

Brain↗
PubMed2001

Dose relationship of limbic-cortical D2-dopamine receptor occupancy with risperidone.

RATIONALE: It has been suggested that the antipsychotic effect of antipsychotics is mediated by the antagonism of the dopamine D2 receptor in the limbic-cortical regions. Risperidone has an atypical property, but its effect on limbic-cortical regions has not been evaluated. OBJECTIVES: In this study, we examined the relationship among doses of risperidone and limbic-cortical dopamine D2 receptor occupancy using positron emission tomography. METHODS: Seven patients with schizophrenia were scanned during the steady state with risperidone. Their occupancies in limbic-cortical regions were determined using positron emission tomography with [11C]FLB 457. RESULTS: The average occupancy ranged from 38% to 80% on doses of 1-6 mg/day. The saturation curve plotted against the drug level fit the data well. CONCLUSIONS: Our results demonstrate that the D2 receptor occupancy with risperidone in the limbic-cortical regions seems to be similar to that of previous reports regarding the striatum, and it would be comparable to that of typical antipsychotics.

Adult↗
PubMed2001

Relationship between exploratory eye movements and clinical course in schizophrenic patients.

Exploratory eye movements are psychophysiological indicators of schizophrenia as well as smooth pursuit eye movements. To investigate whether these eye movements change in accordance with the clinical course of the condition in schizophrenia, exploratory eye movements (number of eye fixations, mean eye scanning length, responsive search score, evaluation of reproduced Fig. 1 and 2) of 28 schizophrenic patients were evaluated in repeat test design, conducted an average of 8 months apart. Subjects were first-medicated schizophrenics, half were outpatients and the remaining half were inpatients at the Neuropsychiatry ward of Tokyo Medical and Dental University Hospital. Exploratory eye movement patterns did not improve despite an improvement in clinical symptoms of schizophrenia. This result and those of previous studies of the exploratory eye movements of schizophrenic patients' families suggest that exploratory eye movements reflect a schizophrenic vulnerability marker. Furthermore, decreased mean eye scanning length (MESL) values were observed in subjects who showed unimproved symptoms, particularly negative symptoms over an extended period of time. The result suggests that a decrease in the MESL value may be the most sensitive indicator in the development of chronicity in schizophrenia.

Adolescent↗
PubMed2001

Association analysis of the pituitary adenyl cyclase activating peptide gene (PACAP) on chromosome 18p11 with schizophrenia and bipolar disorders.

In neurons, pituitary adenyl cyclase activating peptide (PACAP) stimulates signaling cascades, involving cAMP and calcium. PACAP appears to play a role in up-regulation of tyrosine hydroxylase and dopamine beta-hydroxylase via protein kinase C and/or protein kinase A. Furthermore, the PACAP gene (ADCYAP1) is located in chromosome 18p11, where linkage of bipolar disorders and schizophrenia has been reported. In this study, we scanned the coding region of the PACAP gene for mutations in 24 Japanese patients with schizophrenia and 24 Japanese patients with bipolar disorders. No variant in the coding region was found. One polymorphism, INV3-37A/T, in the third intron was detected. Case-control comparisons revealed no significant association between this polymorphism and schizophrenia or bipolar disorders. This study did not provide evidence for the contribution of the PACAP gene to the etiology of schizophrenia or bipolar disorders in the Japanese population.

Adolescent↗
PubMed2001

Alcohol consumption and blood pressure in Japanese men.

In a study of Japanese men, a nonlinear association of alcohol consumption and blood pressure was not observed. This cross-sectional study was conducted to clarify the effect of infrequent or light alcohol consumption on blood pressure in normotensive Japanese men. The subjects were 2,179 male workers ranging in age from 40 to 54 years. Drinking habits were represented by three indices: episodic alcohol consumption, frequency of drinking, and monthly alcohol consumption. Seven items were analyzed as covariates: age, body mass index, salt intake, physical activity, and levels of gamma-glutamyl transpeptidase, uric acid, and plasma glucose. The association between drinking habits and blood pressure was evaluated by using analysis of covariance. Both episodic alcohol consumption and frequency of drinking were significantly associated with blood pressure in subjects aged 45 to 54 years. In those aged 40 to 44 years, there was a significant association between frequency of drinking and diastolic blood pressure. Significant associations of monthly alcohol consumption with blood pressure in every age group also were found. In subjects aged 45 to 54 years, linear associations between episodic alcohol consumption, frequency of drinking, monthly alcohol consumption, and adjusted blood pressure were observed. In those aged 40 to 44 years, nonlinear associations of monthly alcohol consumption and frequency of drinking with adjusted blood pressure were observed, and threshold effects of 540 ml of alcohol per month and a frequency of 1 to 12 days per month were found. In conclusion, habitual alcohol consumption increases blood pressure linearly in normotensive workers aged 45 to 54 years, although light consumption does not affect blood pressure in those aged 40 to 44 years.

Adult↗