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21.
Popken GJ Bunney WE Potkin SG Jones EG 《Proceedings of the National Academy of Sciences of the United States of America》2000,97(16):9276-9280
The hypoactivity of dorsolateral prefrontal cortex in schizophrenics is well known. One cause of this hypoactivity may be defective corticocortical or thalamocortical connections. Recent imaging studies of the thalamus suggest reductions in volume of the whole thalamus and reduced activity in the medial group of thalamic nuclei, which may indicate loss of functional input to the cortex. Using stereological techniques in six pairs of individually matched brains from schizophrenics and controls, we measured the volumes and obtained estimates of the number of neurons in the three subnuclei (parvocellular, pc; densocellular, dc; magnocellular, mc) of the mediodorsal nucleus (MD) and from the ventral posterior medial nucleus. There was a significant reduction in total neuron number in MD as a whole but this neuron loss was largely restricted to MDpc and MDdc [-30.9 and -24.5%, respectively (P = 0.01)]. MDmc and the control ventral posterior medial nucleus showed no significant changes in cell number. Because the subnuclei of MD have different connections and project to different areas of the frontal cortex, the specific loss of neurons in MDpc and MDdc has implications for the functional defects observed in schizophrenia. 相似文献
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23.
Julie V Patterson Curt A Sandman Yi Jin Aaron S Kemp Steven G Potkin William E Bunney Jr 《Bipolar disorders》2013,15(3):314-325
Patterson JV, Sandman CA, Jin Y, Kemp AS, Potkin SG, Bunney WE Jr. Gating of a novel brain potential is associated with perceptual anomalies in bipolar disorder. Bipolar Disord 2013: 00: 000–000. © 2013 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objectives: Our laboratory recently identified the P85 gating ratio as a candidate biomarker for bipolar disorder. In order to evaluate the phenomenological significance of P85 gating, the current study examined reports of perceptual anomalies and their relationship to the P50 and P85 physiological measures of sensory gating. Methods: Reports of perceptual anomalies on the Structured Clinical Interview to Assess Perceptual Anomalies were compared in patients meeting DSM‐IV criteria for paranoid schizophrenia (n = 66), schizoaffective disorder (n = 45), or bipolar I disorder (n = 42), and controls (n = 56), as well as their relationship with P85 and P50 gating. Results: The bipolar disorder group reported significantly more auditory, visual, and total anomalies than both the schizophrenia and control groups. The schizophrenia group also had more anomalies than the control group. Comparison of psychiatric subgroups revealed that the bipolar depressed, bipolar disorder with psychosis, and schizoaffective bipolar type groups reported the most anomalies compared to the other patient groups (bipolar disorder without psychosis, schizoaffective, bipolar manic). The total perceptual anomalies score and the P85 ratio significantly differentiated the bipolar disorder, schizoaffective, and paranoid schizophrenia groups from each other. Conclusions: These findings provide evidence of the phenomenological significance of P85. The results also yield further support not only for the P85 ratio, but also for increased reports of perceptual anomalies as possible markers for bipolar disorder. 相似文献
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25.
In vitro characterization of the human recombinant soluble granulocyte- macrophage colony-stimulating factor receptor 总被引:1,自引:0,他引:1
We have cloned, expressed, and partially purified a naturally occurring, truncated, soluble form of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha subunit to investigate its biochemical and biologic properties. The soluble receptor species lacks the transmembrane and cytoplasmic domains that are presumably removed from the intact receptor cDNA by a mechanism of alternative splicing. The resulting soluble 55- to 60-kD glycosylated receptor species binds GM-CSF with a dissociation constant (kd) of 3.8 nmol/L. The soluble GM-CSF receptor successfully competes for GM-CSF binding not only with the transmembrane-anchored GM-CSF receptor alpha subunit but also with the native oligomeric high-affinity receptor complex. In addition, in human bone marrow colony-forming assays, the soluble GM-CSF receptor species can antagonize the activity of GM-CSF. Our data suggest that the soluble GM-CSF receptor may be capable of acting in vivo as a modulator of the biologic activity of GM-CSF. 相似文献
26.
Clozapine blocks D-amphetamine-induced excitation of dopamine neurons in the ventral tegmental area.
Wei-Xing Shi Xiang-Yang Zhang Chen-Lun Pun Benjamin S Bunney 《Neuropsychopharmacology》2007,32(9):1922-1928
Current antipsychotic drugs are thought to inhibit central dopamine (DA) transmission by blocking DA receptors. Here, we provide evidence that the atypical antipsychotic drug clozapine may produce part of its effect by inhibiting a subset of excitatory inputs to DA neurons. Thus, in chloral hydrate-anesthetized rats, systemic administration of D-amphetamine produced two opposing effects on DA neurons in the ventral tegmental area. Under control conditions, D-amphetamine inhibited the firing of the cell through D2-like receptors. When D2-like receptors were blocked by raclopride, D-amphetamine excited DA neurons, instead of producing no effect. The excitation, expressed as an increase in firing rate and a slow oscillation in firing pattern, was suppressed by the adrenergic alpha1 receptor antagonist prazosin, suggesting an involvement of alpha1 receptors. In rats pretreated with the typical antipsychotic drug haloperidol, D-amphetamine also excited DA neurons. However, when given after clozapine, D-amphetamine produced no significant effects. The failure of D-amphetamine to produce an excitation is not due to an incomplete blockade of D2-like receptors by clozapine because co-treatment with clozapine and raclopride also failed to enable the excitatory effect of D-amphetamine. The suggestion that clozapine inhibits the excitatory effect of D-amphetamine is further supported by the finding that clozapine, given after D-amphetamine, reliably reversed D-amphetamine-induced excitation in raclopride-treated rats. Thus, different from raclopride and haloperidol, clozapine may inhibit DA transmission through two additive mechanisms: blockade of DA receptors and inhibition of an amphetamine-sensitive, excitatory pathway that innervates DA neurons. 相似文献
27.
Bunney WE Bunney BG Vawter MP Tomita H Li J Evans SJ Choudary PV Myers RM Jones EG Watson SJ Akil H 《The American journal of psychiatry》2003,160(4):657-666
OBJECTIVE: An international effort is in progress to discover candidate genes and pathways associated with psychiatric disorders, including two of the most serious diseases, schizophrenia and mood disorders, through the use of new technology-microarrays. Instead of studying one gene at a time, microarrays provide the opportunity to analyze thousands of genes at once. METHOD: This article reviews the steps in this discovery process, including the acquisition and characterization of high-quality postmortem brain tissue, RNA extraction, and preparation and use of microarray technology. Two alternative microarray methods and factors affecting the quality of array data are reviewed. RESULTS: New analytical strategies are being developed to process the massive data sets generated by microarray studies and to define the significance of implicated genes. Array results must be validated by other methods, including in situ hybridization and real-time polymerase chain reaction. Identified genes can also be evaluated in terms of their chromosomal locations and possible overlap with regions of suggestive linkage or association identified with genome-wide linkage analysis in psychiatry and in terms of overlap with genes identified by microarray studies in animals administered psychoactive drugs. Microarray studies are only the first major step in the process. Further efforts in the investigation involve multiple strategies for studying function and gene structure, including transgenic and knockout animal studies. CONCLUSIONS: Microarrays present a methodology that can identify genes or pathways for new and unique potential drug targets, determine premorbid diagnosis, predict drug responsiveness for individual patients, and, eventually, initiate gene therapy and prevention strategies. 相似文献
28.
Myo-Khin Thein-Win-Nyunt S Kyaw-Hla Thein-Thein-Myint TD Bolin 《Archives of disease in childhood》1994,71(4):311-3; discussion 313-4
It has been commonly believed that children in developing countries pass stools that are very different from those of developed countries. A community based study on defecation frequency, stool weight, and consistency was conducted in a cohort of 300 Myanmar (Burmese) children aged 1 to 4 years. Most (80.3%) children opened their bowels daily and none passed more than three stools a day. The mean (SD) defecation frequency was 6.98 (1.94) times a week and total stool weight was 596 (221) g a week. The majority (61%) of children passed soft stools. At all ages, there was no significant difference in the defecation frequency, stool weight, and consistency between boys and girls, those on adult style diet and those partially weaned, and between age groups. 相似文献
29.
Low doses of apomorphine elicit two opposing influences on dopamine cell electrophysiology 总被引:2,自引:0,他引:2
Dopamine (DA) cells are known to be very sensitive to direct acting DA agonists, and inhibition of DA cell firing by low doses of DA agonists is generally considered to be an action of these agonists on DA cell autoreceptors. During intracellular recording from spontaneously discharging DA cells in vivo, intravenous administration of apomorphine (20 micrograms/kg i.v.) elicited a hyperpolarization and an increase in input resistance. The calculated reversal potential of the apomorphine effect was approximately -40 mV. However, in non-firing DA cells the reversal potential of these effects was significantly different (P less than 0.01), being close to the reversal potential of responses induced by stimulation of striatonigral pathways (i.e. -67 mV). In addition, haloperidol (0.01 mg/kg i.v.) reversed the hyperpolarization produced by apomorphine but not the increase in input resistance. Transection of striatonigral pathways eliminated most of the increase in input resistance accompanying apomorphine administration, and shifted the apomorphine reversal potential to a value positive to 0 mV. Low doses of apomorphine were also found to affect a class of zona reticulata (ZR) interneurons. Apomorphine caused decreases in ZR cell firing rate, which were abolished by striatonigral pathway transection. Thus, the following mechanism is proposed for the electrophysiological actions of autoreceptor-selective doses of apomorphine on DA cells: (1) apomorphine directly inhibits spontaneous DA cell discharge by inhibiting the slow depolarization preceding action potentials and thereby hyperpolarizes the DA cell, (2) decreased DA cell firing disinhibits GABAergic striatal cells, whose increased firing preferentially (3) inhibits GABAergic ZR interneurons, and thus (4) removes an inhibitory input to DA cells, resulting in an increase in input resistance. 相似文献
30.
Fifty-eight all-night polygraphic sleep recordings were obtained on an unmedicated female bioplar (manic-depressive) patient who switched into and out of mania eight times. While depressed she was hypersomniac and exhibited elevated Rapid Eye Movement (REM) sleep time and short REM latency. On four nights, she apparently switched into mania while asleep. The last recorded sleep stage in each case was REM sleep. 相似文献