Whole-body biodistribution, radiation absorbed dose, and brain SPET imaging with [123i]5-i-A-85380 in healthy human subjects.

The biodistribution of radioactivity after the administration of a new tracer for alpha4beta2 nicotinic acetylcholine receptors (nAChRs), [123I]5-iodo-3-[2(S)-2-azetidinylmethoxy]pyridine (5-I-A-85380), was studied in ten healthy human subjects. Following administration of 98+/-6 MBq [123I]5-I-A-85380, serial whole-body images were acquired over 24 h and corrected for attenuation. One to four brain single-photon emission tomography (SPET) images were also acquired between 2.

Electrophysiological assessment of neuropsychiatric disorders.

In this article the clinical usefulness and limitations of the routine electroencephalogram (EEG) are discussed. Emphasis is placed on 3 specific clinical situations where EEG can be most useful: the differential diagnosis of dementia versus pseudodementia, the evaluation of episodic behavior disorders including aggressive episodes, and acute confusional states. An atypical clinical presentation is emphasized as the most important indiction for obtaining an EEG evaluation.

Comparison of [(18)F]altanserin and [(18)F]deuteroaltanserin for PET imaging of serotonin(2A) receptors in baboon brain: pharmacological studies.

The regional distribution in brain, distribution volumes, and pharmacological specificity of the PET 5-HT(2A) receptor radiotracer [(18)F]deuteroaltanserin were evaluated and compared to those of its non-deuterated derivative [(18)F]altanserin. Both radiotracers were administered to baboons by bolus plus constant infusion and PET images were acquired up to 8 h. The time-activity curves for both tracers stabilized between 4 and 6 h.

Elevated motor threshold in drug-free, cocaine-dependent patients assessed with transcranial magnetic stimulation.

Background: Transcranial magnetic stimulation (TMS) provides a noninvasive method of examining cortical inhibitory and excitatory processes and cortical excitability in awake subjects. There is evidence from clinical and electroencephalographic (EEG) data that cortical excitability may be abnormal in some psychiatric populations. Chronic cocaine abuse influences a number of neurotransmitters that are involved in the excitatory/inhibitory balance of the cerebral cortex.

Effect of 2'-O-methyl antisense ORNs on expression of thymidylate synthase in human colon cancer RKO cells.

Translation of thymidylate synthase (TS) mRNA is controlled by its own protein end-product TS in a negative autoregulatory manner. Disruption of this regulation results in increased synthesis of TS and may lead to the development of cellular drug resistance to TS-directed anticancer agents. As a strategy to inhibit TS expression, antisense 2'-O-methyl RNA oligoribonucleotides (ORNs) were designed to directly target the 5' upstream cis-acting regulatory element (nucleotides 80-109) of TS mRNA.

Cocaine use and the mid-latency auditory evoked responses.

To examine the effects of chronic cocaine use on the mid-latency auditory evoked responses (MLAERs), we recorded the evoked responses of 15 cocaine-dependent subjects and 13 age-matched healthy control subjects. Two evoked response paradigms were used: a trains paradigm with four different inter-stimulus intervals (ISIs) and a paired-click paradigm. Our data suggest that cocaine-dependent subjects generate smaller P50 components when long ISIs are used with multiple repetitions (in the trains paradigm).

In vitro selection of an RNA sequence that interacts with high affinity with thymidylate synthase.

Previous studies have shown that the repressive effect of thymidylate synthase (TS) mRNA translation is mediated by direct binding of TS itself to two cis-acting elements on its cognate mRNA. To identify the optimal RNA nucleotides that interact with TS, we in vitro synthesized a completely degenerate, linear RNA pool of 25 nt and employed in vitro selection to isolate high affinity RNA ligands that bind human TS protein. After 10 rounds of selection and amplification, a single RNA molecule was selected that bound TS protein with nearly 20-fold greater affinity than native, wild-type TS RNA sequences.

Characterization of a cis-acting regulatory element in the protein coding region of thymidylate synthase mRNA.

Thymidylate synthase (TS) functions as an RNA-binding protein by interacting with two different sequences on its own mRNA. One site is located in the 5'-upstream region of human TS mRNA while the second site is located within the protein coding region corresponding to nt 434-634. In this paper, a 70 nt RNA sequence, corresponding to nt 480-550, was identified that binds TS protein with an affinity similar to that of full-length TS mRNA and TS434-634 RNA.

Comparison of four components of sensory gating in schizophrenia and normal subjects: a preliminary report.

Dysfunction of sensory gating has been implicated in the pathophysiology of schizophrenia. The goal of this study was to provide evidence that sensory gating dysfunction in schizophrenia patients is a compounded problem with difficulty in filtering out irrelevant input and filtering in relevant input at both an early-preattentive stage and a later, early-attentive stage of information processing. Four components of sensory gating were examined in 12 medicated, stable schizophrenia patients and 12 age- and sex-matched normal control subjects.

Development of the Quality of Life in Epilepsy Inventory for Adolescents: the QOLIE-AD-48.

Purpose: We report the development of an instrument to assess health-related quality of life (HRQOL) in adolescents with epilepsy.

Methods: A sample of 197 English-speaking adolescents (aged 11-17 years) with epilepsy completed a test questionnaire of 88 items. Also included were mastery and self-esteem scales to assess external validity.

Regulation of p53 expression by thymidylate synthase.

Previous studies showed that thymidylate synthase (TS), as an RNA binding protein, regulates its own synthesis by impairing the translation of TS mRNA. In this report, we present evidence that p53 expression is affected in a similar manner by TS. For these studies, we used a TS-depleted human colon cancer HCT-C cell that had been transfected with either the human TS cDNA or the Escherichia coli TS gene.

Repression of human thymidylate synthase mRNA translation by antisense 2'-O-methyl oligoribonucleotides.

Previous studies have shown that translation of thymidylate synthase (TS) mRNA is controlled by its own protein end product TS in a negative autoregulatory manner. Disruption of this process results in increased synthesis of TS and may be associated with the development of cellular drug resistance to TS-directed anticancer agents. As one strategy to inhibit TS expression, we have designed antisense RNA oligoribonucleotides (ORNs) that directly target the 5'-upstream binding site (nt 80-109) of TS mRNA, a critical cis-acting regulatory element.

Intraoperative determination of cardiac output using multiplane transesophageal echocardiography: a comparison to thermodilution.

Background: Limitations in the imaging views that can be obtained with transesophageal echocardiography (TEE) have hindered development of a widely adopted Doppler method for cardiac output (CO) monitoring. The authors evaluated a CO technique that combines steerable continuous-wave Doppler with the imaging capabilities of two-dimensional multiplane TEE.

Methods: From the transverse plane transgastric, short-axis view of the left ventricle, the imaging array was rotated to view the left ventricular outflow tract (LVOT) and ascending aorta.

Regulation of the expression of enzymes involved in the replication of DNA in chemically induced monocytic/macrophagic differentiation of HL-60 leukemia cells.

The expression of a number of housekeeping enzymes of DNA biosynthesis was measured in HL-60 promyelocytic leukemia cells undergoing monocytic/macrophagic differentiation following treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) or 1alpha,25-dihydroxyvitamin D3 (vitamin D3). Progressive decreases in the steady-state levels of the mRNAs for thymidylate synthase, topoisomerase II, and hypoxanthine guanine phosphoribosyltransferase occurred following exposure to TPA or vitamin D3. In contrast, the steady-state levels of the mRNAs for thymidine kinase, topoisomerase I, and DNA polymerase-alpha did not decrease until days 3-5 of treatment with vitamin D3 and then progressively declined thereafter.

Regulation of the expression of enzymes involved in the replication of DNA in chemically-induced granulocytic differentiation of HL-60 leukemia cells.

The expression of seven enzymes involved in the biosynthesis of DNA was measured in HL-60 promyelocytic leukemia cells treated with dimethylsulfoxide (DMSO) or all-trans retinoic acid (RA) to gain information on their role in the termination of proliferation in cells undergoing granulocytic differentiation. The steady-state levels of the mRNAs for topoisomerase I, topoisomerase II. DNA polymerase-alpha, thymidylate synthase, thymidine kinase and hypoxanthine-guanine phosphoribosyltransferase progressively declined from day 3 to day 7 of exposure to the polar solvent or the retinoid suggesting that the expression of these enzymes is coordinately regulated.