Characterization of a series of anabaseine-derived compounds reveals that the 3-(4)-dimethylaminocinnamylidine derivative is a selective agonist at neuronal nicotinic alpha 7/125I-alpha-bungarotoxin receptor subtypes.

Investigation of the naturally occurring, nicotinic agonist anabaseine and novel derivatives has shown that these compounds have cytoprotective and memory-enhancing effects. The hypothesis that these arise at least in part through actions on brain nicotinic receptors was evaluated by examining the ability of these compounds to displace the binding of nicotinic ligands and to affect the function of the alpha 4 beta 2 and alpha 7 receptor subtypes expressed in Xenopus oocytes. The derivative 3-(4)-dimethylaminocinnamylidine anabaseine (DMAC) was found to be a selective alpha 7 receptor agonist; it was more potent than nicotine, acetylcholine, anabaseine, and other derivatives at activating the alpha 7 receptor subtype, while displaying little agonist activity at alpha 4 beta 2 and other receptor subtypes.

Safety and efficacy of iopromide in cerebral arteriography.

Rationale And Objectives: Iopromide is a new nonionic monomeric contrast medium for cerebral arteriography. This agent has been approved for sale in over 45 countries; however, it is still undergoing clinical review in the United States. This study evaluated the safety and efficacy of iopromide in comparison with two other nonionic contrast media.

A novel nicotinic agonist facilitates induction of long-term potentiation in the rat hippocampus.

Long-term potentiation (LTP) can be modulated by a number of neurotransmitter receptors including muscarinic and GABAergic receptor types. We have found that a novel nicotinic agonist, 2,4-dimethoxybenzylidene anabaseine (DMXB), facilitated the induction of LTP in the hippocampus in a dose-dependent and mecamylamine-sensitive manner. DMXB displaced high affinity nicotinic [125I]alpha-bungarotoxin and [3H]acetylcholine binding in rat brain.

Inhibition of nicotinic acetylcholine receptors by bis (2,2,6,6-tetramethyl- 4-piperidinyl) sebacate (Tinuvin 770), an additive to medical plastics.

Bis (2,2,6,6-tetramethyl-4-piperidinyl) sebacate (BTMPS; Tinuvin 770), a sterically hindered amine light and radiation stabilizer manufactured by Ciba-Geigy Corp. (Summit, NJ) and used in a wide range of plastics, inhibits nicotinic acetylcholine receptors expressed in Xenopus oocytes in a use-dependent manner. BTMPS is a symmetrical conjugate of methylated piperidines, which are themselves effective inhibitors, but have faster kinetics of inhibition and recovery than BTMPS.

Partial agonist properties of cytisine on neuronal nicotinic receptors containing the beta 2 subunit.

As previously reported by Luetje and Patrick [J. Neurosci. 11:837-845 (1991)], the nicotine-like alkaloid cytisine is relatively ineffective in evoking current responses from nicotinic receptors containing the beta 2 subunit.

Focal hyperintensities in cerebral white matter on MR images of asymptomatic volunteers: correlation with social and medical histories.

Objective: Previous attempts to explain the presence of focal hyperintensities in the cerebral white matter on MR images have focused on the patient's age and cardiovascular risk factors. The purpose of this study was to survey many variables in subjects' social, medical, and surgical histories to identify those factors associated with focal hyperintensities in asymptomatic persons.

Subjects And Methods: Asymptomatic volunteers were examined with MR imaging of the head and questioned concerning smoking history; chemical dependence; alcohol consumption; medical history (e.

The amino terminal half of the nicotinic beta-subunit extracellular domain regulates the kinetics of inhibition by neuronal bungarotoxin.

Subtypes of nicotinic receptors previously reported to be unaffected by neuronal bungarotoxin (NBT), including alpha 3 beta 4-containing and muscle type (alpha 1 beta 1 gamma delta) receptors, are shown to be inhibited by this toxin, but with rapid kinetics of onset and recovery. This inhibition is in contrast to the slow and prolonged inhibition of alpha 3 beta 2-containing receptors, suggesting that the beta subunits determine the kinetics of NBT inhibition of alpha 3 receptors. We have coexpressed chimeric beta subunits with alpha 3, and our results show that the first 121 amino acids of the beta subunit extracellular domain are sufficient to regulate the kinetics of NBT inhibition.

Quantitative MR in the diagnosis of multiple sclerosis.

In patients with multiple sclerosis (MS), the apparently uninvolved cerebral white matter between demyelinated plaques may have biochemical abnormalities. To what degree the changes in the white matter contribute to symptomatology in MS is unknown. In 39 patients with multiple sclerosis, and in 39 age-matched nondiseased volunteers, T1 and T2 were calculated from spin-echo images in four regions of apparently uninvolved white matter.

High-signal foci on MR images of the brain: observer variability in their quantification.

Foci of high signal in the cerebral white matter are common incidental findings on MR images of the brain of control subjects or patients with a variety of diseases. Although the number of foci has been reported to correlate with age and several risk factors, the degree of observer variability in quantifying foci has not been reported. We used kappa statistics to determine radiologists' agreement in counting high-signal-intensity foci on MR images obtained in healthy volunteers and in patients with hypertension.

T1 and T2 in the cerebrum: correlation with age, gender, and demographic factors.

The authors measured the T1 and T2 of cerebral tissue in 164 volunteers aged 5-90 years and correlated T1 and T2 with age, gender, and various demographic variables. A weak correlation with statistical significance was found between age and T1 and T2 in white and gray matter structures. The T1 and T2 in the telencephalon increased by about 0.

Identification of cultured cells expressing ligand-gated cationic channels.

We have identified cultured cells that express ligand-gated cation channels using a simple method which may also be applied to the screening of chemical agents for their use as agonists or antagonists. This assay is based upon the observation that many ligand-gated cation channels are permeable to lithium and agonists induce the flux of lithium into the cells which contain them. Since the accumulation of intracellular lithium can alter the cell cycle, the measurement of [3H]thymidine ([3H]thy) incorporation should reflect this occurrence.

Multiple sclerosis: specificity of MR for diagnosis.

The specificity of magnetic resonance (MR) imaging in the diagnosis of multiple sclerosis (MS) has not been measured systematically. Conventional MR head images with sagittal localizer and axial multiple-echo sequences with long repetition times were obtained in 92 patients with clinically verified MS (Schumacher criteria), 100 healthy volunteers, 60 subjects with hypertension, and eight patients with dementia. Two readers, without the aid of any clinical or demographic information, classified each of the 260 studies as MS or not MS.

The nicotinic receptor genes.

The causative factor(s) of Alzheimer's disease (AD) are presently unknown. However, it has been shown that the number as well as the fraction of high- to low-affinity nicotine binding sites is altered in patients suffering from this disease. This finding, along with the identification of seven genes which code for nicotinic receptors expressed in the mammalian brain, has led to the idea that one nicotinic receptor subtype may be specifically altered in AD.

The role of the beta 4-subunit in determining the kinetic properties of rat neuronal nicotinic acetylcholine alpha 3-receptors.

1. Single-channel currents were recorded from Xenopus oocytes which had been injected with complementary RNAs (cRNAs) for the neuronal nicotinic acetylcholine receptor subunits alpha 3 and beta 4. The co-expression of alpha 3 and beta 4 gave rise to three different channel types with conductances of 22, 18 and 13 pS.

Single-channel currents of rat neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes.

The neuronal nicotinic acetylcholine receptor subunits alpha 2, alpha 3, and alpha 4 form functional receptors with the beta 2 subunit. Each of these subunit combinations shows two distinct open states (referred to as primary and secondary). The primary open states of alpha 2 beta 2, alpha 3 beta 2, and alpha 4 beta 2 receptors were 33.

Contrast enhancement in spinal MR imaging.

We evaluated 44 patients with suspected spinal tumors or previous laminectomies with gadolinium-DTPA MR imaging in order to characterize the enhancement in normal, postoperative, and neoplastic intraspinal tissue. Using the signal intensity of CSF as an internal control, we calculated the percentage increase in signal intensity from pre- to postgadolinium studies. Tumors (astrocytoma, ependymoma, schwannoma) enhanced 70-350%; epidural scar, normal epidural venous plexus, and dorsal root ganglion enhanced up to 200%.

Alzheimer disease: quantitative analysis of I-123-iodoamphetamine SPECT brain imaging.

To enable a more quantitative diagnosis of senile dementia of the Alzheimer type (SDAT), the authors developed and tested a semiautomated method to define regions of interest (ROIs) to be used in quantitating results from single photon emission computed tomography (SPECT) of regional cerebral blood flow performed with N-isopropyl iodine-123-iodoamphetamine. SPECT/IMP imaging was performed in ten patients with probable SDAT and seven healthy subjects. Multiple ROIs were manually and semiautomatically generated, and uptake was quantitated for each ROI.

Mechanisms of noncompetitive inhibition of acetylcholine-induced single-channel currents.

The functional mechanisms of noncompetitive blockade of the nicotinic acetylcholine receptor from the BC3H-1 cell line were examined using single-channel currents recorded from cell-attached patches. Channel open times were distributed as sums of two exponentials and the closed times as sums of at least four exponentials. The single-channel currents of the receptor were analyzed in terms of activation schemes in which the receptor exists in two open states and a number of closed or blocked states.

T1 and T2 measurements on a 1.5-T commercial MR imager.

In order for relaxation times to be used in clinical diagnosis, the precision of the measurement must be determined. The authors measured T1, T2, and proton density in a phantom and in human volunteers to determine the reproducibility of the method. The coefficient of variance of T1 measurements in the phantom during a 15-month period with two software upgrades was 5%.

Characterization of nicotinic acetylcholine receptor channels of the TE671 human medulloblastoma clonal line.

Acetylcholine (ACh)-gated single channel events were studied on the TE671 human medulloblastoma clonal cell line by the use of the cell-attached patch clamp technique. Channel activity was detected (86% probability) in the presence of 0.1-2 microM ACh but not (0% probability) in the absence of agonist or in the presence of 1 microM alpha-bungarotoxin (Bgt).

Sensitivity of Gd-DTPA-enhanced MR imaging of benign extraaxial tumors.

The effect of gadolinium diethylenetriaminepentaacetic acid (DTPA) on the sensitivity of cranial magnetic resonance (MR) imaging was measured in a prospective blinded study. Twenty-two consecutive patients with benign extraaxial tumors underwent MR imaging on a 1.5-T system without and with intravenous administration of Gd-DTPA.

Relationships of agonist properties to the single channel kinetics of nicotinic acetylcholine receptors.

The effects of the systematic variations of the acetylcholine molecule on the microscopic kinetics of channel activation were studied using the patch clamp technique. The modifications consisted of adding either halogens or a methyl group to the acetyl carbon of acetylcholine, which results in a change in both the steric and ionic character of that portion of the molecule. The ionic character of the bond affected both the opening and closing rates of the channel.