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Metabotropic glutamate receptors (mGluRs) were identified in olfactory receptor neurons of the channel catfish, Ictalurus punctatus, by polymerase chain reaction. DNA sequence analysis confirmed the presence of two subtypes, mGluR1 and mGluR3, that were coexpressed with each other and with the putative odorant receptors within single olfactory receptor neurons. Immunocytochemical data showed that both mGluR subtypes were expressed in the apical dendrites and some cilia of olfactory neurons. Pharmacological analysis showed that antagonists to each mGluR subtype significantly decreased the electrophysiological response to odorant amino acids. alpha-Methyl-L-CCG1/(2S,3S,4S)-2-methyl-2-(carboxycyclopropyl++ +)glycine (MCCG), a known antagonist to mGluR3, and (S)-4-carboxyphenylglycine (S-4CPG), a specific antagonist to mGluR1, each significantly reduced olfactory receptor responses to L-glutamate. S-4CPG and MCCG reduced the glutamate response to 54% and 56% of control, respectively, which was significantly greater than their effect on a neutral amino acid odorant, methionine. These significant reductions of odorant response by the antagonists, taken with the expression of these receptors throughout the dendritic and ciliated portions of some olfactory receptor neurons, suggest that these mGluRs may be involved in olfactory reception and signal transduction.     

The muscarinic M1 agonist xanomeline increases soluble amyloid precursor protein release from Chinese hamster ovary-m1 cells

The functionally selective M1 agonist xanomeline, which is currently undergoing clinical trials as a therapy for Alzheimer's disease, was compared to the muscarinic agonist carbachol for effects on secretion of soluble amyloid precursor protein (APPs) from Chinese hamster ovary cells transfected with the human m1 receptor (CHO-m1). Release of APPs from CHO-m1 cells was increased maximally (4-10 fold) by 100 microM carbachol (EC50 = 11 microM) and by 100 nM xanomeline (EC50 = 10 nM). Stimulation of APPs secretion by xanomeline and carbachol was blocked by preincubation with 1 microM atropine. Carbachol did not stimulate APPs secretion from non-transfected CHO cells. Pilocarpine at 1 mM also increased APPs release. The efficacy of carbachol, xanomeline and pilocarpine for stimulating APPs secretion did not differ significantly. Activation of protein kinase C (PKC) in m1 transfected cell lines by 1 microM phorbol dibutyrate (PDBu) increased APPs release, and this was inhibited 97% by the PKC inhibitor bisindolemalemide. The PKC inhibitor decreased xanomeline and carbachol-stimulated APPs secretion by only 25-30%. These results demonstrate that xanomeline increased APPs release by activation of m1 muscarinic receptors and support the possibility that cholinergic replacement therapy for Alzheimer's Disease may reduce amyloid deposition.     

Polar Quantization of a Complex Gaussian Random Variable

We solve numerically the optimum fixed-level non-uniform and uniform quantization of a circularly symmetric complex (or bivariate) Gaussian random variable for the mean absolute squared error criterion. For a given number of total levels, we determine its factorization into the product of numbers of magnitude and phase levels that produces the minimum distortion. We tabulate the results for numbers of "useful" output levels up to 1024, giving their optimal factorizations, minimum distortion, and entropy. For uncoded quantizer outputs, we find that the optimal splitting of rate between magnitude and phase, averaging to 1.52 and 1.47 bits more in the phase angle than magnitude for optimum and uniform quantization, respectively, compares well with the optimal polar coding formula Of 1.376 bits of Pearlman and Gray [3]. We also compare the performance of polar to rectangular quantization by real and imaginary parts for both uncoded and coded output levels. We find that, for coded outputs, both polar quantizers are outperformed by the rectangular ones, whose distortion-rate curves nearly coincide with Pearlman and Gray's polar coding bound. For uncoded outputs, however, we determine that the polar quantizers surpass in performance their rectangular counterparts for all useful rates above 6.0 bits for both optimum and uniform quantization. Below this rate, the respective polar quantizers are either slightly inferior or comparable.     

Cystic fibrosis transmembrane conductance regulator (CFTR) anion binding as a probe of the pore

We compared the effects of mutations in transmembrane segments (TMs) TM1, TM5, and TM6 on the conduction and activation properties of the cystic fibrosis transmembrane conductance regulator (CFTR) to determine which functional property was most sensitive to mutations and, thereby, to develop a criterion for measuring the importance of a particular residue or TM for anion conduction or activation. Anion substitution studies provided strong evidence for the binding of permeant anions in the pore. Anion binding was highly sensitive to point mutations in TM5 and TM6. Permeability ratios, in contrast, were relatively unaffected by the same mutations, so that anion binding emerged as the conduction property most sensitive to structural changes in CFTR. The relative insensitivity of permeability ratios to CFTR mutations was in accord with the notion that anion-water interactions are important determinants of permeability selectivity. By the criterion of anion binding, TM5 and TM6 were judged to be likely to contribute to the structure of the anion-selective pore, whereas TM1 was judged to be less important. Mutations in TM5 and TM6 also dramatically reduced the sensitivity of CFTR to activation by 3-isobutyl 1-methyl xanthine (IBMX), as expected if these TMs are intimately involved in the physical process that opens and closes the channel.     

Fluticasone propionate aqueous nasal spray is safe and effective for children with seasonal allergic rhinitis

INTRODUCTION: Fluticasone propionate aqueous nasal spray, a new topical corticosteroid preparation, is effective when given as 200 micrograms once daily in patients (> 12 years of age) with seasonal allergic rhinitis. STUDY OBJECTIVE: To evaluate the efficacy and safety of fluticasone proprionate aqueous nasal spray in children aged 4 to 11 years with seasonal allergic rhinitis. STUDY DESIGN: Multicenter, randomized, double-blind, placebo-controlled, parallel-group. PATIENTS: Two hundred fifty children aged 4 to 11 years with moderate-to-severe nasal symptoms, a positive skin test reaction to a late-summer or autumn allergen, a history of seasonal allergic rhinitis, and documentation of an unsatisfactory response to conventional treatment. INTERVENTIONS: Children were randomly assigned to receive fluticasone propionate, either 100 micrograms or 200 micrograms, or placebo, given by intranasal spray once daily in the morning for 14 days. MEASUREMENTS AND RESULTS: Severity of nasal symptoms (obstruction, rhinorrhea, itching, and sneezing) was recorded on visual analog scales by investigators at weekly visits and by patients (or adult guardian) daily in the evening. According to investigator and patient ratings, both fluticasone propionate 100 micrograms/d and 200 micrograms/d lowered total nasal symptom scores when compared with placebo. Both dosages of fluticasone propionate were more effective than placebo on the basis of investigator-rated overall clinical evaluation of efficacy at the end of treatment, with significant improvement (as opposed to moderate or mild improvement, no change or worsening) noted in 21% to 29% of the active-treatment groups vs 9% in the placebo group. There were no significant differences between the two fluticasone propionate dosages in any efficacy measurement. Morning plasma cortisol concentrations and frequency of drug-related adverse events were similar in the fluticasone propionate and placebo groups. CONCLUSION: In children as young as 4 years, 100 micrograms of fluticasone propionate aqueous nasal spray given once daily is as effective as 200 micrograms given once daily, the usual adult dose for the treatment of seasonal allergic rhinitis. Both fluticasone propionate dosages were well tolerated and neither dosage appears to interfere with the hypothalamic-pituitary-adrenal axis in children.     

Reverse micellar extraction of antibiotics from aqueous solutions

PURPOSE: We reviewed 1,360 EEG reports for all patients studied in two different neurophysiology laboratories during 1 calendar year to determine whether epileptiform discharges have a hemispheric dominance. METHODS: Both inpatients and outpatients, with or without epilepsy, were included. RESULTS: Ninety-four records (6.9%) demonstrated generalized epileptiform activity. Of 95 EEG reports indicating spikes solely from one hemisphere, spikes arose from the left in 61 and from the right in 34. Among 50 other records with bilateral independent spikes with lateralization, 40 were left hemisphere dominant and 10 were right hemisphere dominant. CONCLUSIONS: These findings raise the possibility that the left cerebral hemisphere may generate focal epilepsy more frequently than the right.     

Institutional arrangements for flood hazard management in Malaysia: an evaluation using the criteria approach

Institutional aspects of flood hazards significantly affect their outcomes in Malaysia. Institutional arrangements to deal with floods include: legislative activity, organisational structures, attitudes and sub-culture, and policies and instruments. When assessed in terms of four specific criteria, institutional aspects of flood hazards are found to be largely inadequate. Disaster reduction programmes are over-dependent on a reactive approach based largely on technology and not even aimed at floods specifically. Structural flood reduction measures are the predominant management tool and, although the importance of non-structural measures is recognised, thus far they have been under-employed. Current laws and regulations with regard to flood management are also insufficient and both the financial and human resources of flood hazard organisations are generally found to be wanting. Finally, economic efficiency, equity and public accountability issues are not adequately addressed by institutional arrangements for flood hazards.