PURPOSE: Development of asthma involves the interaction between genetic factors and environmental stimuli. This study aims to investigate whether major single nucleotide polymorphism (SNP)s and their haplotypes of the ADRB2 (beta2-adrenoceptor) gene are associated with children with asthma in Korea. METHODS: Children with asthma aging 5 to 15 years old were recruited as the patient group, and children without respiratory diseases or asthma of the same age were recruited as the control group. Blood samples of 5 mL were collected and DNA was extracted by standard methods. Genotyping was done for 6 SNPs known to have a frequency of more than 4%, including 1309A>G, 1342C>G, 1515G>A, 1786C>A, 2316G>C, 2502G>A. RESULTS: Overall, 438 subjects (214 patients and 224 controls) were included in this study. Minor allele homozygote frequency of 6 SNP were 22%, 1.8%, 11%, 12.3%, 21.2% and 13.0%, respectively. Differences between both groups of individual SNP frequencies were not statistically significant, although the difference of the frequency of the second SNP (1342C>G) has borderline significance (P=0.06). Overall distributions of haplotypes were not significantly different between both groups. However, analysis of specific SNPs among haplotypes revealed that haplotypes including the 2nd SNP were significantly associated with asthma (odds ratio, 1.7; 95% confidence interval, 1.1 to 2.6). Combinations of haplotypes excluding the 2nd SNP did not show significant difference between both groups. CONCLUSION: This study suggests that the ADRB2 gene polymorphism is associated with susceptibility to childhood asthma and that analysis of haplotypes rather than SNPs is more reliable in this association.
Aging ; Alleles ; Asthma ; Child ; DNA ; Haplotypes ; Homozygote ; Humans ; Polymorphism, Single Nucleotide ; Receptors, Adrenergic, beta-2

BACKGROUND: Although IL-12 has been widely accepted to play a central role in the control of pathogen infection, the use of recombinant IL-12 (rIL-12) as a vaccine adjuvant has been known to be ineffective because of its rapid clearance in the body. METHODS: To investigate the effect of sustained release of IL-12 in vivo in the peptide and protein vaccination models, rIL-12 was encapsulated into poly (DL-lactic-co-glycolic acid) (PLGA). RESULTS: We found that codelivery of IL-12-encapsulated microspheres (IL-12EM) could dramatically increase not only antibody responses, but also antigen-specific CD4(+) and CD8(+) T cell responses. Enhanced immune responses were shown to be correlated with protective immunity against influenza and respiratory syncytial virus (RSV) virus challenge. Interestingly, the enhancement of CD8(+) T cell response was not detectable when CD4(+) T cell knockout mice were subjected to vaccination, indicating that the enhancement of the CD8(+) T cell response by IL-12EM is dependent on CD4(+) T cell "help". CONCLUSION: Thus, IL-12EM could be applied as an adjuvant of protein and peptide vaccines to enhance protective immunity against virus infection.
Animals ; Antibody Formation ; Influenza, Human ; Interleukin-12 ; Mice ; Mice, Knockout ; Microspheres* ; Respiratory Syncytial Viruses ; Vaccination* ; Vaccines, Subunit

(S)-Carbamic acid 2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-1-phenyl-ethyl ester hydrochloride (YKP1447) is a novel "atypical" antipsychotic drug which selectively binds to serotonin (5-HT2A, Ki=0.61 nM, 5-HT2C, Ki=20.7 nM) and dopamine (D2, Ki=45.9 nM, D3, Ki=42.1 nM) receptors with over 10~100-fold selectivity over the various receptors which exist in the brain. In the behavioral studies using mice, YKP1447 antagonized the apomorphine-induced cage climbing (ED50=0.93 mg/kg) and DOI-induced head twitch (ED50=0.18 mg/kg) behavior. In the dextroamphetamine-induced hyperactivity and conditioned avoidance response (CAR) paradigm in rats, YKP1447 inhibited the hyperactivity induced by amphetamine (ED50=0.54 mg/kg) and the avoidance response (ED50=0.48 mg/kg); however, unlike other antipsychotic drugs, catalepsy was observed only at much higher dose (ED50=68.6 mg/kg). Based on the CAR and catalepsy results, the therapeutic index (TI) value for YKP1447 is over 100 (i.p.). These results indicate that YKP1447 has an atypical profile and less undesirable side effects than currently available drugs.
Amphetamine ; Animals ; Antipsychotic Agents ; Brain ; Catalepsy ; Dopamine ; Head ; Mice ; Rats ; Schizophrenia ; Serotonin

OBJECTIVE: Schizophrenia, a devastating mental disorder, displays a wide range of cognitive impairments including attentional impairment. Prepulse inhibition (PPI), in which a startle response to a loud acoustic noise is reduced by a preceding auditory stimulus of a lower intensity, is impaired in schizophrenic patients and rats injected with apomorphine (APO) or phencyclidine (PCP) mimicking attentional deficits in schizophrenics. Here we examined therapeutic efficacy of a newly developed atypical antipsychotic compound (YKP1447;YKP) on PPI impairment induced by various doses of APO and PCP. METHODS: This study was composed of 3 experiments. YKP (0.5-15 mg/kg) or vehicle (VEH) was administered 15 min before the injection of APO (0.5 mg/kg, Exp1) or PCP (2.0 mg/kg, Exp2:1.5 mg/kg, Exp3). They were then tested for PPI in which a mix of startle stimulus and prepulse was presented. RESULTS: APO or PCP treatment effectively impaired PPI in tested animals (VEH/APO or VEH/PCP). Impaired PPI in APO group was reversed in animals that were pretreated with YKP (5-10 mg/kg) (Exp1). However YKP treatment was not effective in PCP group (Exp2-3). CONCLUSION: High concentration of YKP pretreatment had antipsychotic effect on APO-induced impairment in attentional function suggesting that the compound could potentially be used to treat cognitive impairment due to increased dopaminergic receptorbinding.
Acoustics ; Animals ; Antipsychotic Agents ; Apomorphine ; Humans ; Mental Disorders ; Noise ; Phencyclidine ; Rats ; Schizophrenia