Search Results - (Author, Cooperation:N. Richards)

2011-09-13

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Animals ; B-Lymphocytes/cytology/metabolism ; Cell Lineage/genetics ; Chromosomes, Mammalian/genetics/metabolism ; DNA, Intergenic/*genetics ; Enhancer Elements, Genetic/genetics ; Feedback, Physiological ; Gene Rearrangement, B-Lymphocyte, Heavy Chain/*genetics ; Germ Cells/metabolism ; Immunoglobulin Heavy Chains/genetics ; Immunoglobulin Variable Region/genetics ; Mice ; Mutation/genetics ; Recombination, Genetic/*genetics ; Regulatory Sequences, Nucleic Acid/*genetics ; Repressor Proteins/*metabolism ; Thymus Gland/cytology ; Transcription, Genetic/genetics ; VDJ Exons/*genetics

1365-2222

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Background Theoretically, antibacterial agents in early life might influence allergic sensitization in two ways: (i) as an indicator of infectious illness, they might be expected to protect against allergy; (ii) alternatively they might increase the risk through effects on the commensal bowel flora. Epidemiological evidence linking the prescription of antibacterial agents in early life to the subsequent development of hayfever is conflicting.Objective To establish definitively whether an association exists between early-life antibacterial exposure and childhood hayfever diagnosis.Methods Nested case–control studies were based on birth cohorts of children identified within two large UK general practice databases of electronic patient records. One hundred and sixteen thousand and four hundred and ninety-three children from 605 general practices were identified as being continuously registered from birth to at least age 5 years. Seven thousand and ninety-eight cases were diagnosed with hayfever after the age of 2 years. One control per case was matched for practice, birth month, sex and still being registered on case diagnosis date. Odds ratios were derived from conditional logistic regressions within each database followed by pooling using a fixed-effect model.Results The pooled odds ratio for hayfever was 1.11, 95% CI (1.03–1.20) if exposed to antibacterials in the first year of life, 1.35 (1.25–1.46) in year 2 and 1.47 (1.37–1.59) in year 3. Adjusting for consultation frequency reduced these odds ratios to 0.92, 1.05 and 1.10, respectively. There was no evidence that broader spectrum antibacterials, exposure in any specific month of year 1 or in the grass pollen season influenced the risk of hayfever.Conclusion These data exclude any important effect of antibacterial exposure in infancy on subsequent hayfever risk. Associations reported in earlier studies have likely been exaggerated through publication bias and by lack of control for the tendency of some families to consult frequently for a range of conditions.

Electronic Resource

0025-7273

History

Medicine

APRIL

0037-7856

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Medicine

Electronic Resource

1752-7325

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Electronic Resource

1432-0428

Diabetes ; growth hormone releasing factor

Springer Online Journal Archives 1860-2000

Medicine

Summary Human pancreatic growth hormone releasing factor [GRF(1–44)] is the largest molecule of several peptides recently isolated from pancreatic tumours associated with acromegaly. It has been shown to stimulate the release of growth hormone in normal subjects and provides a safe and reliable tool for examining growth hormone release. A study was conducted to examine the release of growth hormone in patients with Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes. GRF(1–44) stimulated the release of growth hormone in normal subjects and produced no side effects. A response of similar magnitude occurred in Type 1 diabetic patients despite their concomitant hyperglycaemia. In contrast, the response in Type 2 diabetes was significantly impaired compared with normal volunteers (p〈0.05) and Type 1 diabetic patients (p〈0.02). These findings may well indicate that there is a defect in central hormonal control in Type 2 diabetes.

Electronic Resource

1432-1912

Key words β-Adrenoceptor receptor ; Insurmountable ; agonist ; Structure activity ; cAMP ; Carbostyril β-agonist

Springer Online Journal Archives 1860-2000

Medicine

Abstract Several carbostyril-based β-agonists have been shown to bind tightly to and slowly dissociate from the β2-adrenoceptor (β2AR). In the present study, the structural features of 8-hydroxy-5-[2-[(1-phenyl-2-methylprop-2-yl)amino]-1-hydroxyethyl]-carbostyril (11a) which contribute to its binding properties at the β2AR were investigated using a series of synthesized analogs. The k off, estimated by the rate of cAMP decline in DDT1 MF-2 (DDT) cells with a reduced receptor density, K i and ligand-induced receptor reductions were determined. All of the derivatives stimulated cAMP accumulation in DDT cells in the sub to mid nanomolar range and elicited the same maximal stimulation as (–)isoproterenol. Derivatives of 11a with side chain N-substitutions comprising 2-methylbutyl, phenyl-ethyl and isopropyl had higher k off-values and lower affinities as compared to 11a. Increasing the number of methylenes between the side chain tertiary alpha carbon and phenyl from 1 in 11a to 3 or reducing the number to 0 also resulted in derivatives with higher k off- and K i-values. In addition, replacement of the 8-hydroxycarbostyril nucleus of 11a with catechol reduced the affinity of the compound for the β2AR by 48-fold and increased its k off. Only those derivatives with the lowest k off-values induced a decrease in the receptor density of DDT cell membranes following a preincubation and extensive washing. The data show that the 8-hydroxycarbostyril nucleus in conjunction with substitutions on the tertiary alpha carbon of the side chain and positioning of the phenyl group are important characteristics determining the high affinity and slow dissociation of 11a from the β2AR.

Electronic Resource