Genetics of rheumatoid arthritis

The haplotype sharing distribution in affected sib pairs are used to demonstrate the linkage of a susceptibility gene for rheumatoid arthritis (RA) to the HLA region. Family and population studies suggest heterogeneity in the etiology of RA.     

Intracellular mechanisms governing the acute phase of β-endorphin secretion from the corticotrope in vitro

It is not certain which protein kinase (A, C or both) is involved in the acute phase of β-endorphin (β-EP) release stimulated in the corticotrope by vasopressin (VP) and corticotropin-releasing factor (CRF). We have employed an isolated ovine anterior pituitary cell superfusion system to determine the dynamic effects of forskolin, a protein kinase A (PKA) stimulator, and phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator. Both secretagogues stimulated β-EP release within 5 min and therefore both PKA and PKC are potential mediators of the acute phase of hormonal stimulation of the corticotrope. Pretreatment with PMA specifically desensitized the pituitary cell columns to subsequent PMA exposure while not significantly altering sensitivity to forskolin or 50 mM KCl.     

Macrophage migration inhibitory factor (MIF) gene polymorphism is associated with susceptibility to but not severity of inflammatory polyarthritis

The aim of the study was to investigate whether polymorphisms of macrophage migration inhibitory factor (MIF) determine susceptibility to or severity of inflammatory polyarthritis (IP). Genotypes for a single-nucleotide polymorphism (MIF-173*G/C) and a tetranucleotide (CATT)(n) repeat mapping to the promoter region of the MIF gene were compared between UK Caucasian IP cases (n=438) and controls (n=343). Both polymorphisms were also investigated for association with features of disease activity and severity at baseline and by 5 years. The MIF-173*C allele (OR 1.7, 95% CI 1.3-2.4, P=1.8 x 10(-4)) and the CATT(7) allele (OR 1.5, 95% CI 1.0-2.1, P=0.02) were found to be associated with increased susceptibility to IP. Furthermore, presence of the haplotype containing both associated polymorphisms was associated with a three-fold increase risk of developing IP. No association with disease severity or activity either at baseline or by 5 years was detected for either of the promoter polymorphisms studied. In conclusion, MIF is a susceptibility gene for the development of IP. The same alleles previously reported to be associated with susceptibility to juvenile idiopathic arthritis account for the increased risk. The promoter polymorphisms of MIF, investigated in this study, do not influence the severity of disease outcome by 5 years.     

An evaluation of three methods of typing organisms of the genus Proteus

An assessment of three simple methods of typing Proteus strains is described. The methods chosen were biochemical typing, bacteriocine typing, and typing by means of the Dienes phenomenon. Dienes typing was deemed to be superior to biochemical typing and bacteriocine typing.A brief discussion on the relationship between the Dienes phenomenon and bacteriocine production is appended.     

Imipenem resistance inEnterobacter

Blood cultures obtained on two separate occasions from a 37-year-old male who received multiple antibiotics (including imipenem) for treatment of repeated episodes of intraabdominal abscesses and bacteremia yielded two isolates ofEnterobacter with reduced susceptibility to imipenem, extended-spectrum cephalosporins, penicillins and aztreonam. Both isolates were unstable, giving rise to different colony types, each of which produced a single, non-inducible Bush group 1 -lactamase (pI=9.6) that hydrolyzed imipenem. Outer membrane proteins were analyzed but no differences were detected between strains with different levels of imipenem resistance. Three-dimensional tests performed in conjunction with disk diffusion susceptibility tests provided a rapid and convenient means of detecting the production of imipenem-hydrolyzing enzymes by theEnterobacter strains. These isolates provided additional evidence that overproduction of the group 1 cephalosporinase ofEnterobacter can contribute to resistance to imipenem.