Detection of human apolipoprotein B polymorphic species with one monoclonal antibody (BIP 45) against low density lipoprotein. Influence of this polymorphism on lipid levels and coronary artery stenosis

The immunoreactivity of apolipoprotein B (apo B) in plasma samples obtained from a variety of subjects was analysed by non-competitive ELISA with a polyclonal and a monoclonal (BIP 45) anti-LDL antibody. Three populations were tested: the first, comprising 244 healthy male volunteers, provided reference values; the second consisted of a population undergoing coronary angiography (n = 88) and was divided into a subgroup with (n = 64) and without (n = 24) coronary artery disease (CAD); the third was made up of 56 patients with heterozygous familial hypercholesterolemia. Total apo B (measured with the polyclonal antibody) was increased in the populations with CAD and in the heterozygous familial hypercholesterolemic subjects compared to the reference population. When monoclonal antibody BIP 45 was used in the non-competitive ELISA, three different patterns emerged in each population, corresponding to weak, intermediate and strong binding of the particles containing apo B to the monoclonal antibody. This may result from genetic polymorphism of apo B, and in the reference population the data fit a model consisting of two co-dominant apo B alleles (BIP(-) and BIP(+]; the 3 subpopulations then correspond to the 2 homozygotes and the heterozygote. The number of patients whose particles bound weakly to monoclonal BIP 45 antibody was low in the CAD population, while intermediate binding was increased in this group. Nevertheless, when the analysis of variance of allele BIP(-) was studied no significant difference between groups was established. This finding indicates that the genetic difference in apo B detected by BIP 45 may not be significant in the development of CAD. Furthermore, the apo B genetic polymorphism detected by BIP 45 is not associated with a particular lipoprotein level in the reference population.     

Retroregulation of the synthesis of ribosomal proteins L14 and L24 by feedback repressor S8 in Escherichia coli.

Previous studies on regulation of the spc operon containing genes for ribosomal proteins have shown that S8, encoded by the fifth gene of the operon in Escherichia coli, is a translational repressor and regulates the synthesis of the third gene product (L5) and distal gene products by acting at a site near the L5 mRNA translation initiation site. We have now shown that S8 also regulates the synthesis of the first and second gene products (L14 and L24) of the operon by acting at the same mRNA target site--that is, the site located distal to sites coding for L14 and L24--and that mRNA degradation is involved in this retroregulation. It was shown that single base substitutions in the target site, which abolish repression of the synthesis of L5 and L5-distal gene products by S8, also cause derepression of L14-L24 synthesis. Inhibition of L14-L24 synthesis by S8 was also shown by overproducing S8 in trans from a plasmid carrying the S8 gene under lac promoter/operator control. A strain carrying temperature-sensitive mutations in genes for polynucleotide phosphorylase and RNase II was found upon shift to nonpermissive temperature to show higher differential synthesis rates of L14-L24 (and L5) relative to those of several L5-distal spc operon gene products. We suggest that repression of distal ribosomal protein synthesis by S8 triggers nucleolytic cleavage of spc operon mRNA, followed by mRNA degradation by these 3'- to 5'- exonucleases, which is then responsible for inhibition of L14-L24 synthesis.     

Identification of Possible Virulence Marker from Campylobacter jejuni Isolates

A novel protein translocation system, the type-6 secretion system (T6SS), may play a role in virulence of Campylobacter jejuni. We investigated 181 C. jejuni isolates from humans, chickens, and environmental sources in Vietnam, Thailand, Pakistan, and the United Kingdom for T6SS. The marker was most prevalent in human and chicken isolates from Vietnam.     

Predictive utility of cyclo-oxygenase-2 expression by colon and rectal cancer

Background

Cyclo-oxygenase-2 (COX-2), an inducible enzyme expressed in areas of inflammation, is a target of interest for colorectal cancer therapy. Currently, the predictive significance of COX-2 in colorectal cancer remains unclear.

Methods

Tissue microarrays were constructed using 118 colon cancer and 85 rectal cancer specimens; 44 synchronous metastatic colon cancer and 22 rectal cancer lymph nodes were also evaluated. COX-2 expression was assessed by immunohistochemistry. Univariate analysis was used to determine the predictive significance of clinicopathologic variables. Overall survival, disease-specific survival, and disease-free survival were the main outcomes examined.

Results

COX-2 was found to be expressed in 93% of colon cancers and 87% of rectal cancers. Decreased COX-2 expression was related to decreased disease-specific survival (P = .016) and decreased disease-free survival (P = .019) in the rectal cancer cohort but not in the colon cancer cohort.

Conclusions

COX-2 expression has predictive utility for management of rectal but not colon cancer.     

Fetuin-A and thyroxin binding globulin predict rituximab response in rheumatoid arthritis patients with insufficient response to anti-TNFα

Clinical Rheumatology - Rheumatoid arthritis (RA) is a debilitating disease, but patient management and treatment have been revolutionized since the advent of bDMARDs. However, about one third of...     

Phylogenetic and Phylogeographic Analyses of Porcine Circovirus Type 2 Among Pig Farms in Vietnam

This study demonstrated the prevalence of Porcine circovirus type 2 (PCV2) among pig farms in Vietnam. Analyses of the genome, capsid protein and phylogeny classified all 30 Vietnamese PCV2 strains as the PCV2b genotype, belonging to the clusters of 1A, 1B, 1C and recombinant forms. Each viral genome was 1767 nucleotides long and shared 96.0–100% nucleotide sequence identity. The amino acid substitutions in the capsid protein of the Vietnamese PCV2 strains were in immunodominant regions, and the majority of strains (24/30) contained a lysine extension at the C‐terminus. Bayesian phylogeographic analysis revealed epidemic links of the PCV2 recombinant cluster within and among countries, which supports a circulating recombinant form of PCV2. Further analysis by the Jameson–Wolf antigenic index indicated antigenic alterations at important sites in the capsid protein (sites 131–133) among the recombinant cluster and the other clusters of PCV2b.