C-reactive protein is an inflammatory marker believed to be of value in the prediction of coronary events. We report data from a large study of C-reactive protein and other circulating inflammatory ...markers, as well as updated meta-analyses, to evaluate their relevance to the prediction of coronary heart disease.
Measurements were made in samples obtained at base line from up to 2459 patients who had a nonfatal myocardial infarction or died of coronary heart disease during the study and from up to 3969 controls without a coronary heart disease event in the Reykjavik prospective study of 18,569 participants. Measurements were made in paired samples obtained an average of 12 years apart from 379 of these participants in order to quantify within-person fluctuations in inflammatory marker levels.
The long-term stability of C-reactive protein values (within-person correlation coefficient, 0.59; 95 percent confidence interval, 0.52 to 0.66) was similar to that of both blood pressure and total serum cholesterol. After adjustment for base-line values for established risk factors, the odds ratio for coronary heart disease was 1.45 (95 percent confidence interval, 1.25 to 1.68) in a comparison of participants in the top third of the group with respect to base-line C-reactive protein values with those in the bottom third, and similar overall findings were observed in an updated meta-analysis involving a total of 7068 patients with coronary heart disease. By comparison, the odds ratios in the Reykjavik Study for coronary heart disease were somewhat weaker for the erythrocyte sedimentation rate (1.30; 95 percent confidence interval, 1.13 to 1.51) and the von Willebrand factor concentration (1.11; 95 percent confidence interval, 0.97 to 1.27) but generally stronger for established risk factors, such as an increased total cholesterol concentration (2.35; 95 percent confidence interval, 2.03 to 2.74) and cigarette smoking (1.87; 95 percent confidence interval, 1.62 to 2.16).
C-reactive protein is a relatively moderate predictor of coronary heart disease. Recommendations regarding its use in predicting the likelihood of coronary heart disease may need to be reviewed.
The mechanism of a novel assay technique for nanoparticle-enhanced immunoturbidimetric assays is investigated. In a mixture of latex particles of two different sizes, coated with antibodies of ...different affinities, the aggregation behavior is monitored, which correlates with the antigen concentration. At low antigen concentrations, only the bigger latex particles coated with the high-reactivity antibody aggregate, whereas at higher antigen concentrations, the smaller latices coated with a lower reactivity antibody follow up in the aggregation process. This is shown for an immunoassay (C-reactive protein) by theoretical considerations based on a diffusion-controlled reaction and by transmission electron microscopy, analytical ultracentrifugation, and static light scattering as complementary qualitative and quantitative analytical techniques.
Indian Asians in the United Kingdom have increased coronary heart disease (CHD) mortality compared with European whites, but the causes are not well understood. Increased circulating concentrations ...of C-reactive protein (CRP) are an independent risk factor for CHD. Therefore, we investigated this marker of inflammation in healthy UK Indian Asian and European white men. Methods and Results-- We measured serum CRP concentrations and conventional CHD risk factors in 1025 healthy male subjects (518 Indian Asians and 507 European whites) aged 35 to 60 years who were recruited at random from general practitioner lists. The geometric mean CRP concentration was 17% higher (95% confidence interval, 3% to 33%) in Indian Asians compared with European whites. CRP values were strongly associated with conventional CHD risk factors, measures of obesity, and metabolic disturbances associated with insulin resistance in both racial groups. The difference in CRP concentrations between Indian Asians and European whites remained after adjustment for conventional CHD risk factors but was eliminated by an adjustment for central obesity and insulin resistance score in Asians. On the basis of these results, we estimate that the processes underlying elevated CRP and/or increased CRP production itself are associated with an approximately 14% increase in population CHD risk among Indian Asians compared with European whites.
CRP concentrations are higher in healthy Indian Asians than in European whites and are accounted for by greater central obesity and insulin resistance in Indian Asians. Our results suggest that inflammation or other mechanisms underlying elevated CRP values may contribute to the increased CHD risk among Indian Asians.
In order to establish a speedy and convenient assay of serum CA 19-9, we developed a latex photometric immunoassay of the antigen. Latex reagent was prepared by physical binding of F (ab) 2 fragment ...of murine monoclonal antibody (1116 NS 19-9) onto latex particles. Latex reagent showed dose-dependent agglutination after being mixed with CA 19-9 antigen. The latex assay required only 10 minutes and could be automated by using conventional clinical chemistry analyzer, COBAS MIRA. Intensity of signal of the reaction could be adjusted by modifying the concentration of reaction accelerating polymer, polyvinyl pyrrolidone K90 (PVP K90). When we used the assay buffer containing 2 g/l of PVP K90, minimum detection dosage was 2 units/ml and measuring range was up to 400 units/ml; they were similar to those of radioimmunoassav (RIA) and enzyme immunoassay (EIA). Within and between assay precisions were both about 5% in coefficient of variation CVI at normal ranae and about 1-2% in CV at increased level. Correlation versus commercially available EIA was y (Latex assay) =1.08x (EIA) +3.41, r=0.981 (n=101). Prozone phenomenon could be detected by utilizing mechanism of the instrument. These results indicate that this assay can be applied to daily analysis in clinical laboratories as a speedy and convenient substitute of RIA and.EIA.
A new indication has been proposed for C-reactive protein (CRP) as a prognostic risk marker of coronary heart disease (CHD). The new indication calls for accurate (true and precise) measurement of ...CRP within the conventional reference range (<5 mg L). The existing turbidimetric and nephelometric methods do not cover the required measuring range and thus time-consuming and labour-intensive enzyme immunoassays have been used for the clinical studies focusing on CHD risk. We developed a new method based on micro-particle enhanced turbidimetry, which attained the required limit of detection, while keeping the upper measuring limit comparable to the existing turbidimetric and nephelometric methods. The superior characteristics of the new method were realised by mixing two types of microparticle reagents differing in microparticle size and reactivity of coated antibody. The analytical detection limit of the method was 0.28 mg L with use of only 2.5 μ1 serum. The method showed good precision at 2 to 3 mg L, the critical concentration range for CHD risk assessment. Other performance data including dilution linearity, method comparison, and interference study also met the requirements for the practical use in the clinical laboratories. Sera from 354 apparently healthy blood donors were measured in a reference range study. The reference range estimated after log-transformation was 0.16 mg L to 7.57 mg L CRP, with a total range of 0.09 mg L to 21.0 mg L. The distribution of CRP concentrations in this population was comparable to other results that established the use of CRP as a risk marker of CHD in a prospective study.
Cefclidin (CFCL), a newly developed injectable cephalosporin antibiotic, was administered for 7-14 days to 8 patients with complicated urinary tract infections. The therapeutic efficacy, safety and ...recurrence were evaluated. The results obtained were as follows. 1) Overall clinical efficacy rate according to the criteria proposed by the UTI Committee of Japan was excellent in 1, moderate in 2 and poor in 5 patients after 5 days, excellent in 1 and moderate in 1 after 10 days, and excellent in 2, moderate in 2 and poor in 1 after 14 days. 2) Clinical efficacy evaluated according to the presiding doctors was excellent in 2, good in 4 and fair in 2 patients after 5 days. After 10 days, the efficacy was excellent in 1 and good in 1. After 14 days, the efficacy was excellent in 1 and good in 4. 3) Recurrence evaluation by presiding doctors was 5/8 for no recurrence in 8 patients. 4) No severe adverse reactions or abnormal laboratory findings was observed.
Cefetamet pivoxil (CEMT-PI), a novel oral prodrug of cephalosporin type, was administered to 87 patients with uncomplicated or complicated urinary tract infection (UTI) and the following results were ...obtained. 1) After 2 days' treatment, of 8 patients with acute uncomplicated cystitis, excellent response was observed in 6 and moderate in 2, and after 5 days' treatment, excellent in 3, moderate in 2 and poor in one case. 2) In one case of acute uncomplicated pyelonephritis, moderate response was observed. 3) In complicated UTI cases without indwelling catheter, excellent response was observed in 12, moderate in 12 and poor in 19. The overall efficacy rate in complicated UTI was 56%. Bacteriologically, 45% of gram positive cocci were eliminated from urine after 5 days' treatment and 72% of gram negative rods. But 4 patients with indwelling catheter showed poor results. 4) Side effects were observed in 3 cases, namely, sleepiness, chill and abdominal fulness. There were six instances of abnormal laboratory findings related to liver function and blood cell counts.
Nucleoporin proteins (Nups) have been proposed to mediate spatial and temporal chromatin organization during gene regulation. Nevertheless, the molecular mechanisms in mammalian cells are not well ...understood. Here, we report that Nucleoporin 153 (NUP153) interacts with the chromatin architectural proteins, CTCF and cohesin, and mediates their binding across cis-regulatory elements and TAD boundaries in mouse embryonic stem (ES) cells. NUP153 depletion results in altered CTCF and cohesin binding and differential gene expression - specifically at the bivalent developmental genes. To investigate the molecular mechanism, we utilize epidermal growth factor (EGF)-inducible immediate early genes (IEGs). We find that NUP153 controls CTCF and cohesin binding at the cis-regulatory elements and POL II pausing during the basal state. Furthermore, efficient IEG transcription relies on NUP153. We propose that NUP153 links the nuclear pore complex (NPC) to chromatin architecture allowing genes that are poised to respond rapidly to developmental cues to be properly modulated.
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