BPI-ANCA is found in reactive arthritis caused by Yersinia and Salmonella infection and recognise exclusively the C-terminal part of the BPI molecule

OBJECTIVE: To examine the prevalence, binding sites and functional interactions of antineutrophil cytoplasmic autoantibodies (ANCA) against the bactericidal/permeability increasing protein (BPI) in reactive arthritis (ReA). METHODS: Sera were analysed for the occurrence of ANCA by indirect immunofluorescence microscopy (IIF) and ELISA. Binding sites were determined using BPI, lipopolysaccharid binding protein (LBP), and fusion proteins of both proteins in ELISA. In addition, the effect of antibodies on the antibiotic activity of BPI was examined. RESULTS: BPI-ANCA was found in patients with Yersinia- and Salmonella-triggered ReA and directed against the C-terminal portion of BPI. Goat anti BPI antibodies recognising this part inhibited the antibiotic activity of BPI in vitro. CONCLUSION: BPI-ANCA was associated with ReA triggered by Salmonella and Yersinia infection. Directed against the C-terminal part of BPI, it can potentially inhibit its antibiotic activity and might be useful to identify patients with infectious bowel disease prone to extraintestinal sequelae.     

Synthesis and characterization of a potent, selective, radiolabeled substance-P antagonist for NK1 receptor quantitation: ([18F]SPA-RQ).

PURPOSE: To develop and characterize a radiolabelled Substance-P antagonist useful for quantitation of neurokinin-1 receptors in the brain via PET imaging. PROCEDURE: [18F]SPA-RQ (Substance-P antagonist - receptor quantifier) was synthesized in good yield and high specific activity by alkylation of a BOC protected phenolate anion using [18F]bromofluoromethane. Removal of the BOC protecting group with trifluoroacetic acid gave [18F]SPA-RQ. RESULTS: SPA-RQ has high affinity for human, rhesus monkey and guinea pig NK1 receptors (h-IC50=67 pM) and has a log P value of 1.8. Biodistribution studies in guinea pig showed that this tracer penetrates the blood-brain barrier and selectively labels NK1 receptors in the striatum and cortex. CONCLUSION: [18F]SPA-RQ is a potent, high affinity Substance-P antagonist that can be conveniently labeled with high specific activity using [18F]fluoromethylbromide. This tracer is a useful tool for noninvasive imaging of central NK1 receptors.     

Variant rs6749447 (T > G) in the serine threonine kinase gene is associated with cardiovascular complications,the Tampere adult population cardiovascular risk study

We have previously shown an association of STK39 (serine threonine kinase) rs6749447 (T > G) with hypertension in the Tampere adult population cardiovascular risk study in 50-year-old subjects. These 1196 subjects were followed up to the age of 65 years to determine whether rs6749447 is also associated with coronary artery disease (CAD), transient ischemic attack (TIA), or early cardiovascular death.DNA samples were collected by buccal swabs and genotypes were determined by PCR. Hypertension, TIA, and CAD were determined by questionnaire and the National Hospital Discharge Registry. Outcomes for death were collected from the National Statistics Centre. Linkage disequilibrium analysis and gene expression correlations for rs6749447 were done in silico.After following the subjects up to the age of 60 years the rs6749447 G-allele still associated with hypertension (P = .009). The variation did not associate with CAD (P = .959). The risk for TIA was 5.2-fold among G-allele carriers compared to TT genotype even after adjusting for body mass index (P = .036, 95% CI 1.11-24.59). After follow-up of the subjects to the age of 65 years, adjusting for body mass index, the G-allele was associated with 3.2-fold risk of premature cardiovascular death (P = .049, 95% CI 1.00-10.01).In conclusion, the STK39 genetic variant rs6749447 was significantly associated with TIA and premature cardiovascular death in a Finnish cohort. The in silico results of linkage disequilibrium and gene expression analyses also showed associations that were distinct from the retention of salt effect on kidneys proposed earlier for this intronic variation.     

Myocardial perfusion reserve and oxidative metabolism contribute to exercise capacity in patients with dilated cardiomyopathy

BACKGROUND: Exercise intolerance is a hallmark symptom in patients with heart failure; however, myocardial factors contributing to the limited exercise capacity are not fully characterized. METHODS: Twenty patients with stable heart failure resulting from idiopathic dilated cardiomyopathy (DCM) and 13 controls were studied. Myocardial perfusion, biventricular oxidative metabolism, and insulin-stimulated glucose uptake were measured using positron emission tomography and [(15)O]H(2)O, [(11)C]acetate, and [(18)F]FDG. RESULTS: Hyperemic perfusion and perfusion reserve were significantly lower in the DCM patients compared with the healthy subjects. There was no difference in left ventricular oxidative metabolism between the 2 groups; however, the patients had a 19% higher right ventricular oxidative metabolism (P=.005). Consequently, the ratio of right to left ventricular oxidative metabolism was also higher (31%) in the patients. There was a strong inverse association between decreased exercise capacity and the ratio of right to left ventricular oxidative metabolism (r=-.68, P<.01) and a positive association with myocardial perfusion reserve (r=.62, P<.01) in the patient group. These 2 parameters along with resting left ventricular work explained 57% of the variability in peak exercise capacity. CONCLUSIONS: Impaired perfusion reserve and an exaggerated imbalance in right to left ventricular oxidative metabolism appear to significantly contribute to the impaired exercise capacity in these DCM patients.     

Effect of consumption of red wine, spirits, and beer on serum homocysteine

Serum homocysteine increases after moderate consumption of red wine and spirits, not after moderate consumption of beer. Vitamin B6 in beer seems to prevent the alcohol-induced rise in serum homocysteine.     

Relación entre las calcificaciones ateroscleróticas en el tórax detectadas mediante tomografía computarizada y la función pulmonar

Background and objectives

A few recent epidemiological findings indicate a link between atherosclerosis and some lung functions. We studied further the relation between calcified chest atherosclerosis as seen in computed tomography (CT) and several lung functional parameters.

Patients and methods

Male construction workers originally screened for occupational lung cancer with CT had their chest atherosclerosis (aorta, the origins of its cervical branches, the coronary arteries and heart valves) visually classified. The relation between the atherosclerotic calcification scores and lung function (total lung capacity [TLC], forced expiratory volume in one second [FEV₁%], forced vital capacity [FVC%], maximal expiratory flow when 50% of FVC remains to be exhaled, total and specific diffusing capacities; all above expressed as percent of predicted value, and the FEV₁/FVC% ratio) were studied with the general linear model adjusted for smoking, exposure years for asbestos, and body mass index (n=432).

Results

All lung functions except TLC showed significant negative associations with calcifications in aorta and in its branches. TLC showed such association only with atherosclerosis in the ascending aorta.

Conclusions

Aortic atherosclerosis seems to be related with poor lung function. This may be due to deteriorated bronchial circulation, but other mechanisms can also be involved. Lung function poorer than would be expected due to pulmonary reasons may indicate aortic atherosclerosis.     

Association of carbohydrate-deficient transferrin (CDT) and gamma-glutamyl-transferase (GGT) with serum lipid profile in the Finnish population

BACKGROUND: Moderate consumption of alcohol may reduce mortality from vascular diseases. The beneficial effects of alcohol may partly be mediated by its effects on lipoprotein metabolism. We studied the connection between alcohol consumption and the serum lipid profile from a well-documented national health program study. METHODS AND RESULTS: Carbohydrate-deficient transferrin (CDT) and gamma-glutamyl-transferase (GGT) were used as biochemical markers for alcohol consumption. The laboratory analyses were carried out on 5675 subjects (3097 males and 2578 females). The subjects were divided into quartiles on the basis of CDT or GGT value. The highest CDT quartile and the lowest GGT quartile seemed to be associated with a favorable lipid profile and the lowest CDT quartile and the highest GGT quartile were associated with an unfavorable lipid profile. Serum high density lipoprotein (HDL) cholesterol values were significantly higher and triglycerides lower with increasing serum CDT concentrations for both men and women. Increasing serum GGT was associated with higher serum total cholesterol and higher triglycerides in both men and women and lower HDL cholesterol in men. CONCLUSIONS: CDT and GGT seem to detect different populations of subjects in regard to lipid metabolism. These observations may lead to a better understanding of the effects of alcohol consumption on lipids as well as mechanisms behind favorable and detrimental effects of alcohol on vascular diseases. Condensed abstract: Carbohydrate-deficient transferrin (CDT) and gamma-glutamyl-transferase (GGT) were used as biochemical markers for alcohol consumption. A total of 3097 males and 2578 females were divided into quartiles on the basis of their CDT or GGT values. The highest CDT quartiles had higher HDL and lower triglycerides, whereas the highest GGT quartiles appeared to be associated with higher total cholesterol and triglycerides in both genders and lower HDL in men. CDT and GGT seem to detect different populations of subjects in regard to lipid metabolism. These observations may have important clinical and public health implications.     

Associations of 25 structural,degradative, and inflammatory candidate genes with lumbar disc desiccation,bulging, and height narrowing

Objective

To examine the allelic diversity of structural, inflammatory, and matrix‐modifying gene candidates and their association with disc degeneration.

Methods

Subjects were 588 men ages 35–70 years. We investigated associations of single‐nucleotide polymorphisms in AGC1 and in 12 collagen, 8 interleukin, and 4 matrix metalloproteinase genes with quantitative magnetic resonance imaging measurements of disc desiccation and disc bulging and height narrowing scores, after controlling for age and suspected risk factors. Analyses were performed using QTDT software. P values were derived from 1,000 permutations, and empirical P values for global significance also were applied.

Results

Twelve of the 99 variants in 25 selected candidate genes provided evidence of association (P < 0.05) with disc signal intensity in the upper and/or lower lumbar regions. Allelic variants of AGC1 (rs1042631; P = 0.001), COL1A1 (rs2075555; P = 0.005), COL9A1 (rs696990; P = 0.00008), and COL11A2 (rs2076311; P = 0.018) genes provided the most significant evidence of association with disc signal intensity. The same variants of AGC1 (P = 0.010) and COL9A1 (P = 0.014), as well as variants in the COL11A1 gene (rs1463035 [P = 0.004]; rs1337185 [P = 0.015]) were also associated with disc bulging, as was AGC1 with disc height narrowing (rs1516797; P = 0.005). In addition, 4 allelic variants in the immunologic candidate genes (rs2071375 in IL1A [P = 0.027]; rs1420100 in IL18RAP [P = 0.005]) were associated with disc signal intensity.

Conclusion

Genetic variants account for interindividual differences in disc matrix synthesis and degradation. The accuracy of the quantitative disc signal intensity measurements we used likely enhanced our ability to observe these associations. Our findings shed light on possible mechanisms of degeneration and support the view that disc degeneration is a polygenetic condition.