Association between early onset and organ manifestations of systemic lupus erythematosus (SLE) and a down-regulating promoter polymorphism in the MBL2 gene.

The serum concentration of mannose-binding lectin (MBL) is genetically determined by a series of allelic polymorphisms in the MBL2 gene. Since several polymorphisms of the MBL2 gene have been suggested to be risk locus for systemic lupus erythematosus (SLE), we investigated MBL2 polymorphisms in 315 SLE patients from Hungary and 182 geographically matched healthy controls. Within the group of patients, we found that homozygotes for an MBL2 down-regulating promoter polymorphism at position -221 (YA to XA) (rs7096206) were significantly (p=0.017) younger at diagnosis than the other patients. The frequency of juvenile-onset SLE (

Smoking and a complement gene polymorphism interact in promoting cardiovascular disease morbidity and mortality.

We have demonstrated previously that carriers of a genotype called C4B*Q0 (silent allele of the C4B gene) have a substantially increased risk to suffer from myocardial infarction or stroke, and are selected out from the healthy elderly population. Because smoking carries a major risk for cardiovascular disease (CVD), it seemed worthwhile to study if these two factors interact. Study 1 involved 74 patients with angina pectoris (AP), 85 patients with recent acute myocardial infarction (AMI) and 112 survivors of a previous AMI and 382 controls from Iceland. Study 2 involved 233 patients with severe CVD and 274 controls from Hungary. Smoking habits were registered for each subject. The number of C4A and C4B genes was determined by phenotyping or genotyping. Compared to controls, C4B*Q0 carrier frequency was significantly higher at diagnosis in Icelandic smokers with AP (P = 0.005) and AMI (P = 0.0003) and Hungarian smokers with severe coronary artery disease (P = 0.023), while no such difference was observed in non-smoking subjects. Age-associated decrease in C4B*Q0 observed previously in two remote Caucasian populations was found, in the present study, to be associated strongly with smoking, and to already occur in smokers after age 50 years both in Iceland and Hungary. Our findings indicate that the C4B*Q0 genotype can be considered as a major covariate of smoking in precipitating the risk for AMI and associated deaths.

Structural elements responsible for transglutaminase activity of protein disulphide isomerases and thioredoxins.

According to recent results both protein disulphide isomerase (PDI) and thioredoxin (Trx) enzymes have transglutaminase activity which can be linked to the thioredoxin box found in these proteins. Analysis of known protein disulphide isomerase and thioredoxin sequences has revealed the presence of conserved Cys, His and Asp residues required for transglutaminases to catalyze the incorporation of primary amines into protein-bound glutamine residues. The available 3D structures of PDIs and Trxs show that these residues are in close proximity to achieve transglutamylation of substrate proteins. The shared activities of the members of the large protein disulphide isomerase, thioredoxin and transglutaminase enzyme families reviewed here may have general biological significance in the regulation of cellular and tissue processes.

Poor correlation of short- and long-term cosmetic appearance of repaired lacerations.

OBJECTIVE: To describe the consistency of a cosmetic scale for repaired lacerations and to determine whether the appearance of lacerations at the time of suture removal correlates with the appearance six to nine months later. METHODS: A convenience sample of patients who had lacerations repaired in a university teaching hospital were evaluated at the time of suture removal and six to nine months following repair. All lacerations were assigned 0 or 1 point each for the presence or absence of a step-off borders, contour irregularities, margin separation, edge inversion, excessive distortion, and overall appearance. A total cosmetic score (0-6) was calculated by adding the scores for the categories above. The consistency of the cosmetic scale was assessed by comparison of scores given by two different practitioners evaluating each patient at suture removal and long-term follow-up. The 38 evaluating practitioners were assigned based on availability and did not necessarily perform serial evaluations of the same patient. RESULTS: The 41 participating patients had a median age of 19 years (range, 2-82 years). Wounds were located predominantly on the head (73%) and upper extremity (22%). Long-term follow-up was performed at a median of 219 days (range, 155-280 days) after suture removal. Interpractitioner concordance regarding optimal appearance (score of 6 vs < or = 5) was moderate (kappa = 0.52) at the time of suture removal and substantial at the time of long-term follow-up (kappa = 0.68). However, the correlation of actual scores at the time of suture removal vs at long-term follow-up was poor (r = 0.17, p = 0.29). CONCLUSION: For our clinicians, the six-item categorical scale appears consistent as a tool for the assessment of the cosmetic appearance of wounds. However, correlation between laceration appearance at the time of suture removal and six to nine months later is poor.