The interaction of antibody/dna immune complexes with complement

In 28 serum and plasma samples from patients with systemic lupus erythematosus, we examined the importance of antibody class with respect to complement-mediated binding to human red blood cells (RBC) of antibody/DNA immune complexes (IC) prepared with anti-DNA antibodies. We used both ³H–double-stranded DNA and ³H–single-stranded DNA (ssDNA). Generally, double-stranded DNA IC showed considerably higher binding than did ssDNA IC in the RBC binding assay. Further analysis indicated that although ssDNA IC fix complement, it is necessary that these IC contain IgM anti-DNA antibodies in order for them to bind to RBC. The results suggest that the mechanisms of clearance and pathogenic potential of these IC may depend upon both the DNA conformation and antibody class. In particular, complement-fixing IC which contain IgG anti-DNA antibodies and ssDNA may not be cleared via the erythrocyte clearance mechanism, and therefore, could be more likely to deposit in certain tissues and initiate inflammatory reactions.     

A quantitative ultrastructural study of collagen fibril formation in the healing extensor digitorum longus tendon of the rat

A study was made of collagen fibril populations in healing tendon using a window lesion in rat extensor tendon. Two environments were thus created. One (the lesion area) where stress levels were reduced; the other (the non-lesion area) where stress levels were increased. In both areas a population of small diameter (less than 50nm) collagen fibrils were synthesized. Lesion area fibrils increased their diameter only slowly. Non-lesion area fibrils added to a population which increased its diameter distribution comparatively rapidly. It is suggested that in the lesion area fibrils were synthesized in response to tissue damage and low levels of stress. These may be of type III collagen. In the non-lesion area fibrils were synthesized in response to raised levels of stress. These may be of type I collagen. Implications of these events, especially as they might relate to gap formation in flexor tendon surgery are discussed.     

24-Hour QT variability in heart failure

Background

Previous studies have shown that increased temporal variability of repolarization, as reflected by QT interval variability measured for 10 minutes, predicted spontaneous ventricular arrhythmias in implantable cardioverter defribrillator patients, but it is unclear how these measures perform in 24-hour recordings.

Methods

Twenty-four-hour digital Holter recordings from 372 subjects with chronic heart failure enrolled in Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca, (GISSI) Heart Failure study were analyzed using a template-matching, semiautomatic algorithm to measure QT and heart rate time series in sequential 5-minute epochs for 24 hours. QT variability was expressed as normalized QT variance (QTVN) or as the log ratio of the QTVN over normalized heart rate variance (QT variability index, or QTVI).

Results

A pronounced diurnal variation was seen in both QTVI and QTVN. Both were lowest in the midnight to 6 am time frame and increased throughout the day, peaking at noon to 6 pm, then decreasing 6 pm to midnight. For QTVI, all 4 time points were significantly different (P < .0001). QT variability index correlated with heart rate (r = 0.38, P < .0001) and was significantly higher for those in higher New York Heart Association (NYHA) classes (r = 0.22, P = .0003). Normalized QT variance did not correlate with heart rate or NYHA but correlated negatively with serum potassium (r = −0.22, P = .0002) and manifested the greatest increase during midmorning hours.

Conclusions

Repolarization lability as reflected in QT variability has a pronounced diurnal variation and increases significantly after 6 am, the time of greatest arrhythmic risk. QT variability for 24 hours might improve risk prediction in chronic heart failure patients and should be tested in appropriate trials.     

Thiopurine methyltransferase activity in a Spanish population sample: decrease of enzymatic activity in multiple sclerosis patients

The present study was performed in order to obtain the thiopurine methyltransferase (TPMT) activity frequency distribution histogram in a Spanish population. A total of 3640 Spanish clinical laboratory samples were evaluated, which included 1249 patients with Crohn's disease, 589 with ulcerative colitis, 348 with multiple sclerosis (MS), 487 with several autoimmune diseases different from the above-mentioned diseases and 967 a donor group. We have measured the TPMT activity in red blood cells (RBCs) by a radiochemical method, using S-adenosyl-L-[methyl-3H]methionine as methyl donor. The different groups present in their entirety a normal distribution histogram and a wide range of TPMT activity from 0 to 41 U/ml RBCs. The differences found between the Spanish population TPMT activity frequency distribution histogram and the pattern previously described in a North American population were not due to azathioprine treatment or gender. The effect of autoimmune diseases on TPMT activity was evaluated: the enzymatic activity was similar in the donor group (19.9 +/- 6.3 U/ml RBCs) and in the patients with Crohn's disease (20.0 +/- 5.8 U/ml RBCs) and ulcerative colitis (19.7 +/- 6.1 U/ml RBCs); however, it decreased significantly (p<0.0001) in MS patients (17.1 +/- 6.1 U/ml RBCs) with respect to the donor group. In conclusion, our results show that the Spanish population TPMT distribution is closer to that of the Jewish population of Israel than to North American populations, and that in MS the enzymatic activity of TPMT decreases significantly. This observation may take into account the usage of azathioprine as therapeutic agent in Spanish MS patients.