Metacarpophalangeal pattern (MCPP) profile analysis in a family with triphalangeal thumb.

Triphalangeal thumb (TPT) is a rare congenital disorder characterised by a long, finger-like thumb with three phalanges instead of two. It can occur as an isolated defect, in association with other abnormalities of the hands and feet, or as a part of a syndrome. Sporadic cases have been described, but it is usually inherited as an autosomal dominant trait. In order to examine skeletal morphology in different phenotypic variations of this disorder, we performed metacarpophalangeal pattern profile analysis in one kindred with this disorder. A characteristic profile occurred in all affected people, based on the individual lengthening or shortening of the thumb bones. Comparison of the affected and unaffected people from this family with people with a different genetic background suggests that the described profile is specific for TPT and could be used as a helpful diagnostic tool in syndromes which include TPT.

Role of the N-terminal regions of hog C3a, C5a and C5a-desArg in their biological activities.

The N-terminal regions of the complement peptides C3a, C5a and C5a-desArg (purified from yeast-activated hog serum) were gradually shortened by incubation with leucine amino peptidase. This treatment led to the following changes in the biological activities of these peptides: the potencies of C5a and C5a-desArg in aggregation of human polymorphonuclear leukocytes and of guinea-pig platelets, and their ability to deactivate these cells were gradually diminished; the chemotactic effect of C5a-desArg on human leukocytes was similarly lowered, while the chemotactic potency of C5a was even increased up to the loss of the first 12 N-terminal amino acids. However, after removal of the whole N-terminal region (i.e. 20 amino acids distal of the first disulfide bridge) the potency of both peptides was decreased to a few percent. In contrast, C3a totally lost its platelet-aggregating as well as deactivating activity already after cleavage of 10-15 N-terminal amino acids by LAP. On leukocytes, on the other hand, C3a retained some activity even after the loss of the whole N-terminal region. These results indicate that the N-terminal regions play an important role for biological activities of the three complement peptides, possibly by stabilizing the optimal conformation of their C-terminal regions which contain the receptor-activating domains.

Influence of the anti-inflammatory serine esterase inhibitor gabexate mesilate (Foy) on aggregation, locomotion and adhesion of polymorphonuclear leukocytes.

The effects of the anti-inflammatory serine esterase inhibitor, gabexate mesilate (Foy) were studied, on locomotion, autoaggregation and adhesion of polymorphonuclear leukocytes stimulated with the complement peptide C5a-desArg. The drug inhibited aggregation as well as spontaneous and directed migration of human leukocytes at concentrations of about 10(-3) M. Adhesion of peritoneal guinea-pig leukocytes to autologous aortic strips was reduced at about 20 times lower drug concentrations. The inhibitory drug effects were highly time- and temperature-dependent. Experiments with the two major drug metabolites, pHB and epsilon GC, indicate that gabexate mesilate is not active by itself but rather by its hydrolytic aromatic metabolite pHB. The results further suggest that the inhibitory effects on leukocyte activities observed are not related to the anti-inflammatory effects of gabexate mesilate.