Maxadilan is a vasodilatory peptide derived from sand flies that is an agonist at the pituitary adenylate cyclase-activating peptide (PACAP) type 1 receptor. Surprisingly, maxadilan does not share significant sequence homology with PACAP. To examine the relationship between structure and activity of maxadilan, several amino acid substitutions and deletions were made in the peptide. These peptides were examined in vitro for binding to crude membranes derived from rabbit brain, a tissue that expresses PACAP type 1 receptors; and induction of cAMP was determined in PC12 cells, a line that expresses these receptors. The peptides were examined in vivo for their ability to induce erythema in rabbit skin. Substitution of the individual cysteines at positions 1 and 5 or deletion of this ring structure had little effect on activity. Substitution of either cysteine at position 14 or 51 eliminated activity. Deletion of the 19 amino acids between positions 24 and 42 resulted in a peptide with binding, but no functional activity. The capacity of this deletion mutant to interact with COS cells transfected with the PACAP type 1 receptor revealed that this peptide was a specific antagonist to the PACAP type 1 receptor.
Normal coordinate analyses were performed on three molecular models of the rubredoxin of Desulfovibrio vulgaris, Desulfovibrio gigas, and Clostridium pasteurianum. The total 1081, 1093, and 1148 internal coordinates were specified by the X-ray analyzed coordinates of the 390, 399, and 423 atoms, respectively, in a mass-group approximation. The appropriately assumed values of Urey–Bradley force constants as well as some diagonal values of out-of-plane bending and torsional forces gave 146, 146, and 148 normal modes, respectively, in 250–450 cm−1 region. These are the deformational vibrations within the peptide skeleton of the protein molecules. The Fe–S stretching displacements of the FeS4 core contribute to a limited number of these vibrations. The modes having a totally symmetric Fe–S stretching contribution confined within a frequency region of 290–330 cm−1 in which the principal resonance Raman band of rubredoxin has been reported, and the several minor resonance Raman bands reported in the higher frequency region of 330–420 cm−1 were assigned to noraml modes having a non-totally symmetric Fe–S stretching character. The PED values indicated that all of these modes are constructed mostly by the deformational displacements in the peptide skeleton widely spread into the molecule around the FeS4 core. This feature is very similar to the case of the blue-copper protein studied previously.
There are several case reports of systemic vasculitis associated with chronic suppurative lung diseases. We describe a 46-year-old female, previously diagnosed as having diffuse panbronchiolitis (DPB), presenting with hemosputum and dyspnea. Her serum titer of MPO-ANCA was positive together with a high titer of BPI-ANCA. Chest X-ray and chest CT scan showed pulmonary hemorrhage, and the renal biopsy specimen revealed necrotizing, crescentic glomerulonephritis. She was diagnosed as having ANCA-associated vasculitis, and more specifically, microscopic polyangiitis accompanied by DPB. She was treated with methylprednisolone pulse therapy, followed by intravenous cyclophosphamide. This case suggested a possible association with chronic bacterial infection, which may play a role in the pathogenesis of ANCA-associated vasculitis.
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