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Biomedical subjects

J Spragg

Publications and source records attributed to J Spragg.

51 records · Page 3Linked to original sources
PubMed1977

Immunologic release of heparin from purified rat peritoneal mast cells.

High m.w. [35S]heparin, labeled in vivo or in vitro, was released from purified rat mast cells by challenge with rabbit anti-rat F(ab')2, guinea pig anti-rat IgE, or calcium ionophore. The released and the residual heparin were isolated by Dowex 1 chromatography and were of comparable size by Sepharose 4B gel filtration. The majority of the released heparin was found by differential centrifugation to be granule-associated. Net percentage of mast cell heparin release, quantitated by metachromasia after isolation on Dowex 1 chromatography, correlated in a linear fashion with net percentage of histamine release, with heparin exhibiting a threshold requirement for onset of release. The correlation of histamine and high m.w. heparin release provides chemical support for the conclusion of others from ultrastructural studies that mast cell activation by immunologic means or by the calcium ionophore results in secretion of the whole granule.

Animals↗
PubMed1977

Immunologic reactivity of purified human urinary kallikrein (urokallikrein) with antiserum directed against human pancreas.

Donkey antiserum to normal human pancreas absorbed with lyophilized human plasma recognized human urokallikrein in concentrated crude urine or after an approximately 500-fold purification. The urokallikrein antigen was associated with kinin-generating and alpha-N-p-tosyl-L-arginine methyl ester (TAMe) cleaving activity on isoelectric focusing, with the isoelectric point being 3.8 to 4.4. Both kiningenerating and esterolytic activity were removed from the purified urokallikrein by an immunoadsorbent prepared by coupling the IgG fraction of the absorbed donkey antiserum to Sepharose 6B. The failure of anti-plasma kallikrein to react in immunodiffusion with purified urokallikrein indicates that urinary kallikrein is distinct from plasma kallikrein although antigenically related to glandular kallikreins.

Animals↗
PubMedDate not supplied

Intraarticular activation of the complement system in patients with juvenile rheumatoid arthritis.

Analyses of CH50, complement components, properdin factors, and kininogen in synovial fluid of patients with juvenile rheumatoid arthritis revealed evidence of activation of the classic complement pathway in all clinical subgroups. Juveniles with the adult pattern of disease had the greatest incidence of complement abnormalities. Evaluation of individual components by both activity determination and protein measurement showed decreased synovial fluid specific functional activity (activity per microgram protein) to the more marked in synovial fluids with profound depressions of complement activity. These findings provide further evidence that nonfunctional, antigenically intact component protein may remain after complement activation. Radial immunodiffusion measurements of properdin factors and kininogen failed to support their involvement in joint inflammation. Serum complement component measurements by activity but not protein concentration correlated with other parameters or inflammation. Four patients had isolated depressions of serum C2 activity. Immunoglobulin levels, particularly IgA, correlated with some complement measurements and with the sedimentation rate.

Adolescent↗
PubMedDate not supplied

The inhibition of glandular kallikrein by peptide analog antagonists of bradykinin.

Bradykinin sequence analog receptor antagonists exhibit at their carboxyl termini features which contribute to the affinity of peptide inhibitors of glandular kallikreins. These features include a preference for L-Arg over L-Lys at position P1 and bulky D-amino acids at P3. There is minimal steric restriction at P2. Three representative receptor antagonists were examined for their capacity to inhibit the amidolytic activity of human urinary kallikrein (HUK). The Ki values for B4307 (DArg-Arg-Pro-Hyp-Gly-Thi-Ser-DPhe-Thi-Arg), B4308 (Lys-Lys-Arg-Hyp-Hyp-Gly-Thi-Ser-DPhe-Thi-Arg), and B3852 (Arg-Pro-Hyp-Gly-Phe-Ser-DPhe-Phe-Arg) are 0.5, 0.3 and 2.5 microM, respectively. B4308 and B3852 were also shown to inhibit rat urinary kallikrein with Ki's of 1.0 and 5.5 microM. In the estrous rat uterus assay, 0.4 to 1.6 microM quantities of B4308 gave 5 to 10 times as much inhibition of contractile activity when added at the beginning of the incubation of HUK with human low molecular weight kininogen than when added upon addition of the mixture to the organ bath. These antagonists may inhibit the kallikrein-kinin system not only by blocking the binding of kinins to their receptor(s) but also by inhibiting the release of kinins from kininogens.

Bradykinin↗
PubMedDate not supplied

Specificity of substrate analogue inhibitors of human urinary kallikrein.

A series of acetyl-peptidyl-amides containing the amino acid sequence around the Arg-Ser kallikrein cleavage site of bovine kininogen were synthesized and tested for their ability to inhibit both the kinin-releasing activity and the amidase activity of purified human urinary kallikrein. The substrate analogues were competitive inhibitors for human urinary kallikrein and the heptapeptides (P4-P3'), hexapeptides (P3-P3'), and pentapeptides (P2-P3') gave Ki values of 140, 64, and 18 microM respectively, while the tetrapeptides (P1-P3'), tripeptides (P1'-P3') and dipeptides (P2'-P3') had little or no inhibitory activity. The effective analogues had neither kinin-like nor kinin-blocking activity on the rat uterus either before or after exposure to human urinary kallikrein. The effective human urinary kallikrein inhibitors were further examined for their effect on other serine proteases, including human plasma kallikrein, plasmin, complement components (C1s, C1r), bovine coagulation factors (IIa, IXa, and Xa), elastase, and trypsin. These peptides showed little inhibition of the circulating serine proteases but yielded a Ki for the nonspecific protease trypsin in the microM range. These results should provide the basis for the development of highly specific tissue kallikrein inhibitors to aid in elucidating the in vivo role(s) of tissue kallikreins.

Animals↗