Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 46 year old white man presented with subcutaneous and intramedullary fat necrosis, destructive polyarthritis, and osteolytic bone lesions, complicating a poorly differentiated adenocarcinoma of the tail of the pancreas with metastases in the liver and omentum. There was a 100-fold increase in serum lipase and trypsin activity. His condition deteriorated rapidly, was characterised by rapid tumour growth, formation of ascites, a 20 kg weight loss, extensive subcutaneous fat necrosis, and fistula formation in the left calf. Treatment with 5-fluorouracil 300 mg/m2 on days 1-5 and doxorubicin 50 mg/m2 and cisplatin 100 mg/m2 on day 1, every three weeks, was well tolerated and resulted in rapid clinical improvement. After three courses of treatment a partial remission was seen and after seven courses further improvement occurred with a return to normal of serum lipase and trypsin activity. One year after starting chemotherapy the tumour relapsed but responded again to chemotherapy (epirubicin 40 mg/m2 and carboplatin 300 mg/m2 on day 1, every three weeks).
 ...
PMID:Pancreatic carcinoma with polyarthritis, fat necrosis, and high serum lipase and trypsin activity. 238 23

Rat blood plasma contains three high molecular weight thiol ester-containing proteinase inhibitors, alpha 1-macroglobulin (alpha 1M), alpha 1-inhibitor III (alpha 1I3), and alpha 2-macroglobulin (alpha 2M). Rat serums have been analyzed using a two-dimensional gel electrophoretic technique which optimizes recovery of high molecular weight proteins. alpha 1M, and (alpha beta)4-tetramer in native solution, separated in the second sodium dodecyl sulfate-containing electrophoretic dimension as a disulfide-linked (alpha beta)2-dimer with an approximate Mr of 360 kDa. alpha 1I3 separated in the gels as a single 190-kDa polypeptide. It is also a monomer in native solution by ultracentrifugation criteria. Native rat alpha 2M is a tetramer, but it separates in the gels as a disulfide-linked dimer with an Mr of approximately 360 kDa. The kinetics of changes in concentration of these proteins during the induction of polyarthritis was also measured by quantitative immunoelectrophoresis. In rats with adjuvant-induced polyarthritis, the concentration of alpha 1I3 dramatically decreases and alpha 2M appears and continues to increase in a biphasic manner for 2 weeks. The alpha 1M concentration remains relatively constant. All three macroglobulins were purified utilizing modern rapid chromatographic techniques, and parallel comparisons of their native physicochemical properties were carried out. The N-terminal sequence of the alpha-chain of rat alpha 1M was also shown to share sequence homology with that of alpha 2M. In agreement, Esnard et al. (Esnard, F., Gutman, N., El Moujahed, A., and Gauthier, F. (1985) FEBS Lett. 182, 125-129) recently reported that alpha 1I3 also contains a thiol ester bond, as do alpha 1M and alpha 2M, since it reacts covalently with [14C]methylamine and is cleaved autolytically at 80 degrees C. We have examined negatively stained preparations of native, trypsin-treated, and methylamine-treated human alpha 2M, rat alpha 2M, and rat alpha 1M in the electron microscope. Trypsin appears to convert globular ring-shaped native molecules to rectangular box-like structures, in agreement with the conclusions of a recent report on human alpha 2M (Tapon-Bretaudiere, J., Bros, A., Couture-Tosi, E., and Delain, E. (1985) EMBO J. 4, 85-89).
 ...
PMID:Three high molecular weight protease inhibitors of rat plasma. Isolation, characterization, and acute phase changes. 243 67

An 82-year-old man presented with a two-week history of three painful, inflamed nodules on his lower extremities with symmetric arthritis of multiple joints. He was under the care of hospice for end-stage acinar cell carcinoma of the pancreas. His serum amylase and lipase levels were markedly elevated. An incisional biopsy revealed lobular inflammation of subcutaneous fat, focal fat necrosis with saponification/ghost cells and scattered foreign-body type giant cells consistent with pancreatic fat necrosis/pancreatic panniculitis. This is hypothesized to be initiated by autodigestion of subcutaneous fat secondary to systemic spillage of excess digestive pancreatic enzymes. Enzymes such as amylase, lipase and trypsin are increased in the bloodstream and can affect remote tissues, such as the subcutaneous fat and articular surfaces of joints. This report, along with the patient's clinical findings, was consistent with PPP syndrome: pancreatic disease, polyarthritis and panniculitis. Although the pancreatic disease of PPP syndrome usually includes pancreatitis, this case represents a report of polyarthritis and panniculitis occurring in the presence of pancreatic carcinoma.
 ...
PMID:Subcutaneous fat necrosis/panniculitis and polyarthritis associated with acinar cell carcinoma of the pancreas: a rare presentation of pancreatitis, panniculitis and polyarthritis syndrome. 2086 49