Chemistry: analytical and immunological testing – Involving an insoluble carrier for immobilizing immunochemicals
Patent
1991-12-19
1995-07-25
Scheiner, Toni R.
Chemistry: analytical and immunological testing
Involving an insoluble carrier for immobilizing immunochemicals
436536, 436549, 436811, 435 71, 435 792, 435810, 5303871, 5303879, 5303793, 5303913, G01N 33532, G01N 3353, C07K 1644
Patent
active
054361699
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to proteins associated with acute pancreatitis and agents for the diagnosis of this disease.
Acute pancreatitis is an inflammatory disease of the pancreas which, pathologically speaking, extends from the simple edematous form to the complete hemorrhagic necrosis of the gland. Necrohemorrhagic hepatitis is a very serious disease since, depending on the authors, its mortality is estimated to vary from 30 to 70%. In certain cases it is very difficult to establish the diagnosis of acute pancreatitis with certainty (Sarner, M. et al, Gastroenterol. (1984), 13: 865-870). This diagnosis is based in particular on clinical examination (acute abdominal pain), on the determination of a certain number of substances in the plasma or in the peritoneal fluid (Bradley, J. et al., Br. J. Surg. (1981), 68: 245-246; and Dubick, M. et al., Dig. Dis. Sci. (1987), 32: 305-312). The analytical determinations employed include those for amylase, lipase, trypsin, elastase, ribonuclease, phospholipase A2, .alpha.-2 macroglobulin, calcium, LDH, protease inhibitors and others. However, none of them has proved to be specific, practical or above all, discriminating. Hence, it is usually considered sufficient to determine amylasemia. Recently, ultrasonography and computerized tomography have appeared to be able to facilitate the diagnosis of pancreatitis without, however, decisive progress being made (Silverstein, W. et al., Am. J. Roentgenol., (1981), 137: 497-502).
In 1984, Keim et al. published (Digestion, (1984), 29: 242-249) results of the consequences of cannulation of the pancreatic duct and the induction of pancreatitis on the protein composition of the pancreatic juice in the rat, this animal being used as an experimental model. After the operation of cannulation (1 to 2 days later), the authors observed a fall in the level of amylase in the pancreatic juice followed, 3 to 4 days after the operation, by a return to the normal amylase level.
Separation of the proteins of the pancreatic juice during this period of remission by means of electrophoresis on polyacrylamide gel (PAGE) showed an additional protein band, detectable as early as 12 hours after the operation and as late as 3 to 4 days after the operation. This protein band did not exist in the untreated control rat. This secretory protein has been called PAP ("pancreatitis-associated protein").
Subsequently, Keim et al. carried out measurements of the amount of PAP present in the pancreatic tissue of the rat, after induction of pancreatitis, by means of tests involving the detection of complement binding.
However, up to now these tests have not made it possible to detect the existence of the PAP in the serum of the rat in which pancreatitis has been induced.
The agents hitherto suggested in the prior art had thus not enabled an adequate identification of the PAP protein in the rat, which raises the question as to the relevance of an investigation in man in order to investigate whether such a protein can be detected.
Furthermore, the results available up to now have not made it possible to estimate the usefulness of PAP for carrying out a diagnosis of pancreatitis.
The inventors have observed that rat polyclonal antibodies which recognize the rat PAP protein do not show significant recognition of a protein in human serum.
Thus, after making this observation, the inventors investigated a more adequate identification of the rat PAP protein, with a view to defining tools of investigation in man: the inventors have now clearly identified the PAP protein in the rat and have determined its amino acid sequence. On the basis of these results, they have developed agents which should make it possible to detect and identify whether a protein corresponding to rat PAP exists in man.
The cloning and sequencing of the PAP messenger RNA starting from a library of rat pancreatic cDNAs has also made it possible to demonstrate unambiguously that the PAP is indeed synthesized by the pancreas. The inventors have also shown that the protein is very weakly expressed i
REFERENCES:
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Dagorn Jean-Charles
Iovanna Juan-Lucio
Volker Keim
Institut National de la Sante et de la Recherche Medicale
Parsons Nancy J.
Scheiner Toni R.
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