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Biomedical subjects

E Fink

Publications and source records attributed to E Fink.

At least 55 records · Page 3Linked to original sources
PubMed1993

[Enzyme liberation and activation of the kallikrein-kinin system in experimental pancreatitis. Studies of portal vein blood, pancreatic lymph and peritoneal effusion].

The clinical course of acute pancreatitis is strongly influenced by secondary cardiac, pulmonary and renal damage. The aim of the present study was to gather information about the compartment promoting the systemic damage. Therefore the activity of lipase, phospholipase A and plasma pro-kallikrein and the concentration of tissue kallikrein and kininogen were measured in portal venous blood, pancreatic lymph and peritoneal exudate. Anaesthetized pigs were subjected to fluid resuscitation to keep systemic haemodynamic parameters constant. The pancreas was isolated in situ. The pigs were randomly assigned to a control group (n = 9) or one of the two pancreatitis groups (n = 10 each). Pancreatitis was induced by i.a. infusion of free fatty acid (FFS) or retrograde infusion of 5% sodium taurocholate intraductally (NaT). In both pancreatitis groups the activity of lipase and phospholipase A increased. The most pronounced changes were seen in the peritoneal exudate (phospholipase A activity 40 min after induction: control 10.0 U/l, NaT 72.2 U/l). In both pancreatitis groups there was evidence for activation of the tissue kallikrein kinin system in the form of an increase in the kallikrein concentration and a decrease in the kininogen concentration. Again the changes were most pronounced in the peritoneal exudate (tissue kallikrein 40 min after induction: control 14.7 ng/ml, NaT 452 ng/ml).

Acute Disease↗
PubMed1993

Inhibition of plasma kallikrein with aprotinin in porcine endotoxin shock.

Activation of the contact phase of coagulation has been implicated in the pathogenesis of septic shock. We wanted to determine if inhibition of plasma kallikrein can prevent arterial hypotension and liberation of kinins from kininogen, induced by an infusion of bacterial lipopolysaccharide (LPS) in anesthetized, ventilated 20-kg pigs. The LPS was given IV in a dose of 5 micrograms/kg/h for 8 hours. The plasma kallikrein inhibitor aprotinin, 537 mumol, was given IV during 8 hours, resulting in plasma levels above 10 mumol/L. Ten animals (SA) received LPS and aprotinin and ten randomized controls (SC) received LPS and saline. Kinin-containing kininogen was determined on the basis of the amount of kinin releasable in plasma samples by incubation with trypsin. Kininogen decreased to 58% +/- 4% of the baseline value without any difference between groups. This may indicate participation of other processes than degradation by plasma kallikrein in the decrease of kininogen. Arterial blood pressure was higher at 7 hours in the SA animals than in the SC group (101% +/- 11% vs. 68% +/- 8%; mean +/- SEM; p = 0.026). Fibrin monomer and C3adesArg plasma levels were attenuated by aprotinin treatment. These findings underscore the important role of the contact system in LPS shock.

Animals↗
PubMed1993

Role of bradykinin in anaphylactoid reactions during hemodialysis with AN69 dialyzers.

In vitro experiments have related anaphylactoid reactions in patients treated with angiotensin-converting enzyme (ACE) inhibitors during dialysis with AN69 membranes to excessive bradykinin generation using this negatively charged dialysis membrane. In the present clinical trial plasma bradykinin levels were followed during the early phase of dialysis in 10 patients, not being treated with ACE inhibitors, using AN69, cuprophane, and polysulfone membranes. Bradykinin was measured after extraction by radioimmunoassay. During this study one episode of anaphylaxis occurred during dialysis with the AN69 membrane. Blood samples were collected during the first 5 min of the adverse reaction and showed a more than 100-fold increase in the venous effluent of the AN69 dialyzer (baseline 40 +/- 3 vs. 4,900 +/- 130 fmol/ml after 5 min). Even though none of the patients received ACE inhibitors, there were 4 more asymptomatic individuals who displayed a more than two-fold increase in their plasma bradykinin concentrations in the venous effluent of the AN69 dialyzer. When these patients were treated either with cuprophane or with polysulfone dialyzers, no significant bradykinin formation was detected, nor were there any adverse events. Taken together, these findings show that anaphylactoid reactions with the AN69 membrane are due to excessive bradykinin generation which even may occur in the absence of ACE inhibitors.

Acrylic Resins↗
PubMed1992

The nucleotide and partial amino acid sequences of rat fetuin. Identity with the natural tyrosine kinase inhibitor of the rat insulin receptor.

Fetuins are among the major plasma proteins, yet their biological role has remained elusive. Here we report the molecular cloning of rat fetuin and the sequence analysis of a full-length clone, RF619 of 1456 bp with an open reading frame of 1056 bp encoding 352 amino acid residues. The coding part of RF619 was identical with the cDNA sequence of the natural inhibitor of the insulin receptor tyrosine kinase from rat (pp63) except for four substitutions and a single base insertion causing divergence of the predicted protein sequences. Partial amino acid sequences of rat plasma fetuin were in agreement with the predictions based on the RF619 cDNA. Purified rat fetuin inhibited the insulin receptor tyrosine kinase in vitro. Therefore, we conclude that RF619 and pp63 cDNA encode the same protein, i.e. authentic rat fetuin which is a functional tyrosine kinase inhibitor.

Amino Acid Sequence↗
PubMed1992

Immunoassays for the determination of human tissue kallikrein (TK) in different body fluids based on monoclonal antibodies.

A monoclonal antibody produced against human tissue kallikrein was used to develop solid phase immunoassays for the determination of total immunoreactive tissue kallikrein, of the complex of tissue kallikrein with alpha 1-proteinase inhibitor, and of enzymatically active tissue kallikrein. The assays permit the specific determination of various forms of tissue kallikrein in body fluids and should be very useful in studies on the biological function of tissue kallikrein-kinin systems.

Amino Acid Sequence↗
PubMed1992

Effects of protease inhibitors in experimental septic shock.

Endotoxin shock and contact system activation were used to study effects of hirudin, antithrombin III, eglin C, aprotinin, and [Arg15]-aprotinin in anesthetized pigs. Alterations in the systemic and pulmonary circulation were in part prevented by administration of the inhibitors.

Animals↗
PubMed1992

Human plasma kallikrein processing: proteolysis as an alternative control.

Human plasma kallikrein (HuPK) was detected in normal non-activated and dilution-activated plasma by immunoblotting, using polyclonal antibodies. In non-activated plasma, the predominatly detected protein corresponds to prokallikrein (Mr 80,000-90,000). Activated plasma, besides kallikrein, contains larger proteins (Mr > 130,000) that possibly represent complexes between kallikrein and proteinase inhibitors. Plasma also contains species (Mr 43,000) which corresponds to kallikrein heavy chain. In activated plasma, monoclonal antibodies against kallikrein heavy chain detected, besides these same bands described above, two additional bands (Mr 30,000 and 20,000) possibly correspondent to fragments of kallikrein heavy chain.

Antibodies↗
PubMed1991

Molecular cloning and sequence analysis of the cDNA encoding the human acrosin-trypsin inhibitor (HUSI-II).

A complete cDNA clone encoding the human acrosin-trypsin inhibitor HUSI-II has been isolated from a cDNA library of human testis and completely sequenced. The cDNA of 594 bp contained an open reading frame of 252 base pairs. The deduced amino acid sequence comprised the complete amino acid sequence of HUSI-II and a putative signal peptide. Northern blotting analysis revealed that HUSI-II is synthesized in testis, epididymis and seminal vesicle, but not in the prostate gland.

Amino Acid Sequence↗
PubMed1990

Amino acid sequence elucidation of human acrosin-trypsin inhibitor (HUSI-II) reveals that Kazal-type proteinase inhibitors are structurally related to beta-subunits of glycoprotein hormones.

The amino acid sequence of the acrosin-trypsin inhibitor HUSI-II from human seminal plasma is presented which unequivocally identifies HUSI-II as being of Kazal-type. In addition, the HUSI-II sequence shows a striking similarity to the middle part of glycoprotein hormone beta-subunits thus revealing a hitherto unknown structural and evolutionary relationship between Kazal-type inhibitors and glycoprotein hormones.

Acrosin↗
PubMed1990

Lithium treatment reduces the renal kallikrein excretion rate.

Lithium salts are widely used agents for the prophylactic treatment of affective disorders. Lithium salts may be associated with distal nephron dysfunction. Kallikrein is a protease which is generated by the distal nephron. We used an amidolytic assay of chromatographically purified enzyme to determine the urinary excretion rate of active kallikrein in relation to lithium treatment. All plasma lithium concentrations were within the therapeutic range (0.4 to 0.9 mmol/liter). In 15 patients the urinary excretion rate of active kallikrein was 267.4 +/- 65.6 mU/24 hrs before lithium treatment, and fell to 117.8 +/- 39.6 mU/24 hrs (P less than 0.05) on day 14 of lithium treatment. This reduction was associated with a decrease of immunoreactive kallikrein in the same urines by 66%. In another 15 patients who had undergone lithium therapy for an average period of 5.6 years, the urinary excretion rate of active kallikrein was 86.1 +/- 14.5 mU/24 hrs, while 21 age-matched healthy controls had an excretion rate of 364.1 +/- 58.4 mU/24 hrs (P less than 0.05). Measurements of immunoreactive kallikrein in the same urine samples demonstrated a reduction of kallikrein after long-term lithium treatment by 78%. These observations could not be attributed to changes in creatinine clearance, renal sodium or potassium excretion rates or plasma concentrations of aldosterone and vasopressin. Addition of lithium to the urine in vitro had no demonstrable effect on kallikrein measurement by amidolytic assay. We conclude that lithium in therapeutic plasma concentrations may directly suppress the secretion of kallikrein by renal connecting tubule cells.

Adult↗
PubMed1990

Human leukocyte elastase inhibitors: designed variants of human pancreatic secretory trypsin inhibitor (hPSTI).

Variants of human secretory trypsin inhibitor were constructed with the aim of producing inhibitors specific for human leukocyte elastase. Models of the hPSTI/HLE and hPSTI/chymotrypsin complexes were generated by computer aided protein design and used to plan better HLE inhibitors. This resulted in the production of the strongest and most specific inhibitors of HLE known.

Animals↗