Serum amyloid A protein (SAA) in colorectal carcinoma.

The changes in serum levels of serum amyloid A protein were studied in 67 patients suffering from colorectal carcinoma and compared to three other major acute phase proteins: C-reactive protein, alpha1-antichymotrypsin and alpha1-acid glycoprotein. Although the presence of colorectal carcinoma caused an increase in serum levels of all the acute phase reactants studied, serum amyloid A protein showed the most powerful reaction in pre-operative disease stage, with the mean value of 330 mg/l (range 7-2506 mg/l) as compared to the normal values of <1.2 mg/l obtained in 30 healthy adults. The mean serum amyloid A protein concentration increased to 487 mg/l after surgery, declining during the post-operative clinical course until the sixth chemotherapy cycle (from 167 mg/l to 64 mg/l), but never returned to the normal range. In the later chemotherapy cycles, mean serum amyloid A protein increased to 163 mg/l, probably as a result of the disease relapse. According to the statistical relations among exact confidence intervals for proportions, serum amyloid A protein showed the best specificity for colorectal carcinoma of all the acute phase proteins studied (83-100%) and also a sensitivity of 100%. We concluded that serum amyloid A protein seems to be a reliable parameter, which could be recommended for clinical routine as a non-specific tumour marker for colorectal carcinoma.

Serum amyloid A protein in the prediction of postburn complications and fatal outcome in patients with severe burns.

Fifty adults hospitalized with extensive burns formed the basis of the present study. Serum amyloid A protein, C-reactive protein, alpha 1-antichymotrypsin and alpha 1-acid glycoprotein were measured in serum samples taken on admission, and 3 and 7 days later. Fatal outcome was observed in 13 out of 14 (93%) patients with serum amyloid A protein over 100 mg/l on admission and in only 2 of the remaining 36 (6%) patients with serum amyloid A protein below 100 mg/l. The median serum amyloid A protein concentration on admission in 15 patients with fatal outcome was 134 mg/l, and only 30 mg/l in 35 patients who recovered (p < 0.00005). As a reference value, the level of 100 mg serum amyloid A protein per litre on admission gave an evident predictive value (93%) and sensitivity (87%) for fatal outcome. The difference between serum amyloid A protein concentrations in patients with complications (median 642 mg/l) and those without complications (median 250 mg/l) was statistically very significant (p = 0.0003) three days after burn injury. The level of 400 mg/l as a reference value 3 days after burn injury gave a reasonable predictive value (80%) and sensitivity (74%) for the development of postburn complications, but patients who died did not develop a hypermetabolic reaction and their serum amyloid A protein concentration remained below 400 mg/l, despite high serum amyloid A protein concentrations observed on admission (above 100 mg/l). No statistical significance was observed for the other 3 acute phase proteins investigated in this study.

The diagnostic capacity of serum amyloid A protein for early recognition of kidney allograft rejection.

We used new micro-ELISA test with sequence-specific antibody for every day monitoring of serum amyloid A protein (SAA) in 20 patients with kidney allografts in order to facilitate an early diagnosis of rejection. Altogether 44 SAA peaks were observed (beside those caused by surgery) and 22 of them were caused by allograft rejections. When allograft rejection occurred in postsurgical period (first 4 days), SAA levels rose to mean 706 +/- 161 mg/l while initial SAA peaks (caused by surgical trauma) reached the mean value 306 +/- 55 mg/l. The statistical significance was very high, P < 0.0001. In all nine rejection episodes in this period SAA peaks were higher than 400 mg/l, so we chose this level as a reference limit for this period. SAA peaks caused by allograft rejection in later period were also markedly higher (mean 461 +/- 176 mg/l) than those caused by infections or other complications (mean 133 +/- 82 mg/l, P < 0.001). Baseline mean level was 9 +/- 5 mg/l. In all 13 rejection episodes in this period SAA peaks were higher than 200 mg/l, so we chose this level as a reference limit for this period. In 20 of 22 rejection episodes (91%) SAA elevation predicted rejection and usually started to rise sharply 2 days before it. An excellent correlation between kidney allograft rejection and SAA reaction was found in this study (better than with CRP reaction) so we recommend everyday monitoring of SAA concentrations in patients with kidney allograft as a valuable aid in the early diagnosis and prediction of acute allograft rejection.

Serum amyloid A protein in patients with acute myocardial infarction.

The concentrations of four acute phase proteins were measured in sera of 40 patients with acute myocardial infarction (AMI) to evaluate their behaviour from day-to-day and to find out if they can serve for early prediction of postinfarction complications and mortality rate. Peak levels of serum amyloid A protein (SAA) were increased up to 5000-fold above the normal value and those of C-reactive protein (CRP) about 100-fold, 3 days after AMI. alpha 1-antichymotrypsin (ACT) and alpha 1-acid glycoprotein (AGP) peak levels were increased up to eightfold above their normal values. Patients who developed postinfarction complications had significantly higher SAA values on admission than those without complications (mean values of 379 and 45 mg/L, respectively; P < 0.0001). Using a level of 100 mg/L on admission as a reference value gave a reasonable sensitivity and predictive value for complications (73%) and a very good sensitivity (80%) for early prediction of fatal outcome. Patients with SAA values above this limit had double the risk of complications and four times the risk of a fatal outcome. The correlation with CRP values was lower than it was with SAA values (P = 0.028) using a level of 15 mg/L on admission as reference value gave low sensitivity (55%) and predictive value (60%) for complications as well as low sensitivity for early prediction of fatal outcome (60%). The present study did not allow prediction of complications or mortality based on ACT or AGP values.

The differential diagnostic capacity of serum amyloid A protein between infectious and non-infectious febrile episodes of neutropenic patients with acute leukemia.

We studied the behavior of four major acute phase proteins (SAA, CRP, ACT and AGP) in pyrexial occurrences of 16 neutropenic patients with acute leukemia. Altogether 37 febrile episodes were recorded; 27 were infectious in origin (microbiologically documented infection and clinically documented infection, MDI/CDI group) and 10 were pyrexias of unknown origin (PUO group). In the MDI/CDI group the mean value for the highest individual SAA concentration was 282 +/- 161 mg/l and in the PUO group 95 +/- 79 mg/l. The corresponding mean values were 4.0 mg/l (range 0.2-5.5 mg/l) in 10 control patients with 1 year remission and 0.8 mg/l (range < 0.1-1.2 mg/l) in 30 healthy adults. The peak value of SAA rose above 100 mg/l in 85% of our MDI/CDI pyrexias and in 40% of PUO. More reliable results were obtained when the difference between the value on the day when pyrexia occurred and the previous day was calculated. In that case, the difference was above 75 mg/l in 23 of 27 (85%) MDI/CDI pyrexias and in none of 10 (0%) PUO. In the MDI/CDI group the mean difference was 204 +/- 137 mg/l while it was only 26 +/- 19 mg/l in the PUO group. The statistical significance was very high (p < 0.0001). The CRP monitoring was very inferior to SAA while ACT and AGP monitorings were unsatisfactory.

Clinical relevance of serum amyloid A protein monitoring in urinary tract infections.

We have evaluated the clinical relevance of monitoring acute phase proteins in severe urinary tract infection. Body temperature, white blood cell count, erythrocyte sedimentation rate, serum amyloid A protein (SAA), C-reactive protein (CRP), alpha-1-antichymotrypsin (ACT) and alpha-1-acid glycoprotein (AGP) were determined daily in sera from 18 treated patients. Two patterns of response could be identified: responders and non-responders whose therapy had to be changed. Mean values for each acute phase protein were calculated daily in both responders and non-responders. Statistical evaluation of the significance between the means for each protein was also performed on a daily basis and showed P < 0.01 for SAA and CRP on day 3, for ACT on day 5, and for AGP on day 6. SAA and CRP appear to be the most reliable markers for antimicrobial therapy monitoring in patients with urinary tract infections.

A rapid enzyme-linked immunosorbent assay for serum amyloid A using sequence-specific antibodies.

A microtitre plate based enzyme-linked immunosorbent assay for determining the concentration of serum amyloid A (SAA) is described. The method employs easily produced sequence-specific rabbit antibodies and the preferential absorption of SAA to polystyrene, which obviates the use of capture antibodies and allows an assay time of only 3.5 h, so that the diagnostic potential of the SAA level as a rapid and reliable marker for inflammation can be fully exploited. The assay has a working concentration range of 0.1-2500 mg/L, which embraces the known biological variation of the SAA concentration. The intra-assay coefficient of variation (CV) for SAA concentrations above 10 mg/L is between 1.6 and 3.3% and the interassay CV between 3.0 and 4.2%. Recovery of SAA added to serum is from 96 to 102%.

Elevated serum level of glycolipid sulfotransferase in patients with hepatocellular carcinoma.

Activity of glycolipid sulfotransferase (cerebroside sulfotransferase) in serum was elevated in 21 (33%) of 63 patients with hepatocellular carcinoma (HCC, mean +/- S.E., 349 +/- 32 pmol/ml per h, n = 63, P less than 0.001) compared to healthy subjects (172 +/- 12, n = 85). Ho significant elevation of the sulfotransferase level was observed in liver cirrhosis (219 +/- 28, n = 10) in which many of biochemical HCC markers increase concomitantly. The elevation of sulfotransferase was independent of the production of alpha-fetoprotein and of aminotransferase levels in HCC, providing complementary value for alpha-fetoprotein-negative HCC cases. However, the sulfotransferase levels (234 +/- 21, n = 32, P less than 0.01) in sera from patients with renal cell carcinoma, in whose involved tissues the enzyme was demonstrated to increase markedly, were less than in HCC.

Histochemical demonstration of a delta 5,3 beta-hydroxysteroid dehydrogenase activity of cumulus cells related to the maturity and developmental potential of recovered oocytes.

A simple and rapid histochemical technique is described for demonstration of delta 5,3 beta-hydroxysteroid dehydrogenase activity in cumulus cells from preovulatory follicles aspirated for in vitro fertilization (IVF) of corresponding oocytes. Histochemical activity of delta 5,3 beta-hydroxysteroid dehydrogenase was demonstrated in samples of cumulus obtained from 62 oocytes recovered from 24 women. Patients were treated with clomiphene citrate in combination with human menopausal gonadotropins and human chorionic gonadotropin injections. The cumulus was found to contain small and large cell types. Small cells possessed more delta 5,3 beta-hydroxysteroid dehydrogenase activity predominantly in the area near the oocyte. Cytoplasmic vacuolation has been noted in large, pale cells with moderate or low enzyme activity. The most active cells were predominant in cumulus from which oocytes were fertilized. Significant differences have been found between high and low delta 5,3 beta-hydroxysteroid dehydrogenase activity of cumulus cells from mature oocyte-corona-cumulus complexes leading to a successful fertilization and cleavage of oocytes and between groups with different histochemical activity when aspirated complexes were scored immature and the IVF of oocytes has failed.

Presence and characterization of glycolipid sulfotransferase in human cancer serum.

Sulfotransferase, which catalyzes sulfation of the carbohydrate of galactosylceramide (GalCer) and is localised in the Golgi membrane of cells, was assayed for activity in human serum. To do this, an organic solvent was added to the incubated reaction mixture containing GalCer as an acceptor and phosphoadenosine phospho[35S]-sulfate as a donor of sulfate to dissociate the synthesized sulfolipid from serum protein. This was followed by isolation of the sulfolipid on an anion-exchange column. Through this procedure, human serum was found to contain sulfotransferase activity. The serum enzyme was activated by Mn2+. Km values of the enzyme for GalCer and 'active sulfate' were 4.6 microM and 5.2 microM, respectively. The enzyme activity was assayed in sera of cancer patients. The serum activity (mean +/- SE, 0.27 +/- 0.027 pmol.microliter-1.h-1) in renal cell carcinoma patients, whose activity has been demonstrated to be elevated, was significantly (P less than 0.005) increased compared to that of the normal control (mean +/- SE, 0.18 +/- 0.0014 pmol.microliter-1.h-1) and of other urological tumors examined.