Acute Phase Reactant Protein Research Articles

Localization of amyloid P component in human brain: Vascular staining patterns and association with alzheimer's disease lesions

Amyloid P component is a normal serum protein that is highly conserved across phylogeny. Although it resembles the classic acute-phase reactant C-reactive protein, and is considered to be a normal extracellular matrix component, its physiologic role in humans is unknown. Amyloid P component is also colocalized with accumulations of all recognized forms of amyloid. The present study uses light and electron microscopy to compare the cerebral localization of amyloid P component in cases with (n = 19) and without (n = 15) Alzheimer's disease (AD). In non-AD cases, amyloid P component was predominantly localized to the cerebrovasculature. Perivascular staining was observed in most cases, more so in the white than in the gray matter. In AD cases, amyloid P component was localized to all three characteristics histopathologic lesions, namely, neurofibrillary tangles, senile plaques, and amyloid angiopathy. Furthermore, in cases with prominent staining of gray matter parenchymal lesions, intravascular staining was decreased. Given the fixation and processing methods used, amyloid P component was never seen to be localized to the cerebrovascular basement membrane. These data argue against amyloid P component's postulated role as the anchor for vascular beta-amyloid deposition. Because there is no evidence for intrinsic amyloid P component production in brain, its perivascular and parenchymal distributions suggest either compromise of the blood-brain barrier or transport across vascular endothelium.

Acute-phase reactant proteins and antioxidants in rats intoxicated chronically with paraquat.

Paraquat dichloride at 250 ppm in the diet was fed continuously to rats. Though no apparent effect of paraquat was observed until 10 d, some rats then began to show several symptoms such as diarrhea, anorexia, epistaxis, and hypokinesia, and in some cases rats died after this period. The biochemical examination of plasma components revealed appreciable changes in the concentrations of an acute-phase reactant protein and some vitamins that act as antioxidants. alpha-Cysteine proteinase inhibitor increased by 5-fold, and vitamin C and its radical increased by 1.5- and 1.7-fold, respectively, whereas alpha 1 proteinase inhibitor decreased slightly. Paraquat enhanced the cysteine proteinase inhibitor levels in lung, liver, and kidney by 6.2-, 6.0-, and 4.5-fold of control, respectively. Among three components of alpha-cysteine proteinase inhibitor, the T kininogen level of treated rat plasma was about eight-fold higher than control, whereas the high-molecular-weight kininogen level was unchanged. The large increment of T kininogen was also seen in lungs of the treated rats.

Prognostic factors in lung cancer: tables and comments.

Prognostic factors (PF) have a pivotal role in Clinical Oncology. They are helpful in the selection of treatment, provide insights into the disease process and the therapeutic response, and are fundamental in the design of clinical trials or in the interpretation of data from the literature. The number of possibly useful PFs in lung cancer is large (certainly more than one hundred). This paper attempts to provide a comprehensive listing of PFs and other variables potentially associated with outcome of lung cancer. This is achieved using tables, where studies relevant to each PF are referenced in relationship to their results, statistical power, type of analysis, number of variables incorporated in multivariate tests, and cell type. Tables include the outcome of an extensive retrieval of the literature and indicate visually where much of the evidence resides for the contribution of a variable to prognosis. Each table is briefly discussed and systematically comprises one group of PFs. Among the many pinpointed, the best predictive models still belong to studies based on clinical and routine laboratory data. Recent researches have clarified the role of new PFs (such as the biological factors); others (e.g. quality of life measures, the serum content of acute phase reaction proteins or the pathological evidence of tumour neoangiogenesis) might be recognized as important in the future. Like infinity, the fate of the individual patient will never become a completely measurable entity. However, as the discovery of new PFs proceeds, the assessment of the future prospects for patients is becoming more reliable.

Fibrinogenolysis by a neutrophil membrane protease generates an A alpha 1-21 fragment.

The 600 kDa neutrophil membrane neutral protease, which had been shown to generate bioactive peptides from the acute-phase reactant C-reactive protein, has now been shown to have fibrinogenolytic activity that is distinct from fibrinogenolysis by plasmin and neutrophil lysosomal enzymes. This protease gradually reduces the apparent molecular mass of fibrinogen (340 kDa) to non-clottable products and generates terminal products with apparent molecular mass values of 270 kDa, 200 kDa, 100 kDa and less than 40 kDa through cleavage of all three of the constituent chains. Characteristics of fibrinogenolysis by this neutrophil protease are cleavage of the bond between amino acids valine and glutamic acid at positions 21 and 22 respectively from the N-terminus of the A alpha chain to release an A alpha 1-21 peptide, digestion of the B beta chain at positions within the C-terminus, and proteolysis of the bond between amino acids isoleucine and glycine at positions 394 and 395 respectively from the N-terminus of the gamma chain. This generates products that lack anticoagulant activity. The thrombin clotting time of the product with an apparent molecular mass of 330 kDa was prolonged, although clot formation was still observed. Loss of coagulability and inability to clot was found with further degradation of fibrinogen to an apparent molecular mass of 290 kDa. Activity of this neutrophil membrane protease in vivo could be important for the regulation of fibrin deposition at sites of inflammation, and may contribute to the reported plasma levels of the A alpha 1-21 peptide.

Expression of the pancreatic secretory trypsin inhibitor gene in the liver infected with hepatitis B virus

Pancreatic secretory trypsin inhibitor, an acute phase reactant protein, is expressed in the liver in response to inflammatory cytokines, especially in hepatocellular carcinoma. Northern blots of 25 dissected liver tissues from non-hepatitis, chronic hepatitis and cirrhosis patients revealed that 10 (40%) expressed pancreatic secretory trypsin inhibitor. The expression seemed to be closely associated with hepatitis B viral infection, since among the 11 hepatitis B virus-infected samples, nine (81%) were pancreatic secretory trypsin inhibitor-positive. In contrast, this augmented expression was absent in non-infected livers (0/5; 0%), and rare in those infected with hepatitis C virus (1/9; 11%). There was no significant correlation between the pancreatic secretory trypsin inhibitor expression in the liver and the serum level of glutamic pyruvic transaminase, the hepaplastin test, the 15-min retention rate of indocyanine green, or the histological findings of the liver tissues such as lymphocyte infiltration and pseudolobular formation. Furthermore, we identified an almost three-fold increase in the transactivation of pancreatic secretory trypsin inhibitor gene expression in HepG2 cells after transient transfection with HBV-DNA or the X gene in an expression vector. These results suggest that the induction of pancreatic secretory trypsin inhibitor gene expression in livers with chronic hepatitis and cirrhosis is directly affected by hepatitis B virus.

Il-6 levels, area of burn and the acute-phase reactant protein response

Il-6 levels, area of burn and the acute-phase reactant protein response

Ascites levels of haptoglobin in patients with ovarian cancer

Haptoglobin is an acute-phase reactant protein involved in immune regulation. It has been isolated from malignant ovarian ascites and has been shown to be capable of mediating nonspecific immune suppression in vitro in humans and in vivo in experimental animals. The range of concentrations under which such a nonspecific suppression is observed lies well within concentrations of haptoglobin observed in vivo. This immune suppression could adversely affect patient outcome. Based on this information, ascites haptoglobin levels of 21 consecutive patients with ovarian cancer who underwent initial surgical debulking were determined. After the patients received chemotherapy, they were divided into those having a positive and those have a negative second-look operation. Seventeen patients with positive pathology at second look had an initial mean ascites haptoglobin level of 99 +/- 49 mg/dl. The mean haptoglobin level in the four patients with negative findings was 67 +/- 42 mg/dl. The difference in these mean haptoglobin levels is not statistically significant (P > 0.05). Although the number of patients in this study is small, the wide range of values documented in both groups make it doubtful that an initial absolute ascites haptoglobin level will prove clinically prognostic of eventual disease status at the time of second look laparotomy.

Evaluation of serum amyloid A protein as an acute-phase reactive protein in horses.

Serum amyloid A protein (SAA) was isolated from equine acute-phase serum by repeating Sephadex G-75 gel filtration 3 times. Quantitative measurement of equine SAA was performed by the single radial immunodiffusion technique with rabbit anti-equine SAA serum. In clinically normal horses, the SAA concentration remained relatively high from immediately after birth up to 1 week of age. After this the concentration showed periodic fluctiation in the range of approximately 13 to 30 micrograms/ml. The mean (+/- SD) concentration of SAA in foals (< or = 12 months old) and in adult horses (> or = 18 months old) was 19.37 +/- 9.41 and 21.53 +/- 9.81 micrograms/ml, respectively. In mares during the perinatal period, the SAA concentration remained stable and within the normal range for 4 months before parturition. After foaling, it increased quickly and reached a peak value of 136.78 +/- 56.74 micrograms/ml on day 3 postpartum, and then began to decrease at 2 weeks postpartum returning to within the normal range by 1 month postpartum. In horses with experimentally induced inflammation, the SAA concentration increased quickly, and reached the highest value, approximately 4 to 20 times higher than pre-treatment values, on day 2 after treatment. It then returned to the base line values within 10 days to 4 weeks, concurrent with the disappearance of local inflammatory signs. The SAA concentration was very high in most horses with clinical signs of inflammation. It was concluded from these data that equine SAA was a sensitive acute-phase reactive protein which increased in the early phase of various acute inflammations.

Elevation of serum ceruloplasmin levels in brain tumours.

Serum ceruloplasmin levels have been estimated in 80 patients with various intracranial space occupying lesions and in 30 controls. The ceruloplasmin levels were significantly increased in all brain tumours except in meningiomas. After therapy, the ceruloplasmin levels were still significantly increased when compared to controls and their respective preoperative values. However, the rise in levels of ceruloplasmin in malignant tumours compared to benign was statistically not significant. It is concluded that ceruloplasmin may have a role to play as an acute phase reactant protein in brain tumours.

Acute phase reactant proteins--an aid to monitoring surgical treatment of laryngeal carcinoma.

The serum concentration of four acute phase reactant proteins (haptoglobin, sialic acid, alpha 1-antitripsin, ceruloplasmin) were determined in 160 patients with laryngeal cancer. In 50 cases treated by surgery serial determinations were performed. The control group included healthy persons and patients with non-neoplastic diseases. The levels of haptoglobin, alpha 1-antitripsin and sialic acid were significantly higher in cancer patients than in control group. The levels of ceruloplasmin reveals no statistically significant difference between particular groups of patients. The serum concentrations of haptoglobin, alpha 1-antitripsin and sialic acid correlated with the clinical status of cancer patients. We suggest that serial determination of certain acute phase reactant proteins may be useful as a prognostic acid in following patients with laryngeal carcinoma.

Differential induction of heme oxygenase in the hepatocarcinoma cell line (Hep3B) by environmental agents.

In situ hybridization and Northern analysis of heme oxygenase (HO) mRNA was used to determine the induction and expression of HO by various environmental agents. Exposure of Hep3B cells to hemin (10 microM) for as little as 5 min resulted in significant production of HO transcripts and mRNA expression as seen by in situ hybridization. We followed the pattern of HO transcript accumulation by heme and results indicate that the peak of induction of HO by heme was reached between 10 and 20 minutes. Other metalloporphyrins were all effective in inducing HO mRNA after 1 h exposure. On the other hand, CoCl2 caused accumulation of HO mRNA at a later time than seen with the metalloporphyrins. However, lipopolysaccharide (LPS) gave a more immediate effect on HO induction which was somewhat similar to heme in its time course. Direct measurements of HO activity revealed that enzyme activity could be detected after about 20 min exposure to hemin, and this activity was inhibited by tin protoporphyrin (SnPP). The different pattern of HO mRNA induction by LPS as contrasted with CoCl2 suggests that LPS may act through a different translational factor, or stimulate free radical formation and the subsequent release of heme and induction of HO. These results indicate that heme causes accumulation of HO mRNA by a different mechanism than that of CoCl2. Finally, LPS shares a concomitant effect on induction of HO as an acute phase reactant type protein.

Isolation and characterization of α1-acid glycoprotein from horses, and its evaluation as an acute-phase reactive protein in horses

Summary Equine α1-acid glycoprotein (α1ag) was isolated from equine serum by successive ammonium precipitation, anion- and cation-exchange chromatographies, and gel filtration. Purified equine α1ag had a molecular weight of 46,000 ± 1,000, and contained 31.4% carbohydrate. Gel isoelectric focusing revealed an isoelectric point range of 2.8 to 3.7. With immunoelectrophoresis, it was found that α1ag migrated to the α1-globulin region. Single radial immunodiffusion was used for quantitative measurement of α1ag in equine serum. In clinically normal foals, serum α1ag was undetectable (≤ 20 ng/ml) in ≤ 7-day-old foals, but was detected by 14 days. The α1ag concentration (mean ± sd) increased to reach mean adult values of 99.23 ± 26.90 μg/ml by 1 year of age. The α1ag concentration in pregnant mares decreased at 2 to 3 months before parturition, then gradually increased until 1 day after parturition, when a brief decrease was observed. The concentration increased again at 2 weeks after foaling, then a decrease was observed, after which the α1ag concentration increased again by 2 to 4 months after parturition. The concentration of serum α1ag quickly rose to peak values 2 to 3 days after castration and jejunojejunostomy in adult horses, returning to baseline values by 14 to 28 days after surgery. The α1ag was concluded to be an acute-phase reactive protein in horses.

Relationship between fumonisin contamination of feed and mystery swine disease. A case-control study.

Fumonisin is a recently identified mycotoxin that has been shown to be the cause of pulmonary edema disease in swine and leukoencephalomalacia in horses. Mystery Swine Disease (MSD), is an economically devastating disease complex of unknown etiology that has been reported to have occurred in several swine producing states since 1988. To determine the relationship between MSD and fumonisin, a case-control study was carried out in Illinois in mid-1990. Feed samples collected from 12 case and 9 control farms were analyzed for fumonisin. Sera from swine on all farms was screened for titers against encephalomyocarditis (EMC) virus and concentrations of alpha-1 acid glycoprotein (an acute phase reactive protein). Fumonisin concentrations greater than or equal to 20 ppm were found on 1 control farm (1/9) and 8 case farms (8/12). Titers against EMC virus (greater than or equal to 1:16) were found on 5 control farms (5/9) and on 6 case farms (6/12). Farms with greater than or equal to 20 ppm fumonisin in the feed were at significantly increased risk (OR = 11.2, Fisher's exact test p = 0.037) for MSD. Furthermore, the pi2 test for trend was (p = 0.017), meaning that as the level of fumonisin in the feed increased, the risk of MSD also increased. The presence of EMC virus titers in the sow herd was not a significant risk for MSD (OR = 1.25, Fisher's exact test p = 0.75). Alpha-1 acid glycoprotein concentrations obtained from a 2-week old nursing pigs differed significantly (p = 0.0005) between MSD case and control herds.

Further explorations of abnormalities in serum proteins following burns

This report extends our earlier studies of the abnormal protein bands found in burn sera by use of Western blotting and ion exchange chromatography. The current studies indicated that some of the protein bands contained materials with immunosuppressive activity. One of these materials cross reacted with anti human haptoglobin antibody. Many of the other proteins in the bands were found to be acute phase reactant proteins without immunosuppressive activity. Some proteins in these bands have not yet been characterized or tested for immunosuppressive activity.

Isolation, characterization, and quantitative analysis of ceruloplasmin from horses

SUMMARY Ceruloplasmin (Cp) was isolated from fresh equine plasma by precipitation, cellulose chromatography, and improved ion-exchange chromatography. Purified equine Cp is a glycoprotein having a molecular weight of approximately 115,000. In electrophoresis, equine Cp migrated to the α1-globulin region, its isoelectric point was about 4.15 and consisted of about 890 amino acid residues. Serum Cp concentration was measured by use of the single radial immunodiffusion method. In clinically normal horses, the mean (± sd) serum Cp concentration of newborn foals was 2.87 ± 0.40 mg/ml and that of 3-month-old foals was 5.02 ± 0.92 mg/ml, which was similar to the adult value. It reached a peak of 6.06 ± 0.74 mg/ml in 2-year-old horses. The Cp concentration in mares was not statistically different for the perinatal period, but it decreased immediately before and after delivery. Concentration of Cp increased at 6 days after im administration of turpentine oil, castration, or jejunojejunostomy in adult horses, and increased to peak values twice as high as baseline values at 7 to 14 days, returning to baseline values at 28 days after treatment. We concluded that equine serum Cp is an acute-phase reactive protein increased in the intermediary or later phase of acute inflammation.

Haemostasis and parturition revisited: Comparative profiles in mammals

The influence of parturition on plasma concentrations of fibrinogen, fibronectin and von Willebrand factor is compared in the canine, porcine, equine, bovine and human species. The significance of the alterations in these proteins at parturition is discussed in relation to their role in haemostasis, cellular adhesion reactions, and as acute-phase reactant proteins. The effect of hormones on the expression of these proteins in whole animal and cultured cell systems is briefly reviewed

Reduced Levels of Galactose-Terminated Glycoproteins in Rat Serum during Perinatal Development

Asialoglycoprotein receptor is an abundant protein localized in the sinusoidal domain of the hepatocyte plasma membrane. Its principle function is the clearance of serum glycoproteins which include several acute phase reactant proteins that have lost their terminal sialic acid residue. It has been reported that asialoglycoprotein receptor is nearly absent in mammalian fetal liver but rises to adult levels during the early postpartum period. The hypothesis to be tested was to determine whether defective glycoproteins, those lacking terminal sialic acid residues, are accumulated in fetal serum as a result of reduced receptor content. It was found that low levels of asialoglycoprotein receptor in 18-day-old fetal liver correlated to a threefold higher level of total asialoglycoproteins in fetal serum than adult serum as determined by a modified Western blot protocol employing radioiodinated ricinus communis agglutinin, a galactose-binding lectin. As hepatic asialoglycoprotein receptor accumulated at the time of birth, the elevated level of serum asialoglycoproteins decreased to adult values in an opposite manner. This study indicates that the hepatic asialoglycoprotein receptor plays an important role in reducing the amount of circulating defective glycoproteins at the time of birth.

Serum C-Reactive Protein(CRP) in Horses: The Effect of Aging, Sex, Delivery and Inflammations on Its Concentration.

The serum concentration of C-reactive protein (CRP) in horses was measured by single radial immunodiffusion (SRID) using rabbit anti-equine CRP serum to evaluate the significance of CRP as an acute-phase reactive protein. In serum samples of clinically normal newborn thoroughbred foals before being given colostrum, serum CRP was not detectable (less than or equal to 1 microgram/ml). The serum CRP concentration was found to increase quickly and reach a peak level of approximately 14.1 micrograms/ml in 12-month-old horses. Then, it decreased gradually to reach a low value of 5.4 micrograms/ml in the 4-year-old. In horses over 5-year-old, serum CRP concentration was stable at values of 7 to 8 micrograms/ml. In mares during the peri-natal period, serum CRP concentration decreased at 2 months before delivery, showed moderate changes just before and after delivery, and then increased to relatively high level by 2 months after delivery. The concentration of serum CRP was found to be increased at 24 hours after experimentally inflammatory stimuli in adult horses, and reached peak values of 3 to 6 times as high as the base line values at 3 to 5 days. Serum CRP concentration returned to base line values by 2 to 3 weeks after treatments. It is clear from these data that CRP is one of the acute-phase reactive proteins in horses.

Acute phase protein levels as an index of severity of physical injury

Inflammation resulting from any form of tissue injury causes an increase in plasma concentration of a number of liver-derived proteins (the acute phase reactant proteins), the measurement of which provides an indication of the magnitude of the inflammatory response. C reactive protein (CRP) is an example of an acute phase protein. Although concentrations increase particularly dramatically in response to inflammation and reflect the degree of ongoing tissue damage, this method has yet to be used to assess severity of injury in traumatology and forensic medicine. The rate at which the acute phase protein response occurred after injury was therefore explored in a series of 16 patients with maxillofacial skeletal injuries and in a series of 22 age- and sex-matched control patients. Increases in the plasma concentration of CRP were not detected until 6–12 h after injury and peaked at 48–72 h. Concentration of CRP was <10 mgm/l in all control patients. There was significant relation between peak levels and Abbreviated Injury Scale and Injury Severity scores. Results suggest that this method of assessing the severity of traumatic injury deserves further investigation and may be of use clinically, medico-legally and in relation to compensation awards.

Partial hepatectomy and mediators of inflammation decrease the expression of liver α2-HS glycoprotein gene in rats

Liver mRNA levels of two acute phase reactant (APR) proteins, α2-HS glycoprotein (a major negative APR) and α1,-acid glycoprotein (a major positive APR) were measured in male rats at different times after the administration of turpentine, of tumor necrosis factor, or following partial hepatectomy. In every case, a marked decrease in mRNA levels of α2HS glycoprotein was observed which reached a maximum at 24 h. A concomitant increase of α1,-acid glycoprotein mRNA levels was observed under the same conditions. These results indicate that the decreased levels of α2-HS glycoprotein induced by the acute-phase response following inflammatory mediators and partial hepatectomy are due to a down-regulation of the gene expression of this protein in rat liver.