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P Kuusela

Publications and source records attributed to P Kuusela.

At least 19 recordsLinked to original sources
PubMed1992

Elevated CA19-9 as the most significant prognostic factor in advanced colorectal carcinoma.

Tumor markers such as carcinoembryonic antigen (CEA) and CA19-9 were analyzed as response indicators and prognostic factors in advanced colorectal carcinoma. Eighty-five patients participated in a phase II chemotherapy study from October 1984 to July 1990. A three-drug schedule was administered including low dose epirubicin and sequential methotrexate 5-fluorouracil, followed by leucovorin rescue. Serum specimens for CEA and CA19-9 were obtained prior to the initiation of chemotherapy, and subsequently at 4-6 weeks' intervals. In univariate analysis Karnofsky, the site of the primary tumor, the extent of metastases, the presence of abdominal or liver metastases, serum CEA (cut-off of 20 micrograms/l), and CA19-9 levels correlated with survival. In stepwise multivariate analysis an elevated CA19-9 level, a poor Karnofsky, and the presence of liver metastases were independent adverse prognostic factors. Tumors originating from the left colon had a better prognosis than the others. This was related to a higher response rate in this patient group. Serum CA19-9 level was the most significant prognostic factor whether it was entered as a continuous or as a dichotomized variable into the model. The median survival of patients with a normal CA19-9 level was 30.0 months (lower 95% confidence interval: 16.4 months; upper limit was not calculable), and with an elevated CA19-9 value 10.3 months (8.0-12.6 months, 95% confidence interval). Five of 85 patients had a complete response and 20 a partial response, the overall response rate being 29%. When compared with tumor shrinkage, "CEA response" and "CA19-9 response" had a sensitivity of 84% and 88% and specificity of 77% and 67%, respectively. In conclusion, serum CEA value seems to be the best tumor marker for response prediction, while CA19-9 level is one of the best available prognostic indicators in advanced colorectal carcinoma.

Adult↗
PubMed1992

Binding of plasminogen to Neisseria meningitidis and Neisseria gonorrhoeae and formation of surface-associated plasmin.

Forty-two strains of Neisseria meningitidis and 17 of Neisseria gonorrhoeae were tested for their ability to interact with 125I-labeled Glu-plasminogen. All strains tested reacted substantially with plasminogen, resulting in uptake values of 20%-48%. Scatchard analysis with selected N. meningitidis strains demonstrated a dual-phase receptor interaction, one more avid receptor with a Kd of 50 nM and 3000-6000 receptors per bacterium and a second receptor with a Kd of 200 nM and 10,000-20,000 receptors per bacterium. Plasminogen uptake could be completely eliminated by low concentrations of epsilon-aminocaproic acid, suggesting that the lysine binding sites on the plasminogen molecule are involved in the receptor-ligand interaction. The binding of plasminogen to the bacterial receptor facilitates the tissue-type plasminogen activator-mediated conversion to Glu-plasmin, which also modifies itself to the Lys form. Receptor-associated plasmin is enzymatically active, monitored as a breakdown of the chromogenic substrate S-2251, and retains its activity in the presence of naturally occurring inhibitors in plasma.

Aprotinin↗
PubMed1992

Surface-associated activation of plasminogen on gram-positive bacteria. Effect of plasmin on the adherence of Staphylococcus aureus.

In this article we review a novel type of plasminogen activation on staphylococcal and streptococcal cells. The activation mechanism implies a specific binding of glu-plasminogen to bacterial surface via the lysine-binding sites of plasminogen. Association of plasminogen with bacterial surfaces greatly enhances the t-PA mediated activation which takes place only poorly in solution. The end product, surface-associated plasmin, is enzymatically active, protected against high molecular weight plasmin inhibitors and capable of converting itself from glu-plasmin to the lys-form. The modification is associated with an increased affinity of the bound lys-plasmin towards the binding molecules on bacterial surface. This novel way of retaining plasmin on the surface may be important for the bacteria to invade and penetrate surrounding tissues. Our data on the effect of plasmin on staphylococcal adherence indicate that plasmin is not very effective in cleaning bacteria from surfaces coated with extracellular matrix components, fibronectin and fibrinogen.

Bacterial Adhesion↗
PubMed1992

Tissue-type plasminogen activator-mediated activation of plasminogen on the surface of group A, C, and G streptococci.

The interaction of Glu-plasminogen with group A, C, and G streptococci and subsequent formation of surface-associated plasminogen by tissue-type plasminogen activator (t-PA) were studied. Binding of 125I-Glu-plasminogen to streptococci greatly facilitated its activation to 125I-Glu-plasmin by exogenous t-PA, whereas activation in the absence of bacteria took place only slowly. Glu-plasmin formed on the streptococcal surface was further converted to the Lys form. Similar activation and modification took place also in the presence of plasminogen-depleted plasma, containing functional t-PA and plasmin inhibitors, indicating that the surface-associated enzymes were protected against these inhibitors. Lys-plasminogen was 10- to 30-fold more potent than Glu-plasminogen or Glu-plasmin in inhibiting the binding of 125I-Glu-plasminogen to streptococci. This indicated a higher affinity of the Lys form towards plasminogen-binding molecule(s) on the streptococcal surface. The surface-associated plasmin was also enzymically active as judged by digestion of chromogenic substrate S-2251. Surface-associated plasmin activity was observed only when the incubations were carried out in the presence of t-PA and Glu-plasminogen or human plasma as the source of plasminogen. Under these conditions, soluble enzymatic activity was also recovered in the supernatant of group A streptococci. This favors the idea that plasmin can be released from the bacterial surface. The findings provide a mechanism for streptococci to adopt proteolytic activity by binding a host-derived enzyme zymogen on their surface, where the subsequent activation then takes place. The results suggest a role for surface-associated plasmin activity in tissue tropism and tissue invasiveness of streptococci.

Aprotinin↗
PubMed1992

Adhesion protein YadA of Yersinia species mediates binding of bacteria to fibronectin.

The interaction between fibronectin and Yersinia strains was studied. Wild-type Y. enterocolitica strains expressing the virulence-plasmid-encoded adhesion protein YadA adhered strongly to fibronectin-coated coverslips, while their plasmid-cured variants expressed weaker binding. The cloned yadA gene of Y. enterocolitica or Y. pseudotuberculosis conferred fibronectin-binding ability both to Escherichia coli and to Y. psuedotuberculosis strains lacking the YadA protein. The YadA protein did not mediate binding to isolated fragments of fibronectin or to soluble fibronectin.

Adhesins, Bacterial↗
PubMed1992

Tumour markers CA 19-9 and CA 50 in digestive tract malignancies.

CA 19-9 and CA 50 are tumour marker tests measuring the same carbohydrate structure, sialosyl-fucosyl-lactotetraose--that is, the sialylated Lewis blood group antigen. In addition, the C50 antibody reacts with sialosyl-lactotetraose, which may be expressed in small amounts in some carcinomas. In this study we compared these tests in sera from patients with benign and malignant digestive tract diseases. The sensitivity of the markers for different cancers was also compared at several specificity levels with patients with benign diseases as reference groups. Both markers showed a high sensitivity for pancreatic cancer (77% for CA 19-9; 69% for CA 50) and biliary cancer (88%). The figures in colorectal cancer were almost as high as those reported for CEA; 16-21% elevated values in Dukes A and B tumours and 44-47% in Dukes C and D tumours. The sensitivity for gastric cancer was 48% for both markers. CA 50 had a higher sensitivity for liver cancer (55%) than CA 19-9 (9%), but the proportion of elevated values in benign liver diseases was also higher (33% versus 15%, respectively). Overall, there was good correlation between the CA 19-9 and CA 50 levels, and the difference in sensitivity and specificity was marginal. In clinical practice the greatest value of CA 19-9 and CA 50 is in the diagnosis of pancreatic cancer.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1991

Disulfide-bonded dimerization of fibronectin in vitro.

Human plasma fibronectin was denatured with 8 M urea and reduced with dithiothreitol. Dialysis or dilution of the solution led to formation of fibronectin dimers which migrated in non-reducing SDS/PAGE similarly to untreated control protein. When the redimerized fibronectin was reduced and re-electrophoresed it formed a doublet of alpha and beta chains of equal intensity indicating that it was a heterodimer. Low concentrations (less than 1 mM) of Fe3+ enhanced the redimerization of fibronectin, suggesting that metal ions may mediate oxidative reactions in the formation of the disulfides. Consequently, redimerization of fibronectin was completely prevented by deferoxamine, an iron chelator. Dimerization of fibronectin took place most effectively at pH greater than or equal to 8.8 but decreased strongly at lower pH, representing more unfavourable conditions for the action of the thiolate anion in the thiol/disulfide exchange reaction. Redimerized fibronectin, however, lost many of its binding properties to macromolecular ligands, suggesting that the disulfide bonding did not entirely regenerate the proper conformation of the protein. Pulse/chase experiments of fibroblast cultures showed that the initially monomeric fibronectin was rapidly and quantitatively dimerized under conditions representing natural pH and environment. SDS/PAGE analysis of the dialyzed urea-denatured/reduced thrombin and plasmin digests of fibronectin revealed that the NH2-terminal 30-kDa fragment and other fragments that contained intrachain disulfides quantitatively regained their non-reduced electrophoretic mobility. The results show that the dimerization and formation of intrachain disulfides of fibronectin may occur, in part, spontaneously, based on the amino acid sequence information of the protein. However, complete disulfide formation may also need other factors, present only in living cells, as suggested by pulse/chase experiments in fibroblasts.

Cells, Cultured↗
PubMed1991

Biphasic reduction and concanavalin A binding properties of serum alpha-fetoprotein in preterm and term infants.

Reference values for postnatal serum alpha-fetoprotein (AFP) and concanavalin A (ConA) binding subfractions of AFP in preterm and term infants are presented. Preterm infants had 10-fold higher serum concentrations of AFP than did term infants at birth. The reduction of serum values of AFP was biphasic in both groups and differed significantly between the two groups. The first declining phase continued for approximately 4 months in preterm and for 2 months in term infants, and was related to the degree of prematurity. The AFP values reached adult levels by 12 months in preterm and by 9 months in term infants. The developmental pattern of the carbohydrate moiety of AFP was determined by ConA fractioning. The proportion of the ConA nonreactive subfraction of AFP in preterm and term infants at birth was 6% and 13%, respectively; it increased more rapidly in term than in preterm infants but reached 85% to 95% by the age of 6 months in both infant groups. Our results indicate that the postnatal maturation of AFP synthesis is dependent on gestational age. Malignant recurrences of neonatal sacrococcygeal teratomas were associated with an increase in serum concentration of AFP and a decrease in the proportion of the ConA nonreactive subfraction of AFP.

Concanavalin A↗
PubMed1991

Comparison of a new tumour marker CA 242 with CA 19-9, CA 50 and carcinoembryonic antigen (CEA) in digestive tract diseases.

The levels of CA 242, a new tumour marker of carbohydrate nature, were measured in sera of 185 patients with malignancies of the digestive tract and of 123 patients with benign digestive tract diseases. High percentages of elevated CA 242 levels (greater than 20 U ml-1) were recorded in patients with pancreatic and biliary cancers (68%). The sensitivity was somewhat lower than that of CA 19-9 (76%) and CA 50 (73%). On the other hand, in benign pancreatic and biliary tract diseases the CA 242 level was less frequently elevated than the CA 19-9 and CA 50 levels. The serum CA 242 concentration was increased in 55% of patients with colorectal cancer. CA 242 detected more Dukes A-B carcinomas (47%) than CEA (32%), whereas CEA was more often elevated (71% vs 59%) in Dukes C-D carcinomas. CA 242 was slightly elevated (ad 41 U ml-1) in 10% of patients with benign colorectal diseases. CA 50 and CA 19-9 had lower sensitivities than CA 242 using the recommended cut-off values. When cut-off levels based on relevant benign colorectal diseases were used, the sensitivities of these markers were similar and somewhat higher than that of CEA. Less than half of patients with gastric cancer (44%) had an elevated CA 242 serum level. CA 242 is a promising new tumour marker, that may be of additional value in the diagnosis of pancreatic and biliary, as well as colorectal cancer, and may be useful in monitoring cancer patients after radical surgery.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1991

Multifunctional nature of P fimbriae of uropathogenic Escherichia coli: mutations in fsoE and fsoF influence fimbrial binding to renal tubuli and immobilized fibronectin.

P fimbriae of the F7(1) serotype of Escherichia coli are composed of a major subunit, FsoA, and of three minor proteins named FsoG, FsoE, and FsoF. FsoG is the Gal alpha(1-4)Gal-specific lectin. We assessed mutated recombinant strains each deficient in one fimbrial component for adhesion to frozen sections of rat cortical kidney and to fibronectin immobilized on glass. Rat kidney lacks the Gal alpha(1-4)Gal-containing glycolipids. The fsoG mutant strain was as adhesive to sections of rat kidney and to fibronectin-coated glass as was the recombinant strain expressing the complete fso gene cluster. The fsoA mutant strain was highly adhesive to fibronectin and to kidney sections. In the rat kidney, the adhesion of these strains was predominantly localized to sites of basolateral membranes of tubuli. The fsoE and the fsoF mutant strains were slightly less adhesive to kidney structures and failed to adhere to fibronectin. The fsoE, fsoF double mutant strain adhered neither to fibronectin nor to kidney sections. None of the fso recombinant strains reacted with soluble fibronectin, suggesting that the interaction is dependent on the conformation of the fibronectin molecules. Recombinant strains expressing the F7(2), F8, F11, F13, and F14 serovariants of the P fimbria also showed adherence to immobilized fibronectin. The results show that in addition to binding to globoseries of glycolipids via the G protein, the P fimbriae of uropathogenic E. coli exhibit a tissue-binding property influenced by fsoE and fsoF gene products and with affinity for basolateral membranes and fibronectin.

Amino Acid Sequence↗
PubMed1991

Tumour marker CA 125 in patients with digestive tract malignancies.

The serum levels of tumour marker CA 125 were measured in 162 patients with various digestive tract malignancies and in 155 patients with benign digestive tract diseases. The highest frequency of elevated CA 125 values (greater than 35 U ml-1) was found in patients with liver cancer (78%), but the level was equally often elevated in liver cirrhosis (78%). Two-thirds of the patients with biliary tract cancer had an increased CA 125 concentration, while four patients with benign biliary diseases had an elevated value. The serum level of CA 125 was elevated in only 20% of 60 patients with primary colorectal cancer, and in none of those with local disease (Dukes A or B). The CA 125 concentration seldom increased in patients with recurrent colorectal carcinoma. Twenty-three per cent of 44 patients with gastric cancer had an elevated CA 125 value. Two of 33 patients with benign colorectal and one of 68 patients with benign gastric diseases had an increased CA 125 concentration. The serum values of CA 125 showed no correlation with those of tumour markers alphafetoprotein (AFP), carcinoembryonic antigen (CEA) or CA 19-9. AFP was superior to the other markers in the diagnosis of liver diseases, while CA 19-9 showed the greatest accuracy in gastric diseases. In colorectal diseases, CEA had a higher sensitivity, but a lower specificity than CA 125 and CA 19-9. CA 125 and CA 19-9 had similar sensitivities for biliary tract cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1991

Serum carcinoembryonic antigen and DNA ploidy in colorectal carcinoma. A prospective study.

We have analysed the relationship between carcinoembryonic antigen (CEA) and DNA ploidy prospectively in 130 colorectal carcinoma patients. CEA was elevated preoperatively significantly more often in patients with DNA-aneuploid tumours than in DNA-diploid or DNA-tetraploid tumours--that is, in 48% (36 of 75) of patients with aneuploid tumours, in 34% (14 of 41) of patients with diploid tumours, but only in 14% (2 of 14) of patients with tetraploid tumours (p less than 0.05). Aneuploid tumours had an elevated CEA level in 38% of stage A-B disease and in 61% of stage C-D disease. The elevated CEA values (greater than or equal to 5.0 micrograms/l) correlated with tumour stage in patients with aneuploid tumours but not in patients with diploid tumours. Whereas CEA is a suitable marker for aneuploid carcinomas, other more sensitive tumour markers should be sought for diploid and also for tetraploid tumours. If such markers are found, flow cytometry could provide the most important information in selecting individual follow-up programmes for colorectal cancer patients.

Adult↗
PubMed1991

Evaluation of three slide agglutination tests for rapid identification of Staphylococcus aureus.

Three slide agglutination tests for identification of Staphylococcus aureus were compared. The agglutination tests used for evaluation were Staphaurex (Wellcome Diagnostics), Staphyslide-Test (BioMerieux), and ANI S. aureus TEST (Ani Biotech Oy). A total of 347 isolates were analyzed, including 288 strains of S. aureus, 49 of S. epidermis, 11 of S. intermedius, 12 strains of other staphylococci and 14 non-staphylococcal strains. One hundred of the S. aureus strains were isolates from cases of food poisoning, 129 from mastitis and 59 from other clinical cases. The sensitivities of the tests were also compared using diluted suspensions of S. aureus strains and with purified Protein A dilutions. The results showed that the sensitivities of the tests were 98.6%, 97.9% and 99.0% for Staphaurex, Staphyslide-test and ANI S. aureus TEST, respectively. The specificities were 100% for the Staphyslide test and 98.8% for both the ANI S. aureus TEST and the Staphaurex test. The sensitivities measured with diluted S. aureus strain suspensions and Protein A solutions were equal with the Staphaurex and ANI S. aureus TEST. All the agglutination tests studied proved to be practical, easy to use and accurate for the rapid identification of S. aureus strains from culture isolates.

Agglutination Tests↗
PubMed1990

Binding and activation of plasminogen at the surface of Staphylococcus aureus. Increase in affinity after conversion to the Lys form of the ligand.

Untreated Staphylococcus aureus cells, strain Cowan I, specifically bound 125I-Glu-plasminogen. The binding was inhibited by both unlabeled Glu-plasminogen and Glu-plasmin. The Lys form of plasminogen, which lacks the 8-kDa amino-terminal activation peptide, was approximately 100-fold more effective than the Glu form in competing with the binding of 125I-labeled Glu-plasminogen. This suggests an increase in binding affinity upon removal of the activation peptide. Fibronectin, fibrinogen and IgG, plasma components known to bind to the staphylococcal surface, did not significantly interfere with the binding. The competing activity in plasma was abolished by specifically absorbing plasminogen from the plasma sample. L-Lysine and a fragment of plasminogen containing three of the first five protein attachment domains present in the molecule (kringle structures) also competed with plasminogen for binding suggesting that the lysine-binding sites of plasminogen were involved in its interaction with staphylococci. Scatchard analysis revealed high- and low-affinity binding sites. Kd and the number of high-affinity binding sites were 1.7 nM and 780 binding sites/bacterial cell, respectively. 125I-Glu-plasminogen bound to staphylococcal surface was converted to plasmin by tissue-type plasminogen activator. The conversion took place also in the presence of plasma. If the conversion was carried out in the absence of low-molecular-mass plasmin inhibitors such as aprotinin, the bound Glu-plasmin was further converted to Lys-plasmin. The surface-bound plasmin was enzymically active, as judged by digestion of the synthetic substrate, S-2251. The plasminogen conversion shown by the present experiments not only leads to the surface-bound plasmin but seems to considerably increase the affinity of plasmin for its binding site. This may represent a physiologically relevant method for a bacterial cell to retain surface-bound active plasmin which is also protected from its soluble plasma inhibitors. This novel mechanism for staphylococci to adopt surface-bound proteolytic activity, without the interference of plasma components, may have some role in the tissue penetration and invasion of microbes during infection.

Aprotinin↗
PubMed1990

Type V collagen as the target for type-3 fimbriae, enterobacterial adherence organelles.

Tissue-binding specificity of the type-3 fimbriae of pathogenic enteric bacteria was determined using frozen sections of human kidney. A wild-type Klebsiella sp. strain and the recombinant strain Escherichia coli HB101(pFK12), both expressing type-3 fimbriae, as well as the purified type-3 fimbriae effectively bound to sites at or adjacent to tubular basement membranes, Bowman's capsule, arterial walls, and the interstitial connective tissue. Bacterial adherence to kidney was decreased after collagenase treatment of the tissue sections. Recombinant strains expressing type-3 fimbriae specifically adhered to type V collagen immobilized on glass slides, whereas other collagens, fibronectin or laminin did not support bacterial adherence. In accordance with these findings, specific binding of purified type-3 fimbriae to immobilized type V collagen was demonstrated. Specific adhesion to type V collagen was also seen with the recombinant strain HB101(pFK52/pDC17), which expresses the mrkD gene of the type-3 fimbrial gene cluster in association with the pap-encoded fimbrial filament of E. coli, showing that the observed binding was mediated by the minor lectin (MrkD) protein of the type-3 fimbrial filament. The interaction is highly dependent on the conformation of type V collagen molecules since type V collagen in solution did not react with the fimbriae. Specific binding to type V collagen was also exhibited by type-3 fimbriate strains of Yersinia and Salmonella, showing that the ability to use type V collagen as tissue target is widespread among enteric bacteria.

Acetates↗
PubMed1989

Interaction of Campylobacter jejuni with extracellular matrix components.

The adhesion of three strains of Campylobacter jejuni to coverslips and microwells coated with isolated extracellular matrix components, fibronectin, laminin and types I, III, IV and V collagens was studied. Fibronectin mediated the adherence of C. jejuni, but there were differences in the binding capacities of the strains. Type I, III and V collagens mediated very strongly the attachment of two strains of C. jejuni. All three strains attached weakly to basement membrane-specific type IV collagen. Laminin was capable of mediating the adhesion only when present at a higher concentration. The observations indicate that extracellular matrix components may serve as anchor molecules for C. jejuni adhesion and that several attachment mechanisms occur simultaneously.

Bacterial Adhesion↗
PubMed1989

A novel lectin-independent interaction of P fimbriae of Escherichia coli with immobilized fibronectin.

Binding of P fimbriae of uropathogenic Escherichia coli to purified human fibronectin and human placental type IV collagen was studied. In an enzyme immunoassay, purified P fimbriae bound strongly to immobilized intact fibronectin and to the aminoterminal 30-kDa fragment and the 120-140-kDa carboxyterminal fragments of fibronectin. Binding to the gelatin-binding 40-kDa fragment of fibronectin was considerably weaker. No binding to immobilized type IV collagen was seen. The interaction between P fimbriae and immobilized fibronectin was not inhibited by alpha-D-Gal-(1-4)-beta-D-Gal-1-O-Me, a receptor analog of P fimbriae. Moreover, a mutated P fimbria lacking the lectin activity behaved similarly in the adherence assays. Recombinant strains expressing the corresponding cloned fimbriae genes bound to immobilized fibronectin, but no binding to soluble 125I-labelled fibronectin was found. The results suggest that P fimbriae interact with immobilized fibronectin and that the binding mechanism does not involve the lectin activity of the fimbriae.

Bacterial Adhesion↗