Search PubMed⌕ Search

Biomedical subjects

P Kuusela

Publications and source records attributed to P Kuusela.

At least 73 records · Page 4Linked to original sources

The O75X adhesin of uropathogenic Escherichia coli is a type IV collagen-binding protein.

Interaction of the basement-membrane binding O75X adhesin of uropathogenic Escherichia coli with various extracellular matrix proteins was studied. The adhesin showed strong binding to type IV collagen immobilized on microtitre plates, whereas other collagens, laminin and fibronectin, were only weakly recognized. Similarly, specific binding of [125I]-labelled type IV collagen to O75X-positive bacteria was shown. Interaction of the two proteins was also demonstrated by affinity chromatography of the O75X adhesin on immobilized type IV collagen. The adhesin bound strongly to the immobilized N-terminal 7S domain of type IV collagen, and the binding of [125I]-labelled type IV collagen to O75X-positive bacteria was inhibited by the soluble 7S domain. Binding of O75X to type IV collagen and to its 7S domain was specifically inhibited by chloramphenicol but was not affected by periodate or endoglycosidase-H treatment of the glycoproteins. Our results show that the 7S domain of type IV collagen is the basement membrane receptor for the O75X adhesin and suggest an interaction based on protein-protein recognition. Inhibition of the interaction by chloramphenicol favours the supposition that a modified tyrosine is involved in the binding site.

Acetylglucosaminidase↗

Tumour markers in gastric cancer.

We still lack clinically useful tumour markers in gastric cancer. To be of clinical value markers should be elevated in the early stages of the disease, when surgery for cure is possible. However, tumour markers available today, like CEA, CA 19-9 and CA 50, mainly detect advanced gastric cancer, for which only palliative treatment is available. The use of tumour markers in the follow-up of radically operated patients seems to be of only academic interest, mainly because a recurrence of gastric cancer is incurable. The preoperative tumour marker level may have a prognostic value and may be clinically useful in selecting patients for adjuvant treatment. To elucidate this, prospective controlled trials are needed. A short review of tumour markers in gastric cancer will be presented.

Antigens, Tumor-Associated, Carbohydrate↗

Tumour markers in pancreatic cancer.

Patients with pancreatic cancer usually lack signs and symptoms in the early course of the disease. Even when malignancy is suspected, differential diagnosis between benign and malignant pancreatic disorders may be difficult with current methods. An increasing interest has been focused on the utility of immunological tumour markers. CEA has been widely used since the early seventies, but the results in diagnosis of pancreatic cancer have been disappointing. Tumour marker tests for CA 19-9 and CA 50 are based on monoclonal antibodies to colonic carcinoma cell lines. CA 19-9 and CA 50 are strongly expressed in most tissue specimens from pancreatic carcinomas, but are also found in normal pancreas and benign pancreatic diseases. The CA 19-9 and CA 50 antigens are shed or released into the circulation, and are found in increased concentrations in 70-80% of patients with pancreatic cancer. Also 50-65% of patients with small resectable carcinomas have elevated CA 19-9 and CA 50 levels, although very high serum concentrations usually indicate advanced disease. Slightly elevated serum CA 19-9 and CA 50 levels are seen in some patients with benign pancreatic diseases, more often in acute than in chronic pancreatitis. Elevated values are often observed in patients with benign obstruction of the common bile duct, particularly in patients with cholangitis. In patients with jaundice of hepatocellular origin, the CA 19-9 and CA 50 levels are lower than in extrahepatic cholestasis. CA 19-9 and CA 50 have better diagnostic accuracy for pancreatic cancer than CEA, CA 125, DU-PAN-2, TPA and PSTI/TATI. However, the sensitivities and specificities of CA 19-9 and CA 50 are too low for screening of an asymptomatic population. Nevertheless, CA 19-9 and CA 50 have in our experience shown to be useful complements to other diagnostic methods in symptomatic patients with suspicion of pancreatic cancer. Combinations of different markers improve the sensitivity only slightly compared to the use of CA 19-9 or CA 50 alone. Follow-up using CA 19-9 and CA 50 is a simple and sensitive way of monitoring the postoperative course of patients with pancreatic cancer, and may give a lead time of several months for a recurrence compared to conventional methods.

Antigens, Neoplasm↗

The ovarian cancer associated antigen CA 125 in patients with pleural effusions.

The concentration of the ovarian cancer associated antigen CA 125 was determined in the pleural fluid of 25 patients with lung cancer and of 40 patients with benign diseases. Paired serum and pleural fluid samples were measured in 21 tumor patients and 34 patients with nonmalignant diseases. Serum CA 125 was elevated (greater than 35 U/ml) in 16 of 25 (64%) patients with carcinoma and 13 of 34 (38%) patients with benign diseases. The CA 125 level in serum was markedly elevated (greater than 200 U/ml) in five of six adenocarcinomas whereas a slightly elevated level was associated with only one of four mesotheliomas and with one of three secondary carcinomas. The pleural fluid concentration of CA 125 was higher than the serum value in 90% of the patients, showing a median ratio of 4.9, respectively. Pleural fluid values higher than 250 U/ml were seen in 18 of 25 (72%) subjects with pleural effusion due to malignancy and in 10 of 40 (25%) patients in the benign group. There were no apparent differences in the pleural fluid CA 125 levels in patients having different types of cancer and different benign diseases.

Adenocarcinoma↗

Demonstration of tumor necrosis factor in human amniotic fluids and supernatants of placental and decidual tissues.

Human amniotic fluid samples obtained from normal pregnancies and supernatants of normal full-term placental and decidual tissues were assayed in a specific radioimmunoassay (RIA) and in a sensitive bioassay for tumor necrosis factor (TNF). TNF was detected in 91% of amniotic fluid samples and in all placental and decidual supernatants assayed by the RIA. Amniotic fluid samples collected during the second trimester of pregnancy contained significantly higher concentrations of TNF than samples collected during the third trimester, average concentrations being 2.5 ng/ml and 0.9 ng/ml, respectively. Parallel testing in the bioassay showed that most of the amniotic fluid TNF is biologically inactive, whereas placental and decidual supernatants had biologic activity correlating with TNF levels detected by the RIA. The quantities of TNF detected by the RIA ranged from 1.1 to 2.8 ng/ml in placental supernatants and from 3.9 to 8.5 ng/ml in decidual supernatants. The presence of TNF in normal amniotic fluids and in placental and decidual supernatants suggest that this cytokine has a physiologic role in human pregnancy.

Amniotic Fluid↗

Serum CA 50 as a tumor marker in pancreatic cancer: a comparison with CA 19-9.

CA 50 is a new tumor marker based on a monoclonal antibody (MAb) against a human colorectal carcinoma cell line. The CA 50 antigen is similar, but not identical, to the tumor marker CA 19-9. The serum concentrations of CA 50 were measured by an immunoradiometric assay (CA 50 IRMA) in 95 patients with pancreatic cancer and in 94 patients with benign pancreatic, biliary and hepatocellular diseases. The CA 50 concentration was above the cut-off limit of 17 U/ml in 71% of the patients with pancreatic cancer. Elevated CA 50 levels were also seen in 29% of the patients with benign diseases (up to 250 U/ml), especially in patients with extra-hepatic cholestasis (34%) and hepatocellular jaundice (46%). The results of the immunoradiometric assay were compared to those of the commercially available CA 50 RIA inhibition test. The sensitivities of the two CA 50 assays for pancreatic cancer were similar, but the specificity of the IRMA assay was higher. The CA 50 and CA 19-9 values showed a strong positive correlation and the assay parameters of the tests were almost similar. CA 50 seems a promising tumor marker in the detection and follow-up of patients with pancreatic cancer.

Antigens, Neoplasm↗

Comparison of CA-50, a new tumour marker, with carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) in patients with gastrointestinal diseases.

Serum levels were determined in 434 patients with benign and malignant gastrointestinal diseases and compared with the serum concentrations of carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP). The highest proportion of elevated CA-50 levels (greater than 17 U ml-1) was found in patients with pancreatic cancer (73%). High levels were mainly associated with advanced cancer, but also half of the patients with a resectable pancreatic tumour had an increased CA-50 concentration. The CA-50 level was elevated in 37-58% of patients with colorectal, gastric, hepatocellular and biliary tract cancers. In all gastrointestinal cancers, CA-50 gave additional information compared with CEA and AFP, except in hepatocellular carcinoma where AFP was the best marker.

Antigens, Neoplasm↗

Dental papilla cells synthesize but do not deposit fibronectin in culture.

The dental papilla cells play a major regulatory role during tooth morphogenesis, and they are the only mesenchymal cells capable of differentiating into odontoblasts secreting dentin. In this paper, we have extended our studies on the behavior of cultured dental papilla cells which have been disaggregated from 17-day mouse embryo teeth. Quite unexpectedly, we observed that these cells, which in vivo are embedded in a fibronectin-rich extracellular matrix, lose all surface-associated fibronectin when cultured as monolayers. Fibronectin was, however, detected intracellularly, and metabolic labeling and immunoprecipitation studies indicated that the dental papilla cells continued to synthesize fibronectin in culture. Furthermore, when purified plasma fibronectin was added at 50 micrograms/mL to the culture medium, it became incorporated as fibrillar matrix on the surfaces of dental papilla cells. This indicates that the cells are not deficient in cell-surface receptors or other surface-associated molecules which bind fibronectin. When pieces of dental papillae were cultured as explants, an abundant matrix containing fibronectin was deposited on their surfaces. This matrix was gradually lost as the cells migrated from the explants. Furthermore, when the cells were disaggregated and cultured at high cell density, the cells in the central area of the pellet were covered by fibronectin containing fibrillar structures which were lost as the cells spread out. This indicates that the maintenance of close contacts between the dental papilla cells is required for the assembly of fibronectin into the extracellular matrix.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Beta-adrenergic stimulation of fatty acid release from brown fat cells differentiated in monolayer culture.

The ability of brown adipocytes differentiated in monolayer culture to respond to norepinephrine was investigated. It was found that fatty acid release in confluent brown adipocytes in monolayer culture was induced by norepinephrine, thus these cells were hormone-sensitive. After confluence, the rate of fatty acid release successively declined. The norepinephrine-stimulated fatty acid release was inhibited by propranolol, but not by phentolamine, indicating a mediation via beta-adrenergic receptors. It was concluded that there exist in the brown adipose tissue of nonfetal rats preadipocytes which possess the ability to express in culture a fully developed beta-adrenergic lipolytic response.

Adipose Tissue, Brown↗

Evaluation of CA 19-9 as a serum tumour marker in pancreatic cancer.

Serum concentrations of the CA 19-9 antigen were determined in 91 patients with pancreatic cancer and in 111 patients with benign pancreatic, biliary and hepatocellular diseases. The CA 19-9 concentration was above the cut-off limit (37 U ml-1) in 78% of the patients with pancreatic cancer and high levels (greater than 500 U ml-1) were seen in 56% of these patients. Elevated levels were also seen in benign diseases (22%), especially in patients with extrahepatic cholestasis (up to 440 U ml-1). Hepatocellular jaundice and pancreatitis were associated with normal values (84% of the patients), or with only slightly elevated CA 19-9 levels (up to 88 U ml-1). The CA 19-9 test can be useful as an additional diagnostic tool for the detection of pancreatic cancer. Preliminary results suggest that the CA 19-9 assay can be used in the monitoring of surgically treated patients.

Alkaline Phosphatase↗

The relationship between the keratocyst antigen (KCA) and keratin.

The relationship of the keratocyst antigen (KCA), the soluble component present in most keratocyst fluids, and keratin, was studied with immunofluorescence microscopy comparing their distribution in developing mouse embryonic teeth and in human ameloblastomas. In these tissues both molecules showed a strong codistribution in epithelial cells. In the embryonic teeth both molecules were present in the stratum intermedium cells between the stellate reticulum cells and ameloblasts, but the secretory ends of the ameloblasts showed fluorescent staining only for keratin. The relationship was further investigated by comparing the physicochemical characteristics of KCA and keratin. Results on immunoblotting and two-dimensional gel electrophoresis showed that KCA existed in keratocyst fluid as a 60-68,000 dalton polypeptide with an isoelectric point of pI 6.8. Immunoblotting analysis of various isolated keratins revealed a typical polypeptide pattern of each keratin when anti-KCA antiserum was used for staining. These findings suggest that KCA and keratin are related molecules and that KCA may be a soluble component of keratin.

Ameloblastoma↗

Is swimming exercise or cold exposure for rats?

Rats were trained by daily swimming sessions (up to 3 h per day) for at least 6 weeks in water at 30, 36 and 38 degrees C. After this training, the adaptive changes obtained were compared with those typical of cold-acclimated (cold-specific changes) and running-trained (training-specific changes) rats. The most typical training-specific change, an increased activity of oxidative muscle enzymes was negligible for swimming-trained rats, while the lowered activity of muscle lactate dehydrogenase was evident for all trained groups. Cold-specific changes, such as increased food intake, increased calorigenic response to injected noradrenaline, an increase both in mass and metabolic capacity of brown adipose tissue, and maintenance of the stores of ascorbic acid and muscle glycogen during cold exposure, were observed for rats trained at 36 and 30 degrees C. The cold tolerance test in cold air did not make any distinct difference between the rats trained at different water temperatures, while in cool water the 30 degrees C -swimmers were clearly superior to other groups, that is, their cooling rate was slowest. Other adaptive changes were found, to a variable extent, for all trained groups. These included loss of body fat, cardiac hypertrophy, reduced urinary catecholamine excretion after test swimmings either in cold or warm water, increased tail-skin temperature response to isoprenaline, and a higher tail-skin temperature in response to cold. Generally, however, the adaptive changes observed for 30- and 36 degrees C-swimmers were similar, while the changes observed for 38 degrees C-swimmers were different. The latter group neither displayed any cardiac enlargement nor any cold-specific changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Tumour markers in pancreatic cancer.

The serum levels of three new tumour markers defined by monoclonal antibodies, CA 19-9, CA 50 and CA 125, were analysed and compared with carcinoembryonic antigen (CEA) in samples from 91 patients with pancreatic cancer and from 111 patients with benign pancreatic, biliary tract and hepatocellular diseases. High serum concentrations of CA 19-9 and CA 50 were found in most patients with pancreatic cancer, 78% and 72%, respectively. The serum levels of these two markers showed a positive correlation, while no other correlation was found between the markers. Benign extrahepatic cholestasis was often associated with moderately elevated CA 19-9 and CA 50 levels. The CA 125 and CEA levels were elevated in about half of the patients with pancreatic cancer. Both CA 19-9 and CA 50 seem promising in the follow-up of patients with pancreatic cancer.

Antigens, Neoplasm↗

The cellular origin of fibronectin in the basement membrane zone of developing tooth.

The cellular source of fibronectin in the dental epitheliomesenchymal interface was studied in interspecies combinations of mouse and quail tissue. Species-specific fibronectin antibodies were produced by immunizing rabbits with purified mouse or chicken fibronectin and by absorbing both antisera with purified heterologous fibronectin and insoluble tissue extract. The absorbed antisera to mouse and chicken fibronectin showed fluorescent staining only in mouse and chicken tissue sections, respectively, but not vice versa. When the mouse mesenchymal dental papilla was combined and cultured either with the mouse enamel organ or with the quail pharyngeal epithelium, mesenchymal cell differentiation was initiated and typical alignment of mesenchymal cells along the basement membrane was seen. Examination with transmission electron microscope revealed a typical bilaminar basal lamina with adherent fibrillar matrix on its mesenchymal aspect. Immunofluorescent localization of fibronectin with the mouse-specific fibronectin antiserum showed a brilliant staining in the mesenchymal tissue and in the basement membrane zone. When the chicken-specific fibronectin antiserum was used, no staining was detected in either tissue recombinations. We have suggested earlier that fibronectin in the dental basement membrane plays an important role during the differentiation of mesenchymal cells into odontoblasts. The present study demonstrates that fibronectin in the basement membrane of the developing tooth is produced exclusively by the differentiating mesenchymal cells.

Animals↗

Isolation of a novel cell-attachment and spreading-promoting protein from human serum.

A protein with potent cell-attachment and spreading-promoting activity was isolated from fibronectin-free human serum. The purification steps included affinity chromatography on heparin-agarose and preparative isoelectric focusing. The purified protein was homogeneous as judged from dodecyl sulphate/polyacrylamide-gel electrophoresis. It had an isoelectric point of 5.0 and an Mr of 52 000. The protein promoted the spreading of Chinese-hamster ovary cells to plastic in a manner similar to that observed with fibronectin.

Animals↗

Attachment of staphylococci and streptococci on fibronectin, fibronectin fragments, and fibrinogen bound to a solid phase.

The attachment of Staphylococcus aureus (Cowan I) and two strains of group A and G streptococci on glass cover slips coated with fibronectin, fibronectin fragments, or fibrinogen was studied. The attachment was quantitated by counting the attached bacteria on glass surfaces coated with a similar molarity of the proteins. Fibronectin was a more effective attachment factor than fibrinogen for staphylococci, while group G streptococci attached better on fibrinogen- than on fibronectin-coated cover slips. In this system, group A streptococci bound almost exclusively to substrate-bound fibrinogen. Attachment experiments involving the use of staphylococci pretreated with soluble fibronectin or fibrinogen revealed that bacterium-bound fibronectin and fibrinogen were able to enhance the adherence on cover slips coated with fibronectin. The 30-kilodalton NH2-terminal and the 120- to 140-kilodalton COOH-terminal fragments of fibronectin, both of which contain bacterial binding sites, mediated the staphylococcal attachment, suggesting that both parts of the molecule are involved in the attachment mediated by fibronectin.

Adhesiveness↗