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Biomedical subjects

T Palosuo

Publications and source records attributed to T Palosuo.

At least 37 records · Page 2Linked to original sources
PubMed2001

Association of autoantibodies to filaggrin with an active disease in early rheumatoid arthritis.

OBJECTIVE: To evaluate the clinical significance of antifilaggrin antibodies (AFA) measured by an enzyme linked immunosorbent assay (ELISA) in serial specimens from patients with recent onset rheumatoid arthritis (RA). METHODS: Filaggrin was purified from human skin and used as an antigen in ELISA. The AFA test was applied to five serial specimens from 78 patients with recent onset RA followed up for three years. Rheumatoid factor (RF) had been measured earlier from the same samples by quantitative immunoturbidimetry. RESULTS: The mean AFA level was highest at entry (54% positive), followed by a statistically significant decline at six months and a slight increase at three years. AFA were persistently positive in 23 patients and persistently negative in 28 patients. Eleven of the latter patients were persistently negative for RF. At study entry AFA levels correlated to some degree with RF levels. In general, raised AFA levels at entry were associated with an active and treatment resistant disease, but they did not predict radiological progression. CONCLUSIONS: The test for AFA has potential for an additional immunological test for RA.

Adult↗
PubMed2001

Immunologic and hematologic properties of antibodies to prothrombin and plasminogen in a mouse model.

Antibodies to prothrombin have been associated with venous and arterial thrombosis, and they cross-react with a structurally closely related protein plasminogen. We immunised 16 mice with human prothrombin and 15 mice with human plasminogen. Mice immunised with prothrombin developed cross-reactive antibodies to plasminogen (12/16), beta2-glycoprotein I (4/16), tissue-type plasminogen activator (6/16) and cardiolipin (11/16). Mice immunised with plasminogen developed cross-reactive antibodies to prothrombin (8/15), tissue-type plasminogen activator (2/12) and cardiolipin (5/12). Functional effects of antibodies were examined. Immunisation with prothrombin induced lupus anticoagulant activity in 9/14 mice. In mice immunised with plasminogen, radial fibrinolysis was inhibited in 8/10 and plasminogen activation in the chromogenic assay was inhibited in 9/11. No cross-functionality was observed. In conclusion, antibodies to prothrombin and plasminogen cross-react in vivo. Antibodies to prothrombin and plasminogen have different functional profiles, immunisation with prothrombin leads to prolonged blood clotting time, and immunisation with plasminogen induces antibodies interfering with fibrinolysis.

Animals↗
PubMed2000

Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset.

STATEMENT OF FINDINGS: An inception cohort of 238 patients having peripheral joint synovitis of less than 12 months duration was evaluated clinically and followed prospectively for 1 year to determine the clinical significance of a number of rheumatoid arthritis (RA) associated autoantibodies. Serum samples collected at the time of the initial evaluation were tested for rheumatoid factor (RF) and antibodies to Sa (anti-Sa), RA-33, (pro)filaggrin [antifilaggrin antibody (AFA)], cyclic citrullinated peptide (anti-CCP), calpastatin, and keratin [antikeratin antibody (AKA)]. RF had a sensitivity of 66% and a specificity of 87% for RA. Anti-Sa, AFA, and anti-CCP all had a specificity of more than 90%, but a sensitivity of less than 50% for this diagnosis. Overall, there was a high degree of correlation between AFA, AKA, anti-Sa or anti-CCP, this being highest between anti-Sa and anti-CCP (odds ratio, 13.3; P < 0.001). Of the 101 patients who were positive for at least one of these four autoantibodies, 57% were positive for only one. Finally, anti-SA identified a subset of predominantly male RA patients with severe, erosive disease. Anti-SA, AFA and anti-CCP are all specific for early RA but, overall, have little additional diagnostic value over RF alone. Although these antibodies may preferentially recognize citrullinated antigens, the modest degree of concordance between them in individual patient sera suggests that it is unlikely a single antigen is involved in generating these responses.

Acute Disease↗
PubMed2000

Infections, inflammation, and the risk of coronary heart disease.

BACKGROUND: The role of infections and inflammation in the pathophysiology of coronary heart disease is emerging. We studied the independent and joint effects of these 2 components on coronary risk. METHODS AND RESULTS: We measured baseline levels of C-reactive protein (CRP) and antibodies to adenovirus, enterovirus, cytomegalovirus, and herpes simplex virus as well as to Chlamydia pneumoniae (Cpn) and Helicobacter pylori in 241 subjects who suffered either myocardial infarction or coronary death during the 8.5-year trial in the Helsinki Heart Study, a coronary primary prevention trial. The 241 controls in this nested case-control study were subjects who completed the study without coronary events. Antibody levels to herpes simplex type I (HSV-1) and to Cpn were higher in cases than in controls, whereas the distributions of antibodies to other infectious agents were similar. Mean CRP was higher in cases (4.4 versus 2.0 mg/L; P<0.001), and high CRP increased the risks associated with smoking and with high antimicrobial antibody levels. The odds ratios in subjects with high antibody and high CRP levels were 25.4 (95% CI 2.9-220.3) for HSV-1 and 5.4 (95% CI 2.4-12.4) for Cpn compared with subjects with low antibody levels and low CRP. High antibody levels to either HSV-1 or to Cpn increased the risk independently of the other, and their joint effect was close to additive. CONCLUSIONS: Two chronic infections, HSV-1 and Cpn, increase the risk of coronary heart disease. The effect is emphasized in subjects with ongoing inflammation, denoted by increased CRP levels.

Adult↗
PubMed2000

Relation of inflammation to vascular function in patients with coronary heart disease.

Endothelium plays a pivotal role in the regulation of vascular relaxation. Inflammation may in turn induce endothelial dysfunction and thus increase the risk of atherothrombosis. We investigated 31 men with angiographically verified coronary heart disease, aged 57. 7+/-5.3 years, in regard to endothelium-dependent, acetylcholine-induced, and to endothelium-independent, sodium nitroprusside-induced vasodilatation in the forearm vasculature by strain-gauge plethysmography. Logistic regression analysis served to determine the relation between forearm vascular function and the inflammatory factors measured, concentration of C-reactive protein, subtypes of peripheral blood T-lymphocytes, and other factors potentially affecting endothelial function (lipoprotein and glucose levels). Concentration of C-reactive protein was an independent determinant of endothelium-dependent vascular function (P<0.001 for low dose acetylcholine, P=0.01 for high dose acetylcholine). Other determinants of endothelium-dependent vascular dysfunction were CD8-lymphocytes expressing ICAM-1 (P=0.001), antibodies to oxidized low-density lipoprotein (P<0.001), and body weight (P=0.007). The present data showed an association between inflammatory risk factors linked to atherothrombosis and endothelial dysfunction in coronary heart disease patients. It is possible that endothelial dysfunction in coronary heart disease patients is related to the chronic inflammation or infection coexisting with atherosclerosis.

Aged↗
PubMed2000

IgE reactivity to patatin-like latex allergen, Hev b 7, and to patatin of potato tuber, Sol t 1, in adults and children allergic to natural rubber latex.

BACKGROUND: Patients allergic to natural rubber latex (NRL) frequently show positive skin prick tests (SPT) and hypersensitivity reactions to various fruits, such as avocado, banana, and kiwi, as well as to vegetables such as potato. METHODS: Hev b 7 was purified from NRL "C-serum" and Sol t 1 from potato extract, and they were detected by immunoblotting. IgE antibodies to Hev b 7 and Sol t 1 were measured with ELISA in sera from 35 adults and 35 children allergic to NRL. ELISA inhibition and immunoblotting were used to study allergen cross-reactivity. The in vivo reactivity of Hev b 7 and Sol t 1 were demonstrated in the SPT. RESULTS: Seventeen (49%) of the 35 NRL-allergic adults had IgE antibodies to Hev b 7, in contrast to only one of the 35 NRL-allergic children. Fifteen (43%) of the NRL-allergic adults and 29 (83%) of the NRL-allergic children had IgE antibodies to Sol t 1. Ten (29%) of the adult sera showed IgE binding to both Sol t 1 and Hev b 7, and crosswise inhibition tests with pooled sera revealed marked cross-reactivity. In the SPT, both natural Hev b 7 and Sol t 1 were able to produce a wheal and flare reaction. CONCLUSIONS: One-half of the NRL-allergic adults, but only one of the NRL-allergic children, had IgE antibodies to natural Hev b 7. These results suggest that Hev b 7 is an important NRL allergen for adults, but not for children. Elucidation of the clinical importance of the observed cross-reactivity between Hev b 7 and Sol t 1 requires further studies.

Adolescent↗
PubMed2000

Natural rubber latex allergy in children: a follow-up study.

BACKGROUND: Natural rubber latex (NRL) allergy occurs frequently in children with spina bifida and other children with disorders requiring multiple operations. Also atopic children who have not undergone surgery can be sensitized to NRL, but the outcome of these children has not been studied. OBJECTIVE: To study how NRL-allergic children manage at home and whether their skin prick test (SPT) reactivity, latex RAST or IgE antibody levels to NRL allergens change during the follow-up. METHODS: Twenty-four NRL-allergic children who had not undergone surgery and eight children with histories of multiple operations were followed up for a mean of 2.8 years. Clinical symptoms were recorded and all children were re-examined with SPT, latex RAST and ELISA for IgE antibodies to prohevein (Hev b 6.01), hevein (Hev b 6.02) and rubber elongation factor (REF, Hev b 1). RESULTS: Nineteen of the 24 NRL-allergic children (79%) who had not undergone surgery had occasionally contacts to balloons and other NRL products at home, and 10 of them experienced symptoms ranging from contact urticaria to systemic reactions. Three of the eight NRL-allergic children with a history of multiple operations had contacts to rubber balloons without any symptoms, and five children underwent 1-8 uneventful operations in a latex-free environment. SPT reactivity to NRL allergens, latex-RAST or IgE antibody levels to prohevein or hevein did not change in either group of NRL-allergic children during the follow-up. CONCLUSIONS: Occurrence of clinical symptoms and no decrease in SPT reactivity or IgE levels to NRL allergens in the course of the present follow-up study imply that more attention should be paid to the protection of NRL-allergic children from rubber contacts in the home environment.

Adolescent↗
PubMed2000

Serum C-reactive protein does not predict rheumatoid arthritis.

OBJECTIVE: Clinical rheumatoid arthritis (RA) is preceded by an immunological process. Our objective was to investigate C-reactive protein (CRP) for its prediction of RA. METHODS: A case-control study was nested within a Finnish cohort of 19,072 adults who had no arthritis and no history of the disease at the baseline examination conducted between 1973 and 1977. By late 1989, 124 had developed RA. Three controls for each incident case were individually matched for sex, age, and municipality. The CRP concentration was measured by a sensitive ELISA. RESULTS: No difference was noted in serum CRP levels between cases and controls. The odds ratios (95% confidence intervals) of RA in the quintiles of CRP were 1.0, 0.89 (0.45-1.76), 1.11 (0.59-2.08), 0.99 (0.51-1.91), and 0.95 (0.49-1.87). Similarly, there was no difference when the data were analyzed in strata of sex, age, rheumatoid factor (RF) status at baseline, and length of time from taking the specimens to the onset of clinical disease. CONCLUSION: Pre-rheumatoid immunological process as reflected in RF production is not associated with any marked inflammation or tissue injury heightening CRP.

Adult↗
PubMed2000

Antifilaggrin antibodies within "normal" range predict rheumatoid arthritis in a linear fashion.

OBJECTIVE: Increasing attention has been paid to the significance of antifilaggrin antibodies (AFA) in rheumatoid arthritis (RA). We studied the prediction of RA by AFA in serum specimens from the period prior to the onset of clinical RA. METHODS: A case-control study was nested within a Finnish cohort of 19.072 adults who had neither arthritis nor a history of it at the baseline examination during 1973-77. Pre-illness serum specimens for the assay of AFA by ELISA, using filaggrin purified from human skin as the antigen, were available from 124 of the 126 patients who had developed RA by late 1989. Of the incident cases 89 were positive for rheumatoid factor (RF). Three controls per each incident case were individually matched for sex, age, and municipality. RESULTS: Pre-illness serum AFA level was found to be directly proportional to the risk of RF positive RA. The odds ratio (95% confidence interval) in the highest quintile compared to the lowest quintile was 5.4 (2.2-13.6). In the subgroup of subjects positive for RF at baseline the figure was 24 (4.0-140). AFA did not predict the development of RF negative RA. A close association of the same order of magnitude between RF and AFA was noted in the pre-illness sera and in the control sera. CONCLUSION: AFA still within the "normal" range predicts RA in a linear fashion. AFA and RF are associated markers of the rheumatoid immunological process.

Adult↗
PubMed1999

Avidin is a promising tag for fusion proteins produced in baculovirus-infected insect cells.

The baculovirus expression vector system (BEVS) has become one of the most versatile and powerful eukaryotic systems for recombinant protein expression. We have constructed a novel baculovirus transfer vector (pbacAVs+C) which allows for the efficient production, detection, and single-step purification of the desired molecule as a secretion-compatible avidin fusion protein in insect cells. It also enables fast construction of the baculoviruses by site-specific transposition in Escherichia coli. To demonstrate the power of this vector, we report here on the production of immunologically intact hevein, a major cysteine-rich latex allergen, as avidin fusion protein. Our results indicate that avidin is a stable and versatile tag in the BEVS. It retains its extraordinarily high biotin-binding activity and also enables independent folding of the fusion partner. The versatility with which avidin fusion proteins can be detected, purified, and immobilized is the basis for the use of our system as a useful alternative in eukaryotic fusion protein production.

Amino Acid Sequence↗
PubMed1999

Cow's milk casein, a hidden allergen in natural rubber latex gloves.

BACKGROUND: We have previously noted that one natural rubber latex (NRL) glove brand used for skin prick testing in the diagnosis of NRL allergy contained cow's milk casein. OBJECTIVE: We sought to examine whether other commonly marketed NRL glove brands contain cow's milk casein. METHODS: The casein content of 30 NRL glove extracts (1:5 wt/vol) was measured by RAST inhibition and by rocket immunoelectrophoresis and rocket radioimmunoelectrophoresis by using casein-specific rabbit antiserum, a serum pool from patients with cow's milk allergy, and radiolabeled anti-human IgE. The NRL allergen content was measured by ELISA inhibition. RESULTS: The casein content of the glove used in NRL allergy screening (Triflex, Baxter) was rather high (ie, about 400 microgram/g of glove). Its total protein content was 1000 microgram/g of glove. Rocket radioimmunoelectrophoresis detected distinct amounts of casein in 8, minimal amounts in 7, and no casein in the remaining 15 NRL glove brands. CONCLUSIONS: Several brands of NRL gloves were found to contain casein, implying that extracts prepared from such gloves can cause false-positive skin prick test reactions when diagnosing NRL allergy. The use of casein as a stabilizer in glove manufacture without appropriate labeling should be stopped because it can also cause contact urticaria syndrome in individuals with cow's milk allergy.

Allergens↗
PubMed1999

Increased allergen production in turnip (Brassica rapa) by treatments activating defense mechanisms.

BACKGROUND: Practical applications to enhance the productivity of agriculture by using plants with improved resistance to pathogens are expected to increase in the near future. Defense proteins play an important role in pathogen resistance, and some defense-related proteins are significant cross-reacting allergens. For example, cross-allergies are common among patients allergic to natural rubber latex (NRL), which contains many defense-related proteins. OBJECTIVE: Using a model plant (ie, turnip), we studied whether allergen contents increase after treatments activating defense mechanisms of the plants. METHODS: Whole or wounded turnips treated with salicylic acid, ethephon, or water were incubated for 2, 4, or 8 days. Allergen content was investigated by IgE immunoblotting with sera from patients allergic to NRL. An induced protein that bound IgE most intensively was purified and further characterized by mass analysis, amino acid sequencing, IgE-ELISA, and skin prick tests. RESULTS: In immunoblotting, clear IgE-binding bands were discernible only in samples from chemically treated plants. IgE was bound most intensively to a protein with an apparent molecular weight of 25 kd in SDS-PAGE and with a determined molecular weight of 18.7 kd. Sequenced peptides of the 18.7-kd protein showed over 70% homology to prohevein, a major allergen of NRL, and to many other prohevein-like defense proteins. In ELISA, sera from 30 of 34 (88%) adults and 21 of 26 (81%) children previously shown to have IgE against prohevein bound to the purified protein. In skin prick testing with the protein, 4 of 6 patients allergic to NRL had positive reactions. CONCLUSION: These results demonstrate that activating defense mechanisms of plants may considerably increase their allergen content.

Adult↗
PubMed1999

Identification of patatin as a novel allergen for children with positive skin prick test responses to raw potato.

BACKGROUND: Peeling of raw potatoes may cause allergic symptoms, such as sneezing, wheezing, and contact urticaria, for adults. For children, potatoes as food may cause various allergic reactions. However, the identity and molecular structure of the putative allergens in potato have remained unknown. OBJECTIVE: The aim of our study was to identify possible major allergens in potato by using sera of atopic children suspected of having food allergy and having positive skin prick test responses to raw potato. METHODS: Potato proteins were purified by standard methods of protein chemistry and characterized with amino-terminal sequencing and mass spectrometry. The IgE-binding ability of the purified proteins was verified by immunoblotting and ELISA with IgE antibodies from the sera of atopic children having positive skin prick test responses to raw potato. RESULTS: Immunoblotting showed strong IgE binding to a 43-kd protein, identified as patatin, the main storage protein of potato tubers. In ELISA, 20 of 27 (74%) children with positive skin prick test responses to potato and none of the control subjects showed specific binding of IgE antibodies to purified patatin. A positive wheal-and-flare reaction was seen in 8 of 14 children prick tested with purified patatin. CONCLUSION: These results show that patatin in potatoes is a significant, previously unrecognized,IgE-binding protein for children with a positive skin prick test response to raw potato. Further studies are needed to confirm the clinical importance of potatoes, and especially patatin, as a food allergen.

Allergens↗
PubMed1999

Antifilaggrin antibodies in recent-onset arthritis.

We evaluated the sensitivity and prognostic value of an enzyme-linked immunosorbent assay (ELISA) for the measurement of antifilaggrin antibodies (AFA), using filaggrin purified from human skin as an antigen. The AFA test was applied to a series of 306 patients with various recent-onset inflammatory joint diseases. The results were compared to those of the conventional immunofluorescence tests for antikeratin antibody (AKA) and antiperinuclear factor (APF) and of the rheumatoid factor (RF) tests from a previous study. There was a very good agreement between the results of the tests for APF and AFA (kappa-value 0.79 in patients with peripheral poly/oligoarthritis). The agreement between the tests for AKA and AFA was significant but less pronounced (kappa-value 0.50). The AFA test detected 10/22 of the RF-negative erosive cases, particularly those with a large number of erosive joints. Thus, the test for AFA supplements RF in the prediction of erosiveness.

Adult↗
PubMed1998

Prediction of myocardial infarction in dyslipidemic men by elevated levels of immunoglobulin classes A, E, and G, but not M.

BACKGROUND: Immune mechanisms have been suggested to play an important role in the development of coronary atherosclerosis and its thrombotic complications. We evaluated the predictive value of the levels of various serum immunoglobulin classes in middle-aged men at increased risk of myocardial infarction. METHODS: Using nested case-control design and logistic regression analysis, we estimated the association between serum immunoglobulins and the risk of coronary end points (nonfatal or fatal myocardial infarction or sudden cardiac death) in dyslipidemic men (levels of non-high-density lipoprotein cholesterol >5.2 mmol/L [>201 mg/dL]) participating in the Helsinki Heart Study. The cases consisted of 135 subjects in whom a coronary end point occurred during the 5-year observation period of the study, and the controls were 135 subjects who did not suffer coronary end points during this period. Levels of IgA, IgE, IgG, and IgM were determined in serum samples collected at study entry. RESULTS: Levels of IgA, IgE, and IgG, but not IgM, were significantly higher in cases than in controls. After adjustment for other risk factors, such as age, smoking, and blood pressure, the risk of coronary disease showed a significant relation to the levels of IgA, IgE, and IgG. The risk in the highest quartile of each distribution as compared with the lowest quartile was 2.2-fold for IgA (95% confidence interval, 1.0-4.5), 2.8-fold for IgE (1.3-5.9), and 2.8-fold for IgG (1.3-5.9). Hypertriglyceridemia and a low level of high-density lipoprotein cholesterol were associated with increased risk of a coronary end point only if the levels of IgA, IgE, or IgG were also elevated. CONCLUSION: Elevated levels of IgA, IgE, and IgG are associated with myocardial infarction and cardiac death in men with dyslipidemia. The present data suggest that, for dyslipidemia to cause coronary atherothrombosis, an immune response reflected by elevated levels of these immunoglobulin classes is an important determinant.

Adult↗
PubMed1998

IgE antibodies to prohevein, hevein, and rubber elongation factor in children with latex allergy.

BACKGROUND: Prohevein (Hev b 6.01) and hevein (Hev b 6.02) have been shown to be major IgE-binding allergens in health care workers and other adult patients allergic to natural rubber latex (NRL). Rubber elongation factor (REF; Hev b 1) and the 23/27 kd NRL allergen (Hev b 3) are characteristic of children with latex allergy who have spina bifida and other children requiring multiple operations at an early age. In addition, there are children with latex allergy and no history of multiple operations in whom sensitizing allergens are not known. OBJECTIVES: We studied IgE antibodies to NRL allergens in children with latex allergy who had not undergone surgery and compared the findings with those in children with latex allergy and a history of multiple operations. METHODS: Sera from 30 children with latex allergy who had not undergone surgery, 12 children with latex allergy with a history of multiple operations, and 19 control children without evidence of NRL allergy were examined. Immunoblotting was used to study IgE binding to NRL proteins, and purified prohevein, hevein, and REF were used in ELISA to measure specific IgE antibodies. RESULTS: In immunoblotting, sera from 21 (70%) children who had not undergone surgery and from 4 (33%) children with a history of multiple operations showed IgE binding to a 20-kd protein band (known to contain prohevein), and 9 (30%) and 8 (67%) sera, respectively, to a 14-kd protein band (known to contain REF). In ELISA, sera from 26 (86%) children who had not undergone surgery and from 7 (58%) children with a history of multiple operations had IgE antibodies to prohevein and 19 (63%) and 7 (58%) sera, respectively, to hevein. Eight (27%) sera from the children who had not undergone surgery had IgE antibodies to REF in contrast to 8 (67%) sera from children with a history of multiple operations. CONCLUSIONS: The IgE antibody pattern differs between children with latex allergy who had not undergone surgery and those with a history of multiple operations. The major allergens in children with no history of surgery appear to be prohevein and hevein and not REF, a finding that agrees well with that reported for health care workers with allergy to latex.

Adolescent↗
PubMed1998

Hevein-like protein domains as a possible cause for allergen cross-reactivity between latex and banana.

BACKGROUND: Patients allergic to natural rubber latex (NRL) frequently exhibit immediate hypersensitivity reactions to banana, but the molecular basis of these putative cross-reactions is unknown. OBJECTIVE: We wanted to examine whether proteins resembling hevein, a major NRL allergen, exist in banana and whether coexisting allergy to NRL and banana can be explained by IgE cross-reactivity to these proteins. METHODS: Allergens in banana cross-reacting with hevein were identified by IgE immunoblot inhibition. The cross-reacting proteins were purified by reversed-phase chromatography and characterized by amino acid sequencing. Allergen cross-reactivity was further assessed by IgE ELISA, IgE ELISA inhibition, and skin prick testing. RESULTS: In immunoblotting, 9 of 15 sera from patients allergic to NRL with IgE to hevein showed IgE binding to 32- and 33-kd banana proteins. These 2 protein bands were also targets to IgG from a hevein-immunized rabbit. IgE binding to both 32- and 33-kd protein bands was totally inhibited by hevein (10 ng/mL) in all 5 sera from patients allergic to NRL sera studied. N-terminal sequencing of the purified 32- and 33-kd proteins revealed 80% identity to the N-terminus of hevein. An internal peptide (19 amino acids) of the 33-kd protein gave over 90% identity to endochitinases of several plants. In ELISA all 15 sera from patients allergic to NRL had IgE to the purified 32-kd banana protein. In ELISA inhibition hevein (10 ng/mL) inhibited approximately 50% of IgE binding to the solid-phase 32-kd banana protein in a pool of sera from patients allergic to NRL. CONCLUSION: These results suggest that the commonly occurring hypersensitivity to banana in patients allergic to NRL could be explained by cross-reacting IgE antibodies binding to epitopes in hevein and in a hevein-like domain of a previously undescribed endochitinase in banana.

Adult↗