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Biomedical subjects

K Aho

Publications and source records attributed to K Aho.

At least 55 records · Page 3Linked to original sources
PubMed1998

Purification of filaggrin from human epidermis and measurement of antifilaggrin autoantibodies in sera from patients with rheumatoid arthritis by an enzyme-linked immunosorbent assay.

BACKGROUND: The so-called antikeratin antibody (AKA) and the antiperinuclear factor (APF) that recognize proteins related to human epidermal filaggrin belong to the most specific serological markers of rheumatoid arthritis (RA). However, assays for the detection of AKA and APF are currently based on immunofluorescence, a method that is subject to arbitrary interpretation and inadequate standardization of the substrates. METHODS: Proteins extracted from human epidermis were separated by reversed-phase high-performance liquid chromatography (HPLC). Filaggrin-containing fractions, identified in immunoblotting by monoclonal antifilaggrin antibodies, were then subjected to gel filtration HPLC and, finally, to a second reversed-phase HPLC step. Tryptic digestion, amino acid sequencing and mass spectrometry were used to confirm the identity of the purified protein. Filaggrin was used as antigen in enzyme-linked immunosorbent assay (ELISA) to measure IgG class antifilaggrin antibodies. RESULTS: The filaggrin preparation obtained gave a single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, binding monoclonal antifilaggrin antibody in immunoblotting. Amino acid sequences of all 10 tryptic peptides analyzed were shown to originate from human filaggrin. Antifilaggrin antibody levels exceeded the 99th percentile level of 100 middle-aged blood donors in 26/55 (47%) RA sera. At a similar cutoff level 28/55 (51%) of the RA sera were positive in the AKA test. Of the 26 antifilaggrin-positive sera, 21 were also AKA-positive. CONCLUSION: Human filaggrin can be purified by standard biochemical techniques, despite the heterogeneity of the protein, and used in ELISA for testing autoantibodies to filaggrin. The sensitivity of the assay equals that of the AKA test.

Adult↗
PubMed1997

HLA-DRB1 in eight Finnish monozygotic twin pairs concordant for rheumatoid arthritis.

This study presents the results of HLA-DRB1 typing of the eight monozygotic twin pairs with both members affected by rheumatoid arthritis (RA), sampled in the nationwide Finnish twin cohort. The shared epitope, associated with RA in case-control studies, was present in all eight twin pairs, being significantly more frequent than among RA patients in a recent Dutch case-control study. Furthermore, 4 out of 8 twin pairs were homozygous for the shared epitope, while in 73 Dutch healthy controls encoding the shared epitope only 13 (18%) were homozygous: this suggests a gene dose effect in RA susceptibility. Combining these results with data from other sources may help to clarify the contribution of HLA alleles in the genetic predisposition to RA.

Arthritis, Rheumatoid↗
PubMed1997

Serum immunoglobulins and the risk of rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is associated with several autoantibodies that can precede the clinical disease. The immunoglobulin concentrations in serum samples before illness were studied to learn more about the immunological process before 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 1973-1977. By late 1989, 124 had developed RA, of which 89 were positive for rheumatoid factor (RF). Three controls per each incident case were individually matched for sex, age, and municipality. The concentrations of IgG, IgA, and IgM were measured from stored serum samples. RESULTS: Serum IgG before illness was found to be directly proportional to the risk of RF positive RA, and a non-linear association was present between serum IgA and the risk of RF positive RA. These associations were constant between men and women and other subgroups of the study population and not confounded by serum orosomucoid concentration, level of education, smoking, alcohol intake or body mass index. As adjusted for these factors, the odds ratios (95% confidence intervals) of RF positive RA in the lowest, mid, and highest tertiles of IgG distribution were 1.00, 1.55 (0.81, 2.97), and 2.22 (1.16, 4.26), and in the tertiles of IgA 1.00, 2.23 (1.14, 4.36), and 1.78 (0.89, 3.57), respectively. The associations persisted throughout the entire observation period but were most distinct when the period to the onset of clinical RA was > or = 10 years. IgM carried no predictive significance. None of the serum immunoglobulins predicted the development of RF negative RA. CONCLUSIONS: Increased IgG levels may reflect some, at present unknown process in the early events leading to the development of RA, typically occurring > or = 10 years before the onset of clinical disease.

Adult↗
PubMed1997

Antibody to stratum corneum (antikeratin antibody) and antiperinuclear factor: markers for progressive rheumatoid arthritis.

The purpose of this study was to examine the relationship between circulating antibodies to stratum corneum (AKA) and antiperinuclear factors (APF) on one hand, and the x-ray progression of joint damage in chronic poly/oligoarthritis on the other hand. The analysis involved 133 patients with either rheumatoid or nonspecific arthritis derived from a cohort of 442 patients with recent onset arthritis. The patients were followed up for eight years with regular clinical, laboratory, and radiological evaluations. Radiographic evidence of joint destruction was quantitated by a radiographic index based on the Larsen grading. AKA and APF were detected, either at entry or at follow-up, in 26 and 54 patients, respectively. Seventy-six of the 133 patients had developed erosions. All AKA-positive patients had a rheumatoid factor-positive erosive poly-arthritis. The presence of APF was also associated with a progressive arthritis although four APF-positive patients had a non-erosive disease. Neither AKA nor APF were able to distinguish a particularly severe form of progressive RA.

Adolescent↗
PubMed1997

Incidence and prevalence of ankylosing spondylitis in Finland.

OBJECTIVE: To determine the incidence and prevalence of clinically significant ankylosing spondylitis (AS) in Finland. METHODS: The incidence study covered patients entitled under the nationwide sickness insurance scheme to receive specially reimbursed medication for AS in 5/21 central hospital districts in Finland (population base about one million adults > or = 16 years of age) in 1980, 1985, and 1990. The prevalence study covered a representative sample of the Finnish population > or = 30 years of age, initially comprising 8000 persons, of whom 7217 participated in the field survey carried out in 1978-1980. RESULTS: The annual incidence of AS requiring antirheumatic medication was 6.9/100,000 [95% confidence interval (CI), 6.0-7.8] adults. Eleven cases of clinically significant AS were encountered in the prevalence study, corresponding to a prevalence of 0.15% (95% CI, 0.08-0.27%). The ratio between the prevalence rate and the annual incidence rate was 22. CONCLUSION: This study provides population based data on the incidence and prevalence of clinically significant AS in Finland. The incidence rates of AS remained similar for the 3 study years.

Adult↗
PubMed1997

High antibody levels to prothrombin imply a risk of deep venous thrombosis and pulmonary embolism in middle-aged men--a nested case-control study.

Antibodies against phospholipid-binding plasma proteins, such as beta2-glycoprotein I (beta2-GPI) and prothrombin, are associated with thromboembolic events in patients with systemic lupus erythematosus and also in subjects with no evident underlying diseases. We wanted to examine whether increased levels of antibodies to negatively-charged phospholipids (cardiolipin), to phospholipid-binding plasma proteins beta2-GPI and prothrombin and to oxidised low-density lipoprotein (LDL) were associated with risk of deep venous thrombosis or pulmonary embolism in subjects with no previous thrombosis. The antibodies were measured in stored serum samples from 265 cases of deep venous thrombosis of the lower extremity or pulmonary embolism occurring during a median follow-up of about 7 years and from 265 individually matched controls. The study subjects were middle-aged men participating in a cancer prevention trial of alpha-tocopherol and beta-carotene and the cases of thromboembolic events were identified from nationwide Hospital Discharge Register. The risk for thrombotic events was significantly increased only in relation to antiprothrombin antibodies. As adjusted for body mass index, number of daily cigarettes and history of chronic bronchitis, myocardial infarction and heart failure at baseline, the odds ratio per one unit of antibody was 6.56 (95% confidence interval 1.73-25.0). The seven highest individual optical density-unit values of antiprothrombin antibodies were all confined to subjects with thromboembolic episodes. In conclusion, the present nested case-control study showed that high autoantibody levels against prothrombin implied a risk of deep venous thrombosis and pulmonary embolism and could be involved in the development of the thrombotic processes.

Aged↗
PubMed1997

Azathioprine in patients with juvenile chronic arthritis: a longterm followup study.

OBJECTIVE: To evaluate drug survival, efficacy, side effects, and longterm toxicity of azathioprine treatment in patients with juvenile chronic arthritis (JCA). METHODS: In an uncontrolled, prospective study we evaluated 129 consecutive patients with JCA refractory to therapy in whom azathioprine treatment was begun during 1980-1989. In the first 29 patients, a 2 year trial was planned, while for the remaining 100 patients the protocol was to continue until remission or dropout. The median treatment period was 13 months (range 3 days-8.5 yrs). Patients were assessed every 2 months for 2 years for efficacy, side effects, growth and need for glucocorticoids, and outcome evaluated in late 1996. RESULTS: Remission without drugs was attained in 19 patients (15%); in addition, temporary remission in patients continuing treatment was attained in 18 cases (14%). Treatment was discontinued due to side effects in 18 cases (14%); in two-thirds of these cases side effects occurred during the first 2 months. Of the total number of patients, 49 (38%) completed 2 years of treatment, with significant improvement in both clinical and laboratory indices of disease activity. Treatment had no noticeable effect on iridocyclitis. One patient died of cytomegalovirus infection during azathioprine treatment. CONCLUSION: Azathioprine is a useful drug in severe JCA, with a sustained effect and acceptable side effects. Even in cases of incomplete remission, its glucocorticoid sparing effect was noteworthy.

Adolescent↗
PubMed1996

Antibodies to phospholipid-binding plasma proteins and occurrence of thrombosis in patients with systemic lupus erythematosus.

There is accumulating evidence that anti-phospholipid (aPL) antibodies in the sera of patients with autoimmune diseases bind to a complex of anionic phospholipids and plasma phospholipid-binding proteins, namely beta 2-glycoprotein I (beta 2-GPI) and prothrombin. It has been suggested that a conformational change in beta 2-GPI, induced by binding either to anionic phospholipids or to the oxygen molecules on the irradiated microtiter plate, reveals cryptic antigenic epitope(s) in the native protein. We used an enzyme-linked immunoassay for measuring antibodies against two phospholipid-binding proteins, i.e., beta 2-GPI and prothrombin, absorbed to an irradiated plate in an unselected series of 139 patients with systemic lupus erythematosus (SLE). Elevated levels of antibodies against beta 2-GPI were found in 49% of patients and antibodies against prothrombin in 34% of patients. Both antibodies were significantly associated with deep venous thrombosis in patients with SLE (P = 0.009 for both antibodies). Accordingly, testing of these antibodies seems to be clinically useful in evaluating the risk of thrombosis.

Adolescent↗
PubMed1996

Affinity-purified cardiolipin-binding antibodies show heterogeneity in their binding to oxidized low-density lipoprotein.

Antiphospholipid antibodies in autoimmune sera have been shown to react with a complex of phospholipids (cardiolipin) and a plasma phospholipid-binding protein, beta 2-glycoprotein I (apolipoprotein H). The binding of these antibodies was inhibited by oxidized low-density lipoprotein (LDL) in sera from patients with systemic lupus erythematosus (SLE), suggesting cross-reactivity between antiphospholipid antibodies and antibodies binding to oxidized LDL. We purified antiphospholipid antibodies by cardiolipin-polyacrylamide column from seven SLE sera and studied the reactivity of eluted fractions with cardiolipin-beta 2-glycoprotein I complex and oxidized LDL (malondialdehyde-conjugated LDL) in solid-phase enzyme immunoassay. In four sera the binding of IgG antibodies to cardiolipin-beta 2-glycoprotein I complex and to oxidized LDL appeared in the same fractions, whereas in three sera reactivities against cardiolipin and oxidized LDL were observed, at least in part, in separate fractions. The binding to solid-phase cardiolipin was dependent on the presence of exogenous beta 2-glycoprotein I in all fractions. Our findings show that antiphospholipid antibodies are heterogeneous in their binding to oxidized LDL, indicating that these two antibodies may have different subspecificities. Some eluted fractions reacted only with oxidized LDL, and did not show binding to cardiolipin-beta 2-glycoprotein I complex, suggesting that the lipid part in the antigenic complex might be responsible for the cross-reactivity of these antibodies. Accordingly, the biological functions of antibodies against phospholipid-beta 2-glycoprotein I complex and antibodies against oxidized LDL may also be different.

Adult↗
PubMed1996

Incidence of rare systemic rheumatic and connective tissue diseases in Finland.

OBJECTIVE: To obtain information on the incidence of rare systemic rheumatic and connective tissue diseases in Finland. DESIGN: Population-based epidemiological study. SETTING: Five out of 21 central hospital districts in Finland (population: about 1 million adults > or = 16 years of age). SUBJECTS: Subjects entitled under the nationwide sickness insurance scheme to receive specially reimbursed medication for rare systemic rheumatic or connective tissue diseases in 1990. MAIN OUTCOME MEASURE: Incidence. RESULTS: A total of 30 incident cases occurred. Nine patients had mixed connective tissue disease, four had systemic sclerosis, four had dermato/polymyositis and one patient had inclusion body myositis; the corresponding annual incidence rates were 8, 4, 4 and 1/million of the adult population. Only one patient had adult Still's disease. The overall annual incidence rate of systemic vasculitides was 9/million of the adult population. CONCLUSION: This study provides population-based figures on the incidence of rare systemic rheumatic and connective tissue diseases in Finland.

Adolescent↗
PubMed1996

Serum cholesterol and risk of rheumatoid arthritis in a cohort of 52 800 men and women.

Recent epidemiological studies have suggested that joint risk factors occur for rheumatoid arthritis (RA) and coronary heart disease. We studied serum cholesterol concentration for its association with the incidence or RA in 28 362 men and 24 444 women free from arthritis at baseline. During a mean follow-up of 21 yr, 161 men and 351 women developed RA. Of these incident cases, 119 men and 229 women were rheumatoid factor (RF) positive. The serum cholesterol concentration was directly proportional to the risk of RF-positive RA among women and RF-negative RA among men; the age-adjusted relative risks (95% confidence intervals) per S.D. (1.4 mM/l) of the cholesterol distribution were 1.20 (1.05-1.38) and 1.56 (1.15-2.10), respectively. No association was observed, however, for RF-negative RA among women or RF-positive RA among men. The results suggest that a still unknown factor closely associated with serum cholesterol may be involved in the aetiology of RA, but complex interactions with sex and RF status seem to occur.

Adolescent↗
PubMed1996

Incidence of rheumatoid arthritis in Finland during 1980-1990.

OBJECTIVE: To obtain information on the incidence of rheumatoid arthritis and on its recent trends in Finland. METHODS: The study covered those subjects entitled to receive specially reimbursed medication for rheumatoid arthritis under the nationwide sickness insurance scheme in five out of 21 central hospital districts in Finland (population basis about one million adults) during three years: 1980, 1985, and 1990. RESULTS: The annual incidence of rheumatoid arthritis in 1980 and 1985, satisfying the American Rheumatism Association 1987 classification criteria, was 39/100,000 of the population > or = 16 years of age. The combined incidence of rheumatoid factor (RF) positive arthritis and RF negative polyarthritis was 46/100,000. A decline of approximately 40% occurred in the number of RF negative rheumatoid arthritis cases in 1990 compared with the earlier years. The declining trend was statistically significant (P = 0.008). CONCLUSION: The decline in incidence of RF negative rheumatoid arthritis in Finland may reflect changes in the environment specifically affecting the risk of RF negative disease.

Arthritis, Rheumatoid↗
PubMed1996

Declining incidence and mortality rates of stroke in Finland from 1972 to 1991. Results of three population-based stroke registers.

BACKGROUND AND PURPOSE: We aimed to determine trends in stroke incidence, mortality rates, case-fatality rates, and their relation in Finland. METHODS: We compared the results of three population-based stroke registers that included first-ever strokes in people aged > or = 15 years. Two registers were kept in Espoo-Kauniainen, the first in 1972 to 1973 (EK 72-73) and the second in 1978 to 1980 (EK 78-80). The present register of the Finnish Heart Association (FHA 89-91) was kept in four districts in Finland in 1989 to 1991. RESULTS: The age-adjusted incidence rates were 240.9, 174.4, and 191.6, and the 1-year mortality rates were 121.9, 77.0, and 65.3 in the EK 72-73, EK 78-80, and FHA 89-91 registers, respectively. The overall decline from 1972 to 1991 was 20% in the stroke incidence rate and 46% in the stroke mortality rate. One-month case-fatality rates decreased from 34.8% to 29.4% in the EK 72-73 and EK 78-80 registers and to 23.3% in the present register. CONCLUSIONS: The decline in the stroke incidence rate during the 1970s stabilized during the late 1980s and early 1990s; however, the case-fatality rate is still decreasing. Their combined effects may explain the continuing decline in stroke mortality.

Adolescent↗
PubMed1996

Antibodies to prothrombin imply a risk of myocardial infarction in middle-aged men.

Antiphospholipid antibodies in patients with "antiphospholipid syndrome" may be directed at least in part against plasma phospholipid-binding proteins, such as beta 2-glycoprotein I or prothrombin, which are involved in the control of thrombosis and haemostasis. IgG-class antibodies against prothrombin and beta 2-glycoprotein I were measured by enzyme-linked immunoassay in initially healthy middle-aged dyslipidaemic men (non-high-density lipoprotein > 5.2 mml/l). Serum samples had been drawn at entry to a 5-year coronary primary-prevention trial with gemfibrozil from 106 subjects who experienced either a non-fatal myocardial infarction or cardiac death during the follow-up and from 106 subjects without coronary episodes, matched for treatment group (gemfibrozil/placebo) and geographical area. The antiprothrombin antibody level, as expressed in optical density units, was significantly higher in patients than in controls (0.26 +/- 0.17 versus 0.22 +/- 0.09; p < 0.02). A high level of antiprothrombin antibodies (highest tertile of distribution) predicted a 2.5-fold increase in the risk (95% confidence interval 1.2-5.3) of myocardial infarction or cardiac death. The distribution of IgG-class antibodies against beta 2-glycoprotein I did not differ significantly between cases and controls. The joint effect of antiprothrombin antibodies and other factors associated with hypercoagulative state: triglyceride level, lipoprotein(a) and smoking, was multiplicative for the risk. Antiprothrombin antibodies are a new immunological predictor of myocardial infarction and the effect of these antibodies may be mediated by hypercoagulative mechanisms.

Apolipoproteins↗
PubMed1995

Anti-cardiolipin antibodies and risk of myocardial infarction in a prospective cohort of middle-aged men.

BACKGROUND: Data concerning the relation between antiphospholipid (aPL) antibodies and myocardial infarction in subjects without evidence of overt autoimmune disease are conflicting. All published studies have been performed on survivors of myocardial infarction or in patients with established coronary heart disease. The purpose of the present study was to determine whether the presence of aPL antibodies, namely, anti-cardiolipin (aCL) antibodies, carries a risk for myocardial infarction in a prospective cohort. METHODS AND RESULTS: The sera to be studied were drawn at entry from middle-aged dyslipidemic men (non-high-density lipoprotein cholesterol, > or = 5.2 mmol/L) participating in the Helsinki Heart Study, a 5-year coronary primary prevention trial with gemfibrozil. Samples were tested for IgG-class antibodies to cardiolipin by an ELISA. The risk was estimated with logistic regression analysis using a nested case-control design with 133 patients (myocardial infarction or cardiac death) and 133 control subjects, matched for treatment (gemfibrozil/placebo) and geographical area. The aCL antibody level, as expressed in optical density units, was significantly higher in patients than in control subjects (0.417 versus 0.361; P < .005). Subjects with the antibody level in the highest quartile of distribution had a relative risk for myocardial infarction of 2.0 (95% confidence interval, 1.1 to 3.5) compared with the remainder of the population. This risk was independent of confounding factors, such as age, smoking, systolic blood pressure, low-density lipoprotein (LDL), and high-density lipoprotein. There was a correlation between the levels of aCL antibodies and antibodies to oxidized LDL (r = .40, P < .001), and their joint effect was additive for the risk. CONCLUSIONS: In a prospective cohort of healthy middle-aged men, the presence of a high aCL antibody level is an independent risk factor for myocardial infarction or cardiac death. Antibodies to cardiolipin and oxidized LDL may, at least in part, represent cross-reactive antibody populations.

Antibodies, Anticardiolipin↗
PubMed1995

Mortality in rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) have a substantially reduced life expectancy. The standardized mortality ratio in different studies has ranged from 1.13 to 2.98. This mainly applies to rheumatoid factor (RF)-positive cases, although there is a subgroup of RF-negative cases with an adverse long-term prognosis. Clinically based studies probably overestimate the true shortening of life span and population-based studies may underestimate it. Excess mortality from infection and from renal disease likely reflects the presence of severe disease, whereas most of the added mortality from gastrointestinal causes is treatment related. The reasons for the surplus of mortality from cardiovascular causes are not fully known. RF may have a direct role, and preillness factors such as smoking may predipose patients to RA and also render them susceptible to cardiovascular diseases. The excess mortality associated with RA is appreciably higher than is apparent from the cases in which RA is regarded as an underlying cause of death. The effect of treatment on mortality remains largely unknown.

Arthritis, Rheumatoid↗