Biomedical subjects

A Karjalainen

Publications and source records attributed to A Karjalainen.

At least 19 recordsLinked to original sources

PubMed2006

Inhibitory characteristics of citrullinated telopeptides of type I and II collagens for autoantibody binding in patients with rheumatoid arthritis.

OBJECTIVE: To study how soluble citrullinated telopeptides of type I and II collagens inhibit the binding of autoantibodies to the respective antigens immobilized onto solid phase, and to use modifications of previous methods to re-analyse rheumatoid arthritis (RA) and control serum samples. METHODS: Autoantibody binding was inhibited with normal or citrullinated carboxytelopeptides using enzyme-linked immunosorbent assay (ELISA) methods. Serum samples were available from 120 patients with RA and 81 controls. RESULTS: Autoantibodies that bind normal C-telopeptides were not inhibited with soluble normal or citrullinated telopeptides. However, the antibodies that bind only citrullinated telopeptides could be inhibited with corresponding citrullinated telopeptides. Thus, it is not necessary to study the binding of autoantibodies to normal collagens if the specificity of their binding is assessed by immunological inhibition. For type I telopeptide, there are two arginines, the latter of which, when citrullinated, is important for binding. For type II telopeptide, there is one arginine, which is important when citrullinated. The other amino acids, e.g. the last alanine, have only a slight effect on binding. These improved methods differentiate better between RA patients, who have specific citrullinated autoantibodies, and controls than previous ELISA methods. CONCLUSIONS: Based on inhibition assay, it is possible to measure the autoantibodies binding specifically to citrullinated telopeptides of type I and II collagens. When only one assay is involved, variance is decreased and the overall performance is easier than before.

Adult↗

PubMed2006

Polymorphism at position +896 of the toll-like receptor 4 gene interferes with rapid response to treatment in rheumatoid arthritis.

The aim of this study was to determine whether the +896 A-->G substitution of the Toll-like receptor 4 (TLR4) gene, causing the Asp299-->Gly change in the extracellular domain of TLR4, influences treatment response in recent-onset rheumatoid arthritis. 169 patients with rheumatoid arthritis were genotyped from the Finnish Rheumatoid Arthritis Combination Therapy trial, in which they were treated either with only one disease-modifying antirheumatic drug (DMARD) with or without prednisolone (single group), or with three DMARDs and prednisolone (combination group). Patients homozygotic for the wild-type +896A allele were compared with those having the polymorphic G allele in terms of early clinical response (at 6 months) by the 28-joint Disease Activity Score (DAS28). 1 of 20 (5%; (95% (confidence interval (CI) 1 to 5)) patients of the single group with TLR4 +896AG or GG and 29 of 67 (43%; (95% CI 31 to 56)) patients with AA were in remission (p = 0.001). DAS28 of the single group with TLR4 +896AG or GG was higher than with AA (p = 0.019). In the combination group, remission rates and DAS28 values were comparable between the genotypes. The polymorphic TLR4 +896G allele may impair treatment response to single DMARD treatment in recent-onset rheumatoid arthritis.

Antirheumatic Agents↗

PubMed2006

Biological treatment in rheumatic diseases: results from a longitudinal surveillance: adverse events.

The objective of this study was to assess the long-term safety and tolerability of biologicals in a clinical setting. Data on adverse events (AEs) have been collected over a 5-year period by means of detailed reports sent in to the National Register of Biological Treatment in Finland (ROB-FIN) and validated by information collected by the National Agency for Medicines. Three hundred and eight reports on AEs were filed, concerning a total of 248 patients; this corresponds to 17% of all patients in the ROB-FIN register who started biological treatments. Skin reactions and infections comprised 35 and 28% of the AEs, respectively. Some cases of tuberculosis and other infections, heart failure and demyelinating conditions were seen. Our work demonstrates no unexpected AEs in a Finnish patient cohort consisting of rheumatoid arthritis and spondylarthropathy patients, although many of them were treated with combination treatments in common use in Finland. Biological treatment appears safe in the hands of the Finnish rheumatologists.

Adolescent↗

PubMed2006

Increased expression of high mobility group A proteins in lung cancer.

High mobility group A (HMGA) proteins play an important role in the regulation of transcription, differentiation, and neoplastic transformation. In this work, the expression of HMGA 1 and 2 in 152 lung carcinomas of mainly non-small-cell histological type has been studied by immunohistochemistry in order to evaluate their feasibility as lung cancer markers. In 17 lung cancer cases, the related bronchial epithelial changes were also studied for HMGA1 and 2 expression. RNA expression of HMGA1a and b isoforms and of HMGA2 was determined by real-time semi-quantitative RT-PCR in 23 lung carcinomas. High expression of HMGA1 and HMGA2 at both mRNA and protein levels was detected in lung carcinomas, compared with normal lung tissue. Nuclear immunostaining for HMGA1 and 2 proteins also occurred in hyperplastic, metaplastic, and dysplastic bronchial epithelium. Increased nuclear expression of HMGA1 and 2 correlated with poor survival (for adenocarcinomas, HMGA1, p=0.006; HMGA2, p=0.05). While the expression of HMGA2 was significantly associated with cell proliferation (p=0.008), HMGA1 expression did not show any association with proliferation or apoptotic index. Sequencing of HMGA2 transcripts from tumours with very high expression showed a normal full-length transcript. As HMGA proteins were expressed in about 90% of lung carcinomas and their expression was inversely associated with survival, they may provide useful markers for lung cancer diagnosis and prognosis.

Aged↗

PubMed2005

Are there autoantibodies reacting against citrullinated peptides derived from type I and type II collagens in patients with rheumatoid arthritis?

OBJECTIVES: To assess the possible presence in patients with rheumatoid arthritis (RA) of autoantibodies recognising citrullinated peptides derived from type I and II collagens. METHODS: Firstly, the binding of four pairs of synthetic peptides (arginine-containing and artificially citrullinated forms) related to different regions of human type II collagen were tested with sera from 120 patients with RA and 81 controls. Secondly, two similar pairs of peptides related to the carboxy terminal telopeptides of the alpha1 and alpha2 chains of human type I collagen were tested. RESULTS: 42-53% of the RA sera showed increased binding of arginine peptides related to type II collagen. However, 12 RA sera bound the citrullinated form of the alpha1(II) telopeptide more strongly than the corresponding arginine peptide. 20 RA sera bound the citrullinated carboxytelopeptide from the alpha1 chain of type I collagen (alpha1(I) telopeptide) more strongly than the respective arginine peptide. The correlation between the autoantibodies to type I and II collagen telopeptides was r(s) = 0.576, p < 0.001. Anti-cyclic citrullinated peptide (anti-CCP) assay was positive in 71/120 (59%) patients with RA. An anti-CCP assay detects a different subgroup of antibodies than anti-telopeptide assays. However, both anti-telopeptide and anti-CCP antibodies were increased in patients with RA. CONCLUSION: Some patients with RA were identified whose sera contained antibodies that specifically bound citrullinated peptides related to the carboxy terminal telopeptides of the alpha1 and alpha2 chains of type I collagen and the alpha1 chains of type II collagen (sequences YYXA, FYXA, and YMXA, where X stands for citrulline).

Adolescent↗

PubMed2003

Prevalence of work-aggravated symptoms in clinically established asthma.

This population-based cross-sectional survey assessed the prevalence of work-aggravated asthma symptoms and the effect of the work environment on the aggravation of symptoms of established asthma. A questionnaire was sent to 2,613 persons (aged 20-65 yrs) with asthma. The analyses were restricted to the 969 respondents who were currently employed. The effect of occupational exposure on the aggravation of asthma symptoms at work was assessed according to both self-reported and expert-evaluated exposure. Approximately 21% of the respondents reported work-aggravated asthma symptoms at least weekly during the past month. The prevalence of those with work-aggravated symptoms increased by age, self-reported occupational exposure to dusts, abnormal temperatures or poor indoor air quality, physically strenuous work, and chemicals, and expert-evaluated probability of daily occupational exposure to airborne dusts, gases or fumes. Aggravation of asthma symptoms at work is common among employed adults with asthma. Both self-reported and expert-evaluated exposure to dusts, abnormal temperatures or poor indoor air quality, physically strenuous work, and chemicals explained the significant worsening of symptoms. The findings suggest a marked role of the work environment in the aggravation of symptoms of established asthma.

Adult↗

PubMed2002

Excess incidence of asthma among Finnish cleaners employed in different industries.

The incidence and risk of asthma among female cleaners employed in different industries was explored. An increased risk of asthma has been associated with the cleaning profession, in some but not all studies. All Finnish females employed as cleaners and all those employed in administrative work were followed for asthma incidence through a record linkage in 1986-1998. An individual was defined as an "incident case of asthma" if they received rights for special reimbursement of asthma medication from the national health insurance or were recognized as having occupational asthma. Age-adjusted relative risks (RR) were estimated for cleaners in comparison with those employed in administrative work. There were 2,414 and 5,235 cases of asthma among the cleaners and administrative workers, respectively. The RR was 1.50 (95% confidence interval (CI) 1.43-1.57) in cleaners. The risk was increased in cleaners working in nearly all major sectors of economic activity, but cleaners employed by companies concerned with the manufacture of basic metals (RR 2.47; 95% CI 1.68-3.64) and food products (RR 2.19; 95% CI 1.69-2.85) had the highest risk. Only 25 of the "cases of asthma" among cleaners had been recognized as being occupational asthma. It could be concluded that cleaners have an increased risk of persistent adult-onset asthma. Factors inherent to the environment where cleaning is performed or differences in the cleaning agents used may explain the observed differences between industries.

Adult↗

PubMed2001

Work is related to a substantial portion of adult-onset asthma incidence in the Finnish population.

There are no population-based follow-up studies to estimate the fraction of asthma incidence that is attributable to work. In Finland, individuals with clinically well-established persistent asthma are registered for reimbursement of medication from the national health insurance scheme. We combined, at an individual level, these data with the population census data of 1985, 1990, and 1995 to estimate the attributable fraction of work in adult-onset persistent asthma. Our follow-up study covered the entire 25- to 59-yr-old employed population of Finland in 1986-1998. Relative risks (RR) for occupational categories were estimated in comparison to those employed in administrative work. There were 49,575 incident cases of asthma. The attributable fraction of occupation was 29% (95% CI 25-33%) for men and 17% (95% CI 15-19%) for women. The risk was increased especially in agricultural work, manufacturing work, and service work. In addition to already established risk occupations of occupational asthma, such as food and beverage work, the analysis identified a large number of occupations with significant excess of asthma incidence. The results indicate that the impact of occupational factors in the inception of adult-onset persistent asthma, and consequently the potential for prevention, is much larger and more widely spread than generally assumed.

Adult↗

PubMed2001

Effects of peroral and transdermal oestrogen replacement therapy on glucose and insulin metabolism.

OBJECTIVE: Conflicting data have been reported previously on the effects of oestrogen replacement therapy on glucose tolerance, and the effects on glycosylated haemoglobin GHbA(1c) have been studied only among diabetics. The objective of this study was to evaluate the effects on glucose and insulin metabolism among nondiabetic women and to compare the outcomes of peroral and transdermal modes of administration. DESIGN: The effects of peroral oestradiol valerate 2 mg/day with placebo gel were compared to those of transdermal 17 beta-oestradiol gel (1 mg oestradiol/day) and placebo tablets in a randomised, double-blind, double-dummy study for six months. PATIENTS: Seventy-nine hysterectomised, nondiabetic postmenopausal women, 39 women in the peroral oestrogen group and 40 in the gel group. MEASUREMENTS: Oral glucose tolerance tests (OGTT) with blood glucose, serum C-peptide and insulin determinations were performed. GHbA(1c), IGF-I and IGFBP-1 were measured at baseline and after six months of therapy. In addition, insulin sensitivity and insulin secretion indices were obtained from OGTT. RESULTS: A small significant reduction in the GHbA(1c) concentration was observed during both peroral (P < 0.05) and transdermal oestrogen therapy (P < 0.05). However, no effect on insulin sensitivity was observed. The response to a standard 75 g oral glucose load was similar in the study groups. Compared with the baseline values, the area under the curve for C-peptide decreased by 8% both in the peroral group (P < 0.05) and in the gel group (P < 0.01). The fasting and postchallenge glucose and insulin levels or insulin release indices were not significantly altered. Peroral oestrogen decreased IGF-I and increased IGFBP-1, but these findings were not associated with the changes in glucose metabolism. CONCLUSIONS: Neither peroral nor transdermal oestradiol replacement therapy seemed to induce any negative effects on glucose metabolism over a time period of 6 months.

Administration, Cutaneous↗

PubMed2001

CYP1A1 levels in lung tissue of tobacco smokers and polymorphisms of CYP1A1 and aromatic hydrocarbon receptor.

Induction of a polycyclic aromatic hydrocarbon-metabolizing cytochrome P450 isoform CYP1A1 is regulated by aromatic hydrocarbon receptor (AHR). High inducibility of CYP1A1, possibly due to genetic polymorphisms, has been considered to be a risk factor for lung cancer in tobacco smokers. The relationship between low or high pulmonary expression of CYP1A1 and polymorphic genotypes of CYP1A1 and AHR was investigated in 73 active smokers. CYP1A1 expression was determined in surgical lung samples by measuring ethoxyresorufin O-deethylase (EROD) activity and by immunostaining for CYP1A1 protein. The most common allelic variants of CYP1A1 and AHR in Finns, i.e. the MspI variant (CYP1A1*2A), I462V variant (CYP1A1*2B), and -459C to T variant of CYP1A1 and the R554K variant (AHR*2) of AHR were studied using polymerase chain reaction based methods. EROD activity correlated positively with the daily cigarette consumption (r = 0.45). There was additional variation in EROD activity independent of the amount of smoking e.g. among those who smoked one pack per day until the day of operation, EROD activity ranged from 4-142 (median 48) pmol/min/mg. The frequencies of the MspI, 462V, and -459T variant alleles of CYP1A1 and 554K variant allele of AHR were 0.158, 0.055, 0.055 and 0.075, respectively. No differences were observed in the frequencies of polymorphic genotypes between the smokers with low and those with high expression, when the relationship was studied using a regression analysis adjusted for cigarette consumption. Our results thus indicate that the interindividual variation of CYP1A1 levels in smokers' lung tissue is not attributable to genetic polymorphisms of CYP1A1 or AHR tested in this study.

Cytochrome P-450 CYP1A1↗

PubMed2001

Association between pleural plaques and coronary heart disease.

OBJECTIVE: The aim of this study was to verify a clinical impression that patients with coronary heart disease disproportionately frequently have calcified pleural plaques. METHODS: Chest X-rays were collected from 148 patients referred consecutively to the Helsinki University Central Hospital for coronary angiography and from 100 consecutive lung cancer patients seen at the same hospital. The radiographs were analyzed for the presence of calcified pleural plaques according to the classification the International Labour Office. A generalized linear model with binomial distribution and log link was used to estimate the relative risks and their 95% confidence intervals (95% CI). RESULTS: The prevalence of calcified pleural plaques was 35% for the coronary patients and 19% for the lung cancer patients. Calcified pleural plaques were more common among the men than the women, and the risk increased with age. The relative risk of calcified pleural plaques, adjusted for age and gender, was 2.19 (95% CI 1.44-3.32) for the coronary patients as compared with the lung cancer patients. CONCLUSIONS: Further studies with better information on past exposure to asbestos and other potential risk factors are warranted to confirm the observations and to examine whether the association between coronary heart disease and calcified pleural plaques is related to an etiologic or an individual susceptibility factor common to both of these conditions.

Adult↗

PubMed2001

Epidemiologic estimate of the proportion of fatalities related to occupational factors in Finland.

OBJECTIVES: This study attempts to estimate the proportion of annual deaths related to occupational factors in Finland and considers related methodological issues and associated uncertainties. METHODS: Statistics on causes of death, numbers of subjects exposed, and risk ratios obtained from the epidemiologic literature were used to estimate the population attributable fraction and disease burden for causes of death from work-related diseases. Gender-, age- and disease-specific numbers of deaths were provided by Statistics Finland for 1996. Information on the size of the population, broken down by gender, age, occupation, and industry, was acquired from population censuses. A Finnish job-exposure matrix supplied data on the prevalence of exposure for specific agents and the level of exposure among exposed workers. RESULTS: The attributable fraction of work-related mortality in the relevant disease and age categories was estimated to be 7% (10% for men and 2% for women), and for all diseases and ages the fraction was 4%. For the main cause-of-death categories, the attributable fraction became 12% for circulatory system diseases, 8% for malignant neoplasms, 4% for respiratory system diseases, 4% for mental disorders, 3% for nervous system diseases, and 3% for accidents and violence. The following estimates were obtained for specific important diseases: 24% for lung cancer, 17% for ischemic heart disease, 12% for chronic obstructive pulmonary disease, and 11% for stroke. Based on these fractions, the total number of work-related deaths that occurred in Finland in 1996 was calculated to be on the order of 1800 (employed work force of 2.1 million); 86% involved men. CONCLUSIONS: High-quality epidemiologic studies and national survey data are essential for obtaining reliable estimates of the proportion of deaths attributable to occupational factors. The magnitude of work-related mortality is an insufficiently recognized contributor to total mortality in Finland, especially from circulatory diseases and other diseases caused by exposure to agents other than asbestos.

Adult↗

PubMed2000

Survival in operable non-small-cell lung cancer: role of p53 mutations, tobacco smoking and asbestos exposure.

Validated markers are needed to identify operable lung cancer patients with poor prognosis. About one-half of non-small-cell lung cancers (NSCLCs) carry a mutation in the p53 tumor-suppressor gene. We examined 101 NSCLC patients for surgical stage, completeness of resection, tobacco smoking, asbestos exposure, age, gender and p53 gene mutations as prognostic factors after a follow-up period of 4 years. Cox's multivariate regression model was applied to quantify the associations with overall and cancer-related survival. Patients with a wild-type p53 gene had an overall 4-year survival of 43% and those with a mutated p53 gene, 35%. In squamous-cell carcinoma, stage and heavy smoking, defined as the median of pack-years smoked, had prognostic significance for overall survival. Only stage was associated with poor cancer-related survival. Asbestos exposure was not associated with overall survival or cancer-related survival in squamous-cell carcinoma or adenocarcinoma. In adenocarcinoma, p53 mutation, in addition to stage, emerged as a significant predictor of poor cancer-related survival.

Adult↗

PubMed2000

Incidence of occupational asthma by occupation and industry in Finland.

BACKGROUND: Systematic research on occupation or industry-specific incidence of occupational asthma (OA) is sparse. We calculated the incidence of notified OA by occupation, industry and causative agent in Finland for the years 1989-95. METHODS: The numbers of cases of reported OA were retrieved from the Finnish Registry of Occupational Diseases for the population between 20 and 64 years of age. The numbers of employed workers were retrieved from Statistics Finland. Incidence rates were calculated for each occupation, industry and the total workforce. RESULTS: Altogether 2602 cases of OA were notified and the mean annual incidence rate was 17.4 cases/100,000 employed workers. The incidence rate was the highest in bakers, other painters and lacquerers, veterinary surgeons, chemical workers, farmers, animal husbandry workers, other food manufacturing workers, welders, plastic product workers, butchers and sausage makers, and floor layers. Cases caused by animal epithelia, hairs and secretions or flours, grains, and fodders accounted for 60% of the total. CONCLUSIONS: Estimation of occupation and industry-specific incidence rates forms the basis for successful prevention of OA, but necessitates collection of data over several years from well-established surveillance systems.

Adult↗

PubMed2000

Insulin-like growth factor binding protein-1 (IGFBP-1) and IGF-I during oral and transdermal estrogen replacement therapy: relation to lipoprotein(a) levels.

Low levels of insulin-like growth factor binding protein-1 (IGFBP-1) have recently been associated with several risk factors for cardiovascular disease. The effects of estrogen replacement therapy (ERT) on plasma IGFBP-1 levels are, however, unclear. A double-blind, placebo-controlled study for 6 months was conducted in 73 hysterectomized postmenopausal women randomized into two groups: oral estradiol (E2) valerate, 2 mg/day (n = 35) and transdermal E2 gel, 1 mg/day (n=38). Plasma IGFBP-1, insulin-like growth factor-I (IGF-I) and lipoprotein(a) (Lp(a)) were determined at baseline, 3 and 6 months. The groups were similar for age and BMI. The baseline levels of estrone (E1), E2, IGFBP-1, IGF-I and Lp(a) did not differ between the groups. During treatment, serum estradiol concentrations increased in both groups. During oral ERT, IGFBP-1 levels increased by 104% (P<0.001), whereas IGF-I levels decreased by 13% (mean, P<0.05). IGF-I and IGFBP-1 levels remained unchanged in the transdermal group. Lp(a) levels decreased by 23% (median, P<0.001) in the oral group, but were unaffected by transdermal therapy. The change in IGFBP-1 concentrations during oral ERT showed an inverse correlation to that in Lp(a) (r = -0.40, P<0.05, Spearman correlation). In conclusion, oral ERT seems to enhance plasma levels of IGFBP-1, which may be one reason for the reduced Lp(a) levels.

Administration, Cutaneous↗

PubMed2000

Regulation of plasma low density lipoprotein levels in postmenopausal women.

To study the regulation of plasma low density lipoprotein (LDL) cholesterol in postmenopausal women (n = 79), fasting plasma lipids and lipoproteins, the fractional catabolic rate (FCR) and production rate for LDL apolipoprotein B (apo B), cholesterol absorption, apolipoprotein E phenotype and polymorphisms of the apo B and 7alpha-hydroxylase genes were determined. The level of LDL cholesterol was related to FCR (r= -0.757, P < 0.001) and the production (r= 0.531, P < 0.001) of LDL apo B and body mass index (r = 0.265, P <0.05). In contrast, cholesterol absorption efficiency, apolipoprotein E phenotype, EcoRI and XbaI polymorphisms of the apo B gene and the polymorphism of 7alpha-hydroxylase gene were found to have no significance for the regulation of LDL cholesterol concentration in these postmenopausal women.

Apolipoproteins E↗

PubMed2000

A broad amplification pattern at 3q in squamous cell lung cancer--a fluorescence in situ hybridization study.

Frequent DNA copy number gain at 3q, with minimal overlapping area at 3q24-qter, has previously been reported in squamous cell carcinoma of the lung (SQCC), implicating the importance of genes at 3q in the tumorigenesis of SQCC. To further characterize the gain of DNA sequences at 3q, we performed interphase fluorescence in situ hybridization (FISH) analysis on 16 paraffin-embedded SQCC tumor samples that had previously been studied by comparative genomic hybridization (CGH). Eleven yeast artificial chromosome (YAC) probes located at 3q25-q27 and a chromosome 3-specific centromeric probe were used in the analysis. All SQCC tumors showed increase in DNA sequence copy number with 9-11 probes. In 5 tumors (31%) the number of centromeric signals varied from 3 to 5 and the YAC/centromeric signal ratio was 1.0, suggesting that the increase in DNA sequence copy number at 3q in these cases resulted from polysomy of chromosome 3. In 11 tumors (69%), the YAC/centromeric signal ratio varied between 1.5 and 4.7, indicating that the increase in DNA sequence copy number was due to intrachromosomal gain of DNA sequences at 3q. In each case, several YACs showed increased number of signals, demonstrating that the gained area was relatively large. Our findings therefore suggest that multiple genes located at 3q25-q27 are involved in the tumorigenesis of SQCC.

Carcinoma, Squamous Cell↗

PubMed2000

Synthesis of new potent and selective aromatase inhibitors based on long-chained diarylalkylimidazole and diarylalkyltriazole molecule skeletons.

A series of long-chained diarylalkylimidazoles and diarylalkyltriazoles were synthesized and evaluated for the inhibitory potency for aromatase (estrogen synthetase) activity in human placental microsomes. The relative specificity of inhibition was evaluated by measuring the inhibition of cholesterol side-chain cleavage enzyme (desmolase) in human placental mitochondria and the inhibition of 7-ethoxycoumarin O-deethylase (a typical drug-metabolizing enzyme activity) in rat liver microsomes. The structural requirements including substituent effects for the strongest potency and for the highest specificity were delineated. alpha,omega-Diarylalkyltriazoles and imidazoles were the most interesting molecules, in which the geometric and optical isomerism displayed remarkable selectivity for aromatase inhibition.

Animals↗