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P Pelkonen

Publications and source records attributed to P Pelkonen.

At least 19 recordsLinked to original sources
PubMed2002

Campylobacter-triggered reactive arthritis: a population-based study.

OBJECTIVE: To study the incidence and clinical picture of Campylobacter-associated reactive arthritis (ReA) and other reactive musculoskeletal symptoms in the population. METHODS: A questionnaire on enteric and extraintestinal, including specifically musculoskeletal, symptoms was sent to 870 consecutive patients with Campylobacter-positive stool culture and 1440 matched controls. Analysis of self-reported musculoskeletal symptoms with clinical examination was performed. RESULTS: Forty-five of the patients (7%) had ReA and eight (1%) had reactive tendinitis, enthesopathy or bursitis. No child had ReA. The arthritis was oligo- or polyarticular, and, in most cases, mild. HLA-B27 was positive in 14% of ReA patients. Of the 45 ReA patients, 37 had C. jejuni and 8 had C. coli infection. No controls had ReA. CONCLUSION: ReA is common following Campylobacter infection, with an annual incidence of 4.3 per 100000. At the population level, acute ReA is mild, more frequent in adults, and not associated with HLA-B27. Besides C. jejuni, C. coli can trigger ReA.

Adult↗
PubMed2001

Construct validity of ILAR and EULAR criteria in juvenile idiopathic arthritis: a population based incidence study from the Nordic countries. International League of Associations for Rheumatology. European League Against Rheumatism.

OBJECTIVE: New classification criteria (ILAR) have been proposed for juvenile idiopathic arthritis (JIA). They are more descriptive than those formerly used [American College of Rheumatology (ACR), European League Against Rheumatism (EULAR)], but require validation against classifications already in use. We validated the ILAR criteria in relation to the EULAR criteria in a prospective, incidence, and population based setting, and analyzed their feasibility. METHODS: Construct validity of ILAR and EULAR classification criteria refers to how closely the 2 instruments are related and how each of them operates in classifying subgroups/categories. Twenty doctors in 5 Nordic countries collected data from the incidence cases within their catchment areas during an 18 month period beginning July 1, 1997. Clinical and serological data from the first year of disease were collected. RESULTS: A total of 322 patients were included. Classification according to the ILAR criteria was possible in 321 patients; 290 patients had a disease duration > or = 3 months and were classified according to the EULAR criteria. One child could only be classified according to the EULAR criteria. Thus, 31/322 (9.6%) children were classified according to the ILAR criteria only. Forty-eight of 321 (15%) patients did not fit into any category and 6% (20/321) fulfilled criteria for2 categories. In the ILAR classification 5 out of 7 categories/subgroups have 2 to 5 specified exclusion criteria that highly discriminate the definition of each patient. In our study the exclusion criteria were fulfilled to only a small extent. CONCLUSION: The EULAR and ILAR criteria differ concerning the operational definitions of the subvariables involved, which complicates their comparison. By using ILAR rather than EULAR criteria the number of cases with juvenile arthritis increased by 10%, considering the first half-year after onset. The validity of the ILAR criteria is low since they often exclude patients from subgroup classification and the possibility of having more than one diagnosis is not negligible. The specified exclusion criteria for some of the subgroups are difficult to fulfill in clinical work and variables involved could be questioned with regard to their consistency.

Adolescent↗
PubMed2000

Elevated serum transferrin receptor concentration in children with juvenile chronic arthritis as evidence of iron deficiency.

OBJECTIVES: Active juvenile chronic arthritis (JCA) is accompanied by anaemia of chronic disease, which may be indistinguishable from anaemia due to iron deficiency. We speculate that elevation of the serum transferrin receptor (sTfR) concentration, which should not be influenced by inflammation, would be useful for detecting the role of iron status in anaemic children with JCA. METHODS: sTfR concentrations were measured in 30 children with JCA. RESULTS: The median sTfR was elevated, 6.1 (range 3.4-13.0) mg/l. In 13 patients (43%) the concentrations exceeded the upper limit for healthy subjects. Haemoglobin (r = - 0.48, P = 0.008), mean corpuscular volume (r = - 0.47, P = 0.009) and mean corpuscular haemoglobin (r = - 0.65, P = 0.0001) correlated inversely with sTfR concentration. CONCLUSIONS: In 13 of the 30 patients with JCA, the sTfR concentration, which is an indicator of iron status and erythropoiesis, was elevated. The results raise the possibility that sTfR is able to distinguish iron-deficiency anaemia from anaemia of chronic disease. It should be further explored as a candidate.

Adolescent↗
PubMed2000

Favourable outcome in 135 children with juvenile systemic sclerosis: results of a multi-national survey.

OBJECTIVE: To increase the current knowledge of the outcome of juvenile systemic sclerosis (jSSc), which is currently limited. METHODS: In order to investigate the patient outcome and prognostic factors, starting October 1994, we distributed questionnaires to 324 paediatric rheumatology centres. RESULTS: Until 15 May 1998 responses from 46 centres were received, 34 of which returned completed questionnaires on a total of 135 patients. One hundred and twenty-two of the 135 patients were Caucasian, 100 were female. The mean age at disease onset was 8.8 yr (S.D. +/- 3.3 yr). The mean disease duration at the last follow-up was 5 yr(S.D. +/- 3.3 yr). At the last follow-up the disease was still active and required medication in 82 patients, 36 had inactive disease on medication, and 16 were in remission. Ninety per cent of the living patients were fully active in daily life at the last follow-up. Eight of the 135 patients had died. These patients had a median age at onset of the disease of 10.5 yr (range 6.7-15.8 yr). The median disease duration until death was 2 yr (range 1-8 yr). The causes of death were heart failure (five), renal failure (one), sepsis (one) and in one case the cause was not defined. The 1 yr survival rate was 99%, the 2 yr was 97% and the 4 yr was 95%. CONCLUSIONS: At a mean follow-up of 5 yr, the current results show a favourable outcome in most patients with childhood onset jSSc and a significantly better survival than in the adult SSc patients.

Adult↗
PubMed1998

Reactive arthritis following an outbreak of Salmonella Bovismorbificans infection.

A large, single-source Salmonella outbreak caused by a rare serovar Bovismorbificans (6,8:r:1,5) occurred in southern Finland in 1994. The origin of the outbreak was sprouted alfalfa seeds. A questionnaire was mailed to all 210 subjects with positive stool culture. Ninety-one percent (191/210) returned the questionnaire. One hundred and fifty-three (80%) were adults. One hundred and fifty-nine out of one hundred and ninety-one (83%) reported diarrhoea, 109 (57%) fever, 104 (54%) abdominal pains, 83 (43%) fatigue, 66 (35%) articular symptoms and 20 (10%) had no symptoms. The median duration of diarrhoea was 5 days (range 1-35), that of other symptoms 4 days (range 1-30). Those reporting articular symptoms were examined (51 patients) or contacted by telephone (13 patients). Twelve percent (22/191) fulfilled the criteria for reactive arthritis (ReA). The difference in the incidence of ReA between children and adults was not significant (8%, vs. 12%). The median onset of joint symptoms was 8.5 days; symptoms were oligoarticular in 14 (67%) and polyarticular in four (19%) patients. Mostly ReA was mild, but in four patients (18%) the joint symptoms lasted for more than 4 months. Ten (45%) ReA patients had HLA-B27 tissue type. The duration and severity of ReA did not differ between HLA-B27 positive and negative patients. Fourteen (64%) ReA patients had received fluoroquinolone treatment before reactive joint or tendon symptoms manifested, but this treatment did not prevent ReA symptoms.

Adult↗
PubMed1998

Detection of mass lesions with MR colonography: preliminary report.

PURPOSE: To evaluate the performance of magnetic resonance (MR) colonography in the detection of colorectal mass lesions. MATERIALS AND METHODS: Twenty-three patients underwent MR colonography preceding colonoscopy. The colon was filled with a gadolinium-water mixture (1:100) with MR imaging guidance, and the patient was imaged prone and supine with a breath-hold three-dimensional spoiled gradient-recalled sequence. In addition, two-dimensional spoiled gradient-recalled images were acquired before and after intravenous administration of gadopentetate dimeglumine. Images were interactively analyzed on the basis of multiplanar reconstruction by two radiologists. For regions that were not conclusively assessable with multiplanar reconstruction, virtual intraluminal endoscopic images of the colon were reconstructed. MR findings were correlated with colonoscopic results. RESULTS: Two patients were excluded from the analysis. Findings in eight of 11 patients were correctly assessed as normal and in six of 10 as mass-positive. In the four patients with false-negative findings, one had two 8-mm polyps and the other three had polyps smaller than 5 mm. All nine mass lesions larger than 10 mm, as well as four of the 10 polyps ranging between 5 and 10 mm, were detected, but all polyps smaller than 5 mm were missed. In contrast to the polyps less than 5 mm, the four missed polyps (5-10 mm) could be identified retrospectively on virtual intraluminal endoscopic images. Contrast enhancement was documented in 13 polyps. CONCLUSION: Three-dimensional MR colonography provided virtual colonoscopic viewing and helped detection of colonic polyps.

Adult↗
PubMed1997

Interaction of aflatoxin B1 with cytochrome P450 2A5 and its mutants: correlation with metabolic activation and toxicity.

Among members of the mouse cytochrome P450 2A family, P450 2A5 is the best catalyst of aflatoxin B1 (AFB1) oxidation to its 8,9-epoxide (Pelkonen, P., Lang, M., Wild, C. P., Negishi, M., and Juvonen, R. O. (1994) Eur. J. Pharmacol., Environ. Toxicol. Pharmacol. Sect. 292, 67-73). Here we studied the role of amino acid residues 209 and 365 of the P450 2A5 in the metabolism and toxicity of AFB1 using recombinant yeasts. The two sites have previously been shown to be essential in the interaction of coumarin and steroids with the P450 2A5. Reducing the size of the amino acid at position 209 or introducing a negatively charged residue at this site increased the 8,9-epoxidation of AFB1 compared to the wild type. In addition, replacing the hydrophobic amino acid at the 365 position with a positively charged lysine residue strongly decreased the metabolism of AFB1. These mutations changed the KM values generally less than the Vmax values. The changes in AFB1 metabolism contrast with the changes in coumarin 7-hydroxylation caused by these amino acid substitutions, since reducing the size of the 209 residue strongly reduced coumarin metabolism and increased the K(M) values. On the other hand, the results with AFB1 are similar to those obtained with steroid hydroxylation. This suggests that the size of the substrate is important when interacting with the residue 209 of the protein. The catalytic parameters of AFB1 correlated generally with its toxicity to the recombinant yeasts expressing the activating enzyme and with the binding of AFB1 to yeast DNA. Furthermore high affinity substrates and inhibitors (e.g., methoxsalen, metyrapone, coumarin 311, 7-methylcoumarin, coumarin, and pilocarpine) of P450 2A5 could efficiently block the toxicity of AFB1. It is suggested that the recombinant yeasts expressing engineered P450 enzymes are a useful model to understand the substrate protein interactions, to study the relationship of metabolic parameters to toxicity, and to test potential inhibitors of metabolism based toxicity.

Aflatoxin B1↗
PubMed1997

[3D MRI of the colon: methods and initial results].

PURPOSE: "Exoscopic" and endoscopic identification of colorectal pathologies via MRI. METHODS: 5 patients (36-88 years), two normal and three with different colorectal pathologies (diverticular disease, polyps and carcinoma of the colon), were examined by MRI after colonoscopy. Subsequent to filling of the colon with a gadolinium-water mixture under MRI-monitoring, 3D-data sets of the colon were acquired in prone and supine positions over a 28 sec breath hold interval. Subsequently multiplanar T1-weighted 2D-sequences were acquired before and following i. v. administration of Gd-DTPA (0.1 mmol/kg BW). All imaging was performed in the coronal orientation. The 3D-data were interactively analysed based on various displays: maximum intensity projection (MIP), surface shadowed display (SSD), multiplanar reconstruction (MPR), virtual colonoscopy (VC). RESULTS: All of the colorectal pathologies could be interactively diagnosed by MPR. On MIP images some pathologies were missed. VC presented the morphology of colon haustra as well as of all endoluminally growing lesions in a manner similar to endoscopy. The colon masses showed uptake of contrast media and could thus be differentiated from air or faeces. CONCLUSION: The potential of CMRI in colorectal diagnosis warrants further investigation in a larger series of patients.

Aged↗
PubMed1997

Paediatric rheumatology today.

A brief survey of paediatric rheumatology as a subspecialty is given, stressing the need of training programmes in paediatric rheumatology in the European countries.

Child↗
PubMed1996

Induction of cytochrome P450 2A6 expression in humans by the carcinogenic parasite infection, opisthorchiasis viverrini.

The purpose of this study was to examine in vivo the activity of cytochrome P450 (CYP) 2A6, an enzyme capable of activating carcinogens, including N-nitrosodimethylamine, in humans with the carcinogenic liver fluke infection, opisthorchiasis viverrini, before and after treatment with the antiparasitic agent, praziquantel. Coumarin hydroxylase activity of CYP 2A6 was assessed by administering a probe drug, coumarin, and measuring its metabolite, 7-hydroxycoumarin, in urines collected between 0-2 h and 2-4 h of 106 people with varying intensities of Opisthorchis viverrini infection. Five individuals who did not excrete any detectable 7-hydroxy coumarin (and have a genetic defect probably leading to an absence of catalytic activity of the CYP 2A6 protein) were excluded from analysis. Infected people excreted an average of 22.7 mumol of 7-hydroxycoumarin in the first 2 h after taking the drug, whereas the mean of the uninfected group was 19.4 mumol; this difference did not reach statistical significance (P = 0.10). However, a highly significant increase in CYP 2A6-related activity was observed in infected individuals who also had radiological evidence of biliary fibrosis (28.1 mumol) compared to those without (19.4 mumol; P = 0.01). Reassessments of coumarin hydroxylase activity of CYP 2A6 made 2 months after praziquantel treatment showed highly significant reductions in the amount of 7-hydroxycoumarin excreted among the infected groups but no difference in the uninfected group. These results suggest that expression of CYP 2A6 is induced among chronically infected people who also have fibrosis of the intrahepatic bile duct. As already demonstrated in an animal model and now observed in humans for the first time, this increase in CYP 2A6-related enzyme activity may represent an important mechanistic link between inflammatory products of chronic liver fluke infection (e.g., DNA alkylation damage from endogenously formed N-nitrosamines) and the high risk of cholangiocarcinoma faced by infected individuals.

Analysis of Variance↗
PubMed1995

Childhood systemic lupus erythematosus, vasculitis, and rheumatic fever and neonatal lupus.

Studies on the long-term outcome of patients with systemic lupus erythematosus not only give us survival figures but also uncover flaws in our treatment strategies and reveal both disease-associated and other factors that affect prognosis. Among the latter, compliance with treatment and socioeconomic factors are noteworthy. The pathogenesis of neonatal lupus is under active investigation, and new approaches are being developed. This review also draws attention to a number of vasculitis syndromes that are common in adults but very rarely reported in children. Poststreptococcal reactive arthritis has been described as a new entity; however, such patients should probably receive the same attention as patients with rheumatic fever to avoid recurrences of the disease and cardiac sequelae.

Animals↗
PubMed1994

Activation of aflatoxin B1 by mouse CYP2A enzymes and cytotoxicity in recombinant yeast cells.

The ability of three highly homologous mouse liver CYP2A enzymes to activate aflatoxin B1 was studied by expressing them in recombinant AH22 Saccharomyces cerevisiae yeast cells. The reconstituted monooxygenase complex with CYP2A5 purified from yeast cell microsomes produced epoxide at a rate of 17.2 nmol/min per nmol P450 in the presence of 50 microM aflatoxin B1 while CYP2A4 had about 10% and P4507 alpha only 1.5% of this activity. However, Km values were 530 and 10 microM and Vmax values 12.5 and 14.3 nmol/min per nmol P450 for CYP2A4 and CYP2A5, respectively. When recombinant yeast cells were exposed to aflatoxin B1 LC50 concentrations were 7.5 +/- 5.5 microM for CYP2A4, 0.45 +/- 0.10 microM for CYP2A5 and > 320 microM for P4507 alpha expressing yeast cells. Aflatoxin B1-DNA adduct levels in the same yeast cells were 50, 890 pmol/mg DNA and below detection limit when 3.0 microM aflatoxin B1 was used in the incubation mixture. Coumarin an inhibitor for CYP2A4 and a substrate for CYP2A5 diminished the toxicity of aflatoxin B1 in a dose-dependent manner for these recombinant yeast cells. These data demonstrate that (1) highly homologous mouse CYP2A enzymes activate aflatoxin B1 in a different manner and (2) that recombinant yeast cells expressing mammalian CYP enzymes are a useful and inexpensive system to test the role of different enzymes in aflatoxin B1 toxicity. The data also indicate that mouse CYP2A5 and its counterpart in other species could have a significant role in aflatoxin B1 toxicity in organs where it is expressed at high levels.

Aflatoxin B1↗
PubMed1994

Association of liver fluke (Opisthorchis viverrini) infestation with increased expression of cytochrome P450 and carcinogen metabolism in male hamster liver.

Synergy between exposure to chemical carcinogens (nitrosamines) and infestation with the liver fluke Opisthorchis viverrini has been demonstrated in a hamster model of hepatocarcinogenesis (Flavell et al., Carcinogenesis 4:927-930, 1983; Thamavit et al., Carcinogenesis 8:1351-1353, 1987). To elucidate the mechanisms of this interaction we tested the hypothesis that liver parasitism might influence the expression and activity of carcinogen metabolizing enzymes. We found that one, and perhaps more, hamster liver cytochrome P450 (CYP) isozymes immunorelated to mouse CYP2A5 contributed up to 50 or 60% of the hepatic aflatoxin B1 (AFB) and N-nitrosodiethylamine (NDEA) metabolism, respectively. As inferred from average enzyme activities and from western blot, immunoinhibition, and substrate (coumarin) inhibition analyses, O. viverrini infestation increased the expression of enzymes detectable by anti-CYP2A5 antibody as well as NDEA metabolism in male but not in female hamsters. Immunohistochemical analysis of CYP2A expression by anti-mouse CYP2A5 antibody demonstrated that the O. viverrini-associated increase was not uniformly distributed throughout the liver but occurred in hepatocytes immediately adjacent to areas of inflammation. Immunohistochemical analysis of AFB-DNA adducts in the livers of O. viverrini-infested hamsters treated with AFB showed that the highest levels of adducts were found in the regions of liver where hepatocellular expression of enzymes detectable by anti-CYP2A5 antibody is induced. These results suggest that a high local expression of CYP isozymes in O. viverrini-infested livers could be a contributing risk factor in the development of liver cancers associated with parasitic hepatitis.

Animals↗
PubMed1994

Tissue and sex-dependent differences in CYP2A activities in hamsters.

Three enzymatic activities of the CYP2A subfamily, coumarin 7-hydroxylase (COH), testosterone 15 alpha-hydroxylase (T15 alpha OH) and testosterone 7 alpha-hydroxylase (T7 alpha OH), were characterized in liver, kidney and lung microsomes from control, pyrazole (PYR), 3-methylcholanthrene (MC) and phenobarbital (PB) treated female and male Syrian golden hamsters. Sex-dependent changes in the enzymatic activities were found. Among control animals COH and T15 alpha OH activities were higher in males. T7 alpha OH activity was five times higher in female kidneys than in males. Inducers changed this metabolic profile. MC and PB were potent CYP2A inducers in extrahepatic tissues: significant increases were found in COH (5-fold) and T15 alpha OH (12-fold) activities in female MC lung microsomes and T7 alpha OH (7-fold) in MC male kidney microsomes. PB increased significantly activities of COH (5-fold), T15 alpha OH (3-fold) and T7 alpha OH (10-fold) in male kidney microsomes. All inducers significantly increased T7 alpha OH activity in male kidney microsomes but decreased hepatic T7 alpha OH activity in both sexes. PYR treatment decreased hepatic CYP2A activities. Anti-mouse CYP2A4/5 antibody inhibited COH activity by a variable extent depending on the tissue and pretreatment and recognised three 52-, 49-, 48-kDa bands in liver and two major bands in kidney (48 and 49 kDa) and lung (49 and 52 kDa) microsomes. COH and T15 alpha OH activities correlated well with 49 kDa protein (r = 0.95 and r = 0.99, respectively) in lung microsomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Metabolism of nitrosamines and aflatoxin B1 by hamster liver CYP2A enzymes.

Using a specific antibody against mouse CYP2A5 and coumarin as inhibitors, and pretreatments known to affect the activities of CYP2A-related enzymes, we studied the contribution of hamster liver CYP2As in the dealkylation of N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA) and hydroxylation of aflatoxin B1 (AFB1). CYP2A5 antibody inhibited AFB1 and NDEA metabolism by 40-60% in untreated hamsters and after treatment with phenobarbital (PB) or 3-methylcholanthrene (MC). After pyrazole (PYR) treatment, there was no inhibition, although PYR increased the metabolism above the controls. NDMA metabolism was inhibited only weakly in all groups. This suggests that CYP2As may contribute significantly to NDEA and AFB1 metabolism and less to NDMA metabolism in untreated hamster liver and after MC or PB treatments, but that PYR treatment may change the expression pattern of CYPs so that the metabolism is mainly catalysed by CYPs not recognized by the antibody. Coumarin inhibited NDEA and NDMA metabolism in all groups of hamsters, including pyrazole-pretreated animals, suggesting that it interacts not only with CYP2As but also with other CYPs that are important in nitrosamine metabolism. On the other hand, coumarin inhibited AFB1 metabolism significantly only in control and PB-treated animals but not at all after PYR or MC treatment. This suggests that enzymes involved in AFB1 metabolism may be different depending on the pretreatment. It is concluded that CYP2As may contribute significantly to nitrosamine and aflatoxin metabolism in hamster liver. However, in view of previous results showing essential differences in their regulation between mouse and hamster, interspecies comparisons may be difficult.

Aflatoxin B1↗
PubMed1993

Comparison of hamster and mouse reveals interspecies differences in the regulation of hepatic CYP2A isozymes.

Three CYP2A-related activities [coumarin 7-hydroxylase (COH), testosterone 7 alpha- (test7 alpha) and 15 alpha-hydroxylases (test15 alpha)], identified in hamster liver and analysed by immunoinhibition, and western and northern blotting, were found to be similar to mouse and human CYP2As. In the microsomal fractions, anti-mouse CYP2A5 antibody recognised three bands of about 48, 49 and 52 kDa, suggesting the presence of at least three proteins immunologically similar to mouse CYP2A5. The 49 kDa band migrated close to mouse CYP2A5 and changes in its expression followed COH and test15 alpha activities. Test7 alpha activity did not associate with any of the individual bands detected on western blots despite its strong inhibition by the antibody. Despite the immunological and catalytic similarities between mouse and hamster CYP2A enzymes, their regulation is different. In mice, the enzyme activities are higher in females than males, are induced by pyrazole (PY) and phenobarbital (Pb), and are not affected by 3-methylcholanthrene (MC). In hamsters, activities are not higher in females, induced by MC and reduced by PY. MC and PY appear to regulate expression at the mRNA level, while Pb seems to act post-transcriptionally by increasing either the synthesis or the stability of the protein. Our data indicate that the modes of expression and regulation of CYP2A-related enzymes make the hamster different from mice and humans with respect to the mechanism of metabolism of certain drugs and carcinogens.

Animals↗