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1.
Scand J Immunol ; 72(3): 185-8, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20696014

ABSTRACT

Congenital heart block is the most severe manifestation of neonatal lupus syndrome. It is a passively acquired disease where transplacental passage of maternal autoantibodies is associated with irreversible damage of the foetal cardiac conduction system. It is well established that the condition, in the absence of structural abnormalities, is strongly associated with maternal autoantibodies to the Ro/La antigens. More specifically the disease has been closely linked to antibodies to the Ro52 component of the antigen complex. Congenital heart block constitutes a unique model where specific autoantibodies target and mediate organ-specific disease. A wide panel of maternal antibodies has been discussed in literature in association with the disease and are described in this review.


Subject(s)
Autoantibodies/immunology , Heart Block/congenital , Heart Block/immunology , Cross Reactions/immunology , Female , Heart Block/etiology , Humans , Maternal-Fetal Exchange/immunology , Pregnancy
2.
Int J Obes (Lond) ; 34(6): 1011-9, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20157327

ABSTRACT

CONTEXT: Regulation of fat mass appears to be associated with immune functions. Studies of knockout mice show that endogenous interleukin (IL)-6 can suppress mature-onset obesity. OBJECTIVE: To systematically investigate associations of single nucleotide polymorphisms (SNPs) near the IL-6 (IL6) and IL-6 receptor (IL6R) genes with body fat mass, in support for our hypothesis that variants of these genes can be associated with obesity. DESIGN AND STUDY SUBJECTS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based cross-sectional study of 18- to 20-year-old men (n=1049), from the Gothenburg area (Sweden). Major findings were confirmed in two additional cohorts consisting of elderly men from the Osteoporotic Fractures in Men (MrOS) Sweden (n=2851) and MrOS US (n=5611) multicenter population-based studies. MAIN OUTCOME: The genotype distributions and their association with fat mass in different compartments, measured with dual-energy X-ray absorptiometry. RESULTS: Out of 18 evaluated tag SNPs near the IL6 and IL6R genes, a recently identified SNP rs10242595 G/A (minor allele frequency=29%) 3' of the IL6 gene was negatively associated with the primary outcome total body fat mass (effect size -0.11 standard deviation (s.d.) units per A allele, P=0.02). This negative association with fat mass was also confirmed in the combined MrOS Sweden and MrOS US cohorts (effect size -0.05 s.d. units per A allele, P=0.002). When all three cohorts were combined (n=8927, Caucasian subjects), rs10242595(*)A showed a negative association with total body fat mass (effect size -0.05 s.d. units per A allele, P<0.0002). Furthermore, the rs10242595(*)A was associated with low body mass index (effect size -0.03, P<0.001) and smaller regional fat masses. None of the other SNPs investigated in the GOOD study were reproducibly associated with body fat. CONCLUSIONS: The IL6 gene polymorphism rs10242595(*)A is associated with decreased fat mass in three combined cohorts of 8927 Caucasian men.


Subject(s)
Adiposity/genetics , Interleukin-6/genetics , Obesity/genetics , Polymorphism, Single Nucleotide/genetics , Receptors, Interleukin-6/genetics , Absorptiometry, Photon , Adolescent , Aged , Body Mass Index , Cross-Sectional Studies , Gene Frequency/genetics , Gene Frequency/physiology , Genetic Variation/genetics , Genotype , Humans , Interleukin-6/physiology , Male , Obesity/physiopathology , Receptors, Interleukin-6/physiology , Sweden , White People/genetics , Young Adult
3.
Int J Obes (Lond) ; 33(5): 525-33, 2009 May.
Article in English | MEDLINE | ID: mdl-19290009

ABSTRACT

CONTEXT: Immune functions seem to have connections to variations in body fat mass. Studies of knockout mice indicate that endogenous interleukin (IL)-1 can suppress mature-onset obesity. OBJECTIVE: To systematically investigate our hypotheses that single-nucleotide polymorphisms (SNPs) and/or haplotypes variants in the IL-1 gene system are associated with fat mass. SUBJECTS: The Gothenburg osteoporosis and obesity determinants (GOOD) study is a population-based cross-sectional study of 18-20 year-old men (n=1068), from Gothenburg, Sweden. Major findings were confirmed in elderly men (n=3014) from the Swedish part of the osteoporotic fractures in men (MrOS) multicenter population-based study. MAIN OUTCOME MEASURE: The genotype distributions and their association with body fat mass in different compartments, measured with dual-energy X-ray absorptiometry (DXA). RESULTS: Out of 15 investigated SNPs in the IL-1 receptor antagonist (IL1RN) gene, a recently identified 3' untranslated region C>T (rs4252041, minor allele frequency=4%) SNP was associated with the primary outcome total fat mass (P=0.003) and regional fat masses, but not with lean body mass or serum IL-1 receptor 1 (IL1RN) levels. This SNP was also associated with body fat when correcting the earlier reported IL1RN+2018 T>C (rs419598) SNP (in linkage disequilibrium with a well-studied variable number tandem repeat of 86 bp). The association between rs4252041 SNP and body fat was confirmed in the older MrOS population (P=0.03). The rs4252041 SNP was part of three haplotypes consisting of five adjacent SNPs that were identified by a sliding window approach. These haplotypes had a highly significant global association with total body fat (P<0.001). None of the other investigated members of the IL-1 gene family displayed any SNPs that have not been described previously to be significantly associated with body fat. CONCLUSIONS: The IL1RN gene, shown to enhance obesity by suppressing IL-1 effects in experimental animals, have not [corrected] previously described gene polymorphisms and haplotypes that are associated with fat, but not lean mass in two populations of men.


Subject(s)
Adipose Tissue , Haplotypes , Interleukin 1 Receptor Antagonist Protein/genetics , Polymorphism, Single Nucleotide , Absorptiometry, Photon , Adolescent , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Humans , Male , Prospective Studies , Sweden , Young Adult
4.
Clin Exp Immunol ; 154(1): 30-7, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18727629

ABSTRACT

Maternal autoantibodies to the p200-epitope of Ro52 have been suggested to correlate with development of congenital heart block. The aim of the present study was to evaluate the clinical relevance and predictive value of p200-antibodies in high-risk pregnancies. Sera from 515 Finnish, Swedish and American women were included in the study. Sera originated from 202 mothers with an infant affected by second- or third-degree atrioventricular block (AVB), 177 mothers with rheumatic disease having infants with normal heart rate and female blood donors (n = 136). A novel serological assay for Ro52 p200-antibodies with intra- and inter-assay variability of 3% and 3.8% respectively was developed. Mothers of children affected by AVB II-III had significantly higher p200-antibody levels than mothers with rheumatic disease having children with normal heart rate (P < 0.001). In the Swedish cohort, a distinction between foetuses with normal conduction, AVB I, AVB II and III was possible. A significant difference in anti-p200 levels between AVB I and AVB II-III groups compared with foetuses with normal conduction (P < 0.05 and P < 0.01) was observed. Using p200-antibodies as a second step analysis in Ro52-positive pregnancies increased the positive predictive value for foetal cardiac involvement (AVB I, II or III) from 0.39 (0.27-0.51) to 0.53 (0.37-0.68). In conclusion, Ro52 p200-antibodies may occur in women with unaffected children, but levels are significantly higher in mothers of children with congenital heart block and are suggested as a relevant marker in evaluating the risk for foetal AV block.


Subject(s)
Autoantibodies/blood , GTPase-Activating Proteins/immunology , Heart Block/congenital , Heart Block/immunology , Ribonucleoproteins/chemistry , Adult , Analysis of Variance , Atrioventricular Block/immunology , Autoantibodies/immunology , Biomarkers/blood , Case-Control Studies , Enzyme-Linked Immunosorbent Assay/methods , Female , Finland , Humans , Pregnancy , Risk Factors , Sweden , United States
5.
Lupus ; 15(6): 346-53, 2006.
Article in English | MEDLINE | ID: mdl-16830880

ABSTRACT

Congenital heart block occurs in fetuses of Ro/SSA and La/SSB positive women. To investigate the stability of maternal autoantibody levels during pregnancy, we followed Ro52, Ro60 and La autoantibody IgG level variation and Ro52 subclass profiles longitudinally in selected congenital heart block risk pregnancies. Serum samples were obtained from 12 Ro/La positive women diagnosed with a systemic rheumatic disease and followed on average 60 months (range two to 84) which included 13 pregnancies. Seven children were affected by neonatal lupus, whereof four developed complete congenital heart block. Serum was also collected from the babies at birth. Ro52, Ro60 and La IgG as well as subclass antibodies were analysed by ELISA using recombinant antigens. Six Ro/La negative rheumatic patients were included as controls for antibody levels during pregnancy. Ro52, Ro60 and La IgG levels decreased progressively from early to late pregnancy, significantly for Ro52 and Ro60 (P < 0.01). No peaks or persistent elevation of antibody levels were noted in any of the CHB risk pregnancies. Ro52 IgG1 antibody levels were significantly higher than IgG2 (P < 0.01), IgG3 (P < 0.01) and IgG4 (P < 0.05) levels in the mothers during pregnancy. Ro52 IgG1 and IgG4 levels decreased significantly from early to late pregnancy (P = 0.02), while levels of IgG2 and IgG3 were low and the decrease was not significant. All IgG subclasses were transferred to the children. We conclude that maternal levels of Ro52, Ro60 and La autoantibodies tended rather to decrease than to increase during pregnancy.


Subject(s)
Antibodies, Antinuclear/immunology , Autoantigens/immunology , Heart Block/congenital , Immunity, Maternally-Acquired , Immunoglobulin G/immunology , Lupus Erythematosus, Systemic/immunology , Pregnancy Complications/immunology , RNA, Small Cytoplasmic/immunology , Ribonucleoproteins/immunology , Sjogren's Syndrome/immunology , Adult , Antibodies, Antinuclear/blood , Antiphospholipid Syndrome/blood , Antiphospholipid Syndrome/immunology , Cohort Studies , Female , Follow-Up Studies , Heart Block/epidemiology , Heart Block/immunology , Humans , Immunoglobulin G/blood , Infant, Newborn , Lupus Erythematosus, Systemic/blood , Maternal-Fetal Exchange , Mixed Connective Tissue Disease/blood , Mixed Connective Tissue Disease/immunology , Pregnancy , Pregnancy Complications/blood , Risk , Sjogren's Syndrome/blood , SS-B Antigen
6.
J Intern Med ; 254(3): 244-50, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12930233

ABSTRACT

OBJECTIVES: To investigate the prognostic value of plasma C-reactive protein (CRP) and fibrinogen determinations in patients with acute myocardial infarction treated with thrombolysis. DESIGN: Longitudinal study of morbidity and mortality. SETTING: Coronary care unit at Danderyd Hospital, Stockholm, Sweden. SUBJECTS: A total of 222 patients aged 75 years or below, treated with thrombolysis because of typical symptoms of myocardial infarction and electrocardiogram showing ST-segment elevation or bundle branch block were included in the study. The patients were followed for 24-60 months (mean 40 +/- 16 months). MAIN OUTCOME MEASURES: Cardiovascular death or new myocardial infarction. RESULTS: Concentrations of CRP were significantly higher at 48 h than at 3 months, whilst the levels of fibrinogen were similar. CRP and fibrinogen concentrations measured during the acute phase of myocardial infarction were associated with cardiovascular death or a new myocardial infarction during follow-up in univariate analysis. CRP levels measured 3 months after the acute event were not associated with subsequent events whereas fibrinogen concentrations showed a borderline prognostic significance (P = 0.05). When CRP and fibrinogen were entered into multivariate analysis together with the previously established prognostic factors in the patient group (age, diabetes mellitus and left ventricular function), these markers of inflammation did not add further prognostic information. CONCLUSION: C-reactive protein and fibrinogen do not carry the same independent prognostic information after acute myocardial infarction treated with thrombolysis as in studies previously reported for patients with unstable angina or non-Q-wave myocardial infarction.


Subject(s)
C-Reactive Protein/analysis , Fibrinogen/analysis , Myocardial Infarction/drug therapy , Thrombolytic Therapy/methods , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Myocardial Infarction/blood , Prognosis , Regression Analysis
7.
Food Addit Contam ; 19(8): 779-95, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12227942

ABSTRACT

Concentrations and composition profiles of polychlorinated biphenyls (PCBs) were investigated in composite samples of 10 species of edible fish from the Gulf of Gdansk, in the southern part of the Baltic Sea, Poland, to understand the status of contamination and possible human exposure risk. Apart from the total PCBs, planar non-ortho (IUPAC nos 77, 126, 169) and mono-ortho (nos 105, 114, 118, 123, 156, 157, 167, 189) chlorobiphenyls were also quantified and their dioxin-like toxicity assessed. The absolute total PCB concentrations in fish ranged from 43 to 490 ng g(-1) wet wt (910-11000 ng g(-1) lipids), while of TCDD TEQs of planar members were from 0.15 to 3.1 pg g(-1) wet wt (8.1-81 pg g(-1) lipids). The penta- and hexa-CBs usually comprised 70-80% of the total PCBs and were followed by hepta-, tetra- and tri-CBs, and for a specific site tri- and tetra-CBs comprised as much as 22%. Among the individual CB congeners, nos 118, 153 (+132) and 138 (+160 +163 +164) were the most abundant, while no. 110 comprised between 6.8 and 9.3% of the total PCBs in some species. Principal component analysis (PCA) was applied to examine the interdependences among CB congeners in the factor space. The PCA model and cluster analyses were further used to examine site- and species-specific differences and similarities of PCB composition, and the results are discussed. An assessed daily intake rate of TCDD TEQ of planar PCBs with the fishmeal of the Gulf of Gdansk in the 1990s was between 78 and 96 pg per capita or between 1.3 and 1.6 pg kg(-1) body weight.


Subject(s)
Fishes , Food Contamination/analysis , Polychlorinated Biphenyls/analysis , Animals , Baltic States , Cluster Analysis , Humans , Polychlorinated Biphenyls/chemistry , Polychlorinated Biphenyls/toxicity , Principal Component Analysis
8.
Environ Sci Technol ; 35(21): 4163-9, 2001 Nov 01.
Article in English | MEDLINE | ID: mdl-11718327

ABSTRACT

Chlordane components (CHLs) and their metabolites (heptachlor, cis-heptachlor epoxide, U82, MC4, trans-chlordane, MC5, cis-chlordane, MC7, oxychlordane, MC6- and trans- and cis-nonachlor) and aldrin, dieldrin, endrin, isodrin, endosulfan 1, endosulfan 2, and mirex were quantified in the soft tissues of blue mussel, a whole crab, and whole fishes collected from the spatially different sites in the Gulf of Gdansk. Six to twelve chlordane compounds and metabolites and dieldrin were detected in all organisms examined while aldrin, endrin, isodrin, endosulfans 1 and 2, and mirex were not found above the detection limit of the method. The lipid weight based concentrations in Baltic biota were relatively small and ranged from 12 to 150 and 7.6-77 ng/g, while between 0.16 and 6.8 and 0.10-6.6 ng/g in fresh tissue, respectively. The profile (%) of chlordane compounds was very similar between various fish species with trans-nonachlor (28 +/- 17), cis-chlordane (23 +/- 18), oxychlordane (13 +/- 7), and heptachlor epoxide (11 +/- 5) as major constituents and was totally different in crab with oxychlordane as the most dominating (>65%) compound. Blue mussel, lamprey, and three-spined stickleback exhibited a smallest ability to metabolize CHLs, and such fishes as cod, lesser sand-eel, sand-eel, pikeperch, perch, round goby, flounder, and herring showed a slightly better ability, while crab was able to effectively metabolize most of CHL compounds except trans-nonachlor. A value of the quotient of the trans-nonachlor to cis-chlordane concentrations (N/C quotient) was 1.0 in blue mussel, 3.1 in crab, and between 0.9 and 1.8 in fish. Both the small concentrations of CHLs in all organisms and the values of N/C quotients close to 1 imply on a long-range aerial transport through movement of the air masses from the remote regions of the northern hemisphere as a main source of this pesticide in the Gulf of Gdansk. The interdependences between the CHL profiles for various fish species and between different sampling sites were examined using the principal component analysis (PCA) method. Applying the PCA model the first four significant components explained 90% (43% + 23% + 15% + 8%) of the total variance in the data matrix.


Subject(s)
Bivalvia/metabolism , Brachyura/metabolism , Fishes/metabolism , Pesticide Residues/metabolism , Pesticides/metabolism , Water Pollutants, Chemical/metabolism , Animals , Chlorine Compounds/analysis , Chlorine Compounds/metabolism , Pesticide Residues/analysis , Pesticides/analysis , Poland , Seawater , Water Pollutants, Chemical/analysis
9.
Cardiology ; 95(2): 112-8, 2001.
Article in English | MEDLINE | ID: mdl-11423717

ABSTRACT

UNLABELLED: Beta-blocker therapy is used to decrease myocardial ischemia during exercise but may cause suboptimal diagnostic performance in exercise stress testing. The aim of the present study was to compare results of quantitative technetium-99-sestamibi single photon emission tomography (SPECT), following exercise stress test or pharmacological stress test with adenosine. We chose adenosine as comparison, since betablockers may not interfere with adenosine induced vasodilatation and therefore possibly may not interfere with its diagnostic performance. Sixteen patients with angiographically documented coronary disease (5 single-vessel, 6 two-vessel and 5 three-vessel disease), who were chronically treated with beta-blockers, performed SPECT imaging at rest, following bicycle exercise and following adenosine infusion in random order. The SPECT data were analyzed visually and quantitatively, using dedicated computer software (CEqual). According to both visual and quantitative SPECT analysis, adenosine was superior to show reversibility. Higher reversibility extent (50 +/- 15 vs. 26 +/- 12 pixels, p < 0.01) and more intense reversibility severity (110 +/- 29 vs. 49 +/- 23 sum of SDs, p < 0.05) were observed during adenosine than exercise. CONCLUSIONS: Less myocardial perfusion abnormalities during exercise than during adenosine stress in patients treated with beta-blockers may indicate less ischemia but also an impaired diagnostic performance. Thus adenosine stress test should be preferred to optimize the diagnostic sensitivity in patients during beta-blocker treatment.


Subject(s)
Adenosine , Adrenergic beta-Antagonists/therapeutic use , Coronary Disease/drug therapy , Heart Function Tests , Vasodilator Agents , Adult , Aged , Coronary Disease/diagnostic imaging , Coronary Disease/physiopathology , Female , Humans , Male , Middle Aged , Tomography, Emission-Computed, Single-Photon
10.
Protein Eng ; 14(1): 67-74, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11287680

ABSTRACT

Antibody binding sites provide an adaptable surface capable of interacting with essentially any molecular target. Using CDR shuffling, residues important for the assembly of mucin-1 specific paratopes were defined by random recombination of the complementarity determining regions derived from a set of mucin-1 specific clones, previously selected from an antibody fragment library. It was found that positions 33 and 50 in the heavy chain and 32, 34, 90, 91 and 96 in the light chain were conserved in many of the clones. These particular residues seem to be located centrally in the binding site as indicated by a structure model analysis. The importance of several of these conserved residues was supported by their presence in a mouse monoclonal antibody with a known structure and the same epitope specificity. Several of these corresponding residues in the mouse monoclonal antibody are known to interact with the antigen. In conclusion, critical residues important for maintaining a human antigen-specific binding site during the process of in vitro antibody evolution were defined. Furthermore, an explanation for the observed restricted germline gene usage in certain antibody responses against protein epitopes is provided.


Subject(s)
Antibodies, Monoclonal/genetics , Complementarity Determining Regions/chemistry , Mucin-1/chemistry , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/metabolism , Binding Sites , Binding Sites, Antibody , Conserved Sequence , Epitopes/chemistry , Evolution, Molecular , Humans , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Light Chains/genetics , Immunoglobulin Variable Region/chemistry , Mice , Models, Molecular , Molecular Sequence Data , Molecular Structure , Peptide Library , Protein Binding , Sequence Homology, Amino Acid , Tandem Repeat Sequences
11.
Ergonomics ; 44(13): 1102-17, 2001 Oct 20.
Article in English | MEDLINE | ID: mdl-11794760

ABSTRACT

The main objective of this paper is to give an overview of basic concepts and definitions of terms related to the 'measurement of slipperiness' from the onset of a foot slide to a gradual loss of balance and a fall. Other unforeseen events prior to falls (e.g. tripping) are sparingly dealt with. The measurement of slipperiness may simply comprise an estimation of slipping hazard exposures that initiate the chain of events ultimately causing an injury. However, there is also a need to consider the human capacity to anticipate slipperiness and adapt to unsafe environments for avoiding a loss of balance and an injury. Biomechanical and human-centred measurements may be utilized for such an approach, including an evaluation of relevant safety criteria for slip/fall avoidance and procedures for validation of slip test devices. Mechanical slip testing approaches have been readily utilized to measure slipperiness in terms of friction or slip resistance but with conflicting outcomes. An improved understanding of the measurement of slipperiness paradigm seems to involve an integration of the methodologies used in several disciplines, among others, injury epidemiology, psychophysics, biomechanics, motor control, materials science and tribology.


Subject(s)
Accidental Falls/prevention & control , Floors and Floorcoverings/standards , Postural Balance/physiology , Foot/physiology , Friction , Gait/physiology , Humans , Risk Factors , Surface Properties
12.
Ergonomics ; 44(13): 1217-32, 2001 Oct 20.
Article in English | MEDLINE | ID: mdl-11794765

ABSTRACT

Friction has been widely used as a measure of slipperiness. However, controversies around friction measurements remain. The purposes of this paper are to summarize understanding about friction measurement related to slipperiness assessment of shoe and floor interface and to define test conditions based on biomechanical observations. In addition, friction mechanisms at shoe and floor interface on dry, liquid and solid contaminated, and on icy surfaces are discussed. It is concluded that static friction measurement, by the traditional use of a drag-type device, is only suitable for dry and clean surfaces, and dynamic and transition friction methods are needed to properly estimate the potential risk on contaminated surfaces. Furthermore, at least some of the conditions at the shoe/floor interface during actual slip accidents should be replicated as test conditions for friction measurements, such as sliding speed, contact pressure and normal force build-up rate.


Subject(s)
Accidental Falls/prevention & control , Floors and Floorcoverings/instrumentation , Floors and Floorcoverings/statistics & numerical data , Friction , Biophysics/instrumentation , Biophysics/methods , Gait/physiology , Humans , Shoes , Surface Properties
13.
Ergonomics ; 44(13): 1233-61, 2001 Oct 20.
Article in English | MEDLINE | ID: mdl-11794766

ABSTRACT

This paper seeks to address questions related to friction measurement such as how friction is related to human-centred assessment and actual slipping, and how repeatable friction measurements are. Commonly used devices for slipperiness measurement are surveyed and their characteristics compared with suggested test conditions from biomechanical observations summarized in Part 1. The issues of device validity, repeatability, reproducibility and usability are examined from the published literature. Friction assessment using the mechanical measurement devices described appears generally valid and reliable. However, the validity of most devices could be improved by bringing them within the range of human slipping conditions observed in biomechanical studies. Future studies should clearly describe the performance limitations of any device and its results and should consider whether the device conditions reflect these actual human slipping conditions. There is also a need for validation studies of more devices by walking experiments.


Subject(s)
Accidental Falls/prevention & control , Floors and Floorcoverings/instrumentation , Floors and Floorcoverings/standards , Friction , Biophysics/instrumentation , Biophysics/methods , Equipment Design , Humans , Reproducibility of Results , Shoes , Surface Properties
14.
Rocz Panstw Zakl Hig ; 51(2): 119-28, 2000.
Article in Polish | MEDLINE | ID: mdl-10959191

ABSTRACT

Concentrations, composition and spatial variations of the residues of the pesticide Chlordane were determined in several species of fish caught in Gulf of Gdansk. The residues of Chlordane (cis-i trans-chlordane, cis-i trans-nonachlor, oxychlordane, heptachlor, heptachlor epoxide, MC4, MC5, MC6, MC7, U82 and U83) were found in all fish examined, however, the concentrations noted were low, i.e. from 0.40 to 12 ng/g wet weight. Among the Chlordane constituents and metabolites determined trans-naonachlor, cis-chlordane, oxychlordan, heptachlor epoxide, cis-nonachlor, MC5, MC6 and trans-chlordane were dominated, and MC4, MC7, U82 and U83 were minor compounds. No heptachlor residues were found in fish examined. A small concentrations and specific composition of the residues of Chlordane and its metabolites determined in fish from the Gulf of Gdansk do indicate on a distant sources of pollution with that pesticide--mainly transported and deposited via the atmosphere.


Subject(s)
Chlordan/analysis , Fishes , Animals , Humans , Oceans and Seas , Poland
15.
J Intern Med ; 248(2): 119-25, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10947890

ABSTRACT

OBJECTIVES: To assess the long-term prognostic values of baseline demographic data, occurrence of vectorcardiographic signs of reperfusion, left ventricular function and coronary angiographic features. DESIGN: Longitudinal study of morbidity and mortality. SETTING: Coronary care unit at Danderyd Hospital, Stockholm, Sweden. SUBJECTS: A total of 222 patients (mean age 61 years) with a suspected acute myocardial infarction treated with thrombolysis were investigated and followed for 2-5 years (mean 1216 days). MAIN OUTCOME MEASURES: Death or a new myocardial infarction. RESULTS: Age above 55 years (P < 0.05), a previous diagnosis of diabetes mellitus (P < 0.005), hypertension (P < 0.05), heart failure (P < 0.001) and myocardial infarction (P < 0.05), a previous use of beta-blockers (P < 0.05) and an ejection fraction below 60% (P < 0.01) were predictors for death or a new myocardial infarction in univariate analysis. Sex, a previous history of smoking or angina pectoris, vectorcardiographic signs of reperfusion or degree of coronary artery disease had no prognostic values. In multivariate analysis including age above 55 years, a previous diagnosis of diabetes mellitus, hypertension and myocardial infarction, and an ejection fraction below 60%, only age (P < 0.05), diabetes mellitus (P < 0. 01) and ejection fraction (P < 0.05) were predictors for death or a new myocardial infarction. CONCLUSIONS: The results of the present study emphasize the importance of diabetes mellitus as a long-term prognostic risk factor in patients with myocardial infarction treated with thrombolysis. Further studies are needed to determine the mechanisms behind this increased risk.


Subject(s)
Diabetic Angiopathies/drug therapy , Myocardial Infarction/drug therapy , Thrombolytic Therapy , Aged , Diabetic Angiopathies/mortality , Female , Humans , Male , Middle Aged , Multivariate Analysis , Myocardial Infarction/mortality , Prognosis , Survival Analysis , Vectorcardiography
16.
Nat Biotechnol ; 18(8): 852-6, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10932154

ABSTRACT

We constructed a single-chain Fv antibody library that permits human complementarity-determining region (CDR) gene fragments of any germline to be incorporated combinatorially into the appropriate positions of the variable-region frameworks VH-DP47 and VL-DPL3. A library of 2 x 109 independent transformants was screened against haptens, peptides, carbohydrates, and proteins, and the selected antibody fragments exhibited dissociation constants in the subnanomolar range. The antibody genes in this library were built on a single master framework into which diverse CDRs were allowed to recombine. These CDRs were sampled from in vivo-processed gene sequences, thus potentially optimizing the levels of correctly folded and functional molecules, and resulting in a molecule exhibiting a lower computed immunogenicity compared to naive immunoglobulins. Using the modularized assembly process to incorporate foreign sequences into an immunoglobulin scaffold, it is possible to vary as many as six CDRs at the same time, creating genetic and functional variation in antibody molecules.


Subject(s)
Germ-Line Mutation , Immunoglobulin Variable Region/genetics , Recombination, Genetic , Humans , Immunoglobulin Fragments/genetics , Recombinant Proteins/genetics
17.
Rocz Panstw Zakl Hig ; 51(1): 7-13, 2000.
Article in Polish | MEDLINE | ID: mdl-10846931

ABSTRACT

The residues of PCBs, DDTs, HCHs, HCBz, PCBz, CHLs, aldrin, dieldrin, endrin, isodrin, endosulfan 1, endosulfan 2, mirex, TCPM-H and TCPM-OH were determined in breast muscles and an egg of white-tailed sea eagles collected in Poland in 1991-1995. The method of measurement was capillary gas chromatography and low resolution mass spectrometry (HRGC/LRMS) after a non-destructive extraction, clean-up and fractionation of the sample. Only aldrin, endrin, endosulfan 1 and endosulfan 2 were absent in birds and egg examined. Some of the adult white-tailed sea eagles collected dead from the coastal area of the Baltic Sea still remain relatively high contaminated with organochlorines, and the concentrations of PCBs and DDTs in those birds ranged between 2300-2600 and 490-2000 micrograms/g lipids, respectively. In dead egg concentration of PCBs was 390 micrograms/g lipids (25 micrograms/g wet weight), while of DDTs 270 micrograms/g lipids (18 micrograms/g w.w.).


Subject(s)
Eagles , Hydrocarbons, Chlorinated , Insecticides/analysis , Animals , Poland
18.
Rocz Panstw Zakl Hig ; 50(2): 131-8, 1999.
Article in Polish | MEDLINE | ID: mdl-10523931

ABSTRACT

The residues of dieldrin, aldrin, endrin, isodrin, endosulfan 1 and 2 has been determined in a several species of fish caught in the Gulf of Gdansk in 1992. The method of measurement was capillary gas chromatograph and low resolution mass spectrometry (HRGC/LRMS) after a nondestructive extraction and clean-up step with a further fractionation of the extract on Florisil column. Apart from dieldrin no other cyclodiene pesticides studied were found in fishes in detectable amounts, and for dieldrin concentrations ranged from 0.84 to 6.6 ng/g wet weight.


Subject(s)
Benzothiepins/analysis , Fishes , Hydrocarbons, Chlorinated/analysis , Water Pollutants/analysis , Water/chemistry , Animals , Poland
19.
J Biol Chem ; 274(11): 7153-6, 1999 Mar 12.
Article in English | MEDLINE | ID: mdl-10066774

ABSTRACT

Archetypal members of the chymotrypsin family of serine proteases, such as trypsin, chymotrypsin, and elastase, exhibit relatively broad substrate specificity. However, the successful development of efficient proteolytic cascades, such as the blood coagulation and fibrinolytic systems, required the evolution of proteases that displayed restricted specificity. Tissue-type plasminogen activator (t-PA), for example, possesses exquisitely stringent substrate specificity, and the molecular basis of this important biochemical property of t-PA remains obscure. Previous investigations of related serine proteases, which participate in the blood coagulation cascade, have focused attention on the residue that occupies position 192 (chymotrypsin numbering system), which plays a pivotal role in determining both the inhibitor and substrate specificity of these enzymes. Consequently, we created and characterized the kinetic properties of new variants of t-PA that contained point mutations at position 192. These studies demonstrated that, unlike in coagulation serine proteases, Gln-192 does not contribute significantly to the substrate or inhibitor specificity of t-PA in physiologically relevant reactions. Replacement of Gln-192 with a glutamic acid residue did, however, decrease the catalytic efficiency of mature, two-chain t-PA toward plasminogen in the absence of a fibrin co-factor.


Subject(s)
Blood Coagulation , Tissue Plasminogen Activator/metabolism , Amino Acid Substitution , Base Sequence , Catalysis , DNA Primers , Fibrinolysis , Mutagenesis, Site-Directed , Plasminogen/metabolism , Substrate Specificity , Tissue Plasminogen Activator/chemistry , Tissue Plasminogen Activator/genetics
20.
Rocz Panstw Zakl Hig ; 50(4): 345-51, 1999.
Article in Polish | MEDLINE | ID: mdl-10789205

ABSTRACT

The residues of DDT and its metabolites (DDTs; p,p'-DDT, o,p'-DDT, p,p'-DDD, o,p'-DDD, p,p'-DDE, o,p'-DDE i p,p'-DDMU) has been determined in ten species of edible fish caught in the Gulf of Gdansk in 1992. The method of measurement was capillary gas chromatography and low resolution mass spectrometry (HRGC/LRMS) after a nondestructive extraction and clean-up step with a further fractionation of the extract on Florisil column. All fish examined contained detectable residues of DDTs, and the concentrations ranged from 28 to 310 ng/g wet weight. o,p'-DDT accounted from 0.4 to 2.5% to DDTs content. The residue concentration of DDTs in herring (110 ng/g wet weight and 1100 ng/g lipid weight) in 1992 was threefold lower than in the years 1979-1983 and fourteen fold lower than in 1969-1973.


Subject(s)
DDT/analysis , DDT/metabolism , Fishes , Animals , Humans , Oceans and Seas , Poland
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