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Biomedical subjects

M Köster

Publications and source records attributed to M Köster.

At least 37 records · Page 2Linked to original sources
PubMed1999

Retrospective versus original information on physical and psychosocial exposure at work.

OBJECTIVES: Retrospective exposure assessments are often performed in epidemiologic studies. The presence of an eventual misclassification, both nondifferential and differential, is debated but can rarely be investigated. The aim of this study was to compare self-reported information on the same physical and psychosocial work exposures with 25 years' difference. METHODS: In 1969-1970 a survey of randomly chosen men and women in Stockholm county, concerning, among other things, work exposures, was undertaken. During 1993-1994, 280 subjects participated in a reexamination, regarding psychosocial and physical factors at work and musculoskeletal disorders. The questions were all formulated in the same way as in 1969-1970. RESULTS: When self-reported information on work exposures, collected with a 25-year interval, was compared, acceptable, although not high, agreement was found for 3 out of 4 physical factors and for 4 out of 10 physical environmental factors. Questions measuring psychosocial load had somewhat lower agreement. Current exposure status influenced the memory of past exposures. Study subjects who reported low-back disorders at the reexamination tended to show a better agreement in their assessments of retrospective exposures than those without current symptoms. When relative risks from original and retrospective data were calculated, hardly any influence on the estimates due to that differential misclassification could be found. For persons with and without neck or shoulder symptoms no apparent differences in assessments were found. CONCLUSIONS: Retrospective assessments of exposures at the workplace showed misclassifications to a certain degree. However, the influence of the misclassifications on the risk estimates was limited.

Adult↗
PubMed1998

Functional domains of interferon regulatory factor I (IRF-1).

Interferon (IFN) regulatory factors (IRFs) are a family of transcription factors among which are IRF-1, IRF-2, and IFN consensus sequence binding protein (ICSBP). These factors share sequence homology in the N-terminal DNA-binding domain. IRF-1 and IRF-2 are further related and have additional homologous sequences within their C-termini. Whereas IRF-2 and ICSBP are identified as transcriptional repressors, IRF-1 is an activator. In the present work, the identification of functional domains in murine IRF-1 with regard to DNA-binding, nuclear translocation, heterodimerization with ICSBP and transcriptional activation are demonstrated. The minimal DNA-binding domain requires the N-terminal 124 amino acids plus an arbitrary C-terminal extension. By using mutants of IRF-1 fusion proteins with green fluorescent protein and monitoring their distribution in living cells, a nuclear location signal (NLS) was identified and found to be sufficient for nuclear translocation. Heterodimerization was confirmed by a two-hybrid system adapted to mammalian cells. The heterodimerization domain in IRF-1 was defined by studies in vitro and was shown to be homologous with a sequence in IRF-2, suggesting that IRF-2 also heterodimerizes with ICSBP through this sequence. An acidic domain in IRF-1 was found to be required and to be sufficient for transactivation. Epitope mapping of IRF-1 showed that regions within the NLS, the heterodimerization domain and the transcriptional activation domain are exposed for possible contacts with interacting proteins.

Amino Acid Sequence↗
PubMed1998

Structural and functional analysis of the BMP-4 promoter in early embryos of Xenopus laevis.

The Xenopus laevis BMP-4 gene shows an evolutionary conserved structure containing two coding exons and a leader exon. The transcripts which are detected after zygotic activation of the gene in ventral mesoderm of late blastula stage embryos do either contain the leader exon or begin within the first intron. Luciferase reporter/promoter studies revealed multiple elements being required for the activation and for the spatial control of transcription. These elements are located within the upstream region and within the second intron and they interact with a most proximal located basal promoter being indispensable for transcriptional activation. The auto-activatory capacity of BMP-4 is mediated by several enhancer elements being responsive not only to BMP-4 but also to BMP-2 signaling. BMP-2 might thus function as a natural activator of the BMP-4 gene in the early embryo. Since reporter activity obtained with distinct BMP-2/4 responsive promoter deletion mutants is simultaneously inhibited by the dominant negative BMP receptor as well as by chordin, we suggest that down-regulation of the BMP-4 gene by chordin results from an interference with the auto-regulatory loop at the level of protein-protein interactions.

Amino Acid Sequence↗
PubMed1998

Expression pattern of the winged helix factor XFD-11 during Xenopus embryogenesis.

We have identified a cDNA encoding a novel Xenopus winged helix transcription factor termed as XFD-11 (Xenopus fork head domain). The DNA binding domain is most closely related to those of human or murine FREAC-3 (FKHL7/MF-1/FKH-1) proteins. The XFD-11 gene is activated at late blastula/early gastrula and transcription proceeds throughout embryogenesis. Early expression is found in ventral and lateral but not in dorsal mesoderm. At neurula stages, transcripts are found in posterior mesoderm except for the dorsal midline, and the gene is also transcribed at the lateral border of the neural plate and within anterior neuroectoderm. At later stages of development, transcripts are detected within the pronephros, the heart, within neural crest cells surrounding the eye, in the mandibular, hyoid and branchial arches, and within the tail.

Amino Acid Sequence↗
PubMed1998

Psychosocial and physical risk factors associated with low back pain: a 24 year follow up among women and men in a broad range of occupations.

OBJECTIVES: To investigate the relation between psychosocial and physical factors at work, as well as conditions during leisure time, and low back pain (LBP) over 24 years. METHODS: The study group consisted of 252 women and 232 men. From a previous study conducted in 1969, data on psychosocial and physical conditions and LBP were available. Data on LBP for 1971-93 were obtained retrospectively in 1993. RESULTS: The prevalence of LBP in 1969 among women and men were 34% and 24%, the cumulative incidences of LBP during 1970-92 were 38% and 43%, and the prevalences in 1993 of having had LBP during the past 12 months were 44% and 39%, respectively. Monotonous work and few or unsatisfactory social contacts outside work were risk factors for LBP in 1969 among women. LBP in 1969 and dissatisfaction with leisure time were risk factors among both sexes for LBP in 1970-92. LBP in 1969 was a risk factor for LBP in 1993 among women and dissatisfaction with leisure time a risk factor among men. Interactions between few or unsatisfactory social contacts outside work, as well as dissatisfaction with leisure time, and several factors related to work were found to increase the risk of LBP among both sexes during the studied periods. CONCLUSIONS: Conditions in leisure time exert a long term influence on LBP. In this study factors related to work had a long term effect only in interaction with leisure time factors.

Adult↗
PubMed1998

No paternal effect on monozygotic twinning in the Swedish Twin Registry.

Previous research has provided evidence for a genetic effect in monozygotic twinning, indicated by an increased risk for monozygotic women to have monozygotic offspring. However, since the biological mechanism for this trait is unknown, it is not clear if there exists a paternal inheritance. In this study we investigated twin pregnancies in offspring born in 1941-1996 to male twins in the Swedish Twin Registry and population controls born in 1926-1980. In total 4,225,331 offspring, of which 89,286 were twins, were studied. There was neither an increase in the probability for monozygotic men to have like-sexed twin offspring risk ratio (RR = 0.95; 95% CI = 0.77-1.13) nor an increase in the estimated number of monozygotic twin births. Thus, there is no evidence for a paternal effect on monozygotic twinning, suggesting that the gene(s) increasing the liability for division of the embryo are expressed in the mother and not in the fertilised egg.

Cohort Studies↗
PubMed1997

Reproducibility of a questionnaire for assessment of present and past physical activities.

OBJECTIVE: The aim of this study was to evaluate the reproducibility of a self-administered questionnaire about present and past physical activities at work and during leisure time. METHODS AND DESIGN: The questionnaire, covering the period 1970-1993, comprised 12 questions on physical activities at work, and 12, with similar wording, for such activities in leisure time. There were also four questions on physical training. Two-week reproducibility (test-retest reliability) concerning the period 1970-1993 was analysed in a group of 44 subjects, and 1-year reproducibility, concerning current activities in 1993, was analysed in a second group of 123 subjects in relation to gender, age and low-back health. RESULTS: Test-retest reliability calculated as intraclass correlation coefficients (ri) for physical activities at work (ri 0.41-0.98) exceeded that for leisure time and physical training activities (ri 0.33-0.68). Calculated correlations did not differ markedly between past and present activities. No distinct influence of gender or low back health on 1-year reproducibility was found, in contrast to a slight tendency towards higher reproducibility among subjects of 50 years and older compared with younger subjects. CONCLUSIONS: Reproducibility of this questionnaire about physical activities at work showed no clear tendency to deteriorate regarding activities during the immediately preceding two decades. The questions about physical activities during leisure time have to be revised. Reliable retrospective information about physical activities in leisure time could perhaps not be collected by self-administered questionnaires and other methods, e.g. interview-based questionnaires, may be more suitable.

Adult↗
PubMed1996

Regulation and function of SF/HGF during migration of limb muscle precursor cells in chicken.

Limb muscles of vertebrates are derived from migratory dermomyotomal cells which emanate from a limited number of somites located adjacent to the developing limb buds. We have generated additional limb buds in chicken embryos by implantation of FGF-beads into the interlimb region in order to analyze whether these somites can be programmed to supply ectopic limbs with myogenic precursor cells. We show that migrating myogenic precursor cells are released from somites at the level of the newly formed limb, even when cell migration into the natural limb has been completed. The implantation of FGF beads in the lateral plate mesoderm rapidly induces SF/HGF expression. FGF beads implanted between HH stages 10 and 12 inhibit limb bud formation or shift the normal limb position. When an additional FGF bead was implanted at the original limb position at HH stage 15, SF/HGF expression was transiently induced to low levels without inducing a new limb. This demonstrates that the initial induction of SF/HGF by FGF does not require limb formation. Expression of SF/HGF during early limb bud stages was found in the entire developing bud and the adjacent lateral plate mesoderm with direct contacts to the lateral edge of the dermomyotome. Later, the SF/HGF expression domain retracts to a distal region below the apical ectodermal ridge. To investigate the role of SF/HGF in the migratory process, we implanted beads soaked in SF/HGF-alone or together with FGF into different locations of the developing chick embryo. In the experiments SF/HGF caused delamination of migratory cells from the dermomyotomal epithelium but no chemotactic attraction of migrating cells toward the SF/HGF source.

Animals↗
PubMed1996

Reproducibility of a questionnaire for assessment of physical load during work and leisure time. Stockholm MUSIC I Study Group. MUSculoskeletal Intervention Center.

A self-administered questionnaire on physical load in lifetime occupational work, in present job, and in present leisure activities was tested for reproducibility with the test-retest method in 126 male and 217 female workers from 30 occupations. The questionnaire contained 92 questions and nine different response scales. The results indicated that questions concerning physical activity retrospectively and in the present job, vibrations in the present job, working postures involving the whole body, and questions concerning specific leisure activities (eg ball games, skiing, etc) seem to offer sufficient reproducibility to be worth testing for validity, at least at a 5-point ordinal level. Questions concerning working postures involving parts of the body, including awkward postures, and questions concerning manual materials handling seem to offer too poor reproducibility to be used in studies in which the aim is to quantify duration in proportions of a typical working day and frequencies in times per hour. Questions concerning level of physical activity and exertion in domestic work seem to offer too poor reproducibility to be used at a 5-point ordinal level. Gender, age, and musculoskeletal complaints did not influence the reproducibility to any great extent.

Adolescent↗
PubMed1996

Musculoskeletal Symptoms among Computer-assisted Design (CAD) Operators and Evaluation of a Self-assessment Questionnaire.

A self-administered questionnaire with questions related to the physical workload at video display units (VDUs) was tested for intra- and intermethod reliability among 36 men and 64 women working with research and documentation. The results showed an acceptable test-retest agreement. The answers to three questions were validated by direct measurements: the locations of keyboard and mouse on the table, and the distance between elbow and keyboard heights when working. The self-reported locations of keyboard and mouse showed good agreement with the direct measurements. A revised version of the questionnaire was used at a telecommunication laboratory to study work postures and musculoskeletal symptoms. Among CAD operators with identical work tasks, the women (n = 67) reported a higher prevalence of musculoskeletal symptoms than did the men (n = 475). Calculated prevalence rate ratios (women/men) for musculoskeletal symptoms ranged from 1.4 (low back) to 3.4 (left elbow). The CAD operators with at least 5.6 hours of mouse use/week (median) reported more symptoms in the arms than did the CAD operators with fewer hours' work. Operators with the mouse located outside an "optimal" area on the table reported more symptoms from shoulder joints (upper arms), shoulders (scapular), elbows, and wrists than did operators with the optimal mouse location. Thus, long hours of work with the mouse, as well as working with the mouse non-optimally located on the table, seemed to be risk factors for upper-limb symptoms.

Journal Article↗
PubMed1995

Repression of the macrophage scavenger receptor in macrophage-smooth muscle cell heterokaryons.

Macrophage scavenger receptors mediate the uptake of chemically modified LDL in an unregulated manner, leading to massive intracellular accumulation of lipid and thus a foamy cellular morphology. In atherosclerotic lesions, foam cells originate not only from macrophages but also from smooth muscle cells, yet smooth muscle cells do not normally express scavenger receptors, and when exposed to chemically modified LDL in vitro, lipid accumulation does not occur. The mechanism of conversion of smooth muscle cells into foam cells in the arterial wall is thus still under discussion. To investigate whether direct interaction between macrophages and smooth muscle cells may be involved and to explore the effects of components of the two cell types on the expression of scavenger receptors, we report here experiments using somatic cell hybrids formed by fusion of the two cell types. Immunofluorescent labeling and confocal microscopic techniques were applied to investigate and measure (1) lipid accumulation (using Nile Red staining), (2) the binding and uptake of acetylated LDL (using 1,1'-dioctadecyl-1-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate-labeled acetylated LDL), and (3) receptor expression (assessed using a specific anti-receptor antibody) in smooth muscle cell-macrophage heterokaryons, macrophage-macrophage homokaryons, smooth muscle cell-smooth muscle cell homokaryons, and unfused macrophages and smooth muscle cells. The results demonstrate that scavenger receptor expression becomes repressed in macrophage-smooth muscle cell heterokaryons but not in macrophage-macrophage homokaryons. One possible explanation for the observed repression would be the existence of a negative regulatory cytoplasmic factor produced by smooth muscle cells.

Animals↗
PubMed1994

The FAR domain defines a new Xenopus laevis zinc finger protein subfamily with specific RNA homopolymer binding activity.

The zinc finger motif defines a large superfamily of nucleic acid binding proteins. Conserved amino acid sequence elements associated with structurally variant zinc finger clusters define subfamilies of zinc finger proteins (ZFPs). The FAR domain (Finger Associated Repeats) is a novel type of repeat element found at the amino-terminus in a subfamily of Xenopus laevis ZFPs. Northern blot analyses of three different members of the FAR subfamily (XFO 6, XFO 9-3 and XFG 68) revealed that each of these genes is transcribed during oogenesis, embryogenesis and in all investigated tissues of adult animals thereby indicating a ubiquitous distribution of transcripts. All FAR-ZFPs tested so far have specific RNA homopolymer binding activity; they associate preferentially with poly(U). The FAR repeats possess limited primary sequence homology with a sequence in the nucleolar shuttling protein NO38, within a region that contains a casein kinase II phosphorylation site.

Amino Acid Sequence↗
PubMed1994

Spatial and temporal transcription patterns of the forkhead related XFD-2/XFD-2' genes in Xenopus laevis embryos.

Two novel fork head related cDNA sequences, termed XFD-2 and XFD-2', have been isolated from a Xenopus laevis gastrula stage cDNA library. XFD-2 and XFD-2' proteins share 88% sequence identity; a comparison of their fork head domains yields 96% identity. Such close homology suggests that the two genes represent pseudo-allelic variants of a common ancestor and probably arose by the ancient tetraploidization event in this species. Both genes are activated at midblastula transition. Main transcriptional activity is found during blastula and gastrula stages of development; thereafter, there is a gradual decrease of transcripts until somite segregation stages. Whole mount in situ hybridisation of blastula stage embryos reveals that the genes are initially transcribed within the animal hemisphere. Subsequently, we observe their transcription in a circumferential mode along the marginal zone, i.e., within the forming mesoderm. During gastrulation, these cells enter the blastoporus at the ventral, lateral and dorsal sites. At the end of gastrula and during neural stages transcripts are localized within somitogenic mesoderm, notochord, lateral and ventral mesoderm, neural floor plate, spinal cords and in the developing brain.

Amino Acid Sequence↗
PubMed1994

Etiologic fractions for physical work load, sports and overweight in the occurrence of coxarthrosis.

OBJECTIVES: The aim of this study was to estimate the impact of physical work load, sports, and overweight on the incidence of coxarthrosis. METHODS: A case-referent study was made of 239 male recipients of a hip prosthesis and 302 men randomly selected from the general population. Information was obtained by means of an interview and questionnaire. Exposures to physical work load and sports were measured as the cumulative number of hours of exposure up to 49 years of age. Overweight was measured as the estimated body mass index at 30 or 40 years of age. RESULTS: The etiologic fraction related to the three risk factors was 40% for physical work load, 55% for sports, and 15% for overweight. Various measures of physical work load were considered, but they all proved to be correlated. CONCLUSIONS: Approximately 80% of the idiopathic coxarthrosis was explained by the presence of the three risk factors.

Age Factors↗
PubMed1994

Characterization of protein kinase CK2 protein subunits and p53 in F9 teratocarcinoma cells in the absence and presence of cisplatin.

The effect of cis-diaminedichloroplatinum(II) (cisplatin) on the induction of p53 and protein kinase CK2 activity was studied in the mouse teratocarcinoma cell line F9. Treatment of the cells with the chemotherapeutic agent cisplatin led to the detection of p53 3 h after addition of the drug. F9 cell extracts treated with and without cisplatin were analyzed by ion exchange chromatography for protein kinase CK2 alpha/beta subunits and p53 distribution. The following results were obtained: (a) in crude extracts of cisplatin-treated cells, CK2 activity was sometimes reduced by as much as 50%; (b) after separation by anionic exchange chromatography (MA7Q, BioRad) of the crude cellular extracts from cisplatin-treated cells, lower CK2 activity was found in the peak fractions confirming the results obtained with crude cellular extracts; (c) besides the detection of CK2 alpha subunit by immunostaining, we have detected, at a concentration of approximately 200 mM NaCl, a protein of approximately 46 kDa which reacted with the CK2 alpha-specific antibody. This fraction was devoid of CK2 activity; and (d) cisplatin-treated cells exhibited p53 protein, which was mostly eluting ahead but also partly together with CK2 holoenzyme.

Amino Acid Sequence↗
PubMed1993

Gene structure and alternative splicing of XFG 5-1, a X. laevis Zn finger protein with RNA homopolymer binding activity.

We describe the fine-structure of the Xenopus laevis XFG 5-1 gene which codes for an RNA homopolymer binding Zn finger protein of the FAR (Finger Associated Repeat) subfamily. The gene contains six exons, i.e., a leader exon (I), four exons (II-V), each of them encoding one individual copy of the FAR repeat, and one exon (VI) encoding the linker as well as the complete multifinger-region of the corresponding protein. Isolation and characterization of distinct cDNAs revealed that primary transcripts are alternatively spliced, thereby leading either to mRNAs containing different copy numbers of the FAR repeat or, by utilization of an alternative splice acceptor site in front of exon VI, to an extension of the linker region between the FAR repeats and the multifinger domain. We also describe the fine-structure of a closely related gene, termed XFG 5-2, which is located downstream to the XFG 5-1 gene. The general structural organization in both genes is identical, but point mutations should give rise to a XFG 5-2 protein with a different number of Zn finger units.

Alternative Splicing↗
PubMed1992

Activin A induced expression of a fork head related gene in posterior chordamesoderm (notochord) of Xenopus laevis embryos.

A gene family encoding the fork head/HNF-3 domain has been identified in the South African clawed frog, Xenopus laevis. Screening of genomic DNA and gastrula stage derived cDNA libraries with a DNA fragment encoding the Drosophila fork head domain led to the isolation of a number of different clones encoding this motif. While one of the Xenopus fork head sequences, XFD-3, represents the Xenopus counterpart to rat HNF-3 beta, all other sequences encode novel types of fork head related proteins. Here we report on XFD-1, a DNA binding protein which can bind to the HNF-3 alpha target sequence. Analysis of temporal and spatial expression revealed that the gene is activated at blastula stage and that transcripts are localized in a rather thin stripe of cells invaginating the dorsal blastopore lip (organizer) during gastrulation. XFD-1 mRNA is localized within the notochord and, by the end of neurulation, is no longer detectable. In the animal cap assay the gene is activated by incubation with the vegetalizing factor (activin A) but not with bFGF.

Activins↗