Externally assessed psychosocial work characteristics and diagnoses of anxiety and depression.

BACKGROUND: Interpretations of relationships between work characteristics and psychiatric disorders may be biased by over-reporting of unfavourable work characteristics among those with psychiatric disorders. This study attempts to account for this bias by using external assessments of work characteristics. METHODS: Psychiatric symptoms were assessed in an interview and psychiatric diagnoses were established according to DSM-IV. Current work characteristics and work characteristics three years ago were assessed in an interview with predetermined criteria and included cognitive requirements, possibility of influence, and required conformance to schedule, time pressure, and hindrances concerning goals, resources and instrumental support. Deterioration in work characteristics during the study period was also assessed. The sample consisted of 672 employed men and women in different occupations. RESULTS: Lack of instrumental support from colleagues and supervisors (OR 6.4, 95% CI 2.6 to 15.8) assessed as a hindrance to work performance, and deterioration in work characteristics during the study period (OR 2.8, 95% CI 1.3 to 6.1) were associated with increased odds ratios for depression after adjustment for confounding factors, including symptoms of mental illness at baseline. Findings for anxiety were similar but not statistically significant. CONCLUSION: Externally assessed lack of instrumental social support at work and deteriorating work characteristics were associated with an increased risk for depression.

Does psychological distress influence reporting of demands and control at work?

AIMS: To investigate whether self reporting of psychological demands and control at work is as valid for psychologically distressed subjects as for subjects with psychological wellbeing. METHOD: Self reported demands and control (according to the model of Karasek) were compared to expert assessments through direct observations of each subject's work conditions concerning time pressure, hindrances, qualification for work tasks, and possibility of having influence. The comparison was made between respondents reporting and not reporting psychological distress as measured by the general health questionnaire with 12 questions (GHQ-12). The sample consisted of 203 men and women in 85 occupations. RESULT: No systematic differences between self reported and externally assessed working conditions for respondents reporting different levels of psychological distress were found. CONCLUSION: Over-reporting of work demands or under-reporting of work control is unlikely at the levels of psychological distress studied.

The role of an exposed loop in the alpha2 domain in the mouse MHC class I H-2Dd molecule for recognition by the monoclonal antibody 34-5-8S and the NK-cell receptor Ly49A.

Natural killer (NK) cells express major histocompatibility complex (MHC) class I-specific inhibitory receptors. The region mediating the protective effect of the MHC class I molecule H-2Dd (Dd), recognized by the inhibitory receptor Ly49A, has been mapped to the alpha1/alpha2 domains. Here we have focused on an exposed loop in the N-terminal part of the alpha2 domain, which constitutes a major structural motif that differs between Dd (strong binding to Ly49A) and Db (weak binding to Ly49A at best). We mutated the residues 103, 104 and 107 in Dd to the corresponding amino acids in Db. The Dd mutant molecule retained the ability to be stabilized by a Dd-binding peptide. However, the mutation totally abolished the recognition by the conformational dependent monoclonal antibody (MoAb) 34-5-8S, known to inhibit the interaction between Dd and Ly49A. In addition, there was a marked impairment of the binding to Ly49A as evaluated by the ability of tetramers of the Dd mutant molecule to bind to Ly49A-transfected reporter cells and spleen cells. These results demonstrate that the introduced changes at positions 103, 104 and 107 directly or indirectly affect the epitopes for the MoAb 34-5-8S and the Ly49A receptor.

The influence on seeking care because of neck and shoulder disorders from work-related exposures.

The aim of this study was to assess the influence of work-related physical and psychosocial factors on seeking care for neck or shoulder disorders among men and women in a general working population. The study population comprised gainfully employed (>17 hours per week) men and women in the municipality of Norrtälje, altogether 392 cases and 1,511 controls. Cases were defined as persons seeking care because of neck or shoulder disorders by any caregiver in the region. The study began in 1994 and continued to 1997. We assessed physical and psychosocial exposures by questionnaires and interviews. The pattern of seeking care for neck or shoulder disorders differed between men and women. Among men, work with vibrating tools [relative risk (RR) = 1.6], not having a fixed salary (RR = 1.9), and low demands in relation to competence (RR = 1.5) were the strongest risk indicators obtained in analyses stratified for age and previous symptoms. Among women, repetitive hand or finger movements (RR = 1.6), constrained sitting (RR = 1.6), not having a fixed salary (RR = 2.0), and solitary work (RR = 1.8) were the strongest risk indicators. A large proportion of the general population was exposed to several of these moderately harmful conditions, and their concomitant effect may explain the high incidence of neck and shoulder disorders in the general working population.

To what extent do current and past physical and psychosocial occupational factors explain care-seeking for low back pain in a working population? Results from the Musculoskeletal Intervention Center-Norrtälje Study.

STUDY DESIGN: A population-based case referent study. OBJECTIVES: To determine whether current and past physical and psychosocial occupational factors are associated with care-seeking for low back pain in working men and women. SUMMARY OF BACKGROUND DATA: The importance of physical and psychosocial workloads as causal factors of low back pain has mostly been investigated in special occupational groups and with a cross-sectional design, which makes generalizability and interpretations more difficult. METHODS: The study comprised 2118 working men and women 20 to 59 years old (695 cases, and 1423 referents). Cases were defined as persons seeking care by any caregiver for low back pain. The exposure assessments were made through questionnaires and interviews about current and past physical and psychosocial loads during work and leisure time. RESULTS: In a logistic regression analysis, physical load from forward bending in men (RR = 1.8) and high physical load, in general, in women (RR = 2.0) showed increased relative risks. Psychosocial factors alone seemed to be of less importance in women, but "poor job satisfaction" and "mostly routine work without possibilities of learning" increased the risk in men. Combined current and past exposures further increased the risks. A combination of high physical and psychosocial loads increased the risk substantially, but few were exposed to such loads. Adjustment for lifestyle and other loads outside work did not change the results. CONCLUSION: Current and past physical and psychosocial occupational factors, both separately and combined, seem to be gender-specific, and to have a moderate impact on care-seeking for low back pain in a general working population.

Differences in the association between psychosocial work conditions and physical work load in female- and male-dominated occupations. MUSIC-Norrtälje Study Group.

This study investigated whether there is a relationship between high physical work load and adverse psychosocial work factors, and whether this relationship is different for women and men. Separate analyses for female registered nurses and assistant nurses were made because these are common occupations involving high physical and psychological demands. This study was part of the MUSIC-Norrtälje study, a population study with the overall aim of identifying risk factors for musculoskeletal disorders. The respondents, 1423 gainfully employed men and women, were randomly selected from the study population. The exposure assessments referred to a typical workday during the previous 12 months. Physical exposure was investigated by interview, psychosocial work factors by interview and questionnaire. For the women, but not the men, mainly routine work and a job strain situation, according to the model of Karasek and Theorell, increased the probability of having a high physical work load, assessed as a time-weighted average of energy expenditure in multiples of the resting metabolic rate. Results indicated that in female-dominated occupations, high physical work load might also imply adverse psychosocial conditions. A higher frequency of high physical work load and job strain was observed among assistant nurses compared with registered nurses. Covariance between physical and psychosocial demands makes it difficult to determine the relative influence of each in health problems. Results of the present study imply that this is a larger problem in studies of women than men.

Impaired MHC class I (H-2Dd)-mediated protection against Ly-49A+ NK cells after amino acid substitutions in the antigen binding cleft.

The MHC class I molecule H-2Dd (Dd) acts as a ligand for the inhibitory NK cell receptor Ly-49A. We have constructed altered Dd molecules by site-directed mutagenesis, replacing residues with the corresponding amino acids from the Db molecule, which fails to inhibit via Ly-49A. Mutations at positions 73 and 156 (DdS73WD156Y) impaired the protective effect of the Dd molecule, as evaluated by testing lymphoma cells transfected with the mutant gene for sensitivity to killing by Ly-49A+ NK cells in vitro and rejection by NK cells in vivo. The altered residues form a hydrophobic ridge across the floor of the antigen binding cleft. A mutation in the alpha helix of the alpha2 domain, facing the solvent and without direct contact with the peptide (DdA150S) had no effect. Dd recognition by Ly-49A+ NK cells is considered to be peptide dependent, but not peptide specific. Our results indicate that alterations of residues buried in the antigen binding cleft can induce changes in peptide binding patterns and/or conformational changes in the Dd molecule that make the trimolecular complex less permissive for inhibition of Ly-49A+ NK cells.

Interview reliability for assessing mental work demands.

This study presented and evaluated an interview method for the analysis of tasks included in a work situation. What mental demands and possibilities do the work tasks give rise to? When was the work more or less automatic? When was use of active knowledge required? When were problem solving and planning needed? The study included an assessment of the interobserver reliability of the interviews with employees from 5 different careers: bus drivers (n = 10), home service workers (n = 32), carpenters (n = 11), farmers (n = 14), and teachers (n = 26). The extent to which this method can be reproduced in studies of different occupations is discussed. The interobserver reliability was good (.75-.82). There is support for the stability and usefulness of the interview for most types of work concerning the 3 categories of mental demands: routine, active knowledge, and problem solving/creativity.

The alpha2 domain of H-2Dd restricts the allelic specificity of the murine NK cell inhibitory receptor Ly-49A.

Mouse NK lymphocytes express Ly-49 receptors, which inhibit cytotoxicity upon ligation by specific MHC I molecules on targets. Different members of the lectin-like mouse Ly-49 receptor family recognize distinct subsets of murine H-2 molecules, but the molecular basis for the allelic specificity of Ly-49 has not been defined. We analyzed inhibition of natural killing by chimeric MHC I molecules in which the alpha1, alpha2, or alpha3 domains of the Ly-49A-binding allele H-2Dd were exchanged for the corresponding domains of the nonbinding allele H-2Db. Using the Ly-49A-transfected rat NK cell line, RNK-mLy-49A.9, we demonstrated that the H-2Dd alpha2 domain alone accounts for allelic specificity in protection of rat YB2/0 targets in vitro. We also showed that the H-2Dd alpha2 domain is sufficient to account for the allele-specific in vivo protection of H-2b mouse RBL-5 tumors from NK cell-mediated rejection in D8 mice. Thus, in striking contrast to the alpha1 specificity of Ig-like killer inhibitory receptors for human HLA, the lectin-like mouse Ly-49A receptor is predominantly restricted by the H-2Dd alpha2 domain in vitro and in vivo.

Rejection of tumors in mice with severe combined immunodeficiency syndrome determined by the major histocompatibility complex. Class I expression on the graft.

This study addresses the role of MHC class I molecules in the rejection of tumor grafts by SCID mice. Tumor cell lines, their corresponding MHC class I transfectants, and MHC class I-deficient mutants were inoculated to SCID mice. This allowed a study of tumor rejection responses in an environment with normal numbers of natural killer cells but largely devoid of functional T and B cells. C.B-17 (H-2d) SCID mice were found to reject low (10(2)) but not high (10(4)) doses of allogeneic (H-2b) tumor cells. The introduction of H-2Dd into such allogeneic tumor cells abrogated the rejection response with progressive tumor growth as a consequence. Introduction of H-2Kd or Ld had no or only marginal effects. The protective ability of H-2Dd was mapped to the alpha 1/alpha 2 domains of the molecule. H-2Dd protected allogeneic tumors from rejection also in C3H SCID mice of the H-2k haplotype, demonstrating that this ability was not dependent on H-2Dd expression in the host. Expression of endogenous H-2Kb and/or Db molecules partially protected wild-type allogeneic tumor cells from rejection since mutant allogeneic cells, devoid of class I expression, were rejected even after high-dose inoculation. Introduction of either allogeneic or xenogeneic class I molecules did not lead to rejection of otherwise MHC class I syngeneic (H-2d) tumor cells. The observed tumor cell rejection in SCID mice was dependent on natural killer cells. After depletion of asialo-GM1+ cells, all inoculated tumor cell lines grew progressively, independently of MHC class I expression. These results are compatible with a model where expression of certain, but not all, class I molecules protect from natural killer cell-mediated rejection. There was no evidence for rejection occurring as a consequence of the expression of allogeneic or xenogeneic class I molecules on the grafted cells. MHC class I expression may thus influence tumor cell recognition in mice lacking T-cell receptor expression.

Role of major histocompatibility complex class I alpha 1/alpha 2 domain polymorphism and in vivo expression pattern in tumor resistance: studies with transgenic mice and lymphoma cell transfectants.

The influence of major histocompatibility complex (MHC) class I molecules on target cell sensitivity and natural killer cell specificity was investigated. H-2b lymphoma cells grew progressively in syngeneic nontransgenic C57Bl/6 (B6) mice, but were rapidly rejected (within 24 h) in H-2Dd transgenic B6 mice (D8). Rejection required transgene expression in hematopoietic tissues, as revealed in experiments using transgenic mice with tissue-specific expression of the transgene into the target cells as well as bone marrow chimeric mice. The rejection was abrogated by transfection of the H-2Dd gene, providing evidence of "missing self" recognition in vivo triggered by a single class I allelic difference between host and graft. Lymphoma cells transfected with nonrelated class I molecules (H-2Dp and H-2Ld) did not lead to escape from rejection in D8 mice. Furthermore, transfection with exon shuffled constructs between H-2Dd and H-2Ld allowed mapping of the "protective" parts of H-2Dd. Only the transfectant expressing the alpha 1/alpha 2 domains of H-2Dd (the alpha 3 domain of H-2Ld) escaped elimination in D8 mice, while the transfectant expressing the opposite exon shuffled gene (the alpha 1/alpha 2 domains of H-2Ld in connection with the alpha 3 domain of H-2Dd) was rejected like the nontransfected wild type. The results showed that (a) introduction of a novel MHC class I gene in transgenic mice altered the specificity of natural killer cells, and (b) protection from transgenic NK cells required expression of the alpha 1/alpha 2 domains of H-2Dd at the target level.

Replication of bovine papillomavirus vectors in murine cells.

Varying capacities for autonomous replication have been obtained with bovine papillomavirus type 1 (BPV-1)-based expression vectors in mouse C127 cells. Both integration of the vector DNA into the genome of the host cell and replication as monomeric extrachromosomal elements have been observed. In this study, we have examined what features of BPV-1 vectors influence their replication potential. Transfection of the entire BPV-1 genome into C127 cells resulted in the replication of extrachromosomal monomeric BPV-1 elements. The same result was obtained when a plasmid sequence was inserted into the BPV-1 DNA. However, introduction of foreign, transcriptionally active units resulted in chromosomal integration of the expression vectors. This result was obtained with clones isolated by co-transfection followed by neomycin selection, as well as with clones isolated from neoplastic foci. Supertransfection of a BPV-1-based expression vector into cells harbouring unintegrated replicating BPV-1 genomes resulted in integration of the vector DNA, whereas replication of the resident BPV-1 genomes was unaffected. Extrachromosomal replication of such a vector was achieved when the enhancer and promoter region of the foreign gene were deleted.

Synthesis and secretion of a fibrinolytically active tissue-type plasminogen activator variant in Escherichia coli.

A gene encoding a variant (lacking amino acids 6-173) of human tissue-type plasminogen activator (t-PA), consisting only of the second kringle domain (K2) and the serine protease domain (P), was fused to a DNA segment coding for the signal peptide of staphylococcal protein A and a synthetic gene coding for a protein with ability to bind immunoglobulin G (IgG). The fusion protein which was synthesized in Escherichia coli and secreted into the growth medium, was found to be fibrinolytically active. Purification of the fusion protein was performed in a single step by affinity chromatography with immobilized IgG. Enzymatically active K2P was liberated from the fusion protein by cleavage at a unique Asn-Gly dipeptide sequence using hydroxylamine. These results demonstrate that a variant of human t-PA can be synthesized and secreted by E. coli as a fibrinolytically active fusion protein, which upon specific cleavage yields an active variant t-PA of the expected size.