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Biomedical subjects

A B Bakker

Publications and source records attributed to A B Bakker.

At least 19 recordsLinked to original sources

Determinants of change in the intention to use benzodiazepines.

OBJECTIVE: To examine attitudes and beliefs associated with changes in the intention to use benzodiazepines during the six-month period after first benzodiazepine use. DESIGN: Population-based 6-month follow-up with 3 measurement points (baseline, 2 weeks after inclusion, 6 months after inclusion). SETTING: Starting or initial benzodiazepine users were included during a period of 4 months from November 1994 in the only pharmacy of a Dutch community of 13,500 people. MEASURES: Variables proposed by the Model of Planned Behaviour and the Health Belief Model. Drug exposure data from automated pharmacy records. RESULTS: At baseline, the intention to use benzodiazepines was primarily predicted by the perceived norm of the general practitioner regarding benzodiazepine use, and by the participants' own attitudes. After fourteen days, the determinants of change in the intention to use benzodiazepines were the initially perceived norm of the general practitioner and the change in the severity of participants' illnesses. After six months, the change in the severity of the illness and the perceived health benefits of benzodiazepines at the time of inclusion were the main determinants of the change in the intention to use benzodiazepines between the second and third measurement point. The intention to use benzodiazepines showed a decrease during follow-up. The three intention measures were significant predictors of actual benzodiazepine use during the year following baseline assessment. CONCLUSION: The study sheds light on interesting determinants of decrease or increase in the intention to use during the six-month period after first benzodiazepine use.

Adult↗

Burnout and engagement at work as a function of demands and control.

OBJECTIVES: The present study was designed to test the demand-control model using indicators of both health impairment and active learning or motivation. METHODS: A total of 381 insurance company employees participated in the study. Discriminant analysis was used to examine the relationship between job demands and job control on one hand and health impairment and active learning on the other. RESULTS: The amount of demands and control could be predicted on the basis of employees' perceived health impairment (exhaustion and health complaints) and active learning (engagement and commitment). Each of the four combinations of demand and control differentially affected the perception of strain or active learning. Job demands were the most clearly related to health impairment, whereas job control was the most clearly associated with active learning. CONCLUSIONS: These findings partly contradict the demand-control model, especially with respect to the validity of the interaction between demand and control. Job demands and job control seem to initiate two essentially independent processes, and this occurrence is consistent with the recently proposed job demands-resources model.

Burnout, Professional↗

The job demands-resources model of burnout.

The job demands-resources (JD-R) model proposes that working conditions can be categorized into 2 broad categories, job demands and job resources. that are differentially related to specific outcomes. A series of LISREL analyses using self-reports as well as observer ratings of the working conditions provided strong evidence for the JD-R model: Job demands are primarily related to the exhaustion component of burnout, whereas (lack of) job resources are primarily related to disengagement. Highly similar patterns were observed in each of 3 occupational groups: human services, industry, and transport (total N = 374). In addition, results confirmed the 2-factor structure (exhaustion and disengagement) of a new burnout instrument--the Oldenburg Burnout Inventory--and suggested that this structure is essentially invariant across occupational groups.

Adult↗

The ITAM-bearing transmembrane adaptor DAP12 in lymphoid and myeloid cell function.

DAP12, an ITAM-bearing transmembrane adaptor protein, associates non-covalently with receptors in natural killer (NK) and myeloid cells, and provides signaling function via the Syk and ZAP-70 tyrosine kinase activation pathways. Humans and mice lacking DAP12 (DAP12(-/-)) show normal development of hematopoietic cells. However, DAP12(-/-) humans develop presenile dementia and bone cysts, and DAP12(-/-) mice show impaired immune responses.

Adaptor Proteins, Signal Transducing↗

NK cell activation: distinct stimulatory pathways counterbalancing inhibitory signals.

A delicate balance between positive and negative signals regulates NK cell effector function. Activation of NK cells may be initiated by the triggering of multiple adhesion or costimulatory molecules, and can be counterbalanced by inhibitory signals induced by receptors for MHC class I. A common pathway of inhibitory signaling is provided by immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in the cytoplasmic domains of these receptors which mediate the recruitment of SH2 domain-bearing tyrosine phosphate-1 (SHP-1). In contrast to the extensive progress that has been made regarding the negative regulation of NK cell function, our knowledge of the signals that activate NK cells is still poor. Recent studies of the activating receptor complexes have shed new light on the induction of NK cell effector function. Several NK receptors using novel adaptors with immunoreceptor tyrosine-based activation motifs (ITAMs) and with PI 3-kinase recruiting motifs have been implicated in NK cell stimulation.

Adaptor Proteins, Signal Transducing↗

DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming.

DAP12 is an ITAM-bearing membrane adaptor molecule implicated in the activation of NK and myeloid cells. In mice rendered DAP12 deficient by targeted gene disruption, lymphoid and myeloid development was apparently normal, although the activating Ly49 receptors on NK cells were downregulated and nonfunctional. To analyze the consequences of DAP12 deficiency in vivo, we examined the susceptibility of DAP12-/- mice to experimental autoimmune encephalomyelitis (EAE). DAP12-/- mice were resistant to EAE induced by immunization with myelin oligodendrocyte glycoprotein (MOG) peptide. Resistance was associated with a strongly diminished production of IFNgamma by myelin-reactive CD4+ T cells due to inadequate T cell priming in vivo. These data suggest that DAP12 signaling may be required for optimal antigen-presenting cell (APC) function or inflammation.

Adaptor Proteins, Signal Transducing↗

Retinoic acid early inducible genes define a ligand family for the activating NKG2D receptor in mice.

Here we describe a family of GPI-anchored cell surface proteins that function as ligands for the mouse activating NKG2D receptor. These molecules are encoded by the retinoic acid early inducible (RAE-1) and H60 minor histocompatibility antigen genes on mouse chromosome 10 and show weak homology with MHC class I. Expression of the NKG2D ligands is low or absent on normal, adult tissues; however, they are constitutively expressed on some tumors and upregulated by retinoic acid. Ectopic expression of RAE-1 and H60 confers target susceptibility to NK cell attack. These studies identify a family of ligands for the activating NKG2D receptor on NK and T cells, which may play an important role in innate and adaptive immunity.

Amino Acid Sequence↗

Characteristics of current benzodiazepine users as indicators of differences in physical and mental health.

The relationship between characteristics of benzodiazepine exposure and health-status was examined in order to investigate risk profiles of benzodiazepine users. In the only pharmacy of a Dutch community of 13,500 inhabitants, all current benzodiazepine users that presented with a benzodiazepine prescription in November 1994 were invited to participate. On the basis of the RAND-36 questionnaire, summary scores for both physical and mental health were calculated, the Physical Component Summary (PCS) and the Mental Component Summary (MCS). After dichotomization with a cut-off point indicating seriously impaired health and after the combination of the PCS and MCS, four different categories of health status could be identified. We used logistic regression to study the relation between these four different groups with respect to benzodiazepine exposure. In total a group of 360 current benzodiazepine users was studied. Results showed that almost one-third of the participants had no significant impaired health; this group was further classified as reference group. We classified three other groups: one with physical problems (31%), one with mental problems (18%), and one with a combination of the two (22%). Multivariate analysis showed differences in risk factors for an impaired health status. The group with impaired physical health was associated with self-reported indication for muscle relaxation, hypnotic use, and a high CDS (Chronic Disease Score). The group with impaired mental health was associated with more frequent consulting of a mental health care specialist and with a low sense of self-efficacy. The group with both impaired physical as well as mental health was associated with a higher incidence of widowhood, a lower sense of self-efficacy, a high CDS, using benzodiazepines more than prescribed, and reporting depression as reason for their benzodiazepine use. In particular, two groups need critical examination: a group of apparently healthy users with long-term benzodiazepine use; and a frail group with impaired physical and mental health and using a higher dose than prescribed. Patient counseling and management of these four groups can be tailored to the specific needs of each group.

Adolescent↗

Financial problems and health complaints among farm couples: results of a 10-year follow-up study.

Over a 10-year period, this survey study of 91 Dutch dairy farm couples investigated both causal and reversed causal relationships between couples' financial problems and husbands' and wives' mental and physical health complaints, as well as crossover effects of mental and physical health complaints between spouses. These relationships were tested simultaneously using structural equation modeling analyses. Results showed that financial problems were not predictive of health complaints for either spouse but that husbands' health complaints did predict both couples' financial problems and wives' health complaints 10 years later. These findings emphasize the importance of mental and physical health as resources for both the business and the family. For wives, these effects were not found, which may reflect the different positions of husbands and wives at the farm and, hence, the different ways they allocate their resources.

Age Factors↗

Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts.

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL; MIM 221770), also known as Nasu-Hakola disease, is a recessively inherited disease characterized by a combination of psychotic symptoms rapidly progressing to presenile dementia and bone cysts restricted to wrists and ankles. PLOSL has a global distribution, although most of the patients have been diagnosed in Finland and Japan, with an estimated population prevalence of 2x10-6 (ref. 2) in the Finns. We have previously identified a shared 153-kb ancestor haplotype in all Finnish disease alleles between markers D19S1175 and D19S608 on chromosome 19q13.1 (refs 5,6). Here we characterize the molecular defect in PLOSL by identifying one large deletion in all Finnish PLOSL alleles and another mutation in a Japanese patient, both representing loss-of-function mutations, in the gene encoding TYRO protein tyrosine kinase binding protein (TYROBP; formerly DAP12). TYROBP is a transmembrane protein that has been recognized as a key activating signal transduction element in natural killer (NK) cells. On the plasma membrane of NK cells, TYROBP associates with activating receptors recognizing major histocompatibility complex (MHC) class I molecules. No abnormalities in NK cell function were detected in PLOSL patients homozygous for a null allele of TYROBP.

Adaptor Proteins, Signal Transducing↗

Effort-reward imbalance and burnout among nurses.

This study among a sample of 204 German nurses tested the hypothesis that an imbalance of high extrinsic efforts spent (i.e. job demands) and low extrinsic rewards obtained (e.g. poor promotion prospects) are associated with the burnout syndrome: the depletion of nurses' emotional resources. The results of a series of analyses of variances confirmed this hypothesis, by showing that those nurses who experienced an effort-reward imbalance (ERI) reported higher levels on two of the three core dimensions of burnout (i.e. emotional exhaustion and depersonalization) than those who did not experience such an imbalance. Moreover - as additionally hypothesized - significant interaction effects indicated that burnout (i.e. emotional exhaustion and reduced personal accomplishment) was particularly prevalent among those nurses who experienced ERI and put relatively high intrinsic effort into their jobs, as reflected by their strong tendency to be personally in control over job conditions.

Adult↗

A model of burnout and life satisfaction amongst nurses.

This study, among 109 German nurses, tested a theoretically derived model of burnout and overall life satisfaction. The model discriminates between two conceptually different categories of working conditions, namely job demands and job resources. It was hypothesized that: (1) job demands, such as demanding contacts with patients and time pressure, are most predictive of exhaustion; (2) job resources, such as (poor) rewards and (lack of) participation in decision making, are most predictive of disengagement from work; and (3) job demands and job resources have an indirect impact on nurses' life satisfaction, through the experience of burnout (i.e., exhaustion and disengagement). A model including each of these relationships was tested simultaneously with structural equations modelling. Results confirm the strong effects of job demands and job resources on exhaustion and disengagement respectively, and the mediating role of burnout between the working conditions and life satisfaction. These findings contribute to existing knowledge about antecedents and consequences of occupational burnout, and provide guidelines for interventions aimed at preventing or reducing burnout among nurses.

Adult↗

Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor involved in the activation of myeloid cells.

Crosslinking of immunoreceptor tyrosine-based activation motif (ITAM)-containing receptor complexes on a variety of cells leads to their activation through the sequential triggering of protein tyrosine kinases. Recently, DAP12 has been identified as an ITAM-bearing signaling molecule that is noncovalently associated with activating isoforms of MHC class I receptors on natural killer cells. In addition to natural killer cells, DAP12 is expressed in peripheral blood monocytes, macrophages, and dendritic cells, suggesting association with other receptors present in these cell types. In the present study, we report the molecular cloning of the myeloid DAP12-associating lectin-1 (MDL-1), a DAP12-associating membrane receptor expressed exclusively in monocytes and macrophages. MDL-1 is a type II transmembrane protein belonging to the C type lectin superfamily and contains a charged residue in the transmembrane region that enables it to pair with DAP12. Crosslinking of MDL-1/DAP12 complexes in J774 mouse macrophage cells resulted in calcium mobilization. These findings suggest that signaling via MDL-1/DAP12 complexes may constitute a significant activation pathway in myeloid cells.

Adaptor Proteins, Signal Transducing↗

An activating immunoreceptor complex formed by NKG2D and DAP10.

Many immune receptors are composed of separate ligand-binding and signal-transducing subunits. In natural killer (NK) and T cells, DAP10 was identified as a cell surface adaptor protein in an activating receptor complex with NKG2D, a receptor for the stress-inducible and tumor-associated major histocompatibility complex molecule MICA. Within the DAP10 cytoplasmic domain, an Src homology 2 (SH2) domain-binding site was capable of recruiting the p85 subunit of the phosphatidylinositol 3-kinase (PI 3-kinase), providing for NKG2D-dependent signal transduction. Thus, NKG2D-DAP10 receptor complexes may activate NK and T cell responses against MICA-bearing tumors.

Amino Acid Sequence↗

Specific determinants of intrinsic work motivation, burnout and turnover intentions: a study among nurses.

This study of 156 Dutch general hospital nurses tested a theoretically derived model of specific relationships between work stressors and stress reactions. The model proposes four central domains of the work situation, namely work content, working conditions, social and labour relations, and conditions of employment. In addition, the model proposes three important stress reactions, namely a diminished intrinsic work motivation, occupational burnout and an inclination to leave the job. More specifically, it was hypothesized that (i) intrinsic work motivation is primarily determined by work content variables, (ii) burnout is primarily determined by both work load and limited social support, and (iii) propensity to leave is primarily determined by conditions of employment. All these relationships were simultaneously tested using a structural equations modelling technique. The results of a series of LISREL analyses indicate that the postulated model fits well to the data. The present study used conceptually integrated measures that cover the area of work stress and stress reactions, and provides directions for interventions aimed at preventing or reducing specific negative outcomes of work-related stress in general hospitals.

Adult↗

Persuasive communication about AIDS prevention: need for cognition determines the impact of message format.

Adolescents were classified as being high or low in need for cognition (NFC) (Cacioppo & Petty, 1982) and expressed their knowledge about AIDS, attitudes toward condom use, and perceived supportive norms after being exposed to a cartoon or a written message about safe sex. Both messages have a positive impact on knowledge and attitudes. Theoretically interesting is the finding that the cartoon message is more effective in bringing about change in attitudes and subjective norms than the written message for low-NFC adolescents, and that the written message is more effective than the cartoon message for high-NFC adolescents. These results are consistent with the theory-based prediction that a persuasive communication will be most effective when the format of the message is tailored to people's information-processing proclivities. The practical implications of the findings for AIDS education are discussed.

Acquired Immunodeficiency Syndrome↗

Ly-49D and Ly-49H associate with mouse DAP12 and form activating receptors.

Several members of the Ly-49 receptor family inhibit NK cell-mediated lysis of targets expressing appropriate MHC class I molecules. Ly-49D and Ly-49H, two Ly-49 molecules that lack immunoreceptor tyrosine-based inhibitory motifs (ITIM) in their cytoplasmic domains, associate with mouse DAP12, a molecule that possesses an immunoreceptor tyrosine-based activation motif (ITAM). Cotransfection of either Ly-49D or Ly-49H with DAP12 induces surface expression of both Ly-49 and DAP12. The Ly-49/DAP12 complex was coimmunoprecipitated from the transfected cells, demonstrating a physical association of DAP12 with Ly-49D or Ly-49H in the plasma membrane. Stimulation of transfectants with Abs recognizing either Ly-49D or Ly-49H results in cellular activation, as assessed by induction of tyrosine phosphorylation of multiple cellular substrates.

Adaptor Proteins, Signal Transducing↗

Killer cell inhibitory receptors for MHC class I molecules regulate lysis of melanoma cells mediated by NK cells, gamma delta T cells, and antigen-specific CTL.

NK cells and T cells express killer cell inhibitory receptors (KIR) recognizing polymorphic MHC class I molecules. Although prior studies have established that MHC class I can protect normal and transformed hematopoietic cells from NK cell lysis, the role of MHC class I on the recognition of solid tumors has been controversial. In this study, we investigated whether interactions of KIR with their ligands on melanoma tumor cells could inhibit tumor cell lysis by NK and gamma delta T cell clones. Ligation of the NK cell receptor KIR3DL1 by HLA-Bw4 allotypes resulted in inhibition of cytotoxicity against HLA-B*4403-transfected melanomas as well as against melanomas endogenously expressing HLA-Bw4 allotypes. Similarly, interactions of KIR2DL2 or KIR2DL3 (KIR2DL2/3) with HLA-Cw3-related allotypes on melanomas resulted in decreased tumor cell lysis. We also investigated whether signaling via KIR affected melanoma recognition by CTL. Introduction of KIR3DL1 molecules into HLA-A*0201-restricted gp100-specific CTL resulted in inhibition of lysis of gp100+ melanomas co-expressing HLA-A*0201 and HLA-Bw4 allotypes. These results suggest that disrupting interactions of KIR with their ligands on tumor cells in vivo may enhance antitumor responses mediated by both innate and adaptive immune effector cells.

Animals↗