Biomedical subjects

J Höög

Publications and source records attributed to J Höög.

8 recordsLinked to original sources

PubMed2001

Crystal structure of sorbitol dehydrogenase.

Sorbitol dehydrogenase (SDH) is a distant relative to the alcohol dehydrogenases (ADHs) with sequence identities around 20%. SDH is a tetramer with one zinc ion per subunit. We have crystallized rat SDH and determined the structure by molecular replacement using a tetrameric bacterial ADH as search object. The conformation of the bound coenzyme is extended and similar to NADH bound to mammalian ADH but the interactions with the NMN-part have several differences with those of ADH. The active site zinc coordination in SDH is significantly different than in mammalian ADH but similar to the one found in the bacterial tetrameric NADP(H)-dependent ADH of Clostridiim beijerinckii. The substrate cleft is significantly more polar than for mammalian ADH and a number of residues are ideally located to position the sorbitol molecule in the active site. The SDH molecule can be considered to be a dimer of dimers, with subunits A-B and C-D, where the dimer interactions are similar to those in mammalian ADH. The tetramers are composed of two of these dimers, which interact with their surfaces opposite the active site clefts, which are accessible on the opposite side. In contrast to the dimer interactions, the tetramer-forming interactions are small with only few hydrogen bonds between side-chains.

Animals↗

PubMed2001

Mammalian alcohol dehydrogenase of higher classes: analyses of human ADH5 and rat ADH6.

Alcohol dehydrogenases (ADH) of classes V and VI, ADH5 and ADH6, have been defined in man and rodents, respectively. Sequence data have been obtained at cDNA and genomic levels, but limited data are available for functionality and substrate repertoire. The low positional identity (65%) between the two ADHs, place them into separate classes. We have shown that the ADH5 gene yields two differently processed mRNAs and harbors a gene organization identical to other mammalian ADHs. This is probably due to an alternative splicing in the eighth intron that results in a shorter message missing the ninth exon or a normal message with the expected number of codons. The isolated rat ADH6 cDNA was found to be fused to ADH2 at the 5'-end. The resulting main open reading frame translates into an N-terminally extended polypeptide. In vitro translation results in a polypeptide of about 42 kDa and further, protein was possible to express in COS cells as a fusion product with Green Fluorescent Protein. Both ADH5 and ADH6 show genes and gene products that are processed comparably to other mammalian ADHs and the deduced amino acid sequences indicate a lack of ethanol dehydrogenase activity that probably explains why no corresponding proteins have been isolated. The functionality of these ADHs is therefore still an enigma.

Alcohol Dehydrogenase↗

PubMed2001

Class II alcohol dehydrogenase (ADH2)--adding the structure.

Class II alcohol dehydrogenase (ADH2) represents a highly divergent class of alcohol dehydrogenases predominantly found in liver. Several species variants of ADH2 have been described, and the rodent enzymes form a functionally distinct subgroup with interesting catalytic properties. First, as compared with other ADHs, the catalytic efficiency is low for this subgroup. Second, the substrate repertoire is unique, e.g. rodent ADH2s are not saturated with ethanol as substrate, and while omega-hydroxy fatty acids are common substrates for the human ADH1-ADH4 isoenzymes, including ADH2, these compounds function as inhibitors rather than substrates. The recently determined structure of mouse ADH2 reveals a novel substrate-pocket topography that accounts for the observed substrate specificity and may, therefore, be important for the exploration of orphan substrates of ADH2. It is possible to improve the catalytic efficiency of mouse ADH2 by an array of mutations at position 47. Residue Pro47 of the wild type ADH2 enzyme seems to strain the binding of coenzyme, which prevents a close approach between the coenzyme and substrate for efficient hydrogen transfer. Based on crystallographic and mechanistic investigations, the effects of residue replacements at position 47 are multiple, affecting the distance for hydride transfer, the pK(a) of the bound alcohol substrate as well as the affinity for coenzyme.

Alcohol Dehydrogenase↗

PubMed1998

Physical and psychosocial work-related risk factors associated with musculoskeletal symptoms among home care personnel.

The aim of this cross-sectional study was to investigate physical and psychosocial aspects of the work environment, sociodemographic data and certain lifestyle factors, and the relationship between these variables and complaints in the shoulder/neck and low back area among female home care personnel. A questionnaire was completed by 361 randomly selected women. Multiple logistic regression analyses were conducted to evaluate the importance of several exposure factors for complaints in the shoulder/neck and low back areas. The results of this study clearly indicate that 'standing in forward-bent and twisted postures' can be viewed as a risk factor for shoulder/neck pain. A combination of this physical exposure and 'no possibility of influencing the planning of work' gave an increase in odds ratio, indicating an interaction between these two exposure indices. However, this interaction was not found for low back pain. 'Standing in forward-bent and twisted postures', 'standing in awkward positions' and whether the subject had children staying at home were significantly correlated to complaints about the low back. In fact, the latter factor decreased the risk of having complaints. The results indicated that certain physical and psychosocial work risk factors could influence shoulder/neck and low back pain.

Adult↗

PubMed1997

The psychosocial work environment and skin symptoms among visual display terminal workers: a case referent study.

BACKGROUND: This study is a part of the interdisciplinary project The Office Illness Project in Northern Sweden, which was initiated with a questionnaire study in late 1988. Previously published results from the project have shown that facial skin symptoms reported among visual display terminal (VDT) workers are associated with a number of exogenous factors. This part of the project investigated the relation between the psychosocial work environment and facial skin complaints. METHODS: From an initial questionnaire study among 4943 office workers, 163 VDT workers were selected for a case referent study of facial skin symptoms. The data comprise a self-administered questionnaire filled out by 149 subjects and interviews with representatives of the organizations concerned. RESULTS: Psychosocial conditions, especially lack of social support from co-workers, were associated with an increased risk of reporting skin symptoms. Stratification by sex showed that the associations between some psychosocial factors and health differed between men and women. The results indicate that there might be an interaction between psychosocial factors and electric fields in the workplace which increases the risk of reporting skin symptoms. CONCLUSIONS: This study supports the idea that the aetiological basis of facial skin symptoms among VDT-workers includes physical as well as psychosocial factors, and that the interaction between such factors might be significant in the understanding of skin complaints among VDT workers.

Adult↗

PubMed1997

Facial skin symptoms in office workers. A five-year follow-up study.

This longitudinal study is a part of the interdisciplinary project. The Office Illness Project in Northern Sweden, which was initiated with a questionnaire study in late 1988. Among 3233 visual display terminal (VDT) workers, an initial case-referent group of 163 individuals was selected. The data acquisition included two questionnaires, assessments at the workplaces, interviews with personnel staff of the organizations concerned, and a clinical examination of the respondents. Subjects participating in the case-referent study 1988 filled out a questionnaire in the beginning of 1994. The primary objective of this study is to discuss changes in and causes of facial skin symptoms among VDT workers in the long term. The results show that (1) facial skin symptoms among VDT workers seem to be of a transitory nature for most of those with isolated skin symptoms, whereas the prognosis for those with a more complex symptom picture is more negative, (2) assumptions that measures taken in the work environment-including those involving the VDT and other electric devices-would have a positive effect on symptoms were not supported, and (3) the strongest external risk indicators for lasting skin symptoms seem to be found in the psychosocial work environment. Therefore, one important issue for the understanding of facial skin symptoms is organizational climate and personnel policies. The results also imply that individual factors, both constitutional and psychological, must be considered.

Adult↗

PubMed1995

Facial skin symptoms in visual display terminal (VDT) workers. A case-referent study of personal, psychosocial, building- and VDT-related risk indicators.

BACKGROUND: The Office Illness Project in northern Sweden, comprising both a screening questionnaire study of 4943 office workers and a case-referent study of facial skin symptoms in 163 subjects was recently completed. Previously published results from the survey showed that female gender, asthma/rhinitis, high psychosocial work load, visual display terminal (VDT) and paperwork were related to an increased prevalence of facial skin symptoms. METHODS: The case-referent study presented in this paper used data from the questionnaire supplemented by information from a clinical examination, a survey of psychosocial factors at work, building data and VDT-related factors from inspection and measurements taken at the work site. RESULTS: Psychosocial conditions and exposure to electromagnetic fields or conditions associated with such factors were related to an increased occurrence of skin symptoms. The results also indicated that personal factors such as atopic dermatitis and physical exposure factors influencing indoor air quality, such as paper exposure and cleaning frequency were related to an increased prevalence of symptoms. CONCLUSIONS: The results suggest that skin symptoms reported by VDT users have a multifactorial background.

Administrative Personnel↗

PubMed1994

The Sick Building Syndrome (SBS) in office workers. A case-referent study of personal, psychosocial and building-related risk indicators.

BACKGROUND: The Office Illness Project in Northern Sweden, comprising both a screening questionnaire study of 4943 office workers and a case-referent study of Sick Building Syndrome (SBS) in 464 subjects was recently completed. Previously published results from the survey showed that female gender asthma/rhinitis, high psychosocial work load, paper and visual display terminal (VDT) work were related to an increased prevalence of SBS symptoms. METHODS: The case-referent study presented in this paper used data from the questionnaire supplemented with information from a clinical examination, a survey of psychosocial factors at work building data from inspection and measurements taken at the work sites. RESULTS: Personal factors such as atopy and photosensitive skin, psychosocial conditions and physical exposure factors influencing indoor air quality (IAQ), such as outdoor air flow rates and the presence of photocopiers were related to an increased prevalence of the reported SBS symptoms. The results were established using multivariate analysis. CONCLUSIONS: The rate response relationship between actually measured ventilation rates and the prevalence of perceived SBS symptoms presents strong evidence for the association between IAQ factors and health.

Adult↗