Showing papers by "University of Düsseldorf published in 1998"
TL;DR: It is revealed that the temporal evolution of the peripheral tremor rhythms directly reflects the time course of the synchronization of abnormal activity between cortical motor areas.
Abstract: We use the concept of phase synchronization for the analysis of noisy nonstationary bivariate data. Phase synchronization is understood in a statistical sense as an existence of preferred values of the phase difference, and two techniques are proposed for a reliable detection of synchronous epochs. These methods are applied to magnetoencephalograms and records of muscle activity of a Parkinsonian patient. We reveal that the temporal evolution of the peripheral tremor rhythms directly reflects the time course of the synchronization of abnormal activity between cortical motor areas.
1,369 citations
TL;DR: The science base that underpins the argument that oxidative damage is a significant causative factor in the development of human diseases and that antioxidants are capable of preventing or ameliorating these disease processes is assessed critically.
Abstract: This paper assesses critically the science base that underpins the argument that oxidative damage is a significant causative factor in the development of human diseases and that antioxidants are capable of preventing or ameliorating these disease processes. The assessment has been carried out under a number of headings, and some recommendations for future research are made based on the present day knowledge base. The knowledge database (1) Consideration of the basic science that underlies understanding of the role of free radicals in causing cellular pathologies, and the role of antioxidants in preventing this, shows that an imbalance of reactive oxygen species and antioxidant defence systems may lead to chemical modifications of biologically relevant macromolecules. This imbalance provides a logical pathobiochemical mechanism for the initiation and development of several disease states. Experimental data obtained in vivo provide evidence that antioxidants function in systems that scavenge reactive oxygen species and that these are relevant to what occurs in vivo. The relevance in vivo of these observations depends inter alia on knowledge of the uptake and distribution of the antioxidant within the human body, and on what tissue levels of the antioxidant may be expected in relation to dietary levels. (2) There is some way to go until validated precise methods are available for measuring biomarkers of oxidative damage in human subjects in vivo under minimally invasive conditions. With respect to oxidative damage in DNa, HPLC and GC-mass spectrophotometry methods have both merits and limitations. Lipid oxidation products in plasma are best measured as isoprostanes or as lipid hydroperoxides using specific HPLC techniques. Development of isoprostane measurement will advance specificity and precision. The measurement of oxidative damage to proteins has some potential but such methods have not been effectively exploited. (3) Epidemiological studies support the hypothesis that the major antioxidant nutrients vitamin E and vitamin C, and beta-carotene (which may or may not be acting as an antioxidant in vivo), may play a beneficial role in prevention of several chronic disorders. More research is needed on the impact of other non-nutrient compounds, such as other carotenoids and flavonoids, on human health. In general, human intervention studies using hard end-points are the gold standard. Trials are restricted mainly to the major antioxidants and do not allow firm conclusions because of inconsistent findings, an insufficient number of studies and the use of varying doses. There is evidence that large doses of beta-carotene may be deleterious to the health of certain subgroups of the population such as heavy habitual smokers. (4) With respect to the safety of administration of supplementary vitamins, vitamin C is safe at levels of supplementation up to 600 mg/d, and higher levels, up to 2000 mg/d, are without risk. Vitamin E has a very low human toxicity and an intake of 1000 mg/d is without risk; 3200 mg/d has been shown to be without any consistent risk. Large intakes of beta-carotene must be viewed with caution because they have been shown to confer detriment to a population at high risk of lung cancer when administered after many years of high risk (smoking) behaviour. Until further work clarifies the situation in heavy smokers with respect to taking supplements, larger doses should be avoided by such individuals. There is little reliable information about the human toxicology of flavonoids and related non-nutrient antioxidant constituents of the diet. (5) The food industry has long experience in the control of oxidative damage in foods and this experience can be used to advantage for the protection of food antioxidants which are beneficial. Some of these, such as vitamins C and E and beta-carotene, are well known, and strategies for their protection in foods are already exploited by food technologies. (ABSTRACT TRUNCATED)
801 citations
TL;DR: It is unclear whether detrimental effects of inflammation outweigh neuroprotective mechanisms or vice versa, and in global ischemia inflammatory responses are limited, but micro- and astroglia are also strongly activated.
797 citations
TL;DR: The process of gene loss from chloroplast genomes across the inferred tree is mapped and it is found that independent parallel gene losses in multiple lineages outnumber phylogenetically unique losses by more than 4:1.
Abstract: Photosynthetic eukaryotes, particularly unicellular forms, possess a fossil record that is either wrought with gaps or difficult to interpret, or both. Attempts to reconstruct their evolution have focused on plastid phylogeny, but were limited by the amount and type of phylogenetic information contained within single genes. Among the 210 different protein-coding genes contained in the completely sequenced chloroplast genomes from a glaucocystophyte, a rhodophyte, a diatom, a euglenophyte and five land plants, we have now identified the set of 45 common to each and to a cyanobacterial outgroup genome. Phylogenetic inference with an alignment of 11,039 amino-acid positions per genome indicates that this information is sufficient--but just rarely so--to identify the rooted nine-taxon topology. We mapped the process of gene loss from chloroplast genomes across the inferred tree and found that, surprisingly, independent parallel gene losses in multiple lineages outnumber phylogenetically unique losses by more that 4:1. We identified homologues of 44 different plastid-encoded proteins as functional nuclear genes of chloroplast origin, providing evidence for endosymbiotic gene transfer to the nucleus in plants.
754 citations
TL;DR: It is proposed that the development of skin lesions in AD patients results from sequential activation of T helper 2 (Th2)- and Th1-type cells.
708 citations
TL;DR: It is suggested that 5-aminolevulinic acid-induced porphyrin fluorescence may label malignant gliomas safely and accurately enough to enhance the completeness of tumor removal.
Abstract: Objective Survival after surgery and radiotherapy for the treatment of malignant gliomas is linked to the completeness of tumor removal. Therefore, methods that permit intraoperative identification of residual tumor tissue may be of benefit. In a preliminary investigation, we have studied the value of fluorescent porphyrins that accumulate in malignant tissue after administration of a precursor (5-aminolevulinic acid) for labeling of malignant gliomas in nine patients. Methods Three hours before the induction of anesthesia, 10 mg 5-aminolevulinic acid/kg body weight was administered orally. Intraoperatively, red porphyrin fluorescence was observed with a 455-nm long-pass filter after excitation with violet-blue (375-440 nm) xenon light and was verified by analysis of fluorescence spectra. Fluorescing and nonfluorescing samples taken from the tumor perimeters were examined histologically or used to study the photobleaching of porphyrins by excitation light and white light from the operating microscope. Plasma and erythrocyte porphyrin levels were determined by fluorescence photometry. Results Normal brain tissue revealed no porphyrin fluorescence, whereas tumor tissue was distinguished by bright red fluorescence. For a total of 89 tissue biopsies, sensitivity was 85% and specificity was 100% for the detection of malignant tissue. For seven of nine patients, visible porphyrin fluorescence led to further resection of the tumor. Under operating light conditions, fluorescence decayed to 36% in 25 minutes for violet-blue light and in 87 minutes for white light. Plasma and erythrocyte porphyrin contents increased slightly, without exceeding normal levels. Conclusion Our observations suggest that 5-aminolevulinic acid-induced porphyrin fluorescence may label malignant gliomas safely and accurately enough to enhance the completeness of tumor removal.
636 citations
TL;DR: It is suggested that interferon therapy has a long‐term clinical benefit, although it did not reduce the risk of liver cancer.
626 citations
TL;DR: The splanchnic nerve in regulating adrenocortical neural function and the influence of adrenal innervation on adrenOCortical function are studied.
Abstract: I. Introduction: The Adrenal Functional Unit II. Interaction Between Adrenal Medulla and Adrenal Cortex A. Relationship between medullary and cortical cells B. Paracrine control of adrenocortical function by the adrenal medulla C. Gap junctions in the adrenal cortex D. Summary III. Innervation of the Adrenal Cortex A. Evidence for a nerve supply to the adrenal cortex B. The source of adrenocortical innervation C. Regulation of adrenocortical innervation D. Role of the splanchnic nerve in regulating adrenocortical neural function E. Influence of adrenal innervation on adrenocortical function F. Effects of neurotransmitter substances on adrenocortical function G. Summary IV. The Vascular System of the Adrenal Gland A. Regulation of blood flow B. Relationship between blood flow and steroid secretion C. Effects of vascular endothelial cell products on steroid secretion D. Summary V. The Intraadrenal CRH/ACTH System A. Extrapituitary effect of CRH B. Intraadrenal ACTH C. Intraadrenal CRH and CRH receptors D. F...
588 citations
TL;DR: In this article, the authors show that scalar couplings across the hydrogen bond are observable for 15N-labeled RNA for Watson−Crick base pairs in 15N labeled RNA.
Abstract: Hydrogen bonds play a key role in the stabilization of protein and nucleic acid secondary structure. Currently, most of the experimental evidence for the interaction of hydrogen bond donor and acceptor atoms is indirect. Here we show that scalar couplings across the hydrogen bond are observable for Watson−Crick base pairs in 15N-labeled RNA. These scalar couplings correlate the imino donor 15N nucleus and the corresponding acceptor 15N nucleus on the complementary base. The two-bond JNN couplings between the N3 of uridine and the N1 of adenosine, and between the N1 of guanosine and the N3 of cytidine, have values of approximately 7 Hz as determined by a novel quantitative J-correlation experiment for the 69-nucleotide T1 domain of the potato spindle tuber viroid. In contrast, for non-Watson−Crick base pairs the hydrogen bond acceptor is usually not a nitrogen, but an oxygen atom, and thus, the two-bond JNN couplings are not observed.
587 citations
TL;DR: The current understanding of the role of iNOS in human diseases is reviewed to determine how regulated short pulsative synthesis versus constant NO production differentiates between physiological and pathophysiological actions of NO.
Abstract: Since its discovery as a biologically active molecule in the late 1980s, nitric oxide (NO) has been found to play an important role as signal molecule in many parts of the organism as well as cytotoxic or regulatory effector molecule of the innate immune response. The signal molecule NO is synthesized on demand for short periods of time (seconds to minutes) following enzyme activation of constitutively expressed endothelial NO synthase (eNOS) or neuronal NO synthase (nNOS). In contrast, the inducible NO synthase (iNOS) is expressed after cell activation only and then produces NO for comparatively long periods of time (hours to days). Thus, regulated short pulsative synthesis versus constant NO production differentiates between physiological and pathophysiological actions of NO (for review see [1]). As human monocytes in contrast to rodent ones do not produce large amounts of NO when activated in vitro, iNOS expression in human diseases has long been questionable. However, in the last 3 years data have accumulated on iNOS expression in a variety of human diseases or disorders. We here try to review our current understanding of the role of iNOS in human diseases.
575 citations
TL;DR: It is shown by optoelectronic movement recordings that patients with cortical lesions involving the anterior lateral bank of the intraparietal sulcus have selective deficits in the coordination of finger movements required for object grasping, whereas reaching is much less disturbed.
Abstract: It has been shown in nonhuman primates that the posterior parietal cortex is involved in coordination of arm and eye movements in space, whereas the anterior intraparietal area in the anterior lateral bank of the intraparietal sulcus plays a crucial role in fine finger movements, such as grasping. In this study we show by optoelectronic movement recordings that patients with cortical lesions involving the anterior lateral bank of the intraparietal sulcus have selective deficits in the coordination of finger movements required for object grasping, whereas reaching is much less disturbed. Patients with parietal lesions sparing the cortex lining the anterior intraparietal sulcus showed intact grasping behavior. Complementary evidence was obtained from functional MRI in normal control subjects showing a specific activation of the anterior lateral bank of the intraparietal sulcus during grasping. In conclusion, this combined lesion and activation study suggests that the anterior lateral bank of the intraparietal sulcus, possibly including the human homologue of the anterior intraparietal area, mediates the processing of sensorimotor integration of precisely tuned finger movements in humans.
TL;DR: This sesquiterpene lactone helenalin is the first anti-inflammatory agent shown to exert its effect by directly modifying NF-κB, the central mediator of the human immune response.
TL;DR: In this paper, the effective pair potential between star polymers is exponentially decaying for large distances and crosses over, at a density-dependent corona diameter, to an ultrasoft logarithmic repulsion for small distances.
Abstract: Combining statistical-mechanical theories and neutron-scattering techniques, we show that the effective pair potential between star polymers is exponentially decaying for large distances and crosses over, at a density-dependent corona diameter, to an ultrasoft logarithmic repulsion for small distances. We also make the theoretical prediction that in concentrated star polymer solutions, this ultrasoft interaction induces an anomalous fluid structure factor which exhibits an unusually pronounced second peak. [S0031-9007(98)06148-1]
Journal Article•
TL;DR: The results indicate that both PTCH and SMOH represent important targets for genetic alterations in sporadic BCCs and PNETs.
Abstract: About one-third of sporadic basal cell carcinomas (BCCs) of the skin and 10-15% of primitive neuroectodermal tumors (PNETs) of the central nervous system show mutations in the PTCH tumor suppressor gene The PTCH gene product (Ptch) functions as a transmembrane receptor for the Sonic hedgehog protein (Shh) and interacts with another transmembrane protein called Smoh To further elucidate the significance of alterations in the Shh signaling pathway, we investigated 31 sporadic BCCs and 15 PNETs for the mutation and/or expression of SMOH, PTCH, SHH, and GL11 In addition, we fine-mapped the SMOH gene locus by fluorescence in situ hybridization to chromosomal band 7q32 Mutational analysis identified four BCCs with somatic missense mutations in SMOH affecting codon 535 (TGG==>TTG: Trp==>Leu) in three tumors and codon 199 (CGG==>TGG: Arg==>Trp) in one tumor A missense mutation at codon 533 (AGC==>AAC: Ser==>Asn) was found in one PNET PTCH mutations were detected in eight BCCs and one PNET Two BCCs demonstrated mutations in both SMOH and PTCH The majority of tumors showed an increased expression of SMOH, PTCH, and GL11 transcripts as compared with that of normal skin and nonneoplastic brain tissue, respectively In contrast, only one BCC and one PNET expressed SHH mRNA at levels detectable by reverse transcription-PCR, and no SHH gene mutations were found In summary, our results indicate that both PTCH and SMOH represent important targets for genetic alterations in sporadic BCCs and PNETs
TL;DR: In this article, an international treatment protocol has been developed for FHL and IAHS, which has a high fatality rate, justifying immunomodulatory treatment if the disease is progressive.
Abstract: Hemophagocytic lymphohistiocytosis represents a spectrum of pathogenetically different diseases in which a T-cell induced, uncontrolled activation of phagocytosing macrophages may lead to fever, organomegaly, and pancytopenia. The underlying immunologic disturbance can either be genetically transmitted, like in FHL, or acquired, as in IAHS or MAHS. Triggering infections can be found in all these diseases and do not allow a reliable differentiation. An international treatment protocol has been developed for FHL. IAHS and MAHS also have a high fatality rate, justifying immunomodulatory treatment if the disease is progressive.
TL;DR: The data show for the first time that the amygdala is active in human phobics when they are exposed to potentially fear-relevant stimuli.
Abstract: Functional magnetic resonance imaging was used to determine the activation of the amygdala while seven social phobics and five healthy controls were exposed to slides of neutral faces as well as aversive odor stimuli. The amygdala was selectively activated in the social phobics during presentation of the face stimuli. The data show for the first time that the amygdala is active in human phobics when they are exposed to potentially fear-relevant stimuli. Further research is needed to determine the extent to which overactivation of the amygdala precedes or is a consequence of phobia.
TL;DR: Motor recovery after cortical infarction in the middle cerebral artery territory appears to rely on activation of premotor cortical areas of both cerebral hemispheres, with short-term output from motor cortex likely to be initiated.
Abstract: Objective To study the mechanisms underlying recovery from middle cerebral artery infarction in 7 patients with an average age of 53 years who showed marked recovery of hand function after acute severe hemiparesis caused by their first-ever stroke. Interventions Assessment of motor functions, transcranial magnetic stimulation, somatosensory evoked potentials, magnetic resonance imaging, and positron emission tomographic measurements of regional cerebral blood flow during finger movement activity. Results The infarctions involved the cerebral convexity along the central sulcus from the Sylvian fissure up to the hand area but spared the caudate nucleus, thalamus, middle and posterior portions of the internal capsule, and the dorsal part of the precentral gyrus in each patient. After recovery (and increase in motor function score of 57%,P Conclusions Motor recovery after cortical infarction in the middle cerebral artery territory appears to rely on activation of premotor cortical areas of both cerebral hemispheres. Thereby, short-term output from motor cortex is likely to be initiated.
TL;DR: A biophysical method that uses the principle of seeded polymerization in combination with fluorescence correlation spectroscopy to enable easy in vivo detection of the cerebral amyloid β-protein pathology of Alzheimer's disease and might be of potential value to facilitate its routine diagnosis.
Abstract: Alzheimer's disease is associated with the intraparenchymal growth of plaque-like amyloid deposits. Amyloid plaques are formed by the progressive deposition and transformation of soluble amyloid beta-protein monomers into insoluble and fibrillar aggregates that contain amyloid beta-protein in a beta-pleated sheet conformation. This process is described as 'seeded polymerization' of the monomers with slow-nucleation and fast-growth kinetics. Soluble amyloid beta-protein monomers are present in the cortical extracellular space and in the cerebrospinal fluid, whereas insoluble aggregates so far can be found only by the examination of brain tissue by biopsy or autopsy. Here we present a biophysical method that uses the principle of seeded polymerization in combination with fluorescence correlation spectroscopy, which allowed us to detect single amyloid beta-peptide aggregates in the cerebrospinal fluid samples from Alzheimer's patients. All of 15 Alzheimer's samples but none of the 19 age-matched control samples produced large peaks with fluorescence correlation spectroscopy indicating the rapid aggregation of the fluorescent labelled synthetic amyloid beta-protein probe onto the amyloid beta-protein 'seeds' present in the cerebrospinal fluid. Our method could enable easy in vivo detection of the cerebral amyloid beta-protein pathology of Alzheimer's disease and might be of potential value to facilitate its routine diagnosis.
TL;DR: Mixtures of carotenoids were more effective than the single compounds and this synergistic effect was most pronounced when lycopene or lutein was present.
TL;DR: Guidelines on the out‐patient management of diabetic peripheral neuropathy have been developed from an international consensus meeting attended by diabetologists, neurologists, primary care physicians, podiatrists and diabetes specialist nurses.
Abstract: Guidelines on the out-patient management of diabetic peripheral neuropathy have been developed from an international consensus meeting attended by diabetologists, neurologists, primary care physicians, podiatrists and diabetes specialist nurses. A copy of the full document follows this summary (Appendix 1). The document arose out of suggestions from Neurodiab, a subgroup of the European Association for the Study of Diabetes, that there was a need for guidelines developed by consensus, for the outpatient management of patients with diabetic neuropathy. An international consensus group was created, chaired by two of the authors. A pilot working party met in 1995, followed by a full working party of 39 experts, neurologists and diabetes physicians (Appendix 2). This compiled a draft guideline document which was circulated to a number of international bodies. After consultation with its members, the final guidelines were approved by Neurodiab (chairman F.A. Gries) towards the end of 1997. © 1998 John Wiley & Sons, Ltd.
TL;DR: Many aquatic animal species can survive sulfide exposure to some extent through oxidation of the sulfide, which results mainly in thiosulfate, which requires oxygen and results in an increase in oxygen consumption of some species.
Abstract: Many aquatic animal species can survive sulfide exposure to some extent through oxidation of the sulfide, which results mainly in thiosulfate. In several species, sulfide oxidation is localized in the mitochondria and is accompanied by ATP synthesis. In addition, blood-based and intracellular compounds can augment sulfide oxidation. The formation of thiosulfate requires oxygen, which results in an increase in oxygen consumption of some species. If not all sulfide is detoxified, cytochrome c oxidase is inhibited. Under these conditions, a sulfide-dependent anaerobic energy metabolism commences.
TL;DR: In a multicenter setting, intensive treatment of osteosarcoma according to protocol COSS-86 led to long-term disease-free survival for two thirds of patients and saw no benefit of using the intraarterial route to administer cisplatin.
TL;DR: The results showed that NCAM, which is expressed mainly in the adult nervous system, plays an important role in rabies infection, and the description of NCAM as a new rabies virus receptor would be another example of the use by viruses of more than one receptor to gain entry into the host.
Abstract: Previous reports strongly suggest that, in addition to the nicotinic acetylcholine receptor, rabies virus can use other, as-yet-unidentified receptors. We found that laboratory cell lines susceptible to rabies virus infection express the neural cell adhesion molecule (NCAM) (CD56) on their surface, whereas resistant cells do not, supporting the idea that NCAM could be a rabies virus receptor. We observed that (i) incubation with rabies virus decreases the surface expression of NCAM; (ii) treatment of susceptible cells with heparan sulfate, a ligand for NCAM, or with NCAM antibodies significantly reduces the rabies virus infection; and (iii) preincubation of rabies virus inoculum with soluble NCAM protein as a receptor decoy drastically neutralizes the capacity of rabies virus to infect susceptible cells. Moreover, we demonstrated that transfection of resistant L fibroblasts with the NCAM-encoding gene induces rabies virus susceptibility whereas absence of NCAM in the primary cortical cell cultures prepared from NCAM-deficient mice reduces the rabies virus infection and virus production. This provides evidence that NCAM is an in vitro receptor for the rabies virus. Moreover, the in vivo relevance for the use of NCAM as a receptor was demonstrated by the infection of NCAM-deficient mice, in which rabies mortality was delayed and brain invasion by rabies virus was drastically restricted. Our results showed that NCAM, which is expressed mainly in the adult nervous system, plays an important role in rabies infection. However, it cannot be excluded that receptors other than NCAM are utilized. Thus, the description of NCAM as a new rabies virus receptor would be another example of the use by viruses of more than one receptor to gain entry into the host.
TL;DR: The findings suggest that ECP is a safe and effective adjunct therapy for both acute and extensive chronic GVHD with skin and visceral involvement and resistance to conventional therapy.
TL;DR: The discovery of a short-lived chaperone that is required for the correct maturation of the eukaryotic 20S proteasome and is destroyed at a specific stage of the assembly process is reported and it is shown that the propeptide of the Pre2p/Doa3p beta subunit is necessary for Ump1p's function in proteasomes maturation.
TL;DR: These guidelines for depot antipsychotic treatment in schizophrenia were developed during a two-day consensus conference held on July 29 and 30, 1995 in Siena, Italy and consider previous experience, personal patient preference, patients history of response, and pharmacokinetic properties.
TL;DR: Whole lung irradiation and megatherapy improve outcome in subgroups of patients with disseminated Ewing tumors is 0.27, and whole lung irradiated patients with combined pulmonary/skeletal metastases with combined lung plus bone/BM metastases improve outcome.
TL;DR: The results demonstrate for the first time a biological correlate of handedness in human motor cortex and suggest the expansion of hand motor cortex in the dominant hemisphere may provide extra space for the cortical encoding of a greater motor skill repertoire of the preferred hand.
Abstract: The cortical representation of five simple hand and finger movements in the human motor cortex was determined in left- and right-handed people with whole-head magnetoencephalography. Different movements were found to be represented by spatially segregated dipolar sources in primary motor cortex. The spatial arrangement of neuronal sources for digit and wrist movements was nonsomatotopic and varied greatly between subjects. As an estimator of hand area size in primary motor cortex, we determined the smallest cuboid volume enclosing the five dipole sources within the left and right hemisphere of each subject. Interhemispheric comparison revealed a significant increase of this volume in primary motor cortex opposite to the preferred hand. This asymmetry was due to a greater spatial segregation of neuronal dipole generators subserving different hand and finger actions in the dominant hemisphere. Mean Euclidean distances between dipole sources for different movements were 10.7 +/- 3.5 mm in the dominant and 9.4 +/- 3.5 mm in the nondominant hemisphere (mean +/- SD; P = 0. 01, two-tailed t-test). The expansion of hand representation in primary motor cortex could not simply be attributed to a greater number of pyramidal cells devoted to each particular movement as inferred from current source amplitudes. The degree of hemispheric asymmetry of hand area size in the primary motor cortex was correlated highly with the asymmetry of hand performance in a standardized handedness test (r = -0.76, P < 0.01). These results demonstrate for the first time a biological correlate of handedness in human motor cortex. The expansion of hand motor cortex in the dominant hemisphere may provide extra space for the cortical encoding of a greater motor skill repertoire of the preferred hand.
TL;DR: Findings lend support to the hypothesis that effort-reward imbalance represents a specific constellation of stressful experience at work related to cardiovascular risk.
Abstract: STUDY OBJECTIVE: To examine associations between measures of work stress (that is, the combination of high effort and low reward) and cardiovascular risk factors. DESIGN: Cross sectional first screening of a prospective cohort study. SETTING AND PARTICIPANTS: The study was conducted among 5720 healthy employed men and women living in the greater Stockholm area aged 19-70 years. All analyses were restricted to subjects with complete data (n = 4958). The investigation of associations between indicators of effort-reward imbalance and cardiovascular risk factors was restricted to the age group 30-55 years (n = 3427). MAIN RESULTS: Subjects reporting high effort and low reward at work had a higher prevalence of well known risk factors for coronary heart disease. After adjustment for relevant confounders, associations between a measure of extrinsic effort and reward (the effort-reward ratio) and hypertension (multivariate prevalence odds ratio (POR) 1.62-1.68), increased total cholesterol (upper tertile 220 mg/dl)(POR = 1.24) and the total cholesterol/high density lipoprotein(HDL)-cholesterol ratio (upper tertile 4.61)(POR 1.26-1.30) were found among men. Among women a measure of high intrinsic effort (immersion) was related to increased low density lipoprotein (LDL)-cholesterol (upper tertile 130 mg/dl)(POR 1.37-1.39). Analyses of variance showed increasing mean values of LDL cholesterol with an increasing degree of the effort-reward ratio among men and increased LDL-cholesterol among women with high levels of intrinsic effort (upper tertile of immersion). CONCLUSIONS: Findings lend support to the hypothesis that effort-reward imbalance represents a specific constellation of stressful experience at work related to cardiovascular risk. The relation was not explained by relevant confounders (for example, lack of physical exercise, body weight, cigarette smoking).
TL;DR: Data that suggest a role for NO in autoimmune diseases as an important regulator of the T helper 1 (Th1)/Th2 balance are discussed.