Epidemiologic studies on the health effects of ambient particulate air pollution.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
F Nyberg
Publications and source records attributed to F Nyberg.
Influence of smoking and donor age on the spectrum of in vivo mutation at the HPRT-locus in T lymphocytes of healthy adults.
Types and frequencies of in vivo mutation in the hypoxanthine-guanine phosphoribosyl-transferase (HPRT) gene was studied in 142 T cell mutants from 78 healthy nonsmoking and smoking adults with a mean of 65 years. The HPRT mutant frequency in the nonsmokers was 18.7 +/- 12.0 x 10(-6), and in the smokers 26.6 +/- 18.5 x 10(-6) (mean +/- S.D., P < 0.01). Among 107 single base pair substitutions (SBS) in the coding region of the HPRT gene, one new mutable site, one novel nonsense mutation and three not previously reported SBS were identified. Transitions accounted for 59% of the SBS and transversions for 41%. GC > AT transitions were the predominant type of mutation, with 50% of all SBS. The mutations showed a nonrandom distribution along the coding sequence, with three significant hotspots at positions 143, 197 and 617 (13, 14 and 7 mutations, respectively). There was no difference between smokers and nonsmokers with regard to the distribution of mutations at these hotspot positions. However, 85% of the mutations at GC base pairs and 88% of the mutations at AT base pairs in smokers occurred at sites with guanine or thymine, respectively, in the nontranscribed DNA strand. Moreover, smokers had a higher frequency of transversions and lower frequency of transitions than nonsmokers did. Particularly, GC > TA transversions were increased in smokers (11%) compared to nonsmokers (2%), which suggests that tobacco-smoke induced adducts at guanine bases in the nontranscribed DNA strand contributes to the increase of HPRT mutation in smokers. Overall, these results were very similar to the mutational spectra in two younger study populations reported previously [K.J. Burkhart-Schultz, C.L. Thompson, I.M. Jones, Spectrum of somatic mutation at the hypoxanthine phosphoribosyltransferase (HPRT) gene of healthy people, Carcinogenesis 17 (1996) 1871-1883; A. Podlutsky, A.-M. Osterholm, S.-M. Hou, A. Hofmaier, B. Lambert, Spectrum of point mutations in the coding region of the hypoxanthine-guanine phosphoribosyltransferase, Carcinogenesis 19 (1998) 557-566]. With the possible exception of an increase of mutations at hotspot position 143, and a decrease of 5-methylcytosine deamination mediated transitions at CpG-sites in the older individuals, there were no differences between the mutational spectra of old and young adults. In conclusion, both smoking and ageing seem to have minor influences on the spectrum of HPRT mutation in T cells.
Adult↗
Risk of lung cancer from exposure to environmental tobacco smoke from cigars, cigarillos and pipes.
Explore the source record for details and available documents.
Case-Control Studies↗
Exposure to environmental tobacco smoke and risk of adenocarcinoma of the lung.
We conducted a case-control study of adenocarcinoma of the lung and exposure to environmental tobacco smoke (ETS) in 7 countries. We interviewed 70 cases of adenocarcinoma of the lung and 178 population or hospital controls. All subjects had smoked fewer than 400 cigarettes in their lifetimes. Ever exposure to ETS from the parents during childhood was associated with a decreased risk [odds ratio (OR) 0.6, 95% confidence interval (CI) 0.3-1.2], and there was a suggestion of a decreasing trend in risk with increasing duration of exposure. Ever exposure to ETS from the spouse was not associated with an increased risk (OR 1.0, 95% CI 0.5-1.8), while the OR of ever exposure to ETS at the workplace was 1.5 (95% CI 0.8-3.0). For both exposure sources, an increased risk was observed among the highly exposed, and the OR among those with the highest duration of exposure to ETS from the spouse or at the workplace was 1.8 (95% CI 0.5-6.2). A similar risk was estimated for current exposure to ETS from either source. Our results confirm previous reports of a weak effect of adult ETS exposure on risk of adenocarcinoma of the lung. Bias and confounding cannot be excluded as explanations for the apparent decrease in risk from childhood exposure.
Adenocarcinoma↗
Angiotensin II analogues encompassing 5,9- and 5,10-fused thiazabicycloalkane tripeptide mimetics.
A simple experimental procedure on solid phase for the construction of new tripeptidic 5,9- and 5,10-fused thiazabicycloalkane scaffolds that adopt beta-turns has been developed. This N-terminal-directed bicyclization, relying on masked aldehyde precursors derived from glutamic acid as key building blocks, provides a complement to the related bicyclization previously reported, where an aspartic acid-derived precursor was employed to induce cyclization toward the C-terminal end of the peptide. Thus, the regioselectivity of the bicyclization can be altered simply by varying the chain length of the incorporated aldehyde precursor. Four analogues of the hypertensive octapeptide angiotensin II, comprising the new scaffolds in the 3-5- and 5-7-positions, were synthesized. One of these conformationally constrained angiotensin II analogues exhibited AT(1) receptor affinity (K(i) = 750 nM). Results from theoretical conformational analysis of model compounds of the bicyclic tripeptide mimetics are presented, and they demonstrate that subtle differences in geometry have a strong impact on the affinity to the AT(1) receptor.
Angiotensin II↗
Cigar and pipe smoking and lung cancer risk: a multicenter study from Europe.
BACKGROUND: Because limited information is available on the quantitative association between consumption of tobacco products other than cigarettes and lung cancer risk, we undertook a case-control study of this relationship. METHODS: We investigated lung cancer risk among smokers of cigars and/or cigarillos only and of pipes only and compared these risks with the risk of smokers of cigarettes only in a case-control study conducted in seven European areas. Our study population consisted of 5621 male case patients with lung cancer and 7255 male control subjects. Each subject or his proxy was interviewed with respect to the subject's smoking history and other risk factors for lung cancer. RESULTS: The odds ratio (OR) for smoking cigars and cigarillos only was 9.0 (95% confidence interval [CI] = 5.8-14.1), based on 43 exposed case patients and 77 exposed control subjects, and the OR for smoking a pipe only was 7.9 (95% CI = 5.3-11.8), representing 61 case patients and 129 control subjects. The OR for smoking cigarettes only was 14.9 (95% CI = 12.3-18.1), based on 4204 case patients and 3930 control subjects. A dose-response relationship was present for duration of use and cumulative consumption both for cigars and cigarillos and for pipe tobacco. An effect was also suggested for inhalation of cigar and cigarillo smoke. The dose-response relationships between lung cancer risk and either duration of smoking or average and cumulative consumption were similar for cigar and cigarillo smoking, pipe smoking, and cigarette smoking. CONCLUSION: Our results suggest that smoking of European cigars, cigarillos, and pipe tobacco might exert a carcinogenic effect on the lung comparable to that of cigarettes.
Age Factors↗
Upregulation of COX-2 and CGRP expression in resident cells of the Borna disease virus-infected brain is dependent upon inflammation.
Infection of immunocompetent adult rats with Borna disease virus (BDV) causes severe encephalitis and neural dysfunction. The expression of COX-2 and CGRP, genes previously shown to be implicated in CNS disease and peripheral inflammation, was dramatically upregulated in the cortical neurons of acutely BDV-infected rats. Neuronal COX-2 and CGRP upregulation was predominantly seen in brain areas where ED1-positive macrophages/microglia accumulated. In addition, COX-2 expression was strongly induced in brain endothelial cells and the number of COX-2 immunoreactive microglial cells was increased. In contrast, despite increased expression of viral antigens, neither COX-2 nor CGRP expression was altered in the CNS of BDV-infected rats treated with dexamethasone, or tolerant to BDV. Thus, increased CGRP and COX-2 expression in the BDV-infected brain is the result of the inflammatory response and likely to be involved in the pathogenesis of virus-induced encephalitis.
Animals↗
Elevated soluble E-selectin in cutaneous lupus erythematosus.
UNLABELLED: Elevated levels of soluble adhesion molecules (sCAMs); sE-Selectin, sICAM-1, and sVCAM-1 have been reported in various inflammatory and autoimmune diseases such as systemic lupus erythematosus (SLE), but not in cutaneous LE. 1.1. PATIENTS AND METHODS: Sixty-nine serum samples from 51 LE patients, 24 with SLE, 19 with chronic cutaneous (DLE) and 8 with subacute cutaneous (SCLE) and sera from 32 controls were examined for sE-Selectin, sICAM-1 and sVCAM-1 using commercially available ELISA kits. Thirty serum samples from different time points were available from 12 LE patients. 1.2. RESULTS: Significantly elevated levels of sE-Selectin were found in DLE patients with wide-spread lesions. In contrast, patients with SLE and SCLE did not have elevated levels of sE-Selectin but in concordance with earlier reports, sICAM-1 and sVCAM-1 were elevated in these patients. In serial samples it seemed that sE-Selectin correlated significantly with active cutaneous skin lesions while sICAM-1 remained elevated irrespective of disease activity. 1.3. CONCLUSION: Since activated endothelial cells are the only source for sE-Selectin, our results suggest a more important role of endothelial cells in cutaneous LE than has previously been assumed. Further it might be speculated that selective inhibition of E-Selectin could have therapeutic implication in cutaneous LE.
Adult↗
Modulation of peripheral inflammation by locally administered endomorphin-1.
OBJECTIVES: Neurogenic inflammation is mediated via sensory peptides released from the peripheral terminals of sensory nerves and can be modulated by locally released opioid peptides at the site of injury. Endomorphins are recently discovered endogenous opioid peptides with high selectivity and affinity for the mu-opioid receptor. The aim of this study was to examine the ability of endomorphin-1 (EM-1) to modulate the inflammatory response under different injury conditions. METHODS: A vacuum-induced blister model in anaesthetised rats (nembutal 60 mg/kg i.p.) was used to examine the effect of EM-1 on the acute inflammatory response induced by; (1) electrical stimulation (ES) of the distal portion of the exposed/cut sciatic nerve at 20 V, 5 Hz, 2 ms for 1 min or; (2) superfusion of substance P (SP) over the blister base. In addition, the effect of EM-1 on the inflammatory response to SP was examined under acute, recurrent (repeated blister induction) and chronic (chronic sciatic nerve lesion) injury conditions. RESULTS: Prior and concomitant perfusion of EM-1 (100 microM) significantly inhibited the vascular response to ES by 58% compared to controls. EM-1 also inhibited the inflammatory response to SP (both vasodilatation and plasma extravasation) in a dose-dependent manner. Significant inhibition was achieved at 100 microM and 1 mM concentrations of EM-1. Naloxone (1 mg/kg i.v.) reversed the inhibitory effect of EM-1 on the inflammatory response to SP. EM-1 (100 microM) was equally potent in inhibiting the inflammatory response to SP under acute (34% inhibition) recurrent (39%) and chronic (42%) injury conditions. CONCLUSIONS: The current results demonstrate a greater inhibitory effect of EM-1 on the inflammatory response to electrical nerve stimulation (58% inhibition) compared to SP (34% inhibition) suggesting the involvement of both pre- and post-terminal mechanisms in the inhibitory modulatory actions of EM-1. Evidence is provided for the involvement of opioid receptors in this inhibitory effect. The results also suggest that EM-1 is equipotent in inhibiting the inflammatory response under different injury conditions.
Administration, Topical↗
Calcitonin gene-related peptide gene expression in collagen-induced arthritis is differentially regulated in primary afferents and motoneurons: influence of glucocorticoids.
Calcitonin gene-related peptide is involved in peripheral and spinal mechanisms of inflammatory pain. In this paper, we used collagen II-induced arthritis in the rat as a model to investigate the influence of chronic arthritic pain on calcitonin gene-related peptide gene expression in sensory and motor pathways. Additionally, we examined the effect of the glucocorticoid drug budesonide on arthritis-induced changes of calcitonin gene-related peptide expression and constitutive calcitonin gene-related peptide expression. Thirteen days after the immunization with native rat collagen type II rats developed a progressive and chronic polyarthritis which was scored with respect to the degree of swelling and/or redness of the paw and ankle joints. Budesonide significantly attenuated the extent of arthritis. Changes in calcitonin gene-related peptide expression were evaluated by semiquantitative in situ hybridization and immunocytochemistry on day 21 post-immunization. In sensory neurons of dorsal root ganglia of arthritic rats, a significant increase in calcitonin gene-related peptide messenger RNA and protein levels was seen. These increases were completely blocked by budesonide. Also in dorsal root ganglia of non-arthritic rats, budesonide had an effect, with reduced calcitonin gene-related peptide messenger RNA levels below constitutive concentrations. Image analysis of calcitonin gene-related peptide immunoreactivity revealed that changes in calcitonin gene-related peptide expression were due to alterations in calcitonin gene-related peptide expression levels rather than to de novo synthesis or changes in the numbers of calcitonin gene-related peptide expressing neurons. In spinal motoneurons of arthritic rats, marked decreases in calcitonin gene-related peptide messenger RNA and protein levels were measured. These reductions were attenuated by budesonide. The changes in calcitonin gene-related peptide expression in motoneurons correlated with the severity of arthritis in the ipsilateral hind paw. Budesonide had no effects on calcitonin gene-related peptide messenger RNA levels in motoneurons of non-arthritic rats. The opposite regulation of calcitonin gene-related peptide gene expression in primary sensory and spinal somatomotor pathways in collagen-induced arthritis suggests that calcitonin gene-related peptide plays a specific role in both chronic inflammatory pain and arthritis-induced motor dysfunction. The sensitivity of constitutive and inflammation-induced sensory calcitonin gene-related peptide expression to budesonide treatment may indicate that the beneficial effects of steroid treatment in inflammation is partly mediated by down-regulation of calcitonin gene-related peptide in sensory neurons involved in neurogenic inflammation.
Administration, Topical↗
Factors associated with adolescent use of doping agents: anabolic-androgenic steroids.
AIMS: The purpose was to assess the importance of risk factors such as socio-demographics, sports activities, tobacco use, alcohol consumption, use of certain psychotropic substances and violence in the use of doping agents in adolescents. DESIGN: Cross-sectional survey using anonymous closed response questionnaire. SETTING: Eight senior high schools in Uppsala, Sweden. PARTICIPANTS: A total of 2742 senior high school students; 1592 were in their first year (aged 16-17 years) and 1150 in their third (aged 18-19 years). FINDINGS: Multiple logistic regression analyses revealed that strength training, tobacco use, heavy alcohol consumption, truancy at least once a week and living alone were significantly independently associated in the use of doping agents. Further, the study showed that use of cannabis oil, LSD, amphetamine and opioids were related specifically to anabolic-androgenic steroid use. CONCLUSIONS: Use of doping agents probably involves more than a desire to enhance appearance or sports performance and appears to have much in common with use of alcohol, tobacco and psychotropic drugs.
Adolescent↗
Elevated plasma levels of neuropeptide Y in female fibromyalgia patients.
Neuropeptide Y(NPY) co-exists with norepinephrine in the sympathetic nervous system, and NPY may represent the sympathetic-neuronal output. Fibromyalgia syndrome (FMS) patients have perturbations in the hypothalmic-pituitary-adrenal (HPA) axis and in the sympathetic stress axis as well. As opioid peptides, monoamines and sex steroids are integrated in the regulation of stress, it is interesting to further explore the role of NPY in FMS patients, as they show many symptoms that are related to perturbations of those systems.In this study, plasma NPY levels were assessed in subgroups of FMS patients: cyclic (regular menstrual cycles), non-cyclic (post-menopausal), depressed and non-depressed patients. In order to examine whether pain and other symptoms seen in FMS patients are correlated to the NPY levels, the patients were also registering 15 different symptoms daily during 28 days. Sex and age-matched healthy controls were recruited for comparisons. Non-parametric tests were used for the statistical analyses.The results showed that the NPY levels were significantly elevated in the patients compared to the controls. In the luteal phase of the cyclic patients, the levels of the peptide were higher than in the corresponding controls. For the non-cyclic patients, there was a positive correlation between physical symptoms and NPY levels, however, pain per se did not reach the significant level of correlation. The non-depressed patients had the same levels of NPY as the depressed FMS patients, who also had a positive correlation between anxiety and NPY levels.These results suggest that FMS patients have an altered activity in the NPY system, most likely due to prolonged and/or repeated stress, and that the hormonal state and time of the menstrual cycle also may be of importance in the complex pathophysiologic mechanism behind the development of FMS. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.
Journal Article↗
Low calcitonin gene-related, peptide-like immunoreactivity in cerebrospinal fluid from chronic pain patients.
Cerebrospinal fluid (CSF) levels of calcitonin gene-related peptide-like activity (CGRP-LI), were determined in 35 patients with painful orthopaedic disorders and the activity was compared to that of 12 healthy controls without pain. Fourteen patients had pain from osteoarthritis of the hip or the knee, 11 had rhizopathic pain due to a herniated lumbar disc and 10 had pain from a hip fracture. In all patients, decreased CGRP-LI was observed in CSF compared to the controls. The lowest values were found in the patients with osteoarthritis, while there was less, but still significant, reduction of CGRP-LI in the patients with herniated lumbar disc and those with a hip fracture. In most of the patients, CGRP-LI was also analysed at a second lumbar puncture after operative treatment, when pain had subsided or was reduced. However, the CGRP-LI remained low after treatment, which may suggest the influence of factors other than pain.
Adult↗
Effects of human growth hormone on the porto-arterial concentration differences of glucose and amino acids in the newborn piglet.
It is known that growth hormone (GH) increases the mitotic index of duodenal crypt cells. In early life, such an effect could be of particular importance for the functional development of the intestine in terms of absorptive capacity. In this study, osmotic mini pumps were introduced into the abdominal cavity of newborn piglets. The pumps permitted a continuous infusion of either recombinant human growth hormone (rhGH) at a rate of 0.1 IU GH x kg(-1) x 24 h(-1) or of vehicle. After 7 days of treatment, a bolus of amino acids and glucose was infused into the duodenum. Following this bolus, there was a prompt rise in the plasma concentration of both amino acids and glucose, especially in blood withdrawn from the portal vein. Thus, when the differences in concentrations of both amino acids and glucose between portal and arterial blood plasma were calculated, these differences reached maximum values between 30 and 60 minutes after the bolus. In animals treated with GH, maximum values occurred at a lower level than in control animals. These reductions were in the order of 60% (P > 0.01) if calculated over the first hour of absorption. From this study, it might be concluded that GH does not improve the absorptive capacity of the small intestine in newborn piglets. Instead, GH seems to reduce the absorption dynamics of glucose and amino acids. The reason for this is obscure, but could imply a specific effect of GH on enterocyte function.
Amino Acids↗
Early events in ultraviolet light-induced skin lesions in lupus erythematosus: expression patterns of adhesion molecules ICAM-1, VCAM-1 and E-selectin.
In our previous study, photoprovocation induced lupus erythematosus (LE) and polymorphous light eruption-like lesions in photosensitive LE patients. In this new study we examined the expression of ICAM-1, VCAM-1 and E-selectin, in early lesions in particular. A total of 32 patients with cutaneous LE, 25 with "classic" discoid LE, and 7 with systemic LE, including 3 patients with subacute cutaneous LE, were provoked with UVA and UVB on normal appearing skin. Induced lesions were followed up with serial biopsies. LE-like histopathology was seen within 1 week of provocation in some cases. Adhesion molecule expression was statistically significantly affected by the factors clinical diagnosis and wavelength (UVA or UVB). Strong keratinocyte ICAM-1 expression was found 1 week after provocation in reactions that eventually developed into long-standing ones. It is possible that these early changes reflect an underlying defect in the mechanisms that regulate adhesion molecule expression in LE.
Adolescent↗
Hypophysectomy enhances interleukin-1beta, tumor necrosis factor-alpha, and interleukin-10 mRNA expression in the rat brain.
Although the effects of various cytokines as regulators of hormone synthesis and production are well documented, the role for pituitary hormones as modulators of cytokine synthesis is not fully understood. In this study, we investigated the effect of pituitary hormones' depletion on cytokine synthesis after short- (21 days) and long- (35 days) term hypophysectomy (ST-HX and LT-HX, respectively). The expresssion of the proinflammatory cytokine interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) and the anti-inflammatory cytokines IL-10 and transforming growth factor-beta (TGF-beta) in the rat brain was studied using in situ hybridization. Our results indicate that IL-1beta mRNA-expressing cells were significantly upregulated at day 21 in hypophysectomized rats compared to sham-operated controls. This enhanced expression was also detected later at day 35 post hypophysectomy. However, TNF-alpha mRNA expression was significantly increased only at the later sampling interval. IL-10 mRNA-expressing cells were increased after long-term hypophysectomy compared to controls. TGF-beta mRNA-expressing cells were not increased after hypophysectomy. In conclusion, these results suggest a role for pituitary hormones in IL-1beta, TNF-alpha, and IL-10 synthesis.
Analysis of Variance↗
Hprt mutant frequency and aromatic DNA adduct level in non-smoking and smoking lung cancer patients and population controls.
T cell cloning and 32P-post-labelling methods were used to study the mutant frequency (MF) at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus and the aromatic DNA adduct level (AL) in peripheral lymphocytes of newly diagnosed lung cancer patients (92 ever-smokers and 87 never-smokers) and matched population controls (82 ever-smokers and 79 never-smokers). Overall, the MF (total mean 20.6 x 10(-6)) and AL (4.1 x 10(-8)) were similar in cases and controls with the same smoking status, indicating that the disease has limited effect on the two endpoints. When cases and controls were combined, the AL was significantly higher in current smokers than in former or never-smokers (P = 0.0003) and the MF was significantly higher in ever-smokers than in never-smokers (P = 0.004). Age affected the MF significantly in ever-smokers (1.6%/year, 95% CI 0.6-2.5, adjusted for pack-years and years since last smoking), especially among cases (2.1%/year, 95% CI 0.5-3.7). An increase of AL with age was observed in currently smoking cases only (2.3%/year, 95% CI 0.3-4.2, adjusted for smoking dose). For currently smoking cases, there was also a more pronounced effect of smoking dose on both endpoints and a significant correlation between AL and MF (r = 0.52, P = 0.04) was observed among those with the highest dose. Our data also provide additional evidence for the different turnover times of smoking-induced DNA adducts and hprt mutations. The stronger increase of MF and AL with age and dose in currently smoking patients compared with controls is consistent with an interaction between smoking and genetic host factors.
Adenocarcinoma↗
Dietary factors and risk of lung cancer in never-smokers.
We studied dietary risk factors for lung cancer among never-smokers in a population-based case-control study in Stockholm, 1989-1995. Study subjects were older than 30 years of age and had never smoked regularly. A total of 124 cases (35 men, 89 women) and 235 controls (72 men, 163 women) participated. Exposure information was obtained at interview with study subjects. The never-smoking status was validated by interviews with next-of-kin. A protective effect was suggested for vegetables, mediated primarily by carrots (relative risk [RR], 0.7; 95% confidence interval [CI], 0.4-1.3, and 0.6, 0.3-1.1 for intermediate and high consumption of carrots, respectively). Non-citrus fruits appeared to lower the risk as well, with RR 0.6, 95% CI 0.3-1.3 and 0.5, 0.3-1.0 for intermediate and high consumption, respectively. A protective effect with dose-response was also seen for intake of beta-carotene and total carotenoids. Increased risks were seen for cultured milk products in both genders (RR 2.0, 95% CI 1.1-3.9 for intermediate and 1.6, 0.9-2.9 for high consumption), but for milk only among male high consumers. Our results support evidence linking a diet rich in vegetables and non-citrus fruit with decreased lung cancer risk and suggests that among vegetables, carrot consumption is the most important component or marker for this effect in Sweden. The results regarding milk products could be consistent with dietary fat as a risk factor for lung cancer, although a more comprehensive assessment of fat intake is necessary to explore this relation.
Adult↗