| 1. |
- Gallo, Valentina, et al.
(författare)
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Smoking and risk for amyotrophic lateral sclerosis : analysis of the EPIC cohort
- 2009
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Ingår i: Annals of Neurology. - New York : J. Wiley & Sons. - 0364-5134 .- 1531-8249. ; 65:4, s. 378-385
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Cigarette smoking has been reported as "probable" risk factor for Amyotrophic Lateral Sclerosis (ALS), a poorly understood disease in terms of aetiology. The extensive longitudinal data of the European Prospective Investigation into Cancer and Nutrition (EPIC) were used to evaluate age-specific mortality rates from ALS and the role of cigarette smoking on the risk of dying from ALS. Methods: A total of 517,890 healthy subjects were included, resulting in 4,591,325 person-years. ALS cases were ascertained through death certificates. Cox hazard models were built to investigate the role of smoking on the risk of ALS, using packs/years and smoking duration to study dose-response. Results: A total of 118 subjects died from ALS, resulting in a crude mortality rate of 2.69 per 100,000/year. Current smokers at recruitment had an almost two-fold increased risk of dying from ALS compared to never smokers (HR = 1.89, 95% C.I. 1.14-3.14), while former smokers at the time of enrollment had a 50% increased risk (HR = 1.48, 95% C.I. 0.94-2.32). The number of years spent smoking increased the risk of ALS (p for trend = 0.002). Those who smoked more than 33 years had more than a two-fold increased risk of ALS compared with never smokers (HR = 2.16, 95% C.I. 1.33-3.53). Conversely, the number of years since quitting smoking was associated with a decreased risk of ALS compared with continuing smoking. Interpretation: These results strongly support the hypothesis of a role of cigarette smoking in aetiology of ALS. We hypothesize that this could occur through lipid peroxidation via formaldehyde exposure.
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| 2. |
- Johansen, Dorthe, et al.
(författare)
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Different Markers of Alcohol Consumption, Smoking and Body Mass Index in Relation to Risk of Pancreatic Cancer. A Prospective Cohort Study within the Malmö Preventive Project.
- 2009
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Ingår i: Pancreatology. - : Elsevier BV. - 1424-3903. ; 9:5, s. 677-686
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: The association between alcohol consumption and pancreatic cancer is not clear. This study investigates different prediagnostic measurements of alcohol consumption, a laboratory marker (gamma-glutamyltransferase; gamma-GT), and a score measuring alcohol addiction (Mm-MAST), in relation to the risk of pancreatic cancer. Furthermore, the study investigated whether smoking and alcohol consumption interact with each other, or if the risk of pancreatic cancer associated with these factors is modified by obesity or weight gain. Methods: A cohort of 33,346 subjects provided prediagnostic information on the above factors. During a mean follow-up of 22.1 years, 183 cases of pancreatic cancer occurred. Cox's analysis yielded relative risks (RR) with 95% confidence intervals (CI). Results: The highest gamma-GT quartile was associated with a high risk of pancreatic cancer (RR = 2.15, 95% CI = 1.34-3.44), and this association was even stronger in subjects that reported a previous weight gain (RR = 3.61, 95% CI = 1.29-10.09). A high Mm-MAST score was also associated with pancreatic cancer (p = 0.02). Current smoking was associated with pancreatic cancer (RR = 2.34, 95% CI = 1.60-3.43), and obese smokers had an even higher risk (RR = 7.45, 95% CI = 1.65-33.64). Conclusion: High alcohol intake is associated with subsequent risk of pancreatic cancer and this risk may be higher following weight gain. The risk associated with smoking may be even higher in obese subjects. and IAP.
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| 3. |
- Lindkvist, Björn, et al.
(författare)
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A Prospective Cohort Study of Smoking in Acute Pancreatitis.
- 2008
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Ingår i: Pancreatology. - : Elsevier BV. - 1424-3903. ; 8:1, s. 63-70
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Little is known about risk factors for acute pancreatitis other than gallstones and alcohol consumption. The aim of this study was to investigate if smoking or body mass index (BMI) are associated with acute pancreatitis and to determine relative risks (RR) for acute pancreatitis related to smoking, BMI, and alcohol consumption. Methods: From 1974 to 1992, selected birth-year cohorts of residents in Malmo, Sweden (born 1921-1949) were invited to a health-screening investigation including physical examination, blood sampling and a questionnaire. In total, 33,346 individuals participated. Cases of acute pancreatitis were identified from diagnosis registries (n = 179). Incidence rates were calculated in different risk factor categories. A Cox's analysis revealed RR. Results: Current versus never smoking at baseline was associated with acute pancreatitis (RR 2.14, 95% confidence interval (CI) 1.48-3.09) after adjustment for age, sex, BMI and alcohol consumption. This association was stronger in heavy smokers (20-30 cigarettes/day) (RR 3.19, 95% CI 2.03-5.00). Smoking was associated with a RR of 3.57 (95% CI 0.98-13.0) for acute pancreatitis in subjects who reported no alcohol consumption. An increased risk for acute pancreatitis was also found for high versus low risk, self-reported alcohol consumption (RR 2.55, 95% CI 1.59-4.08) and for gamma-GT levels in the highest versus the lowest quartile (RR 2.14, 95% CI 1.32-3.49). There was also a weak correlation between BMI and acute pancreatitis. Conclusions: Smoking is associated with the incidence of acute pancreatitis in a dose-response manner. Copyright (c) 2008 S. Karger AG, Basel and IAP.
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| 4. |
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| 5. |
- Lindkvist, Björn
(författare)
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Acute Pancreatitis. Studies on smoking and protease activation.
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: Activation of pancreatic proteases is considered to be a crucial event in the early phase of acute pancreatitis but the cause of this activation is not known. Most cases of acute pancreatitis can be attributed to either gallstone disease or alcohol abuse. However, little is known about other risk factors. The aim of this thesis is to investigate the mechanisms involved in the initiation of acute pancreatitis, trends in the incidence, and risk factors for the disease. The potential role of smoking as a risk factor was given special attention and the effect of nicotine on exocrine pancreas was studied in a rat model. Results and conclusions: Cathepsin B activated trypsinogen but not proelastase or procarboxypeptidase B. Hence, if cathepsin B is to play a role in the activation of digestive enzymes in acute pancreatitis, this probably occurs through activation of trypsinogen. The incidence of gallstone-related acute pancreatitis increased by 7.6% per year (95% confidence interval (CI), 4.0 to 11.4) in Malmö 1985?1999. The incidence of alcohol-related acute pancreatitis decreased by ?5.1% per year (95 % CI, ?7.4 to ?2.8). The risk for acute pancreatitis was increased in smokers (relative risk 2.14, (95% CI, 1.48 to 3.09)), after adjustment for age, sex, body mass index and alcohol consumption. There was a weak association between body mass index and the risk for acute pancreatitis (p=0.02). Nicotine induced increased concentrations of pancreatic proenzymes in pancreatic extract but had no impact on the production of the same enzymes. These findings suggest that nicotine impairs acinar cell secretion. We propose that this might be a contributory mechanism behind the association between smoking and pancreatic disease.
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| 6. |
- Lindkvist, Björn, et al.
(författare)
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Cathepsin B activates human trypsinogen 1 but not proelastase 2 or procarboxypeptidase B
- 2006
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Ingår i: Pancreatology. - : Elsevier BV. - 1424-3903. ; 6:3, s. 224-231
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Activation of trypsinogen to trypsin is a crucial step in the development of acute pancreatitis. The cause of this activation is not known although suggested explanations include autoactivation, cathepsin B-mediated activation and activation by mast cell tryptase. The aim of this study was to investigate cathepsin B and tryptase activation of pancreatic zymogens. Methods: Trypsinogen-1, proelastase, and procarboxypeptidase B were purified from human pancreatic juice. Human cathepsin B and beta I- tryptase are commercial products. Activation and degradation of zymogens were measured by activity towards specific substrates for trypsin and pancreatic elastase, ELISAs for procarboxypeptidase B and its activation peptide, and a radioimmunoassay for the trypsinogen activation peptide. Results: Cathepsin B caused activation of trypsinogen-1 with a trypsin yield of about 30% of that produced by enterokinase. Proelastase and procarboxypeptidase B was not activated by cathepsin B. None of the zymogens were inactivated by cathepsin B. Neither monomeric nor tetrameric tryptase could activate any of the examined zymogens. Conclusion: Cathepsin B is a competent activator of trypsinogen-1, although not as efficient as enterokinase. If cathepsin B is to play a role in protease activation in acute pancreatitis, this most probably occurs by activation of trypsinogen.
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| 7. |
- Lindkvist, Björn, et al.
(författare)
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Long-term nicotine exposure causes increased concentrations of trypsinogens and amylase in pancreatic extracts in the rat.
- 2008
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Ingår i: Pancreas. - 0885-3177. ; 37:3, s. 288-294
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Tidskriftsartikel (refereegranskat)abstract
- To develop radioimmunoassays (RIAs) for rat trypsinogens 1 and 2 and to investigate the effect of nicotine exposure on concentration and production of pancreatic zymogens in the rat. METHODS: Male Sprague-Dawley rats were supplied with either normal or nicotine-containing (0.77 mM) water for 28 days and were then killed. Rabbit antibodies for the activation peptides of trypsinogens 1 and 2 were obtained for use in the RIAs. Concentrations of the both trypsinogens in pancreatic extracts were measured by the RIAs after activation by enterokinase. DNA and amylase were measured using commercial kits. mRNA for trypsinogens 1 and 2, procolipase, and cholecystokinin receptor was measured by in situ hybridization. RESULTS: The specificity of the RIA for the trypsinogen 1 activation peptide was satisfactory. The RIA for the trypsinogen 2 activation peptide showed a limited cross-reaction toward the synthetic trypsinogen 1 activation peptide, but the importance of this cross-reaction was moderate when investigated in samples of activated trypsinogens. Weight gain was reduced in nicotine-treated animals. Concentrations of amylase, trypsinogen 1, trypsinogen 2, and the ratio of trypsinogen 2 to 1 were all increased in pancreatic extracts of nicotine-fed animals. Total DNA and mRNA for the trypsinogens, procolipase, and cholecystokinin receptor were not affected by nicotine exposure. CONCLUSIONS: The combination of increased proenzyme concentrations and unaffected mRNA levels suggests that nicotine impairs secretion rather than production of pancreatic zymogens.
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| 8. |
- Pumphrey, Nick, et al.
(författare)
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Cutting edge: Evidence of direct TCR alpha-chain interaction with superantigen.
- 2007
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Ingår i: Journal of immunology (Baltimore, Md. : 1950). - 0022-1767. ; 179:5, s. 2700-4
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Tidskriftsartikel (refereegranskat)abstract
- Superantigens are known to activate a large number of T cells. The SAg is presented by MHC class II on the APC and its classical feature is that it recognizes the variable region of the beta-chain of the TCR. In this article, we report, by direct binding studies, that staphylococcal enterotoxin (SE) H (SEH), a bacterial SAg secreted by Staphylococcus aureus, instead recognizes the variable alpha-chain (TRAV27) of TCR. Furthermore, we show that different SAgs (e.g., SEH and SEA) can simultaneously bind to one TCR by binding the alpha-chain and the beta-chain, respectively. Theoretical three-dimensional models of the penta complexes are presented. Hence, these findings open up a new dimension of the biology of the staphylococcal enterotoxins.
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