Guest guest Posted November 6, 2008 Report Share Posted November 6, 2008 Hi , Thanks for the info! Could you sum this info up if you have time? I just can't seem to understand the point. I am just not good at reading these technical terms. Lori A. "Aggressively Pursuing Solutions To Your Real Estate Needs!" First Weber Group Cell: 1507 E. Sunset Drive Waukesha, WI 53189 LoriUSA@... www.Lori.FirstWeber.com New PSC leads From: The Liver Meeting® 2008 (http://www.aasld. org/Pages/ Default.aspx) Enteric dendritic cells determine recruitment of mucosal T cells to the liver in Primary Sclerosing Cholangitis B. Eksteen1; S. M. Curbishley1; A. Aspinall2; D. H. 1 1. Liver Research Group, University Of Birmingham, Birmingham, West Midlands, United Kingdom. 2. Foothills Hospital, University of Calgary, Calgary, AB, Canada. Background and aims: Lymphocytes primed by dendritic cells (DCs) in the gut express the gut-homing receptors CCR9 and a4ß7 which recognise CCL25 and MADCAM-1 expressed in the intestine. In mice this programming is dependent on retinoic acid and subject to plasticity to allow the development of T-cells that can react to antigen at different anatomical sites. In humans tissue-specificity is lost in primary sclerosing cholangitis (PSC), an extra-intestinal manifestation of inflammatory bowel disease, when ectopic expression of MADCAM-1 and CCL25 in the liver promotes recruitment of CCR9 and a4ß7+ T cells to the liver. This led us to investigate whether the ability to imprint CCR9 and a4ß7 in humans is restricted to intestinal DCs and dependent on retinoic acid and thereby to determine whether T cells that infiltrate the liver in PSC are primed in the gut or liver. Methods: DCs isolated from human gut, liver or portal lymph nodes were used to activate CD8 T-cells in the presence or absence of retinoic acid. Imprinting of CCR9 and a4ß7 and functional migration responses were determined and cross-over activation protocols used to assess plasticity of gut-homing. Results: Gut-derived DCs imprinted functional CCR9 and a4ß7 expression on T-cells whereas DCs from other human tissues including the liver and portal lymph nodes of patients with PSC were unable to do so. Imprinting was retinoic acid-dependent and demonstrated plasticity. Conclusions: Imprinting and plasticity of gut homing human CD8 T-cells requires primary activation or reactivation by gut DCs and is retinoic acid dependent. The inability of liver DCs to imprint gut-tropism implies that a4ß7+CCR9+ T cell that infiltrate the liver in PSC are primed in the gut and provides further evidence that gut-derived lymphocytes contribute to inflammation in the PSC liver. ____________ _________ _________ __ Factors responsible for MAdCAM-1 expression in human liver: potential targets for treatment of inflammatory bowel diseases (IBD) and its manifestations in the liver. E. Liaskou1; C. J. Weston1; B. Eksteen1; P. F. Lalor1; D. H. 1 1. Liver Labs, Institute of Biomedical Research, Birmingham, United Kingdom. MAdCAM-1 is a tissue-specific endothelial adhesion molecule which orchestrates immune responses in the gut by promoting the rolling and firm adhesion of lymphocytes on mucosal endothelium. Recent studies report the expression of MAdCAM-1 on liver endothelium in patients with primary sclerosis cholangitis and autoimmune hepatitis complicating inflammatory bowel disease (IBD). Understanding the factors that drive hepatic expression of MAdCAM-1 will thus elucidate the pathogenesis of these diseases. Liver endothelium expresses a cell surface enzyme, AOC-3 or vascular adhesion protein-1 (VAP-1), which is also an adhesion molecule. We have shown that activation of VAP-1 by substrates including methylamine, an aliphatic amine ingested from food and wine, drives NFkB-dependent activation of ICAM-1 and VCAM-1. In the current study we tested the hypothesis that VAP-1 enzyme activity can synergise with proinflammatory signals to drive MAdCAM-1 expression on liver endothelium.METHODS: We stimulated human sinusoidal endothelial cells (HSEC) and umbilical vein endothelial cells (HUVEC) with cytokines including TNFa (20ng/ml), rVAP-1 (50ng/ml) and methylamine (50µM) and then with combinations of TNFa plus methylamine. MAdCAM-1 expression was examined by ELISA, RT-PCR and Western blotting and function investigated in a flow-based adhesion assay, in which it was tested under physiological shear stress (0.05PA) the ability of lymphocytes expressing the MAdCAM-1 receptor a4ß7 to bind MAdCAM-1 induced in activated HSEC was tested. MadCAM-1 and a4ß7 were blocked with antibodies, P1 and ACT1 respectively.RESULTS: We detected for the first time levels of MAdCAM-1 mRNA and protein in untreated HSEC and HUVEC, though the encoded protein was inactive to support adhesion. However, treatment with methylamine and methylamine plus TNFa induced expression of functional MAdCAM-1 that supported significant levels of lymphocyte adhesion under flow. Blocking studies confirmed this adhesion was a4ß7-dependent.CONCLUSION: We report induction of ectopic MAdCAM-1 on human hepatic endothelium by the dietary amine constituent methylamine and suggest that methylamine in the portal blood of patients with IBD might act as an environmental factor to drive hepatic MAdCAM-1 expression resulting in the recruitment of disease-associated mucosal T cells in PSC. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted November 6, 2008 Report Share Posted November 6, 2008 Hi Lori; I'll do my best to try to explain this information, although it is awfully complicated, and I might have to simplify things a lot. Here goes .... In the gut there are lymphoid tissues that produce immune cells whose main job is to take care of various foreign organisms (e.g. bacteria). The gut lymphoid tissue produces dendritic cells which secrete various substances that activate and educate T cells. For instance, the dendritic cells produce retinoic acid (from vitamin A) that tells the T cells to produce molecules on their surfaces that act as zip-codes, and which instruct the T cells where they should be delivered in the body. CCR9 and a4ß7 are the zip-codes on the T cells. The T cells then go roaming around the body until they find their correct mail-box. They are usually delivered to cells that express MADCAM-1 and CCL25, and these are usually found only in the gut. In this way the T cells are delivered (like a piece of mail) to the correct address, where they then can do their job of orchestrating the neutralization or killing of invading organisms in the gut. In PSC, however, it seems that the mail box (MAdCAM-1 and CCL25) is incorrectly expressed in the liver, so the T cells go to the liver instead of to the gut, and cause inflammation in the liver. It appears that only the dendritic cells in the gut do the " zip-code " imprinting of the T cells. But it's still not clear to me whether something else may be going awry with this " zip-code " imprinting system or mail delivery system? A disgruntled postal worker? The interesting new " lead " is that the dietary substance methylamine is an inducer of MAdCAM-1 in the liver, suggesting that this dietary substance may be a key to why the mail-box is incorrectly expressed in the liver in PSC patients? Increased expression of MAdCAM-1 caused by methylamine allows the T cells (mail) to be delivered to the wrong address! Because a certain type of T cells called Th17 cells are now being implicated in inflammatory bowel disease, autoimmune hepatitis and primary biliary cirrhosis (see the other abstracts posted earlier) it will be interesting to see if such Th17 cells are being delivered inappropriately to the liver in PSC? The Th17 cells are very pro-inflammatory. Their production in the gut can be inhibited by retinoic acid (vitamin A). There is also some evidence that production of Th17 cells can be inhibited by eicosapentaenoic acid (EPA); a component of fish oils. They can also be suppressed by anti-inflammatory regulatory T cells (Tregs). Several of the susceptibility genes involved in inflammatory bowel disease seem to be involved in Th17 cell production and impairments in Tregs. Best regards, Dave (father of (23); PSC 07/03; UC 08/03) Quote Link to comment Share on other sites More sharing options...
Guest guest Posted November 6, 2008 Report Share Posted November 6, 2008 Hi Lori; I'll do my best to try to explain this information, although it is awfully complicated, and I might have to simplify things a lot. Here goes .... In the gut there are lymphoid tissues that produce immune cells whose main job is to take care of various foreign organisms (e.g. bacteria). The gut lymphoid tissue produces dendritic cells which secrete various substances that activate and educate T cells. For instance, the dendritic cells produce retinoic acid (from vitamin A) that tells the T cells to produce molecules on their surfaces that act as zip-codes, and which instruct the T cells where they should be delivered in the body. CCR9 and a4ß7 are the zip-codes on the T cells. The T cells then go roaming around the body until they find their correct mail-box. They are usually delivered to cells that express MADCAM-1 and CCL25, and these are usually found only in the gut. In this way the T cells are delivered (like a piece of mail) to the correct address, where they then can do their job of orchestrating the neutralization or killing of invading organisms in the gut. In PSC, however, it seems that the mail box (MAdCAM-1 and CCL25) is incorrectly expressed in the liver, so the T cells go to the liver instead of to the gut, and cause inflammation in the liver. It appears that only the dendritic cells in the gut do the " zip-code " imprinting of the T cells. But it's still not clear to me whether something else may be going awry with this " zip-code " imprinting system or mail delivery system? A disgruntled postal worker? The interesting new " lead " is that the dietary substance methylamine is an inducer of MAdCAM-1 in the liver, suggesting that this dietary substance may be a key to why the mail-box is incorrectly expressed in the liver in PSC patients? Increased expression of MAdCAM-1 caused by methylamine allows the T cells (mail) to be delivered to the wrong address! Because a certain type of T cells called Th17 cells are now being implicated in inflammatory bowel disease, autoimmune hepatitis and primary biliary cirrhosis (see the other abstracts posted earlier) it will be interesting to see if such Th17 cells are being delivered inappropriately to the liver in PSC? The Th17 cells are very pro-inflammatory. Their production in the gut can be inhibited by retinoic acid (vitamin A). There is also some evidence that production of Th17 cells can be inhibited by eicosapentaenoic acid (EPA); a component of fish oils. They can also be suppressed by anti-inflammatory regulatory T cells (Tregs). Several of the susceptibility genes involved in inflammatory bowel disease seem to be involved in Th17 cell production and impairments in Tregs. Best regards, Dave (father of (23); PSC 07/03; UC 08/03) Quote Link to comment Share on other sites More sharing options...
Guest guest Posted November 6, 2008 Report Share Posted November 6, 2008 Hi Lori; I'll do my best to try to explain this information, although it is awfully complicated, and I might have to simplify things a lot. Here goes .... In the gut there are lymphoid tissues that produce immune cells whose main job is to take care of various foreign organisms (e.g. bacteria). The gut lymphoid tissue produces dendritic cells which secrete various substances that activate and educate T cells. For instance, the dendritic cells produce retinoic acid (from vitamin A) that tells the T cells to produce molecules on their surfaces that act as zip-codes, and which instruct the T cells where they should be delivered in the body. CCR9 and a4ß7 are the zip-codes on the T cells. The T cells then go roaming around the body until they find their correct mail-box. They are usually delivered to cells that express MADCAM-1 and CCL25, and these are usually found only in the gut. In this way the T cells are delivered (like a piece of mail) to the correct address, where they then can do their job of orchestrating the neutralization or killing of invading organisms in the gut. In PSC, however, it seems that the mail box (MAdCAM-1 and CCL25) is incorrectly expressed in the liver, so the T cells go to the liver instead of to the gut, and cause inflammation in the liver. It appears that only the dendritic cells in the gut do the " zip-code " imprinting of the T cells. But it's still not clear to me whether something else may be going awry with this " zip-code " imprinting system or mail delivery system? A disgruntled postal worker? The interesting new " lead " is that the dietary substance methylamine is an inducer of MAdCAM-1 in the liver, suggesting that this dietary substance may be a key to why the mail-box is incorrectly expressed in the liver in PSC patients? Increased expression of MAdCAM-1 caused by methylamine allows the T cells (mail) to be delivered to the wrong address! Because a certain type of T cells called Th17 cells are now being implicated in inflammatory bowel disease, autoimmune hepatitis and primary biliary cirrhosis (see the other abstracts posted earlier) it will be interesting to see if such Th17 cells are being delivered inappropriately to the liver in PSC? The Th17 cells are very pro-inflammatory. Their production in the gut can be inhibited by retinoic acid (vitamin A). There is also some evidence that production of Th17 cells can be inhibited by eicosapentaenoic acid (EPA); a component of fish oils. They can also be suppressed by anti-inflammatory regulatory T cells (Tregs). Several of the susceptibility genes involved in inflammatory bowel disease seem to be involved in Th17 cell production and impairments in Tregs. Best regards, Dave (father of (23); PSC 07/03; UC 08/03) Quote Link to comment Share on other sites More sharing options...
Guest guest Posted November 7, 2008 Report Share Posted November 7, 2008 You said that methylamine is a dietary substance. Where is methylamine found in the diet and I wonder if they find a connection between the Th-17 cells to PSC, and also find more support for MAdCAM-1 if limiting this substance will help.Thank you for passing the research along.nnenne Duluth, Minnesota UC 2002, PSC 2008Subject: Re: New PSC leadsTo: Date: Friday, November 7, 2008, 5:15 AM Hi Lori; I'll do my best to try to explain this information, although it is awfully complicated, and I might have to simplify things a lot. Here goes .... In the gut there are lymphoid tissues that produce immune cells whose main job is to take care of various foreign organisms (e.g. bacteria). The gut lymphoid tissue produces dendritic cells which secrete various substances that activate and educate T cells. For instance, the dendritic cells produce retinoic acid (from vitamin A) that tells the T cells to produce molecules on their surfaces that act as zip-codes, and which instruct the T cells where they should be delivered in the body. CCR9 and a4ß7 are the zip-codes on the T cells. The T cells then go roaming around the body until they find their correct mail-box. They are usually delivered to cells that express MADCAM-1 and CCL25, and these are usually found only in the gut. In this way the T cells are delivered (like a piece of mail) to the correct address, where they then can do their job of orchestrating the neutralization or killing of invading organisms in the gut. In PSC, however, it seems that the mail box (MAdCAM-1 and CCL25) is incorrectly expressed in the liver, so the T cells go to the liver instead of to the gut, and cause inflammation in the liver. It appears that only the dendritic cells in the gut do the "zip-code" imprinting of the T cells. But it's still not clear to me whether something else may be going awry with this "zip-code" imprinting system or mail delivery system? A disgruntled postal worker? The interesting new "lead" is that the dietary substance methylamine is an inducer of MAdCAM-1 in the liver, suggesting that this dietary substance may be a key to why the mail-box is incorrectly expressed in the liver in PSC patients? Increased expression of MAdCAM-1 caused by methylamine allows the T cells (mail) to be delivered to the wrong address! Because a certain type of T cells called Th17 cells are now being implicated in inflammatory bowel disease, autoimmune hepatitis and primary biliary cirrhosis (see the other abstracts posted earlier) it will be interesting to see if such Th17 cells are being delivered inappropriately to the liver in PSC? The Th17 cells are very pro-inflammatory. Their production in the gut can be inhibited by retinoic acid (vitamin A). There is also some evidence that production of Th17 cells can be inhibited by eicosapentaenoic acid (EPA); a component of fish oils. They can also be suppressed by anti-inflammatory regulatory T cells (Tregs). Several of the susceptibility genes involved in inflammatory bowel disease seem to be involved in Th17 cell production and impairments in Tregs. Best regards, Dave (father of (23); PSC 07/03; UC 08/03) Quote Link to comment Share on other sites More sharing options...
Guest guest Posted November 7, 2008 Report Share Posted November 7, 2008 You said that methylamine is a dietary substance. Where is methylamine found in the diet and I wonder if they find a connection between the Th-17 cells to PSC, and also find more support for MAdCAM-1 if limiting this substance will help.Thank you for passing the research along.nnenne Duluth, Minnesota UC 2002, PSC 2008Subject: Re: New PSC leadsTo: Date: Friday, November 7, 2008, 5:15 AM Hi Lori; I'll do my best to try to explain this information, although it is awfully complicated, and I might have to simplify things a lot. Here goes .... In the gut there are lymphoid tissues that produce immune cells whose main job is to take care of various foreign organisms (e.g. bacteria). The gut lymphoid tissue produces dendritic cells which secrete various substances that activate and educate T cells. For instance, the dendritic cells produce retinoic acid (from vitamin A) that tells the T cells to produce molecules on their surfaces that act as zip-codes, and which instruct the T cells where they should be delivered in the body. CCR9 and a4ß7 are the zip-codes on the T cells. The T cells then go roaming around the body until they find their correct mail-box. They are usually delivered to cells that express MADCAM-1 and CCL25, and these are usually found only in the gut. In this way the T cells are delivered (like a piece of mail) to the correct address, where they then can do their job of orchestrating the neutralization or killing of invading organisms in the gut. In PSC, however, it seems that the mail box (MAdCAM-1 and CCL25) is incorrectly expressed in the liver, so the T cells go to the liver instead of to the gut, and cause inflammation in the liver. It appears that only the dendritic cells in the gut do the "zip-code" imprinting of the T cells. But it's still not clear to me whether something else may be going awry with this "zip-code" imprinting system or mail delivery system? A disgruntled postal worker? The interesting new "lead" is that the dietary substance methylamine is an inducer of MAdCAM-1 in the liver, suggesting that this dietary substance may be a key to why the mail-box is incorrectly expressed in the liver in PSC patients? Increased expression of MAdCAM-1 caused by methylamine allows the T cells (mail) to be delivered to the wrong address! Because a certain type of T cells called Th17 cells are now being implicated in inflammatory bowel disease, autoimmune hepatitis and primary biliary cirrhosis (see the other abstracts posted earlier) it will be interesting to see if such Th17 cells are being delivered inappropriately to the liver in PSC? The Th17 cells are very pro-inflammatory. Their production in the gut can be inhibited by retinoic acid (vitamin A). There is also some evidence that production of Th17 cells can be inhibited by eicosapentaenoic acid (EPA); a component of fish oils. They can also be suppressed by anti-inflammatory regulatory T cells (Tregs). Several of the susceptibility genes involved in inflammatory bowel disease seem to be involved in Th17 cell production and impairments in Tregs. Best regards, Dave (father of (23); PSC 07/03; UC 08/03) Quote Link to comment Share on other sites More sharing options...
Guest guest Posted November 7, 2008 Report Share Posted November 7, 2008 I also read that people who smoker were less likely to have UC.AOL Search: Your one stop for directions, recipes and all other Holiday needs. Search Now. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted November 7, 2008 Report Share Posted November 7, 2008 I also read that people who smoker were less likely to have UC.AOL Search: Your one stop for directions, recipes and all other Holiday needs. Search Now. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted November 7, 2008 Report Share Posted November 7, 2008 Thanks for that wonderful explanation Dave. In addition, I googled " methylamine, " and found this free-use abstract regarding cigarette smoking and methylamine. Another reason for PSCers not to smoke? But then I'm confused, as I thought smokers were less likely to get PSC than non-smokers? . 1) Neuropsychiatry Research Unit, Department of Psychiatry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada, S7N 5E4. Abstract Methylamine is a constituent of cigarette smoke and the major end product of nicotine metabolism. Smoking or nicotine can induce the release of adrenaline, which is in turn deaminated by monoamine oxidase, also producing methylamine. We found that the urinary level of methylamine was significantly elevated following administration of nicotine (25 mg/Kg, i.p.). Semicarbazide-sensitive amine oxidase (SSAO) inhibitors further increased the excretion of methylamine induced by nicotine. Following administration of L-(—)-[N-methyl-3H]nicotine long-lasting irreversible radioactive adducts were detected in different mouse tissues and such adduct formation could be blocked by selective SSAO inhibitors. These adducts are probably cross-linked oligoprotein complexes cross-linked by formaldehyde. The findings support the idea that nicotine can enhance SSAO/methylamine-mediated increase of formaldehyde and oxidative stress and this could in part contribute the adverse effect of health associated with smoking. http://www.springerlink.com/content/m72935j154766688/ Quote Link to comment Share on other sites More sharing options...
Guest guest Posted November 7, 2008 Report Share Posted November 7, 2008 Hi nne; Good question. I'm not sure whether the authors of the abstract were suggesting that methylamine present in food might be responsible, or whether it is bacteria in the colon that generate methylamine from normal dietary constituents that are responsible. There are studies showing that certain colonic bacteria can make a lot of different amines, including methylamine. The methylamine produced by these bacteria is made from a normal amino acid found in all protein, glycine. This is described in detail in this paper: Appl. Environ. Microbiol. 55: 2894-2898 (1989) Influence of pH, nutrient availability, and growth rate on amine production by Bacteroides fragilis and Clostridium perfringens. C, Macfarlane GT http://aem.asm.org/cgi/reprint/55/11/2894?view=long&pmid=2560361 I don't know whether they have tried feeding this substance to lab animals to see whether it alters MAdCAM-1 expression in the liver as it does in cell cultures. I'm sure that this will be on their list of experiments to try next! Best regards, Dave (father of (23); PSC 07/03; UC 08/03) > > You said that methylamine is a dietary substance. Where is methylamine found in the diet and I wonder if they find a connection between the Th-17 cells to PSC, and also find more support for MAdCAM- 1 if limiting this substance will help. > > Thank you for passing the research along. > > nne > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted November 7, 2008 Report Share Posted November 7, 2008 Hi nne; Good question. I'm not sure whether the authors of the abstract were suggesting that methylamine present in food might be responsible, or whether it is bacteria in the colon that generate methylamine from normal dietary constituents that are responsible. There are studies showing that certain colonic bacteria can make a lot of different amines, including methylamine. The methylamine produced by these bacteria is made from a normal amino acid found in all protein, glycine. This is described in detail in this paper: Appl. Environ. Microbiol. 55: 2894-2898 (1989) Influence of pH, nutrient availability, and growth rate on amine production by Bacteroides fragilis and Clostridium perfringens. C, Macfarlane GT http://aem.asm.org/cgi/reprint/55/11/2894?view=long&pmid=2560361 I don't know whether they have tried feeding this substance to lab animals to see whether it alters MAdCAM-1 expression in the liver as it does in cell cultures. I'm sure that this will be on their list of experiments to try next! Best regards, Dave (father of (23); PSC 07/03; UC 08/03) > > You said that methylamine is a dietary substance. Where is methylamine found in the diet and I wonder if they find a connection between the Th-17 cells to PSC, and also find more support for MAdCAM- 1 if limiting this substance will help. > > Thank you for passing the research along. > > nne > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted November 7, 2008 Report Share Posted November 7, 2008 Hi ; That's interesting. However, I don't think the amount of methylamine that one would get by smoking would be as much as that obtained from bacteria in the colon, but I'm certainly not an expert on this! With regard to the PSC - smoking issue, this abstract appears in the AASLD 2008 Liver Meeting Abstracts, and includes your favorite doc, Dr. Karlsen, as co-author: Final ID: 670 Smoking may delay disease onset and disease progression in primary sclerosing cholangitis J. R. Hov; 1; K. K. nsen; 1; T. H. Karlsen; 1; E. Schrumpf; 1; K. M. Boberg; 1; 1. Department of Medicine, Rikshospitalet University Hospital and University of Oslo, Oslo, Norway. Abstract Body: Introduction. Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the biliary tree leading to liver cirrhosis and often requiring liver transplantation. The etiology is unknown, but epidemiological studies point to the presence of both genetic (strong associations in the HLA complex on chromosome 6p21) and environmental (protective effect of smoking) risk factors. Little is known on the possible relationship between these risk factors and to what extent smoking may influence disease course in PSC. Material and methods. 147 consecutive PSC patients (74% male) in the Medical Department of Rikshospitalet University Hospital were recruited over a 2 year period. PSC diagnosis was based on accepted criteria and typical findings on cholangiography. All patients were interviewed by the same gastroenterologist regarding smoking history including age of onset and duration. HLA genotyping was performed using DNA sequencing based technology. Statistical analysis was performed in SPSS 15.0. Results. At diagnosis of PSC only 7% (10/147) were current smokers. 24% (35/147) were ever smokers (previous or current smokers) and 76% (112/147) were never smokers. Median age at diagnosis was 32 years (range 13-77) for never smokers compared with 41 years (range 19-65) for ever smokers (p<0.001, Mann-Whitney U test). 42% (16/38) of the female patients were ever smokers compared with 17% (19/109) of the male (p=0.002, chi-square test). Median follow-up from diagnosis was 5 years (range 0-28). Liver transplantation or death occurred in 55% (81/147). In an age and gender-adjusted regression model ever smoking was independently associated with prolonged time from diagnosis to death or liver transplantation (odds ratio 0.51; 95% confidence interval 0.29-0.89, p=0.019). We found no significant differences in smoking prevalence between patients of different HLA types in the present dataset. Conclusion. In this PSC cohort from a tertiary referral centre, a history of smoking was associated with higher age at diagnosis and slower disease progression. It is noteworthy that the proportion of female patients with a history of smoking was significantly higher than among male patients. We did not detect any significant differences in smoking prevalence between patients of different HLA types. Best regards, Dave R. > > Thanks for that wonderful explanation Dave. In addition, I googled > " methylamine, " and found this free-use abstract regarding cigarette > smoking and methylamine. Another reason for PSCers not to smoke? But > then I'm confused, as I thought smokers were less likely to get PSC than > non-smokers? . Quote Link to comment Share on other sites More sharing options...
Guest guest Posted November 7, 2008 Report Share Posted November 7, 2008 Hi ; That's interesting. However, I don't think the amount of methylamine that one would get by smoking would be as much as that obtained from bacteria in the colon, but I'm certainly not an expert on this! With regard to the PSC - smoking issue, this abstract appears in the AASLD 2008 Liver Meeting Abstracts, and includes your favorite doc, Dr. Karlsen, as co-author: Final ID: 670 Smoking may delay disease onset and disease progression in primary sclerosing cholangitis J. R. Hov; 1; K. K. nsen; 1; T. H. Karlsen; 1; E. Schrumpf; 1; K. M. Boberg; 1; 1. Department of Medicine, Rikshospitalet University Hospital and University of Oslo, Oslo, Norway. Abstract Body: Introduction. Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the biliary tree leading to liver cirrhosis and often requiring liver transplantation. The etiology is unknown, but epidemiological studies point to the presence of both genetic (strong associations in the HLA complex on chromosome 6p21) and environmental (protective effect of smoking) risk factors. Little is known on the possible relationship between these risk factors and to what extent smoking may influence disease course in PSC. Material and methods. 147 consecutive PSC patients (74% male) in the Medical Department of Rikshospitalet University Hospital were recruited over a 2 year period. PSC diagnosis was based on accepted criteria and typical findings on cholangiography. All patients were interviewed by the same gastroenterologist regarding smoking history including age of onset and duration. HLA genotyping was performed using DNA sequencing based technology. Statistical analysis was performed in SPSS 15.0. Results. At diagnosis of PSC only 7% (10/147) were current smokers. 24% (35/147) were ever smokers (previous or current smokers) and 76% (112/147) were never smokers. Median age at diagnosis was 32 years (range 13-77) for never smokers compared with 41 years (range 19-65) for ever smokers (p<0.001, Mann-Whitney U test). 42% (16/38) of the female patients were ever smokers compared with 17% (19/109) of the male (p=0.002, chi-square test). Median follow-up from diagnosis was 5 years (range 0-28). Liver transplantation or death occurred in 55% (81/147). In an age and gender-adjusted regression model ever smoking was independently associated with prolonged time from diagnosis to death or liver transplantation (odds ratio 0.51; 95% confidence interval 0.29-0.89, p=0.019). We found no significant differences in smoking prevalence between patients of different HLA types in the present dataset. Conclusion. In this PSC cohort from a tertiary referral centre, a history of smoking was associated with higher age at diagnosis and slower disease progression. It is noteworthy that the proportion of female patients with a history of smoking was significantly higher than among male patients. We did not detect any significant differences in smoking prevalence between patients of different HLA types. Best regards, Dave R. > > Thanks for that wonderful explanation Dave. In addition, I googled > " methylamine, " and found this free-use abstract regarding cigarette > smoking and methylamine. Another reason for PSCers not to smoke? But > then I'm confused, as I thought smokers were less likely to get PSC than > non-smokers? . Quote Link to comment Share on other sites More sharing options...
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