Keystone Symposia 2008 Conference Schedule Sign up for PNAS Online eTocs
Link: Info for AuthorsLink: Editorial BoardLink: AboutLink: SubscribeLink: AdvertiseLink: ContactLink: Sitemap Link: PNAS Home
Proceedings of the National Academy of Sciences
Link: Current Issue "" Link: Archives "" Link: Online Submission ""  Link: Advanced Search



This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mishina, D.
Right arrow Articles by Greenstein, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mishina, D.
Right arrow Articles by Greenstein, R. J.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg  
What's this?

 Previous Article  | Table of Contents |  Next Article 

Vol. 93, Issue 18, 9816-9820, September 3, 1996

Medical Sciences
 On the etiology of Crohn disease

(inflammatory bowel disease / mycobacterial infection / Mycobacterium paratuberculosis / Mycobacterium avium / cytokines)

D. Mishina*, P. Katsel*,dagger , S. T. BrownDagger , E. C. A. M. Gilberts*, and R. J. Greenstein*,dagger ,§,

* Laboratory of Molecular Surgical Research, and Departments of Dagger  Medicine and § Surgery, Veterans Affairs Medical Center, Bronx, NY 10468; and dagger  Department of Surgery, Mount Sinai School of Medicine, City University of New York, New York, NY 10029

Communicated by Rosalyn S. Yalow, Veterans Affairs Medical Center, Bronx, NY, June 10, 1996 (received for review March 18, 1996)

Crohn disease (CD) is a chronic, panenteric intestinal inflammatory disease. Its etiology is unknown. Analogous to the tuberculoid and lepromatous forms of leprosy, CD may have two clinical manifestations. One is aggressive and fistulizing (perforating), and the other is contained, indolent, and obstructive (nonperforating) [Gilberts, E. C. A. M., Greenstein, A. J., Katsel, P., Harpaz, N. & Greenstein, R. J. (1994) Proc. Natl. Acad. Sci. USA 91, 12721-12724]. The etiology, if infectious, may be due to Mycobacterium paratuberculosis. We employed reverse transcription PCR using M. paratuberculosis subspecies-specific primers (IS 900) on total RNA from 12 ileal mucosal specimens (CD, n = 8; controls, n = 4, 2 with ulcerative colitis and 2 with colonic cancer). As a negative control, we used Myobacterium avium DNA, originally cultured from the drinking water of a major city in the United States. cDNA sequence analysis shows that all eight cases of Crohn's disease and both samples from the patients with ulcerative colitis contained M. paratuberculosis RNA. Additionally, the M. avium control has the DNA sequence of M. paratuberculosis. We demonstrate the DNA sequence of M. paratuberculosis from mucosal specimens from humans with CD. The potable water supply may be a reservoir of infection. Although M. paratuberculosis signal in CD has been previously reported, a cause and effect relationship has not been established. In part, this is due to conflicting data from studies with empirical antimycobacterial therapy. We conclude that clinical trials with anti-M. paratuberculosis therapy are indicated in patients with CD who have been stratified into the aggressive (perforating) and contained (nonperforating) forms.

   To whom reprint requests should be addressed at: Laboratory of Molecular Surgical Research, Veterans Affairs Medical Center Bronx (151-19), 130 West Kingsbridge Road, Bronx, NY 10468. e-mail: BGAxis{at}aol.com.

0027-8424/96/939816-5/0
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg    What's this?


This article has been cited by other articles in HighWire Press-hosted journals:


Home page
 Proc. Natl. Acad. Sci. USAHome page
D. N. Frank, A. L. St. Amand, R. A. Feldman, E. C. Boedeker, N. Harpaz, and N. R. Pace
Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases
PNAS, August 21, 2007; 104(34): 13780 - 13785.
[Abstract] [Full Text] [PDF]

Home page
 Am J EpidemiolHome page
I. Abubakar, D. J. Myhill, A. R. Hart, I. R. Lake, I. Harvey, J. M. Rhodes, R. Robinson, A. J. Lobo, C. S. J. Probert, and P. R. Hunter
A Case-Control Study of Drinking Water and Dairy Products in Crohn's Disease--Further Investigation of the Possible Role of Mycobacterium avium paratuberculosis
Am. J. Epidemiol., April 1, 2007; 165(7): 776 - 783.
[Abstract] [Full Text] [PDF]

Home page
 Appl. Environ. Microbiol.Home page
E. C. Stanley, R. J. Mole, R. J. Smith, S. M. Glenn, M. R. Barer, M. McGowan, and C. E. D. Rees
Development of a New, Combined Rapid Method Using Phage and PCR for Detection and Identification of Viable Mycobacterium paratuberculosis Bacteria within 48 Hours
Appl. Envir. Microbiol., March 15, 2007; 73(6): 1851 - 1857.
[Abstract] [Full Text] [PDF]

Home page
 J Med MicrobiolHome page
K. Lucke, S. Miehlke, E. Jacobs, and M. Schuppler
Prevalence of Bacteroides and Prevotella spp. in ulcerative colitis.
J. Med. Microbiol., May 1, 2006; 55(Pt 5): 617 - 624.
[Abstract] [Full Text] [PDF]

Home page
 Appl. Environ. Microbiol.Home page
R. J. Whittington, I. B. Marsh, and L. A. Reddacliff
Survival of Mycobacterium avium subsp. paratuberculosis in Dam Water and Sediment
Appl. Envir. Microbiol., September 1, 2005; 71(9): 5304 - 5308.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
R B. Sartor
Does Mycobacterium avium subspecies paratuberculosis cause Crohn's disease?
Gut, July 1, 2005; 54(7): 896 - 898.
[Full Text] [PDF]

Home page
 Clin Med ResHome page
N. M. Parrish, C. G. Ko, J. D. Dick, P. B. Jones, and J. L.E. Ellingson
Growth, Congo Red Agar Colony Morphotypes and Antibiotic Susceptibility Testing of Mycobacterium avium subspecies paratuberculosis
Clin. Med. Res., May 1, 2004; 2(2): 107 - 114.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
C. N. Bernstein, J. F. Blanchard, P. Rawsthorne, and M. T. Collins
Population-Based Case Control Study of Seroprevalence of Mycobacterium paratuberculosis in Patients with Crohn's Disease and Ulcerative Colitis
J. Clin. Microbiol., March 1, 2004; 42(3): 1129 - 1135.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
C. N. Bernstein, G. Nayar, A. Hamel, and J. F. Blanchard
Study of Animal-Borne Infections in the Mucosas of Patients with Inflammatory Bowel Disease and Population-Based Controls
J. Clin. Microbiol., November 1, 2003; 41(11): 4986 - 4990.
[Abstract] [Full Text] [PDF]

Home page
 Clin Med ResHome page
J. L.E. Ellingson, J. C. Cheville, D. Brees, J. M. Miller, and N. F. Cheville
Absence of Mycobacterium avium subspecies paratuberculosis Components from Crohn's Disease Intestinal Biopsy Tissues
Clin. Med. Res., July 1, 2003; 1(3): 217 - 226.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
W. S. Lim, R.J. Powell, I.D. Johnston, Z. Zhang, H. Correa, R. E. Begue, F. G. De Rosa, S. Bonora, G. Di Perri, A. Myers, et al.
Tuberculosis and Treatment with Infliximab
N. Engl. J. Med., February 21, 2002; 346(8): 623 - 626.
[Full Text] [PDF]

Home page
 GutHome page
P Quirke
Mycobacterium avium subspecies paratuberculosis is a cause of Crohn's disease
Gut, December 1, 2001; 49(6): 757 - 760.
[Full Text]

Home page
 Clin. Microbiol. Rev.Home page
N. B. Harris and R. G. Barletta
Mycobacterium avium subsp. paratuberculosis in Veterinary Medicine
Clin. Microbiol. Rev., July 1, 2001; 14(3): 489 - 512.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
M. T. Collins, G. Lisby, C. Moser, D. Chicks, S. Christensen, M. Reichelderfer, N. Høiby, B. A. Harms, O. O. Thomsen, U. Skibsted, et al.
Results of Multiple Diagnostic Tests for Mycobacterium avium subsp. paratuberculosis in Patients with Inflammatory Bowel Disease and in Controls
J. Clin. Microbiol., December 1, 2000; 38(12): 4373 - 4381.
[Abstract] [Full Text]

Home page
 Appl. Environ. Microbiol.Home page
N. Sung and M. T. Collins
Effect of Three Factors in Cheese Production (pH, Salt, and Heat) on Mycobacterium avium subsp. paratuberculosis Viability
Appl. Envir. Microbiol., April 1, 2000; 66(4): 1334 - 1339.
[Abstract] [Full Text]

Home page
 J. Clin. Microbiol.Home page
S. L. Williams, N. B. Harris, and R. G. Barletta
Development of a Firefly Luciferase-Based Assay for Determining Antimicrobial Susceptibility of Mycobacterium avium subsp. paratuberculosis
J. Clin. Microbiol., February 1, 1999; 37(2): 304 - 309.
[Abstract] [Full Text]

Home page
 GutHome page
D A Lafontaine, S Mercure, and J-P Perreault
Identification of a Crohn's disease specific transcript with potential as a diagnostic marker
Gut, June 1, 1998; 42(6): 878 - 882.
[Abstract] [Full Text] [PDF]

Home page
 Appl. Environ. Microbiol.Home page
N. Sung and M. T. Collins
Thermal Tolerance of Mycobacterium paratuberculosis
Appl. Envir. Microbiol., March 1, 1998; 64(3): 999 - 1005.
[Abstract] [Full Text]

Home page
 BMJHome page
G O Barbezat
Recent advances: Gastroenterology
BMJ, January 10, 1998; 316(7125): 125 - 128.
[Full Text]