|
1
|
Ayaki M, Manabe N, Fujita M, Katsumata R, Nakamura J, Kamada T, Murota M, Inoue K, Haruma K. Prevalence of Autoimmune Disease in Patients with Eosinophilic Esophagitis: A Cross-sectional Study of Three Hospitals in Japan. Intern Med 2021; 60:3525-3531. [PMID: 34024859 PMCID: PMC8666211 DOI: 10.2169/internalmedicine.7389-21] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Accepted: 04/07/2021] [Indexed: 11/06/2022] Open
Abstract
Objective Recent studies have found higher rates of autoimmune diseases, such as celiac disease, Crohn's disease, and ulcerative colitis, in patients with eosinophilic esophagitis (EoE) than in the general population. This study investigated the concomitant rate of autoimmune disease among Japanese patients with EoE and evaluated the clinicopathological characteristics of EoE patients with autoimmune disease. Methods The medical records of patients diagnosed with EoE between April 1, 2016, and June 30, 2020, were reviewed. We analyzed the concomitant rate of autoimmune diseases in patients with EoE and compared the clinical and histological differences between patients with and without autoimmune disease. Results Sixty-four patients with EoE were enrolled. Of them, 1 had ulcerative colitis (1.6%), 1 had autoimmune polyendocrine syndrome type 2 (1.6%), and 6 had endometriosis (28.5% of women, 44.4% of reproductive-aged women). No significant differences in the clinical course or histological findings were found between EoE patients with and without autoimmune diseases. No complications, including stenosis, were seen in EoE with autoimmune disease, and most patients with EoE and autoimmune diseases were responsive to proton pump inhibitors (PPIs). Conclusion In this study, 8 out of 64 patients with EoE had an autoimmune-related disease, including ulcerative colitis (n=1, 1.6%), autoimmune polyendocrine syndrome type 2 (n=1, 1.6%), or endometriosis (n=6, 44.4% of women of reproductive age), which is higher than that previously reported in the general population. Further investigations are required to clarify the relationship between EoE and autoimmune diseases.
Collapse
Affiliation(s)
- Maki Ayaki
- Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, Japan
| | - Noriaki Manabe
- Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, Japan
| | - Minoru Fujita
- Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, Japan
| | - Ryo Katsumata
- Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, Japan
| | - Jun Nakamura
- Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, Japan
| | - Tomoari Kamada
- Department of Health Care Medicine, Kawasaki Medical School, Japan
| | - Masayuki Murota
- Department of Internal Medicine, Sakaide City Hospital, Japan
| | | | - Ken Haruma
- Division of Gastroenterology, Department of Internal Medicine 2, Kawasaki Medical School, Japan
| |
Collapse
|
|
2
|
Lim HW, Schuster IP, Rajapakse R, Monzur F, Khan S, Sultan K. The impact of corticosteroid use on inpatients with inflammatory bowel disease and positive polymerase chain reaction for Clostridium difficile. Intest Res 2019; 17:244-252. [PMID: 30739437 PMCID: PMC6505088 DOI: 10.5217/ir.2018.00101] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Revised: 11/10/2018] [Accepted: 11/12/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND/AIMS Optimal management of inflammatory bowel disease (IBD) with concomitant Clostridium difficile infection (CDI) is controversial, especially when CDI diagnosis is made by polymerase chain reaction (PCR) testing, which may reflect colonization without infection. METHODS We performed a multicenter review of all inpatients with IBD and PCR diagnosed CDI. Outcomes included length of stay, 30- and 90-day readmission, colectomy during admission and within 3 months, intensive care unit (ICU) admission, CDI relapse and death for patients who received corticosteroid (CS) after CDI diagnosis versus those that did not. Propensity-adjusted regression analysis of outcomes based on CS usage was performed. RESULTS We identified 177 IBD patients with CDI, 112 ulcerative colitis and 65 Crohn's disease. For IBD overall, CS after CDI diagnosis was associated with prolonged hospitalization (5.5 days: 95% confidence interval [CI], 1.5-9.6 days; P=0.008), higher colectomy rate within 3 months (odds ratio [OR], 5.5; 95% CI, 1.1-28.2; P=0.042) and more frequent ICU admissions (OR, 7.8; 95% CI, 1.5-41.6; P=0.017) versus no CS. CS use post-CDI diagnosis in UC patients was associated with prolonged hospitalization (6.2 days: 95% CI, 0.4- 12.0 days; P=0.036) and more frequent ICU admissions (OR, 7.4; 95% CI, 1.1-48.7; P=0.036). CONCLUSIONS CS use among IBD inpatients with CDI diagnosed by PCR is associated with poorer outcomes and would seem to reinforce the importance of C. difficile toxin assay to help distinguish colonization from infection. This adverse effect appears more prominent among those with UC.
Collapse
Affiliation(s)
- Huei-Wen Lim
- Division of Gastroenterology and Hepatology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA
| | - Isaiah P. Schuster
- Division of Gastroenterology and Hepatology, Stony Brook University Hospital, Stony Brook, NY, USA
| | - Ramona Rajapakse
- Division of Gastroenterology and Hepatology, Stony Brook University Hospital, Stony Brook, NY, USA
| | - Farah Monzur
- Division of Gastroenterology and Hepatology, Stony Brook University Hospital, Stony Brook, NY, USA
| | - Sundas Khan
- Division of Gastroenterology and Hepatology, The Feinstein Institute for Medical Research, Manhasset, NY, USA
| | - Keith Sultan
- Division of Gastroenterology and Hepatology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA
| |
Collapse
|
|
3
|
Leigh LY, Spergel JM. An in-depth characterization of a large cohort of adult patients with eosinophilic esophagitis. Ann Allergy Asthma Immunol 2018; 122:65-72.e1. [PMID: 30223114 DOI: 10.1016/j.anai.2018.09.452] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Revised: 08/21/2018] [Accepted: 09/11/2018] [Indexed: 12/27/2022]
Abstract
BACKGROUND Eosinophilic esophagitis (EoE) is a chronic, allergic, immune-mediated disease associated with increased risk of comorbid atopic conditions. OBJECTIVE To perform an in-depth characterization of a large cohort of manually verified adult patients with EoE, including evaluation of less studied associations, such as pollen food allergy syndrome, anaphylaxis, autoimmunity, and psychiatric comorbidities. METHODS We performed a manual retrospective electronic medical record review of 1,218 patients with EoE identified by International Classification of Diseases, Ninth Revision and International Classification of Disease, 10th Revision codes from the University of Pennsylvania Health Systems. Through manual medical record review, we evaluated patient demographics, family and smoking history, laboratory and endoscopic findings, treatment, and comorbid atopic, autoimmune, and psychiatric conditions. RESULTS A total of 950 of the 1,218 patients had biopsy-proven EoE. This cohort was predominantly male, white, and never-smokers who presented most commonly with dysphagia, with an initial biopsy results showing 49 eosinophils per high-powered field, a serum absolute eosinophilic count of 446,000/µL, and mean total IgE level of 243 IU/mL. Of the patients, 55% had impaction (of which 38% required endoscopic removal), and 56% had strictures or fibrosis (of which 56% underwent dilatation). Therapy used was predominantly (77%) medical only. Comorbid atopy, pollen food allergy syndrome, drug allergy, anaphylaxis, autoimmunity, and psychiatric illnesses were higher in the EoE cohort compared with the general University of Pennsylvania Health Systems population. CONCLUSION Our adult cohort of manually verified, biopsy-proven EoE had an increased risk of pollen food allergy syndrome, anaphylaxis, and comorbid autoimmune and psychiatric conditions compared with the University of Pennsylvania Health Systems population. There was also an increased prevalence of impaction and stricture or fibrosis requiring endoscopic intervention compared with the pediatric population.
Collapse
Affiliation(s)
- Lyvia Y Leigh
- Section of Allergy and Immunology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; Division of Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
| | - Jonathan M Spergel
- Division of Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| |
Collapse
|
|
4
|
Espaillat MP, Snider AJ, Qiu Z, Channer B, Coant N, Schuchman EH, Kew RR, Sheridan BS, Hannun YA, Obeid LM. Loss of acid ceramidase in myeloid cells suppresses intestinal neutrophil recruitment. FASEB J 2017; 32:2339-2353. [PMID: 29259036 DOI: 10.1096/fj.201700585r] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Bioactive sphingolipids are modulators of immune processes and their metabolism is often dysregulated in ulcerative colitis, a major category of inflammatory bowel disease (IBD). While multiple axes of sphingolipid metabolism have been investigated to delineate mechanisms regulating ulcerative colitis, the role of acid ceramidase (AC) in intestinal inflammation is yet to be characterized. Here we demonstrate that AC expression is elevated selectively in the inflammatory infiltrate in human and murine colitis. To probe for mechanistic insight into how AC up-regulation can impact intestinal inflammation, we investigated the selective loss of AC expression in the myeloid population. Using a model of intestinal epithelial injury, we demonstrate that myeloid AC conditional knockout mice exhibit impairment of neutrophil recruitment to the colon mucosa as a result of defective cytokine and chemokine production. Furthermore, the loss of myeloid AC protects from tumor incidence in colitis-associated cancer (CAC) and inhibits the expansion of neutrophils and granulocytic myeloid-derived suppressor cells in the tumor microenvironment. Collectively, our results demonstrate a tissue-specific role for AC in regulating neutrophilic inflammation and cytokine production. We demonstrate novel mechanisms of how granulocytes are recruited to the colon that may have therapeutic potential in intestinal inflammation, IBD, and CAC.-Espaillat, M. P., Snider, A. J., Qiu, Z., Channer, B., Coant, N., Schuchman, E. H., Kew, R. R., Sheridan, B. S., Hannun, Y. A., Obeid, L. M. Loss of acid ceramidase in myeloid cells suppresses intestinal neutrophil recruitment.
Collapse
Affiliation(s)
- Mel Pilar Espaillat
- Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA.,Department of Medicine, Stony Brook University, Stony Brook, New York, USA
| | - Ashley J Snider
- Department of Medicine, Stony Brook University, Stony Brook, New York, USA.,Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, USA.,Northport Veterans Affairs Medical Center, Northport, New York, USA
| | - Zhijuan Qiu
- Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA
| | - Breana Channer
- Department of Medicine, Stony Brook University, Stony Brook, New York, USA.,Department of Biology, Stony Brook University, Stony Brook, New York, USA
| | - Nicolas Coant
- Department of Medicine, Stony Brook University, Stony Brook, New York, USA
| | - Edward H Schuchman
- Plexcera Therapeutics, New York, New York, USA.,Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Richard R Kew
- Department of Pathology, Stony Brook University, Stony Brook, New York, USA
| | - Brian S Sheridan
- Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA
| | - Yusuf A Hannun
- Department of Medicine, Stony Brook University, Stony Brook, New York, USA.,Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, USA
| | - Lina M Obeid
- Department of Medicine, Stony Brook University, Stony Brook, New York, USA.,Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, USA.,Northport Veterans Affairs Medical Center, Northport, New York, USA
| |
Collapse
|
|
5
|
Nitzan O, Elias M, Chazan B, Raz R, Saliba W. Clostridium difficile and inflammatory bowel disease: Role in pathogenesis and implications in treatment. World J Gastroenterol 2013; 19:7577-7585. [PMID: 24282348 PMCID: PMC3837256 DOI: 10.3748/wjg.v19.i43.7577] [Citation(s) in RCA: 94] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2013] [Revised: 10/05/2013] [Accepted: 10/14/2013] [Indexed: 02/06/2023] Open
Abstract
Clostridium difficile (C. difficile) is the leading cause of antibiotic associated colitis and nosocomial diarrhea. Patients with inflammatory bowel disease (IBD) are at increased risk of developing C. difficile infection (CDI), have worse outcomes of CDI-including higher rates of colectomy and death, and experience higher rates of recurrence. However, it is still not clear whether C. difficile is a cause of IBD or a consequence of the inflammatory state in the intestinal environment. The burden of CDI has increased dramatically over the past decade, with severe outbreaks described in many countries, which have been attributed to a new and more virulent strain. A parallel rise in the incidence of CDI has been noted in patients with IBD. IBD patients with CDI tend be younger, have less prior antibiotic exposure, and most cases of CDI in these patients represent outpatient acquired infections. The clinical presentation of CDI in these patients can be unique-including diversion colitis, enteritis and pouchitis, and typical findings on colonoscopy are often absent. Due to the high prevalence of CDI in patients hospitalized with an IBD exacerbation, and the prognostic implications of CDI in these patients, it is recommended to test all IBD patients hospitalized with a disease flare for C. difficile. Treatment includes general measures such as supportive care and infection control measures. Antibiotic therapy with either oral metronidazole, vancomycin, or the novel antibiotic-fidaxomicin, should be initiated as soon as possible. Fecal macrobiota transplantation constitutes another optional treatment for severe/recurrent CDI. The aim of this paper is to review recent data on CDI in IBD: role in pathogenesis, diagnostic methods, optional treatments, and outcomes of these patients.
Collapse
|
|
6
|
He HH, Shen H, Zhu XX, Gu PQ, Liu YJ, Zhu L, Zheng K. Radix cynanchi paniculati ameliorates 2,4,6-trinitrobenzenesulfonic acid-induced colitis in rats. Shijie Huaren Xiaohua Zazhi 2012; 20:2237-2242. [DOI: 10.11569/wcjd.v20.i24.2237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effects of radix cynanchi paniculati in the treatment of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats.
METHODS: Forty male Sprague-Dawley (SD) rats were randomly divided into four groups: control group, model group, radix cynanchi paniculati group, and balsalazide group. Experimental colitis was induced in rats by intragastric administration of TNBS. Rats in the radix cynanchi paniculati and balsalazide groups were treated by gavage with radix cynanchi paniculati (4 g/kg) or balsalazide (1 g/kg) for ten consecutive days following TNBS administration. After treatment, general status, macroscopic lesions and histological injuries were observed, and serum levels of cytokines, including interleukin (IL)-1β, tumor necrosis factor (TNF)-α and lL-10 were determined by enzyme-linked immunosorbant assay (ELISA).
RESULTS: Body weight was improved in rats of the two treatment groups, but there was no statistical difference in body weight between the treatment groups and model group. Disease activity index (DAI) was significantly lower in the two treatment groups than in the model group (0.70 ± 1.06, 0.67 ± 0.71 vs 2.38 ± 1.51, both P < 0.05). Both radix cynanchi paniculati and balsalazide could improve colonic macroscopic morphology and pathohistology compared to the model group (1.05 ± 0.83, 1.06 ± 0.85 vs 2.94 ± 0.94; 1.65 ± 1.67, 2.00 ± 1.80 vs 6.00 ± 1.67, all P < 0.01). Serum levels of TNF-α and IL-1β were significantly lower in the radix cynanchi paniculati group than in the model group (both P < 0.01), but there was no statistical difference in IL-10 level between the two groups. Serum levels of TNF-α, IL-1β and IL-10 were significantly lower in the balsalazide group than in the model group (all P < 0.01).
CONCLUSION: Radix cynanchi paniculati could effectively ameliorate TNBS-induced colitis in rats possibly via mechanisms associated with altering the levels of cytokines.
Collapse
|
|
7
|
Mulder DJ, Hookey LC, Hurlbut DJ, Justinich CJ. Impact of Crohn disease on eosinophilic esophagitis: evidence for an altered T(H)1-T(H)2 immune response. J Pediatr Gastroenterol Nutr 2011; 53:213-5. [PMID: 21788765 DOI: 10.1097/mpg.0b013e318213bf79] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Daniel J Mulder
- Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario, Canada
| | | | | | | |
Collapse
|
|
8
|
Lin J, Hackam DJ. Worms, flies and four-legged friends: the applicability of biological models to the understanding of intestinal inflammatory diseases. Dis Model Mech 2011; 4:447-56. [PMID: 21669933 PMCID: PMC3124049 DOI: 10.1242/dmm.007252] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Diseases of intestinal inflammation, including Crohn's disease, ulcerative colitis and necrotizing enterocolitis, cause substantial acute and chronic disability in a large proportion of the population. Crohn's disease and ulcerative colitis, which are collectively referred to as inflammatory bowel disease (IBD), lead to recurrent episodes of intestinal dysfunction and systemic illness, whereas necrotizing enterocolitis is characterized by the development of dramatic and all too often fatal intestinal necrosis in infants. To determine the molecular underpinnings of these disorders, investigators have explored a variety of animal models that vary widely in their complexity. These experimental systems include the invertebrate nematode Caenorhabditis elegans, the more complex invertebrate Drosophila melanogaster, and vertebrate systems including mice, rats and other mammals. This review explores the experimental models that are used to mimic and evaluate the pathogenic mechanisms leading to these diseases of intestinal inflammation. We then highlight, as an example, how the use of different experimental models that focus on the role of Toll-like receptor 4 (TLR4) signaling in the gut has revealed important distinctions between the pathogenesis of IBD and necrotizing enterocolitis. Specifically, TLR4-mediated signaling plays a protective role in the development of Crohn's disease and ulcerative colitis, whereas this signaling pathway plays a causative role in the development of necrotizing enterocolitis in the newborn small intestine by adversely affecting intestinal injury and repair mechanisms.
Collapse
Affiliation(s)
- Joyce Lin
- Division of Pediatric Surgery, Children's Hospital of Pittsburgh, Pittsburgh, PA 15213, USA
| | | |
Collapse
|
|
9
|
Shu X, Ji J, Sundquist J, Sundquist K, Hemminki K. Survival in cancer patients hospitalized for inflammatory bowel disease in Sweden. Inflamm Bowel Dis 2011; 17:816-22. [PMID: 20645319 DOI: 10.1002/ibd.21380] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND The increased cancer risk among patients diagnosed with inflammatory bowel disease (IBD) is well reported, whereas studies regarding the cancer prognosis with IBD have shown conflicting results. We aimed at assessing and quantifying the cause-specific and overall mortality among cancer patients with IBD compared to those without IBD. METHODS The population-based Swedish registers were used to identify cancer patients diagnosed with or without IBD. We used a Cox regression model to estimate hazard ratios (HRs) for cause-specific and overall mortality, showing the probability of death in the study group compared to the reference. RESULTS A total of 2462 cancer patients with IBD and 1,011,894 cancer patients without IBD were ascertained from 1964 to 2006, showing a significant survival disparity (overall HR, 1.26; 95% confidence interval [CI]: 1.20-1.33 versus cause-specific HR, 1.22; 95% CI: 1.15-1.29). Although worse overall cancer mortality with IBD was widely observed, the worse cause-specific mortality was only confined to colorectal cancer (CRC). There was no difference in TNM staging among cancer patients with or without IBD. Stratified analyses showed that a worse prognosis was more pronounced in younger patients (<60 years) and in men. Discordant malignant neoplasms and cardiovascular diseases were noted to be associated with increased mortality in the study group. CONCLUSIONS Previously diagnosed IBD worsens the prognosis of cancers, especially for CRC. The more pronounced effect was noted among younger patients and in men. The underlying mechanisms warrant further investigation.
Collapse
Affiliation(s)
- Xiaochen Shu
- Center for Primary Health Care Research, Lund University, Malmö, Sweden.
| | | | | | | | | |
Collapse
|
|
10
|
Harel E, Rubinstein A, Chen W, Breuer E, Tirosh B. Aminoalkylcarbamoylphosphonates reduce TNFα release from activated immune cells. Bioorg Med Chem Lett 2010; 20:6518-23. [DOI: 10.1016/j.bmcl.2010.09.048] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2010] [Revised: 09/08/2010] [Accepted: 09/10/2010] [Indexed: 12/20/2022]
|
|
11
|
Gilbert RE. Eisenhower's 1955 heart attack: medical treatment, political effects, and the "behind the scenes" leadership style. Politics Life Sci 2008; 27:2-21. [PMID: 19213302 DOI: 10.2990/27_1_2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/27/2023]
Abstract
During his first term as President of the United States, Dwight D. Eisenhower suffered several serious illnesses. Particularly important was the massive heart attack he experienced in the fall of 1955. Drawing on primary sources as well as prior scholarship, this article analyzes varying interpretations of Eisenhower's 1955 medical treatment in light of his previous illnesses and their management. It explores the handling of public disclosure by the White House, by Eisenhower himself, and by his medical team. And it reconsiders Republican strategists' efforts to allay public concerns about the President's health. Current understanding is called into question in several respects. Although it sharpened speculation about his fitness and willingness to run in the 1956 presidential campaign, the 1955 heart attack made Eisenhower more likely, rather than less likely, to run. Although often sick, and in several instances critically so, Eisenhower was clearly the dominant player--intentionally "behind the scenes"--both in the management of his illnesses and in the health-perceptual aspects of his drive toward a second term. These findings should lead us to a better reading of Eisenhower as a president and to a better appreciation of health's linkage to legacy in presidential politics.
Collapse
Affiliation(s)
- Robert E Gilbert
- Department of Political Science, 319 Meserve Hall, Northeastern University, Boston, MA 02115, USA.
| |
Collapse
|
|
12
|
|
|
13
|
Hoffmann U, Heilmann K, Hayford C, Stallmach A, Wahnschaffe U, Zeitz M, Günthert U, Wittig BM. CD44v7 ligation downregulates the inflammatory immune response in Crohn's disease patients by apoptosis induction in mononuclear cells from the lamina propria. Cell Death Differ 2007; 14:1542-51. [PMID: 17479111 DOI: 10.1038/sj.cdd.4402153] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Deletion of exon CD44v7 abrogates experimental colitis by apoptosis induction in intestinal mononuclear cells. Here we show that CD44v7 expression was upregulated upon CD40 ligation in human mononuclear cells, and examined whether ligation of CD44v7 also affects activation and apoptosis in lamina propria mononuclear cells (LPMC) from Crohn's disease (CD) patients. Thirty five patients with chronic inflammatory bowel disease (IBD), fourteen controls and four patients with diverticulitis were evaluated. CD44v7 was upregulated predominantly in the inflamed mucosa of CD patients. Furthermore, incubation with an anti-CD44v7 antibody induced apoptosis in LPMC isolated from inflamed mucosa of CD patients, but not from non-inflamed mucosa, from patients with ulcerative colitis (UC) or from normal controls. CD40 ligation and simultaneous incubation with anti-CD44v7 significantly downregulated CD80 in dendritic cells, thus inhibiting a critical second signal for naive T-cell activation. The apoptotic signal was mediated via the intrinsic mitochondrial pathway with decreased Bcl-2 and increased 7A6 (a mitochondrial membrane protein) expression. It was Fas independent and required caspases-3 and -9 activation. The process is highly specific for macrophage activation via CD40. These findings point to a novel mechanism of apoptosis induction in CD patients mediated by CD44v7 ligation.
Collapse
Affiliation(s)
- U Hoffmann
- Medical Clinic 1, Department for Gastroenterology, Infectiology and Rheumatology, Charité University Medicine Berlin, Campus Benjamin Franklin, Berlin D 12200, Germany
| | | | | | | | | | | | | | | |
Collapse
|