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Biomedical subjects

J F Colombel

Publications and source records attributed to J F Colombel.

At least 127 records · Page 7Linked to original sources
PubMed1996

Specific antibody response to oligomannosidic epitopes in Crohn's disease.

Elevated antibody levels against the yeast Saccharomyces cerevisiae have been reported in sera from patients with Crohn's disease and not with ulcerative colitis. The aim of the study was to identify the nature of the epitopes supporting this antibody response. Whole cells from different S. cerevisiae strains were selected in immunofluorescence assay for their ability to differentiate the antibody responses of patients with Crohn's disease and ulcerative colitis. Their cell wall phosphopeptidomannans were then tested as antigen in enzyme-linked immunosorbent assay (ELISA) against sera from 42 patients with Crohn's disease, 20 patients with ulcerative colitis, and 34 healthy controls. Graded chemical degradations were performed on the most reactive strain phosphopeptidomannan. The discriminating epitope was determined through gas-liquid chromatography-mass spectrometry. The greatest discrimination among patients with Crohn's disease, ulcerative colitis, and controls was obtained with Su1, a S. cerevisiae strain used in brewing of beer. ELISA directed against phosphopeptidomannan of this strain was 64% sensitive and 77% specific for discriminating Crohn's disease versus ulcerative colitis and 71% sensitive and 89% specific for Crohn's disease versus controls. Periodate oxidation and selective degradation demonstrated that the most important polysaccharide epitope was shared by both the acid-stable and the alkali-labile domains of the phosphopeptidomannan. The determination of oligomannose sequences of S. cerevisiae Su1 phosphopeptidomannans suggested that a mannotetraose, Man (1 --> 3)Man(1 --> 2)Man(1 --> 2)Man, supported the serological response seen in Crohn's disease. Further identification of the immunogen eliciting this antibody response as a marker of the disease may help to understand its etiology.

Adult↗
PubMed1996

Association of HLA class II genes with susceptibility to Crohn's disease.

BACKGROUND: Published studies on the association between HLA class II genes and inflammatory bowel disease are contradictory perhaps because of the limited size and ethnic heterogeneity of the populations studied. AIM: To compare the frequencies of HLA class II genes in a large number of French patients with Crohn's disease and in an ethnically matched control group. METHODS: 344 patients (196 F, 148 M, mean age 23.6 years) with Crohn's disease were molecularly genotyped for the HLA-DQB1 and DRB1 alleles. The results were compared with those for an ethnically matched control population of 488 white adults. RESULTS: There were two significant variations of alleles at the DQB1 locus: an increase in DQB1*0501 allele frequency (chi 2 = 10.6, corrected p value (pc) = 0.01, odds ratio (OR) = 1.61) and a decrease in DQB1*0602/0603 allele frequencies (chi 2 = 8.43, pc = 0.037, OR = 0.66). DRB1 analysis showed associations with three allelic variations: an increase in the frequencies of DRB1*01 (chi 2 = 12.86, pc = 0.003, OR = 1.75) and DRB1*07 alleles (chi 2 = 11.18, pc = 0.008, OR = 1.58) and a very significant decrease in that of the DRB1*03 allele (chi 2 = 19.7, pc = 9.10(-5), OR = 0.46). CONCLUSION: The alleles DRB1*01 and DRB1*07 are associated with susceptibility to Crohn's disease. The strong negative association between the DRB1*03 allele and Crohn's disease suggests that the HLA-DRB1*03 allele mediates 'resistance' to Crohn's disease.

Adolescent↗
PubMed1996

[Quality of life in chronic inflammatory bowel diseases. Validation of a questionnaire and first French data].

UNLABELLED: Inflammatory bowel diseases have an important impact on the daily life of patients. This impact can be measured by the evaluation of the health related quality of life. The aim of this study was to develop and to validate a questionnaire of quality of life in a French population. METHODS: The questionnaire comprised 70 items and was completed in 15 min. It was made up of a) a general questionnaire of 36 items (SF-36) exploring daily physical and social functioning, mental and general health, body pain and vitality. A sleep module of 6 items was added. b) a specific questionnaire of 28 items (RFIPC), exploring the concerns of the patients. The questionnaire was self-administered to 101 patients with Crohn's disease (57 F. 44 M. mean age: 35 years, acute disease: 28%, inpatients: 27%), 96 patients with ulcerative colitis (38 F. 58 M. mean age: 39 years, acute disease: 53%, inpatients: 21%). Each patient was sex and age matched with a healthy control. RESULTS: The psychometric analysis confirmed the validation of the questionnaire for the item's convergent validity, internal consistency (Cronbach's coefficient being > 0.70), analyses of discrimination. Scores of each scale of SF-36 were worse in patients than in controls. Scores of patients with active disease were worse than those of patients with quiescent disease. Scores were comparable in patients with Crohn's disease and with ulcerative colitis except for score of pain which was worse in acute Crohn's disease. The most important concerns of patients were the uncertain nature of the disease, energy level and having surgery. CONCLUSION: This study allowed the validation of a questionnaire for the evaluation of the quality of life in French patients with inflammatory bowel disease and provides first indications which need to be confirmed by future epidemiological studies.

Adult↗
PubMed1995

Immunoreactivity for interleukin 3 and 5 and granulocyte/macrophage colony-stimulating factor of intestinal mucosa in bronchial asthma.

T lymphocytes and eosinophils are important components of the inflammatory cell infiltrate in bronchial mucosa in asthma. Because activated lymphocytes migrate through the thoracic duct and the general circulation to remote glandular and mucosal sites, we initiated this study to evaluate pathological abnormalities and immunoreactivity for interleukin (IL) 3, IL-5, and granulocyte/macrophage colony-stimulating factor (GM-CSF) of intestinal mucosa in bronchial asthma. 15 asthmatic patients, 8 nonasthmatic patients with chronic obstructive pulmonary disease, 6 atopic nonasthmatic healthy controls, and 6 nonatopic healthy controls were studied. Duodenal biopsies were performed by endoscopy. A significantly increased number of intraepithelial lymphocytes and eosinophils and a significant accumulation of mononuclear cells (lymphocytes and mast cells) and eosinophils in the lamina propria were detected in asthmatics and atopic controls. Immunostaining with antibodies directed against IL-3, IL-5, and GM-CSF was positive in asthmatics and atopic controls, whereas no staining was observed in nonatopic controls and chronic obstructive pulmonary disease. Combined ultrastructural study and immunogold labeling demonstrated that IL-3, IL-5, and GM-CSF were localized in eosinophils and mast cells. Although devoid of gastrointestinal symptoms, asthmatics and asymptomatic atopics had duodenal pathological abnormalities mimicking those observed in the bronchial mucosa in asthma, suggesting that the whole mucosal immune system is involved in bronchial asthma.

Adolescent↗
PubMed1995

Distinct production of autoantibodies to nuclear components in ulcerative colitis and in Crohn's disease.

Despite extensive research, the pathogenesis of inflammatory bowel disease (IBD) is still unclear. Immunological disorders have been described in patients with both Crohn's disease (CD) and ulcerative colitis (UC). In this work serum samples collected from 58 patients with CD and 55 patients with UC were tested in ELISA against a panel of nuclear and cytoplasmic proteins and peptides in order to determine whether specific autoantibodies are produced in these patients. Low levels of IgG antibodies to histones H1, H2A, H2B, H3, and H4, to Hsp-70 and ubiquitin stress proteins, Ro/SSA and La/SSB proteins and myosin were detected in some of these sera. In contrast, the following antibodies of IgG isotype could be much more frequently demonstrated: antibodies to ubiquitinated H2A (U-H2A) peptide T4 (51.7% in CD; 18.2% in UC), antibodies to the zinc-finger peptide F2 of poly-(ADP-ribose polymer)ase (PARP) involved in DNA repair (58.6% in CD; 25.5% in UC) and actin antibodies (43.1% in CD; 7.3% in UC). In a follow-up study of 12 patients with CD and UC (75 additional samples), we found IgG antibodies to several histone peptides occurring essentially in the serum of patients with CD. Although we found no obvious correlation between the presence or level of these various antibodies and C-reactive protein, or the location of the disease, in a number (but not all) of patients, we observed a strikingly good relationship between antibodies to histone peptides, U-H2A peptide T4, and PARP peptide F2 and the Crohn's disease activity index. The mechanism of induction of these antibodies still remains obscure.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1995

Hyperbaric oxygenation in severe perineal Crohn's disease.

PURPOSE: Perineal involvement in Crohn's disease is a common and distressing condition, often refractory to medical or surgical treatments. Recent reports suggest the efficacy of hyperbaric oxygenation (HBO) in the healing of perineal lesions. We evaluated HBO in severe patients with perineal Crohn's disease. METHODS: Ten consecutive patients (8 women, 2 men; mean age, 30 years) were studied. There were four superficial fissures, four cavitating ulcers, six low or superficial fistulas, two high fistulas, and one irreversible anal stenosis. All patients had received one or more medical treatments without healing the perineal lesions, and all had had previous surgery for perineal lesions. RESULTS: Two patients discontinued HBO after a few sessions and did not complete treatment. Eight patients completed at least 30 HBO sessions and were evaluable. At the end of the procedure, six of eight patients treated were healed, three completely and three partially. All patients who healed completely received HBO as an additional treatment to local perineal surgery. CONCLUSION: HBO might be useful as a last resort treatment of chronic perineal Crohn's disease, resistant to other treatments or as a complement to surgery.

Adult↗
PubMed1995

Bacterial enzymes used for colon-specific drug delivery are decreased in active Crohn's disease.

Enzymes produced by colonic microflora have been proposed for triggering local delivery of antiinflammatory azo-bond drugs and prodrugs to the colon. This approach could be advantageous in steroid treatment of inflammatory bowel diseases, thus sparing steroids' side effects. We recently demonstrated that the metabolic activity of digestive flora, assessed on the activity of fecal glycosidases, was decreased in patients with active Crohn's disease. In the present study, the azoreductase activity in feces of 14 patients with active Crohn's disease was decreased (11.39 +/- 7.93 mU/g F) as compared with 12 healthy subjects (51.13 +/- 21.39 mU/g F). beta-D-Glucosidase and beta-D-glucuronidase activities in fecal homogenates incubated under anaerobic conditions were also decreased in patients. These data bring into question the therapeutic usefulness for those patients of azo-bond drugs and glycoside prodrugs. They could explain the therapeutic failure of some of those drugs in active ileocolic and colic Crohn's disease.

Adult↗
PubMed1995

Immunocytochemical evidence of Listeria, Escherichia coli, and Streptococcus antigens in Crohn's disease.

BACKGROUND/AIMS: Infectious agents have long been suspected of playing a role in the initiation of Crohn's disease. The objective of this study was to search for likely microbial agents in diseased tissues using immunocytochemical techniques. METHODS: Intestines and mesenteric lymph node specimens of 21 patients from two French families with a high frequency of Crohn's disease and from Connecticut were studied. The microbial agents searched for included Bacteroides vulgatus, Borrelia burgdorferi, Escherichia coli, Listeria monocytogenes, Streptococcus spp., bovine viral diarrhea virus, influenza A virus, measles virus, parainfluenza virus, and respiratory syncytial virus. RESULTS: Seventy-five percent of the patients with Crohn's disease (12 of 16) were positively labeled with the antibody to Listeria. Macrophages and giant cells immunolabeled for this antigen were distributed underneath ulcers, along fissures, around abscesses, within the lamina propria, in granulomas, and in the germinal centers of mesenteric lymph nodes. In addition, 57% (12 of 21) of the cases contained the E. coli antigen, and 44% (7 of 16) contained the streptococcal antigen. The immunolabeling for the latter two agents also occurred within macrophages and giant cells, distributed in a pattern similar to that of Listeria antigen. CONCLUSIONS: The results suggest that Listeria spp., E. coli, and streptococci, but not measles virus, play a role in the pathogenesis of Crohn's disease.

Antigens, Bacterial↗
PubMed1995

Impaired secretion and mRNA expression of monokines by alveolar macrophages from nonsmoking patients with alcoholic liver cirrhosis.

Alveolar macrophages (AM) exposed to microorganisms secrete cytokines that are important to lung defense. Since alcoholic liver cirrhosis (ALC) patients are susceptible to lung infections, the ability of AM in such patients to produce the cytokines tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-6 was evaluated by mRNA expression and protein secretion. Adherent AM from ALC and alcoholic patients and controls were cultured with and without lipopolysaccharide (LPS): Mean cytokine levels in ALC and alcoholic subjects were not significantly different than in controls. However, LPS-stimulated AM from 13 of 29 ALC patients exhibited a reduced ability, compared with that from controls, to secrete the cytokines (P < .05 for all 3). Specific mRNA expression was also impaired in the 13 patients, and their liver diseases were more severe than those of other patients. Impaired cytokine production by AM in ALC patients with severe cirrhosis may account for their increased susceptibility to lung infections.

Adult↗
PubMed1995

Secretion of immunoglobulins and plasma proteins from the colonic mucosa: an in vivo study in man.

There are no available data on immunoglobulins and albumin outputs into the normal human colon. We thus measured the intracolonic secretion rates of IgA, IgG, IgM, secretory component (SC) and plasma proteins (albumin (Alb), orosomucoid (Oro), transferrin (Transf) and alpha 2-macroglobulin (alpha 2-M)). Using a pancolonic perfusion technique in 10 healthy volunteers (six females, four males, mean age 24 years), concentrations and outputs of Alb, immunoglobulins, SC, Oro, Transf and alpha 2-M were measured in the rectal effluents by immunoradiometric assay. Monomeric (m) and polymeric (p) IgA distribution was analysed by sucrose density ultracentrifugation. The secretion of polymeric IgA (p-IgA) was 153 micrograms/min, i.e. 220 mg/day, exceeding that of other immunoglobulins (m-IgA 8.5 micrograms/min; IgG 33.5 micrograms/min; IgM 17 micrograms/min) and of non-immunoglobulin proteins (Alb 104 micrograms/min; Oro 9 micrograms/min; Transf 7 micrograms/min; alpha 2-M 4.5 micrograms/min). p-IgA was entirely linked to SC (secretory IgA) and 12% of SC was in free form. About 62% of total IgA was IgA2. For each protein, a relative coefficient of excretion (RCE) was calculated (colon to serum concentration ratio expressed relative to that of Alb). The p-IgA, IgM and m-IgA RCE were 277, 6 and 2.2 times higher than the values predicted from their molecular weight. RCE of non-immunoglobulin proteins also exceeded the values expected from a passive seepage from the vascular compartment. The intracolonic clearance of Alb extrapolated to 24 h was only 3.7 ml/day. These results show the high local production and/or the facilitated transport to the colonic lumen of p-IgA, and are in very good agreement with the distribution of plasma cells in the colonic mucosa.

Adult↗
PubMed1995

Parallel interleukin 5 synthesis by eosinophils in duodenal and skin lesions of a patient with dermatitis herpetiformis.

A 59 year old man is presented with a diagnosis of dermatitis herpetiformis. Duodenal and skin biopsy specimens from blisters of both recent and late onset were collected before treatment. Electron microscopy, immunohistochemistry, and in situ hybridisation were performed to analyse the presence of activated eosinophils and the local synthesis of interleukin 5 (IL5). Parallel state of eosinophil activation and IL5 synthesis was found in the duodenal mucosa with total flat mucosa and in skin vesicles of recent onset. It is suggested that duodenal and cutaneous eosinophils can synthesise IL5 and then participate in small bowel and skin lesions.

Dermatitis Herpetiformis↗