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PubMed1987

Expression of HLA-DR antigens on colonic epithelium in ulcerative colitis.

Although the expression of HLA-DR antigens on colonic epithelium in ulcerative colitis has been observed by several groups, the results of the expression in remission have been conflicting and there has been virtually no study concerning the expression in non-inflamed area in active ulcerative colitis. We studied systematically HLA-DR expression on colonic epithelium in 37 patients with ulcerative colitis chronologically, namely in remission as well as in the active stage and inflamed and non-inflamed areas simultaneously in the active stage. HLA-DR antigens were detected by indirect peroxidase staining using anti-HLA-DR monoclonal antibody. We confirmed the previous observation that epithelium from control colon does not express HLA-DR antigens, while epithelium from ulcerative colitis expresses the antigens with high frequency (83.3 percent). In addition, we demonstrated that HLA-DR expression on colonic epithelium in active ulcerative colitis disappeared in remission. Our new finding was that there is no HLA-DR expression on colonic epithelium in non-inflamed mucosa in active ulcerative colitis. Namely HLA-DR antigens were expressed only on inflamed epithelium of ulcerative colitis. These results lead to the conclusion that the expression of HLA-DR antigens on colonic epithelium in ulcerative colitis is closely related to the inflammation of mucosa.

Colitis, Ulcerative↗
PubMed1991

Clinical course and long-term prognosis of Japanese patients with ulcerative colitis.

The course and prognosis of 308 patients with ulcerative colitis who visited Tohoku University Hospital during the period from 1954 to 1987 were investigated. Based these investigations, the following results were obtained. 1) In 27.6% of patients with proctitis, extension to the proximal colon developed during the observation period. 2) Surgical intervention was necessary in 33.9% of patients with total colitis and in 9.7% of those with left-sided colitis. 3) Of 1,566 patient-years in which the course was observed, 988 (63.1%) were active-years. When the course of ulcerative colitis was analyzed according to the duration and extent of involvement, the frequency of the attack-years in patients with proctitis or left-sided colitis steadily decreased with time. However, that of total colitis was constant, 65-85%, regardless of the follow-up period. Patients younger than age 20 at onset were prone to relapse during their course, compared with patients older than 20. 4) Ten patients died from causes related to ulcerative colitis in our hospital: 5 of them due to postoperative complications. Two patients developed colorectal cancer accompanying ulcerative colitis. 5) With respect to the cumulative survival rate, the 95% confidence limits of the observed curve was lower than the expected curve during the first 2 years and 12-16 years after the onset. The main causes of death were postoperative complications in the former and unrelated deaths of older patients in the latter.

Adult↗
PubMed2003

Enhanced histamine metabolism: a comparative analysis of collagenous colitis and food allergy with respect to the role of diet and NSAID use.

OBJECTIVES AND DESIGN: To compare clinical data and histamine metabolism of patients with collagenous colitis with those of food allergy. METHODS: In 17 patients with collagenous colitis, clinical findings (diarrhoea, abdominal pain) were recorded. Plasma (for histamine) and 12-h-urine (for histamine and n-methylhistamine, all measured by RIA) were collected during two days with an unrestricted diet followed by two days with an hypoallergenic. The clinical data and measured values were compared with those from patients with confirmed food allergy (n = 21) and controls (n = 41). RESULTS: Patients with collagenous colitis were found to present with significantly more liquid stools than patients with food allergy (p < 0.001) during both types of diet, but they did not experience more abdominal pain. N-methylhistamine in 12-h-urine was significantly increased during both types of diet in patients with collagenous colitis and food allergy when compared with controls (p < 0.001 for all). Patients with food allergy--but not those with collagenous colitis--showed a significant decrease of severity of pain (p < 0.05) when the diet was changed to the elimination protocol. CONCLUSION: Histamine is extensively produced and metabolised in patients with collagenous colitis. In contrast to food allergy, the allergenic potency of the administered food seems not to influence histamine production in collagenous colitis. However, histamine metabolism corresponds with the clinical activity in both patients with food allergy and collagenous colitis.

Aged↗
PubMed2006

Blockade of STAT3 by antisense oligonucleotide in TNBS-induced murine colitis.

BACKGROUND AND AIMS: The expression of signal transducers and activators of transcription 3 (STAT3) is increased in Crohn's disease (CD), and nuclear translocated STAT3 is also found in the disease. However, the role of STAT3 protein on the pathogenesis of CD is not clear. This study was executed to investigate the role of STAT3 protein on the pathogenesis of trinitrobenzene sulfonic acid (TNBS)-induced colitis, the pathogenesis of which is CD-like. METHODS: TNBS-induced colitis was produced, and STAT3 antisense oligonucleotide was administrated intracolonically during the early phase of colitis. The mice were killed 7 days later, and the expressions of STAT3 and phosphorylated STAT3 were identified by Western blot and immunofluorescence. The lamina propria mononuclear cells (LPMCs) were isolated freshly, and the percent of cell death and the expressions of Bcl-2 and Bax in LPMCs were evaluated. Colonic tissue damage and the production of inflammatory cytokines were measured also. RESULTS: Administration of STAT3 antisense oligonucleotide effectively inhibited STAT3 expression and phosphorylation in inflamed colonic mucosa of colitis. The mice that were administered STAT3 antisense oligonucleotide showed less colonic tissue damage with decreased production of inflammatory cytokines such as TNF-alpha and INF-gamma in mucosa compared with that of those TNBS-induced colitis. Administration of STAT3 antisense oligonucleotide successfully induced apoptosis of LPMCs and counteracted the unbalanced expressions of Bcl-2 and Bax in LPMCs from colitis. CONCLUSIONS: STAT3 activation may play an important role in the inflammatory process of TNBS-induced colitis, and inhibiting STAT3 activation during the early phase of the inflammatory response may have a beneficial effect on the colitis.

Animals↗
PubMed2004

Outcome after colectomy for Clostridium difficile colitis.

PURPOSE: Clostridium difficile colitis is a relatively common entity, yet large series of patients with fulminant C. difficile colitis are infrequently reported. This study was designed to identify risk factors, clinical characteristics, and outcome of patients who required colectomy for fulminant C. difficile colitis. METHODS: A population-based study on all patients in 159 hospitals of the Department of Veterans Affairs from 1997 to 2001 was performed. Data were compiled from several national computerized Department of Veterans Affairs data sets. Supplementary information including demographic information, discharge summaries, operative reports, and pathology reports were obtained from local medical records. Patient variables were entered into a computerized database and analyzed using the Pearson chi-squared and Fisher's exact tests. Statistical significance was designated as P < 0.05. RESULTS: Sixty-seven patients (mean age, 69 (range, 40-86) years; 99 percent males) were identified. All 67 patients had C. difficile verified in the colectomy specimens. Thirty-six of 67 patients (54 percent) developed C. difficile colitis during a hospitalization for an unrelated illness, and 30 of 36 patients (87 percent) after a surgical procedure. Thirty-one of 67 (46 percent) developed C. difficile colitis at home. There was no history of diarrhea in 25 of 67 patients (37 percent). Thirty of 67 patients (45 percent) presented in shock (blood pressure, <90 mmHg). Forty-three of 67 patients (64 percent) presented with an acute surgical abdomen. Mean white blood cell count was 27.2; mean percent bands was 12. Twelve of 67 patients (18 percent) had a negative C difficile colitis stool assay. Abdominal computed tomography correctly diagnosed 45 of 46 patients (98 percent) who were imaged. Twenty-six of 67 patients (39 percent) underwent colonoscopy; all 26 were found to have severe inflammation or pseudomembranes. Fifty-three of 67 patients (80 percent) underwent total colectomy; 14 of 67 underwent segmental colonic resection. Perforation and infarction were found in 59 of 67 patients (58 percent) at surgery. Overall mortality was 48 percent (32/67). Mean hospitalization was 36 (range, 2-297) days. CONCLUSIONS: Patients with fulminant C. difficile colitis often present with an unexplained abdominal illness with a marked leukocytosis that rapidly progresses to shock and peritonitis. Although frequently developed during a hospitalization and often after a surgical procedure, it may develop outside of a hospital setting. Diarrhea may be absent and stool cytology may be negative for C. difficile toxin. Perforation and infarction are frequently found at surgery. In those patients who survive, a prolonged hospitalization is common. Mortality from fulminant C. difficile colitis remains high despite surgical intervention.

Adult↗
PubMed2004

Dye spraying and magnifying endoscopy for dysplasia and cancer surveillance in ulcerative colitis.

PURPOSE: The aim of this study was to investigate detection of dysplasia or colitic cancer with ulcerative colitis by use of magnifying endoscopic observation. METHODS: From 1986 through 2000, ulcerative colitis was diagnosed and treated in 886 patients at Kitasato University East Hospital. Of the total, we studied 25 patients in depth: 14 who had dysplasia alone, 5 in whom cancer was diagnosed during follow-up after the detection of dysplasia, and 6 who had colitic cancer. RESULTS: Dysplasia was detected in 11 (3.2 percent) of 345 patients with extensive colitis and in 8 (3.7 percent) of 217 with left-sided colitis. Colorectal cancer was diagnosed in nine patients (2.6 percent) with extensive colitis and in two (0.9 percent) with left-sided colitis. Neither dysplasia nor colitic cancer was found in patients with proctitis-type colitis. Endoscopically, dysplasia and early cancer were characterized by granular or nodular protruding mucosa or by lowly protruding or flat mucosa, often associated with redness. Dye-spraying endoscopy was useful for detection. Magnifying endoscopy of ten regions of dysplasia (7 patients) and five early cancers (4 patients) showed IIIS to IIIL type pits or IV type pits. Biopsy of sites showing tumorous pits on magnifying endoscopy revealed dysplasia and early cancer. Observation of the pit pattern was found to be diagnostically useful. CONCLUSIONS: Dye spraying and magnifying endoscopy are useful for the detection, targeted biopsy, and diagnosis of dysplasia and colitic cancer in patients with ulcerative colitis.

Adult↗
PubMed2007

Can we predict the development of ischemic colitis among patients with lower abdominal pain?

PURPOSE: This study was performed to find clinical risk factors for developing ischemic colitis in patients experiencing lower abdominal discomfort with or without bloody diarrhea. METHODS: A total of 467 patients who underwent sigmoidoscopy or colonoscopy because of lower abdominal discomforts with or without blood in stool were consecutively enrolled; 147 patients were diagnosed endoscopically and histologically as having ischemic colitis. The control group was composed of the remaining 320 patients with nonspecific endoscopic/histologic findings. Clinical variables were compared between the ischemic colitis group and the control group. RESULTS: After excluding 67 patients in the ischemic colitis group, we compared the remaining 80 patients to the control group, using various clinical parameters. According to the logistic regression analysis, six factors were significantly related to ischemic colitis: older than aged 60 years (adjusted odds ratio, 5.7; 95 percent confidence interval: 2.6-11.7), hemodialysis (5; 1.2-21.6), hypertension (4.9; 2.3-10.5), hypoalbuminemia (3.5; 1.8-6.7), diabetes mellitus (3.4; 1.3-8.8), and constipation-inducing medications (2.8; 1.1-7.1). Through our analysis, we were able to predict the development of ischemic colitis for the patients with 0, 1, 2, 3, or 4+ risk factors: 8, 21, 55, 79, and 100 percent, respectively. CONCLUSIONS: Old age, hemodialysis, hypertension, diabetes mellitus, hypoalbuminemia, and constipation-inducing medications are clinically important risk factors for ischemic colitis in patients experiencing lower abdominal discomfort with or without bloody stool. By considering these factors, we were able to predict with high accuracy the development of ischemic colitis.

Abdominal Pain↗
PubMed2006

Endothelin-1 receptor antagonist (LU-135252) improves the microcirculation and course of TNBS colitis in rats.

The role of microcirculation in the pathogenesis and course of chronic inflammatory bowel disease is still unclear. The aim of this study was the evaluation of the role of microcirculation in colitis activity in the rat TNBS (trinitrobenzenesulfonic acid) colitis model using endothelin-1 and a selective endothelin-1 receptor antagonist (LU-135252). Target parameters were capillary blood flow, functional capillary density, vascular permeability, and leukocyte sticking as well as recording of hematocrit, weight course, diuresis, stool quality, and degree of inflammation using a histological colitis score. The acute phase of TNBS colitis is characterized by an extensive disturbance of microcirculation (a significant decrease in capillary blood flow and capillary density and a significant increase in capillary permeability and leukocyte sticking in the mucosa). There is also a significant increase in hematocrit and a significant decrease in diuresis and weight. An exogenous supply of endothelin-1 does not lead to an aggravation of these disorders because of a possible blockage of the endothelin-1 receptors by endogenous endothelin-1 in this florid inflammatory phase. Applying the selective endothelin-1 receptor A antagonist LU-135252 leads to a significant improvement of all microcirculatory parameters and clinical findings compared to the untreated colitis group. Direct improvement of capillary blood flow in the early phase of colitis leads to reduced colitis activity, which underscores the pathogenetic role of the microcirculation in the progression of colitis.

Animals↗
PubMed1994

Restorative proctocolectomy and indeterminate colitis.

One hundred seventy-five patients underwent restorative proctocolectomy between November 1984 and December 1992. The pathologic results were reviewed by two pathologists, one being a gastrointestinal pathologist. One hundred fifty-eight patients had a confirmed diagnosis of ulcerative colitis, and 16 patients were diagnosed with indeterminate colitis. In addition, one patient was diagnosed with familial adenomatous polyposis. Eight of the 158 patients with ulcerative colitis required removal of their pouches, and 3 of the 16 patients with indeterminate colitis required pouch removal. By this definition, the success rate for restorative proctocolectomy in patients with ulcerative colitis was 95% and the success rate for restorative proctocolectomy in patients with indeterminate colitis was 81%. Of the 16 patients with indeterminate colitis, 8 have satisfactory pouch function and 5 have some ongoing problems. We recommend this pathology-review approach to more clearly define which patients have indeterminate colitis and, therefore, to more accurately present to the patient the likelihood of success or failure of restorative proctocolectomy with this diagnosis.

Adult↗
PubMed1987

Anorectal sensitivity and responses to rectal distention in patients with ulcerative colitis.

Anorectal function in ulcerative colitis was assessed by measuring pressures at multiple sites in the anus and rectum under basal conditions and during balloon distention of the rectum in 29 patients with ulcerative colitis (12 active, 11 quiescent, and 6 during both phases) and in 12 normal controls. Resting and squeeze sphincter pressures were similar in the three groups. The lowest rectal volume that could be perceived, the volume required to induce a desire to defecate, and the maximum tolerable rectal volume were all lower in patients with active colitis than in patients with quiescent colitis (p less than 0.001) and controls (p less than 0.001). The rectal volume required to cause a sustained anal relaxation was lower in patients with active colitis (p less than 0.05) than in controls. Both peak and steady state rectal pressures in response to rectal distention were significantly higher in patients with active colitis than in patients with quiescent colitis (p less than 0.05) and controls (p less than 0.02). Paired studies showed that during remission of disease there was a decrease in rectal sensitivity (p less than 0.05) and an increase in rectal compliance (p less than 0.05). These results suggest that the frequent and urgent defecation, i.e., the predominant feature of active colitis, is related to a hypersensitive and poorly compliant rectum, which, upon distention, is more reactive and is more likely to induce prolonged sphincter relaxation.

Adult↗
PubMed1992

Exacerbation of experimental colitis by nonsteroidal anti-inflammatory drugs is not related to elevated leukotriene B4 synthesis.

The ability of nonsteroidal anti-inflammatory drugs to exacerbate experimental colitis, and the possible contributions of the "shunting" of arachidonate via the 5-lipoxygenase pathway, were investigated using a rat model in which colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid in a vehicle of 50% ethanol. Twice daily treatment with indomethacin (0.1-1 mg/kg SC) during the first week after trinitrobenzene sulfonic acid/ethanol administration resulted in dose-dependent increases in the severity of colitis and in the incidence of mortality. Mortality was not observed in vehicle-treated colitic rats or in normal rats treated with indomethacin. Similar exacerbation of colitis was observed in rats treated with naproxen (5 mg/kg). Whereas treatment with a 5-lipoxygenase inhibitor, PF-5901 (100 mg/kg PO), resulted in a significant reduction of the severity of colitis, concomitant administration of PF-5901 and indomethacin (0.5 mg/kg SC) did not inhibit the exacerbative effects of the indomethacin in this model. In separate studies, administration of indomethacin was found to significantly increase colonic myeloperoxidase activity (a measure of tissue granulocyte numbers) and suppress colonic prostaglandin E2 synthesis, while not significantly affecting colonic leukotriene B4 synthesis. The effect on myeloperoxidase activity was seen during the period 21-24 hours after trinitrobenzene sulfonic acid ethanol administration, but not during the period 45-48 hours after induction of colitis. In in vitro studies using samples of inflamed colon and in vivo studies in which colonic eicosanoid production was measured by colonic dialysis, inhibition of prostaglandin E2 synthesis was not accompanied by significant changes in leukotriene B4 synthesis. These results suggest that inhibitors of colonic prostaglandin synthesis can markedly exacerbate colitis, and that this effect is unrelated to alterations in colonic leukotriene B4 synthesis. Endogenous prostaglandins may exert anti-inflammatory effects during the acute stages of colitis.

Animals↗
PubMed1995

Molecularly defined HLA-DR2 alleles in ulcerative colitis and an antineutrophil cytoplasmic antibody-positive subgroup.

BACKGROUND/AIMS: Although HLA-DR2 is associated with Japanese ulcerative colitis, data regarding an HLA-DR2 association in other populations are conflicting. A recent study suggests that HLA-DR2 is only associated with antineutrophil cytoplasmic antibody-positive ulcerative colitis. The aim of this study was to determine whether HLA-DR2 or the molecularly defined alleles within the HLA-DR2 group are associated with ulcerative colitis or a perinuclear antineutrophil cytoplasmic antibody-positive subgroup. METHODS: Unrelated white patients with a history of ulcerative colitis (n = 97) and control subjects matched to patients for Jewish ethnicity and sex (n = 149) were studied. An immunofluorescence assay was used to detect perinuclear antineutrophil cytoplasmic antibodies. A molecular, DNA-based method was used to perform HLA-DR2 typing. RESULTS: HLA-DRB1*1601 was present in 11 of 149 controls and 1 of 97 patients (P = 0.031, corrected P, not significant; Fisher's Exact Test). There were no other significant differences between ulcerative colitis or ulcerative colitis stratified by perinuclear antineutrophil cytoplasmic antibody status and controls. CONCLUSIONS: The HLA-DR2 group of alleles is not associated with ulcerative colitis or a perinuclear antineutrophil cytoplasmic antibody-positive subgroup. The unexpected finding of a decreased frequency of HLA-DRB1*1601 in ulcerative colitis should be further investigated.

Alleles↗
PubMed2004

Clinical evaluation of granulocyte/monocyte apheresis therapy for active ulcerative colitis.

BACKGROUND: Recent evidence suggests that peripheral blood granulocytes and monocytes/macrophages have a major role in the exacerbation of ulcerative colitis. AIMS: Our objective was to investigate if selective granulocyte and monocyte adsorptive apheresis with Adacolumn promotes remission of active ulcerative colitis and spares corticosteroid. SUBJECTS: Sixty patients with active ulcerative colitis were studied, of whom 39 had relapsing-remitting ulcerative colitis, 15 had chronic continuous and 6 had their first episode of ulcerative colitis. METHODS: Granulocytapheresis was done with an Adacolumn filled with cellulose acetate beads as apheresis carriers that adsorb FcgammaR and complement receptors bearing leucocytes (granulocytes, monocytes and a small fraction of lymphocytes). Patients received up to 10 Adacolumn sessions over 12 weeks, one session was 60-90 min at 30 mL/min. No additional medication was given. Efficacy was assessed with Seo's activity index (AI) [Seo M, Okada M, Yao T. An index of disease activity in patients with ulcerative colitis. Am J Gastroenterol 1992;87:971-6]. The mean AL was 197.5 and range 154.4-277.7. AI < 150 was considered significant improvement and AI < 100 was considered clinical remission. RESULTS: Of 60 patients, 50 (83.3 %) improved, 14 achieved remission, granulocytapheresis was most effective in steroid-dependent patients. At entry, the mean dose of prednisolone was 15.3 mg/day per patient and was reduced to 3.6 mg/day after 10 sessions. Granulocytapheresis was well tolerated and no serious side-effects were observed. CONCLUSION: Based on our experience in patients with diverse ulcerative colitis disease expression and long-term exposure to conventional drug therapy, we believe that granulocytapheresis is an effective adjunct to conventional medication for promoting remission and sparing steroids in patients with active ulcerative colitis.

Adolescent↗
PubMed2006

Curcumin inhibits trinitrobenzene sulphonic acid-induced colitis in rats by activation of peroxisome proliferator-activated receptor gamma.

Curcumin is a widely used spice with anti-inflammatory and anti-cancer properties. It has been reported that curcumin held therapeutic effects on experimental colitis by inhibition of nuclear factor kappa B (NF-kappaB). The peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor with anti-tumor and anti-inflammatory effects and its activation may inhibit the nuclear translocation of NF-kappaB. Several studies have shown that PPARgamma ligands had an important therapeutic effect in colitis. However there is no report about the alteration of PPARgamma in trinitrobenzene sulphonic acid (TNBS)-induced colitis treated with curcumin. In this study, we administered curcumin (30 mg/kg/day) by intraperitoneal injection immediately after colitis was induced and the injection lasted for two weeks. have evaluated the effects of curcumin on the colitis induced by trinitrobenzene sulphonic acid (TNBS). Curcumin (30 mg/kg d) was administered by intraperitoneal just after colitis was induced and lasted for two weeks. Therapeutic effects of dexamethasone (Dex, 2 mg/kg d) alone and the combined effects of curcumin+Dex were also examined. We found that curcumin improved long-term survival rate of disease-bearing rats, promoted rat body weight recovery, and decreased macroscopic scores of the colitis. The expression levels of PPARgamma, 15-deoxy-D12,14-prostaglandin J(2) (15d-PGJ(2)) and prostaglandin E(2) (PGE(2)) were all increased, but the expression level of cyclooxygenase-2 (COX-2) was decreased in rats after administration of curcumin. Treatment with Dex improved PPARgamma expression and inhibited the expression of COX-2, 15d-PGJ(2) and PGE(2). Combined effects of curcumin+Dex were similar to that of Dex. In summary, curcumin showed therapeutic effects on TNBS-induced colitis and the mechanisms by which curcumin exerts its effects may involve activation of PPARgamma and its ligands.

Animals↗
PubMed2000

Antibiotic therapy attenuates colitis in interleukin 10 gene-deficient mice.

BACKGROUND & AIMS: Interleukin (IL)-10 gene-deficient mice, raised under germfree conditions, do not develop colitis, implying a role for bacteria. This study mapped the appearance of luminal colonic bacteria and, using antibiotic treatment, determined their association with colitis in IL-10 gene-deficient mice. METHODS: Mice were treated with ciprofloxacin or with neomycin and metronidazole. The intestine was harvested for histological scoring and bacterial assessment. RESULTS: At 2 weeks of age, before the development of colitis, IL-10 gene-deficient mice demonstrated an earlier appearance of Streptococcus and Clostridium sp., and had a greater proportion (P < 0.01) of bacteria adherent to the colonic mucosa. This pattern of increased adherent bacteria persisted for the 12 weeks of study. Treatment of mice before the onset of colonic inflammation, with either antibiotic regime, reduced mucosal adherent bacteria and prevented colitis (P < 0.01). In contrast, treatment of established colitis with neomycin and metronidazole did not reduce adherent bacterial levels, yet was more efficacious (P < 0.05) in treating established colitis than ciprofloxacin, which did reduce adherent colonic bacteria. CONCLUSIONS: In the IL-10 gene-deficient mouse model, the appearance and number of mucosal adherent colonic bacteria are altered before the onset of colitis. Antibiotics both prevent and treat the colitis through correction of this primary bacterial alteration.

Age Factors↗
PubMed1999

The critical role of interleukin 4 but not interferon gamma in the pathogenesis of colitis in T-cell receptor alpha mutant mice.

BACKGROUND & AIMS: T-cell receptor alpha mutant (TCRalpha-/-) mice spontaneously develop colitis resembling ulcerative colitis (UC). The role of interleukin (IL)-4 and interferon (IFN)-gamma in the pathogenesis of colitis was examined by creating IL-4- or IFN-gamma-deficient TCRalpha-/- mice. METHODS: Double-mutant mice were created by crossing TCRalpha-/- mice with IL-4- or IFN-gamma-deficient mice. Colitis was grossly and histologically assessed at 6 months of age, and the cytokine profile in the mesenteric lymph nodes and colons in these mice was analyzed. RESULTS: The lack of IL-4 dramatically suppressed the development of colitis at 6 months of age. In contrast, IFN-gamma-/- x TCRalpha-/- mice developed colitis similar to that present in TCRalpha-/- mice. Furthermore, proliferation of colonic epithelial cells was markedly increased in TCRalpha-/- mice and IFN-gamma-/- x TCRalpha-/- mice compared with IL-4(-/-) x TCRalpha-/- mice. Continuous administration of recombinant IL-4 led to increased colonic epithelial cell proliferation in IL-4(-/-) x TCRalpha-/- mice. CONCLUSIONS: IL-4 plays an important role in the development of colitis in TCRalpha-/- mice. In contrast, severe colitis in TCRalpha-/- mice can develop in the absence of IFN-gamma.

Animals↗
PubMed1998

Colonic histopathology in untreated celiac sprue or refractory sprue: is it lymphocytic colitis or colonic lymphocytosis?

Colonic histopathology in some patients with untreated celiac sprue and refractory sprue has been said to be indistinguishable from lymphocytic colitis, but there have been no objective comparisons on which this is based. The purpose of this study was to determine the prevalence and to characterize the nature of colonic histopathology at the time of diagnosis in patients with celiac or refractory sprue. Colonoscopic biopsy specimens obtained at the time of diagnosis from 16 patients with celiac sprue, six patients with refractory sprue, nine patients with lymphocytic colitis, and five normal controls were analyzed blindly by histological and morphometric methods, quantitating the number and specific subtypes of inflammatory cells within the lamina propria and epithelium. Immunoperoxidase staining of intraepithelial lymphocytes with a monoclonal antibody to CD8 also was performed. Three of 16 patients with untreated celiac sprue (19%) were thought to have colonic histological abnormalities, which by morphometry consisted of slightly increased numbers of lymphocytes in the surface epithelium and lamina propria, many of which were CD8-positive. These abnormalities were distinguishable from lymphocytic colitis by the lack of increased overall lamina propria cellularity and surface epithelial abnormalities, and by fewer intraepithelial lymphocytes. In refractory sprue, colonic histological abnormalities were more frequent than in celiac sprue, occurring in four of six patients (67%), more pronounced, and identical to those in the lymphocytic colitis syndrome. However, colonic intraepithelial lymphocytes in lymphocytic colitis were mostly CD8-positive, whereas those in the colitis of refractory sprue rarely were. Mild colonic lymphocytosis in patients with untreated celiac sprue should be distinguished from lymphocytic colitis by the lack of surface epithelial abnormalities, the lack of increased cellularity of the lamina propria, and the lack of ongoing watery diarrhea after treatment with a gluten-free diet. In contrast, colonic histopathology in refractory sprue is indistinguishable from lymphocytic colitis, although immunohistochemical differences do exist.

Adolescent↗
PubMed1995

Increased expression of CD44v6 and CD44v3 in ulcerative colitis but not colonic Crohn's disease.

Immune mechanisms, possibly involving cell-surface molecules such as CD44, have been invoked to explain the pathogenesis of inflammatory bowel disease. We used monoclonal antibodies against epitopes encoded within the variable region of CD44 to investigate CD44 isoform expression in colon, small intestine, and liver in patients with various intestinal disorders and in controls. Biopsy samples from patients with ulcerative colitis showed significantly increased epithelial expression of CD44 isoforms containing the v6 and v3 epitopes, detected with antibodies 2F10 and 3G5, respectively. CD44v6 was detected on colonic crypt epithelial cells in 23 of 25 ulcerative colitis samples compared with 3 of 18 colonic Crohn's disease samples (p = 3.0 x 10(-6); odds ratio 57.5 [95% CI 6.83-702]) and 3 of 52 controls (22 normal colon, 10 infective colitis, 2 radiation colitis, and 18 colonic Crohn's disease; p < 1 x 10(-8); odds ratio 199 [25.5-2294]). No significant expression of CD44v6, CD44v3, or CD44v8/9 was found in samples of normal proximal colon from 4 patients with distal ulcerative colitis, whereas samples from the affected area showed staining for CD44v6 and CD44v3. No expression of CD44 variants was found in 15 samples of normal small intestine, 11 small-bowel pouchitis, 8 coeliac disease, 3 small-bowel Crohn's disease, 6 normal liver, 6 primary biliary cirrhosis, or 9 primary sclerosing cholangitis. The high intensity of CD44v6 and v3 epitope expression on crypt epithelial cells in ulcerative colitis suggests that CD44 isoforms may have an important role in ulcerative colitis. Their detection could have diagnostic potential in differentiating ulcerative colitis from other forms of colonic inflammation including Crohn's disease.

Antibodies, Monoclonal↗