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Aim: To determine whether the carbon monoxide (CO)-releasing molecules (CORM)-liberated CO suppress inflammatory responses in the small intestine of septic mice., Methods: The C57BL/6 mice (male, n = 36; weight 20 ± 2 g) were assigned to four groups in three respective experiments. Sepsis in mice was induced by cecal ligation and puncture (CLP) (24 h). Tricarbonyldichlororuthenium (II) dimer (CORM-2) (8 mg/kg, i.v.) was administrated immediately after induction of CLP. The levels of inflammatory cytokines [interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)] in tissue homogenates were measured with enzyme-linked immunosorbent assay. The levels of malondialdehyde (MDA) in the tissues were determined. The levels of nitric oxide (NO) in tissue homogenate were measured and the expression levels of intercellular adhesion molecule 1 (ICAM-1) and inducible nitric oxide synthase (iNOS) in the small intestine were also assessed. NO and IL-8 levels in the supernatants were determined after the human adenocarcinoma cell line Caco-2 was stimulated by lipopolysaccharide (LPS) (10 g/mL) for 4 h in vitro., Results: At 24 h after CLP, histological analysis showed that the ileum and jejunum from CLP mice induced severe edema and sloughing of the villous tips, as well as infiltration of inflammatory cells into the mucosa. Semi-quantitative analysis of histological samples of ileum and jejunum showed that granulocyte infiltration in the septic mice was significantly increased compared to that in the sham group. Administration of CORM-2 significantly decreased granulocyte infiltration. At 24 h after CLP, the tissue MDA levels in the mid-ileum and mid-jejunum significantly increased compared to the sham animals (103.68 ± 23.88 nmol/mL vs 39.66 ± 8.23 nmol/mL, 89.66 ± 9.98 nmol/mL vs 32.32 ± 7.43 nmol/mL, P < 0.01). In vitro administration of CORM-2, tissue MDA levels were significantly decreased (50.65 ± 11.46 nmol/mL, 59.32 ± 6.62 nmol/mL, P < 0.05). Meanwhile, the tissue IL-1β and TNF-α levels in the mid-ileum significantly increased compared to the sham animals (6.66 ± 1.09 pg/mL vs 1.67 ± 0.45 pg/mL, 19.34 ± 3.99 pg/mL vs 3.98 ± 0.87 pg/mL, P < 0.01). In vitro administration of CORM-2, tissue IL-1β and TNF-α levels were significantly decreased (3.87 ± 1.08 pg/mL, 10.45 ± 2.48 pg/mL, P < 0.05). The levels of NO in mid-ileum and mid-jejunum tissue homogenate were also decreased (14.69 ± 2.45 nmol/mL vs 24.36 ± 2.97 nmol/mL, 18.47 ± 2.47 nmol/mL vs 27.33 ± 3.87 nmol/mL, P < 0.05). The expression of iNOS and ICAM-1 in the mid-ileum of septic mice at 24 h after CLP induction significantly increased compared to the sham animals. In vitro administration of CORM-2, expression of iNOS and ICAM-1 were significantly decreased. In parallel, the levels of NO and IL-8 in the supernatants of Caco-2 stimulated by LPS was markedly decreased in CORM-2-treated Caco-2 cells (2.22 ± 0.12 nmol/mL vs 6.25 ± 1.69 nmol/mL, 24.97 ± 3.01 pg/mL vs 49.45 ± 5.11 pg/mL, P < 0.05)., Conclusion: CORM-released CO attenuates the inflammatory cytokine production (IL-1β and TNF-α), and suppress the oxidative stress in the small intestine during sepsis by interfering with protein expression of ICAM-1 and iNOS.

Since first described in the mid 1990s, there has been burgeoning literature on IgG4-related sclerosing disease. The number of sites that may be involved is ever increasing, with the pancreas, salivary glands, and lymph nodes being the most commonly affected organs. There are no well-documented cases arising in the gastrointestinal tract. In this report, we present the first case to our knowledge of IgG4-related sclerosing disease involving the small bowel with a distinctly unusual clinicopathologic presentation. A previously well 46-year-old woman presented with a 2-year history of intermittent abdominal pain with recent worsening due to small bowel obstruction. Following imaging, which showed jejunitis with surrounding mesenteric inflammatory changes, she proceeded to a segmental small bowel resection. The resected jejunum revealed an isolated, stenosing chronic ulcer associated with a necrotizing mesenteric arteritis. A transmural inflammatory infiltrate rich in IgG4 plasma cells was seen in the wall of the bowel and mesenteric artery. Abundant IgG4 interfollicular plasma cells were also identified in a mesenteric lymph node. The serum IgG4 level was elevated at >800 mg/dL (reference range 8 to 140 mg/dL). Although phlebitis is an almost constant feature of this disease, arteritis is not described other than in the lung and aorta. In this report, we also discuss the diagnostic pitfalls and the differential diagnoses that should be considered when this condition arises in the gastrointestinal tract.

Eosinophil responses in extraintestinal and intestinal tissues were examined in August and Sprague-Dawley rats infected with Nippostrongylus brasiliensis or Eimeria nieschulzi (or both), and in uninfected controls to test the hypothesis that E. nieschulzi suppresses the systemic N. brasiliensis-induced eosinophil response. Caudal vein blood, femoral bone marrow, bronchoalveolar lavage fluid, peritoneal lavage fluid, and duodenal and jejunal samples were collected on day 8 postinfection (PI) with E. nieschulzi, on day 16 PI of the N. brasiliensis infection, when these days coincided in the concurrently infected rats, and from uninfected controls. Differential white blood cell counts were made from blood smears and cytocentrifuged preparations, and duodenal and jejunal eosinophils per villus crypt unit were quantified. Eimeria nieschulzi significantly reduced N. brasiliensis-induced eosinophil levels in peripheral blood, lavage fluids, and duodenal and jejunal tissues in both rat strains. August and Sprague-Dawley rats monospecifically infected with N. brasiliensis and concurrently with both parasites demonstrated elevated eosinopoiesis compared with uninfected controls and rats infected with only E. nieschulzi; however, despite this, concurrently infected rats had a significantly greater level of eosinopoiesis than those infected with only the nematode. In addition, E. nieschulzi induced elevated neutrophil levels in both monospecifically and concurrently infected rats in all extraintestinal tissues examined in both rat strains, whereas lymphocyte counts decreased concomitantly. This study suggests that the intestinal coccidian E. nieschulzi has the ability to modulate the systemic inflammatory response to N. brasiliensis and that this is not a rat strain-specific phenomenon.

Salmonella enterica serovar Choleraesuis is an enteric pathogen of swine, producing septicemia, enterocolitis, pneumonia, and hepatitis. The initial molecular events at the site of Salmonella infection are hypothesized to be critical in the initiation of innate and adaptive immune responses; however, the acute immune response elicited by porcine intestinal tissues is not well understood. To address this need, we employed explants of jejunal Peyer's patch (JPP) mucosa from pigs to examine Salmonella-induced immune responses under controlled conditions as well as to overcome limitations of whole animal approaches. JPP explants mounted in Ussing chambers maintained normal histological structure for 2 h and stable short-circuit current and electrical conductance for 2.5 h. After ex vivo luminal exposure to Salmonella serovar Choleraesuis, JPP responded with an increase in mRNA expression of IL-1beta and IL-8, but not TNFalpha. Increased IL-1beta and IL-8 expression were dependent on efficient Salmonella adhesion and internalization, whereas mutant Salmonella did not induce inflammatory cytokine expression. Commensal enteric bacteria, present in some experiments, also did not induce inflammatory cytokine expression. These findings indicate that Salmonella uptake by Peyer's patch is important in the induction of an innate response involving expression of IL-1beta and IL-8, and that ex vivo intestinal immune tissue explants provide an intact tissue model that will facilitate investigation of mucosal immunity in swine.

TNF-alpha, including other proinflammatory cytokines alone or in combination, induces iNOS expression and upregulates inflammatory responses. We evaluated the relationship between TNF-alpha and iNOS expression in indomethacin-induced jejunoileitis in male Sprague-Dawley rats. Rats were fed a daily dose of a phosphodiesterase inhibitor-either theophylline or pentoxifylline-for 2 days. Jejunoileitis was induced with two subcutaneous injections of indomethacin (7.5 mg/kg) 24 hr apart and theophylline or pentoxifylline continued for 12 hr or 4 days. Other rats received a single intraperitoneal injection of anti-TNF-alpha monoclonal antibody (TNF-Ab) 30-min before indomethacin. At 4 days TNF-Ab, theophylline, or pentoxifylline treatment significantly decreased indomethacin-induced ulceration, myeloperoxidase activity, and disease activity index. Although indomethacin significantly increased serum TNF-alpha and nitrate/nitrite levels over the control value as early as 12 hr, iNOS expression was detected only after 4 days. Serum IL-1beta level did not change at 12 hr but increased fourfold at 4 days. Treatment with TNF-Ab, theophylline, or pentoxifylline significantly reduced serum/tissue TNF-alpha, IL-1beta, nitrate/nitrite, and iNOS expression. The downregulation of nitrate/nitrite by these inhibitors suggests that TNF-alpha modulates iNOS expression.

Expulsion of the gastrointestinal nematode Trichinella spiralis is associated with pronounced mastocytosis mediated by a Th2-type response involving IL-4, IL-10, and IL-13. Here we demonstrate that IL-18 is a key negative regulator of protective immune responses against T. spiralis in vivo. IL-18 knockout mice are highly resistant to T. spiralis infection, expel the worms rapidly and subsequently develop low levels of encysted muscle larvae. The increased speed of expulsion is correlated with high numbers of mucosal mast cells and an increase in IL-13 and IL-10 secretion. When normal mice were treated with rIL-18 in vivo, worm expulsion was notably delayed, and the development of mastocytosis and Th2 cytokine production was significantly reduced. The treatment had no effect on intestinal eosinophilia or goblet cell hyperplasia but specifically inhibited the development of mastocytosis. Addition of rIL-18 to in vitro cultures of bone marrow-derived mast cells resulted in a significant reduction in cell yields as well as in the number of IL-4-secreting mast cells. In vivo treatment of T. spiralis-infected IFN-gamma knockout mice with rIL-18 demonstrated that the inhibitory effect of IL-18 on mastocytosis and Th2 cytokine secretion is independent of IFN-gamma. Hence, IL-18 plays a significant biological role as a negative regulator of intestinal mast cell responses and may promote the survival of intestinal parasites in vivo.

Eighteen cases of laparotomy-proven acute necrotizing jejunoileitis were treated during the period 1992-1998. Routine laboratory investigations and bacteriological studies were non-contributory towards establishing an etiological basis for the diagnosis. Superior mesenteric artery digital subtraction angiography, carried out in five patients, demonstrated extensive neovascularization. IgG, IgM and IgA were normal in all eight children in whom it was measured; IgE levels were grossly elevated (mean 900 IU/ml; normal range 0-100 IU/ml). Four cases had evidence of hypersensitivity reactions (type I in one patient and type III in three patients) on histopathological examination of the resected small bowel. In addition, histopathological examination also showed the neovascularization observed on angiography. The evidence suggests an immunologically mediated insult resulting in intense vasculitis, which in turn causes ischemic damage to the bowel wall.

Background: The antiphospholipid-antibody syndrome (APS) is a thrombophilic disorder, in which venous and arterial thrombosis can occur. We report the rare case of a patient with mesenteric infarction due to primary APS., Case Report: A 46-year-old male patient was admitted to the hospital because of severe abdominal pain. A laparotomy was performed and revealed infarction of a jejunal loop which was resected. At pathohistological examination mesenteric artery infarction was found. Preoperatively prolonged partial thromboplastin time led to coagulation analysis. Lupus anticoagulant and anticardiolipin antibodies were found., Treatment: The diagnosis of primary APS was made and the patient was treated with aspirin (100 mg/day) and low molecular weight heparin (2,500 IE/day) permanently. Eighteen months after mesenteric infarction the patient is free of further thromboembolic events.

Loss of response to a gluten-free diet (refractory sprue) and ulcerative jejunitis are complications of celiac disease that may progress to enteropathy-associated T-cell lymphoma (EATL). Both conditions are characterized by the presence of a nonlymphomatous monoclonal T-cell population in the enteropathic mucosa. In EATL, a similar monoclonal population that shows clonal identity with the lymphoma itself is also present in the enteropathic mucosa. In this study we show that in all three circumstances the monoclonal T-cell population is constituted by cytologically normal, noninvasive intraepithelial T lymphocytes that share an identical aberrant immunophenotype with EATL. Patients with refractory sprue and/or ulcerative jejunitis are, therefore, suffering from a neoplastic T-cell disorder for which hematological treatment strategies need to be devised.

The changes in the intestinal morphology of murine T-cell-mediated acute semi-allogenic graft-versus-host disease (GvH) are characterized by lymphocytic infiltrates, crypt hyperplasia, and villous atrophy. In the present study, the role of CD40L (gp39)-an important member of the TNF/NGF superfamily of receptors and their ligands-for T-cell costimulation in vivo during the development of mucosal atrophy was investigated. We found that the inhibition of the CD40L-CD40 interaction in GvH animals by the administration of an anti-CD40L antibody (MR-1) completely prevents the development of crypt hyperplasia and villous atrophy in GvH animals. This includes a normalization of the rate of crypt cell apoptosis, which is augmented in untreated GvH animals. In conclusion, the CD40L-CD40 interaction is crucial in the pathogenesis of T-cell-mediated mucosal atrophy., (Copyright 1999 Academic Press.)

Activated T cells, with their secretion of cytokines, probably play an important role in the pathogenesis of mucosal lesions in coeliac disease (COD) and the prominence of a T-helper (Th)1-type cytokine pattern has been reported. As the process of immunological activation in the jejunal mucosa in active CoD has been shown to also cause some differences in peripheral blood lymphocyte populations, we sought to establish any changes in the Th 1/Th2 balance in peripheral blood of patients, at different stages of CoD, relative to healthy individuals. Twenty-two CoD patients and 10 healthy controls were included in the study. The Th1/Th2 balance was examined both in resting cells and after polyclonal stimulation using two different methods: intracytoplasmic cytokine contents were measured using an intracellular staining method and three-colour flow cytometry and cytokine contents of cell culture supernatants were measured using traditional enzyme-linked immunosorbent assays (ELISAs). Interferon-gamma (IFN-gamma)-producing cells (Thl) were as prominent in untreated CoD patients and treated CoD patients as in healthy controls, while cells fitting a Th2 or ThO-type cytokine pattern were few in all groups. In ELISA assays, Th1 type (IFN-gamma or interleukin (IL)-2) cytokines were again prominent in all study groups but no statistically significant differences were found in IFN-gamma, IL-4 or IL-2 levels among the three groups. These results suggest that the increased shift towards a Th1 response is mainly restricted to the actual site of inflammation and that circulating T cells do not show a similar response, presumably because activated cells in peripheral blood are too few. Further research on cytokine profiles measuring T-cell activation in CoD should be focused on the actual tissue of inflammation.

Background: Strongyloides stercoralis can cause a wide spectrum of disease in man, ranging from a chronic asymptomatic infection to a hyperinfective, often fatal syndrome. In rodents, spontaneous expulsion of Strongyloides spp occurs after experimental infection. Mast cells, goblet cells, and eosinophils have been identified as possible effectors of this expulsion., Aims: To investigate intestinal histopathology and mucosal immunity in immunocompetent patients with chronic S stercoralis infection., Methods: Jejunal biopsies were performed in 19 immunocompetent patients with a positive stool examination for S stercoralis and few or no symptoms, and in seven healthy controls. Specimens were processed for histopathological analysis and stained by the immunoperoxidase technique, using the following monoclonal antibodies: CD2, CD3, CD4, CD8, anti-T cell receptor (TcR) gamma/delta, RFD1 and RFD7 (two different macrophage markers), Ki67+ (proliferating) cells, antihuman leucocyte antigen (HLA)-DR, and anticollagen IV. In addition, CD25+ cells, mast cells, IgE expressing cells, calprotectin containing cells, and neutrophil elastase positive cells were stained by the alkaline phosphatase method., Results: Jejunal morphology and the numbers of different T cell subsets, mast cells, IgE expressing cells, eosinophils, and goblet cells were unaffected by S stercoralis infection. Conversely, the numbers of mature macrophages and dividing enterocytes in the crypts were reduced significantly. Crypt enterocytes did not express HLA-DR in both groups. The expression of HLA-DR by villus enterocytes was also comparable in patients and controls. There were no activated (CD25+) cells in the mucosa of either patients or controls., Conclusions: Compared with seven healthy uninfected volunteers, a group of 19 Brazilians with clinically mild strongyloides infection showed no abnormality of mucosal structure and no increase in non-specific inflammatory cells. Likewise, there was no increase in mucosal T cells or macrophages.

Ulcerative jejunitis (UJ) and enteropathy-associated T-cell lymphoma (EATL) are closely related conditions both associated with celiac disease. Benign-appearing inflammatory ulcers are seen in both, which has led to the suggestion that UJ is a manifestation of EATL. The aim of this study was to investigate this relationship using the polymerase chain reaction (PCR) to detect T-cell gene rearrangement. PCR amplification of the T-cell receptor gamma-chain gene was performed on DNA extracted from lymphoma, associated inflammatory ulcers, and intervening mucosa in six EATL cases and from ulcers and intervening mucosa of seven cases of UJ. In two of these cases, DNA from a subsequent lymphoma was also studied. The PCR products from the tumor and an ulcer from one EATL case, two ulcers from one case of UJ, and one ulcer and subsequent cutaneous lymphoma from one UJ case were sequenced. Twenty-five ulcers from twelve cases of Crohn's disease, twenty sections of normal bowel, and nine celiac biopsies were included as controls. A monoclonal T-cell population defined by a dominant band equal in size to that amplified from the lymphoma was identified in at least one ulcer from four informative EATL cases and from intervening mucosa in three. Monoclonality was demonstrated in at least one, and up to thirteen, ulcers from all seven cases of UJ, in intervening mucosa in five, and in the two subsequent lymphomas. Sequencing showed the same clone was present in the tumor and the ulcer in the EATL case, in two of three ulcers from the UJ case, and in an ulcer and subsequent cutaneous lymphoma in one UJ case. All Crohn's disease ulcers and all sections of normal bowel were polyclonal. One of nine celiac biopsies showed a dominant band. In conclusion, we have shown that T-cell monoclonality is a feature of the ulcers in both UJ and EATL and that the same clone is present in EATL and its associated inflammatory ulcers and in UJ and subsequently developing lymphoma.

The authors established that 12 h after development of acute obstructive ileus in inactive neutrophil granulocytes (NG), the anaerobic microorganisms were intact, or at the process of division; in the active NG, they were destroyed, or when forming "halo", might preserve and migrate in the matrix of NG. In interaction of NG with microorganisms, the numerous oval and roundish bacterial bodies with a diameter of 0.2-0.5 micron capable to penetrate into the non-phagocytic cells are formed. A function of the formations revealed is not studied.

Intestinal humoral immunity was examined in eight patients with dermatitis herpetiformis and normal jejunal histology (as determined by quantitative morphometry) on a gluten-containing diet. Jejunal aspirate was taken at the time of jejunal biopsy, and levels of total immunoglobulins (IgA, IgM, IgG) and specific antibody to gliadin and two other dietary proteins, betalactoglobulin and ovalbumin, were measured. The pattern of secretory immune responses in the dermatitis herpetiformis patients was similar to that in twenty-six patients with untreated coeliac disease--ie, higher than normal concentrations of IgA, IgM, and IgG and high levels of specific antibodies (IgA and IgM) to the three dietary proteins. Serum levels of IgA antigliadin were similar in the dermatitis herpetiformis and control (twenty-eight patients who underwent jejunal biopsy to exclude coeliac disease) groups, and serum levels of IgG antigliadin were intermediate between those of the control and coeliac disease groups. These findings suggest that investigation of gut humoral immunity may provide a diagnostic index of latent coeliac disease. The definition of coeliac disease as a permanent gluten-sensitive enteropathy may have to be revised if the proposed two-stage model is confirmed.

As a means of investigating further the pathogenesis of intestinal immunopathology, we have attempted to produce a destructive enteropathy by inducing an acute graft-versus-host reaction (GVHR) in mature, immunocompetent mice. Adult (C57b1/10 X DBA/2)F1 (BDF1) mice given C57B1/10(B10) spleen cells develop a severe GVHR which is associated with marked weight loss and high mortality. In the intestine an initial phase of enteropathy characterized by intense crypt hyperplasia is replaced by more severe intestinal damage which includes villus atrophy and loss of intra-epithelial lymphocytes. These pathological alterations are paralleled by the generation of anti-host cytotoxic T lymphocytes (CTL), marked immunosuppression and the loss of natural killer (NK) cells. In contrast to these findings, adult BDF1 mice given DBA/2 donor cells do not develop an acute systemic GVHR and have no CTL or intestinal pathology, despite prolonged splenomegaly and enhanced NK cell activity. Thus, destructive enteropathy can be induced during a GVHR in intact hosts and our results confirm that this enteropathy has a biphasic pattern, with villus atrophy representing the progression of initial crypt hyperplasia in severe forms of disease associated with weight loss and specific CTL.

Previously we have shown by indirect immunofluorescence (IF) technique that a special IgA antibody in the sera of patients with dermatitis herpetiformis (DH) binds to the structures of the normal jejunum. Now we show by direct IF that specific IgA deposits are present in the proximal jejunum of 11/12 DH and 2/2 celiac patients before a gluten-free diet (GFD). The IgA deposition was in a tubular pattern underlying the villous and crypt epithelial basement membranes and in the lamina propria. This IgA deposition diminished or was not detectable in DH patients under a GFD for a year, and became detectable under gluten challenge in three DH patients. One patient with celiac disease and IgA deficiency, four with other intestinal diseases, and four without jejunal damage had neither jejunal IgA deposition nor circulating IgA anti-jejunal antibody. The deposition of IgA in the jejunum seemed to be correlated with the presence of IgA anti-jejunal antibody in the serum and with the presence of jejunal damage, but the degree of jejunal atrophy, the titer of the anti-jejunal antibody, and the intensity of jejunal IgA deposition in DH patient were not clearly related. Deposition of IgA in the jejunum in DH did not clearly correlate with the activity of the skin symptoms and thus may not be directly related to the pathogenesis of the skin disease of DH.

In these studies we compared jejunal permeability to two probes--chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) (mol wt, 360) and ovalbumin (mol wt, 45,000)--under control conditions, during acute intestinal inflammation, and in response to systemic anaphylaxis. Acute inflammation was produced after infection with Nippostrongylus brasiliensis and rats were studied at day 0 (control), day 4 (early), day 10 (acute), and day 35 (postinfection). At the latter stage, immune rats were also studied during anaphylaxis induced by i.v. N. brasiliensis antigen. In each study, blood and urine were sampled over 5 h after the probes were simultaneously injected into ligated loops in anesthetized rats. In controls, small quantities (less than 0.04% and 0.002% of the administered dose for 51Cr-EDTA and ovalbumin, respectively) appeared in the circulation and plateaued at 1 h. During acute inflammation, the appearance of both probes continued to increase with time. Compared with controls, 5-h values for 51Cr-EDTA and ovalbumin were (a) significantly elevated at day 4 (p less than 0.005), (b) increased approximately 20-fold at day 10 (p less than 0.005 and less than 0.01, respectively), and (c) normal at day 35. Urinary recovery of 51Cr-EDTA followed the same pattern. During anaphylaxis, appearance of the probes in the circulation increased at 1 h to values approximately 10-fold those in controls (p less than 0.001 and less than 0.01, for 51Cr-EDTA and ovalbumin, respectively), and then declined. Urinary recovery of 51Cr-EDTA over 5 h was also significantly increased. We conclude that epithelial barrier function becomes impaired during both acute inflammation and anaphylaxis. In this rat model, gut permeability changes to 51Cr-EDTA reflect gut permeability changes to macromolecular antigens. If similar conditions exist in humans, urinary recovery of 51Cr-EDTA may be useful in monitoring intestinal abnormalities associated with inflammation.

Knowledge of the cytology, ultrastructure and histochemistry of the small intestinal mucosa has advanced considerably over the last 20 years, particularly in regard to the changes associated with coeliac disease. Many of the known structural and cytological changes in coeliac mucosa are probably non-specific, and not directly related to its pathogenesis. It seems important to move away from purely descriptive images of mucosal abnormality such as "villous atrophy', and static measurements, such as crypt-villous ratios. Rather, the mucosa should be viewed as a dynamic, three-dimensional structure and evaluated in terms of total villous cell counts, crypt cell production rates, and so on. The organisation of the lamina propria is still poorly documented, and requires further exploration at the ultrastructural level. More thought should be given to the meaning of mucosal permeability and to its structural counterparts. The immunocytopathology of the coeliac lesion is far from understood; it is questionable whether local humoral activity is central to the pathogenesis of the condition. More needs to be learned of the role of T cells, not only in local mucosal reactions, but also in terms of possible regulatory effects on crypt cell kinetics, villous shape and hence mucosal structure. Increased mitotic activity of epithelial lymphocytes in coeliac disease appears to correlate exclusively with gluten-sensitivity and the use of this presumed immunological marker in the histological diagnosis, and thus prediction, of gluten-sensitised individuals is proposed in this paper.

Serum immunoglobulin A class antibodies reactive to the endomysial lining of the smooth muscle bundles of the gastrointestinal tract have recently been reported to be specific and sensitive indicators of celiac disease (CD). A total of 203 subjects were examined for serum endomysial antibodies (EmA) and in 103 small bowel biopsies were obtained. EmA were detected in 43 cases including 26 CD patients evaluated during the gluten challenge phase of diagnosis by European Society for Pediatric Gastroenterology and Nutrition criteria, 11 of 53 symptomatic patients, and 6 asymptomatic family members. All patients with detectable antibody at the time of biopsy exhibited grade III-IV villous atrophy. Disaccharidase activities performed in 19 cases revealed severe deficiencies. EmA were not detected in 160 subjects including 42 infants and children with chronic nonspecific diarrhea. Eighteen of these possessed grade II-III villous atrophy with moderate disaccharidase deficiency and 24 were found to have normal histology and enzymes. The EmA were also not detected in 3 CD patients who were well maintained on a gluten-free diet for greater than 1 year and 25 asymptomatic family members exhibiting normal histology and enzymes. An additional 90 infants and children with other gastrointestinal and liver diseases were also negative for the serum EmA. Fourteen of these patients underwent biopsies and were demonstrated to have normal histology.

Following allogeneic bone marrow transplantation, graft-versus-host disease (GVHD) develops when the foreign donor lymphoid graft mounts an immunologic reaction against the skin, liver, and gastrointestinal tract of the host. The GVHD syndrome is characterized by skin rash, hepatocellular dysfunction, and secretory diarrhea with destruction of intestinal mucosa. The gastrointestinal radiographic manifestations of proven GVHD were studied in 16 allogeneic marrow recipients transplanted for aplasia (nine) or leukemia (seven). The radiographic findings revealed three distinct phases that correlated with the duration of active gastrointestinal GVHD: (1) Acute phase-seven examinations were performed 4-15 days after the onset of gastrointestinal GVHD, 19-44 days posttransplant. There were simultaneous and uniform changes in the stomach through the small bowel consisting of thickened or flattened mucosal folds, thickening of the bowel wall, rapid transit, and excess luminal fluid. (2) Subacute phase-17 examinations were performed 13-96 days after the onset of gastrointestinal GVHD (40-118 days posttransplant). Abnormalities similar to those of the acute phase were noted, often with a striking segmental distribution. (3) Resolution phase-three patients, who earlier had sequential examinations, were studied when GVHD was no longer clinically active, 43-46 days after the onset of gastrointestinal GVHD (52-94 days posttransplant). These examinations showed improvement, with no abnormalities or effacement of mucosal folds. Mural thickening was confined to the terminal ileum. Gastrointestinal GVHD resolved in the three survivors; it persisted until death in nine of 13. The pathogenic mechanisms and differential diagnosis of the radiographic abnormalities are discussed.

A 13-year-old boy with common variable hypogammaglobulinemia and type I diabetes developed a severe enteropathy that proved to be unresponsive to any treatment, including total parenteral nutrition. No evidence of known etiologies of malabsorption and/or secretory diarrhea was found in this subject. A high titer of complement-fixing enterocyte autoantibody was persistently found in the patient's serum. These features suggest that the enteropathy of this primarily immunodeficient subject had an autoimmune origin. A cycle of cyclophosphamide failed to show any amelioration of the diarrhea or a significant decrease in the autoantibody titer.

Young rats (10- and 21-day-old) were given gliadin by intragastric application, in the form of a 5% and 0.5% solution. A 5% gliadin (1 ml) was intolerable for young rats, destroying the structure of their jejunal mucosa. A 0.5% gliadin (1 ml) was well tolerated by 21-day-old animals and caused no changes in enterocytes. Repeated administration of 0.5% gliadin on days 0 and 17 caused an increased lymphocyte infiltration in the lamina propria and an increase in the number of cells producing IgA immunoglobulins. Repeated intragastric administration of 0.5% gliadin until 1 month of age, followed by a single administration of 0.5% gliadin at 2 months, caused shortening of the jejunal villi and changes in apical enterocytes. The most pronounced immunological changes were observed in these repeatedly treated animals. Increased numbers of lymphocytes producing IgG in the lamina propria were found and the intestinal contents of these animals exhibited an increased level of IgG and IgA anti-gliadin antibodies when compared to control rats. The results indicate that some morphological and immunological changes observed in young rats fed with gliadin resemble those observed in patients with coeliac disease. The described experimental model is supposed to be suitable for studying the pathogenetic aspects of human coeliac disease.