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Biomedical subjects

S Fais

Publications and source records attributed to S Fais.

71 records · Page 4Linked to original sources

Effects of high in vivo levels of vasoactive intestinal polypeptide on function of circulating lymphocytes in humans.

To examine the possible in vivo significance of the immunomodulatory effects of vasoactive intestinal polypeptide described in vitro, several parameters of peripheral blood lymphocyte function were studied in a patient with a pancreatic endocrine tumor and high circulating levels of vasoactive intestinal polypeptide. There was no imbalance of the circulating lymphocyte subpopulations, and the in vitro responses of the patient's lymphocytes to mitogens were normal. However, there was an increased number (32%) of peripheral lymphocytes expressing interleukin 2 receptor. Serum immunoglobulin M levels were higher than in controls, and the patient's lymphocytes exhibited a spontaneous in vitro immunoglobulin M production higher than normal. Comparable increases in both interleukin 2 receptor expression and immunoglobulin M production were induced in vitro in normal peripheral lymphocyte cultures by the addition of vasoactive intestinal polypeptide concentrations similar to that detected in the patient's plasma. These findings indicate that a modulatory effect of vasoactive intestinal polypeptide on lymphocyte activation and immunoglobulin synthesis may be operating in vivo. They also suggest that vasoactive intestinal polypeptide does not mediate major defects in peripheral blood lymphocyte function in vivo.

Adenoma, Islet Cell↗

Ability of human colonic epithelium to express the 4F2 antigen, the common acute lymphoblastic leukemia antigen, and the transferrin receptor. Studies in inflammatory bowel disease and after in vitro exposure to different stimuli.

We investigated the ability of isolated human colonic epithelial cells to express the common acute lymphoblastic leukemia antigen (CALLA), the transferrin receptor, and the 4F2 antigen in response to different types of stimuli. The expression of these markers was assessed by immunofluorescence using monoclonal antibodies. Thirty-two percent of freshly isolated colonic epithelial cells from actively inflamed mucosa of patients with inflammatory bowel disease expressed the 4F2 antigen, 28% the transferrin receptor, and 13% the CALLA. Normal colonic epithelial cells were cultured and the kinetics of expression of the three antigens was studied. A significant increase in the expression of the three markers was observed throughout the culture period in response to the lectin phytohemagglutinin and the epidermal growth factor. The kinetics of expression of the 4F2 antigen and the CALLA after lectin stimulation appeared to differ from that observed after epidermal growth factor. At the end of the cultures one-third of the cells expressed the 4F2 antigen and the transferrin receptor, whereas one-fifth were positive for CALLA. Thus, after these cultures the expression of the three markers was quantitatively similar to that observed with freshly isolated cells from inflamed mucosa. gamma-Interferon markedly induced the 4F2 antigen but had no effect on the transferrin receptor and the CALLA. These data demonstrate that colonic epithelium is capable of expressing the 4F2 antigen and the CALLA in association with the transferrin receptor.

Antibodies, Monoclonal↗

The clinical significance of serum C reactive protein levels in Crohn's disease. Results of a prospective longitudinal study.

We measured the serum C reactive protein (CRP) levels by a sensitive immunochemistry method in 101 outpatients with Crohn's disease enrolled in a prospective longitudinal study. At entry, 51 of the 101 patients had raised CRP levels, which showed good correlation with the clinical score. However, one-third of the patients with clinically active disease had normal CRP while one-third of the patients in clinical remission had a raised CRP. The longitudinal study showed that (a) in patients with active disease, CRP levels tended to decrease as the disease went into remission; (b) in patients who achieved remission, the likelihood of clinical relapse after 2 years of entry was higher in those with persistently raised CRP than in those with persistently normal CRP; and (c) in patients with quiescent disease at entry who remained in remission throughout the first year of the study, the likelihood of clinical relapse during the second year of the study was higher for those with persistently raised CRP than for the others. This study confirms that serum CRP is a useful laboratory index for supplementing clinical scores in patients with Crohn's disease, in monitoring the response to treatment, in helping to predict the course of the disease, and in contributing to defining subgroups of patients.

C-Reactive Protein↗

HLA-D region antigens on isolated human colonic epithelial cells: enhanced expression in inflammatory bowel disease and in vitro induction by different stimuli.

Colonic epithelial cells (CEC) were isolated from actively inflamed mucosa of IBD patients and checked for HLA-DR, HLA-DP, and HLA-DQ. Half of the freshly isolated CEC from IBD tissue expressed DR, and one third were positive for DP and DQ. Normal human CEC were then cultured for 24 h and their expression of these markers in response to different types of in vitro stimulation was investigated. A significant increase in the expression of DR, DP and DQ was observed in response to the nonspecific mitogen phytohaemagglutinin (PHA), the lymphokine gamma-interferon (gamma-IFN) and the epidermal growth factor (EGF). The enhancement of DR expression was more marked than that of DP and DQ. The effect of gamma-IFN was more rapid and significantly more marked than that of either PHA and EGF for all three antigens. EGF appeared to be more potent than PHA in enhancing the expression of DP and DQ. The data from this study indicate that HLA-D region antigens can be induced on human CEC by different types of stimuli and provide further evidence that the expression of these markers in the colonic epithelium is a normal event the magnitude of which can increase under various circumstances. The data also suggest that the increased expression of HLA-D region antigens by IBD CEC occurs as a result of different mechanisms, and that this expression is an indicator of the active participation of the colonic epithelium to the mucosal inflammatory response.

Cells, Cultured↗

Peripheral and intestinal lymphocyte activation after in vitro exposure to cow's milk antigens in normal subjects and in patients with Crohn's disease.

We studied in Crohn's disease and controls the in vitro activation of either peripheral (PBMNC) or intestinal (LPMNC) mononuclear cells in response to the cow's milk antigen beta-lactoglobulin (Blg). The activation of mononuclear cells was investigated by analyzing the kinetics of the transferrin receptor (T9 antigen) and interleukin 2 receptor (Tac antigen) expression. In both controls and Crohn's disease patients Blg (1 microgram/ml) induced a significant (P less than 0.01) increase of T9 and Tac expression by both PBMNC and LPMNC cultured for 3 days. After Blg exposure the counts of T9- and Tac-bearing cells were significantly (P less than 0.05) higher in PBMNC cultures from healthy controls than in those from patients with Crohn's disease. In both groups peripheral T-enriched cell suspensions did not express T9 and Tac when stimulated with Blg but were restored to express either antigen by the addition of 10% autologous adherent cells. In LPMNC cultures from patients with Crohn's disease the Tac expression after 3 days of Blg stimulation was significantly (P less than 0.05) higher than in the autologous PBMNC. Data from this study indicate that in both controls and patients with Crohn's disease lymphocytes sensitized to Blg occur in the circulation as well as in the gut lamina propria. Our data also suggest that in Crohn's disease an increased proportion of lymphocytes sensitized to Blg are recruited from the circulation into the site of the intestinal lesion.

Adult↗

Activation of peripheral blood and intestinal lamina propria lymphocytes in Crohn's disease. In vivo state of activation and in vitro response to stimulation as defined by the expression of early activation antigens.

In the present study the state of activation of either peripheral blood and intestinal lamina propria mononuclear cells in Crohn's disease was defined by investigating the expression of early activation antigens (namely the 4F2 antigen, the transferrin receptor and the interleukin-2 receptor). The expression of 4F2 and T9 antigens was greatly increased--in the peripheral blood and in the intestinal lamina propria whereas the proportion of interleukin-2 receptor bearing cells was much less pronounced. The counts of early activation antigens bearing cells in the lamina propria were quite comparable with those of the autologous peripheral cells. In the peripheral blood counts of 4F2 and T9 positive cells were very high in patients with active Crohn's disease but patients with quiescent disease also had a significantly raised proportion of 4F2 and T9 bearing cells. Only in those patients with no evidence of macroscopic disease (namely those resected without recurrence) the counts of early activation antigens bearing cells were within the normal range. The in vitro mitogen induced expression of early activation antigens on either peripheral and intestinal mononuclear cells of patients with Crohn's disease proved to be both quantitatively and qualitatively similar to that of the controls showing the full expression of 4F2, transferrin receptor, and interleukin-2 receptor. While demonstrating that in Crohn's disease there was no intrinsic defect of generation and expression of growth factors receptors by peripheral and intestinal lymphocytes, these results showed that there was a divergence in the expression of early activation antigens in vivo and in vitro. This would indicate that in Crohn's disease there is an in vivo increased population of preactivated rather than fully activated lymphocytes consisting of 4F2 and T9 bearing cells. The high proportion of these cells in the peripheral blood and in the intestine suggests that a chronic immune activation is present in these patients outside as well as within the affected bowel.

Adult↗

Lymphocyte activation by B. subtilis spores.

The in vitro effect of Bacillus Subtilis spores (BSs) on lymphocyte activation was investigated by analyzing the kinetics of expression of the activation antigens MLR3, MLR4 and HLA-DR in cultures of peripheral mononuclear cells. It was found that BSs over a wide range of concentrations are capable of inducing an increased expression of these three markers and that at high BSs concentration the effect is both quantitatively and qualitatively similar to that induced by the mitogens PHA and ConA. These results suggest that T cells may be involved in the response to Bss.

Bacillus subtilis↗

HLA-DR antigens on colonic epithelial cells in inflammatory bowel disease: I. Relation to the state of activation of lamina propria lymphocytes and to the epithelial expression of other surface markers.

The colonic epithelial expression of HLA-DR molecules and of other markers of cell membrane perturbation was investigated by immunofluorescence in biopsy specimens from patients with ulcerative colitis and Crohn's disease. It was found that in virtually all specimens from either groups showing active inflammation there was a diffuse epithelial expression of HLA-DR molecules. There was no relation between the grading of active inflammation and the epithelial expression of HLA-DR antigens. The epithelium of virtually all specimens from the macro and microscopically uninvolved areas of patients with active colitis and from patients with histologically quiescent colitis showed no detectable expression of HLA-DR molecules. The counts of isolated lamina propria lymphocytes expressing the transferrin receptor and the interleukin 2 receptor were higher in specimens with HLA-DR+ epithelium than in those with a HLA-DR- epithelium. Twenty-nine of the 35 (83%) HLA-DR positive specimens proved to express the 4F2 antigen on their epithelium and 19 (54%) were positive for the transferrin receptor. All sections positive for either the 4F2 antigen or the transferrin receptor were also HLA-DR positive while all HLA-DR negative sections were also negative for either of the two other markers. Data in this study suggest that in active IBD the epithelial participation in active inflammation is associated with a sequence of cell membrane rearrangements, and that the expression of HLA-DR molecules is a part of this sequence.

Antigens, Surface↗

Raised serum levels of IgM-rheumatoid factor and anti-F(ab')2 autoantibodies in patients with active inflammatory bowel disease.

The serum levels of IgM-Rheumatoid Factor and of anti-F(ab')2 autoantibodies were investigated in patients with inflammatory Bowel Disease (IBD) by sensitive radioimmunoassays. Serum levels of the 2 autoantibodies were significantly increased in active IBD. In patients with Crohn's Disease raised titers of the 2 antibodies appeared to be also related to colonic involvement. There was, in Crohn's Disease, a significant association between concordantly positive results with the 2 assays and the occurrence of systemic complications. Immunocomplexes detected by the C1q-SP method were higher in sera of Crohn's Disease patients with raised IgM-RF than in the others. Data from the present investigation indicate that in active IBD and particularly in Crohn's Disease autoantibodies directed against different parts of the immunoglobulin molecule may be produced. These findings add support to the concept that an in vivo polyclonal B-cell activation may occur in these patients.

Adult↗

Isotypic analysis of antibody response to a food antigen in inflammatory bowel disease.

We studied the class-specific antibody response to the cow's milk antigen beta-lactoglobulin (beta-LG) in sera from patients with ulcerative colitis and Crohn's disease. IgG and IgM to beta-LG were significantly higher in patients when compared to healthy non-atopic controls, whereas IgA values were similar, and specific IgE absent in all groups. No correlation between IgG- or IgM-containing immune complexes was found with the corresponding isotype of antibody to beta-LG; however, IgM complexes correlated with serum total IgM in ulcerative colitis. In these patients, IgG antibodies were higher in active cases, whereas IgM increased in patients without signs of disease activity. Antibody titers did not correlate with disease duration or administration of antiinflammatory drugs. This pattern of anti-beta-LG reactivity suggests that the presence of intestinal lesions may be revealed by the selective increase of some antibody isotypes to orally administered antigens. Enhanced mucosal permeability may be studied by this type of serological analysis.

Adrenal Cortex Hormones↗

T cell early activation antigens expressed by peripheral lymphocytes in Crohn's disease.

We studied the expression of early activation antigens (4F2, transferrin receptor, IL-2 receptor) on peripheral lymphocytes (PBL) of patients with Crohn's Disease. We have found that the proportion of PBL expressing these antigens was significantly higher in patients than in controls. The expression of the 4F2 antigen was more pronounced than that of other activation antigens directly involved in promoting cell growth (e.g. transferrin receptor, IL-2 receptor). These results indicate that CD patients have an increased number of T cells in a very early phase of activation.

Adult↗

T cell differentiation antigens expressed by peripheral blood lymphocytes in Crohn's disease.

The aim of the present study was to investigate whether an imbalance of peripheral blood immunoregulatory T cells is a feature of Crohn's disease. The cluster of differentiation antigens 3,4 and 8 were investigated and the relative prevalence of PBL expressing each antigen was defined using a panel of three monoclonal antibodies (OKT3, OTK4 and OKT8). A significant decrease in the OKT3 and OKT4 positive cells was found in CD patients as compared with healthy controls. No significant difference was observed between patients and controls in the proportion of T8 positive cells and in the T4/T8 ratio. While confirming a significant decrease of circulating total resting T cells in patient with CD, the results of this study indicate that the disease is not primarily related to an imbalance of the proportion of the T cells subsets.

Adult↗

Studies of peripheral blood lymphocytes in Crohn's disease. Circulating activated T cells.

Peripheral blood mononuclear cells have been investigated in 43 patients with Crohn's disease (CD) by means of a panel of 4 monoclonal antibodies (UCHT1, UCHT4, 4F2, 5E9). A decrease of total T cells (UCHT1+) (p less than 0.01) and a slight increase of cytotoxic/suppressor T cells (UCHT4+) were observed. Evidence of T-cell activation, as shown by the highly significant increase of 4F2+ and 5E9+ cells, was also found. The latter finding lends support to the concept that cell-mediated immune phenomena are an important feature in CD.

Adult↗

Murine interferon-alpha1 gene-transduced ESb tumor cells are rejected by host-mediated mechanisms despite resistance of the parental tumor to interferon-alpha/beta therapy.

The highly metastatic ESb tumor is totally resistant to murine interferon-alpha/beta (IFN-alpha/beta) therapy, regardless of the number of cells injected or the route of inoculation. In contrast, as we show herein, mouse IFN-alpha1-transduced ESb tumor cells were inhibited markedly when injected subcutaneously into immunocompetent mice. IFN-producing ESb tumor rejection was mediated by the immune system, because these tumor cells grew normally in immunosuppressed mice. Tumor regression was accompanied by extensive necrosis and cellular infiltrates in the tumor area. These results further support the use of IFN-alpha in cytokine gene therapy of cancer and suggest the advantage of using gene transfer rather than cytokine administration to enhance an antitumor immune response.

Animals↗

Antibacterial drugs in Crohn's disease.

The evidence of a beneficial role of antibacterial drugs in Crohn's disease is largely empirical. Data accumulate to show that these drugs may well be used as an adjunctive therapy to oral anti-inflammatory drugs. Circumstantial evidence has also been provided that antibacterial drugs are effective in relieving symptoms related to bacterial overgrowth and when used for specific indications such as perianal lesions.

Anti-Bacterial Agents↗