Biomedical subjects

N Lügering

Publications and source records attributed to N Lügering.

At least 37 records · Page 2Linked to original sources

PubMed1999

Interleukin (IL)-13 and IL-4 are potent inhibitors of IL-8 secretion by human intestinal epithelial cells.

Intestinal epithelial cells are able to produce soluble mediators that initiate or amplify inflammatory events in the intestinal mucosa. Interleukin (IL) -8 is suggested to be a cytokine playing a major role during the acute and chronic processes in inflammatory bowel disease (IBD). TH-2 cytokines have been described as down-regulating the inflammatory response. We analyzed the effects of IL-10, IL-13, and IL-4 on IL-8 secretion in intestinal epithelial cells. The human colonic epithelial cell line Caco-2 and freshly isolated intestinal epithelial cells were used. Cells were stimulated with IL-1beta after treatment with TH-2 cytokines. Levels of IL-8 were determined by employing enzyme-linked immunosorbent assay (ELISA). Stimulation with IL-1beta results in a time-dependent IL-8 secretion. The addition of IL-4 and IL-13, but not IL-10, to activated epithelial cells resulted in a strong decrease in IL-8 secretion. Maximal inhibition required that TH-2 cytokines be added up to 60 min before or simultaneous with stimulatory agents. We present novel findings that IL-4 and IL-13 strongly down-regulate IL-8 secretion from intestinal epithelial cells. A microenvironment containing high concentrations of IL-4 and IL-13 may alter the recruitment of immune cells to enterocytes at least partly by inhibiting IL-8 production. This inhibition might diminish the severity of the intestinal inflammatory response and, thus reduce clinical disease activity.

Caco-2 Cells↗

PubMed1999

Interleukin-15 strongly inhibits interleukin-8 and monocyte chemoattractant protein-1 production in human colonic epithelial cells.

Interleukin-15 (IL-15) is a novel cytokine with actions similar to IL-2 because of common receptor components. Although IL-15 is expressed in colonic epithelial cells and may regulate epithelial cell function, its effects on these cells are not fully defined. We explored the regulatory effects of IL-15 on IL-8 and monocyte-chemoattractant protein-1 (MCP-1) production in the colonic epithelial cell line Caco-2 as well as in freshly isolated human colonic epithelial cells. IL-15 was added to intestinal epithelial cells under various culture conditions. Levels of chemokines were determined by enzyme-linked immunosorbent assay. To determine the elements of the IL-2/IL-15R complex involved we used neutralizing antibodies specific for individual receptor chains. IL-15 down-regulates IL-8 and MCP-1 production in Caco-2 cells as well as in freshly isolated human colonic epithelial cells in a dose-dependent manner. Intestinal epithelial cells became more responsive to IL-15-induced suppression when activated with greater IL-1 doses. Strong chemokine suppression was seen when IL-15 was given prior to, simultaneous with, or after stimulatory agent. Anti-IL-2Rgamma antibodies efficiently blocked (82% inhibition) the suppression induced by IL-15, while anti-IL-2Rbeta antibodies were less effective. The involvement of beta-chain was further suggested by the finding that a mixture of both monoclonal antibodies (mAb) at a suboptimal concentration (1 microgram/ml of each mAb) produced a synergistic inhibitory effect on down-regulation of epithelial chemokine production. These results show that IL-15 can suppress IL-8 and MCP-1 secretion by intestinal epithelial cells. A microenvironment containing high concentrations of IL-15 may alter the recruitment of neutrophils to enterocytes at least partly by inhibiting IL-8 and MCP-1 production.

Antibodies, Monoclonal↗

PubMed1998

Decreased HER-2 tyrosine kinase expression in rectal mucosa of FAP patients following low-dose sulindac chemoprevention.

As a part of the mechanisms of action in reversing FAP adenomas by the low-dose sulindac maintenance therapy (2 x 25 mg/patient per day), the extent of HER-2 proto-oncogene expression in the rectal mucosa seems to be of interest. Immunocytochemical analyses were performed in plasma and in rectal tissue of sulindac-treated FAP patients during an 18 months follow-up and compared with rectal tissue of patients with FAP, Crohn's disease, or rectal cancer or with healthy volunteers. HER-2 was significantly reduced and maintained in tissue under sulindac chemoprevention below base line levels of healthy individuals, but not in plasma. Therefore, a direct or indirect effect of sulindac as a tyrosine kinase inhibitor may be implicated. During NSAID treatment HER-2 protein expression as a prognostic tool seems to be of little clinical relevance.

Adenomatous Polyposis Coli↗

PubMed1998

IL-10 synergizes with IL-4 and IL-13 in inhibiting lysosomal enzyme secretion by human monocytes and lamina propria mononuclear cells from patients with inflammatory bowel disease.

Tissue injury and inflammation in inflammatory bowel disease (IBD) are associated with enhanced monocytic lysosomal enzyme release. In this study, peripheral monocytes and lamina propria mononuclear cells (LPMNC) were isolated from IBD patients and normal controls. Cells were stimulated with lipopolysaccharide after treatment with IL-13, IL-4, and IL-10, and enzyme secretion was assessed by using the corresponding p-nitrophenyl glycosides as substrates. Molecular forms of cathepsin D were examined to describe the mode of enzyme release. IL-10 and IL-4 strongly down-regulate enzyme secretion in IBD monocytes. IBD monocytes showed a diminished responsiveness to the inhibitory effect of IL-13. Impaired monocyte response was not found with combinations of IL-13 and IL-10 or IL-4 and IL-10. LPMNC from involved IBD mucosa showed significantly higher enzyme secretion compared with LPMNC from noninvolved IBD mucosa but responded inefficiently to either IL-4, IL-13, or IL-10 alone. However, combined treatment with IL-10 and IL-4 or IL-10 and IL-13 strongly suppressed enzyme release by these cells. Both the precursor and mature forms of cathepsin D were elevated in IBD patients. While IL-13 reduced mainly the precursor form, the effect of IL-4 and IL-10 concerns both the precursor and mature form of cathepsin D. Our results favor the potent clinical utility of combined treatment, thus improving chances of developing effective treatments for human IBD.

Adult↗

PubMed1998

IL-4, IL-10 and IL-13 down-regulate monocyte-chemoattracting protein-1 (MCP-1) production in activated intestinal epithelial cells.

Several studies have demonstrated that intestinal epithelial cells play a major role in the initiation and perpetuation of intestinal inflammation by secreting proinflammatory cytokines and chemokines. MCP-1 is suggested to be a chemokine that plays a major part during intestinal inflammation in inflammatory bowel disease (IBD). Immunoregulatory cytokines such as IL-4, IL-10 and IL-13 have been described to exert anti-inflammatory properties on various cell types. The aim of our study was to determine the effect of Th2 cytokines on the production of MCP-1 by activated intestinal epithelial cells. We examined Caco-2 cells as well as intestinal epithelial cells which were isolated from surgical specimens. Production of the chemokine MCP-1 was determined under stimulated and non-stimulated conditions. IL-4, IL-10 and IL-13 were added to stimulated epithelial cells under various culture conditions. Supernatants were analysed for cytokine concentrations using ELISAs. Under stimulation with physiological agents like IL-1beta or tumour necrosis factor-alpha (TNF-alpha), we observed markedly increased concentrations of MCP-1 in supernatants of Caco-2 cells and intestinal epithelial cells. IL-4, IL-10 and IL-13 all had the capacity to down-regulate the production of MCP-1 in Caco-2 cells as well as in freshly isolated epithelial cells. Caco-2 cells which were primed with Th2 cytokines 24 h before stimulation were subsequently decreased in their ability to be stimulated by IL-1beta or TNF-alpha for MCP-1 production. As MCP-1 has been shown to play a major role during intestinal inflammation, the in vitro suppression of MCP-1 in enterocytes suggests the in vivo use of regulatory cytokines in patients with active IBD.

Caco-2 Cells↗

PubMed1998

Human intestinal epithelial cells down-regulate IL-8 expression in human intestinal microvascular endothelial cells; role of transforming growth factor-beta 1 (TGF-beta1).

Cytokines produced from intestinal epithelial cells may function as signals to neighbouring immune cells. In the present study we analysed the effects of colonic epithelial cell lines (HT-29, Caco-2, HCT-116, Colo-320) and freshly isolated intestinal epithelial cells on IL-8 expression in the SV-40T transfected human microvascular endothelial cell line (HMEC-1). Epithelial cell-conditioned media and transwells preventing physical contact between epithelial and endothelial cells were used. TGF-beta1 and IL-8 levels were determined by ELISA and Northern blot analysis. Increasing concentrations of IL-1beta led to increasing production of IL-8. The addition of epithelial cell-conditioned medium or epithelial cells to HMEC-1 cells in a two-compartment co-culture system resulted in a strong decrease in IL-8 at the protein and mRNA level. Decrease of IL-8 was markedly stronger when epithelial cells were co-cultured in contact with HMEC-1 cells, indicating that not only soluble factor(s) play a role in the induction of IL-8 suppression in HMEC-1 cells. MoAbs against TGF-beta1 partially inhibited down-regulation of endothelial IL-8 expression. In further studies, IL-8 expression in freshly isolated human intestinal microvascular endothelial cells (HIMEC) was also down-regulated by intestinal epithelial cells. Our results demonstrate that intestinal epithelial cells down-regulate IL-8 expression in HMEC-1 cells. TGF-beta1 is a candidate factor of epithelial-endothelial communication in the colonic mucosa.

Caco-2 Cells↗

PubMed1998

Human intestinal M cells exhibit enterocyte-like intermediate filaments.

BACKGROUND: The derivation and ultrastructural composition of M cells covering the lymphoid follicles of Peyer's patches is still unknown. Results from different animal models have shown that there are species specific differences in the composition of intermediate filaments between M cells and neighbouring enterocytes. Little is known, however, about intermediate filaments of human M cells. AIMS: To compare components of the cytoskeleton of human M cells with those of adjacent absorptive enterocytes. METHODS: The expression and localisation of different cytokeratins, vimentin, and desmin in M cells was determined on follicle associated epithelia of human appendix using immunohistochemistry and immunogold electron microscopy. RESULTS: Cytokeratins specific for human intestinal epithelial cells such as cytokeratins 8, 18, 19, and 20 were expressed in both absorptive enterocytes and M cells with no differences in intensity and cellular distribution between both cell types. Vimentin and desmin, tissue specific markers of either mesenchymal or myogenic cells, as well as other cytokeratins were not detectable in enterocytes or M cells. CONCLUSION: This is the first study on the structure of intermediate filaments in human intestinal M cells. Our results show that in contrast to several animal models, human M cells apparently do not differ from adjacent enterocytes in the composition of their intermediate filament cytoskeleton. The presence of enterocyte like cytokeratins and the absence of other cytokeratins as well as of vimentin and desmin supports the hypothesis of an epithelial origin of human intestinal M cells and suggests that M cells may derive from differentiated enterocytes.

Adult↗

PubMed1998

[A system of nonspecific defense in chronic inflammatory bowel diseases--pathophysiologic and therapeutic aspects].

Monocytes/macrophages are a prominent feature of the inflammatory infiltrate in inflammatory bowel disease (IBD). Progress in the development of monoclonal antibodies has provided a powerful means to identify and study various subsets of macrophages in the intestinal mucosa. In both Crohn's disease and ulcerative colitis distinct macrophage populations have been found being prominent in active disease, but absent from normal mucosa. Studies of our group show that the Ca(2+)-binding proteins MRP8 and MRP14 as well as their heterocomplex MRP8/14 (27E10 epitope) can be immunolocalized in the majority of granulocytes and macrophages in active but not inactive IBD. Serum MRP8/14 concentrations are significantly increased in patients with active IBD compared with patients suffering from inactive/mild disease. In vitro studies revealed that IL-13, IL-10 and IL-4 strongly suppress secretion of monocytic proteins. Differential responses of monocytes and macrophages towards the inhibitory effects of TH2-cytokines can be observed in both patients with IBD and control groups. Combined treatment with TH2-cytokines may effectively suppress the response of activated monocytes/macrophages thus being of potential therapeutic benefit for patients with IBD.

Antigens, Differentiation↗

PubMed1998

Current concept of the role of monocytes/macrophages in inflammatory bowel disease--balance of proinflammatory and immunosuppressive mediators.

Macrophages are important in providing the first line of intestinal defence against microorganisms or toxins that break the epithelial barrier, by presenting antigen to sensitised T cells and releasing a variety of cytokines and inflammatory mediators. During active states in inflammatory bowel disease, large numbers of monocytes leave the bloodstream and migrate into the inflamed mucosa and submucosa. Phenotypic studies have previously shown the presence of much more marked macrophage heterogeneity in inflammatory bowel disease mucosa than in normal mucosa. In both Crohn's disease and in ulcerative colitis, distinct macrophage populations have been found, being prominent in active disease, but absent from normal mucosa. Studies in our institution have shown that the Ca(2+)-binding proteins MRP8 and MRP14 as well as their heterocomplex MRP8/14 (27E10 epitope) are expressed in the majority of granulocytes and macrophages in active but not inactive inflammatory bowel disease. Furthermore, a strong complex MRP8/14 immunoreactivity was present in epithelial cells of the terminal ileum adjacent to ulcerative and fissuring lesions, while epithelial cells of large bowel tissues were consistently negative. In vitro studies revealed that interleukin-13, interleukin-10 and interleukin-4 strongly suppress secretion of different monocytic proteins. A combination of TH2-cytokines even at suboptimal concentrations significantly suppressed protein secretion, much more than using interleukin-13, interleukin-10 or interleukin-4 at a double concentration alone. Our morphological findings demonstrate the presence of MRP8/14 (27E10 antigen) both in monocytes/macrophages and in epithelial cells in active inflammatory bowel disease. Systemic or topical application of combined cytokine treatment might be a new effective therapeutic approach for chronic inflammatory bowel disease especially in those cases in which monocytes/macrophages lose their ability to respond, to some degree, to anti-inflammatory cytokines.

Animals↗

PubMed1997

Cytomegalovirus encephalomyelomeningoradiculitis in acquired immunodeficiency syndrome (AIDS).

Acute inflammatory polyradiculitis represents an uncommon peripheral nerve complication during HIV infection. The case of an HIV-seropositive patient who was admitted to hospital for a cauda equina syndrome is reported. Despite early application of anticytomegalic medication, a cytomegalovrirus (CMV) infection spread out to the central nervous system (CNS), causing the patient's death. A post-mortem examination confirmed the diagnosis of CMV-encephalomyelomeningoradiculitis. To the authors' knowledge, such a progress of a CMV-related polyradiculitis to an encephalomyelomeningoradiculitis has not yet been described. The clinical features of this case will aid in the recognition of CMV-related neurological complications, and may permit earlier and perhaps more successful treatment.

AIDS-Related Opportunistic Infections↗

PubMed1997

Synergistic effect of immunoregulatory cytokines on peripheral blood monocytes from patients with inflammatory bowel disease.

Active inflammatory bowel disease (IBD) is characterized by increased monocyte secretion of proinflammatory cytokines. Immunoregulatory cytokines such as Interleukin (IL)-4, IL-10, and IL-13 are capable of inhibiting the proinflammatory cytokine response of activated monocytes. The aim of our study was to determine the effect of different antiinflammatory cytokines under various culture conditions and to evaluate combinations of antiinflammatory cytokines in down-regulating monocyte response in IBD. Peripheral monocytes from patients with active IBD were isolated and stimulated with pokeweed mitogen (PWM). IL-4, IL-10, IL-13 and a combination of IL-4/IL-10 and IL-10/IL-13 were added at different concentrations and different times. Secretion of IL-1beta and TNF-alpha was assessed using sandwich ELISA systems. There was a diminished down-regulation of TNF-alpha by IL-4 and IL-13 in IBD when the cytokines were added at the time of stimulation, while there was a significantly higher down-regulation when monocytes were primed with these Th-2 cytokines 24 hr before activation. IL-10 plus IL-4 and IL-10 plus IL-13, respectively, inhibited the proinflammatory cytokine response of monocytes as well as matured macrophages much more than IL-4, IL-10, or IL-13 alone. Even at suboptimal concentrations for each cytokine alone, a combination of cytokines showed synergistic inhibitory effects. In summary, a combination of antiinflammatory cytokines is more effective in down-regulating the response of activated monocytes than using the cytokines alone and thus may have a potential therapeutic benefit for patients with IBD.

Cells, Cultured↗

PubMed1997

Importance of combined treatment with IL-10 and IL-4, but not IL-13, for inhibition of monocyte release of the Ca(2+)-binding protein MRP8/14.

Expression of the two myeloic related proteins MRP8 and MRP14 is restricted to distinct stages of monocytic differentiation. Heterodimeric MRP8/14 complexes (27E10 antigen) have been shown to represent their biologically active forms. In this study, we investigated the effects of Th2-cytokines on release of these proteins from freshly obtained blood monocytes and monocytes cultured for 7 days in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF). Monocytes were stimulated with pokeweed mitogen (PWM) in the presence or absence of interleukin-13 (IL-13), IL-4 and IL-10, and secretion of MRP8, MRP14 and MRP8/14 was assessed by using a sandwich enzyme-linked immunosorbent assay system. Peripheral monocytes secreted significantly increased amounts of MRP14 and MRP8/14 but not MRP8 under stimulation with PWM. IL-10 and IL-4, but not IL-13, down-regulated the PWM-stimulated MRP8/14 secretion in a dose-dependent manner. Maximal inhibition required that IL-10 and IL-4 be added up to 1 h before or simultaneous with PWM. A combination of IL-10 and IL-4 even at suboptimal concentrations significantly suppressed protein secretion much more than using IL-10 or IL-4 at a doubled concentration alone. Peripheral monocytes cultured for 7 days in the presence of GM-CSF showed two-to threefold higher protein levels compared with freshly obtained blood monocytes but responded inefficiently to either IL-4, IL-13, or IL-10 alone. However, treatment with IL-10 in combination with IL-4 but not IL-13 strongly suppressed MRP14 and MRP8/14 release by these cells. The unresponsiveness of 7-day-cultured blood macrophages suggests that more differentiated and activated cells may lose their ability to respond to anti-inflammatory cytokines. Combined cytokine treatment may therefore more effectively control the progression of chronic inflammatory processes.

Antigens, Differentiation↗

PubMed1997

Colon carcinoma cell lines stimulate monocytes and lamina propria mononuclear cells to produce IL-10.

Cytokines released from tumour cells may have function as signals to neighbouring immune and inflammatory cells. Several studies have shown that the immunoregulatory cytokines IL-10 and transforming growth factor-beta1 (TGF-beta1) as well as prostaglandin-E2 (PGE2) play an important role in tumour-induced immunosuppression. The aim of the study was to investigate the effect of colon carcinoma cell lines on IL-10 production in peripheral monocytes (PBMC) and lamina propria mononuclear cells (LPMC). We examined four colon carcinoma cell lines (HT-29, Caco-2, Colo-320 and HCT-116) and determined their production of TGF-beta1, IL-10 and PGE2. Peripheral monocytes were isolated by density gradient centrifugation and LPMC were isolated from surgical specimens using a collagenase digestion method. Monocytes and LPMC were cultured with colon carcinoma cell conditioned medium or in co-culture with colon carcinoma cells. Supernatants were then determined for the production of IL-10 by ELISA assays. All colon carcinoma cell lines stimulated peripheral monocytes as well as LPMC to produce markedly increased levels of IL-10. Colon cancer cells secreted negligible levels of IL-10, but high amounts of TGF-beta1 and PGE2. Neutralization of TGF-beta1 by administration of anti-TGF-beta as well as neutralization of PGE2 with anti-PGE2 antisera reduced the IL-10 production of monocytes markedly, indicating that tumour cell-derived TGF-beta1 and PGE2 are major factors for IL-10 stimulation. In vitro stimulation of monocytes with TGF-beta1 and PGE2 could confirm that TGF-beta1 as well as PGE2 at picogram concentrations were able to prime monocytes for enhanced IL-10 production. Our results demonstrate that colon carcinoma cell lines enhance the ability of monocytes and intestinal macrophages to produce IL-10. The stimulation of monocyte IL-10 by colon cancer cell-derived TGF-beta1 and PGE2 may act as a tumour-protecting mechanism by impairing the activation of anti-tumour cytokines.

Carcinoma↗

PubMed1997

Colitis as the initial presentation of Wegener's granulomatosis.

Wegener's granulomatosis is a vasculitis which commonly presents with symptoms referable to the upper airway system, lungs, joints, eyes and kidneys. We present a case in which colitis combined with sinusitis could retrospectively be attributed as the initial manifestations of Wegener's disease.

Adult↗

PubMed1997

Differences in decorin and biglycan expression in patients with gastric ulcer healing.

BACKGROUND: The small interstitial proteoglycans decorin and biglycan have been shown to interact with various extracellular matrix molecules and with transforming growth factor-beta. These interactions are proposed to be important for tissue repair, as the former interactions may affect the diameter and spacing of collagen fibrils, and the latter interaction the proliferation and differentiation of cells embedded in the matrix. The aim of this study is to localize these proteoglycans in the stomach and to investigate their suitability as potential markers of extracellular matrix activity in gastric lesions. METHODS: Immunohistochemical techniques and in situ hybridization were used to study the phenotypic expression of these two proteoglycans in routinely processed specimens of human stomach tissue from 8 patients with gastric ulcer and 10 healthy control persons. RESULTS: In normal gastric tissue, immunostaining for both proteoglycans was found in the interstitium, with a more pronounced staining in the pylorus region than in the corpus area. In addition, biglycan showed a strong staining of parietal cells. In specimens of healing gastric ulcers a larger deposition of decorin throughout scar tissue could be shown, and a higher expression of decorin was also found by in situ hybridization. Biglycan was only found at the edges of the lesions. CONCLUSION: This study shows for the first time the presence of decorin and biglycan in human gastric mucosa. We also showed that these proteoglycans may be involved in the gastric ulcer healing processes.

Adult↗

PubMed1996

Immunoregulatory properties of IL-13 in patients with inflammatory bowel disease; comparison with IL-4 and IL-10.

Activated monocytes with increased expression of proinflammatory cytokines play a major role in inflammatory bowel disease (IBD). Immunoregulatory cytokines such as IL-4 and IL-10 can effectively suppress the proinflammatory response of activated monocytes. IL-13 is a recently described antiinflammatory agent in vitro. The aim of our study was to determine the in vitro immunosuppressive capacity of IL-13, IL-4 and IL-10 in patients with IBD. Peripheral blood monocytes were isolated from 27 patients with ulcerative colitis (UC), 27 patients with Crohn's disease (CD) and 16 healthy controls. Cells were stimulated with pokeweed mitogen (PWM) after treatment with IL-13, IL-4 and IL-10, and secretion of IL-1beta, tumour necrosis factor-alpha (TNF-alpha) and IL-6 was assessed using sandwich ELISA systems. Peripheral blood monocytes secreted significantly increased amounts of TNF-alpha and IL-6 under stimulation with PWM in patients with CD, while UC patients showed significantly elevated levels of IL-1beta. The antiinflammatory cytokines IL-13, IL-4 and IL-10 were all capable of inhibiting monocyte secretion of IL-1beta in a dose-dependent manner. With regard to IL-13 and IL-4, there was no significant suppression of TNF-alpha and IL-6 in patients with active IBD. By contrast, IL-10 was able to down-regulate all proinflammatory cytokines in active IBD as well as in controls. Proinflammatory cytokines from patients with inactive IBD could be significantly down-regulated by all three immunoregulatory cytokines. The inhibitory effect of IL-13 on TNF-alpha and IL-6 production in differentiated macrophages was diminished in IBD patients, as well as in controls. In disease controls we also observed a reduced inhibition of TNF-alpha and IL-6 after treatment with IL-13. In conclusion, the antiinflammatory activity of IL-13 is partially reduced in patients with active IBD. The hyporesponsiveness of activated and differentiated monocytes to IL-13 and IL-4 does not seem to be a disease-specific phenomenon.

Adolescent↗

PubMed1996

Crohn's disease (CD) patients suffering from peripheral arthritis or ankylosing spondylitis reveal restricted T cell receptor V beta regions in different temporal phases of disease.

Little is known about the mechanisms triggering and controlling both the development and perpetuation of extraintestinal complications in CD. The aim of the present study was to test the hypothesis that the T cell immune response in CD patients with joint complications may be altered when compared with patients without extraintestinal manifestations. We used a semiquantitative polymerase chain reaction assay to analyse the T cell antigen receptor repertoire in peripheral blood T cells from eight CD patients suffering from peripheral arthritis and ankylosing spondylitis, 12 CD patients without extraintestinal manifestations, and from seven non-CD patients with ankylosing spondylitis showing typical changes on joint radiographs. Being concerned that different patterns may be seen in different phases of the inflammatory disease process, we have also taken care to analyse sequential samples at various time points of the disease. Expression of all 22 V beta genes was found in each healthy control and in each CD patient without extraintestinal manifestations and showed no major variation over time. Southern hybridization analysis of amplified products revealed a highly restricted V beta repertoire in all CD patients suffering from peripheral arthritis and ankylosing spondylitis. In contrast, non-CD patients with ankylosing spondylitis without signs or symptoms of gastrointestinal problems demonstrated the presence of the entire V beta repertoire. Our longitudinal studies confirmed variable V beta usage over time, as certain transcripts were found only in distinct temporal phases of disease. Our data are not directly suggestive of a common superantigen model of CD, but instead emphasize a specific decrease in signals throughout the T cell receptor V beta repertoire in CD patients suffering from joint complications.

Adult↗

PubMed1996

Results and prognostic factors of splenectomy in idiopathic thrombocytopenic purpura.

BACKGROUND: Splenectomy is the therapy of choice after relapse following different immunosuppressive treatments for idiopathic thrombocytopenic purpura, which is still the most frequent cause of thrombocytopenia. STUDY DESIGN: A prospective clinical study was undertaken to evaluate the rate of complete remission in idiopathic thrombocytopenic purpura after splenectomy, to reveal the influence of preoperative immunosuppression on the postoperative course in groups of patients with different responses to treatment, and to describe possible prognostic factors predicting the postoperative course of idiopathic thrombocytopenic purpura. Difino's classification of remission was used. After fulfilling criteria for admission into the study, 72 patients who had undergone splenectomy (male to female ratio, 1:1.4) were examined. RESULTS: Early postoperative mortality and morbidity rates were 3 percent each. The following degrees of remission were achieved: complete remission, 72 percent; partial remission, 15 percent; partial remission affording further medical support, 6 percent; and no remission, 4 percent. Platelet counts differed significantly between complete and partial remission, but not between patients who did or did not experience a response to different preoperative medical strategies (Tukey-Kramer test, p < .05; t test, not significant). The correlation of megakaryocytopoiesis and the site of thrombocytolysis to the stages of remission was significant (Fisher's exact test). Patients with hyperplasia of splenic follicles had significantly higher platelet counts 2 years after operation than did those without hyperplastic splenic follicles (Student-Newman-Keuls test). CONCLUSIONS: Splenectomy is a low morbidity and low mortality procedure. It is, therefore, a treatment of choice after relapse following immunosuppressive courses. Isolated splenic thrombocytolysis and hyperplasia of megakaryocytopoiesis and of splenic follicles correlated with better postoperative outcome (ie, stable remission and platelet counts) and could serve as possible prognostic factors for the postoperative course in idiopathic thrombocytopenic purpura.

Adolescent↗