[Leptospirosis after a stay in Thailand]. / Leptospirose nach Thailand-Aufenthalt.

HISTORY AND ADMISSION FINDINGS: A 35-year-old man was admitted to our hospital with chills, headache, pain in the calves for five days and a bloody sputum. The day before he had returned from a 4-week trip to the north of Thailand. There he had participated in hiking trips and walked sometimes over wet fields with small skin injuries on his feet. The admission examination was uneventful except fever as high as 39 Celsius, particularly no rash, no conjunctivitis, no spleno- or hepatomegaly and no palpable lymph nodes could be noted. DIAGNOSTIC PROCEDURES: An x-ray of the chest showed confluent opacities, a bronchoscopy revealed diffuse alveolar hemorrhagy. Blood chemistry showed elevated liver enzymes, elevated kidney retention parameters and an increased C-reactive protein. An extended microbiological diagnostic procedure showed elevated antibody titers for leptospira and a PCR detected leptospira-DNA, representing acute leptospirosis. TREATMENT AND OUTCOME: After initiation of an antibiotic regimen including ceftriaxone and erythromycine the fever resolved immediately and the general condition improved. The patient could be discharged after two weeks in a good physical condition. CONCLUSION: The constellation of flu-like symptoms, hepatitis and nephritis, eventually escorted by bloody sputum, may suggest leptospirosis.

Acute CMV-colitis in a patient with a history of ulcerative colitis.

A symptomatic cytomegalovirus (CMV) infection usually occurs in patients with debilitating diseases, immunosuppression, transplantations and acquired immunodeficiency syndrome (AIDS). Gastrointestinal infections with CMV, especially colitis, are usually found in immunocompromised patients and rarely affect immunocompetent subjects. Here we report the case of a young female patient with a history of ulcerative colitis (UC) who presented with an acute attack of colitis caused by CMV infection. This was documented by the presence of CMV early antigen, antibodies and evidence of CMV in the colonic mucosa. After combined anti-inflammatory and antiviral treatment the patient recovered completely. As most attention is given to CMV-pathogeneity in immunocompromised patients, here we discuss the relationship to inflammatory bowel diseases.

Acute CMV-Colitis in a Patient with a History of Ulcerative Colitis.

A symptomatic cytomegalovirus (CMV) infection usually occurs in patients with debilitating diseases, immunosuppression, transplantations and acquired immunodeficiency syndrome (AIDS). Gastrointestinal infections with CMV, especially colitis, are usually found in immunocompromised patients and rarely affect immunocompetent subjects. Here we report the case of a young female patient with a history of ulcerative colitis (UC) who presented with an acute attack of colitis caused by CMV infection. This was documented by the presence of CMV early antigen, antibodies and evidence of CMV in the colonic mucosa. After combined anti-inflammatory and antiviral treatment the patient recovered completely. As most attention is given to CMV-pathogeneity in immunocompromised patients, here we discuss the relationship to inflammatory bowel diseases.

Cellular expression of CCK-A and CCK-B/gastrin receptors in human gastric mucosa.

Gastrin stimulates gastric acid secretion in various species, but the role of the structurally related CCK for the peripheral regulation of acid secretion in humans remains controversial. Moreover, species differences in CCK receptor function and expression have been reported. We therefore sought to identify the cellular targets of CCK and gastrin within the human gastric mucosa in situ. Gastric biopsies were collected from 15 patients without gastric disease. Expression of CCK receptor subtypes was detected in individual cells of the gastric mucosa by reverse transcription (RT)-PCR in situ, immunohistochemistry and confocal laser scanning microscopy, using antisera against the CCK-A or CCK-B/gastrin receptor subtype. Both CCK-A and CCK-B receptors were detected in antral and oxyntic mucosa at the mRNA and protein level. In fundic mucosa, CCK-A receptor mRNA and protein mapped to D cells (37.4+/-7.7). Besides, individual chief cells, mucous neck cells and parietal cells (12.3+/-4.7%) expressed CCK-A receptors. CCK-B/gastrin receptor mRNA and protein were detected in parietal cells (57.4+/-11.1%) and in neuroendocrine cells (33.2+/-4.4%) expressing chromogranin A. Furthermore, epithelial cells within the neck of the gastric gland were found to express the CCK-B/gastrin receptor. We conclude that (i) identification of CCK-A receptors on somatostatin producing D cells in humans provide the anatomical basis for a receptor-mediated mode of action of CCK on somatostatin release and (ii) detection of either CCK receptor subtype in the putative stem cell compartment implies a role of CCK in the maintenance of tissue homeostasis in human gastric mucosa.

[Intestinal tuberculosis: Easier overlooked than diagnosed]. / Darmtuberkulose: leichter zu übersehen als zu sichern.

Intestinal tuberculosis: Easier overlooked than diagnosed. The medical history of two Asian immigrants suffering from intestinal tuberculosis demonstrates the difficulties in finding the correct diagnosis. Intestinal tuberculosis resembles Crohn's disease with regard to clinical symptoms, macroscopic and microscopic intestinal findings. Sonographic, radiologic, endoscopic, and histological examinations facilitate distinguishing both entities. Diagnosis of intestinal tuberculosis is made by identification of the causative microorganism in tissue specimens. As this may be difficult and time-consuming, a therapeutic trial with anti-tuberculous agents may be warranted.

Polymorphism of CC chemokine receptors CCR2 and CCR5 in Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory disease of the intestine that is characterized by mononuclear cell infiltration and a predominant Th1 lymphocyte response. We tested the hypothesis that CC chemokine receptors CCR2 and CCR5 might be important in the regulation of the intestinal immune response in this disease, and we speculated that carriers of a defective 32 base pair deletion mutant of CCR5, CCR5Delta32, which results in a non-functional receptor, might be protected from CD. Using polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (PCR-RFLP) gene frequencies of CCR5Delta32 and of CCR2-641 (replacement of valine-64 by isoleucine in the CCR2 gene) in healthy controls (n=346) and in CD patients (n=235) were determined. In CD patients, subgroup phenotypic analyses were performed according to the Vienna classification. The overall gene frequency of CCR5Delta32 (9.8%) and CCR2-641 (7.6%) in CD patients did not deviate significantly from healthy controls (9.2 and 8.2%, respectively), nor did we observe a significant deviation from the predicted Hardy-Weinberg distribution. No significant differences in the CD phenotype classification for the different CCR5 and CCR2 alleles were observed, except for a trend to disease sparing of the upper gastrointestinal tract (carrier frequency 0 versus 19.6%, Delta=1 9.6%, P=0.079) as well as a more stricturing disease behaviour (23.5 versus 16.2%, Delta=7.3%, P=0.136) in carriers of the mutant CCR5Delta32 allele. These results indicate that the different CCR5 but not CCR2 alleles may influence disease behaviour and thereby contribute to the observed heterogeneity of CD. However, the associations observed are limited and await replication in other datasets. CCR2 and CCR5 polymorphisms are unlikely to be important determinants of overall disease susceptibility.

Trefoil peptides promote restitution of wounded corneal epithelial cells.

The ocular surface shares many characteristics with mucosal surfaces. In both, healing is regulated by peptide growth factors, cytokines, and extracellular matrix proteins. However, these factors are not sufficient to ensure most rapid healing. Trefoil peptides are abundantly expressed epithelial cell products which exert protective effects and are key regulators of gastrointestinal epithelial restitution, the critical early phase of cell migration after mucosal injury. To assess the role of trefoil peptides in corneal epithelial wound healing, the effects of intestinal trefoil factor (ITF/TFF3) and spasmolytic polypeptide (SP/TFF2) on migration and proliferation of corneal epithelial cells were analyzed. Both ITF and SP enhanced restitution of primary rabbit corneal epithelial cells in vitro. While the restitution-enhancing effects of TGF-alpha and TGF-beta were both inhibited by neutralizing anti-TGF-beta-antibodies, trefoil peptide stimulation of restitution was not. Neither trefoil peptide significantly affected proliferation of primary corneal epithelial cells. ITF but not SP or pS2 mRNA was present in rabbit corneal and conjunctival tissues. In summary, the data indicate an unanticipated role of trefoil peptides in healing of ocular surface and demand rating their functional actions beyond the gastrointestinal tract.

[The mechanisms of antigen uptake in the small and large intestines: the roll of the M cells for the initiation of immune responses]. / Mechanismen der Antigenaufnahme im Dünn- und Dickdarm: die Rolle der M-Zellen für die Initiierung von Immunantworten.

The gut-associated lymphoid tissues, e.g., the Peyer's patches and the appendix, constantly internalize antigenic material to rapidly generate an immune response, if necessary. This sampling of antigens is performed by specialized epithelial cells, the "membranous" or "microfold" (M) cells of the dome epithelia. M cells possess a unique ultrastructure and are typically in contact with lymphoid cells. They endocytose macromolecules and particles, including entire microorganisms, at their apical membrane, transport these in vesicles to their basolateral membrane, and exocytose them to the intercellular space. This article reviews the structural and functional characteristics of M cells in the digestive tract in humans and other species. Specializations of M cells for antigen uptake and transport comprise the composition of their apical membrane, a modified cytoskeleton as compared to enterocytes, and a large pocket-like invagination of the basolateral membrane populated by lymphocytes. Besides ultrastructural characteristics, histochemical markers are listed that are available for detecting M cells. The origin and differentiation pathways of M cells and enterocytes of the dome epithelium are outlined and critically commented on. Because M cells are known entry sites of various pathogens and, in the future, might be employed for the oral application of drugs and vaccines, the clinical relevance of M cells in health and disease is discussed.

Expression of leptin and leptin receptor isoforms in the human stomach.

BACKGROUND: Leptin is an important regulator of food intake and energy expenditure. Initially it was thought to be expressed exclusively in and secreted by adipocytes. Recently, leptin expression was also noted in other tissues, including rat gastric mucosa. Information on leptin and leptin receptor expression in the human stomach is lacking. AIM: To investigate expression of leptin and its corresponding receptors in human gastric epithelial cells. METHODS: Fundic and antral gastric mucosal biopsies, primary cultures of human gastric epithelial cells, and the human gastric cancer cell line AGS were screened for expression of leptin and different leptin receptor isoform mRNA by reverse transcriptase-polymerase chain reaction. Immunohistochemistry was performed for localisation of leptin and leptin receptor proteins in gastric mucosa. RESULTS: mRNA of leptin and its four receptor isoforms (huOB-R, long receptor isoform; huB219.1-3, short receptor isoforms) was detected in gastric mucosal biopsies, cultured human gastric epithelial cells, and gastric cancer cells. Immunohistochemistry demonstrated that chief as well as parietal cells were reactive to leptin and leptin receptors. CONCLUSIONS: Leptin and leptin receptors are expressed in human gastric mucosa. These findings suggest a paracrine and/or autocrine effect of leptin on gastric epithelial cell function.

[Sonographic diagnosis of an unusual recurrence of Chilaiditi syndrome after hemicolectomy]. / Sonographische Diagnose eines ungewöhnlichen Rezidivs des Chilaiditi-Syndroms nach Hemikolektomie.

A 71-year old patient presented with acute abdominal pain, nausea and emesis 3 months after right hemicolectomy for Chilaiditi's syndrome. The initial ultrasound examination revealed a loop of thick walled small intestine between the anterior surface of the right liver lobe and the diaphragm. In addition, small amounts of perihepatic fluid were found. The chest x-ray confirmed a recurrence of Chilaiditi's syndrome with intestinal gas under the right diaphragm. Elongation and flaccid of intestinal and hepatic suspensory ligaments are thought to be the principal predisposing factors. However, in our patient, a wedge-shaped enlarged lobus caudatus served as a guide rail for the bowel and facilitated access to the space under the right diaphragm. Although the patient recovered completely after 3 days of conservative therapy a high risk of recurrence remains. In summary, ultrasound examination can reliably diagnose Chilaiditi's syndrome and should also be used, as the method of choice in the follow-up of this rare syndrome, thus avoiding unnecessary x-ray exposure.

Glucocorticoids have pleiotropic effects on small intestinal crypt cells.

Glucocorticoids have long been known to accelerate maturation of the intestinal tract, but the molecular mechanisms that account for their physiological function in the epithelium remain poorly characterized. Using rat intestinal epithelial cell lines (IEC-6, IEC-17, and IEC-18) as models, we have characterized glucocorticoid receptors in crypt cells and documented striking morphological, ultrastructural, and functional alterations induced by these hormones in intestinal cells. They include arrest of growth, formation of tight junctions, appearance of long, slender microvilli, reorganization of the endoplasmic reticulum and trans-Golgi network, and downregulation of the cell cycle regulatory proteins cyclin-dependent kinase 6 and p27(Kip1). These effects are consistent with the activation or modulation of multiple genes important in the physiological function of absorptive villous cells but are probably not directly involved in the induction of cell differentiation.

Diagnosis of Chilaiditi's syndrome with abdominal ultrasound.

Chilaiditi's sign is a radiographic term used when the hepatic flexure of the colon is seen interposed between the liver and right hemidiaphragm. When symptomatic, this is Chilaiditi's syndrome. We report a case of a 70-year-old man who presented with abdominal pain, vomiting, singultus and constipation. Ultrasound was initially performed which showed an intestinal loop between the anterior surface of the right liver lobe and the diaphragm. The chest X-ray revealed colon gas under the right diaphragma and the abdominal CT-scan confirmed the hepatodiaphragmatic interposition of the colon. Colonic elongation and laxity of colonic and hepatic suspensory ligaments are the principal predisposing factors. The advantages of the abdominal ultrasound in the diagnosis and follow-up as well as possible complications and forms of therapy with this syndrome are discussed.

Enhanced production of monocyte chemotactic protein 3 in inflammatory bowel disease mucosa.

BACKGROUND: The beta chemokine monocyte chemotactic protein 3 (MCP-3) has chemoattractant and activating capabilities in monocytes, lymphocytes, eosinophils, and basophils. AIMS: To investigate MCP-3 expression in inflammatory conditions of the human intestinal mucosa. PATIENTS: Forty five colon biopsy specimens from 18 patients with inflammatory bowel disease (IBD; 16 specimens from inflamed and 10 from non-inflamed areas) and 19 control patients were examined. METHODS: Immunohistochemical staining and reverse transcription polymerase chain reaction (RT-PCR) were used for MCP-3 detection in tissue sections. Intestinal epithelial cell lines (HT-29, Caco-2, T-84) were stimulated with interleukin (IL) 1beta, IL-6, and tumour necrosis factor alpha (TNF-alpha) and examined for MCP-3 protein and mRNA expression using immunocytochemistry and RT-PCR, respectively. RESULTS: In tissue sections, MCP-3 protein was detected predominantly in epithelial cells, both in patients with IBD and in controls. MCP-3 staining was particularly pronounced at sites of active mucosal inflammation. The intensity of MCP-3 staining was positively correlated with the extent of epithelial destruction. In intestinal epithelial cell lines, MCP-3 mRNA was expressed, whereas MCP-3 protein was not consistently detected. CONCLUSIONS: Our data show that MCP-3 protein is present in normal and inflamed intestinal tissue. MCP-3 production is substantially enhanced in areas of active inflammation, suggesting an immunoregulatory role of MCP-3 in intestinal inflammation.

Intestinal fibroblasts regulate intestinal epithelial cell proliferation via hepatocyte growth factor.

Although the presence of subepithelial intestinal fibroblasts has been well recognized, the effects of fibroblasts on intestinal epithelial cell (IEC) growth are incompletely understood. In vitro studies were undertaken to evaluate the effects of fibroblasts on the proliferation of model IEC lines. IECs (Caco-2, T84, and IEC-6) were grown alone or in the presence of human intestinal (CCD-18), lung (CCD-37), or skin explant-derived fibroblasts. Cocultures were carried out directly on irradiated fibroblasts or by Transwell coculture technique with fibroblasts and epithelial cells separated by a porous filter. Cell proliferation was assessed by [3H]thymidine incorporation and cell counts. Hepatocyte growth factor (HGF) and c-met transcript expression in IECs and fibroblasts was examined by RT-PCR and Northern blotting; protein expression was evaluated by immunoblotting. Intestinal as well as lung and skin fibroblasts substantially stimulated proliferation of Caco-2, T84, and IEC-6 cells in both direct and Transwell cocultures. In addition, fibroblast-conditioned medium stimulated IEC proliferation, suggesting a paracrine mechanism. Anti-human HGF-neutralizing antibodies blocked the growth-promoting effects in both fibroblasts and fibroblast-conditioned medium. Recombinant human HGF dose dependently promoted IEC proliferation. HGF mRNA and protein expression was restricted to fibroblasts. High levels of c-met expression were found in Caco-2 and T84 cells; in contrast, expression in fibroblasts was weak. In summary, fibroblasts stimulate IEC proliferation through a paracrine mechanism mediated predominantly by HGF.

Rapid mitogen-activated protein kinase activation by transforming growth factor alpha in wounded rat intestinal epithelial cells.

BACKGROUND & AIMS: To define signaling events initiating healing after intestinal epithelial injury, activation of mitogen-activated protein kinase (MAPK) pathways was assessed after wounding using an in vitro model. METHODS: Proteins isolated from wounded monolayers of nontransformed intestinal epithelial cells (IEC-6) were analyzed for tyrosine phosphorylation and MAPK expression by Western blot. Extracellular signal-regulated kinase (ERK) 1, ERK2, and Raf-1 activities were assessed by immune complex kinase assays. RESULTS: Tyrosine phosphorylation of several proteins including ERK1 was substantially increased 5 minutes after injury. Another MAPK, c-Jun-N-terminal protein kinase (JNK), was also activated after wounding. Conditioned medium from wounded but not intact IEC-6 monolayers resulted in increased activity of ERK1, ERK2, and Raf-1 kinase. Wound-conditioned medium stimulated proliferation of subconfluent IEC-6 cells compared with conditioned medium from intact IEC-6 cultures and contained higher amounts of transforming growth factor (TGF)-alpha than supernatants of confluent IEC-6 cultures. Activation of ERK1 and ERK2 was partially inhibited by neutralizing anti-TGF-alpha. CONCLUSIONS: Wounding of intestinal epithelial cells results in activation of Raf-1, ERK1, ERK2, and JNK1 MAPKs and subsequent cell proliferation in vitro. Activation of ERK1 and ERK2 is mediated in part by TGF-alpha.

Sonography under Daylight Conditions.

PURPOSE: Gray scale image assessment in clinical ultrasound requires working in dim light or a dark room. Daylight conditions offer the advantage of shorter visual reaction time and enhanced visual perception. Look-up table manipulations could improve image brightness. MATERIALS AND METHODS: We investigated the possibility of brightness and contrast enhancement of coloured adaptive linear look-up tables (CALUT's) and their artifact resistance. Therefore under real-time conditions red/brown, green and blue CALUT's were calculated using the gray scale distribution (mean and standard deviation) of the actual image. The changes in contrast of several structural features (echo-poor and echogenic lesions, artifacts) were assessed by clinical investigators (n = 7). RESULTS: The CALUT's produced, independent of the original, images with constant brightness and contrast. Even under daylight conditions no artifacts appeared. Under scotopic conditions the red/brown CALUT's showed the best results compared to the unchanged image and the gray, green, and blue CALUT's. Hyper and hypoechoic differences with small contrast to the surrounding tissue are enhanced and can be detected more easily. CONCLUSION: Daylight sonography allows examination even in non-darkened rooms without loss of information. Eye adaptation to changing light conditions is no longer necessary; the offered image information is more suitable for the eye.

Epithelial cell kinase-B61: an autocrine loop modulating intestinal epithelial migration and barrier function.

Epithelial cell kinase (Eck) is a member of a large family of receptor tyrosine kinases whose functions remain largely unknown. Expression and regulation of Eck and its cognate ligand B61 were analyzed in the human colonic adenocarcinoma cell line Caco-2. Immunocytochemical staining demonstrated coexpression of Eck and B61 in the same cells, suggestive of an autocrine loop. Eck levels were maximal in preconfluent cells. In contrast, B61 levels were barely detectable in preconfluent cells and increased progressively after the cells reached confluence. Caco-2 cells cultured in the presence of added B61 showed a significant reduction in the levels of dipeptidyl peptidase and sucrase-isomaltase mRNA, markers of Caco-2 cell differentiation. Cytokines interleukin-1beta (IL-1beta), basic fibroblast growth factor, IL-2, epidermal growth factor, and transforming growth factor-beta modulated steady-state levels of Eck and B61 mRNA and regulated Eck activation as assessed by tyrosine phosphorylation. Functionally, stimulation of Eck by B61 resulted in increased proliferation, enhanced barrier function, and enhanced restitution of injured epithelial monolayers. These results suggest that the Eck-B61 interaction, a target of regulatory peptides, plays a role in intestinal epithelial cell development, migration, and barrier function, contributing to homeostasis and preservation of continuity of the epithelial barrier.

Elevated serum concentrations of soluble selectin and immunoglobulin type adhesion molecules in patients with inflammatory bowel disease.

Adhesion molecules mediate the extravasation of leukocytes and their accumulation in inflamed tissues. In the present study, serum concentrations of the selectin (sP- and sE-selectin) and immunoglobulin supergene family (sICAM-1 and sVCAM-1) of adhesion molecules were measured in 93 patients with inflammatory bowel disease (Crohn's disease, n = 65; ulcerative colitis, n = 28) and 58 age-matched normal controls. sP-selectin serum concentrations (mean +/- SEM ng/ml) of patients with Crohn's disease (399 +/- 33 ng/ml) and ulcerative colitis (385 +/- 42 ng/ml) were increased (P = 0.0067 and P = 0.0193, respectively) compared to controls (251 +/- 33 ng/ml). In contrast, E-selectin serum levels of patients with Crohn's disease (58 +/- 5 ng/ml) and ulcerative colitis (64 +/- 12 ng/ml) were not significantly higher than those of controls (53 +/- 5 ng/ml). sICAM-1 serum concentrations of patients with Crohn's disease (420 +/- 19 ng/ml) and those with ulcerative colitis (375 +/- 40 ng/ml) were elevated (P = 0.0001 and P = 0.0473, respectively) compared to controls (297 +/- 8 ng/ml). Further, sVCAM-1 levels of patients with Crohn's disease (664 +/- 43 ng/ml) and ulcerative colitis (963 +/- 162 ng/ml) were increased (P = 0.0222 and P = 0.0121, respectively) compared to controls (510 +/- 31 ng/ml). With few exceptions, serum levels of soluble adhesion molecules were not significantly correlated to disease activity indices or disease localization. Elevated circulating selectin and immunoglobulin supergene type adhesion molecules may compete with membrane-bound forms for their cognate ligands and thereby limit the rolling and stable adhesion of leukocytes.