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Biomedical subjects

M Zeitz

Publications and source records attributed to M Zeitz.

At least 73 records · Page 4Linked to original sources
PubMed2002

Extracellular nucleotides inhibit growth of human oesophageal cancer cells via P2Y(2)-receptors.

Extracellular ATP is known to inhibit growth of various tumours by activating specific purinergic receptors (P2-receptors). Since the therapy of advanced oesophageal cancer is unsatisfying, new therapeutic approaches are mandatory. Here, we investigated the functional expression and potential antiproliferative effects of P2-purinergic receptors in human oesophageal cancer cells. Prolonged incubation of primary cell cultures of human oesophageal cancers as well as of the squamous oesophageal cancer cell line Kyse-140 with ATP or its stable analogue ATP gamma S dose-dependently inhibited cell proliferation. This was due to both an induction of apoptosis and cell cycle arrest. The expression of P2-receptors was examined by RT-PCR, immunocytochemistry, and [Ca(2+)](i)-imaging. Application of various extracellular nucleotides dose-dependently increased [Ca(2+)](i). The rank order of potency was ATP=UTP>ATP gamma S>ADP=UDP. 2-methylthio-ATP and alpha,beta-methylene-ATP had no effects on [Ca(2+)](i). Complete cross-desensitization between ATP and UTP was observed. Moreover, the phospholipase C inhibitor U73122 dose-dependently reduced the ATP triggered [Ca(2+)](i) signal. The pharmacological features strongly suggest the functional expression of G-protein coupled P2Y(2)-receptors in oesophageal squamous cancer cells. P2Y(2)-receptors are involved in the antiproliferative actions of extracellular nucleotides. Thus, P2Y(2)-receptors are promising target proteins for innovative approaches in oesophageal cancer therapy.

Apoptosis↗
PubMed2002

Screening for oesophageal neoplasia in patients with head and neck cancer.

Due to advanced disease at the time of diagnosis the prognosis of oesophageal cancer is generally poor. As mass screening for oesophageal cancer is neither feasible nor reasonable, high-risk groups should be identified and surveilled. The aim of this study was to define the risk of oesophageal cancer in patients with (previous) head and neck cancer. A total of 148 patients with (previous) head and neck cancer were prospectively screened for oesophageal cancer by video-oesophagoscopy and random oesophageal biopsies. Even in a macroscopically normal looking oesophagus, four biopsy specimens were taken every 3 cm throughout the entire length of the squamous oesophagus. Low- or high-grade squamous cell dysplasia was detected histologically in 10 of the 148 patients (6.8%). All but one dysplasias were diagnosed synchronously with the head and neck cancers. In addition, oesophageal squamous cell carcinoma was diagnosed in 11 of the 148 patients (7.4%). Most invasive cancers (63.6%) occurred metachronously. The risk of squamous cell neoplasia of the oesophagus is high in patients with (previous) head and neck cancer. Surveillance is recommended in this high-risk group.

Aged↗
PubMed2002

[Appendectomy reduces the risk of development of ulcerative colitis].

The etiology and pathogenesis of ulcerative colitis are still unclear. There is, however, a growing consensus that the disease is characterized by a complex interaction between genetic and environmental influences. Many studies in the last few years have suggested that appendectomy reduces the risk of development and improves the course of ulcerative colitis. The underlying mechanism of this effect is unknown. The appendix seems to play a more important role in the development and modulation of the mucosal immune system than believed so far.

Adolescent↗
PubMed2002

The in vitro anti-inflammatory effects of recombinant anti-CD25 immunotoxin on lamina propria T cells of patients with inflammatory bowel disease are not sufficient to cure experimental colitis in mice.

BACKGROUND AND AIMS: In chronic inflammatory bowel disease (IBD) such as Crohn's disease and ulcerative colitis an aberrant mucosal immune regulation is observed accompanied by upregulation of proinflammatory cytokines. Lamina propria T cells of inflamed mucosa have an activated phenotype characterized by increased expression of surface markers such as CD25. We therefore determined the anti-inflammatory effect of a recombinant immunotoxin consisting of an anti-CD25 single chain variable fragment (scFv) fused to a deletion mutant of Pseudomonas exotoxin A [RFT5(scFv)ETA'] on isolated lamina propria lymphocytes of patients with IBD and in the murine model of trinitrobenzene sulfonic acid (TNBS) induced colitis. PATIENTS AND/METHODS: Lamina propria lymphocytes of 25 patients with IBD and 19 control patients were stimulated in absence or presence of RFT5(scFv)ETA'. Interferon-gamma production was determined in the supernatant by ELISA and the induction of apoptosis by flow cytometry after propidium iodide staining. BALB/c mice received TNBS intrarectally and were treated with RFT5(scFv)ETA'. RESULTS: In vitro the administration of RFT5(scFv)ETA' significantly reduced interferon-gamma production and increased apoptosis in lamina propria lymphocytes isolated of inflamed mucosa. However, this contrainflammatory regulation did not result in gain of weight or increased life span in experimental colitis in vivo. CONCLUSION: In addition to the downregulation of the proinflammatory cytokine in vitro, RFT5(scFv)ETA' induced neither a direct nor a bystander effect in an in vivo model of colitis. Therefore our data do not support potential therapeutic implications of targeting CD25 by RFT5(scFv)ETA' in chronic IBD.

Adult↗
PubMed2002

Unusual case of a large midoesophageal diverticulum mimicking unstable angina pectoris.

We describe a 77-year-old lady who presented with progressive retrosternal pain radiating to the left arm and the back. After exclusion of cardiac causes a large midoesophageal diverticulum was found on oesophago-gastro-duodenoscopy. Importantly, the retrosternal pain completely disappeared after endoscopic removal of impacted food from the diverticulum. After the surgical resection the patient became fully asymptomatic. This is the first example of angina-like chest pain which definitively resulted from a midoesophageal diverticulum. Therefore, midoesophageal diverticula should be considered as a rare differential diagnosis of exercise-induced retrosternal pain.

Aged↗
PubMed2002

Expression of CD44v6 has no prognostic value in patients with colorectal cancer.

BACKGROUND AND AIMS: In colorectal cancer patients' mortality is largely influenced by spreading of tumour cells from the primary tumour site and subsequent metastasis formation. CD44 is an adhesion molecule and represents a highly variable family of isoforms. The isoform CD44v6 has been associated with metastatic spread and poor prognosis in animal models and several human cancers. Results of immunohistological studies in primary colorectal cancer are mostly retrospective and contradictory. The aim of our prospective study was to assess the controversial role of CD44v6 as a prognostic factor in colorectal cancer. METHODS: In 93 patients we analysed tumour CD44v6 expression in prospectively sampled stage I-IV colorectal adenocarcinomas using RT-PCR and Southern blotting. The prognostic value of the CD44v6 expression was assessed using univariate and multivariate analysis. RESULTS: CD44v6 expression was found in 47 % of the cases. CD44v6 expression failed to show any association with the clinical or histological variables examined. CD44v6 expression did not correlate with survival in long-term follow-up. The most important prognostic factor in this cohort was tumour stage. CONCLUSIONS: Changes in CD446 expression level do not predict tumour spread or patient survival in colorectal cancer.

Adenocarcinoma↗
PubMed2002

Isolation of Nocardia paucivorans from the cerebrospinal fluid of a patient with relapse of cerebral nocardiosis.

Nocardia paucivorans represents a new species of the genus Nocardia that has recently been isolated from bronchial secretions of a patient with chronic lung disease. Here, we report on the course of a disseminated infection caused by this species: i.e., cerebral and subsequent meningeal manifestations, isolation from the cerebrospinal fluid, and in vitro susceptibility to various antimicrobial agents.

Brain Abscess↗
PubMed2002

Lack of simian immunodeficiency virus (SIV) specific IgA response in the intestine of SIV infected rhesus macaques.

BACKGROUND: Little is known about secretory immunity-the major defence mechanism at mucosal surfaces-in human immunodeficiency virus (HIV) infected patients, especially in the early stages of the disease. AIMS: The aim of the study was to analyse mucosal immunoglobulin production and simian immunodeficiency virus (SIV) specific antibody response in the intestinal mucosa during the course of SIV infection in comparison with serum and saliva. ANIMALS AND METHODS: IgG, IgA, and IgM concentrations were determined in supernatants of short term cultured duodenal biopsies, serum, and saliva from SIV infected rhesus macaques (n=8) and controls (n=2) by ELISA at defined times before and after infection. Specific antibodies to SIV were detected by western blot and/or dot blot analysis. In addition, rectal swabs from two uninfected and 12 SIV infected rhesus macaques (seven without and five with enteritis) were analysed for albumin and IgG concentrations. RESULTS: An increase in total intestinal IgG and a decrease in IgA were observed. SIV specific IgG or IgA responses were detectable as early as one week after SIV infection in the serum of seven of eight animals. In contrast, intestinal SIV specific IgG production was detected only four weeks after infection in six of eight animals, and intestinal SIV specific IgA was not produced in the intestine at any time point. In saliva, the secretory component on SIV specific IgA was only detected in one animal at week 24 after infection. Enteritis is frequent in SIV infected animals and results in a significant increase in albumin and IgG secretion into the intestinal lumen. CONCLUSION: Despite modest quantitative changes in mucosal immunglobulin production there was a total lack of SIV specific IgA synthesis in the intestine during SIV infection. This lack or disturbed secretory SIV specific IgA response at mucosal surfaces may explain the rapid and high HIV/SIV replication in this compartment. In addition, our investigations indicate secretion of serum proteins into intestinal fluids during SIV infection. Previous investigations using intestinal secretions or swabs for analysing quantitative and specific immunglobulins therefore should be interpreted with caution.

Animals↗
PubMed2001

Specific ligands of the peripheral benzodiazepine receptor induce apoptosis and cell cycle arrest in human colorectal cancer cells.

The peripheral benzodiazepine receptor (PBR) has been implicated in growth control of various tumour models. Although colorectal cancers were found to overexpress PBR, the functional role of PBR in colorectal cancer growth has not been addressed to date. Using primary cell cultures of human colorectal cancers and the human colorectal carcinoma cell lines HT29, LS174T, and Colo320 DM we studied the involvement of PBR in the growth control and apoptosis of colorectal cancers. Both mRNA and protein expression of PBR were detected by RT-PCR and flow cytometry. Using confocal laser scanning microscopy and immunohistochemistry the PBR was localized in the mitochondria. The specific PBR ligands FGIN-1-27, PK 11195, or Ro5-4864 inhibited cell proliferation dose-dependently. FGIN-1-27 decreased the mitochondrial membrane potential, which indicates an early event in apoptosis. Furthermore, FGIN-1-27, PK 11195 or Ro5-4864 increased caspase-3 activity. In addition to their apoptosis-inducing effects, PBR ligands induced cell cycle arrest in the G(1)/G(0)-phase. Thus, our data demonstrate a functional involvement of PBR in colorectal cancer growth and qualify the PBR as a possible target for innovative therapeutic approaches in colorectal cancer.

Adult↗
PubMed2001

Immune response to autologous and heterologous Helicobacter pylori antigens in humans.

Infection of humans with Helicobacter pylori results in the development of chronic gastritis and plays an important role in gastric ulcer pathogenesis. Despite the infiltration of the mucosa with specific immunocompetent cells and production of specific antibodies, the infection usually persists for life. This study was performed to investigate if immunologic mechanisms exist which could contribute to the inability of the host to terminate the infection. Therefore, we compared the in vitro immunoreactivity of peripheral blood mononuclear cells (PBMC) from H. pylori-infected patients after stimulation with sonicated H. pylori bacteria from the stomach of the patient (autologous bacterial strain) with stimulation by bacteria from other patients (heterologous bacteria). We measured cell proliferation, expression of T cell activation markers CD25, HLA-DR, and CD71, as well as production ofinterleukin-10 (IL-10), an inhibitory cytokine. We found that the proliferative response of PBMC was significantly lower after autologous than after heterologous stimulation. Furthermore, secretion of IL-10 in the culture supernatants was significantly higher when PBMC were incubated with autologous than with heterologous H. pylori antigens. No significant differences between autologous or heterologous stimulation were observed in the increased expression of T cell activation markers. These data indicate that systemic immunologic response to H. pylori are strain-dependent. For further studies of the immune responses towards H. pylori, the use of an autologous stimulatory system seems necessary.

Adult↗
PubMed2001

[Abdominal tuberculosis: a rare differential diagnosis of pancreatic carcinoma].

HISTORY AND ADMISSION FINDINGS: A 79-year-old local resident, presenting with abdominal pain, sweating and weight loss and suspected of having cancer of the pancreas was referred for diagnosis and treatment. Physical examination was negative except for pain on pressure over the right upper abdomen and the epigastrium. INVESTIGATIONS: Erythrocyte sedimentation rate was increased; as were the transaminases and cholestasis parameters. Ultrasonography and computed tomography of the abdomen revealed an echo-poor mass with cystic areas in the region of the head of the pancreas, as well as extra- and intrahepatic dilatation of the biliary tract. Endoscopic retrograde cholangiopancreatography failed to demonstrate a ductal pancreatic carcinoma. Biopsies of a macroscopically peculiar-looking duodenal ulcer demonstrated a noncaseous epithelioid granuloma. A fine-needle biopsy was performed for further diagnosis. DIAGNOSIS, TREATMENT AND COURSE: Histological examination of the needle biopsy revealed a caseous granuloma and acid-fast bacteria. The tuberculin test (GTI) was strongly positive (14-15 mm), indicating tuberculosis of the pancreas and duodenum. Multiple tuberculostatics rapidly improved the patient's symptoms, and the further course was without complications. CONCLUSION: Tuberculosis should be included in the differential diagnosis of consumptive disease with an atypical presentation, especially because treatment could well be curative.

Aged↗
PubMed2001

Activation of beta(1) integrins mediates proliferation and inhibits apoptosis of intestinal CD4-positive lymphocytes.

A characteristic of lamina propria lymphocytes (LPL) is their low proliferative response to stimuli of the CD3 pathway. beta(1) integrins were expressed on LPL; however, their function is unknown. Therefore, we determined whether beta(1) integrins contribute to T cell responses by providing costimulatory signals. Integrins on CD4(+) LPL of controls and patients with inflammatory bowel disease were characterized by flow cytometry. Cells were stimulated by anti-CD3 or anti-CD2 antibodies either alone or in combination with a stimulatory beta(1) integrin antibody (12G10). Proliferation and apoptosis were measured by [(3)H]thymidine pulsing or flow cytometry. Cytokine mRNA and apoptosis-related transcripts were quantified by reverse transcriptase-PCR. We demonstrated that beta(1) integrin costimulation restored CD3-induced proliferation of CD4(+) LPL and reduced activation-induced apoptosis. Activation of beta(1) integrins by addition of 12G10 antibody to CD3-stimulated cells restored their capacity to express proinflammatory cytokine transcripts. Further, expression of the activated form of beta(1) integrins was significantly elevated on LPL from inflamed mucosa. These studies demonstrate that beta(1) integrin costimulation modulates the response of LPL after TCR stimulation. An increased expression of activated beta(1) integrins on LPL in intestinal inflammation may abolish their unresponsiveness to antigens and perpetuate the inflammatory process.

Adult↗
PubMed2001

Stage-specific alternative cplicing of CD44 and alpha 6 beta 1 integrin in colorectal tumorigenesis.

Recent reports suggest that cancerogenesis induces changes in alternative processing of human genes. However, little is known about the regulation of alternative splicing during malignant transformation. Therefore, we examined changes in alternative splicing of two different adhesion molecules, alpha 6 beta 1 integrin and CD44, in multiple stages of colon tumorigenesis. Using semiquantitative RT-PCR it is shown that the alternatively spliced isoforms of both adhesion molecules, alpha 6A and -B and CD44v6, are significantly upregulated in colorectal adenoma (n = 20) compared to normal colon mucosa (n = 32) (P < 0.01). Although beta1 isoforms were expressed in almost all tissues, there was a significant increase in the intensity of gene expression of beta 1A compared to beta 1B (P <0.05) in adenoma tissue. Interestingly, CD44v6 and alpha 6 variant isoforms were downregulated in carcinoma tissue (n = 28) compared to adenoma. These results establish a link between neoplastic transformation and alternative splicing of cell adhesion molecules. Furthermore, these data suggest that colon epithelial cells carrying splice variants of adhesion molecules might acquire a selective growth advantage during early tumorigenesis.

Adenocarcinoma↗