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Biomedical subjects

M Zeitz

Publications and source records attributed to M Zeitz.

At least 37 records · Page 2Linked to original sources

Evaluation of endosonography in TN staging of oesophageal cancer.

Strategies for the treatment of cancer of the oesophagus depend on the tumour stage at the time of diagnosis. Resection, the only curative treatment, is confined to early tumour stages. Tumours with local infiltration are usually unresectable and require palliative treatment. Computed tomography has been widely used for preoperative staging but often fails to define this correctly. Endoscopic ultrasound allows direct visualisation of the parietal wall and may be useful in staging gastrointestinal tumours. In a comparative prospective study, 52 patients with tumours of the oesophagus were investigated preoperatively both by endoscopic ultrasound and computed tomography to determine the stage of tumour infiltration and local lymph node involvement. Thirty seven of these patients underwent operation, resection, or dissection and entered the study. The intraoperative findings or the histopathological assessment, or both, were taken as a reference. For all TN stages of oesophageal tumours, correct preoperative staging was accomplished by endoscopic ultrasound in 89% for T stage and 69% for N stage compared with 51% and 51% respectively by computed tomography (highly significant using Fisher's exact test). This study shows that endoscopic ultrasound is useful in preoperative TN staging of tumours of the oesophagus.

Adult

The HML-1 antigen of intestinal lymphocytes is an activation antigen.

The Ag recognized by the mAb HML-1 is expressed on more than 90% of human intestinal intraepithelial lymphocytes, whereas in other lymphoid tissues it is rarely or not expressed. In the present study, we have investigated the percentage of HML-1-positive cells in the human intestinal lamina propria and the coexpression of HML-1 with different T cell subset markers. In addition, we studied the inducibility of HML-1 on PBL which normally are HML-1-negative. Flow cytometric analysis of isolated intestinal lamina propria lymphocytes (LPL) showed that about 40% of the cells expressed HML-1, the majority belonging to the CD8-positive subpopulation. Virtually all LPL expressed CD45RO, whereas the percentage of CD29-positive cells was only about 50%, similar to PBL. There were only few cells expressing CD45RA or Leu-8 in the lamina propria. HML-1-positive cells were almost exclusively CD45RA-negative, but were found in both the CD29-positive and the CD29-negative subpopulation of LPL. In vitro stimulation of PBL showed that the expression of HML-1 was inducible on T cells by mitogens, phorbolester, Ag, and rIL-2. Expression of HML-1 was induced with a different time course and with differences in the response to the investigated stimuli compared with CD25. Activated HML-1-positive PBL were also predominantly CD45RA-negative. The findings show that HML-1 is an Ag, which is expressed in vivo on a specific subset of previously activated T cells in the unique environment of the intestinal mucosa, and which can be induced in vitro by different activation signals on PBL.

Antibodies, Monoclonal

Preoperative staging of gastrointestinal tumors by endosonography.

Intracavitary application of ultrasound was first performed for diagnostic purposes in 1967; since that time, it has been more and more widely used. As far as the gastrointestinal tract is concerned, endoscopically controlled ultrasonic probes provide visualization of the various layers of the intestinal wall. It is therefore possible to describe lesions of the esophagus, stomach, and the rectum with regard to their nature and depth of infiltration. Furthermore, periesophageal and perigastric organs can be visualized. It has become evident that endosonography is particularly important for pretherapeutic staging of tumors of the esophagus, stomach, and rectum. Here prospective comparative studies confirm the superiority of this new diagnostic procedure when compared to the methods available to date.

Endoscopy, Gastrointestinal

Tight junction regulation during impaired ion transport in blind loops of rat jejunum.

Epithelial cell tight junction structure in self-filling blind loops of rat jejunum, a model for blind loop syndrome in humans, was analyzed morphometrically along the crypt-villus axis. In control jejunum, the number of strands and junctional depth, including meshwork depth, decreased from crypt to villus tip. In the blind loop, aberrant strands appeared below the meshwork, particularly in crypt cells. Consequently, total junctional depth was greater than in controls. Furthermore, strand number and junctional meshwork depth were increased in blind loops at the villus tip. It is that site along the crypt-villus axis which showed the most shallow junction in control jejunum. This structural change is paralleled by a three-fold increase in epithelial resistance as previously measured by alternating current impedance analysis. Relative Na over Cl permeability (PNa:Cl) was obtained from dilution potential measurements. PNa:Cl was 1.50:1 in control jejunum and 1.35:1 in the blind loop (n.s.). Considering the cation selectivity of the tight junction, the increase in epithelial resistance in blind loops cannot be attributed to a collapse of the lateral intercellular space but is due to changes in tight junctional permeability resulting from structural alteration. The blind loop syndrome represents a further example of diminished epithelial ion transport and concomitant decrease in tight junction permeability, thus supporting the general concept of regulation of the tight junction in response to active transport activity.

Animals

gamma delta T cells in the human intestine express surface markers of activation and are preferentially located in the epithelium.

We have investigated the expression of the alpha beta and the gamma delta T cell receptor (TCR) in the human intestine. By immunohistology we found that 39% of CD3+ intraepithelial lymphocytes (IEL) expressed the gamma delta TCR compared to 3% of CD3+ lamina propria lymphocytes (LPL). Cytofluorometric analysis of isolated cells revealed a significantly higher proportion of gamma delta T cells among CD3+ IEL compared to LPL and peripheral blood lymphocytes. This was due to an increase in both CD8+ (low density) and CD4-CD8- gamma delta T cells in IEL. Most alpha beta IEL expressed high-density CD8. About 30% of both IEL and LPL expressed CD25 (alpha-chain of the IL-2 receptor). HML-1 expression was detected on nearly all IEL and on 27% of LPL. CD25 and HML-1 were preferentially expressed on intestinal alpha beta and gamma delta T cells, respectively. Thus, human gamma delta T cells are located preferentially in the gut epithelium and are phenotypically different from alpha beta T cells, which constitute the majority of both LPL and IEL.

Adult

Special functional features of T-lymphocyte subpopulations in the effector compartment of the intestinal mucosa and their relation to mucosal transformation.

Recent studies indicate that intestinal lamina propria T cells are highly specialized lymphocytes, which differ from T cells in other compartments of the immune system in several respects. In the present study phenotypic and functional characteristics of lamina propria T cells and their possible relation to mucosal growth will be discussed. Lymphocytes from human and nonhuman primate intestine were isolated by an enzymatic procedure. Lymphocytes were studied using dual-color immunofluorescence (FACS) and functional in vitro assays. CD4 positive (helper-) lamina propria T-cells lack the CD45RA antigen and express the CD45RO antigen. This phenotype is characteristic for memory T cells. In addition intestinal T cells express IL-2 receptors and IL-2 receptor mRNA, and are able to synthesize high amounts of IL-2. Functional studies in nonhuman primates infected rectally with Chlamydia trachomatis have shown that lamina propria T cells do not proliferate after stimulation with antigen but rather provide helper function for immunoglobulin synthesis. The intestinal lamina propria therefore contains highly specialized T cells which have the phenotype of memory T cells and which are activated. Functionally these T cells can be characterized as differentiated effector lymphocytes. Recent studies from other laboratories have shown that the pattern of lymphokines produced by lamina propria T cells and the responsiveness to certain lymphokines also differ from those of other lymphocyte populations. Since T-cell-derived lymphokines are also important regulators for epithelial growth and differentiation as well as for connective tissue metabolism, lamina propria T cells might be of major importance in mucosal growth and transformation.

Animals

Mucosal atrophy is associated with loss of activated T cells in the duodenal mucosa of human immunodeficiency virus (HIV)-infected patients.

Gastrointestinal symptoms and malabsorption are frequent in HIV-infected patients even in the absence of opportunistic infections. In earlier studies we found indications that the gastrointestinal mucosa itself may be affected by HIV. Since there is evidence that the mucosal structure is influenced by changes in the gut-associated lymphoid tissue, we have investigated mucosal structure and immune cells in HIV-infected patients. Sixty patients (3 f, 57 m; age 21-61, median 37 years; 11 at CDC stage II or III, 49 at stage IV) with gastrointestinal complaints undergoing upper endoscopy were examined for enteric pathogens. Duodenal biopsies were labelled by immunohistology for HIV antigen p24 and for lymphocyte surface markers; mucosal architecture was studied by three-dimensional morphometry. Biopsies from HIV seronegative patients without abnormal findings served as controls. In 29 patients an enteric pathogen was identified. In 22 patients HIV-infected mononuclear cells were detected in the lamina propria. In the lamina propria CD25+ cells were decreased, CD3+ and CD8+ cells were increased in HIV-infected patients compared with controls, while the numbers of CD4+, Leu8+, and HML-1+ cells, and of macrophages were not different. Patients at stage IV had decreased numbers of CD4+ T cells compared with patients at stage II or III. Villus surface area was reduced in HIV-infected patients compared with controls. Crypt depth was increased in patients with intestinal infection compared with controls while numbers of mitotic figures were normal. Patients without intestinal infection and patients with mucosal HIV-infected cells had decreased numbers of mitotic figures and normal crypt depth compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome

The effect of an anthraquinone laxative on colonic nerve tissue: a controlled trial in constipated women.

Anthraquinone containing laxatives have been accused to cause degenerative changes in the colonic nerve tissue; prospective studies, however, are not available. This article reports the result of a semiprolective study in 11 matched pairs of chronically constipated women. Each pair consisted of one women having regularly taken an anthraquinone containing laxative for at least one year and a control person without such a medication. Six endoscopic biopsies were taken from the left colon and rectum which were evaluated by electron microscopy and subsequent ultramorphometry for the ratio of damaged to intact neurons, density of neurosecretory vesicles, axonal diameter and number of lysosomes. Medians of the three colonic locations were calculated in each individual and for each variable, and they were compared by non-parametric statistics. Medians of the ratio of damaged to intact neurons in anthraquinone treated women and controls were 0.162 and 0.146 (p = 0.0326, one-tail), medians of the number of type I vesicles were 293 and 348.5 per 100 microns 2 (p = 0.0365, one-tail), respectively. None of the other variables were different between groups. These data do not support the hypothesis that anthraquinone containing laxatives are able to provoke relevant degenerative changes in the colonic nerve tissue since the variables are either similar in both groups or only slight differences could be found which are unlikely to be of pathophysiological relevance.

Adult

Small intestinal structure and function in patients infected with human immunodeficiency virus (HIV): evidence for HIV-induced enteropathy.

STUDY OBJECTIVE: To determine small intestinal mucosal structure and function in patients with human immunodeficiency virus (HIV) infection. DESIGN: Prospective, consecutive sample study. SETTING: Referral-based medical clinics at a municipal and a university medical center. PATIENTS: Forty-five HIV-infected patients (44 men, 1 woman) with gastrointestinal complaints. INTERVENTIONS: All patients had esophagogastroduodenoscopy. Distal duodenal biopsy samples were examined morphometrically and by quantitative enzyme histochemical techniques. Immunohistologic studies were done to determine whether HIV antigen p24 was present. Biopsy and stool samples were examined for enteric pathogens and patients were evaluated for malabsorption. MEASUREMENTS AND MAIN RESULTS: Malabsorption was common in HIV-infected patients. In 15 of 38 patients mononuclear cells infected with HIV were found in the mucosa. In 15 of 25 patients there was no detectable lactase (beta-glucosidase) activity in the duodenal brush border; when measurable, lactase (beta-glucosidase) activity was decreased (P less than 0.02). Alkaline phosphatase activity was normal. Crypt depth was greater (P less than 0.05), villous surface area was slightly smaller, and mitotic figures per crypt were not different in HIV-infected patients compared with controls. Patients without additional intestinal infection had a reduced number of mitotic figures per crypt (P less than 0.05) and normal crypt depth. The reduction in mitotic figures was most pronounced in patients with mucosal HIV antigen p24. CONCLUSIONS: The HIV-infected patients with gastrointestinal symptoms show low-grade small bowel atrophy and a maturational defect in enterocytes, which may be caused exclusively by HIV. An additional intestinal infection can mask this mucosal atrophy.

Acquired Immunodeficiency Syndrome

Oral administration of cyclosporin does not prevent expansion of antigen-specific, gut-associated, and spleen lymphocyte populations during Chlamydia trachomatis proctitis in nonhuman primates.

To study the effects of oral cyclosporin (CsA) administration on immune responses in the gastrointestinal tract, humoral and cellular immune responses were studied in CsA-treated nonhuman primates having Chlamydia trachomatis proctitis (lymphogranuloma venereum, LGV). There was no apparent effect of CsA treatment on the gross or microscopic appearance of LGV proctitis, but CsA-treated animals, with or without LGV infection, had lymphoid hyperplasia of spleen and mesenteric lymph nodes. CsA treatment inhibited the primary antibody response to LGV, inhibited peripheral blood lymphocyte mitogen-induced proliferation and IL-2 production, and inhibited LGV-specific proliferation of peripheral blood lymphocytes. In contrast, mitogen-stimulated proliferation of spleen, mesenteric lymph node, and lamina propria lymphocytes was not significantly inhibited in CsA-treated animals. In addition, LGV-specific proliferation of spleen and mesenteric lymph node lymphocytes was not inhibited. High mitogen-stimulated IL-2 production of lamina propria lymphocytes was only partially inhibited in CsA-treated animals. In vitro CsA treatment had the expected inhibitory effects on mitogen- and antigen-induced proliferation of spleen and mesenteric lymph node lymphocytes. Thus, although oral cyclosporin inhibits the antibody and proliferative responses of peripheral blood lymphocytes to antigens and mitogens in animals having Chlamydia trachomatis proctitis, it does not prevent the expansion of antigen-specific, gut-associated, and spleen lymphocyte populations.

Administration, Oral