Search PubMed⌕ Search

Biomedical subjects

M Zeitz

Publications and source records attributed to M Zeitz.

At least 145 records · Page 8Linked to original sources
PubMed1997

Abnormal predominance of IgG in HIV-specific antibodies produced by short-term cultured duodenal biopsy specimens from HIV-infected patients.

The aim of our study was to analyze HIV-specific humoral immunity in the intestinal mucosa at different stages of HIV infection in comparison with serum and saliva. Duodenal biopsy specimens from 30 AIDS patients and 9 HIV-infected patients without AIDS were cultured for 48 hours. Culture supernatants, as well as simultaneously obtained serum and saliva samples, were adjusted to the same immunoglobulin concentrations and tested for HIV-specific IgG and IgA by Western blot. The HIV antigen pattern differed clearly between IgA and IgG but was similar for each isotype independent of its origin (i.e., serum, saliva, or biopsy specimen supernatants). Short-term cultured duodenal biopsy specimens from HIV-infected patients at all stages produced predominantly IgG, which was broadly reactive with HIV antigens. Lower titers of HIV-specific IgA, which recognized few antigens, were found, mostly the glycoprotein gp160. At later stages of the disease compared with earlier stages, the reaction pattern of mucosal IgA from saliva and biopsy supernatants was even more restricted; secretory component was frequently absent. The abnormal predominance of HIV-specific IgG over IgA in mucosal secretions may result from abnormal antibody production in the mucosa rather than from serum leakage. Mucosal inflammation induced by HIV-IgG immune complexes and insufficient immune exclusion by secretory IgA may not only lead to increased mucosal HIV replication but may also contribute to gastrointestinal disease in HIV-infected patients.

Adult↗
PubMed1997

[New therapeutic possibilities in chronic inflammatory bowel diseases].

New therapeutic measures in inflammatory bowel diseases (IBD) are either based on actual data on disease pathogenesis or on new pharmaceutic preparations of known drugs. An overshooting immune response with T cell activation in the local gut associated immune system seems to be central in the etiopathogenesis of IBD. Modulation of the antigenic load in the gut lumen by parenteral or enteral nutrition or antibiotic treatment can alter disease activity. Immunosuppressive drugs are able to decrease the overshooting immune response. Azathioprin has its clear value in chronic active steroid dependent disease courses of Crohn's disease. According to recent studies, Methotrexate seems to be active as well, however, more studies are necessary. Several studies were not able to prove that Cyclosporine is of value in the treatment of Crohn's disease. Newer preparations of aminosalicylates have shown effectiveness in both active disease and prolongation of remission in Crohn's disease in high doses. Local release formulations of steroids with high first-pass-effect as Budesonide will have their indication in subgroups of IBD patients. However, systemic steroid application is still the gold standard in active disease.

Aminosalicylic Acids↗
PubMed1997

The number and proportion of Vgamma9 Vdelta2 T cells rise significantly in the peripheral blood of patients after the onset of acute Coxiella burnetii infection.

We conducted serial studies on peripheral blood lymphocytes from four patients with acute Coxiella burnetii infection. These studies revealed that the proportion of gammadelta T cells in these patients significantly increased after the onset of disease (mean, 16%; range, 13%-30%) as compared with that in five healthy controls (mean, 4%; range, 0.5%-7%; P < .0055) and that in five controls with pneumonia (mean, 2%; range, 1%-3%; P < .0014). Most of the gammadelta T cells from these patients expressed the Vgamma9 Vdelta2 gene product. During the acute phase of disease, most gammadelta T cells expressed the activation marker human leukocyte antigen DR but not CD25. During this phase, gammadelta T cell activation was higher than alphabeta T cell activation. Our findings indicate that gammadelta T cells are predominantly involved in the acute immune response to C. burnetii.

Acute Disease↗
PubMed1997

Mucosal abnormalities in microsporidiosis.

OBJECTIVE: To determine the prevalence of microsporidiosis in HIV-infected patients with and without diarrhoea and to characterize alterations in mucosal architecture and brush border enzyme activities in patients with microsporidiosis. PATIENTS: A total of 259 HIV-infected patients undergoing oesophago-gastroduodenoscopy because of diarrhoea (n = 123) or other symptoms (n = 136) were studied. METHODS: Patients were evaluated for the presence of microsporidia by electron microscopy of duodenal biopsies. Brush border enzyme activities were measured by histochemistry and mucosal architecture was determined by three-dimensional morphometry in biopsies from patients with microsporidiosis and compared with biopsies from a subgroup of HIV-infected patients with or without other enteropathogens. RESULTS: Enterocytozoon bieneusi was detected in 17 patients and Encephalitozoon intestinalis was detected in two patients. Microsporidiosis was significantly more frequent in patients with chronic diarrhoea (19.1%; P < 0.0001) or in patients with acute diarrhoea (7.2%; P = 0.04) than in patients without diarrhoea (1.5%). Microsporidiosis was associated with lactase deficiency (P = 0.03) and a reduced activity of alkaline phosphatase (P = 0.028) and alpha-glucosidase (P = 0.025) at the basal part of the villus compared with brush border enzymes in patients without enteropathogens. Patients with microsporidia had reduced villus height (P = 0.043) and a villus surface reduced by 40% (P = 0.004) compared with patients with enteropathogens other than microsporidia. CONCLUSIONS: Our study confirms the association between microsporidia and diarrhoea. The pathophysiologic mechanism by which microsporidia cause diarrhoea appears in part to be malabsorption, caused by a reduction of absorptive mucosal surface and impairment of enterocyte function.

AIDS-Related Opportunistic Infections↗
PubMed1996

Intestinal T-cell lymphoma: a reassessment of cytomorphological and phenotypic features in relation to patterns of small bowel remodelling.

Intestinal T-cell lymphoma (ITCL) is an uncommon entity among primary gastrointestinal lymphomas. In this study we evaluated tumours from 20 patients presenting with (n = 8) or without (n = 12) a history of coeliac disease (CD). Neoplastic lesions were composed of predominantly small (n = 4), small-to-medium (n = 2), medium/mixed-to-large (n = 7) or large and anaplastic (n = 7) cells. Different patterns of tumour growth and remodelling of the small bowel wall were observed. Pattern a (n = 4) was characterized by an intramucosal spread of small tumour cells with a small growth fraction. This pattern resembles mucosal inflammation in CD. In pattern b (n = 2), ulcerated solitary or multiple tumours composed of small to medium-sized cells were observed. The adjacent or distant mucosa showed a nearly normal architecture. In pattern c (n = 7), ulcerated lesions were composed of medium-sized to large cells. Mucosal flattening occurred in all segments infiltrated by lymphoma. In pattern d (n = 7), bowel remodelling was observed along the small intestine even at sites not affected by lymphoma. The main neoplastic lesions were composed of pleomorphic large or anaplastic cells frequently expressing the CD30 molecule. Intramucosal spread of a small epitheliotropic T-cell population was observed in the vicinity or even at distant segments of the small bowel. The demonstration of clonal rearrangements of T-cell receptor genes helped to trace widespread occurrence of this small intraepithelial neoplastic component. We suggest that different features of tumour cells such as the expression of activation antigens may contribute to the remodelling of small bowel mucosa. The addition of immunophenotyping data to macroscopic and microscopic features of specimens provided evidence that this uncommon lymphoma exhibits a spectrum in cytological composition and growth patterns. However, despite the considerable heterogeneity of the cases analysed, most of them shared a characteristic immunohistochemical profile (CD3+, CD8+/-, CD103+), further substantiating the view that ITCL is the neoplastic equivalent of an intraepithelial T-cell subset of the small intestine. This phenotype and the intraepithelial accumulation of lymphoma cells observed in the surviving mucosa are clues to the diagnosis of this clinicopathological lymphoma entity characterized by a broad range of morphological expressions.

Adult↗
PubMed1996

Special features of the intestinal lymphocytic system.

The gastrointestinal lymphocytic system can be divided in two functional compartments, the organized lymphoid tissue, for example, the Peyer's patches, and the lymphocytes located diffusely in the mucosa, the lamina propria lymphocytes (LPL), and the intra-epithelial lymphocytes (IEL). Antigens enter the Peyer's patches as the afferent part of the GALT via specialized epithelial cells called M cells. After the initiation of the immune response by antigen processing and presentation to B and T cells in Peyer's patches, primed lymphocytes leave the mucosa via the thoracic duct. Finally they migrate back to the mucosa where they exert effector functions. Adhesion molecules, including integrins, especially alpha 4 beta 7 and alpha E beta 7 (HML-1) are involved in these homing and adhesion processes. LPL and LEL differ from peripheral blood lymphocytes in their expression of adhesion molecules and other surface and activation markers. Additionally, they exhibit functional features different from those of other lymphocyte compartments. In the mucosal immune system, plasma cells mainly secrete IgA, which is part of the specialized humoral defence in the gut.

Animals↗
PubMed1996

Stool viruses, coinfections, and diarrhea in HIV-infected patients. Berlin Diarrhea/Wasting Syndrome Study Group.

To examine the prevalence of stool viruses and their role in the pathogenesis of diarrhea in HIV infection, we evaluated biopsies and repeated stool samples of 256 HIV-infected patients undergoing diagnostic endoscopy because of diarrhea (n = 136) or other symptoms (n = 120) for bacterial, protozoal, and viral enteropathogens. In 70% of the patients with diarrhea, at least one potential enteropathogen was detected. Stool virus was detected by electron microscopy in 17% (44 of 256), adenovirus in 6.6% (17 of 256), and coronavirus in 11.3% (29 of 256) of the patients. Adenovirus and coronavirus were detected more frequently in patients with diarrhea than in patients without diarrhea [adenovirus 10% (13 of 136) vs. 3.3% (4 of 120), p = 0.0129; coronavirus 15% (21 of 136) vs. 6.6% (8 of 120), p = 0.0142]. Sixty-one percent of patients harboring stool virus were coinfected by another enteropathogen. Pathogens other than stool virus were detected more frequently in patients harboring adenovirus (82%) than in patients without stool virus (48%, p < 0.025). Adenovirus and coronavirus are frequently detected in stools of HIV- infected patients and may contribute to diarrhea. Adenovirus infection may facilitate the occurrence of other intestinal pathogens. Due to frequent coinfections, detection of stool viruses reduces the rate of diarrhea of unknown origin only by approximately 5%.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Immunological and trophical effects of Saccharomyces boulardii on the small intestine in healthy human volunteers.

Saccharomyces boulardii (S.b.) is used for the prevention and treatment of diarrhea of different etiologies. We prospectively investigated the effects of S.b. on lymphocytes and duodenal mucosa. Before and after oral administration of S.b. for 3 weeks, circulating and intestinal lymphocytes were isolated and characterized by flow cytometry. Trophic effects on duodenal mucosa were investigated by morphometry and determination of brush border enzyme activity. Results were compared intraindividually before and after S.b. In intestinal lymphocytes no phenotypic changes were observed. CD4+ cells of the peripheral blood had a significantly increased expression of CD25 (p < 0.02). None of twelve volunteers had an increase in villous surface area (n.s.). Immunoglobulin A content in small intestine secretion was unaltered. An increase in brush border enzyme activity of lactase, alpha-glucosidase, and alkaline phosphatase was observed (p < 0.01). Our findings indicate that S.b. has a positive effect on the maturation of enterocytes and only a minor influence on lymphocytes.

Administration, Oral↗
PubMed1996

The immunologic aspects of human immunodeficiency virus infection in the gastrointestinal tract.

The intestinal (in particular rectal) mucosa is an important portal of entry of human immunodeficiency virus (HIV) in homosexual men, who represent the vast majority of HIV-infected patients in Europe and North America. There are several possibilities for HIV to reach the CD4+ T cells, macrophages, and follicular dendritic cells in the intestinal mucosa. HIV may be transported through M cells directly to mucosal lymphoid follicles. Alternatively, HIV may infect enterocytes via Fc-receptor by antibody-bound HIV or via a CD4 independent receptor. By successive budding on the basal side of enterocytes, HIV may be released into the lamina propria. Furthermore, in patients not infected by the intestinal route, HIV may also rapidly enter the intestinal mucosa by other mechanisms: intestinal T-lymphocytes are mainly activated memory T cells reentering the mucosal surfaces after circulating through the peripheral blood. In the periphery they may have been preferentially infected by HIV. Accumulation of infected T cells could thus occur in the intestinal mucosa. The special phenotypical and functional characteristics of intestinal T lymphocytes may affect the replication and cytopathicity of HIV, resulting in an accelerated loss of CD4 positive T cells in the lamina propria. CD4 T cells play a critical role in antigen-dependent B cell differentiation, thus the pronounced CD4 T cell depletion in the intestinal mucosa may be responsible for the observed decrease of IgA plasma cells and a reduced secretion of IgA2. Depletion and functional impairment of activated mucosal lamina propria lymphocytes by HIV infection could explain the break-down of the mucosal immune barrier leading to secondary opportunistic or nonopportunistic infections and secondary malignancies. In addition, because of the interrelation between the mucosal immune system and the epithelium these changes might be responsible for the partial small intestinal mucosal atrophy and maturational defects in enterocytes observed in HIV-infected patients. To be effective, a future prophylactic vaccine against HIV has to be able to induce not only systemic but also a local mucosal cellular and humoral protective immune response.

Acquired Immunodeficiency Syndrome↗
PubMed1995

[Ki-ras mutation as a molecular tumor marker for carcinoma of the pancreas].

More than 90% of tumours of the pancreas have mutations on codon 12 of the Ki-ras oncogene. Cellular DNA from pancreatic secretions and fine-needle biopsies, obtained from 69 patients (41 men, 28 women), were amplified by the polymerase chain reaction (PCR) to demonstrate this characteristic marker. All these patients had undergone endoscopic retrograde pancreatography for suspected pancreatitis or carcinoma of the pancreas. Two different methods were developed to demonstrate the mutations. With the aid of one of these methods, enrichment PCR with analysis of the restriction fragment length (FL), mutations on codon 12 of the Ki-ras gene were demonstrated in unstimulated pancreatic secretions of 29 of 33 patients with pancreatic carcinoma. All eleven fine-needle biopsies that had been cytologically examined showed the tumour-specific mutation. After direct sequencing of enrichment PCR a codon 12 mutation was demonstrated in pancreatic secretion from 21 of 24 patients and with the single strand conformation polymorphism analysis in 17 of 33 patients. In two of these 33 patients two different Ki-ras mutations were discovered. No mutations were found in acute inflammations or stone disease, while in five patients with chronic pancreatitis mutations were demonstrated only in those two patients in whom histological examination had revealed precancerous mucinous hyperplasia. This investigation indicates that codon 12 mutations of the Ki-ras gene, found after PCR in pancreatic secretion and biopsies, constitute a sensitive and specific tumour marker whose clinical value is being assessed.

Biomarkers, Tumor↗
PubMed1995

Culture of intestinal biopsy specimens and stool culture for detection of bacterial enteropathogens in patients infected with human immunodeficiency virus. The Berlin Diarrhea/Wasting Syndrome Study Group.

The diagnostic yields of stool cultures and biopsy specimens for the detection of enteric bacterial pathogens in 213 human immunodeficiency virus-infected patients were compared. Forty-five percent (19 of 42) of the pathogens were detected exclusively by stool culture, 2% (1 of 42) of the isolates were detected exclusively by culture of biopsy specimens, and 53% (22 of 42) were detected by both methods. Repeated stool cultures remain the most important means of diagnosing enteric bacterial pathogens, which were encountered in 20% (40 of 213) of all patients. The additional culture of biopsy specimens should be reserved for patients with suspected mycobacteriosis.

AIDS-Related Opportunistic Infections↗
PubMed1995

Loss of CD4 T lymphocytes in patients infected with human immunodeficiency virus type 1 is more pronounced in the duodenal mucosa than in the peripheral blood. Berlin Diarrhea/Wasting Syndrome Study Group.

Although changes in T lymphocyte subset distribution in the peripheral blood of patients infected with human immunodeficiency virus (HIV) are well defined it is not known whether these changes reflect changes in lymphoid compartments clearly involved in HIV related disease like the intestinal mucosa. This study analysed lymphocytes isolated simultaneously from the peripheral blood and duodenal biopsy specimens by three colour flow cytometry in eight asymptomatic HIV infected patients, 26 AIDS patients, and 23 controls. The proportion of CD4, CD8, CD4-CD8-, or gamma delta T cells did not correlate between circulating and duodenal T cells. CD4 T cells were reduced in the peripheral blood (7.5% (25th-75th percentile, 2-16%) v 52% (41-63%), p < 0.0005) and even more reduced in the duodenum (1% (1-2%) v 36% (23-57%), p < 0.0005) of AIDS patients compared with controls. Patients with asymptomatic HIV infection had intermediate CD4 T cells in the peripheral blood (24% (22-35%); p < 0.002 v controls; p < 0.01 v AIDS) but like AIDS patients very low CD4 T cells in the duodenum (3% (1-6%); p < 0.002 v controls). The ratio of duodenal to circulating CD4+ T cells was significantly reduced to 0.2 (0-1) in AIDS patients (p < 0.001) and even to 0.1 (0.04-0.5) in asymptomatic HIV infected patients (p < 0.002) compared with 0.72 (0.44-0.95) in controls. These findings show an early and preferential loss of duodenal CD4 T cells in HIV infection. Immunological abnormalities in HIV infection are distinct between lymphoid compartments, and profound immunodeficiency may occur in the intestinal immune system although circulating T cells are largely preserved.

Acquired Immunodeficiency Syndrome↗