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M Zeitz

Publications and source records attributed to M Zeitz.

At least 19 recordsLinked to original sources
PubMed1992

T cell differentiation antigens on lymphocytes in the human intestinal lamina propria.

Recently, T cell subpopulations presumably representing memory T lymphocytes have been described in vitro. Intestinal lamina propria T cells (LP-T) have characteristics resembling those of memory cells. We therefore investigated the expression of surface Ag associated with memory phenotype in vitro on lamina propria lymphocytes (LPL) and PBL and on the T cell subpopulations defined by the bright expression of CD45R0 by flow cytometric analysis of isolated cell populations. LPL had significantly increased percentages of CD45R0 and CD58 positive cells compared with PBL. Whereas PBL showed bimodal expression profiles of CD45R0, CD58, and CD2, the vast majority of LPL was bright for these Ag. Expression of CD45RA was significantly reduced in both frequency and intensity in LPL, and LPL had significantly reduced percentages of CD11a/CD18 and CD29 positive cells compared with PBL. The CD45R0 bright T cell subpopulations of both PBL and LPL were characterized by a lack of CD45RA. CD45R0 bright T cells from the peripheral blood (PB-T) were predominantly bright for CD2, CD58, CD29, and CD11a/CD18 whereas CD45R0 dim PB-T had bimodal expression profiles and CD45R0 negative PB-T were dim or even negative for these Ag. CD45R0 bright LP-T were also bright for CD2 and CD58 but had significantly reduced surface densities of CD11a/CD18 and CD29 compared with CD45R0 bright PB-T. The surface density of CD29 on CD45R0 bright LP-T corresponded to that of CD45R0 negative PB-T, and a significant proportion of CD45R0 bright LP-T was even negative for CD11a/CD18 and CD29. Additionally, CD45R0 bright LP-T in contrast to PB-T were characterized by a lack of 1-selectin and the expression of CDw49a and the mucosa-specific T cell Ag HML-1 on high percentages of cells. Our results show that the phenotype of CD45R0 bright T cells from the lamina propria clearly deviates from that of memory T cells in vitro and of CD45R0 bright T cells in the peripheral blood. We conclude that memory T cell populations in vivo undergo specific differentiation depending on their tissue localization, leading to unique phenotypic and presumably functional features.

Adult↗
PubMed1992

Development of ulcerative colitis under the immunosuppressive effect of cyclosporine.

In recent studies, cyclosporine has been used for the treatment of both ulcerative colitis and Crohn's disease. The results of these studies were variable. We report on a patient who was treated for 6 years with cyclosporine after kidney transplantation. He developed chronic distal colitis with all the features of ulcerative colitis. An infectious etiology of the colitis was carefully excluded. High-dose treatment with methylprednisolone was required to induce remission. This report shows that immunosuppressive therapy with cyclosporine did not prevent the development of ulcerative colitis in this patient.

Colitis, Ulcerative↗
PubMed1992

Ion transport in the experimental short bowel syndrome of the rat.

The adaptational changes of epithelial ion transport in the short bowel syndrome were studied. Ileal remnants of rats were investigated 8 weeks after 70% proximal small intestinal resection. Pure epithelial resistance measured by impedance analysis decreased from 27 +/- 1 to 21 +/- 1 omega.cm2, and polyethylene glycol 4000 fluxes increased from 2.5 +/- 0.3 to 3.6 +/- 0.3 nmol.h-1.cm-2, indicating increased permeability of the short bowel. Unidirectional flux measurements in control ileum showed absorptive net fluxes of Na+ and Cl- that were assigned to electroneutral NaCl absorption and a short-circuit current that was accounted for by the residual flux (HCO3- secretion). Neither NaCl absorption nor HCO3- secretion were altered in the short bowel. Also, electrogenic Cl- secretion, defined after maximal stimulation by theophylline and prostaglandin E1 was not changed in the short bowel. In contrast, electrogenic Na+/glucose cotransport increased in Vmax from 2.0 +/- 0.3 in controls to 5.0 +/- 1.0 mumol.h-1.cm-2 in the short bowel. Tight junction structure was studied by freeze-fracture electron microscopy. The number of horizontal strands was unchanged, whereas tight junction depth was slightly increased in the short bowel. Microvillus area of short bowels was increased by 20% in villus regions. Under the light microscope, villus height was increased by 30%. In conclusion, the short bowel mucosa undergoes adaptive responses to reduced overall absorptive area by increasing glucose-dependent electrogenic Na+ absorption to 250%, which is partly caused by increased villus and microvillus surface area. Electrogenic Cl- and HCO3- secretion and electroneutral NaCl absorption remained unchanged. The decreased epithelial resistance is caused by mucosal surface amplification.

Adaptation, Physiological↗
PubMed1992

Effects of zidovudine treatment on the small intestinal mucosa in patients infected with the human immunodeficiency virus.

Zidovudine is associated with hematologic toxicity and may also impair the rapidly proliferating intestinal epithelium. However, patients with human immunodeficiency virus (HIV) infection receiving zidovudine gain body weight, indicating improved absorptive function. In the present study, 33 HIV-infected patients with gastrointestinal symptoms who were undergoing duodenoscopy and who had no detectable secondary intestinal pathogens were investigated; 12 of them received zidovudine. HIV antigen p24 was detected in duodenal biopsy specimens by immunohistology in 3 of 12 patients with zidovudine treatment and in 10 of 21 patients without zidovudine treatment. Morphometry of duodenal specimens showed reduced villus surface area (P less than 0.05) without crypt hyperplasia independent of zidovudine therapy and reduced numbers of crypt mitoses in patients with mucosal HIV infection (P less than 0.001) compared with controls. In the duodenal brush border, patients with mucosal HIV infection (P = 0.006) and patients without zidovudine treatment (P = 0.009) had absent lactase/beta-glucosidase activity more frequently than controls, and all HIV-infected patients (P less than 0.025) except zidovudine recipients had decreased alkaline phosphatase activity compared with controls. These findings show a hyporegenerative atrophy of the small intestine and enterocyte dysmaturation associated with mucosal HIV infection. Improved enterocyte maturation, indicated by increased brush border enzyme activity, may contribute to the clinical benefit of HIV-infected patients from zidovudine therapy.

Adult↗
PubMed1992

Enteric immunologic abnormalities in human immunodeficiency virus infection.

The intestinal mucosa is an important portal of entry of HIV, and HIV-infected mononuclear cells are found in the intestinal lamina propria of 30 to 50% of HIV-infected patients even at early stages of the disease. HIV infection of epithelial cells has not consistently been detected and is still controversial. Intestinal T cells are phenotypically and functionally distinct from circulating T cells, especially in their state of activation and differentiation, which both affect the replication and cytopathicity of HIV. An increase in CD8+ cells and variable decreases in CD4+ cells have been found in the intestinal lamina propria by immunohistologic studies, resulting in a decreased CD4 to CD8 ratio; in addition, CD25 expression is reduced. Changes in intraepithelial lymphocytes are unclear. B-cell differentiation seems to be disturbed because IgA plasma cells and IgA2 secretion are reduced. Depletion or functional impairment of activated mucosal lamina propria lymphocytes by HIV infection could explain the breakdown of the mucosal immune barrier leading to opportunistic diseases; in addition, due to the interrelationship between mucosal immune system and epithelium, these changes might be responsible for the partial bowel atrophy and maturational defects in enterocytes of HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Gastrointestinal symptoms in patients infected with human immunodeficiency virus: relevance of infective agents isolated from gastrointestinal tract.

The correlation of gastrointestinal symptoms and infections in 186 consecutive patients with human immunodeficiency virus (HIV) infection undergoing diagnostic endoscopy (oesophagogastroduodenoscopy, n = 124; colonoscopy, n = 37; both, n = 25) was investigated. Biopsy and stool samples were examined for infective agents. Only weight loss (p = 0.003) and dysphagia (p = 0.027) were more common in patients at stage CDC IV compared with earlier stages. In three of 27 patients at stage II/III and in 93 of 159 patients at stage IV an infective agent was identified in stool or gastrointestinal biopsy specimen (p < 0.001). Cytomegalovirus (n = 35), Candida sp (n = 28), M avium complex (n = 10), and Cryptosporidium (eight) were the most frequent agents detected. At stage IV, diarrhoea was more frequent in infected compared with non-infected patients (p = 0.006); however, an infective agent was also found in 39 of 82 patients at stage IV without diarrhoea. The frequency of gastrointestinal symptoms was not consistently increased in patients harbouring specific infective agents compared with non-infected patients. Our findings indicate that the pathogenic relevance of a gastrointestinal infection in HIV infected patients has to be verified and indirectly support the existence of an HIV associated enteropathy.

Adult↗
PubMed1992

A phase I trial of interferon alpha-2b with folinic acid and 5-fluorouracil administered by 4-hour infusion in metastatic colorectal carcinoma.

Preclinical data suggest that both folinic acid and interferon may enhance the efficacy of 5-fluorouracil (5-FU) in colorectal carcinoma. We therefore initiated a phase I trial evaluating the doses, safety, and pharmacokinetics of the combination of recombinant interferon (IFN) alpha-2b with folinic acid (FA) and 5-FU. Seventeen patients with colorectal cancer who failed local chemotherapy received 5-FU as a 4-hour infusion, preceded by a bolus of FA and IFN. The 5-FU dose was escalated over the range of 400 to 650 mg/m2/d for a period of 7 days. Folinic acid was administered as a bolus in a fixed dose of 200 mg/m2/d and IFN as 5 million U/d subcutaneously on days 1 to 7. A total of 89 courses of therapy were completed for the 17 patients, of which there were 10 paired courses with a combination of 5-FU and IFN or 5-FU alone, being performed to analyze the pharmacokinetics and modulation of 5-FU by IFN. The maximum tolerated dose of 5-FU using this combination and a 4-hour schedule was 600 mg/m2/d for 7 days. The dose-limiting toxicity of this regimen was diarrhea. Mucositis and myelosuppression was not a marked problem at dose levels of 400 and 500 mg/m2/d for 7 days. However, at a dose level of 600 to 650 mg/m2/d for 7 days, grade 3 and 4 (WHO) leukopenia occurred in 50% and mucositis occurred in 33%. At a given dose of 5 million U, IFN did not significantly influence 5-FU serum levels. Mean steady-state serum levels of 5-FU at 500 mg/m2 given as a 4-hour infusion were 16.55 +/- 9.34 mumol/L and 18.23 +/- 12.77 mumol/L with and without IFN, respectively. Mean area under the curve (mumol/L x min) was 4,008 +/- 2,133 and 5,114 +/- 2,567 with and without interferon, respectively. Objective responses were seen in one of 17 of these heavily pretreated patients and stable disease was seen in seven of 17 patients. The recommended dose of 5-FU for use of phase II studies is 500 mg/m2/d for 7 days. We conclude that the toxicity of 5-FU plus FA with and without IFN alpha-2b can be reduced by using a 4-hour infusion instead of a bolus.

Adult↗
PubMed1991

AIDS enteropathy.

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Acquired Immunodeficiency Syndrome↗
PubMed1991

Intestinal microsporidiosis in a German patient with AIDS.

Since intestinal microsporidiosis might be of importance in the pathogenesis of gastrointestinal symptoms in patients infected with HIV, we examined duodenal biopsies of HIV-infected patients by electron microscopy. Enterocytozoon bieneusi infection of the small intestine was found in one of 23 patients studied, which gives a 95% confidence interval for the prevalence rate between 0.1% and 22%. The infected patient was a 24-year-old homosexual male with AIDS who underwent upper endoscopy because of acute epigastric pain, nausea, and vomiting. These symptoms were obviously due to mesenterial Kaposi's sarcoma obstructing the duodenal passage, as was later revealed at autopsy. However, microsporidiosis might have caused the patient's eight-month history of diarrhea and weight loss, since infected cells showed signs of degeneration, and no other pathogens were ever detected in stool or biopsy. Our finding of Enterocytozoon bieneusi infection in a German AIDS patient supports the concept of a worldwide distribution of this parasite; further studies are needed to define its exact prevalence in HIV-infected patients and its pathogenic relevance.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Phenotype and function of lamina propria T lymphocytes.

Lamina propria T cells have a low expression of the CD45RA antigen and a high expression of the CD45RO antigen. This phenotype is characteristic for memory T cells (table 2). In addition, T cells in the effector compartment of the mucosa bear surface antigens which are very rarely found in other sites of the immune system. Intestinal T cells also express functional IL-2 receptors and IL-2 receptor alpha chain mRNA, and are able to synthesize high amounts of IL-2. However, another marker of memory T cells, CD29, is not expressed in high density in the lamina propria indicating that lamina propria T cells differ from 'classical' memory T cells. This is supported by functional studies in nonhuman primates infected rectally with C. trachomatis which show that lamina propria T cells do not proliferate after stimulation with antigen but rather provide helper function for immunoglobulin synthesis (table 2). The intestinal lamina propria therefore contains highly specialized T cells which have a distinctive phenotype and are activated. Functionally these T cells can be characterized as differentiated effector lymphocytes which respond to triggering the antigen-specific T cell receptor by secreting helper factors for B cells. This concept is supported by recent studies showing that the pattern of lymphokines produced by lamina propria T cells and the responsiveness to certain lymphokines differ from those of other lymphocyte populations [25]. Lamina propria T cells thus represent a subset of memory T cells with a unique maturational state.

Animals↗
PubMed1991

Role of lymphokines in immunoregulatory function of mucosal T cells in humans and nonhuman primates.

The findings presented above and in other studies provide substantial evidence that lymphocytes in the intestinal lamina propria differ from lymphocyte populations in the circulation or in other tissue sites in a number of ways. First, lamina propria lymphocytes are phenotypically distinct and have evidence of activation. Lymphocytes in the intestinal lamina propria are different in their potential for expression of lymphokine gene products, since activated cells from the lamina propria have high expression of mRNA for IL-2, IL-4, IL-5 and IFN-gamma in comparison to circulating lymphocytes. Mesenteric lymph node T cells also differ from circulating lymphocytes in their high expression of IL-4 and IL-5 mRNA. A further difference between mesenteric lymph node and lamina propria T cells is that the former are capable of proliferating in response to IL-4, whereas the latter are not. These phenotypic and mRNA differences of lamina propria lymphocytes also correlate well with their high helper activity in vitro for immunoglobulin synthesis in the pokeweed mitogen system. Finally, lamina propria T cells at a site of inflammation are able to provide high helper activity in response to specific antigens. These observations are all consistent with the conclusion that T cells in the lamina propria are pleomorphic, but are highly enriched for subpopulations of activated memory cells that are geared for effector functions. These functions are likely to be critical in maintaining normal host defense in the mucosal environment.

Animals↗
PubMed1991

Comparison of enteral nutrition and drug treatment in active Crohn's disease. Results of the European Cooperative Crohn's Disease Study. IV.

This study compared the effect of enteral nutrition as the sole therapy of active Crohn's disease with drug treatment. Patients with active Crohn's disease (Crohn's Disease Activity Index greater than 200) were randomized to receive either enteral nutrition with a liquid oligopeptide diet (n = 55) or a combination of 6-methylprednisolone, 48 mg daily, subsequently tapered, and sulfasalazine, 3 g daily (n = 52). The two groups were not different with respect to age, sex, body weight, location of disease, or treatment before the study. The severity of disease was similar at the beginning of the study in both groups [Crohn's Disease Activity Index (mean +/- SEM), 323 +/- 12 vs. 316 +/- 11]. Remission was defined as a decrease of the initial Crohn's Disease Activity Index by 40% or at least 100 points. Twenty-nine patients in the diet group and 41 patients in the drug group reached remission within 6 weeks of therapy (chi 2 test, P less than 0.01). The median elapsed time to remission was 30.7 days in the diet group compared with 8.2 days in the drug group (Mantel Cox, P less than 0.01). To determine whether one of these treatments was more beneficial for a subgroup of patients, the effectiveness of both treatments was analyzed separately in patients with very severe disease (initial Crohn's Disease Activity Index greater than 300) and less severe disease (initial Crohn's Disease Activity Index less than 300), and in patients with different disease location. However, no influence of initial disease activity or disease location on the effect of either treatment could be shown. These data show that enteral nutrition is less effective than a combination of 6-methylprednisolone and sulfasalazine in treating active Crohn's disease.

Adult↗
PubMed1991

Evaluation of endosonography in sclerotherapy of esophageal varices.

During intravariceal sclerotherapy of esophageal varices with polidocanol in 32 patients with portal hypertension due to liver cirrhosis of various etiologies, endosonographic assessment of both esophageal and gastric intramural vessels was carried out in order to evaluate the usefulness of endosonography in the follow-up of the variceal status. In all cases endosonography demonstrated esophageal and gastric varices; in contrast, only five cases of gastric varices could be demonstrated by endoscopy. Furthermore, different stages of variceal obliteration following sclerotherapy could be demonstrated by means of endosonography, and it was possible to identify incomplete obliteration in about one-third of the patients in whom inadequate sclerotherapy was suspected endoscopically. In addition, the status of gastric varices during sclerotherapy was demonstrated by means of endosonography. Only in cases of adequate sclerotherapy of esophageal varices, as assessed by both endoscopic and endosonographic criteria, were gastric varices plugged. On the basis of these findings endosonography would appear to be a useful technique for the diagnosis and follow-up of esophageal and gastric varices during intravariceal sclerotherapy.

Esophageal and Gastric Varices↗