[What role do intestinal T-lymphocytes play in the pathogenesis of hyperregenerative (sprue-typical) changes in the intestinal mucosa?].
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Biomedical subjects
Publications and source records attributed to M Zeitz.
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To define the characteristics of T cells associated with the gastrointestinal tract, the phenotypes and immunoregulatory function of T cells from mesenteric lymph node (MLN) and lamina propria lymphocytes (LPL) were compared to peripheral blood (PBL) and spleen lymphocytes in normal nonhuman primates. Mesenteric lymph node lymphocytes were characterized by a higher proportion of Leu-3+(CD4+) and 9.3+(alpha-Tp44) lymphocytes and a lower proportion of Leu-2+(CD8) lymphocytes than lymphocytes in other sites. LPL and MLN lymphocytes were both characterized by a higher proportion of cells having the helper-inducer phenotypes (Leu-3+, Leu-8+, Leu-3+, 2H4+) compared to PBL. A lower proportion of cells with the suppressor-inducer phenotypes (Leu-3+, Leu-8+, Leu-3+, 2H4+) was found in LPL, but not in MLN lymphocytes compared to PBL. In studies of the Leu-2+ T cells, it was found that whereas PBL, spleen, and LPL contained approximately equal proportions of Leu-2+, Leu-15+ (suppressor phenotype) and Leu-2+, 9.3+ lymphocytes (cytolytic T-cell phenotype), the MLN T cells were predominantly Leu-2+, 9.3+. Furthermore, the Leu-3/Leu-2 ratio was significantly higher in MLN compared to other sites. In pokeweed mitogen-stimulated cultures, the highest helper function for Ig synthesis was found in MLN. Cells from none of the sites studied showed evidence of increased suppressor cell activity. These results show that MLN and LPL T cells in normal nonhuman primates differ from T cells in peripheral blood and spleen. While both MLN and LPL have a high proportion of T cells with the helper-inducer phenotype, cells with the suppressor-effector phenotype are infrequent in MLN, while cells with the suppressor-inducer phenotype are infrequent in LPL.
To study the role of natural killer cells and immunoregulatory T cells in the pathogenesis of proctitis due to Chlamydia trachomatis (L2 serovar), lymphocytes were obtained from the rectal mucosa and other sites of nonhuman primates and studied by using phenotypic and functional assays. In animals with lymphogranuloma venereum (LGV) proctitis, the percentage of lymphocytes with the natural killer cell phenotype (Leu-11+) was not significantly higher at any site in LGV infection, and natural killer cell function of lymphocytes isolated from the rectum was lower during LGV infection. This was not due to the suppressive effect of factors in serum, rectal lymphocytes, or LGV elementary bodies. In studies of regulatory T cells, the Leu-3+/Leu-2+ ratio was lower in the peripheral blood and the spleen during LGV infection, but the ratio did not decrease in lamina propria T cells. Both peripheral blood and rectal lymphocytes had higher helper T-cell function for polyclonal immunoglobulin G (IgG) synthesis in pokeweed mitogen-stimulated cultures 2 weeks following LGV infection. Increased suppressor T-cell function for pokeweed mitogen-stimulated IgG synthesis was found only in the peripheral blood of animals 2 weeks after infection, but not in isolated rectal lymphocytes. These results indicate that in LGV proctitis natural killer cells are not an important component of the inflammatory infiltrate at the site of infection, and helper T-cell function increases in peripheral blood and rectal lymphocytes.
Complement fixing antibodies against different Escherichia coli lipopolysaccharides were determined in patients with Crohn's disease and in healthy individuals and compared with antitetanus toxoid antibodies. All healthy individuals had antilipopolysaccharide antibodies, 10 of 27 patients with Crohn's disease had no antibodies and six had rapidly changing antibody titres. These abnormalities were found in patients with disease in the colon, with arthropathy and fistula. Antilipid A was found at lower titres in Crohn's disease. Neither antitetanus toxoid antibodies, nor immunoglobulin concentrations were different in patients with or without antilipopolysaccharide antibodies. There was no evidence for circulating immune complexes in patients lacking antilipopolysaccharide antibodies. Certain subgroups of patients with Crohn's disease have altered antibody levels to typical enteral antigens which most likely can be explained by local antibody binding to lipopolysaccharides at inflammatory sites, or by changes in immunoregulation in this disease.
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We have investigated the short-term effects of hydrocortisone (60 mg/kg per day) and placebo on basal and stimulated pancreatic secretion in the conscious rat. Volume and enzyme secretion were determined; fine structural changes were examined simultaneously. The pancreatic and bile ducts were cannulated separately; pancreatic juice was drained via an isolated fistula, and bile was recirculated into the duodenum. The application of hydrocortisone led to an almost complete inhibition of the secretory response of the exocrine pancreas when stimulated with 0.25 U secretin in combination with 5 X 10(-8) g caerulein per h. It strongly affected the secretion rates of volume, protein, lipase, chymotrypsin, trypsin and carboxypeptidase, whereas the secretion rate of alpha-amylase continued to show a slight increase after stimulation. After stimulation with secretin and caerulein, the hydrocortisone-treated animals showed a higher density of zymogen granules in the acinar cell and an increase in the number of autophagic vacuoles in comparison to the equally stimulated placebo-treated rats. It is concluded that the short-term inhibition of pancreatic secretion by hydrocortisone occurs largely as a result of an inhibition of cellular enzyme discharge.
The aim of the present study was to evaluate in terms of quantitative measurements whether the well-known histomorphological and functional adaptive changes in the intestinal mucosa after small bowel resection are accompanied by alterations on the ultrastructural level. Therefore, samples of the ileal remnants after a 60% proximal resection were processed for ultrastructural evaluation and analyzed employing point counting planimetry and direct measurements. Microvillus surface area increased from the bottom of the crypts to the villus tips in both resected and sham-operated animals. This increase in microvillus surface area from the crypt to the villus was significantly less pronounced after proximal resection, while there were no changes in the crypt compartment. No significant differences of the relative areas of the nuclei, mitochondria, and the rough endoplasmic reticulum were observed when comparing the different positions along the villus crypt axis in normal and hyperplastic mucosa. In agreement with functional and enzyme histochemical results, these ultrastructural findings provide further evidence for an altered pattern of enterocyte maturation after proximal resection, which is most probably due to an increase in the migration rate of the enterocytes.
We have studied B-lymphocyte function in 39 patients with Crohn's disease and 35 normal individuals using a reverse haemolytic plaque assay as the effector system. Ten patients had active Crohn's disease, the others being in an inactive state of the disease. Compared with normal individuals, the Crohn's disease patients - especially those in the active state of the disease - had markedly raised numbers of spontaneous immunoglobulin secreting cells and severely decreased responses to the polyclonal activator pokeweed mitogen. The differences between the reactivity of patients with active disease and those with inactive disease were statistically significant. These findings indicate an in vivo polyclonal B-cell activation in Crohn's disease patients, possibly due to antigen(s) or infectious agent(s). In vitro experiments were performed with separated lymphocytes in order to characterise the mechanism responsible for the altered immune reactivity in Crohn's disease. These revealed an intrinsic B-cell defect as well as an impaired T-helper cell capacity in patients with Crohn's disease. Findings supporting the hypothesis of an increased suppressor activity in Crohn's disease patients could not be observed, and marker analyses revealed normal proportions with the exception of raised Leu 7 positive cells that mediate 'natural killer' and 'killer' cytolysis. We conclude that immune dysfunction in peripheral blood lymphocytes of Crohn's disease patients involves B-cells as well as T-helper cells.
Filiform nasoduodenal nutrition tubes in connection with portable infusion pumps are now available and by this way continuous enteral nutrition is given to a certain number of patients, thus avoiding expensive parenteral nutrition which demands a great deal of nursing care and bears a greater risk of complications. In order to study the acceptance and effects of this nutrition, 10 healthy persons were fed by the new system with a fiber-free, low molecular peptide diet. The probands had to write a daily protocol and, at the end of the test, had to answer a questionnaire regarding the effectivity and social consequences of the system and their subjective sensations. Before and after the enteral nutrition phase, different serum parameters were also determined. The results show that a continuous intraduodenal nutrition by tube can be achieved outside the clinic allowing to exercise the profession. The general well-being of the probands was moderately disturbed only by the tube whereas the other points from the questionnaire were less disturbing. Regarding the serum parameters only a reduction in the serum potassium was remarkable.
Due to the immobilisation of patients in intensive care units or to pathologic alterations in the upper gastrointestinal tract caused by stenosis or anastomosis, the insertion of feeding tubes into the duodenum has been difficult in some cases. For this reason an enteral feeding tube has been developed which can be introduced through the biopsy channel of an endoscope so that it is possible to place the tube under visual control. This method has been used in more than 20 patients; in each case the positioning of the tube and the consecutive nutrition were free of complications. The required material is now commercially available.
Immunological parameters and histocompatibility antigens (HLA) were determined in seven patients with non-bacterial cholangitis. Four patients had pericholangitis and ulcerative colitis, three had primary sclerosing cholangitis, one of these with ulcerative colitis. All 7 patients had antinuclear antibodies; however, there were no antibodies against DNA, against mitochondria or liver membrane antigens. One patient had low-titre rheuma factors. Immunoglobulins G, A and M and complement components C3 and C4 were mostly in the normal range. HLA constellation was positive for B8 in 6 patients. These were male patients with disease manifestations between the 12th and 45th year of life. The results support the concept that pericholangitis and primary sclerosing cholangitis with or without ulcerative colitis are related hepatological disease entities with an immunological pathogenesis and an underlying genetical determination.
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The nature of red fluorescent particles in vitally acridine orange stained C 1300 neuroblastoma monolayer cells was evaluated by electron microscopy, cytofluorometry, cytopharmacological and cell fractionation studies. At the ultrastructural level the distribution of red fluorescent granules correlated with that of the Golgi complex and Golgi derived structures during various stages of differentiation, mitosis, and under colcemid treatment. Cytopharmacological studies revealed that red fluorescence was displaced in a concentration and time dependent manner with the basic drugs chloroquine and quinacrine. Subcellular fractionation studies showed that acridine orange was concentrated in fractions that also contained the highest amount of acid phosphatase and electron dense vesicles. Vital acridine orange staining of neuroblastoma cells in culture can give information on the relationship between Golgi-derived vesicles and cell functions like proliferation and differentiation. The influence of drugs on these processes can be studied.
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Collagen metabolism in granulating wounds of rat skin was studied with biochemical, isotopic and electron microscopical methods. Deposition of collagen in rat skin wounds was not only the result of an increase in collagen synthesis but it was also caused by a decrease in collagen degradation. Our investigations showed significant differences in the collagen turnover at different times of wound healing. Decreased collagen catabolism at the early stages of wound healing contributed decisively to collagen accumulation in the wound area. At later stages, during wound contraction and remodelling of the scar, the rate of collagen degradation rose. The above-mentioned results are discussed in the context of general criteria of scar formation.
The remission of a case of Marchiafava-Micheli under therapy with Lynestrenol is represented. The observation period is 16 months. The therapeutical purpose--stabilizing the red cell membrane by increasing the serum cholesterol concentration--is discussed by laboratory findings. Moreover the clinical picture and other common treatments against this disease are demonstrated by the example of this case.
Addition of 6-AN (0.01 mg/ml) to growing cultures of C-1300 neuroblastoma cells strongly reduced cell division. This growth inhibition was accompanied by a higher cell volume and a lower protein content per cell as compared to controls. Concurrently the specific activity of AChE increased markedly incontrols and 6-AN-treated cultures. During the experimental periods the specific activity of AChE was significantly higher after 6-AN. Morphologically, 6-AN-treated cultures showed characteristic signs of differentiation, i.e. enlarged, flattened cells with long branched processes. The described effect of 6-AN on growth and differentiation of neuroblastoma cells was less pronounced if cells received the antimetabolite after a subcultivation period of 5 days.