Search PubMed⌕ Search

Biomedical subjects

C O Elson

Publications and source records attributed to C O Elson.

At least 91 records · Page 5Linked to original sources
PubMed1987

Collagen synthesis by human intestinal smooth muscle cells in culture.

Growth kinetics and collagen production were determined in smooth muscle cells isolated from human jejunum and maintained in cell culture. Collagen synthesis increased during the first 15 days in culture at a time when the rate of cell proliferation was maximal. When confluent, these cells produced significantly more collagen than human dermal fibroblasts cultured under identical conditions. The smooth muscle cells required daily replenishment of ascorbate for maximal collagen synthesis. The types of collagen produced by human intestinal smooth muscle cells in culture were the same as those collagens extracted from strictured human bowel (types I, III, and V). These findings suggest that collagen production by human intestinal smooth muscle cells has a role in the repair as well as the fibrosis of the gastrointestinal tract.

Ascorbic Acid↗
PubMed1986

Intestinal immunity and inflammation: recent progress.

The previous sections illustrate that we are still defining (a) which sets of lymphoid cells are present in the intestine and which are not, (b) which sets are peculiar to the intestine, and (c) how the sets that are there function in the intestinal microenvironment. An understanding of the latter point is going to require knowledge of how these sets communicate with and regulate one another via cell surface molecules such as MHC class I and class II molecules, and via soluble mediators or lymphokines. The recent advances in various technologies make this a particularly exciting time in this field because the tools are now available to address and answer some of these basic and important questions in mucosal immunology. At the same time these advances hold great promise for our eventual understanding of chronic inflammatory diseases of the intestine. As was mentioned at the outset, the immune system has considerable power for both protection and destruction. It remains a puzzle how this latter potential is contained and controlled in the intestine of most individuals, such that they do not have inflammatory disease even in the setting of intense stimulation by substances, such as endotoxin, that are phlogistic elsewhere in the body. An answer to the question of why everyone does not have intestinal inflammation could provide new insights into the mechanisms involved in chronic intestinal inflammatory diseases. The recent advances just detailed, as well as others sure to come, suggest that it is only a matter of time before such questions are answered.

Animals↗
PubMed1985

T cell-B cell regulation in the intestinal lamina propria in Crohn's disease.

Many patients with Crohn's disease have suppressor T cells circulating in the peripheral blood that are potent inhibitors of immunoglobulin synthesis in vitro. The purpose of this study was to examine the regulatory effects of T cells isolated from the lamina propria of patients with Crohn's disease or of patients with other diseases. Lamina propria cells were isolated from surgically resected intestine by sequential ethylenediaminetetraacetic acid and collagenase incubations. T cells were purified from lamina propria either by anti-F(ab)2' affinity columns or by a panning technique using monoclonal anti-T cell antibodies. Changes in the pokeweed mitogen-stimulated synthesis of immunoglobulin M, immunoglobulin G, and immunoglobulin A by normal peripheral blood indicator lymphocytes, as measured by sandwich enzyme-linked immunosorbent assay, was used as an index of help and suppression. Helper T-cell activity was sought by coculturing lamina propria T cells with normal peripheral blood cells plus pokeweed mitogen. Helper T-cell activity was found among lamina propria T-cell populations of patients and controls to a roughly comparable extent; help was provided for all isotypes. Suppressor T-cell activity was sought by coculturing lamina propria T-cells with normal B cells plus irradiated normal T cells plus pokeweed mitogen. No significant suppressor T-cell activity was observed in these cocultures, whether the cells were obtained from control intestine, the grossly uninvolved margin of Crohn's disease intestine, or actively inflamed Crohn's disease intestine. We conclude that suppressor T-cell activity of the sort found previously in the peripheral blood of patients with Crohn's disease is not demonstrable in the intestinal lesions of Crohn's disease. Helper T-cell activity is the predominant regulatory activity in both control and inflamed intestinal lamina propria.

Adolescent↗
PubMed1985

Induction and control of the gastrointestinal immune system.

The stimulation of cells in gut associated lymphoid tissue (GALT) by intestinal antigens can result either in immunity or tolerance to that antigen. The factors that determine which effect predominates are not understood, but the answer seems to lie in a better understanding of the cellular interactions and regulatory mechanisms in GALT. Induction of an immune response in GALT involves the same macrophage-T cell, T cell-T cell, and T cell-B cell interactions that have been described in other lymphoid tissues. Regulatory T cells have now been shown to play an important role in controlling the immune response to intestinal antigens. The presence of helper T cells specific for the IgA isotype in Peyer's patches may partly explain the old observation that the intestinal route is preferential for this antibody class. The stimulation of suppressor T cells in GALT is responsible for many instances in which tolerance rather than immunisation has followed antigen feeding. Although there is experimental evidence supporting the idea that mucosal IgA immunity and systemic IgG tolerance can occur concomitantly after antigen feeding, recent data obtained after the feeding of a variety of protein antigens indicate that this is not the usual result. More commonly either immunity or tolerance occurs concomitantly in both mucosal and systemic systems after antigen feeding, suggesting that the suppressor cells mediating oral tolerance also suppress mucosal IgA responses.

Animals↗
PubMed1985

Genetic control of the murine immune response to cholera toxin.

This study was undertaken to determine whether previously noted differences in the immune response of inbred strains of mice to cholera toxin (CT) might be under immune response gene control. A series of inbred, congenic, and intra-H-2I region recombinant mouse strains were tested for responsiveness to CT after i.p. immunization with 0.1 micrograms CT in alum. Samples of plasma were collected at intervals before and after priming and boosting. IgG and IgA anti-CT were measured by ELISA. In three different sets of congenic strains, the level of IgG anti-CT clearly depended on the H-2 haplotype of the strain rather than on any background or Igh genes. Strains with the H-2b and H-2q haplotypes were high responders, and strains with the H-2k, H-2s and H-2d haplotypes were low responders. Within the H-2 complex, the IgG anti-CT response was mapped to the I-A subregion with the use of congenic intra-H-2I region recombinant strains. In contrast to these results with IgG anti-CT, plasma IgA anti-CT levels were uniformly low and indeterminate. We conclude that the murine IgG anti-CT response is controlled by a locus within the I-A subregion of H-2--a remarkable finding, considering the known abilities of this toxin to bind to and to directly stimulate lymphocytes.

Animals↗
PubMed1984

A lavage technique allowing repeated measurement of IgA antibody in mouse intestinal secretions.

Mouse intestinal secretions can be readily obtained without harm to the mice by administering a lavage solution to them intragastrically followed by pilocarpine intraperitoneally. These secretions are rich in proteases but this enzyme activity can be blocked by addition of a mixture of inhibitors. Both total and specific IgA antibody could be measured in these secretions using ELISA techniques. The total IgA recovered was found to vary considerably, even in the same group of mice sampled on multiple occasions. Specific IgA anti-cholera toxin antibody was easily demonstrable in the intestinal secretions of mice fed cholera toxin but not of mice fed an irrelevant antigen. Expression of the specific IgA antibody per unit of total IgA recovered is desirable in order to correct for the variable recovery of IgA.

Animals↗
PubMed1984

Isolation and culture of human intestinal smooth muscle cells.

Intestinal smooth muscle cells were isolated from human bowel and maintained in culture through several passages. These cells were obtained by enzyme digestion of slices taken from the circular layer of the muscularis propria of human jejunum. When subcultured, they initially flattened out and then began proliferating after 3 days. After 3 weeks in culture, they began aggregating into ridges. Fluorohistochemical staining revealed numerous prominent actin stress fibers. When these cells were exposed to the C-terminal octapeptide of cholecystokinin they contracted in a dose-dependent fashion. The availability of human intestinal smooth muscle cells in culture will considerably enhance our ability to study the contractile, proliferative and connective tissue responses of the smooth muscle of the human gastrointestinal tract.

Cell Division↗
PubMed1984

Hypogammaglobulinemia due to abnormal suppressor T-cell activity in Crohn's disease.

Two patients are described who initially developed Crohn's disease followed by hypogammaglobulinemia. The immunologic profile of both was typical of acquired common variable hypogammaglobulinemia. The peripheral blood lymphocytes of neither patient were able to synthesize immunoglobulin when cultured with pokeweed mitogen in vitro nor were cultures containing mixtures of purified B cells and T cells. A potent suppressor T cell was present in the peripheral blood of both patients that was able to completely suppress immunoglobulin synthesis in cultures of normal B cells and T cells. When the patients' B cells were highly purified and appropriately stimulated in vitro, they were able to synthesize immunoglobulin, providing strong evidence that the circulating suppressor T cell was mediating the hypogammaglobulinemia. We have previously shown that many patients with Crohn's disease have a circulating "covert" suppressor T cell that is not expressed in cultures of unfractionated peripheral blood lymphocytes, but which becomes apparent after isolation of their T cells on antiimmunoglobulin columns. We conclude that these 2 patients represent instances in which the "covert" suppressor T cell of Crohn's disease has become overtly active in the systemic circulation and has resulted in hypogammaglobulinemia.

Adult↗
PubMed1984

Generalized systemic and mucosal immunity in mice after mucosal stimulation with cholera toxin.

Cholera toxin (CT) has been found to be an extremely potent immunogen for mucosal IgA responses when administered via the intestine. This study has examined both mucosal and systemic immune responses after feeding CT and compared these responses with those obtained after feeding keyhole limpet hemocyanin (KLH), another protein that is strongly immunogenic in mice. Feeding CT to mice resulted not only in IgA antibody in intestinal secretions but also resulted in substantial plasma IgG and IgA antibody levels. Feeding KLH in much larger quantity resulted in little or no antibody response in intestinal secretions or plasma. Lymphoid cells from various tissues of mice fed CT were cultured in vitro for 10 days and the supernatant was tested for antibody to CT. Spontaneous antibody synthesis (no antigen added to cultures) was present in cultures of each cell type, but IgG anti-CT was found mainly in cultures of spleen and mesenteric lymph node cells and IgA anti-CT mainly in cultures of Peyer's patch and lamina propria cells. Peyer's patch cells cultured with CT as antigen synthesized both IgG and IgA anti-CT, suggesting that the antibody response to both isotypes originated in this site. Helper T cell activity for both IgA and IgG anti-CT was detected in spleens, mesenteric lymph nodes, and Peyer's patches. Lastly, when KLH and CT were fed to mice at the same time, an intestinal IgA anti-KLH and plasma IgG anti-KLH response was stimulated, a response pattern similar to that occurring to CT after CT was fed alone. We conclude that mucosal stimulation by CT generates both a systemic IgG and mucosal IgA response to this antigen, and that CT can cause a similar pattern of response to an unrelated protein antigen when both are administered into the intestine at the same time. The data favor the idea that both the IgG and IgA responses originate in GALT and then disseminate to other tissues. We propose that CT accomplishes these effects by altering the regulatory environment within GALT.

Administration, Oral↗
PubMed1984

Cholera toxin feeding did not induce oral tolerance in mice and abrogated oral tolerance to an unrelated protein antigen.

The feeding of protein antigens to mice results in a state of tolerance when feeding is followed by parenteral immunization. Cholera toxin (CT) is a protein that has been used extensively as a potent oral immunogen for mucosal IgA responses, but CT feeding also stimulates a substantial plasma IgG antibody response. This latter finding prompted us to study whether or not CT induces oral tolerance. Mice were fed 5 mg keyhole limpet hemocyanin (KLH) or 10 micrograms CT at least twice before parenteral immunization with 1 microgram KLH or CT in alum i.p. Plasma and intestinal secretions were collected at intervals. The specific IgG or IgA antibody in the samples was measured by ELISA. Although KLH feeding did induce oral tolerance, CT feeding did not induce oral tolerance in any of three mouse strains tested or at any dose of CT given orally. The feeding of the B subunit of CT did not result in oral tolerance either. When both CT and KLH were fed together, CT was able to abrogate oral tolerance to KLH, an antigenically unrelated protein. Moreover, feeding CT along with KLH stimulated secretory IgA anti-KLH responses, whereas no such IgA responses were found when KLH was given alone. Thus, in these experiments with protein antigens, IgA immunization and oral tolerance were reciprocally linked and did not occur simultaneously. CT appears to abrogate oral tolerance and to stimulate secretory IgA responses by altering the regulatory environment in gut-associated lymphoid tissue, shifting it toward responsiveness.

Administration, Oral↗
PubMed1983

Human host response to Giardia lamblia. II. Antibody-dependent killing in vitro.

We examined whether peripheral blood monocytes, lymphocytes, polymorphonuclear leukocytes, or eosinophils, obtained from individuals without known exposure to Giardia lamblia, exhibit antibody-dependent cellular cytotoxicity (ADCC) for this organism. Peripheral blood granulocytes but not lymphocytes from each individual were cytotoxic for G. lamblia in the presence of either human or rabbit anti-G. lamblia serum. At an effector to target ratio of 30:1, granulocyte cytotoxicity was 20% in the presence of human antiserum and 36% in the presence of rabbit antiserum. Granulocyte ADCC was concentration dependent with respect to antiserum and was not complement mediated. Most of the ADCC activity was mediated by polymorphonuclear neutrophils, and to a lesser extent by eosinophils. The predominant isotype of the antibodies sensitizing G. lamblia for granulocyte ADCC was IgG. We conclude that human peripheral blood granulocytes are cytotoxic for G. lamblia in the presence of IgG anti-G. lamblia antibodies. This activity, in addition to the previously observed spontaneous monocyte cytotoxicity, is likely to be an important mechanism for host defense against this parasite.

Animals↗
PubMed1982

Human host response to Giardia lamblia. I. Spontaneous killing by mononuclear leukocytes in vitro.

To understand host resistance to Giardia lamblia infection, we investigated the capacity of human peripheral blood effector cells to kill G. lamblia trophozoites. Peripheral blood was obtained from 12 healthy, uninfected individuals without detectable IgG anti-G. lamblia antibody or known exposure to G. lamblia. Isolated mononuclear leukocytes (MNL), granulocytes, lymphocytes, and monocytes were cultured 16 hr with G. lamblia that had been pulsed with (3H)TdR while in log growth. MNL from all 12 individuals were spontaneously cytotoxic for G. lamblia. Specific cytotoxicity ranged from 13% at an E:T of 3:1 to 56% at an E:T of 100:1. Release of 3H directly correlated with a decrease in viable G. lamblia. In contrast to the uniform cytotoxicity by mononuclear cells, granulocytes and lymphocytes had no spontaneous cytotoxic activity for G. lamblia. MNL depleted of phagocytic or adherent cells lost all cytotoxic activity. Also, G. lamblia induced nonspecific MNL cytotoxicity to unrelated target cells. Finally, cytotoxicity against G. lamblia could be inhibited by adding unlabeled Trichomonas vaginalis, suggesting that this may be a more general mechanism of host defense against extracellular protozoa. We conclude that human peripheral blood monocytes-macrophages are spontaneously cytotoxic for G. lamblia and that this may be a major mechanism of host defense against this parasite.

Adult↗
PubMed1981

Covert suppressor T cells in Crohn's disease.

To determine whether patients with Crohn's disease have a defect in immune regulation, suppressor T-cell activity was assessed in 16 patients with mild or inactive Crohn's disease and was compared with that of an equal number of randomly selected normal controls. Pokeweed mitogen-stimulated cultures of peripheral blood lymphocytes from patients synthesized as much IgM as those from normal controls. In addition, cocultures of patient and normal peripheral blood lymphocytes did not result in either suppression or enhancement of immunoglobulin M synthesis. In contrast to these results with cultures of peripheral blood lymphocytes, cultures containing optimal ratios of purified B cells and T cells from patients synthesized significantly less immunoglobulin M (p less than 0.005) than those from normals; in fact, the latter cultures from 6 patients synthesized no detectable immunoglobulin M. Detailed studies of cells from these patients indicated that a suppressor T cell was revealed in vitro during the cell-purification procedure. Finally, in those patients in whom it could be measured, radiation-sensitive suppressor T-cell activity was found to be normal. We conclude that there is no deficiency of suppressor T cells regulating antibody synthesis in patients with Crohn's disease; on the contrary, at least one-half of these patients have suppressor T cells that markedly inhibit the synthesis of immunoglobulin M, but which are revealed only after purification of the T cells.

Adult↗
PubMed1981

Immunoregulatory function of T cells activated in the autologous mixed lymphocyte reaction.

This study was undertaken to define the functional properties of T cells stimulated in the autologous mixed lymphocyte reaction (MLR) by purified B cells or macrophages. In preliminary experiments, it was found that T cells that had been cultured with autologous non-T cells inhibited pokeweed mitogen- (PWM) stimulated immunoglobulin synthesis by autologous B cells. In addition, the T cell-mediated suppression was eliminated by x-irradiation and hydrocortisone treatment, was mediated by a mechanism that occurred early in the PWM-stimulated cultures, and did not involve killing of mature immunoglobulin-secreting cells. T cells were then cultured with either autologous B cells or macrophages in order to determine whether such autoreactive T cells had a similar capacity to regulate PWM-induced immunoglobulin synthesis. Although T cell populations stimulated either by B cells or by macrophages suppressed proliferative responses and immunoglobulin synthesis, both these populations of autoreactive T cells provided help for immunoglobulin synthesis that was not significantly different from that provided by fresh T cells. These results suggest that the predominant functional consequence of activation of T cells in the autologous MLR is the generation of suppressor T cells capable of inhibiting immunoglobulin synthesis. Thus, the autologous MLR may represent a negative feedback mechanism for the regulation of the immune response.

B-Lymphocytes↗
PubMed1980

An evaluation of total parenteral nutrition in the management of inflammatory bowel disease.

Total parenteral nutrition (TPN) is commonly used in the management of inflammatory bowel disease (IBD). Claims of its effectiveness are conflicting, and most reports have been limited to short-term assessments. We undertook a nonrandomized prospective study of the effects of TPN on the course of IBD in 30 patients whose disease was refractory to medical therapy, 20 with Crohn's disease and 10 with ulcerative colitis. Parameters of nutritional improvement, subjective and objective clinical response during TPN, and long-term outcome were assessed. All but one of the patients gained weight. Seven of the 20 Crohn's patients, including 3 of 4 with fistulas, had no response to TPN. The other 13 had reduction of diarrhea, relief of abdominal pain, and an improved sense of well-being during TPN. On long-term follow-up, five of these patients relapsed and required surgery; five remain improved with active disease controlled by medication 2--24 months later, and three are symptom-free and off all medication 20--48 months later. Clinical improvement during TPN was observed in only four of the 10 ulcerative colitis patients; six required colectomy after 9--24 days of TPN. Of the four responders, one relapsed and had colectomy one month later, two continue to have active disease controlled by medication five and 43 months later, and one has been symptom-free and off all medication for over three years. We conclude that TPN is useful adjunctive therapy for IBD patients requiring bowel rest and nutritional repletion. Dramatic clinical improvement occurs in some patients but is unpredictable.

Adolescent↗