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Biomedical subjects

D M Parrott

Publications and source records attributed to D M Parrott.

At least 37 records · Page 2Linked to original sources
PubMed1986

The incidence of monoclonal gammopathy in a population over 45 years old determined by isoelectric focusing.

Immuno-isoelectric focusing (IIEF), a technique previously shown to be sensitive for the detection of paraproteinaemia, was used to test 200 individuals over the age of 45, without history of B cell neoplasm, for the presence of serum paraproteinaemia. 11% of these individuals had evidence of paraproteinaemia detectable by IIEF compared with only 2% by zonal and immunoelectrophoresis. A further 12% had oligoclonal immunoglobulins and the remainder had no qualitative abnormality of the immunoglobulin profile. These results are discussed with particular reference to the aetiology, diagnosis and monitoring of potential B cell neoplasm in high risk individuals or groups.

Aged↗
PubMed1986

Functional characteristics of intraepithelial lymphocytes from mouse small intestine. II. In vivo and in vitro responses of intraepithelial lymphocytes to mitogenic and allogeneic stimuli.

Although isolated intraepithelial lymphocytes (IEL) have been shown to have specific and non-specific cytolytic functions, their ability to proliferate in response to T-cell mitogens or alloantigens is controversial. Here we show that IEL from mouse small intestine do not respond to mitogens such as concanavalin A and phytohaemagglutinin A or in mixed lymphocyte reactions unless an accessory spleen cell is also present. Adherent spleen cells possess the most potent helper function, but a dividing accessory cell may also be required. Supernatants from stimulated lymphocytes also assist IEL to proliferate in vitro, particularly in the presence of adherent accessory cells. IEL could not mediate lethal graft-versus-host disease in irradiated hosts, but could produce popliteal lymph node hypertrophy or splenomegaly in unirradiated hosts. Thus, IEL have the potential for proliferative activities characteristic of T cells, but they require accessory cells and/or factors such as interleukin-2 for their function in vitro and in vivo.

Animals↗
PubMed1986

Hypersensitivity reactions in the small intestine. VII. Induction of the intestinal phase of murine graft-versus-host-reaction by Lyt 2- T cells activated by I-A alloantigens.

This study has examined the nature of the T lymphocytes and the alloantigens that induce the intestinal phase of graft-versus-host reaction in unirradiated F1 mice. Parental spleen cells were depleted of T cells subsets by treatment with anti-Lyt monoclonal antibodies and complement, and we show that Lyt 2- cells alone induce the increased lymphocytic infiltration of the epithelium that characterizes the intestinal graft-versus-host reaction. Lyt 2- cells are also required to induce some of the associated crypt hyperplasia, but the full crypt changes require both Lyt 2- and Lyt 2+ T cells. In intra-H-2 recombinant congenic F1 mice with graft-versus-host reaction, a disparity at the I-A locus was alone sufficient and necessary for crypt hyperplasia and increased intraepithelial lymphocyte counts, while an I-J incompatibility led to suppression of both these indices. The results support the hypothesis that the intestinal pathology of acute GVHD is induced by class II MHC-restricted delayed-type hypersensitivity effector T cells.

Animals↗
PubMed1986

Divergent effects of bacterial lipopolysaccharide on immunity to orally administered protein and particulate antigens in mice.

We have investigated whether bacterial lipopolysaccharide (LPS) influences immune responses to dietary protein antigens in experimental animals. Simultaneous intravenous administration of LPS to normal mice fed ovalbumin (OVA) prevented the induction of tolerance for serum IgG antibody responses but did not alter the tolerance of systemic delayed-type hypersensitivity (DTH). In addition, exogenous LPS did not enhance the ability of spleen accessory cells to present OVA to primed T cells. LPS-unresponsive C3H/HeJ mice developed full tolerance of both humoral and cell-mediated immunity after feeding a range of doses of OVA that was equal in degree and persistence to that seen in normal, congenic C3H/HeOla mice and also had normal antigen-presenting cell (APC) activity for OVA. In contrast, C3H/HeJ mice were primed by feeding SRBC instead of developing the systemic tolerance found in normal C3H mice. Our results indicate the complexity of mechanisms that may regulate systemic immunity to orally administered antigens of different forms. Nevertheless, LPS does not modulate DTH responses to fed OVA and does not enhance APC activity, and we conclude that bacterial LPS may be unable to influence hypersensitivity to dietary proteins in man.

Animals↗
PubMed1985

Natural killer cell activity in atopic dermatitis: a sequential study.

It is well-recognized that patients with atopic dermatitis handle certain cutaneous viral infections poorly. As natural killer (NK) cell activity is considered to contribute to the immune response to viral infection, seven young adults with atopic dermatitis had their NK cell function assessed over a 12-month period. Natural killer cell activity was found to correlate inversely with disease activity. The more active the disease, the greater was the reduction in NK cell function (P less than 0.01. In addition, a strong correlation between clinical activity and IgE was shown (P less than 0.001).

Adult↗
PubMed1985

Augmentation of natural killer cell activity by anti-host delayed-type hypersensitivity during the graft-versus-host reaction in mice.

During a graft-versus-host (GVH) reaction in unirradiated F1 hybrid mice there is a generalized activation of natural killer (NK) cells. We have examined whether the enhanced NK activity is due to an F1 resistance mechanism directed at the parental cells used to induce the GVH reaction. Spleen cells of C57BL/10 origin induce much more NK cell activation in B10F1 hybrids than the opposite parental type, despite a similar intensity of systemic GVH reactions. However, this does not correlate with in vivo resistance of mice with GVH reaction to a local challenge dose of B10 cells. NK cell activation in (CBA X BALB/c)F1 mice with GVH reaction involves both host and donor cells and is preceded by an anti-host delayed-type hypersensitivity (DTH) response. B10 cells have a greater ability to induce DTH in B10F1 mice than cells from the opposite parent. We propose that NK cells are one group of non-specific effector cells recruited by DTH in a GVH reaction and may contribute to the tissue pathology.

Animals↗
PubMed1985

Appearance of delayed-type hypersensitivity effector cells in murine gut mucosa.

Feeding of a protein antigen, human gamma globulin (HGG), to BALB/c mice prior to parenteral immunization resulted in the abrogation of a delayed-type hypersensitivity (DTH) response to challenge with that antigen. Unlike parenterally immunized mice, HGG-fed mice were unable to transfer DTH to naive syngeneic recipients using peripheral lymph node lymphocytes. Co-transfer experiments ruled out the possibility of a suppressor cell in the orally immunized mice operating on DTH effector cells. Intra-epithelial lymphocytes (IELs) from mice immunized either orally or parenterally were able to transfer a DTH reaction to unimmunized recipients, while mesenteric lymph node lymphocytes from orally, but not parenterally, immunized donors were capable of transferring DTH. The implications of these results for investigations of gastrointestinal disorders with a suspected immunological aetiology are discussed.

Animals↗
PubMed1985

Effect of human colostrum and infant formula on the phagocytic activity of macrophages. I. Resident and stimulated mouse peritoneal macrophages.

Phagocytosis and degradation of radiolabelled human transferrin-anti-transferrin immune complexes by resident and stimulated mouse peritoneal macrophages was inhibited by liquid infant formula, particularly in the case of resident cells. Mouse peritoneal macrophages exposed to infant formula were shown by immunofluorescence to bind casein and beta-lactoglobulin, but there was little binding of alpha-lactalbumin. Comparison of various artificial milks, cow's milk and purified casein indicated that both the concentration and the degree of denaturation of casein may be important in the impairment of macrophage function by milk. It is suggested that bottle feeding of infants might result in impairment of macrophage function in the small intestine.

Animals↗
PubMed1984

Natural-killer-cell activity in atopic dermatitis.

Natural-killer (NK)-cell activity was measured in the peripheral blood of twenty patients with atopic dermatitis and in a group of thirteen age-matched non-atopic controls (nine subjects on thirteen occasions). The method uses a chromium-release assay with the human leukaemia cell line, K562, labelled with 51Cr as the target cell. A highly significant reduction in NK-cell activity was found in the patients with atopic dermatitis.

Adolescent↗
PubMed1984

Serum paraproteins in chronic lymphocytic leukaemia.

The presence of paraproteins in the sera of 10 patients with chronic lymphocytic leukaemia (CLL) was investigated using immunoisoelectric focusing. Monoclonal immunoglobulins were found in nine of these 10 sera. Five sera contained a single monoclonal IgM paraprotein, one serum contained a single monoclonal IgG paraprotein, while three sera contained more than one monoclonal paraprotein--namely, IgM + IgD, IgM + IgG, and IgM + IgD + IgG. The results indicate that the malignant B cells of CLL may be at a later stage of differentiation than previously assumed and serum monoclonal immunoglobulin could be of value as a tumour marker.

Aged↗
PubMed1983

Analysis of the effector functions of different populations of mucosal lymphocytes.

Lymphocytes separated from the epithelial layer of mouse small intestine, IEL, were tested for their NK cytotoxicity against Yac-1 targets. There was little NK activity in a 4 hour assay, but high activity in an 18 hour assay, and the NK activity of IEL did not parallel that in the spleen in any of the mouse strains tested. Furthermore, IEL exerted a suppressor activity on mouse spleen NK activity. Specific T-cell cytotoxicity appeared in IEL in mice immunized with an intraperitoneal injection of P-815 tumor cells. By contrast with IEL, LPL had little NK or NK suppressor activity, but higher levels of specific T-cell cytotoxicity in tumor-immunized mice than intraepithelial lymphocytes. A high proportion of IEL had granules that stained with Giemsa and Astra blue. Furthermore many IEL carried Lyt-2+ phenotype and no other T-cell surface antigen. Intraepithelial lymphocytes appeared, therefore, to have staining and phenotype characteristics of both granular NK cells and suppressor cells. It was clear that the intestinal mucosa contained populations of immune effector cells that were heterogeneous in nature and function.

Animals↗
PubMed1983

Augmentation of intestinal and peripheral natural killer cell activity during the graft-versus-host reaction in mice.

We have investigated the possibility that nonspecific cytotoxicity may be involved in the pathogenesis of the intestinal phase of the graft-versus-host reaction (GVHR) in mice. A GVHR was induced in unirradiated (CBA X BALB/c)F1 mice and natural killer (NK) cell activity against YAC-1 followed in the spleen, mesenteric lymph node (MLN), and isolated intraepithelial lymphocytes (IEL). Augmented NK activity developed simultaneously in all tissues in parallel with the progress of the GVHR. The NK activity of IEL also showed a close association with the increased numbers of IEL found on sections of small intestine. Mature T lymphocytes and macrophages did not contribute to the nonspecific cytotoxicity, and antihost cytotoxic T cells were not detected in any tissue. The results indicate that generalized recruitment of NK cells occurs during the GVHR both in peripheral and intestinal lymphoid tissues, and we propose that lymphokines are responsible for this phenomenon. NK cells recruited by a delayed-type hypersensitivity reaction may contribute to the pathogenesis of the GVHR, but an alternative explanation is that NK cells may inhibit the progression of the GVHR.

Animals↗
PubMed1983

Analysis of natural killer effector and suppressor activity by intraepithelial lymphocytes from mouse small intestine.

Intraepithelial lymphocytes (IEL) are morphologically similar to NK cells in other tissues and we have studied the NK activity of IEL isolated from mouse small intestine. In contrast to spleen NK cells, IEL showed little activity against YAC-1 over 4 h but had high levels of NK activity when the assay was extended to 18 h. IEL from nude mice did not show the enhanced NK activity found in other tissues. IEL were also found to suppress the NK activity of spleen cells and this suppressor function was not mediated by T lymphocytes or macrophages. The results indicate that the intestinal epithelium contains a population of potent NK cells which may represent a type of NK cell different to that found in other tissues. In addition, there are also cells capable of regulating NK cell function in the epithelial layer.

Animals↗
PubMed1983

The in-vivo kinetics of lymphoblast localization in the small intestine.

We have studied the in-vivo kinetics of the accumulation of 125I-UdR labelled mesenteric lymphoblasts in the small intestine of mice. The efficiency with which the labelled cells were extracted from the blood and retained by the intestine was quantified by examination of the accumulations observed over the first 4 hr after cell transfer. The kinetic parameters for the uptake and retention of lymphoblasts determined from these early times were found to provide a good approximation to the entire time course of accumulation observed from 1 hr to 22 hr after cell transfer. For normal mice, approximately 1% of lymphoblasts delivered by the blood stream at any given time gained entry to the small intestine and were retained with an average half-time of 6.5 hr. We also studied the accumulation of lymphoblasts in the small intestine of mice undergoing a self-limited enteric infection with the nematode, Trichinella spiralis. There was a greater accumulation of lymphoblasts in the small intestine of these animals. This was the consequence of a prolongation of the half-time for retention of lymphoblasts within the intestine to 15 hr, rather than increased uptake of lymphoblasts from the blood. During a secondary infection with T. spiralis, the half-time for retention of lymphoblasts in the intestine was decreased to 3 hr. These studies show that viewing the accumulation of lymphoblasts as the result of a series of first order kinetic processes provides a suitable model for the migration of lymphoblasts to the small intestine.

Animals↗
PubMed1981

Intestinal mast cell response in thymectomised and normal mice infected with Trichinella spiralis.

In NIH mice, expulsion of Trichinella spiralis from the small intestine and increase in intestinal mast cells were each dependent on the presence of T-lymphocytes. Both changes were deficient in thymectomised mice but could be largely restored by reconstitution of thymectomised mice with syngenetic mesenteric lymph node cells. In both NIH and BALB/C mice the majority of the increased number of mast cells occurred within the intestinal epithelium. In NIH mice increase in the number of intestinal mast cells coincided roughly with expulsion of the parasites. In BALB/C mice increase in the numbers of intestinal mast cells did not appear to be connected with the location or expulsion of parasites and it is concluded that mast cell proliferation, accumulation and discharge per se do not result in or from worm expulsion.

Animals↗
PubMed1981

Regional blood flow and the localisation of lymphoblasts in the small intestine of the mouse: effect of an elemental diet.

To test the hypothesis that food antigens influence the in vivo migration of lymphoblasts to the small intestine, the effect of an elemental diet (Vivonex) on the distribution of lymphoblasts within the small intestine of mice has been examined. Viable lymphoblasts from the mesenteric nodes of conventionally fed animals were labelled in vitro and given intravenously to recipient mice fed either a standard diet or elemental diet. The localisation of these cells within the small intestine was altered in the animals fed the elemental diet but only in the distal half of the small intestine. The relationship of the localisation of blast cells to the delivery of cardiac output along the small intestine was examined by assessing cell localisation in conjunction with the distribution of an isotopic indicator (86RbC1). The results show that the pattern of localisation of lymphoblasts within the small intestine is related to the probability that they will be delivered to different regions by the blood stream. Therefore, the alterations in blast localisation in the small intestine of animals of the elemental diet can be viewed as a consequence of changes in the perfusion of the distal small intestine. These results do not support the concept that antigens directly influence the efficiency with which blast cells migrate into the intestinal mucosa.

Animals↗