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S J Simpson

Publications and source records attributed to S J Simpson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effects of sensory stimuli on the behavioural phase state of the desert locust, Schistocerca gregaria.

The nature of stimuli, emanating from other locusts, which are effective in inducing gregarization in the desert locust was investigated. Isolated-reared fifth-instar nymphs were subjected to tactile, visual and olfactory stimuli, presented singly and in combination, and the effect on the behavioural phase state was quantified using logistic regression analysis. Tactile stimulation provided by rolling paper spheres proved to be highly gregarizing, whether presented alone or in combination with the other stimuli. Olfactory and visual stimuli together caused partial behavioural gregarization. Visual stimulation alone was weakly gregarizing after prolonged exposure, while olfactory stimuli alone were ineffective. Nymphs and pre-reproductive and reproductive adults of both sexes were also treated with synthetic adult male `aggregation' pheromone blend (Torto et al., 1994, Journal of Chemical Ecology 20, 1749). No effect of this blend was found on the behavioural phase state, even when visual stimuli were present. Non-locust related stimuli, including wheat odour and flashing lights, were also tested on nymphs. Neither induced any change in the behavioural phase state, indicating that increased sensory flow is not a sufficient explanation for locust-induced behavioural phase change.

Journal Article↗
PubMed1998

Development of colonic adenocarcinomas in a mouse model of ulcerative colitis.

Mice deficient in both interleukin-2 and beta 2-microglobulin expression (Beta 2mullnull x IL-2null mice) develop an inflammatory disease of the colon resembling ulcerative colitis. To examine long-term complications of disease in these mice, a group of 34 Beta 2mnull x IL-2null mice was monitored for 6-12 months. Development of clinical disease was assessed by wasting, general appearance, and diarrhea. Further analysis included histologic examination of the distal colon for colitis, staining of CD4+ T cells for surface activation markers, and cytoplasmic staining of CD4+ T cells for IFN-gamma and TNF-alpha. These older Beta 2mnull x IL-2null mice had activated CD4+ T cells as assessed by surface markers on flow cytometry. Cytoplasmic staining revealed IFN-gamma production, but not TNF-alpha production by CD4+ T cells. The majority of these older Beta 2mnull x IL-2null mice continued to have colitis on histology. However, they lived much longer and had less wasting in comparison to IL-2null mice. At necropsy, 11 (32%) of 34 of the Beta 2mnull x IL-2null mice had tumors in the proximal half of the colon. Histologic examination confirmed these tumors to be adenocarcinomas. These mice may be useful as a model for studying carcinogenesis in chronic colitis.

Adenocarcinoma↗
PubMed1998

Effects of food nutrient content, insect age and stage in the feeding cycle on the FMRFamide immunoreactivity of diffuse endocrine cells in the locust gut.

We have studied the influence of variations in dietary protein and digestible carbohydrate content, of insect age and of time during the feeding cycle on the endocrine cells of the ampullar region of the midgut in the African migratory locust Locusta migratoria L. Morphometric analysis of FMRFamide-like immunoreactivity was used as an indirect measure of the amount of FMRFamide-related peptides (FaRPs) stored in the gut endocrine cells. There was a highly significant correlation between FaRP content and the nutritional quality of the food, measured relative to the concentrations and ratio of protein to digestible carbohydrate in a nutritionally optimal diet. The direction of the relationship between FaRP content and diet quality varied with age during the fifth stadium. On day 1, FaRP levels increased with the nutritional quality of the food, while on day 4 the opposite relationship was observed. Release of peptide was triggered by the onset of a meal during ad libitum feeding, with cell FaRP levels returning to premeal values within 15 min of the meal ending. The results also suggested that cell contents were released during food deprivation beyond the normal intermeal interval. Locusts switched for a single meal during ad libitum feeding on day 4 from a low- to a high-carbohydrate food did not respond by reducing endocrine cell FaRP content. Our results show a relationship between the diffuse gut endocrine system and feeding and nutrition in locusts. The ampullar endocrine cells are in three-way contact with the midgut luminal contents, with the primary urine from the Malpighian tubules and with the haemolymph. They are thus ideally positioned to play an integrative receptor-secretory function in the regulation of a variety of post-ingestive processes, such as enzyme secretion, absorption, gut motility or nutrient metabolism.

Age Factors↗
PubMed1997

Glutathione reductase turned into trypanothione reductase: structural analysis of an engineered change in substrate specificity.

Trypanosoma and Leishmania, pathogens responsible for diseases such as African sleeping sickness, Chagas' heart disease, or Oriental sore, are two of the very few genera that do not use the ubiquitous glutathione/glutathione reductase system to keep a stable cellular redox balance. Instead, they rely on trypanothione and trypanothione reductase to protect them from oxidative stress. Trypanothione reductase (TR) and the corresponding host enzyme, human red blood cell glutathione reductase (GR), belong to the same flavoprotein family. Despite their closely related three-dimensional structures and although their natural substrates share the common structural glutathione core, the two enzymes are mutually exclusive with respect to their disulfide substrates. This makes the parasite enzyme a potential target for antitrypanosomal drug design. While a large body of structural data on GR complexes is available, information on TR-ligand interactions is very limited. When the two amino acid changes Ala34Glu and Arg37Trp are introduced into human GR, the resulting mutant enzyme (GRTR) prefers trypanothione 700-fold over its original substrate, effectively converting a GR into a TR [Bradley, M., Bücheler, U. S., & Walsh, C. T. (1991) Biochemistry 30, 6124-6127]. The crystal structure of GRTR has been determined at 2.3 A resolution and refined to a crystallographic R factor of 20.9%. We have taken advantage of the ease with which ligand complexes can be produced in GR crystals, a property that extends to the isomorphous GRTR crystals, and have produced and analyzed crystals of GRTR complexes with glutathione, trypanothione, glutathionylspermidine and of a true catalytic intermediate, the mixed disulfide between trypanothione and the enzyme. The corresponding molecular structures have been characterized at resolutions between 2.3 and 2.8 A with R factors ranging from 17.1 to 19.7%. The results indicate that the Ala34Glu mutation causes steric hindrance leading to a large displacement of the side chain of Arg347. This movement combined with the change in charge introduced by the mutations modifies the binding cavity, forcing glutathione to adopt a nonproductive binding mode and permitting trypanothione and to a certain degree also the weak substrate glutathionylspermidine to assume a productive mode.

Animals↗
PubMed1997

CD16-expressing CD8alpha alpha+ T lymphocytes in the intestinal epithelium: possible precursors of Fc gammaR-CD8alpha alpha+ T cells.

T lymphocytes normally express their Ag receptors in association with the CD3 proteins, which include CD3zeta. In CD3zeta eta(null) mice thymic and peripheral T lymphocytes do not express the TCR/CD3 complex on their surface due to retention in the endoplasmic reticulum of the remaining polypeptide chains. However, intestinal intraepithelial lymphocytes (iIEL) of CD3zeta eta(null) mice do express surface TCR, because the Fc epsilonRI gamma chain replaced the CD3zeta chain in the TCR/CD3 complex. Here we report that in a subset of CD8alpha alpha+ iIEL the presence of the Fc epsilonRI gamma chain could be accounted for by the surface expression of the Fc gammaRIII(CD16) complex. Because in wild-type (wt) mice only CD16+ iIEL coexpressed Fc epsilonRI gamma and CD3zeta, we concluded that the presence of Fc epsilonRI gamma was dictated by its required participation of CD16 complex. CD8alpha alpha+ iIEL bearing CD16 and B220 were also detected in the intestinal mucosa of RAG-2(null) mice from 12 days after birth onward. Two independent experimental settings were used in an attempt to demonstrate that CD16+ iIEL matured into CD16- T cells. First, in the RAG-2(null) mice, iIEL responded to in vivo administration of an anti-CD3epsilon mAb by progression to a more mature stage of development, characterized by a loss of CD16 and B220. Secondly, a conversion to CD16- iIEL occurred upon transfer of wt CD16+ iIEL into RAG-2(null) mice. We conclude from these experiments that in both RAG-2(null) and wt mice, a precursor/progeny relationship may exists between CD16+ B220+ CD8alpha alpha+ and CD16- B220- CD8alpha alpha+ iIEL.

Animals↗
PubMed1997

Expression of pro-inflammatory cytokines by TCR alpha beta+ and TCR gamma delta+ T cells in an experimental model of colitis.

An inflammatory bowel disease (IBD) comparable to human ulcerative colitis is induced upon transfer of T cell-depleted wild-type (F1) bone marrow into syngeneic T cell-deficient (tg epsilon26) mice (F1 --> tg epsilon26). Previously we have shown that activated CD4+ T cells predominate in transplanted tg epsilon26 mice, and adoptive transfer experiments verified the potential of these cells to cause disease in immunodeficient recipient mice. Using flow cytometry for the detection of intracellular cytokine expression, we demonstrate in the present study that large numbers of CD4+ and CD8+ TCR alphabeta+ T cells from the intraepithelial region and lamina propria of the colon of diseased, but not from disease-free mice, produced interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). Large numbers of T cells from peripheral lymphoid tissues of these animals also expressed IFN-gamma and TNF-alpha, but few expressed interleukin-4, demonstrating a strong bias towards Th1-type T cell responses in these animals. TCR gammadelta+ T cells, typically minor constituents of the inflammatory infiltrate of the colon in F1 --> tg epsilon26 mice, also expressed IFN-gamma at a high frequency upon CD3 stimulation. In light of these findings we examined the potential involvement of TCR gammadelta+ T cells by testing their ability to induce colitis in tg epsilon26 mice. We report here that tg epsilon26 mice transplanted with T cell-depleted bone marrow from TCR alpha(null) and TCR beta(null) animals developed IBD. Furthermore, disease in these mice correlated with the development of peripheral and colonic TCR gammadelta+ T cells capable of IFN-gamma production. These results suggest that IFN-gamma may be a common mediator of IBD utilized by pathogenic T cells of distinct phenotype.

Animals↗
PubMed1997

Geometric analysis of macronutrient selection in the rat.

A conceptual framework is introduced which has been derived from work on insects. The scheme is intended to integrate studies of diet selection, regulation of amounts eaten, nutrient utilization, body composition and animal performance. Aspects of framework are illustrated with published data on macronutrient selection in the rat. An animal is viewed as moving through a multidimensional nutrient space, which is bounded by axes representing each required nutrient and within which lie optimal points of intake and nutrient allocation ("targets"). The aim is first to estimate the location of these functional optima experimentally, and then to interpret the responses of animals which are constrained from reaching them ("decisions of best compromise"). The framework can then be used to interpret data from animals reared under differing environmental conditions and to compare animals of differing developmental stage, genotype or nutritional state.

Animals↗
PubMed1997

Development and function of T lymphocytes and natural killer cells after bone marrow transplantation of severely immunodeficient mice.

Bone marrow (BM) transplantation experiments were performed in a strain of CD3 epsilon-transgenic mice, termed tg epsilon 26, which are completely deficient in T-cell and natural killer (NK) cell development. We found that an interaction of stromal cells and prothymocytes is required for the induction of a cortical thymic microenvironment. This induction takes place in a time window from fetal development to early neonates. Although the thymic environment is not required for NK-cell development, we found that aberrantly educated alpha beta or gamma delta T lymphocytes can influence NK-cell ontogeny. Surprisingly, BM transplantation of tg epsilon 26 fetuses and neonates results in normal T-cell development, but very low levels of NK cells. The poor NK-cell reconstitution in fetal and neonatal stages could be explained by an inefficient migration of hematopoietic progenitor cells to the BM. By contrast, migration of the progenitor cells to the thymus was efficient to initiate T-cell development. BM transplantation of adult tg epsilon 26 mice resulted in abnormal T-cell development which, in turn, caused an inflammatory bowel disease (IBD) in the recipient mice. Studies in these BM chimeras have revealed that both alpha beta and gamma delta T cells can be pathogenic and, further, that Th1-like cytokines produced by these cells are causal factors in the pathogenesis of IBD.

Animals↗
PubMed1997

Strategies for comprehensive nurse managed occupational health services: focusing on work related health problems while maintaining comprehensive care delivery.

1. Occupational health nurses can position themselves to be valuable assets as human resources become more important in the complicated world of producing products, services, managing employees, and making a profit. 2. An on-site nurse managed occupational health unit provides opportunities for positively influencing employees' health while affording multiple opportunities for the occupational health nurse to impact the bottom line of the business unit. Exploring the opportunities can lead to exciting program development and implementation. 3. The nursing process (assessment, planning, implementation, and evaluation) can be applied to occupational health programs and service development. This technique assists the nurse in identifying an organization's strengths and weaknesses and in developing the strategies for the implementation of a coordinated program.

Ambulatory Care Facilities↗
PubMed1996

Natural killer cell development is blocked in the context of aberrant T lymphocyte ontogeny.

Over-expression of human or mouse CD3-epsilon transgenes profoundly disturbs T lymphocyte and natural killer (NK) cell development. One of these transgenic strains, termed tgepsilon26, displays a very early block in T lymphocyte and NK cell development. We showed previously that the absence of early thymocyte progenitors results in an abnormal thymic microenvironment. Due to this thymic defect, T cell development could not be restored by bone marrow (BM) transplantation in adult tgepsilon26 mice but could in fetal tgepsilon26 mice. Here we examine the effect of this abnormal thymic environment on NK cell development. We demonstrate that NK cell maturation in tgepsilon26 mice was reconstituted by BM derived from completely T cell-deficient mice, i.e. RAG-2(-/-) and TCRbeta x delta-/-, but not from wild-type mice. Moreover, tgepsilon26 mice transplanted with BM from partially T cell-deficient mice, i.e. TCRalpha-/-, TCRbeta-/- and TCRdelta-/- mice, did not reconstitute their NK cell compartment. We conclude from these studies that the thymic environment is not required for NK cell development, but that aberrantly educated alphabeta or gammadelta T lymphocytes can influence NK cell ontogeny. Furthermore, high serum levels of tumor necrosis factor (TNF) were detected in the vast majority of tgepsilon26 mice transplanted with BM cells derived from partially T cell-deficient mice, but never from tgepsilon26 mice transplanted with BM cells derived from completely T cell-deficient mice. The high levels of TNF may play an important role in the observed inhibition of NK cell development, since in vivo treatment with an anti-TNF antibody restored NK cell development.

Animals↗
PubMed1995

Evidence that CD4+, but not CD8+ T cells are responsible for murine interleukin-2-deficient colitis.

Mice deficient in interleukin-2 production (IL-2null mice) develop colonic inflammation closely resembling ulcerative colitis in humans. Although this disease is marked by substantial infiltration of the colon by CD8+ and CD4+ T lymphocytes, no function has yet been assigned to these T cell subsets in the development of colitis in the IL-2null mouse. For the present study, we investigated the involvement of T lymphocytes in the onset of colitis in IL-2null mice, and examined the possible role played by cytotoxic T cells. Both lamina propria lymphocytes (LPL) and intraepithelial lymphocytes (IEL) of the colon of IL-2null mice were potently cytotoxic ex vivo in short-term redirected cytotoxic lymphocyte (CTL) assays. In contrast, colonic T cells of wild-type animals showed little or no constitutive cytotoxic T cell activity. Colonic CTL were detectable prior to the appearance of disease in IL-2null animals and CTL activity was confined to the TcR alpha beta, rather than to the TcR gamma delta IEL subset. IL-2null animals crossed with major histocompatibility complex class I-deficient mice [IL-2null x beta 2 microglobulin (beta 2mnull) mice] also developed colitis, which appeared even earlier than in most IL-2null mice. These findings suggest that neither CD8+ IEL nor LPL were causal in the onset of colitis in IL-2null animals. In IL-2null x beta 2mnull mice, an ulcerative colitis-like disease was evident from histological studies and immunohistological staining which showed very large numbers of CD4+ lymphocytes within the intestinal mucosa. Significant ex vivo killing by CD4+ T cells was observed in IL-2null x beta 2null animals, although this required an extended incubation time compared to colonic CD8+ T cells. Peripheral as well as colonic CD4+ T cells in IL-2null and IL-2null x beta 2mnull animals, were activated as judged by their cell surface phenotype (CD45RBlo, L-selectinlo and CD69+). In light of these findings, we propose that infiltrating CD4+, but not CD8+ T cells are central to the inflammation observed in the intestinal mucosa in IL-2null colitis.

Animals↗
PubMed1995

Severe colitis in mice with aberrant thymic selection.

Tg epsilon 26 mice display an arrest very early in T cell development that has a profound effect on the architecture of thymic stromal cells. We have recently demonstrated that transplantation of wild-type bone marrow cells restores the thymic microenvironment of fetal but not adult Tg epsilon 26 mice. Here, we report that T cell-reconstituted adult Tg epsilon 26 mice develop a spontaneous wasting syndrome characterized by extensive inflammation of the colon, resembling human ulcerative colitis. Colitis in these animals was marked by substantial infiltration of the colon by activated thymus-derived CD4+ T cells. Importantly, bone marrow-transplanted Tg epsilon 26 mice previously engrafted with a fetal Tg epsilon 26 thymus did not develop colitis. These results suggest that T cells selected in an aberrant thymic microenvironment contain a population of cells able to induce severe colitis that can be prevented by T cells that have undergone normal thymic development.

Animals↗
PubMed1995

Detection of tumor cells in the bone marrow, peripheral blood, and apheresis products of breast cancer patients using flow cytometry.

One of the possible drawbacks to autologous bone marrow (BM) and peripheral blood progenitor cell (PBPC) transplantation in breast cancer patients is the potential for tumor cell contamination in the transplanted product. To assess the presence of breast cancer cells, we have developed a flow-cytometric method using cytokeratin-FITC and CD45-phycoerythrin (PE) to detect very low levels of cytokeratin-positive (CK+) tumor cells in mononuclear cell (MNC) preparations. In a model system using PBMNC and the breast cancer cell line CAMA, the sensitivity of detection of this flow-cytometric method was one tumor cell in 200,000 MNC. This method was used to evaluate BM, PB, and apheresis products (AP) from 44 patients with metastatic breast cancer. When possible, stained cytologic examination was performed on smears of the unprocessed specimens and on flow cytometry-sorted cells. Results indicated that CK+ tumor cells could be detected by flow cytometry in all three specimen types. When present, however, the tumor content (per MNC) tended to be higher in BM than in PB or AP. Samples from a given patient taken serially over the course of chemotherapy revealed variable results, suggesting that the presence of tumor contamination may be sporadic and requires evaluation of each stem cell product. Of 75 samples tested with both flow cytometry and cytology, the results were concordant in 54 cases (72%). In the remaining samples, flow cytometry only was positive in 15 cases (20%), and cytology only was positive in six cases (8%). This flow-cytometric technique is useful in the evaluation of transplant products for CK+ tumor cell contamination.

Adenocarcinoma↗
PubMed1994

IL-2-dependent NK cell responses discovered in virus-infected beta 2-microglobulin-deficient mice.

In vivo NK cell responses to lymphocytic choriomeningitis virus were studied in CD8+ T cell-deficient mice. On day 7 after infection, dramatically elevated splenic NK cell activities were observed in both beta 2-microglobulin-negative (beta 2-m-/-) mice deficient in CD8+ T cells and anti-CD8-treated C57BL/6 animals. The enhanced responses could be attributed to increased numbers of activated NK1.1+CD3- cells. The day 7 NK cell responses in beta 2-m-/- mice, but not in normal C57BL/6 animals, were cyclosporin A sensitive and coincided with IL-2 production and high affinity IL-2R expression on NK cells. Proof that IL-2 played an essential role in day 7 responses was provided by the observation that IL-2-/- x beta 2-m-/- mice lacked the late NK cell activation. Taken together, these results showed that NK cells can be activated and expanded by an IL-2-dependent pathway. Because these responses can only be measured in the absence of CD8+ T lymphocytes, an exciting model of networking between T and NK cells in response to viruses is postulated.

Animals↗
PubMed1993

Relationship of C5a receptor modulation to the functional responsiveness of human polymorphonuclear leukocytes to C5a.

The relationship of C5a receptor expression on human polymorphonuclear leukocytes (PMN) to the functional response of these cells to C5a was studied using flow cytometry. C5a receptor expression was determined with a fluorescein conjugate of C5a and oxidative burst activity was monitored by conversion of dichlorofluorescein to dichlorofluorescein (DCF) as a measure of H2O2 production. These studies showed that after incubation of PMN with increasing concentrations of C5a, and allowing for internalization of bound ligand, more than 40% of the cell surface C5a receptors were internalized before the DCF response to optimal concentrations of C5a was decreased below the levels for untreated control cells. Although C5a responsiveness was lost after preincubation with 10(-8) M C5a, cells remained responsive to formyl peptide. In other studies, cells were preincubated with unlabeled C5a under conditions that provided for internalization of nearly all C5a receptors. PMN were then cultured for up to 90 min and monitored for C5a receptor reexpression and return of cell function. In these studies, the DCF response of PMN to C5a returned to 100% much earlier than the cells regained full expression of C5a receptors. The DCF response to formyl peptide remained intact throughout the period of C5a receptor reexpression. These studies showed that once > 40% of the original population of C5a receptors are reexpressed on the PMN, that these cells regain 100% of their functional responsiveness to C5a in the DCF assay. Evaluation of the affinity and number of C5a receptors using 125I-labeled C5a after receptor reexpression showed that maximal receptor reexpression was approximately 73% of that obtained with control cells and the Kd of reexpressed receptors was 0.60 vs 0.94 nM for control cells. These studies demonstrate that only a portion of the total C5a receptors expressed on PMN are essential to stimulate a 100% functional response in PMN and that the reexpressed receptors are capable of transducing a signal that activates the oxidative burst in these cells.

Complement C5a↗
PubMed1993

A flow cytometric method for counting very low levels of white cells in blood and blood components.

Reduction of white cells (WBCs) in blood components may reduce the risk of virus transmission and HLA alloimmunization. Filtration provides a means by which to achieve high-efficiency WBC reduction. A method has been developed using flow cytometry to quantitate the number of WBCs in WBC-reduced packed red cells or platelet concentrates. This method uses a detergent and propidium iodide (PI) solution to label the WBC nuclei and incorporates a known amount of fluorescein isothiocyanate (FITC)-labeled chicken red cells (cRBCs) into the mixture as an indicator of the volume examined. The number of observed WBCs per mL is calculated as follows: Number of PI WBC nuclei events/Number of FITC cRBC events x Number of FITC cRBCs added to mixture/Volume of blood in mixture. The method may allow the detection of WBCs at a concentration as low as 0.01 per microliters (10/mL) in a blood sample. It is an efficient method of collecting data, as it requires less than 10 minutes per sample. This flow cytometric technique is suitable for research purposes and for quality control of WBC-reduced blood components, because it is precise and can be used to quantitate WBCs in large or small numbers in a sample.

4-Aminobenzoic Acid↗
PubMed1993

Immunological consequences of T cell-specific expression of H-2Kb molecules in transgenic mice.

CBA (H-2k) mice carrying a H-2Kb transgene (CD2Kb) linked to transcriptional control elements from the human CD2 gene express H-2Kb at high levels on all thymocytes and peripheral T cells. However, skin grafts from two independent transgenic lineages, CD2Kb-2 and CD2Kb-3, are not rejected by recipient CBA mice. Although mice from both lineages tolerate H-2Kb disparate skin grafts, tolerance is maintained by different mechanisms because H-2Kb-specific cytotoxic T cells cannot be generated in vitro using CD2Kb-2 responder spleen cells, but can be generated when responder cells are from CD2Kb-3 mice. Furthermore, H-2Kb-restricted cytotoxic T cell responses directed against minor histocompatibility antigens can be obtained from CD2Kb-2 responder mice. Thus, negative and positive selection of immature thymocytes seems to take place in CD2Kb-2 mice, even though the pattern of H-2Kb expression is modified by the CD2Kb transgene. In contrast, H-2Kb-specific cytotoxic T cell precursors are not eliminated in CD2Kb-3 mice, even though all thymocytes express H-2Kb in these mice. However, these potentially autoreactive H-2Kb-specific T cells are apparently inactive in vivo and fail to lyse syngeneic CD2Kb-3 target cells in vitro, even when activated to lyse other H-2Kb-expressing cells. These results reveal that tolerance in CD2Kb-3 mice is induced either by a non-deletional mechanism or by partial elimination of a subset of cytotoxic T cell precursors capable of recognizing H-2Kb as a target antigen.

Animals↗