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J Allison

Publications and source records attributed to J Allison.

At least 73 records · Page 4Linked to original sources
PubMed1994

Genetic requirements for acceleration of diabetes in non-obese diabetic mice expressing interleukin-2 in islet beta-cells.

Diabetes was dramatically accelerated in non-obese diabetic (NOD) transgenic mice that expressed interleukin-2 (IL-2) in their beta cells. A single cross to C57BL/6 completely prevented this effect and a further backcross to the NOD genetic background showed that at least two diabetes susceptibility loci (Idd1s and Idd3/10s) were required for the diabetes acceleration T cells activated to islet antigens were not circulating in the mice. The accelerating effect of IL-2 was present; but decreased, in NOD mice that lacked CD8+ T cells as well as in NOD SCID mice. The implications are that in the NOD genetic background, the production of cytokines, such as IL-2, by islet-specific CD4+ T cells can lead to beta cell damage and diabetes and that CD8+ T cells may have a role in accelerating diabetes onset.

Animals↗
PubMed1994

Consequences of in situ production of IL-2 for islet cell death.

Transgenic mice that expressed a single-copy IL-2 transgene in their pancreatic beta cells were previously shown to develop a massive inflammation in and around the islets, but did not progress to diabetes. When these mice were made homozygous for the transgene, diabetes did ensue in most animals by 200 days. Analysis of the T cells present in the pancreatic infiltrates of single-copy and homozygous rat insulin promoter IL-2 mice showed a predominance of CD4+ cells which was especially apparent in the very young mice. Furthermore, many of the CD4+ T cells in young mice displayed a memory-like phenotype in that they expressed higher levels of adhesion molecules and the IL-2R p55 marker. When the IL-2 transgene was introduced into nude mice, an almost identical pathology of inflammation was seen except that the infiltrating cells were mostly B cells. Expression of the same transgene in scid mice also resulted in an inflammatory response and in some situations it was sufficient to induce diabetes. From these results it appears that the T cell product, IL-2, in the absence of antigen-specific T or B cells can induce an inflammatory response of sufficient intensity to cause diabetes.

Animals↗
PubMed1994

Development of the Leeds Dependence Questionnaire (LDQ): a questionnaire to measure alcohol and opiate dependence in the context of a treatment evaluation package.

The Leeds Dependence Questionnaire (LDQ) has been developed as part of a treatment evaluation package. The LDQ is a 10-item, self completion questionnaire designed to measure dependence upon a variety of substances; it has been shown to be understood by users of alcohol and opiates. The questionnaire was designed to be sensitive to change over time and to be sensitive through the range from mild to severe dependence; the follow-up data are insufficient to demonstrate change over time, but are encouraging. It is expected that both clinicians and researchers will find it useful to have a single measure relating to substance use, but not limited by specific substances. All items are scored 0-1-2-3; there are no normative data. The procedure for establishing content validity is described and estimates of concurrent, discriminant and convergent validities are reported; these validities are thought to be satisfactory. A principal components analysis produced a single factor accounting for 64% of the variance. Cronbach's alpha was 0.94. Test-retest reliability was found to be 0.95.

Adult↗
PubMed1994

Now we're talking.

Explore the source record for details and available documents.

Attitude to Health↗
PubMed1994

Islet inflammation and hyperplasia induced by the pancreatic islet-specific overexpression of interleukin-6 in transgenic mice.

Interleukin-6 (IL-6) is thought to be involved in the pathogenesis of autoimmune insulin-dependent diabetes mellitus. To examine this possibility, we developed two lines of transgenic mice (termed RIP-IL6) which overexpressed IL-6 in the pancreatic islet beta cells. RIP-IL6 mice, while showing a modest reduction in body weight, remained normoglycemic throughout their lives. Furthermore, insulin gene expression and glucose tolerance were similar to non-transgenic littermates. Histopathological examination revealed significant changes in the pancreas but not other organs of RIP-IL6 animals, with marked alterations in the architecture of the islets, in the islet cells, and in surrounding tissues. In younger animals these changes included islet hyperplasia with increased mitotic figures, neo-ductular formation, fibrosis, and a scant mononuclear cell infiltration (insulitis). In addition, immunostaining for islet hormones revealed changes in both the topography and density of beta and alpha cells. In older RIP-IL6 mice, a more florid insulitis was observed which was composed predominantly of B220+ B lymphocytes and, to a lesser extent, Mac-1+ macrophages and CD4+ and CD8+ T lymphocytes. Immunostaining for mouse IgG revealed significant numbers of plasma cells in the peri-islet infiltrates, which suggested that IL-6 induced differentiation of the recruited B lymphocytes. Therefore, islet overexpression of IL-6 produces a complex, localized host response implicating this cytokine in not only inflammatory processes that occur in autoimmune diabetes but also cellular neogenesis, which may indicate a role in tissue repair.

Animals↗
PubMed1993

Phorbol 12-myristate 13-acetate-induced phosphorylation of Op18 in Jurkat T cells. Identification of phosphorylation sites by matrix-assisted laser desorption ionization mass spectrometry.

Op18 is a widely expressed, cell cycle-regulated, phosphoprotein involved in signal transduction of a variety of stimuli. In actively proliferating Jurkat T cells which express Op18 at high level, phorbol 12-myristate 13-acetate (PMA) treatment induces a rapid increase in the level of several Op18 phosphorylated forms. To determine phosphorylation sites involved in the PMA effect, the major Op18 phosphorylated forms were resolved in Jurkat T cells, before and after treatment with PMA, using preparative immobilized pH gradient-based two-dimensional polyacrylamide gel electrophoresis. Tryptic fragments of phosphorylated Op18 were analyzed by two-dimensional thin layer peptide mapping and were resolved by reverse-phase high performance liquid chromatography prior to analysis by matrix-assisted laser desorption ionization mass spectrometry. Phosphorylation sites were identified by further treatment of the proteolytic fragments with different enzymes and determination of the mass shifts by matrix-assisted laser desorption ionization mass spectrometry. Two major phosphorylation sites were identified. Low constitutive levels of phosphorylation at Ser25 and Ser38 in Op18a and Op18b was demonstrated. Treatment with PMA resulted in enhanced phosphorylation of Ser25 in Op18a and of both Ser25 and Ser38 in Op18b. Taken together with prior studies of Op18 phosphorylation, the data suggest that Op18 phosphorylation occurs at identical sites in different tissues and organisms.

Amino Acid Sequence↗
PubMed1993

The behavioral economics of production.

In two experiments, thirsty rats licked an empty spout instrumentally for water delivered at a neighboring spout. Each such pair of spouts constituted a work station, and one, two, or three stations were available in the test enclosure. In 1-hr sessions, the rats worked alone or in the company of 1 or 2 other rats, and performed either five, 10, or 40 licks at the empty spout for each water delivery. The total number of empty-spout licks, summed across rats and stations, increased with the empty-lick requirement and, with some exceptions, the number of rats in the enclosure and the number of work stations available. A Cobb-Douglas production function, with instrumental responding as an output and the three independent variables as inputs, accounted for a significant percentage of the variance. Contrary to that function, output failed to increase with additional rats (or work stations) when the number of work stations (or rats) was relatively small.

Animals↗
PubMed1992

Autoimmune diabetes as a consequence of locally produced interleukin-2.

During cell differentiation in the thymus, self-reactive T cells can be generated. The majority of these seem to be deleted after intrathymic encounter with the relevant autoantigen. As all self antigens are unlikely to be present in the thymus, some autoreactive T cells may escape censorship. Here we study the fate of these cells using transgenic mice expressing the class I molecule H-2Kb (Kb) in the insulin-producing beta-cells of the pancreas. These mice were crossed with mice transgenic for genes encoding a Kb-specific T-cell antigen receptor (TCR) which could be detected using a clonotype-specific monoclonal antibody. Although T cells expressing the highest level of transgenic TCR were deleted intrathymically in double-transgenic mice, Kb-specific T cells were detected in the periphery. These cells caused the rejection of Kb-expressing skin grafts, but ignored islet Kb antigens even after priming. But when double-transgenic mice were crossed with transgenic mice expressing the lymphokine interleukin-2 in the pancreatic beta-cells, there was a rapid onset of diabetes. These results indicate that autoreactive T cells that ignore self antigens may cause autoimmune diabetes when provided with exogenous 'help' in the form of interleukin-2.

Animals↗
PubMed1992

Tolerance induction by thymic medullary epithelium.

To study the role of thymic medullary epithelium in tolerance induction, the third and fourth branchial clefts of embryos from E mu-Kb transgenic mice, which express the major histocompatibility complex class I antigen H-2Kb exclusively on medullary thymic epithelium, were grafted to athymic nude mice. The grafts differentiated into tissue that morphologically resembled normal thymus. These grafts expressed the H-2Kb antigen appropriately and gave rise to a functional T cell repertoire. In vivo tolerance to H-2Kb disparate skin grafts was invariably found in mice expressing H-2Kb in the medulla or in both medulla and cortex of C57BL/6 branchial cleft-grafted controls. In marked contrast, in vitro cytotoxicity assays demonstrated reactivity toward H-2Kb in the presence of interleukin 2, and limiting-dilution analyses showed similar frequencies of cytolytic T cell precursors reactive to H-2Kb and to third-party stimulators. Medullary epithelium can, therefore, induce split tolerance, in which in vivo tolerance is accompanied by strong in vitro responses in the presence of interleukin 2.

Animals↗
PubMed1992

Complex mixture analysis based on gas chromatography-mass spectrometry with time array detection using a beam deflection time-of-flight mass spectrometer.

A beam deflection time-of-flight mass spectrometer was developed in conjunction with an integrating transient recorder to provide time array detection, permitting high mass spectral scan file acquisition rates for complex mixture analysis by capillary gas chromatography-mass spectrometry (GC-MS). Results are presented for the analysis of a urinary organic acid mixture by GC-MS at a scan file acquisition rate of 10 scan files per second (sf/s), showing the advantages of such data collection in the deconvolution of partially resolved components. The reconstructed total ion current (RTIC) chromatogram available from data acquired at this scan file generation rate is shown to be comparable to the profile obtained from a flame ionization detector in representing the chromatography performed under identical experimental parameters. The RTIC chromatogram available from the database obtained at 10 sf/s is compared with that available from a database obtained at 1 sf/s, the latter representing that scan rate typically used with most GC-MS instruments. The advantages of the higher scan file acquisition rate in representing the chromatographic profile and in allowing mass spectral data to be obtained for components in the complex mixture that are unresolved chromatographically are discussed.

Acids↗
PubMed1992

Inflammation but not autoimmunity occurs in transgenic mice expressing constitutive levels of interleukin-2 in islet beta cells.

Transgenic mice expressing murine interleukin (IL)-2 constitutively in islet beta cells were generated (RIP-IL-2 mice). They died at an early age, when higher levels of IL-2 were produced, because of a predominant macrophage inflammatory response that destroyed the exocrine pancreas. Animals with lower levels of IL-2 survived and had islets that became increasingly infiltrated with lymphocytes over time. However, in spite of the presence of impressive peri- and intra-islet infiltrates, autoimmunity to islet antigens was not seen. Autoimmunity was also not induced to extrathymic H-2Kb molecules known to induce tolerance by a peripheral mechanism when the RIP-IL-2 mice were mated to other mice expressing H-2Kb in islet beta cells (RIP-Kb mice). Apparently, IL-2 can act only on activated T cells and is unable to reverse tolerance in T cells that have been made unresponsive through inappropriate presentation of antigen.

Animals↗
PubMed1992

Multidimensional aspects of drinking in the rat.

In 60-min test sessions, thirsty rats licked an empty metal spout for 0.2-milliliter shots of water delivered audibly to a neighboring spout that remained accessible after the first delivery. As the instrumental empty-lick requirement increased they drank less water, in accordance with the demand law, but made the same number of licks at the water delivery spout. In terms of water licks/milliliter they, therefore, licked less efficiently at higher behavioral prices, opposite to the relation obtained when rats respond for licks at a spout full of water. Given a continuous supply of free water they licked more efficiently, and licks varied in strict proportion to the amount drunk. Yoked controls with no instrumental requirement drank the same amount and made the same number of water licks as their price-paying experimental partners. Thus, intermittent delivery of a small amount of water induced rats to lick the delivery spout at a relatively high average rate that was unaffected by the behavioral price of the delivery or the interdelivery interval. Opposite efficiency effects suggest that external constraint on any dimension of drinking will affect that dimension more than any other left unconstrained.

Animals↗
PubMed1992

Does interleukin-2 abrogate peripheral immunologic self-tolerance in vivo?

Transgenic mice that constitutively expressed murine IL-2 in islet beta cells (RIP-IL-2 mice) had pancreatitis from birth which resolved into a peri- and intra-islet infiltrate in adult animals. In spite of the impressive infiltration, these mice did not develop autoimmunity to islet antigens. Neither was autoimmunity found to extrathymic H-2Kb molecules known to induce tolerance by a peripheral mechanism, when IL-2 and H-2Kb were coexpressed in the beta cells. Apparently, IL-2 can only act on activated T cells and is unable to reverse tolerance in T cells that have been made unresponsive through inappropriate antigen presentation in our system.

Animals↗