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Biomedical subjects

J Allison

Publications and source records attributed to J Allison.

At least 109 records · Page 6Linked to original sources
PubMed1989

Immunological tolerance: new approaches using transgenic mice.

Transgenic technology allows the introduction into the germline of an animal of a known gene coding for a normally foreign antigen, and by means of a specific promoter, the direction of its expression to specific tissues. The antigen is therefore synthesized by the animal as an authentic self molecule, at a particular stage in development, and in a particular site. In this review, J.F.A.P. Miller and colleagues discuss this radically new approach to the investigation of the mechanism of acquired immunological tolerance to self components.

Animals↗
PubMed1989

Expression in transgenic mice of class I histocompatibility antigens controlled by the metallothionein promoter.

To study the effects of increased expression of major histocompatibility complex class I molecules on the development of self-tolerance, transgenic mice were produced that expressed the H-2Kb gene under the control of the metallothionein promoter. Administration of zinc enhanced transgene expression in liver, kidney and exocrine pancreas. No evidence suggestive of an autoimmune response was found in transgene-expressing tissues in mice otherwise allogeneic to H-2Kb. Despite this lack of responsiveness in vivo, T cells could be stimulated in vitro to lyse H-2Kb-bearing target cells. No infiltration was detected in transgenic mice after irradiation and reconstitution with bone marrow cells. When spleen cells were used for reconstitution, however, dense lymphocytic infiltration was seen, particularly in the portal tracts of the liver, and this was accompanied by piecemeal necrosis and apoptosis of periportal hepatocytes. This aggressive response progressively diminished with time, and by 12 weeks after reconstitution many of the portal tracts were free of infiltration while the others showed no accompanying necrosis. The picture at this stage was similar to that seen in chronic persistent hepatitis. These results suggest that, in addition to negative selection in the thymus, peripheral mechanisms not involving clonal deletion or permanent clonal anergy can prevent immune responses to self molecules.

Animals↗
PubMed1989

Tissue-specific and hormonal regulation of the gene for rat prostatic steroid-binding protein in transgenic mice.

We investigated the tissue-specific and hormonal regulation of the gene for rat prostatic steroid-binding protein by introducing the C3(1) gene with 4-kilobase (kb) upstream and 2-kb downstream flanking sequences into transgenic mice. There was selective expression in the ventral prostate that was stimulated by testosterone, which indicated that the gene together with 6-kb flanking DNA contains the information required for prostate-specific and testosterone-regulated expression.

Androgen-Binding Protein↗
PubMed1989

MHC molecules and beta-cell destruction. Immune and nonimmune mechanisms.

Hyperexpression of major histocompatibility complex (MHC) molecules by islet cells is a prominent, early feature of islet pathology in insulin-dependent diabetes mellitus and concomitant with beta-cell failure after exposure of islets to specific cytokines or viruses. The transgenic expression of a class I MHC gene (H-2Kb) in the beta-cells of either syngeneic or allogeneic mice leads to beta-cell failure by a nonimmune mechanism. Several class II MHC transgenes, with one exception, have the same effect, but the expression of other transgenes that have products that are membrane proteins is not necessarily detrimental. Class I MHC molecules have been shown to interact directly with other membrane proteins. The inappropriate expression of MHC molecules could therefore interfere with key cellular functions. We postulate that the hyperexpression of MHC molecules in the beta-cell, e.g. in response to viruses, is a primary, nonimmune mechanism of beta-cell failure that precedes a secondary autoimmune response.

Animals↗
PubMed1989

Expression of class I histocompatibility antigens in defined tissues: effects on T cell function.

We have generated transgenic mice by introducing into fertilized eggs the major histocompatibility complex class I gene, H-2Kb, linked to various promoters that target gene expression to particular tissues. In one system the gene was expressed in the medullary epithelial cells of the thymus; these were unable to impose tolerance on differentiating T lymphocytes. These findings, together with those of other workers who showed that epithelial thymus grafts can impose tolerance, provide clear evidence of functional heterogeneity among thymus epithelial cells. In other transgenic models the gene was expressed in nonlymphoid tissues, such as the pancreatic islet beta cells or the hepatocytes, exocrine pancreas and kidney tubules. In all these cases the tissues were not subjected to autoimmune attack and the animals were specifically tolerant of H-2Kb-bearing cells in vivo, although some could generate cytotoxic T lymphocytes in vitro. Hence, although the intrathymic environment may be the dominant site for negative selection, it is clear that ancillary mechanisms exist in the periphery to ensure that tolerance is achieved to antigens not synthesized in the thymus.

Animals↗
PubMed1988

Diabetes in transgenic mice resulting from over-expression of class I histocompatibility molecules in pancreatic beta cells.

A class I histocompatibility gene, H-2Kb, linked to the rat insulin promoter, is overexpressed in the pancreatic beta cells of transgenic mice. The mice, whether syngeneic or allogeneic to the transgene, develop insulin dependent diabetes without detectable T cell infiltration, suggesting a direct, non-immune role for the transgenic class I molecules in the disease process.

Animals↗
PubMed1988

Potassium ion ionization of desorbed species (K+IDS): a rapid method for the screening of urine for organic acidemias.

A new desorption/ionization mass spectrometric technique, K+ ionization of desorbed species (K+IDS), is evaluated as a rapid method for differentiating various organic acidemias, conditions in which excessive levels of organic acid metabolites are present in plasma or urine as a result of some inborn error of metabolism. This method requires no derivatization of the isolated organic acids, unlike that required for gas chromatographic and gas chromatographic/mass spectrometric analyses. 'Batch' mass spectrometric analysis is achieved by deposition of the complex organic acid mixture (from urine) onto a K+IDS probe. Rapid heating results in the emission of alkali ions (Na+ or K+) from a thermionic emitter and the intact desorption of analyte. Subsequent gas-phase addition produces a mass spectrum showing alkali ion adducts of the components, providing molecular weight and relative concentration information. This rapid desorption/ionization technique requires no matrix, and analysis times are exceedingly short relative to those required in gas chromatographic/mass spectrometric analyses. Results suggest that differential diagnosis of some of the more commonly occurring organic acidemias (e.g. isovaleric acidemia, maple syrup urine disease, etc.) may be made.

Amino Acid Metabolism, Inborn Errors↗
PubMed1988

Dietary and other characteristics relevant for coronary heart disease in men of Indian, West Indian and European descent in London.

The origins of the high standardized mortality ratio (SMR) for coronary heart disease (CHD) among Indians in Britain, and the low SMR for West Indian immigrants, have been explored by a community survey in London. Serum lipoproteins, plasma glucose, haemostatic factors and other putative risk characteristics were measured in 75 Indian, 64 European and 24 West Indian men aged 45-54 years. These represented 81% of men registered with a general practice and resident within a defined area. In 51 men, diet was assessed by 5-day weighed inventory. Plasma phospholipid fatty acids (PFA) were measured in 18 Indians and 19 Europeans with dietary records. The relatively high HDL and HDL2-cholesterol concentrations, low LDL-cholesterol concentration, reduced fat intake, increased ratio of dietary polyunsaturated/saturated fat, relatively frequent use of alcohol, and lack of obesity in West Indians accorded with their low SMR from CHD. By contrast, only the relatively low HDL and HDL2-cholesterol concentrations, infrequency of alcohol consumption, and lower proportion of PFA as n-3 fatty acids of marine origin afforded explanations for the high SMR of Indians. Hyperglycaemia appeared similarly prevalent in Indians and West Indians, but less common in Europeans. Of the haemostatic factors, West Indians had a relatively low VIIc (not statistically significant), while Indians had an increased platelet count and reduced platelet volume. Improved understanding of these ethnic differences in CHD mortality may depend upon elucidation of the contrasts in HDL-cholesterol concentration.

Blood Coagulation Tests↗
PubMed1988

A psychophysiological differentiation between hypnotic behaviour and simulation.

Psychophysiological differentiation between conditions of hypnosis and simulation were examined with markers evolved from a series of experiments charting neuropsychophysiological accompaniments of hypnotic behaviour. Eighteen subjects participated in two sessions in which bilateral electrodermal activity was monitored to moderate intensity tones. Measurement in Session I, a Baseline-Control, of individual variation in rates of habituation of orienting responses, non-specific responses and tonic levels of skin conductance, enabled allocation of matched groups to Session II in which the same auditory stimuli were mixed with a taped hypnotic induction. Half the subjects were instructed to fake hypnosis and the others to comply. In session II the groups were differentiated as follows: (1) rate of habituation to the tones was retarded in the simulation condition and facilitated in the hypnosis condition compared with baseline; (2) the incidence of non-specific electrodermal responses was elevated in simulators after instructions to 'fake hypnosis'; (3) right-hand levels of skin conductance were elevated in simulators; (4) all but one subject in the hypnosis condition admitted to hearing the tones whereas all but one in the simulation condition claimed not to have heard them.

Adolescent↗
PubMed1986

The temporal pattern of unconstrained drinking: Rats' responses to inversion and identity constraints.

Rats obtained all of their water by licking a metal tube during a series of daily 1-hour sessions. When the tube was freely available throughout, each rat showed the classic temporal pattern of unconstrained drinking: As the session progressed, drinking bouts generally grew shorter and pauses grew longer. In subsequent sessions the tube was opened and closed independently of the rat's behavior, on a schedule that gave the rat a chance to duplicate the exact inverse of its unconstrained baseline pattern. Thus, as the inversion session progressed, the opportunities to drink generally grew longer and the enforced pauses grew shorter. When the rats were forced away from their unconstrained patterns of drinking and pausing, their total time spent drinking consistently fell short of previous values, but total licks and volumetric intake remained at previous levels. The same results occurred under an identity schedule, a series of openings and closings that duplicated the unconstrained pattern of drinking and pausing. The results have implications for theories that assume that instrumental performance under schedule constraint derives from the animal's defense of a measured set-point.

Journal Article↗