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Biomedical subjects

A Wilson

Publications and source records attributed to A Wilson.

At least 379 records · Page 21Linked to original sources

Immature CD4- CD8+ murine thymocytes.

Mature thymocytes are usually defined and separated from other less mature thymocytes on the basis of their mutually exclusive expression of either CD4 or CD8. However, such murine "single positives" include a subpopulation of immature cells with properties resembling CD4- CD8- thymocytes or CD4+ CD8+ cortical blasts. Most of these immature single positives are CD4- CD8+, some expressing relatively low levels of CD8. They are large, dividing cortisone-sensitive cells found in the outer cortex. They express high levels of the heat-stable antigen (recognized by the monoclonals M1/69, B2A2, and J11d) but they are MEL-14-. The absence of detectable surface CD3, the absence of alpha-chain messenger RNA, and the predominance of the truncated form of the beta-chain messenger RNA all indicate that they do not express the T-cell antigen-receptor complex. Strategies for eliminating such immature cells from preparations of mature thymocytes are given, and their developmental significance is discussed.

Animals↗

Subpopulations of mature murine thymocytes: properties of CD4-CD8+ and CD4+CD8- thymocytes lacking the heat-stable antigen.

The heat-stable antigen (HSA), recognized by the monoclonal antibodies M1/69, B2A2, and J11d, is low or absent on the surface of most murine peripheral T cells but present on all but 3% of thymocytes. The CD4-CD8+ and CD4+CD8- or "single positive" thymic populations may be divided into further subgroups based on surface HSA expression. One group, CD4-CD8+ and expressing very high levels of HSA (HSA++), is an immature, T cell antigen receptor (TcR) negative, outer cortical blast cell. However, a further subdivision of CD4-CD8+ and CD4+CD8- single positives may be made, into those negative to low for HSA (HSA-) and those expressing moderate amounts of HSA (HSA+). The proportion of HSA- single positives is low in the thymus of young mice, whereas the proportion of HSA+ single positives is similar to that of the adult. Both the HSA- and the HSA+ subsets of single positive thymocytes from adult mice are CD3+ and express the normal peripheral T cell incidence of V beta 8 determinants on the TcR. On stimulation with concanavalin A in limit-dilution culture both HSA- and HSA+ subsets of single positive thymocytes give a high frequency of proliferating clones, and the clones from both HSA- and HSA+ subsets of CD4-CD8+ thymocytes are cytotoxic. Thus both HSA- and HSA+ single positive thymocytes are functionally mature. The HSA- subsets of single positive thymocytes differ from the HSA+ subsets in being slightly larger in size, in expressing higher levels of MEL-14, in binding more peanut agglutinin, and in including a proportion of cells expressing high levels of the Pgp-1 glycoprotein. It is suggested that HSA- CD4-CD8+ and HSA- CD4+CD8- thymocytes are more mature than their HSA+ counterparts, and might represent a previously activated or "memory" thymic subpopulation.

Animals↗

Molecular characterization of T-cell antigen receptor expression by subsets of CD4- CD8- murine thymocytes.

Precursors of all T-lineage cells are found in a population of thymocytes that lack the CD4 and CD8 surface glycoproteins. These "double-negative" thymocytes are markedly heterogeneous in their expression of other surface markers and include cells at various stages of development. In this study, CD4- CD8- adult murine thymocytes were separated into subsets based on the expression of the "heat stable antigen" (HSA) and of Ly 1 (CD5). The sorted subsets were analyzed directly (without prior expansion in culture) for T-cell antigen receptor (TcR) gene rearrangement and mRNA expression and for TcR and CD3 cell-surface protein expression. Very little surface CD3 or TcR expression was detected on the major HSA+ Ly 1low subset. However, the HSA+ Ly 1high, HSA- Ly 1high, and HSA- Ly 1low subsets all contained cells with surface expression of CD3 and TcR. In contrast to previous studies, we found no subset that exclusively expressed either the alpha beta or gamma delta heterodimer, although the ratio of alpha beta+ to gamma delta+ varied widely. Two of these three subsets (HSA- Ly 1low and HSA- Ly 1high) showed very high usage of V beta 8 gene products in the alpha beta heterodimer, but nevertheless included approximately equal to 15% non-V beta 8 alpha beta forms. All CD4- CD8- subsets were found to have extensively rearranged their TcR gamma genes and to express gamma mRNA. Expression of a high ratio of mature [1.3 kilobases (kb)] to truncated (1.0 kb) beta message and presence of alpha message was largely restricted to subsets with TcR alpha beta surface expression.

Animals↗

Developmental status and reconstitution potential of subpopulations of murine thymocytes.

In this chapter we have summarized our view of the subsets of murine CD4- CD8- thymocytes which can be identified with a range of monoclonal antibodies. We have shown the division rate and turnover time of the main subsets and have listed what we know of the TcR gene rearrangement, and expression at the RNA and protein levels. We have been unable to completely segregate gamma delta-TcR-expressing cells from alpha beta-TcR-expressing cells by any of the markers we have used, although the proportions of the two receptor forms vary widely in the different subsets. Experiments involving intrathymic transfer of the CD4- CD8- subsets are described, which indicate that all the TcR- subsets of the CD4- CD8- thymocytes display some precursor activity and which suggest a progression of at least five stages through the TcR- subpopulations of CD4- CD8- cells. The earliest precursor is a Thy 1 low, HSA low, Pgp-1 high cell which has unrearranged C beta and is non-dividing and which closely resembles the bone marrow prothymocyte. The later precursors are Thy 1 high, HSA high, Pgp-1 low, have rearranged C beta and are rapidly dividing. We tentatively conclude that none of the TcR+ CD4- CD8- cells are precursors of the major thymocyte subsets or of typical peripheral T cells, and we have found no evidence so far of separate precursors for the different mature subsets of thymocytes or peripheral T cells.

Animals↗

Emotion cognition interaction in personality development: a discrete emotions, functionalist analysis.

In this paper we take a discrete emotions approach to personality development. We suggest that individual differences in affective organization, acquired during the course of development, result in affect-specific biases in expressive patterns and idiosyncratic perceptual organizations. These affective biases, which have a pervasive influence on a wide domain of individual and interpersonal behaviours, contribute to psychological continuities that we identify as emotional traits. An array of data in support of this proposition is detailed. We propose a developmental model of how such affective organizations may be established initially, and the mechanisms by which they become consolidated over time. A final section discusses broader implications for developmental theory.

Cognition↗

Measurement of gamma-interferon in culture supernatants of antigen-stimulated lymphocytes from patients with Schistosoma mansoni infections by a reverse passive haemagglutination assay.

An assay for gamma-interferon (IFN gamma) in human lymphocyte culture supernatants, based on reverse passive haemagglutination (RPH) of red cells bearing a monoclonal anti-IFN gamma antibody, was developed and compared with a conventional virus inhibition assay. Test samples comprised supernatants of lymphocytes from patients with Schistosoma mansoni infections, cultured with or without a soluble worm antigen preparation. The two assays gave comparable results, the correlations for individual samples being good. The RPH assay was both specific and sensitive, allowing the detection of IFN gamma at 13 u/ml (1 ng/ml) or less. The advantages of the RPH assay were that it was quick, relatively inexpensive and suitable for testing large numbers of samples. In particular, between-experiment variation was very low, allowing the assay of different samples on different occasions.

Adolescent↗

Phenotype and localization of thymocytes expressing the homing receptor-associated antigen MEL-14: arguments for the view that most mature thymocytes are located in the medulla.

The monoclonal antibody MEL-14 recognizes a lymphocyte surface structure (the MEL-14 antigen) involved in migration of lymphocytes into lymph nodes. Its use as a maturation marker for T cells within the thymus led to the view that a small population (1 to 2%) of MEL-14high thymocytes located in the inner cortex represented fully mature cells about to exit as thymus emigrants. The medulla, in this view, contained only the phenotypically mature but MEL-14low cells, and was not the source of thymus emigrants. The data we present, derived from flow-cytometric analysis of suspension-stained CBA mouse thymocytes, is not in accordance with this view. A high proportion (approximately 20%) of thymocytes express relatively high levels of MEL-14; these include some immature Ly-2- L3T4- and nonmature Ly-2+ L3T4+ thymocytes. Among the 12 to 14% thymocytes of mature phenotype (PNAlow or H-2Khigh or Ly-2+ L3T4- and Ly-2- L3T4+), more than half express relatively high levels of MEL-14. The mature phenotype and MEL-14moderate-to-high cells (8% of thymocytes) appear too numerous to account for the few percent MEL-14high cells seen in the cortex in frozen sections, and the mature phenotype but MEL-14low cells (2 to 3% of thymocytes) too few to fill the medulla; however, both together account numerically for the medullary population. By section staining, the medulla contains Ly-2- L3T4+ and Ly-2+ L3T4- cells in a characteristic 2:1 ratio; by suspension staining this ratio agrees with that of the total mature phenotype population, but not with that of the MEL-14low subset previously claimed to represent medullary cells. Another paradox is apparent when suspension staining and section staining are compared: suspension staining reveals that many mature phenotype cells coexpress high levels of both MEL-14 and H-2K, yet section staining reveals H-2Khigh cells in the medulla but not in the inner cortex, and reveals scattered MEL-14high cells throughout the cortex but not in the medulla. We suggest that section staining for MEL-14 fails to locate the mature cells that stain for MEL-14 in suspension; the few MEL-14high cells localized in both the inner and the outer cortex on section staining are predominantly immature Ly-2- L3T4- and nonmature Ly-2+ L3T4+ thymocytes; the majority of thymocytes of mature phenotype, whether MEL-14high or MEL-14low on suspension staining, are of medullary location; the medulla is the most likely immediate source of thymic emigrants.

Animals↗

The correlation of lectin-stimulated proliferation and cytotoxicity in murine thymocytes with expression of the MEL-14-defined homing receptor.

The relationship between the expression of the MEL-14-defined lymphocyte homing receptor and the proliferation and functional differentiation of thymocytes in response to lectin stimulation was examined. Two-color fluorescent staining with MEL-14 in various combinations with PNA and anti-Ly-2 and anti-L3T4 was used to separate thymocyte populations for functional analysis. A high cloning-efficiency limit-dilution culture system was used to determine the frequency of all cells responsive to concanavalin A (PTL-p) or of all precursors of lectin-enhanced cytolytic lymphocytes (CTL-p). As expected from earlier studies, PTL-p and CTL-p were concentrated in the PNA- thymocytes, PTL-p were in both the Ly-2- L3T4+ and the Ly-2+ L3T4- subpopulations, and CTL-p were predominantely in the Ly-2+ L3T4- subpopulation. Within the PNA- thymocytes, two distinct peaks of PTL-p were found in cells stained with MEL-14, corresponding to MEL-14- and MEL-14medium-to-high cells, whereas the CTL-p frequency increased in fractions showing increasing expression of the MEL-14-defined antigen. Within the Ly-2- L3T4+ subpopulation, two distinct peaks of PTL-p were found corresponding to groups of MEL-14- and MEL-14medium-to-high cells, with the intermediate fraction of MEL-14low cells displaying a very low PTL-p frequency. The Ly-2+ L3T4- subpopulation included fewer MEL-14- cells and more MEL-14high cells than the Ly-2- L3T4+ subpopulation. Within the Ly-2+ L3T4- subpopulation, the few MEL-14- cells expressed a relatively low but definite frequency of CTL-p and PTL-p. The more numerous MEL-14+, Ly-2+ L3T4- cells included a high frequency of CTL-p and PTL-p, which did not vary over the medium-to-high MEL-14 expression range. These results indicate that the correlation of MEL-14 expression with CTL-p frequency among thymocytes is largely a consequence of the relative frequency of Ly-2+ L3T4- cells in the separated fractions, rather than a direct link between MEL-14 expression and function. Nevertheless, MEL-14 does define significant heterogeneity in both the Ly-2+ L3T4- and the Ly-2- L3T4+ subpopulations. In particular, there is a reduced functional response among the small subgroup of Ly-2+ L3T4- MEL-14- cells, suggesting this population includes either immature cells or cells of a different functional type.

Animals↗

Alkanol effects on early potassium currents in Aplysia neurons depend on chain length.

The relationship between alkanol chain length and effects on the transient potassium current, IA, were examined in three identified Aplysia californica neurons with ethanol (EtOH), butanol (BuOH), and hexanol (HxOH). Qualitative differences were found when the actions of EtOH were compared with those of the longer-chain-length alcohols. Whereas EtOH primarily affected the decay time constant of IA, having minimal effects on amplitude, BuOH and HxOH exerted their major effect on the amplitude of IA, reducing it, while their effects on decay kinetics were much less pronounced. The effects of EtOH on IA decay are cell specific among identified neurons of the Aplysia nervous system. The actions of BuOH and HxOH did not mimic these interneuronal differences. These data, coupled with data previously reported by us and others, make it unlikely that EtOH exerts its actions on IA via perturbation of a bulk lipid phase within the membrane.

Alcohols↗

Trends in coronary heart disease in Queensland, 1971-1980. An interpretation.

Routine data on mortality and hospital activity were used to estimate changes in coronary heart disease mortality, case fatality, and hospitalizations in the Australian state of Queensland over the decade 1971-1980. Acute myocardial infarction (International Classification of Diseases (ICD) 410) and other ischemic heart disease (ICD 411-414) were considered separately. For acute myocardial infarction, age-adjusted total mortality declined by about one fourth in both men and women; in-hospital mortality decreased somewhat more and deaths out of hospital correspondingly less. The age-adjusted case fatality ratio fell by the same amount (29%), in both sexes. Similar trends occurred at all ages. Admission rates decreased 11% in men and 18% in women. Similar patterns were evident for other ischemic heart disease except for admissions, which rose 23% among men and remained at the same level in women. These findings suggest that both declining incidence, particularly in the form of fewer deaths out of hospital, and improvements in care may have contributed to the general decline in coronary heart disease mortality in this community. Without direct measures of incidence or changing disease severity, the relative contributions of each factor cannot be examined.

Age Factors↗

Correlation of plasma beta-endorphin levels with mean arterial pressure and cardiac output in hypovolemic shock.

Recent studies have been conducted to evaluate the relationship between plasma beta-endorphin (END) levels and the hemodynamic changes that occur in severely stressed animals. Using our canine hypovolemic shock model, END levels were analyzed during the baseline period, at the beginning of treatment (after a period of fixed-pressure hypovolemic shock), and at the end of treatment. Mean arterial pressure (MAP) and cardiac output were also measured at these intervals. Animals were given iv 5 ml of 0.9% NaCl, 4 mg/kg of naloxone (NAL), 30 mg/kg of methylprednisolone (MP), or 4 mg/kg of NAL and 30 mg/kg of MP. A fifth group was composed of nonsteroid-treated animals. Scatterplots were generated and linear regression lines were drawn comparing END with cardiac output and MAP. In the nonsteroid-treated animals, a significant correlation was found between decreases in both MAP and cardiac output and increasing levels of END. The addition of MP did not seem to alter the relationship, suggesting that MP did not affect END release.

Animals↗

Effect of age and chronic obstructive pulmonary disease on the Breathalyzer estimation of blood alcohol level.

Twenty volunteers, 10 with chronic obstructive pulmonary disease (COPD) and 10 with no disease, ingested a vodka cocktail. Serial determinations of blood alcohol level (BAL) by gas-liquid chromatography and simultaneous Breathalyzer estimations of BAL were used to calculate blood:breath alcohol partition coefficients (PCs). Data from the present study were combined with data obtained in a previous study using identical methodology to examine the relationship between age and BAL estimation. It was found that the Breathalyzer significantly underestimated BAL as a function of age. It was hypothesized that the underestimation may be due to closing volume (CV) as the Breathalyzer samples end-expiratory breath.

Adult↗

Assessment of depression in geriatric medical outpatients: the validity of two screening measures.

The validity of two screening measures for depression was assessed in a geriatric medical outpatient population. Sixty-eight patients completed both questionnaires; 31 also completed a clinical interview allowing for accurate diagnosis. Both screening measures were found to accurately identify those who were depressed. Clinical and research applications are discussed, including the complementary use of these screening measures with the physician's diagnosis.

Aged↗

WAIS scores for a non-clinical British sample.

The Wechsler Adult Intelligence Scale (WAIS) was administered to a British sample of 63 volunteers. The mean Full Scale Intelligence Quotient obtained was 116.5, with a standard deviation of 9.7. This finding is discussed in relation to the accepted (American) WAIS norms, and further study suggested.

Adult↗