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Biomedical subjects

H Levine

Publications and source records attributed to H Levine.

At least 91 records · Page 5Linked to original sources
PubMed1991

A food polymer science approach to structure-property relationships in aqueous food systems: non-equilibrium behavior of carbohydrate-water systems.

Descriptions of the functional significance of carbohydrates based on the familiar equilibrium thermodynamics of very dilute solutions fail for pragmatical time scales and conditions, which are far from equilibrium. This is not too surprising, since limiting partial-molar properties reflect the independent behavior of solute in the limit of infinite dilution where free volume is maximum at a given temperature, while Tg'-Wg' properties reflect the cooperative behavior of solute-plasticizer blends at the limiting minimum value of free volume to observe relaxation within experimental time scales. Carbohydrate-water systems, with well-characterized structure and MW above and below the entanglement limit, provide a unique framework for the investigation of non-equilibrium behavior. Thermal analysis by DSC reveals the central role of water as a plasticizer for carbohydrates and of the glass transition as a physicochemical parameter that governs their properties, processing, and stability. A classical polymer science approach is used to study structure-property relationships of carbohydrates as water-compatible food polymers, which are treated as homologous systems of polymers, oligomers, and monomers with their plasticizers and solvents. Mechanical relaxation behavior is described by a "transformation map" of the critical variables of moisture content, temperature, and time. The glass curve is a reference contour, which represents the limiting isogram for free volume, local viscosity, relaxation rates, and rotational and translational mobility. Map domains are discussed as aspects of "water dynamics," to dispel the myth of "bound water," and "glass dynamics," to relate to macroscopic structure and collapse phenomena. A particular glass with invariant composition and Tg (prepared by freeze-concentration) is identified as a pivotal and practical reference state. The Tg observed during DSC analysis is often an effective Tg, resulting from instantaneous relative relaxation rates and non-uniform distribution of total sample moisture. Non-equilibrium melting, annealing, and gelation/recrystallization of kinetically metastable, partially crystalline carbohydrate systems exhibit non-Arrhenius kinetics which depend on the magnitude of delta T above the appropriate Tg, as defined by WLF relaxation transformations. Thermally reversible aqueous gels (crystallized from an under-cooled, rubbery melt) are described by a "fringed micelle" structural model for a three-dimensional polymer network, composed of microcrystalline junction zones crosslinking plasticized amorphous regions of flexible-coiled, entangled chain segments.

Carbohydrates↗
PubMed1991

Beyond water activity: recent advances based on an alternative approach to the assessment of food quality and safety.

Water, the most abundant constituent of natural foods, is a ubiquitous plasticizer of most natural and fabricated food ingredients and products. Many of the new concepts and developments in modern food science and technology revolve around the role of water, and its manipulation, in food manufacturing, processing, and preservation. This article reviews the effects of water, as a near-universal solvent and plasticizer, on the behavior of polymeric (as well as oligomeric and monomeric) food materials and systems, with emphasis on the impact of water content (in terms of increasing system mobility and eventual water "availability") on food quality, safety, stability, and technological performance. This review describes a new perspective on moisture management, an old and established discipline now evolving to a theoretical basis of fundamental structure-property principles from the field of synthetic polymer science, including the innovative concepts of "water dynamics" and "glass dynamics". These integrated concepts focus on the non-equilibrium nature of all "real world" food products and processes, and stress the importance to successful moisture management of the maintenance of food systems in kinetically metastable, dynamically constrained glassy states rather than equilibrium thermodynamic phases. The understanding derived from this "food polymer science" approach to water relationships in foods has led to new insights and advances beyond the limited applicability of traditional concepts involving water activity. This article is neither a conventional nor comprehensive review of water activity, but rather a critical overview that presents and discusses current, usable information on moisture management theory, research, and practice applicable to food systems covering the broadest ranges of moisture content and processing/storage temperature conditions.

Carbohydrates↗
PubMed1990

Human natural killer cell adhesion molecules. Differential expression after activation and participation in cytolysis.

Cell adhesion molecules (CAM) participate in interactions between lymphocytes, accessory cells, and target cells that are critical in the generation of effective immune responses. To characterize the involvement of CAM in NK and lymphokine activated killer (LAK) activities, we examined the expression of several CAM by freshly isolated human NK cells and by NK cells activated in vitro with IL-2, and compared this to CAM expression by T lymphocytes under similar conditions. Freshly isolated human NK cells were uniformly LFA-3 (CD58)+ and expressed two to three-fold higher surface levels of LFA-1 (CD11a/CD18) than resting T lymphocytes. More NK cells than T cells also expressed phenotypically detectable levels of intercellular adhesion molecule-1 (CD54). After in vitro incubation with IL-2, human NK cells demonstrated four- to sixfold increases in surface levels of CD11a/CD18, CD2, CD54, CD58, and the NK cell-associated Ag NKH-1 (CD56). Furthermore, essentially all NK cells became CD54+ within 3 days of exposure to IL-2. T cells did not demonstrate comparable up-regulation of CAM after incubation with IL-2. Increases in NK cell CAM expression were associated with enhanced formation of E:T cell conjugates, enhanced killing of NK-sensitive targets, and the induction of cytotoxicity for previously NK-resistant targets (LAK activity). The LAK activity induced by exogenous IL-2 could be partially inhibited by anti-CD2, anti-CD11a, or anti-CD54 antibodies and almost completely abrogated by anti-CD2 and anti-CD11a in combination. These studies suggest that CAM play a central role in the regulation of NK cytolysis, and that changes in CAM expression may alter the target cell specificity of activated NK effectors.

Antibodies, Monoclonal↗
PubMed1990

Functional consequences of interleukin 2 receptor expression on resting human lymphocytes. Identification of a novel natural killer cell subset with high affinity receptors.

In this study, we have used radiolabeled IL-2 binding assays, Northern blot analysis, immunofluorescent flow cytometry and cell sorting, as well as proliferation and cytotoxicity assays to perform an extensive phenotypic and functional characterization of the IL-2 receptor in normal resting human peripheral blood lymphocytes. Our results indicate that almost all T cells (greater than 98%) express neither the high affinity IL-2 receptor nor the functional intermediate affinity p75 chain of the IL-2 receptor without prior activation. In contrast, most NK cells constitutively express the isolated intermediate affinity p75 IL-2 receptor. In addition, a subpopulation of NK cells, distinguished by high density expression of the NKH1 antigen, constitutively express the high affinity IL-2 receptor, in addition to an excess of the isolated intermediate affinity p75 IL-2 receptor. These NKH1bright+ cells exhibit a brisk proliferative response to IL-2, similar to that seen with antigen-activated T cells, yet do so in the absence of any known antigenic stimuli. No other resting peripheral blood lymphocyte population, including CD4+, CD8+, and CD20 cells, exhibits this property. The intermediate affinity p75 IL-2 receptor, as it exists in its isolated form on resting NK cells, does not transduce a growth signal equivalent to that seen in NK cells expressing the high affinity IL-2 receptor, despite doses of IL-2 that are known to fully saturate the isolated p75 chain. This strongly suggests that additional structural or functional components are involved in generating the proliferative response following the binding of IL-2 to the high affinity heterodimeric form of the IL-2 receptor. The constitutive expression of this functional high affinity IL-2 receptor on a small population of resting NK cells provides further evidence in support of a role for these cells in the host's early defense against viral infection or malignant transformation, before the more delayed but specific T cell response.

Antibodies, Monoclonal↗
PubMed1990

Differential regulation of Ca2+ mobilization in human thymocytes by coaggregation of surface molecules.

Variations in intracellular Ca2+ levels in developing thymocytes are likely to play a major role in both the activation-associated differentiation of thymocytes and in the selection or clonal deletion of cells. Here we examine the role of CD4, CD8, CD2, and CD45 in the regulation of intracellular Ca2+ levels in mature and immature thymocytes. Mature and immature thymocytes, distinguished on the basis of their CD5 expression, were analyzed simultaneously for their ability to mobilize Ca2+ after coaggregation of their CD3/TCR with other thymic surface Ag. Flow cytometric analysis by using Indo-1 showed that coaggregation of CD4, CD8, and CD2 with CD3/TCR clearly enhances a minimal signal delivered via CD3/TCR on immature thymocytes. Coaggregation with class I MHC had no discernible effect. The responsiveness of immature thymocytes correlated strictly with CD3 surface expression, such that loss of responsiveness occurred with reduced CD3 cell-surface density. However, even thymocytes with very low CD3 expression were able to respond to triggering via CD3 under optimal conditions, indicating that the CD3 signal-transducing mechanism is functional on early thymic cells. Intracellular increases in Ca2+ concentrations induced via CD3, could effectively be inhibited by cross-linking of CD45 and CD3 on immature thymocytes. Although triggering via CD2 alone induced a strong Ca2+ flux, prolonged incubation with activating anti-CD2 antibodies made thymocytes refractory to subsequent triggering. Refractoriness was associated with partial loss of surface CD3 and CD3 zeta. Our results indicate that thymic surface Ag are differentially involved in the regulation of intracellular Ca2+ levels in immature as well as mature thymocytes.

Antigens, CD↗
PubMed1990

A monoclonal antibody reactive with a 15-kDa cytoplasmic granule-associated protein defines a subpopulation of CD8+ T lymphocytes.

We have recently described a novel method for the production and characterization of mAb reactive with T cell-restricted intracellular antigens. From a panel of antibodies that react specifically with permeabilized T lymphocytes but not with permeabilized B lymphocytes or native T cells, we have selected one, designated TIA-1, that reacts with 20 to 36% of digitonin permeabilized peripheral blood T lymphocytes. Flow cytometric analysis of purified CD4+ and CD8+ subsets showed TIA-1 to recognize a subpopulation of 49 to 64% of CD8+ lymphocytes. Little or no reactivity with CD4+ resting T lymphocytes was observed. TIA-1 did not react with any of a panel of T cell lines, B cell lines, or monocytoid cell lines. TIA-1 reacted strongly with NK cell clones and CD8+ cytolytic T cell clones, and less strongly with CD4+-activated T cell clones, suggesting a preferential expression in cells possessing cytolytic potential. Cell fractionation experiments showed TIA-1 to be membrane associated. Furthermore, Percoll gradient fractionation of a cytolytic T cell clone (T4T8C1) showed the majority of TIA-1 to be contained in a low density membrane fraction that also contained serine protease activity. Immunoelectron microscopy showed TIA-1 to decorate the membranes of electron lucent and electron dense cytoplasmic granules in this same cytolytic T cell clone. Biochemical analysis showed TIA-1 to be a 15-kDa protein in unstimulated T cells. Upon activation with Con A or anti-CD3 antibodies. TIA-1 was induced to form disulfide linked dimers, trimers, and tetramers of the basic 15-kDa unit. Taken together, our data suggest that TIA-1 is a cytolytic granule associated protein that may define a subpopulation of resting CD8+ T lymphocytes possessing cytolytic potential.

Antibodies, Monoclonal↗
PubMed1989

Expression of CD1 and class I MHC antigens by human thymocytes.

The acquisition of surface class I MHC molecules is associated with the maturation of thymocytes. Here, surface expression of class I MHC and CD1, which represents a family of MHC-related molecules, was analyzed on various human immature and mature thymocyte subpopulations. Class I expression was inversely related to the expression of CD1. The majority of CD4+ CD8+ cortical type thymocytes expressed low levels of class I MHC Ag, the previously described CD4+ CD8+ thymocyte subpopulation with low CD8 expression exhibited intermediate levels of class I MHC, whereas most of the single positive CD4 and CD8 thymocytes displayed high levels of class I MHC. Biochemical comparison of CD1 and class I showed that thymic class I molecules were post-translationally modified by phosphorylation, whereas CD1 was not phosphorylated. Furthermore, our studies suggested that in addition to CD1/CD8 complexes, thymocytes bear CD8/class I complexes. Chemical cross-linking and peptide mapping studies clearly identified the CD8-associated protein on thymic clones as the class I MHC molecule.

Antigens, CD1↗