Abnormalities of in vitro lymphocyte responses during rubella virus infections.

In vitro rubella virus infections of lymphocytes from normal adult humans impaired their responsiveness to phytohemagglutinin (PHA) stimulations; a situation which seemed analogous to the PHA unresponsiveness of peripheral lymphocytes from babies with the congenital rubella syndrome. Such in vitro viral infection of normal cells also decreased the synthesis of normal nucleic acids and structural proteins, and abrogated the enhanced DNA synthesis induced by pokeweed and specific antigen stimulations. Furthermore, it was shown that live rubella virus, but not ultraviolet-irradiated virus, was necessary for the impaired mitogenic responses of normal leukocytes. These observations are interpreted to favor the view that the virus achieves its inhibitory effect on the action of mitogens by interference either directly or indirectly at an intracellular site. Such an action could reduce the functional potential of lymphocytes and impair their effectiveness as immunologically competent cells or as effectors in immunologic reactions.

First principles determination of the effects of phosphorus and boron on iron grain boundary cohesion.

Toward an electronic level understanding of intergranular embrittlement and its control in steels, the effects of phosphorus and boron impurities on the energy and electronic properties of both an iron grain boundary and its corresponding intergranular fracture surface are investigated by the local density full potential augmented plane wave method. When structural relaxations are taken into account, the calculated energy difference of phosphorus in the two environments is consistent with its measured embrittlement potency. In contrast to the nonhybridized interaction of iron and phosphorus, iron-boron hybridization permits covalent bonding normal to the boundary contributing to cohesion enhancement. Insights into bonding behavior offer the potential for new directions in alloy composition for improvement of grain boundary-sensitive properties.

Effect of amantadine hydrochloride on the response of human lymphocytes to phytohemagglutinin.

Amantadine hydrochloride (Symmetrel), which is an antiviral agent marketed for the prevention of infection by influenza virus, inhibits the mitogenic response of human lymphocytes stimulated with phytohemagglutinin. The concentrations which effectively inhibited the response to phytohemagglutinin were similar to those which maximally inhibit virus replication. The drug inhibited the mitogenic response without affecting the ability of phytohemagglutinin to agglutinate leukocytes. The data suggest that phytohemagglutinin, amantadine, and certain lipid-containing RNA viruses take part in cell-membrane interactions of common nature.

Viral inhibition of lymphocyte response to phytohemagglutinin.

The response to phytohemagglutinin by lymphocytes from eight of fourteen patients with congenital rubella was inhibited, whereas that of lymphocytes from patients with other diseases was not. The response of normal lymphocytes infected in vitro was also inhibited. The results suggest that early association of lymphocytes with virus inhibits the function of the cell and contributes to persistent carrying of virus in congenital rubella. This phenomenon may be a means of detecting viruses not now recognizable by routine methods of tissue culture.

Analysis of the hairless mouse as a model for the effects of aging on the immune system.

Studies into the effects of aging on the immune system are hampered by the lack of a suitable animal model that is readily available and cost efficient. The mutant mouse, hairless (hr/hr genotype), has been shown to undergo an accelerated thymic involution with accompanying immunodeficiency. Thus, this strain of mouse has been proposed as a model for studying the interactions of aging and immune function. We have investigated the effects of homozygous hr gene expression over time on the immune function of these mice. It was observed that homozygous hr gene expression had minimal effects on peripheral lymphocyte subset compositions but did appear to result in changes in thymic differentiation. Further, hr/hr mice displayed decreased proliferative responses to IL2 and mitogen stimulation, although cytotoxic responses (both NK and T cell mediated) appeared normal. These defects appear to be attributable to T helper cell dysfunction. Each of the changes found in hr/hr mice were distinct from those seen with age-matched control mice. Thus, the hr/hr inbred strain of mouse does not appear to be a suitable model for use in analyzing the effects of aging on the immune system.

Computer analysis of defined populations of lymphocytes irradiated in vitro. III. Evaluation of human T and B cells of peripheral blood origin.

The radiosensitivities of lymphocytes of peripheral blood origin obtained from two healthy 45 year old male donors were studied simultaneously at yearly intervals over a three year period. Hypaque-Ficoll purified cells were exposed in vitro to 0, 5, 50, and 500 rads and then evaluated serially for viability of T and B cells, responsiveness to PHA and Con A, and morphologic evidence of injury as documented by standard light microscopy and computer assisted morphometric analysis. The results showed that T cells in both subjects were less radiosensitive than B cells. Differences between the two subjects also existed in the radiosensitivity of these two subpopulations of lymphocytes, differences that remained constant over the three years period of observation. The differences correlated with similar discrepancies in mitogenic responsiveness and are thought to relate to variations in the relative proportions of subpopulations of T and B cells. In the mouse, T and B cell subpopulations differ in radiosensitivity. The data reported herein are consistent with a similar situation in man.

Discrimination between human T and B lymphocytes by computer analysis of digitized data from scanning microphotometry. II. Discrimination and automated classification.

Human B and T lymphocytes were purified and stained according to the Feulgen procedure. Stained preparations were scanned on a microphotometer and the digitized images were processed by analytical programs on a computer. Features of the cells relating to the chromatin distribution were extracted. Computer algorithms automatically derive classification rules and a machine recognition of B cells and T cells results in better than 80% correct assignments. The image data reveal a rich feature structure within both the purified B and T cell populations. Each population appears to contain several subpopulations of cells with distinctive and different chromatin texture.

Computer analysis of defined populations of lymphocytes irradiated in vitro: I. Evaluation of murine thoracic duct lymphocytes.

Computer-assisted morphometric analysis of murine lymphocytes obtained by thoracic duct cannulation demonstrates two populations of cells; the larger population (73 percent) appears to be thymus-derived and the remaining 27 percent is of bone marrow origin. Following exposure to varying amounts of x-radiation, morphologic alterations in both populations are evident. The smaller cell populations are evident. The smaller cell population exhibits some of these changes at lower dose levels than does the larger population. In addition, the character of the radiation-induced changes appears to be different for the two populations of lymphocytes. After 500 rad, the nuclei of the larger population appears unchanged; the nuclei of the population representing 27 percent of the cells have become enlarged and vacuolated and are thought to be edematous. After 2000 rad, the nuclei of the larger population appear pyknotic with coarsely clumped chromatin. In the examined set of cells, the smaller population could no longer be detected after 2000 rad. Such disparate responses to radiation-induced injury may correlate with known differences in immunologic function which serve to distinguish thymic-dependent and bone marrow-derived small lymphocytes.

Delayed-type hypersensitivity responses induced by bovine colostral components.

Transfer factor-type substances obtained from leukocytic cells and fluid portions of bovine colostrum caused effective passive transfer of delayed-type hypersensitivity responses across species barriers. Passive transfer of Brucella abortus sensitivity was obtained with equal regularity when using components derived from peripheral blood and colostrum of dams sensitized at 3 and 9 months of age. Colostral feedings to calves caused the passive transfer of delayed-type hypersensitivity as early as 2 days after parturition. The findings indicated that colostral components were important in the process of cell-mediated immunity.

Biochemical and genetic characterization of Corynebacterium pseudotuberculosis.

Isolates (n = 94) of Corynebacterium pseudotuberculosis were obtained from sheep, goats, horses, and cattle from various parts of the world. The isolates were characterized biochemically and by restriction endonuclease analysis of DNA. We found near homogeneity in the ability of isolates to ferment carbohydrates and to produce urease. All isolates produced phospholipase D and catalase. The ability of isolates from horses to reduce nitrate, the inability of isolates from sheep and goats to do so, and the correlation of this characteristic with results of restriction endonuclease analyses confirmed the existence of 2 biovars of C pseudotuberculosis. We propose that these biovars be referred to as biovar equi for isolates that reduce nitrate and biovar ovis for isolates that fail to do so.

Characterization of lectin-binding lymphocytes in goats with caseous lymphadenitis.

Numbers of lymphoid cells bearing markers for peanut agglutinin, wheat germ agglutinin, and anti-immunoglobulin G in healthy goats and in goats with caseous lymphadenitis were determined by use of immunofluorescent techniques. Results indicated that, when compared with healthy goats, diseased goats had normal numbers of anti-immunoglobulin G-positive cells (B cells), had significantly reduced numbers of peanut agglutinin-positive cells (T cells), and had fewer cells with receptor sites for Lens culinaris agglutinin and concanavalin A. Compared with healthy goats, numbers of peanut agglutinin-positive cells in goats with caseous lymphadenitis indicated that the goats may have had a compromised cell-mediated immunity.

The effects of collagen hydrolysat on symptoms of chronic fibromyalgia and temporomandibular joint pain.

Twenty (20) people who had medically diagnosed fibromyalgia for two to 15+ years participated in and completed a 90-day evaluation to determine effects of collagen hydrolysat on symptoms of chronic fibromyalgia, with twelve reporting temporomandibular joint pain. Collagen hydrolysat is a food supplement that is available without prescription, with no known side effects. Participants were evaluated initially and then at 30-, 60-, and 90-day periods. Final results were obtained and comparisons made. The average pain complaint levels decreased significantly in an overall group average, and dramatically with some individuals. It was concluded that patients with fibromyalgia and concurrent temporomandibular joint problems may gain symptomatic improvement in their chronic symptoms by taking collagen hydrolysat.