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Biomedical subjects

D Skea

Publications and source records attributed to D Skea.

7 recordsLinked to original sources
PubMed1999

Large ex vivo expansion of human umbilical cord blood CD4+ and CD8+ T cells.

The use of human umbilical cord (UC) blood as a source of transplantable hematopoietic stem cells and progenitor cells may present some advantages over the use of BM. For example, it has been suggested that the degree of HLA matching may be less stringent, and the risk of GvHD may be lower. We have been studying the ex vivo expansion of UC blood T lymphocytes with a view to their use in the adoptive immunotherapy of cancer, autoimmunity, and infectious disease. We have developed a new method involving the use of a conditioned medium (XLCM) that consistently results in levels of UC blood T cell expansion not hitherto possible. Primary cultures of unfractionated low-density MNC (LDMNC) derived from UC blood treated with 5% XLCM routinely show expansions greater than 10,000-fold within 4 weeks. By contrast, similar FBS-free cultures treated with IL-2 expand less than 10-fold and not after 1 week, and cultures treated with IL-2 and concanavalin A (ConA) expand to a maximum of only 300-500-fold over 2 weeks and fail to continue to proliferate thereafter. The MAb, OKT3, which, when combined with IL-2 and FBS, is known to stimulate proliferation of adult peripheral blood lymphocytes, permitted only a 17-fold expansion of UC blood lymphocytes under the same conditions. Thus, XLCM, which can also stimulate adult peripheral blood lymphocyte expansion to levels exceeding 100,000-fold in 3-4 weeks, is uniquely able to stimulate proliferation of UC blood lymphocytes to high levels. From initiation of the UC blood or adult peripheral blood LDMNC/XLCM cultures up to approximately 2 weeks, the cultures are dominated by CD4+ T lymphocytes. By 4 weeks, >80% of the cultured cells bear the CD8+ phenotype, whereas UC blood T lymphocytes cultured in the presence of IL-2 are predominantly CD8+. Thus, XLCM not only allows high levels of expansion of UC blood T lymphocytes not heretofore possible but also permits the selective expansion of different T lymphocyte subsets from a single source.

Adult↗
PubMed1999

The selective expansion of functional T cell subsets.

Adoptive cellular immunotherapy is considered a potential treatment for a wide range of diseases, including cancer, infectious diseases, and autoimmune disorders. We have developed a method using a conditioned medium, XLCM, that selectively expands several different T cell subsets with a view to their use in cell therapy. Primary FBS-free suspension cultures of human peripheral blood low-density mononuclear cells treated with XLCM reproducibly expand over 100,000-fold within a period of 4 weeks. CD4+ T cells and CD8+ T cells expand sequentially in the unfractionated cultures, and relatively pure populations of CD4+ and CD8+ T cells may be expanded from populations first enriched in the respective T cell subset. CD4+ T cells cultured in XLCM produce cytokines consistent with the expansion of Th1, Th2, and Th0 subsets, whereas CD8+ T cells cultured in XLCM are cytolytically competent. An interesting feature of T cells cultured in XLCM is the persistence of 5%-10% CD4+CD8+ double-positive T cells in spite of substantial single-positive T cell expansion, suggesting that these cells also proliferate in XLCM. In addition to subsets of TCRalphabeta+ T cells, TCRgammadelta+ T cells are also significantly expanded by XLCM. These results demonstrate that XLCM efficiently expands several functional T cell subsets and provides a means of obtaining selected populations suitable for use in cellular immunotherapy.

Adoptive Transfer↗
PubMed1997

Gender and interactions between care staff and elderly nursing home residents with dementia.

OBJECTIVE: This study explores the relationship between gender and the interactions of care staff and elderly people with dementia in residential care. DESIGN: Non-participant, time-sampling observation and coding of interactions between staff and residents. SETTING: 36-bed independent (not-for-profit) long-term care unit. SUBJECTS: 36 elderly people with dementia (19 men and 17 women); 37 care staff (30 women and 7 men). MEASURES: The Quality of Interactions Schedule (QUIS). RESULTS: Male residents initiated significantly more interactions with staff than female residents. Men did not initiate interactions with female staff significantly more often than with male staff. Women did not initiate any interactions with male staff. Female staff initiated more interactions with residents than did male staff. Both male and female staff initiated a higher proportion of interactions with male residents than with female residents. CONCLUSIONS: These findings suggest that gender may be a significant factor determining the rate of interactions between staff and residents in residential care, but further studies are required to confirm their generalizability across settings.

Adult↗
PubMed1988

Chronic giardiasis in B-cell-deficient mice expressing the xid gene.

The role of antibody in immunity to Giardia muris infection was investigated by studying B-cell-deficient CBA/N mice expressing the xid gene. After gastric administration of infective G. muris cysts, CBA/N male and female mice developed prolonged G. muris infection, whereas BALB/c mice eliminated their infection in 6 to 8 weeks. Male F1 progeny obtained from matings between female CBA/N mice and male BALB/c mice expressed the xid gene and developed prolonged infections. In contrast, all other F1 progeny of CBA/N and BALB/c matings, which did express the xid gene, eliminated G. muris. The link between the xid gene and prolonged infection was confirmed by studies of C57BL/6 mice congenic for the xid gene. When compared with BALB/c or F1 mice, CBA/N mice produced large quantities of immunoglobulin A (IgA) anti-G. muris antibody in serum and gut secretions during prolonged infection. Serum IgG anti-G. muris antibody levels were reduced in CBA/N and F1 male mice that expressed the xid gene. The inability of xid mice to eliminate G. muris is consistent with the importance of antibody in the development of immunity to G. muris. We hypothesize that mice bearing the xid gene fail to produce IgA antibody of appropriate specificity to an antigen or antigens whose recognition by antibody is critical for successful elimination of the parasite.

Animals↗
PubMed1988

Phenol amplifies complement-fixing activity and induces IgG-precipitating activity in grain-dust extract.

The use of phenol as a preservative in extracts of grain dust was found to be associated with an amplification of complement-fixing activity and the appearance of IgG-precipitating activity. Both activities were absorbed by IgG, suggesting that they were due to a single material. Phenol itself neither fixed complement nor formed a precipitate with IgG. 14C-labeled phenol was incorporated into the IgG precipitating material. Both the amplification of complement-fixing activity and the appearance of IgG-precipitating activity in phenol-containing grain-dust extract were dependent on the presence of air and were inhibited by heating the extract before phenol addition. One interpretation of these results is that a component of grain-dust extract, possibly an enzyme, oxidatively modifies phenol to a form that fixes complement and precipitates IgG. The modified material demonstrates properties of a polyphenol (tannin).

Chemical Precipitation↗
PubMed1986

Methanol extract of grain dust shows complement fixing activity and other characteristics similar to tannic acid.

We have found several similarities between tannic acid and grain dust extract prepared with methanol. Both formed a precipitate with IgG, and these interactions were inhibited by albumin. In addition, both preparations fixed complement; this activity was heat stable and was removed by prior adsorption of the preparations with hide powder. Adsorption with polyvinyl polypyrrolidone reduced the complement-fixing activity of tannic acid but not that of the methanol grain dust extract. The similarities between tannic acid and the methanol grain dust extract are consistent with the presence of a tannin or tanninlike material in grain dust.

Animals↗