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Biomedical subjects

L Ramm

Publications and source records attributed to L Ramm.

5 recordsLinked to original sources

Single-cell analysis by RT-PCR reveals differential expression of multiple type 1 and 2 cytokine genes among cells within polarized CD4+ T cell populations.

RT-PCR was used to examine the expression of IFN-gamma, IL-2, IL-4, IL-5, IL-6 and IL-10 mRNAs by single murine CD4+ T cells activated either in a strongly type 1-polarized mixed lymphocyte reaction (MLR) or in the type 2-polarized response to immunization with keyhole limpet hemocyanin (KLH) in alum. The frequencies of expression of each cytokine differed markedly between the two responses, consistent with their polarization at the population level. However, most cells expressed only none to three of the six cytokines assayed, few displayed the canonical type 1 profile and none in either response expressed a full type 2 or type 0 profile. A significant fraction of cells co-expressed IFN-gamma with IL-4 and/or other type 2 cytokines at frequencies that suggested that most of these genes were independently regulated. Collectively, these single-cell expression patterns indicate that polarization at the population level can mask substantial intercellular heterogeneity, and show directly that multiple type 1 and 2 cytokines can be expressed simultaneously in an individual T cell.

Animals↗

The CD4+ T-cell response to protein immunization is independent of accompanying IFN-gamma-producing CD8+ T cells.

By virtue of their strong bias towards production of interferon-gamma (IFN-gamma), CD8+ T cells have the potential to promote the development of type 1 immune responses. We have previously shown that the CD4+ T-cell response to immunization with the protein antigen keyhole limpet haemocyanin (KLH) has a mixed interleukin-4 (IL-4)/IFN-gamma production profile. Here we show that this immunization regimen also stimulates accumulation in the draining lymph nodes of CD8+ T cells, which preferentially contain IFN-gamma mRNA ex vivo and secrete IFN-gamma protein in vitro. This provides a model to test whether CD8+ cell-derived IFN-gamma participates in the normal control of the immune response to a non-viable exogenous antigen. To investigate regulation of the anti-KLH response by the CD8+ population or IFN-gamma produced by this or other cell types, mice were administered depleting antibodies. Depletion of CD8+ cells had no effect on the frequency of clonogenic KLH-specific CD4+ T cells, the IL-4/IFN-gamma profiles of their progeny, or the isotype profiles of the serum antibody response to KLH. In contrast, IFN-gamma neutralization diminished cell accumulation in the lymph nodes and reduced both the frequency of KLH-specific CD4+ T cells that gave rise to IFN-gamma-producing clones and serum titres of KLH-specific IgG2a and IgG3. Therefore, despite the potential for cross-regulation, the CD4+ T-cell response to this immunogen is independent of the IFN-gamma-skewed CD8+ response.

Animals↗

Expression of tumour markers CA125, CASA and OSA in minimal/mild endometriosis.

Ovarian cancer associated antigens CA125, CASA and OSA were measured in serum from 23 patients with mild endometriosis before, during and after medical therapy. Pretreatment CA125 levels were elevated above 35 mu/ml in 4(17%), and above 25 mu/ml in 7 (30%) patients. Mean CA125 levels decreased during treatment, but in only 10 patients did levels reflect disease response. There was no correlation between CA125 levels and disease severity as measured by modified American Fertility Society Scoring. Neither CASA nor OSA were detected in these women.

Antigens, Neoplasm↗

Clomipramine and exposure for chronic obsessive-compulsive rituals: III. Two year follow-up and further findings.

Forty chronic ritualizers were given clomipramine or placebo from weeks 0 to 36; also all had exposure in vivo, half from weeks 4 to 10 (30 hours) and half from weeks 7 to 10 (15 hours). In the 37 patients available at week 114 there were substantial and maintained improvements in rituals, mood and social adjustment compared to week 0. Reduction of rituals was even greater in those who had 30 hours of exposure. There was no drug effect on rituals at two year follow-up. Greater initial anxiety or depression predicted the superiority of clomipramine over placebo from weeks 10 to 36 and more prescription of tricyclics in follow-up. However, two years outcome was not predicted by initial anxiety or depression, nor by sex, age, age of onset nor duration of rituals.

Anxiety↗

Guided mourning for morbid grief: a controlled study.

During 2 weeks on a waiting list 12 patients with morbid grief did not improve significantly. They were then randomly allocated either to guided mourning treatment, in which they were encouraged to face cues concerning their bereavement, or to control treatment in which they were asked to avoid such cues. Each treatment comprised six 1 1/2 hour sessions over 2 weeks. At week 4 guided mourning patients had improved significantly more than had controls on 3 measures, with a supportive trend on 4 measures. Improvement, though modest, was maintained to 10-28 weeks follow-up. Control patients did not improve significantly or show any trend to do so.

Adult↗