Biomedical subjects

C Olsson

Publications and source records attributed to C Olsson.

5 recordsLinked to original sources

PubMed1992

Interleukin (IL1 to IL7) gene expression in fetal liver and bone marrow stromal clones: cytokine-mediated positive and negative regulation.

Mouse bone marrow and fetal liver stromal clones have been analyzed for their cytokine mRNA expression. The reverse transcriptase polymerase chain reaction (RT-PCR) has allowed us to detect interleukin (IL) mRNA levels, even if synthesized at levels not detectable by Northern blot analysis. We found that stromal cells possess the potential to constitutively express a much larger number of interleukins than previously described. The three stromal clones analyzed here expressed mRNA for IL3 and IL2, in addition to mRNA for IL1, IL4, IL6, and IL7. None of the stromal clones synthesized IL5 mRNA. Cytokine mRNA synthesis by stromal cells was found to be subjected to negative and positive regulation by interleukins. IL2, IL3, IL6, and IL7 gene expression was much more sensitive to cytokine regulation than that of IL1 and IL4.

Animals↗

PubMed1991

Structure of the T cell antigen receptor (TCR): two CD3 epsilon subunits in a functional TCR/CD3 complex.

Transgenic mice carrying and expressing the human CD3 epsilon gene incorporate the corresponding protein product into T cell receptor (TCR)/CD3 complexes on thymocyte and T cell surfaces. The chimeric antigen receptors allow normal T cell development and selection of repertoires in vivo and are able to transduce activation signals in vitro. We have exploited the ability to distinguish mouse (m) and human (h)CD3 epsilon chains to analyze the stoichiometry of CD3 epsilon in transgenic mouse TCRs. Immunoprecipitation and fluorescence resonance energy transfer experiments demonstrate that such TCRs can contain both h- and mCD3 epsilon chains, implying that more than one CD3 epsilon subunit occurs per TCR. Antigen comodulation studies are consistent with a stochastic use of h- or mCD3 epsilon during receptor assembly, and further suggest a structure for the TCR/CD3 complex with two CD3 epsilon chains. The determination of CD3 epsilon subunit stoichiometry, together with existing biochemical data, allows the generation of a minimal model for the structure of the TCR and illustrates the potential value of the transgenic approach to the analysis of complex receptors.

Animals↗

PubMed1989

Production and secretion of recombinant soluble CD3 polypeptides by myeloma-derived transfectant clones.

Soluble forms of three human CD3 proteins have been produced by recombinant DNA techniques. The extracellular domain of CD3-gamma, -delta or -epsilon has been linked to the constant region of mouse immunoglobulin kappa light chain to form gamma-kappa, delta-kappa and epsilon-kappa chimaeric proteins. These are secreted by mouse myeloma-derived transfectant cell lines and are immunoprecipitable by CD3- or kappa-specific polyclonal antisera. Yields of 100-500 micrograms secreted recombinant proteins per litre of culture medium were obtained, which could be purified by anti-kappa affinity chromatography. The production of soluble CD3 illustrates the applicability of this technology to a loosely associated protein complex.

Antigens, Differentiation↗

PubMed1989

The majority of human CD3 epitopes are conferred by the epsilon chain.

Transgenic mouse T cells expressing the human CD3 epsilon chain bind the majority (29/36) of monoclonal antibodies (mAbs) specific for human CD3. A proportion of these mAbs are also able to recognize isolated CD3 epsilon in a soluble, recombinant form. Thus, CD3 epsilon can confer most CD3 epitopes on the TCR--CD3 complex, but many determinants may require assembly of the complex for their formation. A number of mAbs did not recognize epsilon-transgenic T cells and probably need other CD3 subunits for binding. CD3-specific mAbs from each of the three groups defined here, as well as mAbs directed against the TCR alpha beta heterodimer, are all able to activate T cells. Therefore mAb attachment at several different sites on the TCR--CD3 complex can give rise to activation signals. This suggests that the cross-linking function of mitogenic antibodies may be their most significant property, rather than the perturbation of a particular 'functional epitope'.

Animals↗

PubMed1976

Pelvic exenteration as palliation of malignant disease.

It has been traditional to exclude patients with radiation-recurrent carcinoma of the uterine cervix or other pelvic neoplasms, incapacitating pelvic pain, postirradiation fistulas, hemorrhage, or malodorous draining tumor necrosis from pelvic exenteration if cure of the malignant disease is not achievable. This negative attitude is a direct result of the reported high morbidity, prohibitive mortality, and low salvage rate previously associated with pelvic exenteration, the only acceptable surgical approach to these diseases. A recent experience with eighteen patients who underwent pelvic exenteration for advanced primary or recurrent carcinoma of the cervix, urinary bladder, or rectum has led us to challenge several traditional concepts regarding this operative procedure. We have observed but one operative death and our morbidity has been minimal. This may reflect our belief that an aggressive pelvic lymphadenectomy in those patients with direct visceral involvement from radiation-recurrent carcinoma of the pelvic viscera is not advantageous since no significant survival has ever been documented for patients with pathologic visceral involvement and positive lymph nodes. In addition, significant morbidity has always been associated directly with pelvic lymphadenectomy in the irradiated pelvis, and elimination of this phase of the operation in selected patients with radiation-recurrent carcinoma is indicated. Moreover, the considerable decrease in morbidity and the minimal mortality observed have led us to adopt a very liberal attitude toward preoperative selection criteria, and we regularly now use pelvic exenteration not only for cure but as intentional palliation in selected patients. We strongly believe that elimination of pain, fistulas, pelvic sepsis, hemorrhage, and malodorous areas of tumor necrosis are important for improving the quality of life for both the patient and family.

Aged↗