36 research outputs found
Canine Immunogenetics
Recognizing the significant advances made in the field of animal genetics in the ten years since the first edition of Genetics of the Dog, this new edition of the successful 2001 book provides a comprehensive update on the subject, along with new material on topics of current and growing interest. Existing chapters on essential topics such as immunogenetics, genetics of diseases, developmental genetics and the genetics of behaviour have been fully updated, while new authors report on the latest advances in areas such as genetic diversity of dog breeds, canine genomics, olfactory genetics and cancer genetics
119DLA-haploidentical stem cell allografts after anti-CD44 therapy and nonmyeloablative conditioning in a preclinical canine model
Ex vivo expanded T regulatory (Treg) cells block the breaking of tolerance in mixed chimeras
Canine Immunogenetics
Recognizing the significant advances made in the field of animal genetics in the ten years since the first edition of Genetics of the Dog, this new edition of the successful 2001 book provides a comprehensive update on the subject, along with new material on topics of current and growing interest. Existing chapters on essential topics such as immunogenetics, genetics of diseases, developmental genetics and the genetics of behaviour have been fully updated, while new authors report on the latest advances in areas such as genetic diversity of dog breeds, canine genomics, olfactory genetics and cancer genetics
Tandem Autologous and Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation (HCT) from HLA-matched Related Or Unrelated Donors for Advanced Lymphoma Or Chronic Lymphocytic Leukemia (CLL)
An epidemiological assessment of lens opacifications that impaired vision in patients injected with radium-224
The incidence of lens opacifications that impaired vision (cataract) was analyzed among 831 patients who were injected with known dosages of 224Ra in Germany shortly after World War II. The dependence of the incidence on dosage, i.e., injected activity per unit body weight, and on time after treatment was determined. The observations are equally consistent with proportionality of the incidence of cataract to the square of dosage or with a linear dependence beyond a threshold of 0.5 MBq/kg. The possibility of a linear dependence without threshold was strongly rejected (P less than 0.001). The analysis of temporal dependences yielded a component that was correlated with the injected amount of 224Ra and a component that was uncorrelated. The former was inferred by a maximum likelihood analysis to increase approximately as the square of the time after treatment. The component unrelated to the treatment was found to increase steeply with age and to become dominant within the collective of patients between age 50 and 60. The relative magnitudes of the two components were such that a fraction of 55 to 60% of the total of 58 cataracts had to be ascribed to the dose-related incidence. Impaired vision due to cataract was diagnosed before age 54 in 25 cases. In terms of injected activity per unit body weight no dependence of the sensitivity on age was found; specifically there was no indication of a faster occurrence of the treatment-related cataracts in patients treated at older ages
7Risks and outcomes of idiopathic pneumonia syndrome after allogeneic hematopoietic stem cell transplantation: The intensity of the conditioning regimen outweighs the effect of acute graft-versus-host disease
Antileukemia and antitumor effects of the graft-versus-host disease: A new immunovirological approach
In leukemic mice, the native host’s explicit and well-defined immune reactions to the leukemia virus (a strong exogenous antigen) and to leukemia cells (pretending in their native hosts to be protected “self” elements) are extinguished and replaced in GvHD (graft-versus-host disease) by those of the immunocompetent donor cells. In many cases, the GvHD-inducer donors display genetically encoded resistance to the leukemia virus. In human patients only antileukemia and anti-tumor cell immune reactions are mobilized; thus, patients are deprived of immune reactions to a strong exogenous antigen (the elusive human leukemia-sarcoma retroviruses). The innate and adaptive immune systems of mice have to sustain the immunosuppressive effects of leukemia-inducing retroviruses. Human patients due to the lack of leukemiainducing retroviral pathogens (if they exist, they have not as yet been discovered), escape such immunological downgrading. After studying leukemogenic retroviruses in murine and feline (and other mammalian) hosts, it is very difficult to dismiss retroviral etiology for human leukemias and sarcomas. Since no characterized and thus recognized leukemogenic-sarcomagenic retroviral agents are being isolated from the vast majority of human leukemias-sarcomas, the treatment for these conditions in mice and in human patients vastly differ. It is immunological and biological modalities (alpha interferons; vaccines; adoptive lymphocyte therapy) that dominate the treatment of murine leukemias, whereas combination chemotherapy remains the main remission-inducing agent in human leukemias-lymphomas and sarcomas (as humanized monoclonal antibodies and immunotoxins move in). Yet, in this apparently different backgrounds in Mus and Homo, GvHD, as a treatment modality, appears to work well in both hosts, by replacing the hosts’ anti-leukemia and anti-tumor immune faculties with those of the donor. The clinical application of GvHD in the treatment of human leukemias-lymphomas and malignant solid tumors remains a force worthy of pursuit, refinement and strengthening. Graft engineering and modifications of the inner immunological environment of the recipient host by the activation or administration of tumor memory T cells, selected Treg cells and natural killer (NKT) cell classes and cytokines, and the improved pharmacotherapy of GvHD without reducing its antitumor efficacy, will raise the value of GvHD to the higher ranks of the effective antitumor immunotherapeutical measures. Clinical interventions of HCT/HSCT (hematopoietic cell/stem cell transplants) are now applicable to an extended spectrum of malignant diseases in human patients, being available to elderly patients, who receive non-myeloablative conditioning, are re-enforced by post-transplant donor lymphocyte (NK cell and immune T cell) infusions and post-transplant vaccinations, and the donor cells may derive from engineered grafts, or from cord blood with reduced GvHD, but increased GvL/GvT-inducing capabilities (graft-versus leukemia/tumor). Post-transplant T cell transfusions are possible only if selected leukemia antigen-specific T cell clones are available. In verbatim quotation: “Ultimately, advances in separation of GvT from GvHD will further enhance the potential of allogeneic HCT as a curative treatment for hematological malignancies” (Rezvani, A.R. and Storb, R.F., Journal of Autoimmunity 30:172–179, 2008 (see in the text)). It may be added: for cure, a combination of the GvL/T effects with new targeted therapeutic modalities, as elaborated on in this article, will be necessary
