The Road to Personalized Myeloma Medicine: Patient-specific Single-domain Antibodies for Anti-idiotypic Radionuclide Therapy.

To this day, multiple myeloma remains an incurable cancer. For many patients, recurrence is unavoidably a result of lacking treatment options in the minimal residual disease stage. This is due to residual and treatment-resistant myeloma cells that can cause disease relapse.

Six weeks of strength endurance training decreases circulating senescence-prone T-lymphocytes in cytomegalovirus seropositive but not seronegative older women.

Background: Ageing is associated with a decline in immune function termed immunosenescence. This process is characterized amongst others by less naive T-cells and more senescent phenotypes, which have been implicated in the pathogenesis of many age-related diseases. Thus far, reports regarding the long-term adaptation effects of exercise on T-cell phenotypes are scant and largely equivocal.

Strength Endurance Training but Not Intensive Strength Training Reduces Senescence-Prone T Cells in Peripheral Blood in Community-Dwelling Elderly Women.

Aging is characterized by a progressive decline in immune function known as immunosenescence. Although the causes of immunosenescence are likely to be multifactorial, an age-associated accumulation of senescent T cells and decreased naive T-cell repertoire are key contributors to the phenomenon. On the other hand, there is a growing consensus that physical exercise may improve immune response in aging.

Association Between Immunosenescence Phenotypes and Pre-frailty in Older Subjects: Does Cytomegalovirus Play a Role?

Frailty is highly prevalent in old age and confers an important mortality risk. Although the causes of frailty are multiple, immunosenescence (IS)-predominantly driven by cytomegalovirus (CMV)-has been implicated in its pathophysiology. Thus far, research examining the association between IS and frailty states is sparse and equivocal.

Lymphoma-like monoclonal B cell lymphocytosis in a patient population: biology, natural evolution, and differences from CLL-like clones.

High-count monoclonal B cell lymphocytosis (MBL) with a chronic lymphocytic leukemia (CLL) phenotype is a well-known entity, featuring 1-4% annual risk of progression towards CLL requiring treatment. Lymphoma-like MBL (L-MBL), on the other hand, remains poorly defined and data regarding outcome are lacking. We retrospectively evaluated 33 L-MBL cases within our hospital population and compared them to 95 subjects with CLL-like MBL (C-MBL).

Effects of Physical Exercise on Markers of Cellular Immunosenescence: A Systematic Review.

Aging affects negatively the immune system, defined as immunosenescence, which increases the susceptibility of elderly persons to infection, autoimmune disease, and cancer. There are strong indications that physical exercise in elderly persons may prevent the age-related decline in immune response without significant side effects. Consequently, exercise is being considered as a safe mode of intervention to reduce immunosenescence.

Shortcomings in the application of multicolour flow cytometry in lymphocyte subsets enumeration.

The lymphoid system is composed of numerous phenotypically distinct subsets of cells, each of which has a unique role in the effectiveness of an immune response. To distinguish specifically between these subsets, it is mandatory to detect simultaneously different cell surface antigens. This became feasible by the development of multicolour flow cytometric technologies.

Preclinical evaluation of invariant natural killer T cells in the 5T33 multiple myeloma model.

Immunomodulators have been used in recent years to reactivate host anti-tumor immunity in several hematological malignancies. This report describes the effect of activating natural killer T (NKT) cells by α-Galactosylceramide (α-GalCer) in the 5T33MM model of multiple myeloma (MM). NKT cells are T lymphocytes, co-expressing T and NK receptors, while invariant NKT cells (iNKTs) also express a unique semi-invariant TCR α-chain.

Cellular aging and senescence characteristics of human T-lymphocytes.

CD28-, CD57+ and KLRG1+ are cell surface markers that have been used to describe senescent T-lymphocytes in humans. However, the relationship among these phenotypes during aging, and their relationship with the concept of in vitro cellular aging have not been well established. Using five-colour flow cytometry, we analyzed peripheral blood T-lymphocytes for their expression of CD28, CD57 and KLRG1 in 11 young (Y) and 11 old (O) apparently healthy human subjects.

Growth factor receptor profile of CD34 cells in normal bone marrow, cord blood and mobilized peripheral blood.

Growth factors regulate the proliferation and differentiation of hemopoietic cells. Their effect on hemopoietic precursors differs according to the ontogenic source of the cells. Cord blood and mobilized blood CD34(+) cells have a higher sensitivity for growth factors than bone marrow CD34(+) cells.

Growth factor receptor profile of CD34+ cells in AML and B-lineage ALL and in their normal bone marrow counterparts.

Leukaemic cells show a low clonogenic activity and a heterogeneous proliferative response to growth factors. We investigated whether this could be due to an altered expression of growth factor receptors on the leukaemic precursors. Receptors for G-CSF, stem cell factor (SCF), IL-3, IL-6 and IL-7 were detected on CD34+ cells in AML and B-lineage ALL with monoclonal antibodies and flow cytometry.

Different expression of adhesion molecules on CD34+ cells in AML and B-lineage ALL and their normal bone marrow counterparts.

The expression of adhesion molecules on CD34+ cells in acute myeloid leukemia (AML) and B-lineage acute lymphoblastic leukemia (B-lineage ALL) was compared with that on the myeloid and B-lymphoid CD34+ cells in normal bone marrow. Bone marrow aspirates of 10 patients with AML, 8 patients with B-lineage ALL and of 6 healthy volunteers were examined. The phenotype of the CD34+ cells was determined with a double immunofluorescence method and flow cytometry.

Circulating CD34+ cells in cord blood and mobilized blood have a different profile of adhesion molecules than bone marrow CD34+ cells.

The expression of adhesion molecules was studied on CD34+ hematopoietic precursors in cord blood, bone marrow and mobilized blood. The samples were labeled in a double immunofluorescence procedure with a CD34 monoclonal antibody and with antibodies against maturation and differentiation antigens and adhesion molecules. Myeloid precursors formed the majority of the CD34+ cells in all samples.

Different expression of adhesion molecules on myeloid and B-lymphoid CD34+ progenitors in normal bone marrow.

The expression of adhesion molecules was studied on B lymphoid and myeloid CD34+ precursors in normal bone marrow. Bone marrow aspirates were labelled in a double fluorescence procedure with the CD34 monoclonal antibody 43A1 and with antibodies directed against maturation and differentiation antigens and adhesion molecules. Three clusters of CD34+ cells could be distinguished by their light scatter characteristics in flow cytometry.

Leukemia and lymphoma immunophenotyping in cell smears with immunogold-silver staining.

The potential of the immunogold-silver staining (IGSS) technique for immunophenotyping leukemia and lymphoma cells in cell smears was examined. Peripheral blood, bone marrow aspirates, lymph node biopsy specimens, fine-needle aspirates, and biologic fluids of 83 patients with acute or chronic leukemias, non-Hodgkin's lymphomas, or Hodgkin's disease were labeled. Cell smears, cytocentrifuge preparations, or imprints were fixed, incubated with the reagents, and counterstained with May-Grünwald-Giemsa.

Flow cytometric immunophenotyping of leukemia cells in clotted blood and bone marrow.

Immunophenotyping of leukemia cells is generally performed on cells in suspension. These suspensions are usually prepared from anticoagulated peripheral blood or bone marrow samples but when anticoagulation is suboptimal clotted samples may reach the laboratory. In this study cell suspensions were prepared from clotted blood and bone marrow samples of leukemia patients by lysis of the clots with streptokinase.

Light microscopical detection of leukocyte cell surface antigens with a one-nanometer gold probe.

The potential of ultrasmall gold particles for the light microscopical detection of leukocyte cell surface differentiation antigens was investigated. Suspensions and cytocentrifuge preparations of peripheral blood leukocytes were first incubated with monoclonal antibodies and then with goat antimouse antibodies coupled to colloidal gold particles of 1-nanometer diameter. Cytocentrifuge preparations were made from the cell suspensions.

An immunogold-silver staining method for detection of cell surface antigens in cell smears.

We developed an indirect immunogold-silver staining method for detection of leukocyte cell surface antigens in cell smears. Air-dried and fixed cytocentrifuge preparations or smears of peripheral blood leukocytes were incubated with monoclonal antibodies (MAb) and colloidal gold-labeled secondary antibodies. The preparations were post-fixed and silver enhancement was performed.

Hematologic values and lymphocyte subsets in fetal blood.

Hematologic values and lymphocyte subpopulations were determined in normal fetal blood during the second trimester of gestation. In these samples the platelet, erythrocyte, and leukocyte counts were significantly lower than in adults. Large red blood cells with a high hemoglobin content were present.

Sensitive detection of immunogold-silver staining with darkfield and epi-polarization microscopy.

We evaluated the contribution of darkfield and epi-polarization microscopy to the detection of leukocyte cell surface antigens with immunogold-silver staining (IGSS). Lymphocyte cell surface differentiation antigens were labeled with monoclonal antibodies and IGSS as described for brightfield microscopy. In darkfield and epi-polarization microscopy the labeling appeared as bright spots on a dark background.

Potential of immunogold-silver staining for the study of leukocyte subpopulations as defined by monoclonal antibodies.

The potential of immunogold-silver staining for study of leukocyte subpopulations, as defined by monoclonal antibodies in cell suspensions, was examined. The cells were labeled in suspension as described for immunogold staining. Cytocentrifuge preparations of the suspensions were then immersed in a physical developer.

Immunogold-silver staining of lymphocyte surface antigens on cells in suspension and in lymph node cryostat sections.

An immunogold-silver staining (IGSS) technique for the light microscopical detection of leucocyte cell surface antigens in cell suspensions and cryostat sections is described. The specimens were first incubated with monoclonal mouse antibodies and then with colloidal gold-labelled goat anti-mouse antibodies. They were then immersed in a physical developer, counterstained and mounted.

An immunogold-silver staining method for detection of cell-surface antigens in light microscopy.

An immunogold-silver staining technique for detection of cell-surface antigens in cell suspensions was developed. Leukocyte cell suspensions were first incubated with monoclonal antibodies directed against cell-surface antigens and then with colloidal gold-labeled goat anti-mouse antibodies. Cytocentrifuge preparations of the cell suspensions were immersed in a physical developer containing silver lactate and hydroquinone as reducing substance.