Psychometric properties of the Spanish version of the Frontal Assessment Battery (FAB-E) and normative values in a representative adult population sample.

BACKGROUND: The Frontal Assessment Battery is a short bedside test used to assess executive functions (EF). The aims of the present study were, first, to evaluate the psychometric proprieties of the Spanish version of the FAB (FAB-E) in a representative sample, and second, to establish cut-off points for impairment in executive function according to age and education level. METHODS: A sample of 798 healthy Spanish adult subjects aged 19 to 91 participated in this study. Neuropsychological assessment of participants was conducted using the FAB-E, Mini-Mental State Examination (MMSE) and Trail Making Test (TMT). We examined internal consistency, intraclass correlation, test-retest reliability, and concurrent and divergent validity. In addition, we established a cut-off point for detecting executive function impairment based on the 5th percentile by age group and education level. RESULTS: The analysis of the psychometric properties of the FAB-E showed good internal consistency (Cronbach's α = 0.60), intraclass correlation (0.72), test-retest reliability (0.70) and concurrent and divergent validity between the TMT (r = -0.523), MMSE (r = 0.426) and the FAB-E. The cut-off points for each age group were 16 points for the ≤ 29 group, 15 points for the 30-39 group, 14 points for the 40-49 and 50-59 groups, 12 points for the 60-69 group, and 10 points for the ≥ 70 age group. CONCLUSIONS: The psychometric analysis showed that the FAB-E has good validity and reliability. Thus, FAB-E may be a helpful tool to evaluate EF in a healthy Spanish population. In addition, this study provides information on reference data that will be very valuable for clinicians and researchers.

Hematological reconstitution and gene therapy: retroviral transfer of the bacterial beta-galactosidase activity into human hematopoietic CD34+ cell populations and into T lymphocytes derived from the peripheral blood.

We report the possibility to transfer marker genes coding for beta-galactosidase activity using retroviral vectors into human peripheral blood CD34+ cells, peripheral blood T-lymphocytes and into the growth factor-dependent human hematopoietic cell line TF-1. Using the MFG-nisLacZ and the FLac vector and various packaging cell lines, we demonstrated retroviral transfer and high expression of a bacterial beta-galactosidase activity induced by the nisLacZ gene or the Sh-ble/LacZ gene. Kinetics of expression of the transgenes were analyzed both in primary cells and cell lines. Absence of cytotoxicity related to the expression of the bacterial beta-galactosidase was assessed in both cell types. These results open interesting prospectives for the use of the beta-galactosidase activity to mark and follow the fate of genetically modified cells isolated from patients prior to reimplantation.

Retroviral transfer of the nlsLacZ gene into human CD34+ cell populations and into TF-1 cells: future prospects in gene therapy.

Few data are available concerning behavior of reimplanted human hematopoietic cells after autologous stem cell transplantation. This paper reports the possibility to transfer gene markers coding for beta-galactosidase (beta-Gal) activity by retroviral vectors into a human leukemic growth factor-dependent cell line, TF-1, and into human hematopoietic progenitors isolated from peripheral blood or bone marrow. Using various combinations of retroviral vectors and packaging cell lines, we demonstrated high expression of a bacterial beta-Gal activity induced by the LacZ gene, the nlsLacZ gene, or the Sh-ble/LacZ gene, in human hematopoietic cells. The expression of the nlsLacZ construct was stable until the end of the culture in infected CD34+ cell-enriched cell populations, and a slow decrease of transgene expression was observed in a transduced TF-1 cell population during a 1-year long-term culture. Data obtained with the nlsLacZ gene demonstrate that both retroviral transfer and corresponding gene expression were not found to modify the pattern of cell proliferation and differentiation. These results open interesting prospectives for the use of the nlsLacZ gene to mark and follow the fate of progenitor cells isolated from patients with cancers prior to reimplantation.

Effects of transforming growth factor beta, tumor necrosis factor alpha, interferon gamma and LIF-HILDA on the proliferation of acute myeloid leukemia cells.

A group of polypeptide factors that regulate cell growth and differentiation has been tested for their biological activities on the growth and differentiation of leukemic cells isolated from patients with Acute Myeloid Leukemias (AML). The effects of Transforming Growth Factor beta 1 (TGF beta), Tumor Necrosis Factor alpha (TNF alpha), Interferon gamma (IFN gamma) and LIF-HILDA were compared on leukemic cells cultured in vitro for seven days. Spontaneously growing leukemic cells were selected in order to study either inhibition or enhancement of proliferation induced by these factors. Only TGF beta 1 was found to induce a clear inhibition of leukemic proliferation in all cases tested. Recombinant TNF alpha and IFN gamma were found to induce either inhibition or enhancement of the proliferation on separate specimens. Under the conditions of culture, it was not possible to document any effect of LIF-HILDA. Cell differentiation and cell maturation were documented studying the modulation of cell surface antigens. TGF beta did not modify antigen expression on the cells surviving after 3 days in culture. Both TNF alpha and IFN gamma were found to enhance the expression of adhesion molecules and to a lesser extent, the expression of some lineage associated antigens. No effect of LIF-HILDA on antigen modulation was documented in the cases tested. These data confirm that TGF beta is by itself a potent inhibitor of the myeloid leukemia cells proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

Recombinant human IL-3 and G-CSF act synergistically in stimulating the growth of acute myeloid leukemia cells.

The effects of combinations of recombinant human growth factors (colony-stimulating factor (CSF], interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and granulocyte colony stimulating factor (G-CSF) for inducing proliferation of leukemic cells were compared in 27 acute myeloid leukemias (AMLs). While functional heterogeneity of AML was clearly shown, we further demonstrated that optimal growth may be obtained with combinations of CSF. The most striking feature was that, in both suspension and semisolid cultures, IL-3 and G-CSF acted synergistically in supporting AML cell proliferation except in cases for which G-CSF was found to be an inhibitory factor. In the majority of cases, the proliferative effects of the IL-3 and GM-CSF combination were significantly higher than the most potent of either factor present alone in the cultures. Finally, preincubation with IL-3 greatly potentiated the responsiveness of AML cells to subsequent addition of either GM-CSF or G-CSF. These results indicate that AML cells respond to growth factor in the same way as normal hemopoietic cells and that stimulation by a second late-acting growth factor such as G-CSF is also required to yield optimal growth.