Distinct In Vitro Myelopoiesis is Dependent on the Self-Renewal of Hematopoietic Progenitors.

Spleen and bone marrow (BM) have been shown to contain the progenitors of a novel dendritic-like antigen-presenting cell type (L-DC). These progenitors are also maintained in both long-term spleen cultures and co-cultures of spleen or BM over the stromal cell line STX3. We examined mouse foetal liver (FL), rich in hematopoietic stem/progenitor cells (HSC/HPC) after embryonic day (E) 12.5, for the presence of L-DC progenitors by testing their capacity to colonize STX3 and produce L-DC. E14.5 FL from wild-type C57BL/6J mice was found to colonize STX3 and produce L-DC for 28 days. By contrast, E14.5 FL from Ikaros Plastic mice gave only short-term production of low numbers of L-DC between 7 and 14 days of co-culture. The transient and weak production of L-DC by FL from Plastic E14.5 mice maps to the loss of self-renewal capacity amongst HSC. L-DC progenitors are, therefore, closely aligned with a subset of self-renewing HSC/HPC in FL.

[A volumetric study of brain structures in subtypes of depression].

The aim of this study is to compare the volumes of hippocampus, amygdala and subgenual prefrontal cortex among patients with melancholic depression, patients with psychotic depression and normal controls. Thirty nine patients with a diagnosis of major depression (22 with melancholic and 17 with psychotic subtype) and 18 normal controls were included in the study. Hippocampal, amygdala, anterior and posterior subgenual cortex volumes were measured by manual tracings on magnetic resonance volumetric images and compared across the 3 groups. We identified larger amygdala volumes and smaller left anterior subgenual cortex volumes in both patient groups compared to controls. There were no differences in hippocampal, right anterior and posterior subgenual cortex volumes across the 3 groups. In conclusion, melancholic and psychotic depression were not differentiated regarding the volumes of the hippocampus, the amygdala, and anterior and posterior subgenual cortex, even though amygdala volumes and left anterior subgenual cortex volume of both patient groups were differentiated compared to controls.

The fatty acid amide hydrolase (FAAH) Pro129Thr polymorphism is not associated with severe obesity in Greek subjects.

Fatty amid acid hydrolase (FAAH) has been implicated at both protein and gene level with obesity. An association between Pro129Thr variant of the FAAH gene and obesity has been described, but various studies have yielded conflicting results. Our aim was to determine whether this polymorphism is related to severe obesity and whether it confers a risk for variability of quantitative metabolic traits in a cohort of Greek obese subjects. Two groups of severely obese subjects (BMI > 40 kg/m (2)) were studied: a group of 158 metabolically healthy and a group of 145 obese subjects with metabolic syndrome, which were compared to a control group consisting of 121 lean individuals. We did not find any association between the Pro129Thr polymorphism with severe obesity in both subgroups of obese subjects, between these two subgroups (p= 0.11) or on basic anthropometric characteristics in the three groups. Statistically significant differences were found for glucose and HDL in metabolically healthy subjects and HDL in the control group. The borderline significant p-values were not significant after correction for multiple testing. We were unable to find robust evidence of an association of the Pro129Thr variant with severe obesity, and any related quantitative traits among the obese Greek subjects examined.

A genomic view of immunology.

The outstanding problems facing immunology are whole system issues: curing allergic and autoimmune disease and developing vaccines to stimulate stronger immune responses against pathogenic organisms and cancer. We hope that the human genome sequence will reveal the molecular checks and balances that ensure both an effective immunogenic response against pathogenic microorganisms and a suitably tolerogenic response to self antigens and innocuous environmental antigens. Three synergistic approaches--sequence homology searches, messenger RNA expression profiling on microarrays, and mutagenesis in mice--provide the best opportunities to reveal, in the genome sequence, key proteins and pathways for targeting by new immunomodulatory treatments.

Antitumor activity of gold(i), silver(i) and copper(i) complexes containing chiral tertiary phosphines.

The in vitro cytotoxicities of a number of gold(I), silver(I) and copper(I) complexes containing chiral tertiary phosphine ligands have been examined against the mouse tumour cell lines P815 mastocytoma, B16 melanoma [gold(I) and silver(I) compounds] and P388 leukaemia [gold(I) complexes only] with many of the complexes having IC(50) values comparable to that of the reference compounds cis-diamminedichloroplatinum(ll), cisplatin, and bis[1,2-bis(diphenylphosphino) ethane]gold(I) iodide. The chiral tertiary phosphine ligands used in this study include (R)-(2-aminophenyl)methylphenylphosphine; (R,R)-, (S,S)- and (R(*),R(*))-1,2-phenylenebis(methylphenylphosphine); and (R,R)-, (S,S)- and (R(*),R(*))-bis{(2-diphenylphosphinoethyl)phenylphosphino}ethane. The in vitro cytotoxicities of gold(I) and silver(I) complexes containing the optically active forms of the tetra(tertiary phosphine) have also been examined against the human ovarian carcinoma cell lines 41M and CH1, and the cisplatin resistant 41McisR, CH1cisR and SKOV-3 tumour models. IC(50) values in the range 0.01 - 0.04 muM were determined for the most active compounds, silver(I) complexes of the tetra(tertiary phosphine). Furthermore, the chirality of the ligand appeared to have little effect on the overall activity of the complexes: similar IC(50) data were obtained for complexes of a particular metal ion with each of the stereoisomeric forms of a specific ligand.