Probing the importance of N-glycosylation for [3H] clobenpropit binding to human H3 receptors expressed in HEK 293 cells

Inflammation Research - .     

Neocortical gray matter volume in first-episode schizophrenia and first-episode affective psychosis: a cross-sectional and longitudinal MRI study.

BACKGROUND: Overall neocortical gray matter (NCGM) volume has not been studied in first-episode schizophrenia (FESZ) at first hospitalization or longitudinally to evaluate progression, nor has it been compared with first-episode affective psychosis (FEAFF). METHODS: Expectation-maximization/atlas-based magnetic resonance imaging (MRI) tissue segmentation into gray matter, white matter (WM), or cerebrospinal fluid (CSF) at first hospitalization of 29 FESZ and 34 FEAFF, plus 36 matched healthy control subjects (HC), and, longitudinally approximately 1.5 years later, of 17 FESZ, 21 FEAFF, and 26 HC was done. Manual editing separated NCGM and its lobar parcellation, cerebral WM (CWM), lateral ventricles (LV), and sulcal CSF (SCSF). RESULTS: At first hospitalization, FESZ and FEAFF showed smaller NCGM volumes and larger SCSF and LV than HC. Longitudinally, FESZ showed NCGM volume reduction (-1.7%), localized to frontal (-2.4%) and temporal (-2.6%) regions, and enlargement of SCSF (7.2%) and LV (10.4%). Poorer outcome was associated with these LV and NCGM changes. FEAFF showed longitudinal NCGM volume increases (3.6%) associated with lithium or valproate administration but without clinical correlations and regional localization. CONCLUSIONS: Longitudinal NCGM volume reduction and CSF component enlargement in FESZ are compatible with post-onset progression. Longitudinal NCGM volume increase in FEAFF may reflect neurotrophic effects of mood stabilizers.     

Effect of perioperative blood transfusion on recurrence of colorectal cancer

The aim of the present study was to examine the outcome of 517 patients undergoing curative surgery for colonic and rectal cancer, and to compare the recurrence and mortality rates in transfused and non-transfused groups of patients. The two groups were evenly matched for age, sex, Dukes' stage and histological differentiation. There were significantly more rectal tumours in the transfused group (P less than 0.01), but the distribution of colonic lesions did not differ. Life table analysis revealed that the transfused patients had a 20 per cent greater probability of recurrence at 5 years (P less than 0.005) and there were 16 per cent more cancer related deaths (P less than 0.01). Even when all rectal cancers were excluded, a similar trend was seen for the colonic lesions: a 24 per cent greater probability of recurrence at 5 years (P less than 0.025) and 15 per cent more cancer related deaths (P less than 0.02). We conclude that blood transfusion may be associated with increased mortality and recurrence in patients undergoing curative surgery for colorectal cancer.     

ELISA tests for dapsone and pyrimethamine and their application in a malaria chemoprophylaxis programme

Enzyme-linked immunosorbent asays (ELISAs) are described for determining levels of dapsone and pyrimethamine in urine. Both assays have a sensitivity of about 20 μg/l and are reproducible, but each produces some false positives. The problem of false positive reactions was partially obviated by requiring positive results in both assays. In a pilot study involving 50 children aged 3 months to 4 years who were given a single dose of Maloprim (pyrimethamine + dapsone), 75% were positive for dapsone 7 days after administration of the drug, while 25% were still positive 15 days after its administration. The corresponding proportions for pyrimethamine were 73% and 30%, respectively. Comparison of the results obtained in a larger chemoprophylaxis trial with those from the pilot study indicated that the assays described could be used to investigate whether antimalarials had been taken.     

Renal allograft rejection: induction and function of adhesion molecules on cultured epithelial cells.

The interaction of graft-infiltrating immune cells with donor parenchymal cells is an important early event in allograft rejection. This binding is stabilized by interaction of antigen-independent 'adhesion' molecules expressed on the two cell types. As the level of expression of these molecules can be altered during inflammation, a series of experiments was performed to examine the effects of the inflammatory cytokines interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) on adhesion molecules expressed by cultured human renal tubular epithelial cells. These cells constitutively expressed ICAM-1 and LFA-3. Incubation with IFN-gamma increased expression of ICAM-1 but had no significant effect on expression of LFA-3 (P greater than 0.05). Incubation with TNF-alpha increased expression of both ICAM-1 and LFA-3; IFN-gamma synergized with TNF-alpha to further augment expression of these molecules. Peripheral blood lymphocytes (PBL) showed an enhanced binding to allogeneic renal epithelial cell monolayers which had been pretreated with IFN-gamma or TNF-alpha. MoAbs specific for ICAM-1 or its ligand LFA-1 inhibited adhesion of PBL to either IFN-gamma- or TNF-alpha-pretreated renal cells. By contrast, antibodies specific for LFA-3 or its ligand CD2 only significantly blocked PBL adhesion to renal cells which had been pretreated with TNF-alpha. Combination of antibodies specific for multiple components of the adhesion systems produced greater inhibition of adhesion than was produced by any single MoAb. These results suggest that the inflammatory cytokines IFN-gamma and TNF-alpha up-regulate expression of functional ICAM-1 and LFA-3 molecules which can augment the binding of potentially graft-damaging lymphoid cells to renal tubular epithelial cells.