Combination of clinical and neuropsychologic information as a better predictor of the progression to Alzheimer disease in questionable dementia individuals.

OBJECTIVES: This study aimed to examine the clinical outcomes of questionable dementia (QD) elderly subjects after three years of follow-up and to compare the ability of a standardized clinical assessment, neuropsychologic tests, the ApoE genotyping, and possible combinations of these methods to predict their progression to Alzheimer disease (AD). METHODS: One hundred six elderly subjects with QD were evaluated with a standardized clinical assessment, neuropsychologic tests, and ApoE genotyping and followed up annually. The Clinical Dementia Rating Sum of Boxes (CDR-SOB) score was used as a quantitative summary score of the standardized clinical assessment on the overall functioning of the subjects. RESULTS: Among the individuals remaining in the study after the 3-year follow-up period, 8.3% had improved to a state of normal cognition, 72.7% were still in the QD state. and 19.4% had progressed to clinically evident AD. Although each of CDR-SOB, Word List Recall (WLR), and ApoE epsilon4 genotype was predictive for AD, the combination of CDR-SOB and WLR was found to predict AD better than any single variable. However, the addition of the ApoE epsilon4 genotype information to CDR-SOB or WLR did not improve their predictive ability. CONCLUSION: The combination of clinical assessment on function and episodic memory test can improve the predictive ability of each measure for progression to AD in QD individuals. However, ApoE genotyping dose not make an additional contribution to AD prediction in QD individuals when used in combination with clinical assessment or memory test.     

Adherence of L1210 murine leukemia cells to sephacryl- aminopropylcobalamin beads treated with transcobalamin-II

Sephacryl beads containing an immobilized aminopropylcobalamin- transcobalamin-II complex serve as foci for the adherence of L1210 murine leukemia cells. Bead-cell interaction does not occur when (A) nonderivatized beads are used; (B) transcobalamin-II is omitted or presaturated with cyanocobalamin in the preparation of the bead complex; (C) intrinsic factor replaces transcobalamin-II; and (D) the complex is removed from beads by photolysis. These observations suggest that adherence results from the ability of transcobalamin-II to form a bridge between immobilized cobalamin on the bead and receptors in the plasma membrane of the cell.     

Characterization of the human neutrophil C1q receptor and functional effects of free ligand on activated neutrophils

The partial characterization and expression of the C1q receptor (C1q-R) in relation to other complement receptors present on the surface of neutrophils has been examined, as well as the effects of free C1q on cell function. A polyclonal anti-C1q-R antibody recognizes a 68-kD neutrophil surface protein. C1q-R expression was not upregulated upon warming, priming, or exposure to FMLP, but decreased after exposure to phorbol myristate acetate (PMA), because of shedding of the receptor into the extracellular medium, as detected by enzyme-linked immunosorbent assay. CR3 and CR1 expression was upregulated from intracellular pools after cell stimulation by PMA. No evidence of intracellular pools of C1q-R was found, as assessed by immunoblotting of subcellular fractions. But C1q-R appeared to be expressed early in cell differentiation, was detected on undifferentiated HL-60 cells, and like CR3 expression, increased upon 5 days differentiation towards a neutrophil lineage. However, C1q-R expression decreased upon additional culture, whereas CR3 expression continued to increase. A large variation in the percentage of peripheral cells expressing C1q receptors in donors was observed, ranging from 13% to 100%, contrasting with CR3 receptors that exhibited less variability. Interactions between free monomeric C1q and neutrophils were also studied. Incubation of stimulated neutrophils with 10 to 100 micrograms/mL C1q resulted in a further increase in CR3 expression and adherence to albumin-coated surfaces. Staphylococci opsonized with low quantities of C1q (0.1 to 1 microgram/mL) mediated a moderate and sustained respiratory burst in neutrophils, whereas a burst of similar magnitude was generated only with free C1q at concentrations 10- to 100-fold higher. Stimulation was only partially inhibited if cells were first treated with anti-C1q-R antibody, suggesting other C1q binding proteins may be present on the cell surface. In summary, neutrophil C1q receptor is approximately 68-kD, exhibits varying expression on different subjects, and is not upregulated from intracellular stores on exposure to soluble stimuli. Stimulated, but not resting, neutrophils selectively respond to raised levels of free C1q, resulting in altered cell function and enhanced CR3 receptor expression. These studies thus suggest complex roles for C1q in neutrophil function.