Effects of educational attainment on the clinical expression of Alzheimer's disease: results from a research registry.

The "reserve" hypothesis suggests that education should affect the clinical expression of Alzheimer's disease (AD), but results from studies examining this idea are not consistent. In a single study, we evaluated the effects of educational attainment on three aspects of the clinical expression of AD: age at symptom onset, rate of cognitive decline, and survival. Subjects were 258 persons with mild- or moderate-stage Alzheimer's, drawn from our AD Research Registry. With statistical adjustment for confounding variables present in a clinic-based design, we found that higher educational attainment was associated with slightly earlier reports of symptom onset and a slower rate of cognitive decline on the Mini-Mental State Exam (MMSE). Education did not affect time of survival until death. We conclude that, for subjects in our sample, education had modest effects on aspects of the clinical expression of AD. These effects were not fully consistent with predictions derived from the "reserve" hypothesis.

The effect of agonists and antagonists on the morphology of non-transformed human smooth muscle cell in vitro.

In the present study we used scanning electron microscopy (SEM) to investigate morphological changes of non-transformed line of human bronchial smooth muscle cells (bSMC) induced by different agonists. Explants of normal bronchi were dissected and subcultured between 2 and 6 passage. In addition, smooth muscle actin content was assessed by SDS-PAGE electrophoresis, and its isoelectric point by IPG followed by immunoblotting. SMC were fixed by 2.0% paraformaldehyde and 2% glutaraldehyde and then were post-fixed by OSO4 and followed by dehydration and gold coating. Cytosolic free calcium was measured using adherent cells incubated with 500 microM Fura-2 acetoxymethylester and monitored by single excitation fluorimetry. Cultured cells possess predominantly charged actin isoforms with pI at 4.95; they respond to acetylcholine (100 microM), bradykinin (5 microM) and sulfidopeptide leukotriens (0.3-1.0 microM) with contraction, marked morphological lesions, such as widespread monolayer disorganization, extension of cell contacts. The number of microvilli on the cell surfaces was correlated with the degree of the alterations of the cellular morphology. Receptor antagonists antagonized these changes: atropine (0.3 microM), HOE 140 (1 microM) and MK 571 (1 microM). Acetylcholine and bradykinin induced a biphasic elevation of cytosolic calcium, which was antagonized by their receptor antagonists. Calcium changes in response to agonists were maintained over repetitive passages. Therefore, morphological changes seen in human bronchial SMC in culture with physiological response to various, structurally unrelated agonists can be future concern for the study the possible testing of the different pharmacological substances.

Vasoactive intestinal peptide as a possible transmitter of nonadrenergic, noncholinergic relaxation of pulmonary artery.

Electrical field stimulation of isolated guinea pig pulmonary artery induced a brief initial contraction followed by a more prolonged relaxation. alpha-Adrenergic blockade prevented the contraction and enhanced the relaxation. beta-Adrenergic and cholinergic muscarinic blockade partially reduced the relaxation, but 44.4% of the relaxation persisted after adrenergic and cholinergic blockade. The PA relaxation was associated with the release of immunoreactive VIP, both before and after this blockade. Tetrodotoxin abolished the nonadrenergic, noncholinergic relaxation and markedly reduced the release of VIP. This relaxation was similarly attenuated by a monoclonal antibody against VIP.