. Slow shifts in the human scalp-recorded EEG, including those related to changes in brain CO 2 levels, have been generally assumed to result from changes in the level of tonic excitation of apical dendrites of cortical pyramidal neurons. We readdressed this issue using DC-EEG shifts elicited in healthy adult subjects by hypo-or hypercapnia. A 3-min period of hyperventilation resulted in a prompt negative shift with a rate of up to 10 V/s at the vertex (Cz) and an extremely steep dependence (up to 100 V/mmHg) on the end-tidal Pco 2 . This shift had a maximum of up to Ϫ2 mV at Cz versus the temporal derivations (T3/T4). Hyperventilation-like breathing of 5% CO 2 -95% O 2 , which does not lead to a significant hypocapnia, resulted in a near-complete block of the negative DC shift at Cz. Hypoventilation, or breathing 5% CO 2 in air at normal respiratory rate, induced a positive shift. The high amplitude of the voltage gradients on the scalp induced by hyperventilation is not consistent with a neuronal origin. Instead, the present data suggest that they are generated by extracortical volume currents driven by a Pco 2 -dependent potential difference across epithelia separating the cerebrospinal fluid and blood. Since changes in respiratory patterns and, hence, in the level of brain Pco 2 , are likely to occur under a number of experimental conditions in which slow EEG responses have been reported (e.g., attention shifts, preparatory states, epileptic seizures, and hypoxic episodes), the present results call for a thorough reexamination of the mechanisms underlying scalp-recorded DC-EEG responses.
Membrane potentials of particles present in a subcellular brain preparation, called synaptoneurosomes, have been monitored by measurement of changes in the absorbance of a cyanine dye, DiS-C2-5. The membrane potential of the particles seems to be dependent on both Cl- and K+ diffusion potentials, as judged from dependence of the absorbance changes on the K+ equilibrium potential across the membrane in the presence of Ba2+ or when Cl- was replaced with gluconate. The apparent high Cl- permeability of the membrane preparation was reduced in the presence of picrotoxin, a finding suggesting endogenous activation of receptor-linked Cl- channels. Glutamate and kainate caused depolarization of the membranes present in the preparation. This effect was only seen if K+ channels had been blocked in the presence of Ba2+ or 4-aminopyridine. No responses were observed with other glutamate receptor agonists (quisqualate or N-methyl-D-aspartate). The membrane potential of particles present in conventional synaptosomal preparations neither had a high Cl- permeability nor reacted to glutamate or kainate in the present conditions. The results suggest that synaptoneurosome preparations may be used for functional studies on postsynaptic neurotransmitter receptor-linked membrane potential changes with optical probes of membrane potential.
Estrogen and progesterone receptors (ER/PR) were measured in primary tumors and metastases of 397 breast cancer patients. Survival following mastectomy was significantly longer in patients with ER and PR positive tumors, as was survival after first recurrence. The prognostic value of ER and PR was compared with such clinical factors as disease-free interval (DFI) and the dominant site of first metastasis by Cox's regression analysis. With all the different therapy modalities long DFI was the best prognostic indicator. However, in the patient group treated with endocrine therapy, ER and PR positivity was the best prognostic indicator, suggesting that longer survival in receptor positive patients was related to the response to endocrine treatment.
The differential sensitivities of A beta, A delta and C fibres of rat vagus nerve to bupivacaine, etidocaine and AL-381 were studied in vitro. In A beta fibres, at 35-37 degrees C, 50 mumole litre-1 of the drugs had similar effects on the action potential amplitude, while at greater concentrations (100 and 200 mumole litre-1) the greatest mean depression of amplitude was seen with etidocaine (n.s.). AL-381 had the most marked effect on the A delta potentials, and it appeared that it was about twice as potent as the others in blocking these fibres. Etidocaine 100 mumole litre-1 was more depressant than the same dose of bupivacaine. The C fibres were blocked most rapidly by AL-381, while etidocaine had the least effect.
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