Voltage-clamp experiments on oxidized cholesterol membranes modified with excitability-inducing material and comparison with a model.

The conductance of oxidized cholesterol membranes modified with excitability-inducing material was observed in membranes containing either single conductance channels or 100-1000 channels. Membranes containing single channels have several conductance states for each voltage polarity, and the current through membranes containing manychannels decays with at least two, and probably three, time constants following a step change in voltage (voltage-clamp). The time constants differ by about an order of magnitude. The multi-state behavior seems more pronounced in membranes made from highly oxidized cholesterol. Although a given conductance state could occur at either positive or negative voltages, each state was much more frequent at one polarity or the other. The most frequently observed single-channel conductance states in 0.1 M NaCl are about 0.3, 0.1, 0.03, and 0.0 n-1 for negative voltages and 0.25, 0.05, 0.03, and 0.0 n-1 for positive voltages. The current following a voltage clamp decays to a quasi-steady state within 1 min for positive voltages and 1-15 min for negative voltages. When the holding voltage is --20 mV, the decay constants and quasi-steady state conductances as functions of clamping voltage are reasonably well described by either a three-state model of the conductance or a two-state model applied independently at negative and positive voltages. However, for high voltages, the quasi-steady state does not appear to approach a state in which all the channels are in a low conductance state.

Transforming growth factor-beta1 inhibits membrane association of protein kinase C alpha in a human prostate cancer cell line, PC3.

The postreceptor signaling pathway(s) that mediates the effects of transforming growth factor-beta1 (TGF-beta1) is incompletely understood. The present study investigated the involvement of protein kinase C (PKC) in the growth-inhibitory action of TGF-beta1 in PC3, a human prostate cancer cell line. PKC alpha, the only conventional PKC isoform detected in PC3 cells, appeared to be constitutively active based on its presence in both Triton-soluble membrane fraction and cytosol. However, levels of membrane-associated PKC alpha were decreased by a growth-inhibitory dose of TGF-beta1. The response to TGF-beta1 was rapid (within 5 min), time dependent, isoform specific, and occurred without apparent changes in levels of total PKC alpha protein. TGF-beta1 also decreased the levels of membrane-associated PKC activity coincident with its inhibitory effect on PKC alpha's membrane association. Inhibition of PKC activity appeared to be associated with growth inhibition in PC3 cells, because chelerythrine (a specific PKC inhibitor) likewise decreased cell proliferation. Taken together, our data suggest that inhibition of PKC activity, at least in part due to inactivation of PKC alpha, is an early event associated with TGF-beta1 postreceptor signaling that might mediate suppression of cell proliferation.

Suicidal tendency and multiple sclerosis.

This article examines the relationship between various physiological, psychological, and social variables and suicidal tendency among people with multiple sclerosis. In 1986, a sample of 147 respondents with multiple sclerosis was obtained. The authors studied the absence of social support systems as an important predictor of suicidal tendency in people with multiple sclerosis. Multiple regression is used to assess the independent effects of predictors. Findings suggest family support, hopelessness, and self-perceived religiosity as predictors of suicidal tendency.

Qualitative analysis of a BSW field placement with a hospital-owned physician practice in a skilled nursing facility.

Health services and medical social work are being reshaped in the wake of managed care and the movement toward community-based delivery systems. In this article, a bachelor's of social work student is assigned to a field placement to work with a hospital-owned physician practice in a skilled nursing facility. Structured interviews are conducted with the field placement student, the physician, a resident (client), the field placement instructor, two social work designees, and the facility administrator to ascertain the student's practice activities. Findings indicate a wide range of duties at both micro- and macro practice levels. Value issues and potential considerations for practitioners entertaining professional associations with physicians are examined.