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Biomedical subjects

D S Weiss

Publications and source records attributed to D S Weiss.

At least 109 records · Page 6Linked to original sources

Fractal models are inadequate for the kinetics of four different ion channels.

The gating kinetics of single ion channels have been well described by models which assume that channels exist in a number of discrete kinetic states, with the rate constants for transitions among the states remaining constant in time. In contrast to such discrete Markov models, it has recently been considered whether gating might arise from transitions among a continuum of states, with the effective rate constants for leaving the collections of states given by a fractal scaling equation (Liebovitch, L.S., J. Fischbarg, J.P. Koniarek, I. Todorova, and M. Wang. 1987. Biochim. Biophys. Acta. 896:173-180; Liebovitch, L.S., and J.M. Sullivan. 1987. Biophys. J. 52:979-988). The present study compares discrete Markov with fractal continuum models to determine which best describes the gating kinetics of four different ion channels: GABA-activated Cl channels, ACh-activated end-plate channels, large conductance Ca-activated K (BK) channels, and fast Cl channels. Discrete Markov models always gave excellent descriptions of the distributions of open and shut times for all four channels. Fractal continuum models typically gave very poor descriptions of the shut times for all four channels, and also of the open times from end-plate and BK channels. The descriptions of the open times from GABA-activated and fast Cl channels by the fractal and Markov models were usually not significantly different. If the same model accounts for gating motions in proteins for both the open and shut states, then the Markov model ranked above the fractal model in 35 of 36 data sets of combined open and shut intervals, with the Markov model being tens to thousands of orders of magnitude more probable. We suggest that the examined fractal continuum model is unlikely to serve as a general mechanism for the gating of these four ion channels.

Animals↗

Whole-cell and single-channel recordings of GABA-gated currents in cultured chick cerebral neurons.

1. gamma-Aminobutyric acid (GABA) (10-500 microM) was applied to cultured chick cerebral neurons by pressure ejection, and the resulting currents (IGABA) were recorded using standard whole-cell voltage-clamp techniques. Plots of the peak IGABA as a function of membrane potential were nonlinear with an outwardly rectifying appearance. 2. IGABA decayed during a prolonged application of GABA. This decay was associated with a decline in the conductance of the cell, suggesting that the decline in IGABA was principally due to receptor desensitization. 3. After 5-7 days in culture, whole-cell recordings revealed the presence of spontaneous synaptic currents. These currents were presumed to be GABA-gated inhibitory postsynaptic currents (IPSCs) because they reversed at the Cl- equilibrium potential (ECl-), were blocked by picrotoxin (25 microM), and were prolonged by pentobarbital (50 microM). 4. Synaptic currents were analyzed by fitting exponential functions to their decay. In normal recording saline, 68% of the decays analyzed could be adequately described by a single exponential function. Two exponentials were necessary to describe the decay of the other 32%. The time constant of the decay (for those adequately fitted by a single exponential) increased with depolarization, from an average value of 15 ms at -80 mV to 60 ms at +40 mV. 5. A relationship was noted between IPSC amplitude and decay time constant; IPSCs with larger peak amplitudes had a slower decay. One possible explanation considered for this finding was that transmitter persists in the synaptic cleft and rebinds to the receptors, thus prolonging the decay of the IPSC. 6. Consistent with the above hypothesis was the observation that the decays of miniature IPCSs (examined under conditions of reduced transmitter release) were faster, showed less variability, and were all adequately described by a single exponential function. Furthermore, the decay times were independent of the membrane potential, suggesting that the kinetic parameters of the GABA channel which shape the decay of these miniature IPSCs are independent of voltage. 7. Single-channel activity underlying whole-cell GABA responses could be recorded in isolated outside-out and inside-out patches of membrane. In isotonic choline chloride, single-channel amplitudes were linearly related to voltage and reversed at -1.8 +/- 11.0 mV (n = 12). Under these conditions, the channel had a main conductance state of 20.8 +/- 3.4 pS (n = 12). Transitions were observed from this main conductance state to other conductance states, e.g., two subconductance states of 6 and 12 pS and one supraconductance state of 30 pS.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Membrane potential modulates the activation of GABA-gated channels.

1. The activity of single gamma-aminobutyric acid (GABA)-gated Cl- channels (GABA = 0.5-2.0 microM) was recorded in inside-out patches of membrane from cultured chick cerebral neurons. 2. The distribution of open intervals of the GABA channel was described by the sum of two exponentials, which suggests the presence of at least two open states of the channel. The time constants of these two components were 0.39 +/- 0.1 and 2.1 +/- 0.9 ms (+/- SD, n = 9). 3. The distribution of shut intervals was described by the sum of either three (n = 5) or four (n = 3) exponentials. This suggests the presence of at least three or four shut states. 4. At all GABA concentrations examined, the activity of the GABA channel decreased over time. This decline in activity was most likely the result of desensitization of the GABA channels. 5. The distribution of open intervals was unchanged during desensitization of the GABA channel. Thus desensitization is not associated with an alteration in either the mean lifetime of the two open states or the relative number of transitions to these two states. Rather, desensitization results from a decrease in the probability of channel opening. 6. There was an e-fold increase in the probability of finding a GABA channel open for every 80 +/- 43 mV (n = 4) of depolarization. The degree of voltage dependence decreased as the GABA channels desensitized. 7. The depolarization-induced increase in open channel probability was not associated with any change in the distribution of open intervals. Thus depolarization does not affect the mean open time of the channel but rather increases the likelihood that it will open. 8. A simple model with three or four shut and two open states is considered for the gating of the GABA channel by the agonist. Possible sites for the voltage dependence within this proposed model are discussed.

Animals↗

A controlled trial of brief psychotherapy and mutual-help group treatment of conjugal bereavement.

Sixty-one women who sought treatment for unresolved grief reactions 4 months to 3 years after the death of their husbands were randomly assigned to either brief dynamic psychotherapy with experienced clinicians or mutual-help group treatment led by nonclinicians. Women in both groups experienced a reduction in stress-specific and general symptoms as well as improvement in social and work functioning. Women in the brief psychotherapy group showed a greater decline in one measure of general symptoms, and there was greater attrition in the group treatment condition. When two subgroups who had completed the majority of sessions were compared, treatments were found to be equally effective.

Adaptation, Psychological↗

Assessing the influence of maternal depression on the validity of the Child Behavior Checklist.

The relative effects of maternal depression, child gender, and child psychiatric status on mothers' ratings of their children were assessed in a study of the validity of the Child Behavior Checklist (CBCL). Both maternal depression and gender were found to be significantly associated with mothers' ratings of their children on the CBCL. Nevertheless, mothers' ratings continued to differentiate groups of children with and without psychiatric problems even after the variance accounted for by maternal depression and child gender was removed. These findings support the criterion validity of the CBCL, and point also to the importance of assessing parents as part of the clinical evaluation of children.

Aggression↗

Effect of head tilt on visual cortical cell function in the intact and labyrinthectomized cat.

The area of the receptive field, its length and width, its position in the visual field, the peristimulus time (PST) histogram (i.e., the response to successive moving light-bar stimuli), the directional preference, the velocity gradient, and the intertrial (spontaneous) firing rate were studied electrophysiologically in complex cortical visual cells in Brodmann's area 18. These characteristics were explored after head tilt, in immobilized cats, both in intact and in bilaterally labyrinthectomized animals. In intact animals (in 64 cells), most of these characteristics changed after head tilts of 10, 20, 30, or 40 degrees to the right or to the left of the horizontal plane. There was always one specific head position in which the receptive field area was at its smallest. In labyrinthectomized animals (in 29 cells), the lengths, widths, and the areas of the receptive fields were only minimally altered during identical tilts. Similarly, in the labyrinthectomized cats, head tilts (40 degrees, to the right or left) caused no substantial changes in the shape and duration of the PST histogram, compared with those in intact cats. No two visual cortical cells responded to head tilts in exactly the same manner. Such uniqueness in response is probably of importance during visual image analysis; in particular, as it relates to cortical reconstruction of stable visual images during continuously changing head movements and positions.

Animals↗

Comprehensive analysis of change after brief dynamic psychotherapy.

This report provides data on symptom levels by using group means as well as categories of clinical relevance as they change over the course of treatment and also examines change "beyond symptoms" as levels of adaptive functioning. This approach allows a more comprehensive analysis of change in a series of patients with pathological grief reactions treated with brief dynamic psychotherapy. The different perspectives on outcome of the patient, the evaluating clinician, the treating clinician, and independent judges are compared. The findings from all perspectives indicate that major symptom relief occurred in the majority of patients, with less change in adaptive abilities.

Adaptation, Psychological↗

A proposed method for measuring change beyond symptoms.

The initial report of the Patterns of Individual Change Scales battery presented the rationale, development, and conceptualization of this measurement package. Empirical data supported the reliability and validity of the scales as measures of patient characteristics that extended beyond the symptomatic domain. This article presents more extensive reliability and validity data. Ratings on two new samples were collected, and the interrater reliability coefficients for the scales were again of appreciable magnitude. Discriminant validity was examined, as was the factor structure of the battery. The results suggested that the scales tap three distinct sources of variance. Comparisons with symptom measures and case illustrations indicated that the measurement of changes in patients' functioning beyond symptoms is necessary and viable.

Adult↗

Effects of nitrous oxide on the functional characteristics of cells in the extrastriate cortex of the cat.

The directional preferences, receptive field areas, peristimulus-time (PST) histograms and spontaneous activities of 112 feline visual cortical (area 18) cells were studied before, during, and after the administration of nitrous oxide. These cellular characteristics were altered by nitrous oxide inhalation; some quite substantially. The data indicate that the functional characteristics of cortical visual cells, such as the receptive field and the directional preference, are variable; and, among other factors, depend also on the anaesthetic administered to the animal.

Animals↗

Brief psychotherapy of bereavement reactions. The relationship of process to outcome.

We studied the relationship of dispositional and process variables with outcome in 52 bereaved patients given time-limited dynamic psychotherapy. Outcomes were generally favorable in symptom relief and improvement in relationship and occupational functioning. Patients' symptoms improved more than did their social and work functioning. Pretreatment levels of impairment or distress were significantly related to outcome, but most demographic and dispositional variables did not predict outcome. Process variables examined in relation to outcome--therapeutic alliance and actions by the therapist--were not significantly related to either type of outcome. When we considered the same process variables in interaction with two dispositional variables, motivation for dynamic therapy and developmental level of the self-concept, we found significant predictions of outcome. The major findings suggest that more exploratory actions were more suitable for highly motivated and/or better-organized patients and less suitable for patients with lower levels of motivation or organization of self-concept. More supportive actions were more suitable for patients at lower dispositional levels and less therapeutic for patients at higher levels.

Adjustment Disorders↗

Interaction of penicillin and pentobarbital with inhibitory synaptic mechanisms in neocortex.

In this study we characterized the responses of neocortical neurons to iontophoretically applied gamma-aminobutyric acid (GABA) and examined how these GABA responses as well as the inhibitory postsynaptic potentials (IPSPs) were affected by the presence of penicillin or pentobarbital. Intracellular recordings were obtained from slices of rat neocortex maintained in vitro; injection of the dye Lucifer yellow indicated that recordings were primarily from pyramidal neurons. Orthodromically evoked responses were always depolarizing at the cell's resting membrane potential. Such depolarizing responses could easily be reversed in polarity by depolarizing the cell 10-15 mV, suggesting that the response consisted partly of an IPSP. In some cases, depolarization unmasked a small, short-latency excitatory postsynaptic potential (EPSP). Responses to iontophoretically applied GABA were also depolarizing at rest. Biphasic hyperpolarizing-depolarizing responses were occasionally observed upon depolarization of the neuron. Bath application of penicillin (1.7-3.4 mM) decreased the amplitude of the IPSPs and increased their time to peak, an effect associated with the development of epileptiform activity. Penicillin also reduced the maximum response to iontophoretically applied GABA without affecting the dose required to obtain a half-maximal response, suggesting a noncompetitive antagonism. Pentobarbital (100-200 microM) prolonged the time course and increased the amplitude of the IPSPs while producing a leftward shift in the GABA charge-response relation. These results suggest that the convulsant penicillin and the anticonvulsant pentobarbital have opposing actions on GABAergic inhibition in the neocortex.

Animals↗

Cluster analysis of visual cortical responses evoked by moving lines.

The cortical evoked responses to a bar of light (line) moving in 8 different directions across the visual field of 6 unanaesthetized, immobilized cats were compared in 18 experimental sessions. The shape of the response is unique for each direction. This is particularly apparent during the first 350 msec of the response. Cluster analysis of the evoked potentials reveals that the recognition of the direction of the moving line is probably less distinct when the line moves in a downward direction. This finding is more pronounced in the left hemisphere. The results of the cluster analysis indicate that the technique may be a useful tool in the analysis and classification of large numbers of evoked potentials. Furthermore, such clustering may eventually reveal some of the physiological mechanisms that contribute to the shape of the evoked response.

Animals↗

Reactions to the death of a parent. Results from patients and field subjects.

The authors studied two groups of persons who had experienced either the death of a mother or father. One group consisted of patients who had sought treatment because of pathological aspects of bereavement. The other group consisted of volunteers selected from a review of hospital death records, which indicated the recent death of their parent. The study used a nonequivalent groups design, where both groups were followed over time. The field subjects were initially seen much sooner after the death than the patients. The patient group received a time-limited dynamic therapy focused on the stress response syndrome induced by the death. At the pretherapy evaluation point, the patient sample had significantly higher levels of symptomatic distress than did the nonpatient sample. The distress declined over a 13-month period, so that patients had comparable levels of distress to that of the field subjects. After adjusting for initial values, the main difference was that patients reduced their avoidant operations more than did the field subjects. Intervening variables were assessed for the prediction of change in symptoms over time as related to the parental death. The variables that showed significant correlations to symptomatic change were cumulative negative life events from varied sources, occupation, social class, developmental level of the self-concept, identity of the deceased parent, and attribution of blame for the death. Social support did not relate to change in symptoms over time.

Adaptation, Psychological↗

Effects of deuterium oxide and galvanic vestibular stimulation on visual cortical cell function.

/he spontaneous and evoked unit activities of complex visual cortical cells were recorded from Brodmann's area 18 in immobilized, unanesthetized cats before, during, and after stimulation of the vestibular system. The vestibular system was stimulated by intravenous injection of deuterium oxide (D2O)--a noted nystagmogenic agent (14)--or by direct galvanic stimulation of the labyrinth. Measures of the receptive-field areas, poststimulus time histograms, directional preferences, and the optimal speed of the light bar stimulating the cell were obtained before and after the application of D2O. Directional preferences were determined in a novel manner, using a method derived from a hierarchical clustering technique (19). Data were collected and analyzed from a) visual cortical cells in cats with intact labyrinths, b) visual cortical cells in cats following bilateral labrinthectomies, and c) nonvisual cortical cells in cats with intact labyrinths. In cats with intact labyrinths, D2O changed the optimal length of the light bar that was able to stimulate the cortical cell as well as the path on which it evoked the response of the cell. Both values, which constitute the receptive field of the cell, changed approximately proportionately. This effect usually lasts for less than 4.5 h. The other cellular characteristics were also altered by the D2O. Galvanic stimulation of the labyrinth resembles, in its effects, the injection of D2O. In labyrinth-intact cats, the time course of area 18 spontaneous activity dramatically increased 30 min or more after D2O was administered. It peaked 2-3 h later and still had not returned to preinjection levels even 7 h after the D2O administration. In bilaterally labyrinthectomized cats, the spontaneous activity of the visual cells (and the other cellular characteristics studied) did not change following D2O administration. In nonvisual cells from labyrinth-intact cats, the spontaneous activity demonstrated a slight but significant decrease over time after D2O injection. (The other measures, however, did not change.) In pilot studies (about 2 wk prior to the electrophysiological experiments), the cats were injected with D2O. Within 8-10 min afterward, signs of positional nystagmus commenced; and within 30 min, problems in maintaining balance were noted. This continued for 7-8 h before disappearing. In the labyrinthectomized animals, such effects were not observed. These results, therefore, add support to other evidence that suggests that D2O works directly through the vestibular apparatus to produce the effects it does (and not through interference with certain cellular processes).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The Stress Response Rating Scale: a clinician's measure for rating the response to serious life-events.

The impact of a serious life-event on an individual's psychological well-being has long been appreciated, but not until recently has it become the subject of more thorough and careful research. Clinical, field, and experimental studies of the effects of potentially distressing life-events have suggested the presence of two primary modes of response: episodes of denial and numbing, oscillating with periods of intrusive thoughts, images, and pangs of emotion. Although self-report measures are available for determining the degree of distress experienced in each of these modes of response, there is no measure that can be used by a clinical observer to assess these same phenomena. We offer the Stress Response Rating Scale (SRRS) as such a measure, and present empirical data to support its reliability and validity. In addition, we present some initial normative data, a discussion of issues encountered in developing the scale, and potential difficulties that may be encountered in its use.

Denial, Psychological↗

Deuterium oxide modification of neuronal characteristics in the visual cortex of the cat.

The receptive field area and the spontaneous activity of complex visual cortical cells were investigated in the cat before, and after, the administration of deuterium oxide (D2O). In cats with intact labyrinths, the receptive field area of the cell usually expands, and the spontaneous activity increases. In bilaterally labyrinthectomized animals, these changes are absent. Also, D2O does not alter the spontaneous firing rate in non-visual cortical cells in normal cats.

Animals↗

Judging change in psychotherapy. Reliability of clinical formulations.

Careful clinical formulation describing the dimensions of core neurotic conflicts is integral to the practice of psychodynamic psychotherapy. Therefore, a method for reliable and valid formulation is a necessary precursor for the empirical investigation of the impact of such therapy. Our study evaluated a method of outcome assessment based on clinical formulations. Results from 18 patients indicate that independently derived formulations of a central conflict do not agree and that these disagreements in formulation are reflected in disagreements in the change ratings that are based on them. Additional analyses suggested that symptomatic change represents the major component in outcome rating.

Adjustment Disorders↗