Androgen status in women with late onset or persistent acne vulgaris.
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Acne Vulgaris↗
Biomedical subjects
J W Moore
Publications and source records attributed to J W Moore.
Long-term follow-up of the effects of behavior therapy.
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Behavior Therapy↗
Dynamics of intracellular calcium and its possible relationship to phasic transmitter release and facilitation at the frog neuromuscular junction.
We have developed a mechanistic model for intracellular influx, diffusion, and efflux of calcium, and we compare its predictions to the dynamics of transmitter release at the frog's motor nerve terminal. The model includes a square wave influx of calcium, a linear or saturable pump for the efflux of calcium, and slow diffusion of calcium within the terminal due to rapid equilibrium binding of the major portion of the influx to fixed, nonsaturable sites in the cytoplasm. Transmitter release is taken as proportional to the fourth power of the calcium concentration in a region within 100 A of the surface membrane. The model predicts phasic release of transmitter with a time course similar to that of the endplate current--it turns on with a lag, rises rapidly to a peak, and then declines more slowly. It also predicts facilitation, the increased transmitter release in response to a second stimulus for many milliseconds after the initial transmitter release has ceased. This facilitation is similar to that reported at the frog neuromuscular junction in its initial amplitude and time course.
Animals↗
Oestrogens and the etiology and clinical course of breast cancer.
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Age Factors↗
The nictitating membrane response: an electrophysiological study of the abducens nerve and nucleus and the accessory abducens nucleus in rabbit.
The nictitating membrane response to periocular electrostimulation was investigated in anesthetized and paralyzed rabbits. Recordings from the abducens nerve, which carries the fibers innervating retractor bulbi muscles that are primarily involved in this reflex, showed two distinct volleys to effective stimulation: a short duration volley with a minimum latency of approximately 4 ms and a longer duration volley beginning approximately 10 ms after stimulus onset and lasting up to 25 ms. Recordings of antidromically evoked field potentials via microelectrodes indicated large responses to abducens nerve stimulation in the vicinity of the accessory abducens nucleus. Single unit recordings from the accessory abducens nucleus produced spike trains with minimal latencies of 3.7-5 ms to eyeshock. The latency of spike discharge was inversely related to stimulus current. Units in the abducens nucleus did not show stimulus-elicited spiking, suggesting that the accessory abducens, but not the abducens, is primarily involved in the reflex pathway. Transverse knife cuts which separated caudal areas of the sensory trigeminal complex from the accessory abducens nucleus did not attenuate the efferent volley to suprathreshold stimulation, suggesting that more rostral components of the trigeminal complex are primarily involved in the reflex pathway.
Abducens Nerve↗
Retention of conditioned inhibition of the nictitating membrane response in decorticate rabbits.
Rabbits were trained on a Pavlovian conditioned inhibition (CI) task using light as the reinforced conditional stimulus (CS) and the same light compounded with a tone as the non-reinforced CS. The conditional response was the nictitating membrane response (NMR). The subjects then received an extensive neocortical lesion or a sham operation. After 9 weeks postoperative recovery, the animals were retrained on the CI task. Sham operated control animals showed immediate and high levels of CI retention but the decorticates showed a profound initial loss, showing that there is a cortical influence in CI. Reacquisition of CI by the decorticates was rapid and showed considerable savings over de novo acquisition. This supports our earlier finding that the neocortex is not essential for the acquisition of CI.
Animals↗
Red nucleus lesions disrupt the classically conditioned nictitating membrane response in rabbits.
Sixteen rabbits received classical conditioning of the right nictitating membrane response using a tone CS and electrostimulation of the right eye as the US. Single electrocoagulating RF lesions of the medial portion of the left magnocellular red nucleus eliminated or severely reduced the previously acquired conditioned response. This finding is consistent with the idea that an essential anatomical substrate of the conditioned response includes a circuit from the cerebellum to the contralateral red nucleus which projects contralaterally in turn to pontine motoneurons mediating the defensive nictitating membrane response.
Animals↗
An HRP study of the brainstem afferents to the accessory abducens region and dorsolateral pons in rabbit: implications for the conditioned nictitating membrane response.
Brain projections to the accessory abducens region and dorsolateral pons were investigated in rabbit using implants of crystalline horseradish peroxidase (HRP). Following implantation of HRP in the accessory abducens region (N = 3), labeled cells were observed in the sensory trigeminal nuclei and other regions implicated in the reflex pathway of the defensive nictitating membrane (NM) response. Neurons in the supratrigeminal zone were also labeled, as were portions of the contralateral red nucleus. Implantation of HRP into the dorsolateral pons (N = 5) revealed ipsilateral projections from deep-cerebellar nuclei in some cases. In addition, the parvocellular reticular formation displayed bilateral labeling of cells and an ipsilateral network of fibers and apparent terminations. Many cells of the contralateral supratrigeminal zone were labeled in these cases. Results were discussed in relation to lesioning and electrophysiological studies implicating the supratrigeminal region and other structures in the control of the classically conditioned NM response. Specifically, the possibility that supratrigeminal neurons are premotor elements responsible for the conditioned response is considered. Alternative hypotheses are discussed, including pathways by which cerebellar nuclei could control conditioned responding.
Abducens Nerve↗
A supratrigeminal region implicated in the classically conditioned nictitating membrane response.
The dorsolateral pontine brain stem was investigated as a possible locus of neural elements mediating the classically conditioned nictitating membrane (NM) response in rabbit. Recording and brain stimulation were employed for this purpose. Low-impedance tungsten monopolar microelectrodes were chronically implanted into the pontine brain stem. Multiple-unit recording during classical conditioning revealed a conditioned increase in multiple-unit activity (MUA) which developed and extinguished concurrently with the acquisition and extinction of the behavioral conditioned response. Pseudoconditioning and conditioned inhibition controls indicated that the increase in MUA was an associative learning phenomenon. Histology indicated that electrode tips recording the CR-associated electrical activity were located mostly adjacent or dorsal to the motor trigeminal nucleus. Periocular shock pulses elicited short latency evoked responses throughout most of the dorsolateral pons, suggesting that information concerning the unconditioned stimulus is relayed to this region. Furthermore, electrical stimulation of this region produced a robust ipsilateral nictitating membrane response in a number of cases, suggesting that neural elements of the dorsolateral pons project to the motoneurons that produce membrane extension. A consideration of several criteria based on these experiments implicates a supratrigeminal zone [22] as containing the neural elements of dorsolateral pons most intimately associated with the conditioned NM response. Other interpretations, concerning fibers of passage through this region and
Abducens Nerve↗
Low dose prednisolone or oestrogen in the treatment of women with late onset or persistent acne vulgaris.
Women with persistent or late onset acne vulgaris were divided into two treatment groups. The first received continuous low dose prednisolone to suppress ACTH-dependent androgen secretion and the second was treated with cyclical oestrogens with medroxyprogesterone to elevate sex hormone binding globulin (SHBG). In both groups there was a significant improvement in the severity of the acne after 4 months' treatment. Although pre-existing hormonal abnormalities were corrected, the improvement in the acne did not correlate with the baseline hormone levels. However, suitable oestrogen-progesterone combinations or low dose prednisolone may be given, alone or in combination, to suppress free circulating androgens in these patients with a high probability of improving their acne.
Acne Vulgaris↗
Action potential propagation and threshold parameters in inhomogeneous regions of squid axons.
The squid giant axon was used as a model system in which to determine the independent contributions of membrane excitability and diameter changes to threshold parameters and propagation of action potentials in inhomogeneous regions. The membrane excitability of a segment of an axon was altered by changes in the bathing solution, while its effective electrical diameter was increased by the insertion of a low-resistance axial wire. In computer simulations of these experiments, similar alterations were made in the membrane's conductance and axon's diameter. The inflexions in the shapes of action potentials propagating into a region with abrupt decreases in axial resistance become more pronounced when the interval between impulses was shortened. At short intervals, propagation of the second impulse failed. In contrast, reduction of membrane excitability produced inflexion-free changes in action potential shape and allowed a close-following second impulse to pass through the inhomogeneity. A combined decrease in membrane excitability and increase in diameter of the same region exaggerated the changes in action potential shape characteristic of the diameter increase alone. Threshold parameters were obtained from 'strength-duration' excitability relationships measured by injection of current at different points along the axon. When only the membrane excitability was reduced, threshold characteristics changed smoothly from one region of the nerve to another. In contrast, lowering the internal resistance or increasing the diameter in one region of a nerve lowered the time constant of excitation and the threshold for brief (relative to rheobasic) current stimuli in the small-diameter region near the transition while raising them in the larger-diameter region.
Action Potentials↗
On the site of impulse initiation in a neurone.
In the preceding paper (Moore & Westerfield, 1983) the effects of changes in membrane properties and non-uniform geometry on impulse propagation and threshold parameters were investigated. In this paper the contributions of these and other parameters to the site of initiation of an impulse were determined by computer simulations using the Hodgkin-Huxley membrane description, the cable equations, and geometry appropriate for a simplified motoneurone with a non-myelinated axon. Antidromic invasion of action potentials into the soma was found to depend upon (a) the ionic channel rate constants (determined by the temperature), (b) the abruptness of the transition from the small-diameter axon to the larger diameter (and increased load) of the soma-dendrite, (c) extensions of active properties into the dendrite, and (d) density of ion channels. The location of the apparent site of initiation of impulses was not necessarily at the site of synaptic input nor the nearest active membrane. Its position depended upon (a) the fraction of the dendritic tree with excitable membrane, and secondarily on (b) the stimulus strength. Even with uniform excitability in the active membrane, the apparent site of initiation could be moved a considerable distance from the soma and the site of stimulation by appropriate choice of the various parameters noted above.
Action Potentials↗
Distribution of 17 beta-estradiol in the sera of normal British and Japanese women.
Normal Japanese women had significantly more of their blood 17 beta-estradiol (E2) bound to sex hormone-binding globulin (SHBG) (53%) than British women (30%) and conversely less bound to albumin. While the proportion of SHBG-bound E2 increased with SHBG capacity and while binding fell as weight increased, the differences between the races do not appear to be explicable in terms of SHBG capacity or weight. At a given SHBG capacity, the Japanese women had more E2 bound to the protein than the British women. Where weights in the 2 populations overlapped, the Japanese women still had more of their E2 bound to SHBG than did the British women. Our results suggested that the affinity of albumin for E2 is lower in Japanese women.
Adult↗
Serum concentrations of total and non-protein-bound oestradiol in patients with breast cancer and in normal controls.
In premenopausal women with breast cancer, total serum oestradiol (E2) concentrations are normal but nonprotein-bound E2 concentration are significantly raised. This is not due to low sex-hormone-binding-globulin (SHBG) binding capacities which are within the normal range and is unlikely to be due to the small but significant decrease in albumin concentrations. In post-menopausal patients, both total and non-protein-bound E2 are significantly raised: this may be explained partially by lower SHBG binding capacities. In patients and controls there is a highly significant correlation between non-protein-bound E2 and SHBG but, for a given SHBG binding capacity, the patients have more non-bound E2 than controls. It is concluded that the breast in women with breast cancer may be exposed to elevated levels of biologically active E2 although the reasons for this remain obscure.
Adult↗
A brain stem region essential for the classically conditioned but not unconditioned nictitating membrane response.
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Animals↗
Latency of the nictitating membrane response to periocular electrostimulation in unanesthetized rabbits.
The latency of the nictitating membrane response (NMR) in rabbit (Oryctolagus cuniculus) to periocular electro-stimulation is a negative exponential function of stimulus current with an asymptote of approximately 17 msec. The NMR was recorded by means of a precision low-torque potentiometer like that employed in previous studies of NMR latency, and the criterion of response initiation employed here was similar to that employed in studies of classical conditioning in this preparation. Using estimates from physiological studies on surgically acute preparations, the minimum latency of the NMR of 17 msec can be decomposed as follows: 4 msec to fire motoneurons of the accessory abducens nucleus; 9 msec for conduction, synaptic transmission, and recruitment of retractor bulbi muscle fibers; 4 msec for the nictitating membrane to initiate its sweep after eyeball retraction. The implications of these estimates for chronic unit-recording studies of the conditioned NMR are discussed.
Animals↗
On the squid axon membrane's response to sequential voltage and current clamps.
Starzak and Starzak (1978. IEEE Trans. Biomed. Eng. 25:201-204.) proposed that, in cyclic application of current and voltage-clamps, the fidelity of the match of the output current with the original stimulus could be used to measure the spatial uniformity of voltage in a membrane. However, they failed to find such a match in experiments on either squid axons or an electronic model of a membrane patch. Computer simulations of such experiments show that the failure to return the initial pattern may arise from shortcomings of the instruments or instability of membrane characteristics. Logical arguments show that such cyclic experiments are not able to provide information about spatial gradients of membrane voltage.
Animals↗
Heterokaryon analysis of the genetic control of pigment synthesis in chick embryo melanocytes.
The genetic control of pigmentation was analyzed using five unlinked mutants, namely, c, pk, Bl, ev and l. Each mutant blocks or reduces pigmentation. Chick melanocyte cultures of each mutant type were fused to produce all ten possible pair combinations of nondividing heterokaryons. Heterokaryons were identified autoradiographically (One partner in each pair was labeled with 3H-thymidine.) Crosses produced comparable pairs of double heterozygotes that were analyzed in vivo and in vitro. Heterokaryon pairs were compared to their corresponding double heterozygotes.--Some combinations showed complementation and produced wild-type pigment. Others showed noncomplementation having little or no pigment. Double heterozygotes complemented each other except in the cases involving the dominant mutant, l. Four heterokaryon pairs gave different results from their corresponding double heterozygotes. The pk-Bl and pk-ev combinations failed to complement as heterokaryons but did complement as double heterozygotes. On the other hand the l-c and I-Bl combinations complemented as heterokaryons but not as double heterozygotes. Based on these differences it is hypothesized that the pk and I loci are nuclearly restricted regulatory elements. Examples in the literature from other systems are cited to support such a hypothesis.
Animals↗