A two-step model of secretion control in neuroendocrine cells

Recent experiments on a variety of neuroendocrine cells indicate that intense stimuli readily depress the secretory response. The most likely explanation for this depression is that a pool of release-ready granules is depleted. We present a two-step model of secretion that allows one to simulate the dynamics of such a pool for different time courses of free intracellular Ca concentration [Ca2+]i. We derive rate constants of the model from two types of experiment and find that, for the simplest type of model, not only the rate of consumption (exocytosis) but also the rate of vesicle supply to the pool of release-ready granules must be made Ca-dependent. Given these functional dependences a variety of results from the literature can be simulated. In particular, the model predicts the occurrence of secretory depression and augmentation under appropriate conditions.     

Prolonged hormone secretion from neuroendocrine cells of Aplysia is independent of extracellular calcium

The role of Ca2+ from extracellular and intracellular sources in stimulating neurosecretion was investigated in four experiments using neuroendocrine bag cells of the marine mollusk Aplysia. (i) Bag cells were treated with either an extracellular calcium chelator (BAPTA) or Co(2+)-substitution within 30 s after onset of an electrical afterdischarge to prevent influx of Ca2+ from extracellular fluid. These treatments shortened the duration of the afterdischarge, but did not significantly affect the overall pattern or total amount of egg laying hormone (ELH) secretion, suggesting that extracellular Ca2+ is not required for maintenance of ELH release. (ii) Substitution of Ba2+ for Ca2+ has previously been shown to support bag cell afterdischarges that trigger transient elevations in intracellular Ca2+. We showed that this treatment also stimulates ELH secretion, suggesting that Ca2+ release from intracellular stores can stimulate ELH secretion. (iii) To raise intracellular Ca2+ levels in the absence of an afterdischarge, the calcium ionophore X537A was used to transport Ca2+ across plasma and organelle membranes. When this treatment was combined with extracellular calcium chelators so that the only source of Ca2+ was from intracellular compartments, ELH secretion was stimulated. Taken together, these findings are consistent with the hypothesis that release of Ca2+ from intracellular stores is sufficient to stimulate ELH secretion.     

The Sceno Game in the course of time

This article describes 50 years of working with the Sceno test, the first decades being in close cooperation with Gerhild von Staabs. After many years experience with the Sceno test in Swiss psychiatric hospitals over 1000 Sceno test games were conducted in the psychosomatic ward of the University of Munich Outpatient Department for Children and evaluated with a special record and slides. These were games carried out by children and adolescents with behavioral disorders, psychosomatic illnesses, and handicaps, in some cases by their mothers in an accompanying simultaneous analysis. Using the projective method the initial Sceno test, vulgar and original answers, key situations, repetition and memory compulsions were recorded. With 100 adults diagnosed as being schizophrenic Sceno tests with chaotic apparent order analogous to pictures painted by schizophrenics were observed. With adults and children with cerebro-organic damage we found an "organic play syndrom" in the game structure. Six medical dissertations dealt with the psychosomatics of children. Along with the depth psychology problems, in principle, the formality of the Sceno test set-up depending on age and development phase of the child also has to be taken into consideration. The Sceno test in its original form has proven itself to be up to date even today and requires only minor changes to some game elements, adapting them to the modern surroundings of children which means that a Sceno-R (Fliegner 1995) with 23 new game elements seems unnecessary. Psychodiagnostics and psychotherapy of our Sceno test game are based on the analytical method of Hans Zulliger and Anna Freud.     

Sex differences in the time course of emotion.

Conventional wisdom holds that women are more "emotional" than men. However, research evidence suggests that sex differences in emotion are considerably more complex. The authors tested hypotheses about sex differences in the engagement of the approach and avoidance motivational systems thought to underpin emotional responses. The authors measured reported emotional experience and startle response magnitude both during the presentation and after the offset of emotional stimuli that engage these motivational systems to assess whether men and women differ in their patterns of immediate response to emotional stimuli and in their patterns of recovery from these responses. Our findings indicated that women were more experientially reactive to negative, but not positive, emotional pictures compared to men, and that women scored higher than men on measure of aversive motivational system sensitivity. Although both men and women exhibited potentiation of the startle response during the presentation of negative pictures relative to neutral pictures, only women continued to show this relative potentiation during the recovery period, indicating that women were continuing to engage the aversive motivational system after the offset of negative emotional pictures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mechanisms of histamine stimulated secretion in rabbit ileal mucosa

Histamine is present in high concentrations in the intestine and we investigated the possibility that it might have a role here in intestinal transport. When added to the basal side of rabbit ileal mucosa in vitro histamine (10(-4)M) induced a short-lived increase in electrical potential difference and short circuit current. It inhibited net chloride absorption but did not influence sodium transport. Alkali secretion, measured by a pH stat technique, was inhibited, suggesting that bicarbonate secretion was reduced. Both the electrical and ion flux responses to histamine were blocked by the H1 receptor blocker diphenhydramine, but not by the H2 receptor blocker cimetidine. The presence of specific H1 histamine receptors was further supported by shifts in the dose-response curve to histamine by four different concentrations of diphenhydramine. Calculation of a pA2 value from these "Schild' plots provided a figure of 7.85, which is similar to that for H1 receptors in other tissues. Aminoguanidine, a histaminase blocker, had no electrical effects alone but shifted the histamine dose response curve to the left. These studies indicate that histamine inhibits chloride absorption and alkali secretion, possibly by influencing a chloride/bicarbonate exchange process, through specific mucosal H1 receptors. Enhancement of histamine effects by a histaminase inhibitor suggests that histaminases are present in the intestinal mucosa and supports the possibility of a role for endogenous histamine in influencing ion transport. The observations indicate a mechanism by which absorption might be impaired in diseases in which histamine is liberated locally in the intestine.     

Prenatal androgens time neuroendocrine puberty in the sheep: effect of testosterone dose

In sheep, prenatal exposure to androgens during a critical period for sexual differentiation of the brain (30-90 days of gestation; 145 days is term) can advance the timing of puberty in females and prevent the preovulatory LH surge. The present study tests the hypothesis that in sheep, the timing of neuroendocrine sexual maturation is related to the amount of prenatal steroid exposure. In addition, we determined if different steroid requirements exist for sexual differentiation of the tonic and surge modes of gonadotropin secretion. Testosterone was administered weekly to three groups of pregnant ewes from days 30-90 of gestation at doses of 200, 80, or 32 mg/week. The resulting androgenized female lambs together with control males and females (n = 5-7/group) were gonadectomized at 3 weeks of age, and gonadal steroids were replaced with a SILASTIC brand estradiol-filled capsule. LH concentrations were measured from biweekly blood samples. Sustained increases in circulating LH were considered to reflect the initiation of neuroendocrine puberty. In male lambs, LH secretion started to increase at 8.3 +/- 0.9 weeks of age (mean +/- SEM). The two highest doses of prenatal androgen advanced the onset of neuroendocrine sexual maturation in females. In the 200 mg androgenized females, the pubertal LH rise (10.2 +/- 2.0 weeks) began about the same time as in males. In the 80 mg treatment group, LH concentrations increased at 16.2 +/- 1.5 weeks, which was later than in males, but well before that in normal females (27.1 +/- 0.7 weeks). For females treated with the lowest dose of androgen (32 mg), the pubertal LH increase (24.6 +/- 1.9 weeks) began about the same time as in normal females. To test the function of the LH surge system, LH was measured every 2 h for 60 h after an acute increase in circulating estradiol was produced by implanting additional estrogen capsules. All control females produced a surge in response to acute estradiol stimulation. LH surges did not occur in males, 200 mg androgenized females, or 80 mg androgenized females. Of six females from the 32 mg treatment group, two produced LH surges in response to the stimulatory feedback action of estradiol. We conclude that the greater the amount of prenatal testosterone, the earlier the initiation of the pubertal LH rise. Moreover, the finding that low doses of testosterone (32 mg/week) are capable of abolishing the LH surge without significantly advancing the timing of puberty supports our hypothesis that different steroid requirements exist for sexual differentiation of tonic and surge modes of LH secretion.     

The time course of intracellular calcium movements in single human umbilical vein smooth muscle cells

Intracellular Ca2+ ([Ca2+]i) was measured in single isolated human umbilical vein smooth muscle cells. Stimulation with histamine, in the absence of external Ca2+, mobilised Ca2+ from intracellular stores. When repeated brief applications of agonist were used, the time to onset, amplitude and rate of rise of the Ca2+ transients were found to change. Two components could often be discerned in the rising phase of the transients, an initial slow "pacemaker" and a second faster and larger component. Following the first histamine-activated transient the basal level of [Ca2+]i was invariably lower than that prior to stimulation. This lower value was maintained whilst the cell remained in Ca(2+)-free solution, but could be returned to a higher level if the cell was exposed to external Ca2+. When the mobilisation of the intracellular store was reduced to undetectable levels, re-exposure to Ca(2+)-containing medium reactivated responses. In the absence of external Ca2+, continuous application of histamine activated a series of transient increases in intracellular Ca2+, which decreased progressively in amplitude and rate of rise. The interval between transients also increased. These findings are discussed in terms of the activation of inositol trisphosphate-sensitive intracellular Ca2+ stores and their sensitivity to cytoplasmic Ca2+ and intrasarcoplasmic reticulum Ca2+.     

Probing the time course of representational momentum.

Observers saw a rectangle at three orientations along a path of rotation. They attempted to remember the third orientation and were then tested with a fourth orientation that was either the same as, or slightly different from, the third. As in previous representational momentum studies we find that memory for position is distorted in the direction of the implied motion, in analogy to physical momentum. We now report that memory shift increases with retention interval for small intervals, as predicted by the analogy. However, instead of reaching some asymptotic value, the memory shift then decreases with retention interval. The results U-shaped curve may be considered the result of two competing effects: a positive memory shift attributable to representational momentum, which dominates at short intervals, and a negative shift attributable to memory averaging effects, which dominates at longer intervals. The memory averaging effect increases with retention interval and is strongest for faster presentation rates. For very short retention intervals the rate of increase in memory shift is proportional to the implied velocity of the inducing display, as predicted from the analogy to physical momentum. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Individual differences in the time course of inferential processing.

Although less skilled readers perform poorly on tasks that require inference generation, it is difficult to know whether their performance results from deficits in inferential abilities or failure to encode accurate discourse representations. These experiments contrasted skilled and less skilled readers' ability (1) to execute a process necessary to represent the meaning of a discourse (i.e., to select the context-appropriate sense of an ambiguous word) and (2) to generate knowledge-based inferences. Ss read passages that contained homograph primes and responded to lexical decision targets. Both skilled and less skilled readers responded faster to appropriate than to inappropriate associates of homograph primes, whereas only skilled readers showed facilitation to topic-related words relative to unrelated control words. It is argued that deficiencies in basic linguistic processes alone cannot account for less skilled readers' failure to generate topic-related inferences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Subcellular localization of epitope-tagged neurotrophins in neuroendocrine cells

Tests of paced serial addition are used to detect diminished information-processing capacity. Nonetheless, performance might be influenced by modality-specific interference or by variables that specifically affect numerical processing. In a series of three experiments with normal adults, we manipulated, respectively, the modality in which addends were presented, the modality in which responses were produced, and the format in which visual addends were displayed. Performance was enhanced when stimuli were presented visually and when responses were made manually. When visual addends were used, Arabic numerals were processed more effectively than number words. Thus, performance was influenced by modality-specific interference and by presentation format. We conclude that paced serial addition tasks may not provide a pure measure of general information-processing capacity.     

Mechanisms of secretion of toxic organic anions in mammalian kidneys

This short review considers the mechanisms of organic anion secretion in renal proximal tubules. Particular attention is given to the energy coupling of p-aminohippurate transport to inorganic anion gradients generated across both basolateral and brush-border membranes. The coupling is considered to be a consequence of the combined operation of the co-transport and anion-exchange mechanisms. A possible coexistence of several organic anion pathways with overlapping substrate specificity and/or energetic dependence of the total ion gradient are suggested. The problem of identification of transporters involved in organic anion secretion is discussed.     

Estimating the time course of the excitatory synaptic conductance in neocortical pyramidal cells using a novel voltage jump method

We introduce a method that permits faithful extraction of the decay time course of the synaptic conductance independent of dendritic geometry and the electrotonic location of the synapse. The method is based on the experimental procedure of Pearce (1993), consisting of a series of identical somatic voltage jumps repeated at various times relative to the onset of the synaptic conductance. The progression of synaptic charge recovered by successive jumps has a characteristic shape, which can be described by an analytical function consisting of sums of exponentials. The voltage jump method was tested with simulations using simple equivalent cylinder cable models as well as detailed compartmental models of pyramidal cells. The decay time course of the synaptic conductance could be estimated with high accuracy, even with high series resistances, low membrane resistances, and electrotonically remote, distributed synapses. The method also provides the time course of the voltage change at the synapse in response to a somatic voltage-clamp step and thus may be useful for constraining compartmental models and estimating the relative electrotonic distance of synapses. In conjunction with an estimate of the attenuation of synaptic charge, the method also permits recovery of the amplitude of the synaptic conductance. We use the method experimentally to determine the decay time course of excitatory synaptic conductances in neocortical pyramidal cells. The relatively rapid decay time constant we have estimated (tau approximately 1.7 msec at 35 degrees C) has important consequences for dendritic integration of synaptic input by these neurons.     

The time course of categorization.

The extended generalized context model (EGCM) is presented as a formal model of the time course of categorization of complex stimuli. The model explains the effects of time constraints on categorization. The EGCM accurately accounts for existing data on categorization under time pressure. The model was tested further in 2 experiments. In both experiments, processing time in a perceptual categorization task was restricted by unpredictable peremptory response signals. In Experiment 1, restrictions of processing time had systematic effects on response proportions, and these effects were well explained by the EGCM. Experiment 2 showed that perceptual salience and utility have independent effects on the time course of categorization, as predicted by the EGCM. The EGCM's relation to other models of the time course of categorization is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tracking the time course of orthographic information in spoken-word recognition.

Two visual-world experiments evaluated the time course and use of orthographic information in spoken-word recognition using printed words as referents. Participants saw 4 words on a computer screen and listened to spoken sentences instructing them to click on one of the words (e.g., Click on the word bead). The printed words appeared 200 ms before the onset of the spoken target word. In Experiment 1, the display included the target word and a competitor with either a lower degree (e.g., bear) or a higher degree (e.g., bean) of phonological overlap with the target. Both competitors had the same degree of orthographic overlap with the target. There were more fixations to the competitors than to unrelated distractors. Crucially, the likelihood of fixating a competitor did not vary as a function of the amount of phonological overlap between target and competitor. In Experiment 2, the display included the target word and a competitor with either a lower degree (e.g., bare) or a higher degree (e.g., bear) of orthographic overlap with the target. Competitors were homophonous and thus had the same degree of phonological overlap with the target. There were more fixations to higher overlap competitors than to lower overlap competitors, beginning during the temporal interval where initial fixations driven by the vowel are expected to occur. The authors conclude that orthographic information is rapidly activated as a spoken word unfolds and is immediately used in mapping spoken words onto potential printed referents. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The precise time course of retention.

Fits of retention data were examined from 5 conditions: 3 types of cued recall, an old–new recognition task, and a remember–know recognition task. In each condition, 100 participants had either 18 recall or 27 recognition trials at each of 10 delays between 0 and 99 intervening items, providing the first data obtained in experimental psychology that were precise enough to distinguish clearly among simple functions. None of the 105 2-parameter functions tested produced adequate fits to the data. The function y?=?a?e–t/1.15?+?a?e–t/T2?+?a? fit each of the 5 retention conditions. The T? parameter in this equation equaled 28 for the 3 recall conditions and the remember–know recognition condition and 13 for the old–new recognition condition. Individuals' recall data fit the same function with parameters varying with gender and scholastic aptitude scores. Reaction times support the claim that the a?e–t/1.15 term describes working memory, and the remaining 2 terms describe long-term memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The time course of object-feature retrieval in recognition.

The time course of perception and retrieval of object features was investigated. Participants completed a perceptual matching task and 2 recognition tasks under time pressure. The recognition tasks imposed different retention loads. A stochastic model of feature sampling with a Bayesian decision component was used to estimate the rate of feature perception and the rate of retrieval of feature information. The results demonstrated that retrieval rates did not differ among object features if only a single object was held in memory. If 2 objects were retained in memory, differences among retrieval rates of features emerged, indicating that features that were quickly perceived were also quickly retrieved. The results from the 2-object retention condition are compatible with process reinstatement models of retrieval. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mechanisms explaining the onset, course and spontaneous resolution of gouty arthritis

Cytogenetic analysis of short-term cultures from three untreated and one recurrent ependymoma revealed clonal aberrations in three of the four tumors. A posterior fossa ependymoma from a 3-year-old male patient showed trisomy 11 as the sole clonal chromosome aberration. A recurrent spinal ependymoma from a 35-year-old male showed hypertriploid clones with abnormalities involving chromosomes 1p11,7q21, and 10p13. A 62-year-old male patient with a cerebellar ependymoma showed a hypodiploid stem-cell line with clonal structural aberrations of both the long and short arms of chromosome 1, an interstitial deletion of 2q, trisomy 7, and monosomy for chromosomes 11, 13, and 16. A 3-year-old female patient with posterior fossa ependymoma showed a normal 46,XX karyotype. Chromosome 1 aberrations appear to be the most consistent finding in this small series of tumors, with the net loss or rearrangement of chromosome 1 pter-->p22 material from two of the four tumors. These findings, in addition to a previously published case [1], suggest a possible role for genes on the short arm of chromosome 1 in the cytogenetic evaluation of ependymomas.     

The characteristics of neuroendocrine regulatory disorders in acute myocardial infarct in relation to the severity of the course of the disease

A total of 45 patients aged 35 to 73 years who had sustained acute myocardial infarction (MI) were studied in a special cardiological unit. On days 1, 5, 14, 28 of hospital stay, each patient underwent measurements of cortisol, insulin, T3 and T4 and calculations of the mathematical clinic severity index after G.I. Marchuk et al. In acute MI, there were elevated plasma levels of cortisol depending on the MI severity with a small repeated peak of its increase on day 14 and its subsequent decrease, except deaths. In severe acute MI there were impairments of reciprocal cortisol/insulin ratios. This was particularly pronounced in patients with lethal outcomes. By the end of hospital rehabilitation, patients with acute MI displayed lower levels of thyroidal hormones. The maximum decrease in T3 and T4 was found in patients with lethal outcomes. There was a direct correlation between the mathematical clinical severity index of the natural history of acute MI and the levels of cortisole triidothyronine at the hospital stage of observation. In the course of the study it was found that the Marchuk clinical severity index serves as an informative severity index of MI course whose determination in its acute period allows one to predict the course of acute MI and to choose a differential therapy of and to make a diagnosis of possible complications.