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Biomedical subjects

J Born

Publications and source records attributed to J Born.

At least 163 records · Page 9Linked to original sources

Endogenous event-related brain potentials and psychometric performance in children at risk for schizophrenia.

Two independent groups of high-risk children for schizophrenia and their matched control children were submitted to the following experiments: an auditory oddball paradigm registrating late event-related potentials (ERPs) and a psychometric test battery including the assessment of Wechsler Intelligence Scales, reaction times (after regular and irregular preparatory intervals), and the d2-attention test. The study was intended to clarify whether long-latency ERPs and the selected psychometric tests would contribute to reliably differentiating between these groups. The results showed significantly prolonged latencies of the P3 component of the ERPs to rare, task-relevant target stimuli in both high-risk groups compared with the controls. Similarly, the N2 latencies were delayed in both groups. By contrast, ERP patterns to frequent, nontask-relevant stimuli were very similar, with no significant differences between high-risks and normals; nor did any ERP amplitudes show significant differences. The data are interpreted as a reflection of a subtle deficit in maintaining attention and a subsequent impairment of stimulus discrimination in high-risk children. This is consistent with the psychometric findings of higher error scores in target counts and d2-test, and significantly prolonged reaction times after regular preparatory intervals (PIs) in the high-risks. The findings may hint at a vulnerability for schizophrenia in high-risk children. Given the high prevalence of the attentional dysfunctions in both high-risk groups, however, it is hypothesized their presence does not necessarily imply an unequivocal manifestation of schizophrenia.

Adolescent↗

Sleep disruption alters nocturnal ACTH and cortisol secretory patterns.

Recent studies have provided evidence that nocturnal cortisol secretion is coupled to ultradian rhythms of sleep. The present study was designed to specify how exogenous and sleep-related endogenous factors influence nocturnal adrenocorticotropin (ACTH) and cortisol secretion. We compared the influences of (1) temporary sleep deprivation, (2) arousals continuously induced during sleep and, (3) undisturbed sleep (baseline) on pituitary-adrenocortical activity in 10 healthy men. Sleep deprivation (DS) and continuous arousals during sleep (AS) were introduced at the beginning of the second rapid eye movement (REM) sleep period which is an epoch close to the first significant nocturnal rise in plasma cortisol. Compared with the baseline nights, plasma cortisol significantly increased immediately after continuous arousals were started or the subject was awakened and remained awake. Despite this exogenously provoked first cortisol peak, average cortisol release during DS and AS was no higher than during undisturbed sleep. The arousal-induced cortisol burst was followed by a temporary inhibition of cortisol secretion, suggesting that once the subject is aroused (i.e., in stage 1 sleep or awake), the hypothalamus-pituitary-adrenal (HPA) system becomes highly sensitive to negative feedback inhibition. Spontaneously occurring endogenous cortisol peaks of comparable size during undisturbed sleep did not exhibit such a temporary inhibition of cortisol secretion. We hypothesize that sleep attenuates negative feedback inhibition within the HPA system, whereas wakefulness (or stage 1 sleep) reflects increased feedback sensitivity of this system.

Adrenocorticotropic Hormone↗

The vegetalizing factor from chicken embryos: its EDF (activin A)-like activity.

The erythroid differentiation capacity of the HPLC-purified mesoderm- and endoderm-inducing vegetalizing factor from chicken embryos and of recombinant erythroid differentiation factor (EDF = activin A), an evolutionary highly conserved member of the TGF-beta protein superfamily have been compared. Both factors stimulate the synthesis of hemoglobin in erythroleukemia cells in the same concentration range. The EDF-activity of the mesoderm-inducing HPLC-fractions is inhibited by follistatin, an EDF-binding protein. The factor induces in ectoderm of Triturus taeniatus all kinds of mesodermal organs. The wide spectrum of organs is very likely to be induced by secondary interactions. At higher concentration (15 ng/ml), notochord- and endoderm-like tissues are induced in a high percentage.

Activins↗

Brain evoked responses, a bioassay for central actions of adrenocorticotropin (ACTH 1-39) and corticotropin releasing hormone (CRH) in humans.

Blood borne hormones of the hypothalamus-pituitary-adrenal (HPA) axis form an afferent humoral system modulating a great variety of brain functions. In humans, bioassays consistently reflecting central nervous system actions have not been developed, so far. The present experiments are part of a series of studies which have been conducted to demonstrate the afferent influences of ACTH and CRH on brain activity by recording of auditory event-related brain potentials (ERPs) in healthy human subjects. In a double-blind within-subject comparison in 12 healthy male students, influences of 4 U ACTH and 100 micrograms CRH (infused within 2 h; the infusion starting 1 h prior to ERP recordings) were compared with the effects of a placebo infusion. Influences of the hormones were tested for the early, brain stem generated ERP components (BAEPs) and for the late components of the ERP associated with cortical stimulus processing. ACTH and CRH showed no consistent effect on BAEPs. ACTH, but not CRH, significantly reduced amplitudes of late ERP components, in particular, the Nd and P3 components which are considered signs of selective attention. These results are consistent with findings from previous studies demonstrating impaired ERP signs of selective attention in humans after administration of the 4-10 fragment of ACTH which lacks the peripheral adrenocorticotropic activity. Together with these foregoing studies, results from the present experiments further establish ERP methodology as a sensitive bioassay for CNS actions of hormones in humans.

Adrenocorticotropic Hormone↗

Gluco- and antimineralocorticoid effects on human sleep: a role of central corticosteroid receptors.

Cortisol modulates brain functions in humans. This principal endogenous glucocorticoid in humans decreases rapid-eye-movement (REM) sleep and increases slow-wave sleep (SWS). Because cortisol exerts its effect on brain functions via mineralocorticoid receptors (MR) and glucocorticoid receptors (GR), we were interested in which type of corticosteroid receptor mediates these steroid effects on sleep. Healthy men were tested in two double-blind experiments. In experiment I (n = 8), the subject's sleep was tested during four nights: 1) after pretreatment with dexamethasone (Dex, 4 mg/day) for 4 or 6 days and after additional infusion of placebo or cortisol (10 mg/h) during the experimental night, 2) after pretreatment with placebo for 4 or 6 days and after infusion of placebo or cortisol (10 mg/h) during the experimental night. In experiment II, subjects (n = 10) slept after intravenous administration of potassium canrenoate (200 mg, at 0800 and 1700 h before experimental nights) or placebo. Cortisol infusion moderately increased the percentage of SWS (P less than 0.05) and markedly decreased REM sleep (P less than 0.01); influence of cortisol on SWS did not depend on pretreatment with Dex. Dex reduced both SWS and REM sleep (P less than 0.05). Canrenoate markedly diminished SWS (P less than 0.01) but left REM sleep unaffected. The results suggest that corticosteroid-induced changes in SWS are mediated via MR-like central receptors in humans, whereas changes in REM sleep involve GR.

Adult↗

Adrenergic influences on cardiac function during ventricular fibrillation in isolated rat hearts.

Effects of norepinephrine (NE, 10(-6) M), epinephrine (E, 10(-6) M), and vehicle on coronary blood flow (CF), oxygen consumption, and lactate release were compared in 32 isolated rat hearts during 5 min of ventricular fibrillation (VF). After VF, tissue concentrations of ATP, AMP, creatinine phosphate (CP), and lactate were measured. Perfusion of treatments started 30 s after onset of VF and was maintained throughout VF. CF during VF was greater (P less than 0.005) during perfusion of E (mean +/- SE, 5.73 +/- 0.15 ml/min) than NE (5.06 +/- 0.32 ml/min) or vehicle (5.11 +/- 0.18 ml/min). Oxygen consumption during VF was higher during perfusion of E (29.5 +/- 0.9 microliters.min(-1).g wet heart wt(-1)) than vehicle (27.3 +/- 0.7 microliters.min(-1).g(-1); P less than 0.05); average oxygen consumption during NE (27.6 +/- 1.4 microliters.min(-1).g(-1)) and vehicle were comparable. After NE, but not E, tissue AMP concentrations were significantly increased, and CP concentrations were reduced compared with vehicle (P less than 0.05). Enhanced consumption of high-energy phosphates during NE suggests that there is also an enhanced demand for oxygen. However, unlike during E, during NE this demand is not met by an augmented CF. Thus, compared with E, NE treatment during VF may increase the risk of hypoxic damage.

Adenosine Monophosphate↗

Evidence for entrainment of nocturnal cortisol secretion to sleep processes in human beings.

The pulsatile patterns of cortisol release have been referred to as 'episodic' rather than 'rhythmic'. We studied plasma cortisol patterns in 31 healthy subjects during night sleep and observed a uniform ultradian rhythm. Using spectral analysis a predominant mean periodicity of 151.2 +/- 8.3 min (mean +/- SEM) was calculated for plasma cortisol oscillations, and of 118.3 +/- 4.3 min for REM sleep occurrence. The rhythmic pattern of plasma cortisol was obscured when data were averaged across subjects, due to the individual onset latencies of the initial cortisol rise. Therefore, the data were analyzed time-locked to a number of somnopolygraphic sleep events: by selecting the end of the second sleep cycle as point of reference, the ultradian rhythm was preserved. These results indicate that both sleep processes and nocturnal plasma cortisol concentrations are subject to ultradian rhythms. Both rhythms are coupled, but have different periodicities.

Adult↗

Sleep-associated augmentation and synchronization of luteinizing hormone pulses in adult men.

We reinvestigated the temporal relationship between sleep and LH secretion in healthy adult males by comparing LH secretion patterns during sleep with those during the 6 h of wakefulness preceding the sleep epoch. Sleep stages were determined by somnopolygraphy. In these subjects LH secretion was augmented during sleep as indicated by increased mean LH concentrations and increased pulse amplitudes; pulse frequency was not different. In addition, LH secretion appeared to be synchronized to the NonREM-REM sleep cycles: initiation of LH pulses occurred preferentially in the mid-portion of a NonREM-REM cycle during Non-REM sleep. Thus, REM sleep was almost uniformly associated with decreasing LH concentration. These findings demonstrate that patterns of LH secretion characteristic for early puberty are principally present also in adult males.

Adult↗

Different regulation of adrenocorticotropin and cortisol secretion in young, mentally healthy elderly and patients with senile dementia of Alzheimer's type.

Previous studies suggest that an alteration of the neuroendocrine system may particularly occur in senile dementia of Alzheimer's type (SDAT). In the present study the reactivity of the hypophyseal-adrenocortical axis (HPA) in the elderly was assessed by hormonal stimulation of the hypophysis. Twelve young men (aged 21-24 yr), 15 mentally healthy elderly (aged 65-90 yr), and 12 patients with SDAT (aged 60-84 yr) received an iv bolus injection containing 50 micrograms CRH and 0.5 IU lysine vasopressin after a baseline period of 2 h. ACTH, cortisol, and dehydroepiandrosterone secretion was monitored over a period of 2 h before and after the injection. The baseline ACTH concentrations were increased in both groups of elderly, the baseline cortisol levels were not different in either group. The peak ACTH and cortisol levels were significantly elevated in the mentally healthy elderly, whereas senile demented patients showed a rise comparable with that in the young subjects. Moreover, in the demented patients the post-stimulus decline in plasma ACTH levels seemed to be delayed. Dehydroepiandrosterone was significantly lowered in subjects of all ages. Our results demonstrate an enhanced reactivity of the HPA in mentally healthy elderly. This is possibly due to a diminished sensitivity of the feedback regulation to glucocorticoids. However, SDAT patients had, compared to healthy elderly subjects, an attenuated response to CRH/lysine vasopressin and a prolonged ACTH secretion, indicating alterations of the HPA in this disease.

Adrenocorticotropic Hormone↗

Influences of peripheral adrenocorticotropin 1-39 (ACTH) and human corticotropin releasing hormone (h-CRH) on human auditory evoked potentials (AEP).

Hormones of the hypothalamus-pituitary-adrenal (HPA) axis have been considered to form part of an efferent humoral system modulating central nervous stimulus processing. The present experiments were designed to compare the effects of iv bolus administrations of placebo, porcine ACTH 1-39 (1.5 U) and h-CRH (25 micrograms) on auditory evoked potentials (AEPs) in healthy men. Also, cardiovascular parameters, cortisol and self-reported mood were assessed. ACTH significantly reduced the amplitude of the N1 component of the AEP; P1 and P2 remained unchanged. The selective reduction of N1 amplitude defies an interpretation of the changes in terms of a reduced stimulus-induced cortical arousal following ACTH; the ACTH-induced changes may rather indicate an influence on frontocortical functions of directing attention. The effect of ACTH on N1 cannot be attributed to its adrenocorticotropic action or to cardiovascular changes, but appears to represent an intrinsic extraadrenal influence of the hormone. The data do not provide evidence for effects of h-CRH on central nervous stimulus processing in humans, after peripheral administration.

Adrenocorticotropic Hormone↗

Isolation of a vegetalizing inducing factor after extraction with acid ethanol. Concentration-dependent inducing capacity of the factor.

A vegetalizing factor has been isolated from chicken embryos by an improved method. The factor is extracted with acid/ethanol and finally purified by four consecutive steps of reversed phase HPLC. The molecular mass is about 25 kDa. The factor dissociates after reduction with dithiothreitol into two subunits of about 13 kDa. The factor was tested on Triturus alpestris by the implantation method, and on isolated ectoderm of Xenopus laevis in solution. The factor induces as the crude fractions all types of mesodermal tissues dependent on the concentration of the factor.

Acids↗

Influences of the cholecystokinin analog ceruletide on human sleep and evoked potentials.

Two experiments are reported, investigating the effects of the cholecystokinin analog ceruletide on central nervous activation in man. In experiment I, 0.55 micrograms/h ceruletide was infused at a constant rate during the night to study its effects on spontaneous EEG activity during sleep. In experiment II, we examined the effects of a bolus injection of ceruletide (0.5 micrograms) on components of the auditory evoked potential reflecting exogenously provoked central nervous arousal. While ceruletide had no effect on sleep, it attenuated stimulus-induced cortical arousal.

Adult↗

Time course of ACTH 4-10 effects on human attention.

Previous studies have demonstrated that the adrenocorticotropic hormone (ACTH) and its 4-10 fragment are potent modulators of attention in humans. In these studies the Nd component ('negative displacement') of the stimulus-evoked brain potential (event-related potential, ERP), which is a neurophysiological indicator of selective attention, proved most sensitive to effects of these peptides. The Nd decreased in amplitude linearly with logarithmically increasing doses of ACTH 4-10 applied. Here we report results complementing these previous findings by establishing a time course of the effects of ACTH 4-10 on human attention. In a double-blind cross-over study, attention performance on a dichotic listening task was tested in 18 healthy volunteers, after having received intravenously either placebo or 1 mg ACTH 4-10. Tests took place 0, 30, 90, 180, 330, 600 min, 24, 48 and 72 h after drug intake and took about 15 min. Each subject was tested on 4 of these occasions, selected according to a random schedule. During task performance ERPs to the different task stimuli were recorded. ERPs were used to determine the Nd (an indicator of controlled processing of stimuli which the subjects selectively attended to) and the mismatch negativity (MMN) reflecting automatic processing of stimulus deviance. ACTH 4-10 diminished the Nd significantly at 30 min after treatment administration. On none of the other occasions significant changes in Nd occurred. MMN was not affected by the peptide. The results indicate a short-term action of ACTH 4-10 on selective attention, which takes about 30 min to develop and does not last longer than 90 min after treatment.

Adrenocorticotropic Hormone↗

Differential effects of human and pork insulin-induced hypoglycemia on neuronal functions in humans.

Insulin has been found to cross the blood-brain barrier, and insulin receptors have been detected in different structures of the brain. However, the biological significance of insulin acting in the brain remains unclear. Reports of differential awareness of hypoglycemic symptoms during human insulin (HI)- and pork insulin (PI)-induced hypoglycemia hint at a modulatory influence of insulin on sensory processing. In a double-blind study, we recorded auditory-evoked potentials (AEPs), indexing neuronal transmission along sensory pathways, in 30 healthy male subjects during a baseline condition and HI- and PI-induced mild hypoglycemia of 2.65 mM. Fifteen subjects were tested after 20 min and another 15 after 50 min of constant hypoglycemia. During hypoglycemia, subjects had to indicate the severity of hypoglycemic symptoms and their current mood. Hypoglycemia increased latencies of the P3 component and reduced amplitudes of the N1, P2, and P3 components. Despite identical blood glucose and serum insulin levels in both sessions, effects of PI-induced hypoglycemia on AEP components were significantly stronger than those of HI-induced hypoglycemia (P less than 0.05). Differences between the effects of the insulins were consistently apparent after 20 min of hypoglycemia, indicating a short-term action of these hormones on central nervous system functions. Also, after 20 min, but not after 50 min, of steady-state hypoglycemia, subjects felt more excited during PI than HI infusion (P less than 0.05). The results indicate different influences of HI and PI on sensory function during hypoglycemia. These differences, occurring during early hypoglycemia, could contribute to the differential awareness of hypoglycemic warning symptoms during HI- and PI-induced hypoglycemia in diabetic patients.

Animals↗