Immaturity of medullary cardiorespiratory neurones leading to inappropriate autonomic reactions as a likely cause of sudden death in Rett's syndrome.
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Biomedical subjects
Publications and source records attributed to S Hansen.
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We report a symptomatic failure of the baroreceptor blood pressure (BP) buffering mechanism in a woman with familial aniridia. Her baseline BP oscillated at 0.1 Hz, the frequency of Mayer waves, with increased amplitude on standing without orthostatic hypotension. Although sudomotor function was normal, cutaneous thermoregulatory function and BP response to Valsalva's maneuver were abnormal. The defective BP buffer mechanism suggests Mayer waves could be a sympathetic mediated cardiovascular resonance. Baroreceptor cardioinhibition was intact. We presume that the lesion is in the rostral aspect of the dorsal medulla oblongata.
BACKGROUND: To date, the intraindividual reproducibility of fasting and postprandial gallbladder (GB) volumes has not been established satisfactorily. Hence we examined the variability of postprandial GB motility, using the biplane Simpson method as a new sonographic tool for GB volume determination. METHODS: The biplane Simpson method was validated in vitro and in vivo and compared with the sum-of-cylinders method. Thereafter, postprandial GB emptying after a defined test meal was examined in 10 healthy volunteers over 108 min on days 1, 31, and 61. RESULTS: The results of the biplane Simpson method correlated with real volumes (r = 0.99) and provided a intra- and inter-observer variation of less than 5%. Intraindividually, differences in fasting GB volume ranged from 1.9 to 24.0 ml within the observation period. The patterns of GB emptying also showed fluctuations characterized by a rather large interindividual and intraindividual variability. CONCLUSIONS: The biplane Simpson method is a reliable tool for measuring GB volumes. The fasting and the postprandial GB volumes vary considerably within individuals when measured over a period of 2 months.
Autonomic activity and respiration were studied in Rett syndrome (RS) and age matched controls. Breathing movements were monitored using a pletysmograph around the chest. Sympathetic activity was monitored by measuring blood pressure (BP) using the Finapres. Cardiac parasympathetic activity was monitored by measuring the cardiac response to baroreflex using the NeuroScope which outputs measure of cardiac vagal tone (CVT) in units of a linear vagal scale (LVS). Resting CVT (means +/- SEM) was 10.5 +/- 0.9 units in the LVS and BP was 94.6 +/- 6.4 mmHg in controls. The BP was 78 +/- 4.33 mmHg and CVT was 3.6 +/- 0.7 units in the LVS in girls with RS, 65% lower than in their age matched controls (p < 0.001), but equal to previously reported level in neonates. Each girl with RS had at least 6 types of breathing dysrhythmias, a sign of instability of the respiratory oscillator. The sympathetic system controlled the HR and BP smoothly during breath holding in control girls, but there were oscillations and rebounds in RS. The HR and BP were under parasympathetic influence during hyperventilation in normal girls but not in RS. The CVT was invariably withdrawn at the height of sympathetic activity during both hyperventilation and breath holding in RS, leading to sympathovagal imbalance with the risk of cardiac arrhythmias and possibly sudden death. Neonatal level of CVT, poor autonomic integration and multiple breathing dysrhythmias shows medullary immaturity in RS. It is the first demonstration of immaturity of the brain which could be used for screening in early childhood and potentially useful for diagnosis and management of RS.
Anterolateral approach to the lumbar spine using a retroperitoneal approach is a common technique. But conventional approaches are performed laterally, resulting in parietal muscular damage, which may alter functional results. The authors present their experience about a minimized pararectal retroperitoneal approach from T12 to S1. Some anatomical aspects are important for a safe and reproductive procedure. The authors used mainly this technique in association with posterior correction and fixation in traumatic and degenerative pathologies. They point out the simplicity of this technique which is performed without special equipment. It seems a real alternative to laparoscopic techniques and micro-surgical antero-lateral interbody fusion, especially because of minimal potential complications and low post operative morbidity.
Activation of the latent DNA binding function of human p53 protein by the bacterial Hsp70, DnaK, represents a unique reaction in which a heat shock protein can interact with a native protein to affect its function. We have localized a likely DnaK interaction site on native human p53 tetramers to a motif flanking the COOH-terminal casein kinase II and protein kinase C phosphorylation sites. Murine p53 is less efficiently activated by DnaK, which has permitted a search for factors that might cooperate in p53 activation by DnaK. We show that optimal activation by DnaK may be dependent upon the phosphorylation state of murine p53, in particular, modification of p53 at the cdc2 phosphorylation site by point mutation decreases the extent of activation by DnaK. Additionally, the monoclonal antibody PAb241, binding in the vicinity of the cdc2 phosphorylation site, is able to activate the specific DNA binding function of p53. This has led us to propose a second regulatory motif flanking the tetramerization domain of p53 that cooperates with factors binding at the negative regulatory domain in the extreme COOH terminus.
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Conformational stability is a prerequisite for the physiological activity of the tumor suppressor protein p53. p53 protein can be allosterically activated for DNA binding by phosphorylation or through noncovalent interaction with proteins such as DnaK, the Escherichia coli homologue of the heat shock protein Hsp70. We present in vitro evidence for a rapid temperature-dependent change in the conformation and tetrameric nature of wild-type p53 upon incubation at 37 degrees C, which correlates with a permanent loss in DNA binding activity. We show that p53 is allosterically regulated for stabilization of the wild-type conformation and DNA binding activity at 37 degrees C by binding of two classes of ligands to regulatory sites on the N and C terminus of the molecule through which an intrinsic instability of p53 is neutralized. Deletion of the domain conferring instability at the C terminus is sufficient to confer enhanced stability to the total protein. DnaK binding to the C terminus can profoundly protect p53 at 37 degrees C from a temperature-dependent loss of the DNA binding activity but does not renature or activate denatured p53. In contrast, another activator of the DNA binding activity of latent p53, the monoclonal antibody PAb421, which also interacts with the C terminus of the protein, is not able to protect p53 from thermal denaturation. Two monoclonal antibodies to the N terminus of p53, PAb1801 and DO-1, do not activate the latent DNA binding function of p53 but can protect the p53 wild-type conformation at 37 degrees C. Thus, activation of the DNA binding function of p53 is not synonymous with protection from thermal denaturation, and therefore, both of these pathways may be used in cells to control the physiological activity of p53. The protection of p53 conformation from heat denaturation by interacting proteins suggests a novel mechanism by which p53 function could be regulated in vivo.
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The present study assessed personality traits in three groups of strength athletes, who self-administered anabolic androgenic steroids (AAS) at the time of testing, had stopped using AAS since at least 6 months, or had never used AAS. The subjects (n = 14/group) completed the Karolinska Scales of Personality, an inventory consisting of 15 subscales measuring traits related to anxiety proneness, extraversion, and aggression-hostility. Current AAS users differed significantly from the other two groups with respect to Verbal aggression. In comparison to subjects with no ongoing AAS exposure (i.e., previous AAS users and drug-free controls), AAS users were also significantly different with respect to Muscular tension, Social desirability, Impulsiveness, and Indirect aggression. On several subscales, the scores of the AAS users were clearly outside the normal range observed in general population. The present results confirm earlier studies that AAS use is associated with enhanced aggressiveness. Our study also suggests that self-administration of AAS might pave the way for disinhibitory psychopathology by amplifying extraversion-related risk factors.
Male Wistar rats bearing intracerebroventricular (ICV) cannulae and with simultaneous access to 6% ethanol and water were subjected to adrenalectomy (ADX) or sham surgery. ADX decreased ethanol intake. Starting a few days later, the animals received ICV infusions with 100 micrograms corticosterone acetate (CORT) with 2-to 3-day intervals for 2 weeks. ICV CORT, but not SC CORT at the same dose, restored ethanol consumption in ADX rats to preoperative levels, whereas vehicle infusions (propylene glycol) did not. Adrenally intact animals, which normally consumed moderate amounts of ethanol (approximately 0.5 g/kg per day), also showed a robust effect of ICV infusions of CORT, whereas this facilitatory effect was not observed in high consumers (approximately 3.0 g/kg per day). The suppressive effect of ADX on ethanol intake was not reproduced by concurrent and repeated ICV infusions of intracellular mineralocorticoid (RU 28318) and glucocorticoid (mifepristone) receptor blockers. It is concluded that CORT stimulates alcohol consumption by acting in the brain, probably by way of neuronal membrane mechanisms.
OBJECTIVE: The complement system has been suggested to play a role in reperfusion injury which may result from an enhanced destruction of myocardial tissue or from an impairment of reflow. We investigated the influence of the C5b-9 complement complex on infarct size, reflow and arrhythmogenesis. METHODS: Twenty-eight C6-competent rabbits and 18 rabbits with congenital C6 deficiency were subjected to either 30 min or 2 h of coronary artery occlusion followed by reperfusion. C6 deficiency was confirmed by the complement titration test and immunohistology. The triphenyl tetrazolium chloride method was used to delineate infarct size. Reflow into infarcted areas was evaluated histologically after an in vivo injection of propidium iodide which served as an early fluorescence microscopic marker of damaged myocardium subjected to reflow. Continuous ECG monitoring allowed the recording of arrhythmias. RESULTS: After 30 min of coronary artery occlusion infarct size was significantly smaller in C6-deficient rabbits (5.0 +/- 2% of the risk region) as compared to C6-competent rabbits (28.4 +/- 8.5%, P = 0.0371). The extent of reflow into damaged myocardium was nearly the same in both animal groups at this time (38 +/- 9 vs. 39 +/- 7% of the risk region). After 2 h of coronary artery occlusion, infarct size was not different between both animal groups, but the extent of reflow into damaged myocardium was significantly smaller in C6-competent rabbits than in C6-deficient rabbits (25 +/- 4 vs. 40 +/- 4%; P = 0.0185). Two of the 18 C6-deficient rabbits had ventricular arrhythmias (Lown II-IV), none of which was fatal. Eleven of the 28 C6-competent animals had major ventricular arrhythmias which were fatal in 6 rabbits. CONCLUSIONS: These results suggest that the lytic C5b-9 complement complex leads to reperfusion injury in the early phase (30 min) of ischaemia, resulting in a larger infarct. After 2 h of ischaemia, complement activation enhances the no-reflow phenomenon but does not affect infarct size. Finally, the C6 status seems to influence the susceptibility to ventricular arrhythmias after coronary artery occlusion, independent of reperfusion.
Given the conspicuous association between aggressive antisocial traits and alcoholism in men, we investigated whether or not a link between defensive aggressive behavior and homecage alcohol consumption could be demonstrated in the laboratory rat. This was accomplished by observing ethanol intake and hyperreactivity towards the experimenter in rats made hyperdefensive by brain lesions. Rats with medial hypothalamic electrocoagulations showed a remarkable degree of hyperdefensiveness, lasting throughout the entire 6-week postoperative period. Alcohol intake, on the other hand, was not different from sham-operated controls when the beverage was offered as a plain 6% solution or in a 0.2% saccharin vehicle. When subjected to the stress of food restriction, which enhances ethanol intake in normal rats, medial hypothalamic subjects actually decreased their alcohol consumption. Electrolytic lesions in the dorsal and median raphe brought about a transient increase in defensive aggression, but no alteration in ethanol drinking. Animals with ibotenic acid-induced extensive lesions to the ventral striatum and septal area were not only viciously aggressive, but also drank considerably more alcohol than controls. Ibotenic acid-lesioned rats did not respond to the saccharin or food-restriction conditions by increasing their alcohol intake further, perhaps because they drank at a maximal rate already during the plain ethanol-phase of the experiment. These observations show that basal forebrain dysfunction in the rat can give rise to excessive alcohol intake and heightened aggression, a constellation of behavioral symptoms observed in male type 2 alcoholics.
BACKGROUND: We reported in a recent study that parity was inversely related to the incidence of Hodgkin's disease (HD) in Norwegian women younger than 56. In this study, another data set was used to estimate the parity effects on incidence at higher ages, and two different data sets were used to assess how parity influences prognosis. METHODS: Multiplicative hazard models were estimated for incidence. A novel approach, based on mixed additive-multiplicative mortality hazard models, was used to assess differences in prognosis. The analysis was based on register and census data. RESULTS: There was no effect of parity within marriage on HD incidence in women aged 40-80. With respect to prognosis, parity was found to have a beneficial influence in the age group 15-56. Excess mortality among two-child mothers with HD compared to otherwise equal two-child mothers without HD, was significantly lower than the corresponding excess mortality among childless women. However, the same pattern appeared for men. By contrast, there were strong indications of an increase in excess mortality from HD across marital parity for women aged 40-80. CONCLUSION: The results lend support to the view that childbearing confers no long-term protection, but the evidence is far from clear. The physiological processes triggered by pregnancies do not seem to have a beneficial effect on survival. Childbearing before diagnosis may influence prognosis in men as well as women through social or emotional factors, and may also be related to prognosis because of parity-differentials in the general physical constitution. In addition, there is likely to be a positive selection of individuals who want to and are able to have a child after diagnosis.
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In a pilot study, 14 Gulf War veterans were randomly selected from a large list of those with unexplained illness, to compare the functional integrity of the peripheral and central nervous system with a group of 13 healthy civilian control subjects using predetermined outcome measures. The controls were matched closely for age, sex, handedness, and physical activity. Outcome measures included scoring of symptoms and clinical neurological signs, quantitative sensory testing of heat, cold and vibration sensibilities, motor and sensory nerve conduction studies on upper and lower limbs, needle EMG of distal and proximal muscles and multimodality evoked potential (visual, brainstem, and somatosensory) studies. Three measurements, all related to peripheral nerve function (cold threshold (P = 0.0002), sural nerve latency (P = 0.034), and median nerve sensory action potential (P = 0.030) were abnormal in the veterans compared with the controls. There may be a dysfunction in the veterans but more studies are required to investigate the findings further and to characterise the dysfunction if confirmed.