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PubMed1989

Left axis deviation in healthy infants and children.

In a series of 1036 routine electrocardiograms, 14 children, without clinical and echocardiographic evidence of heart disease, showed a left axis deviation in the standard electrocardiogram. Six children also had an incomplete right bundle branch block. Left axis deviation is defined as a mean frontal QRS complex axis being -30 degrees or less. The age varied from three months to 10 years, with a clear predominance of males (13/14). The unusual finding of left QRS axis deviation in normal children is emphasized.

Bundle-Branch Block↗
PubMed1989

A step in embryonic axis specification in Xenopus laevis is simulated by cytoplasmic displacements elicited by gravity and centrifugal force.

Determination of the body pattern in Xenopus embryos is known to involve at least six steps. One of these steps can be experimentally simulated by inclining the fertilized egg with respect to gravity or centrifugal force (10-30 g x 4 min, directed 90 degrees to the animal-vegetal axis). In these eggs, the dorsal structures of the body axis form from the side of the egg that was uppermost in the gravitational or centrifugal field. This topography is seen even if the sperm entry point side (the prospective ventral side in control eggs) was uppermost. In addition, conjoined twin embryos form at very high frequencies in response to certain conditions of single or double centrifugation. Cytological analysis shows that the dorsal structures invariably form from the side(s) of the egg away from which vegetal cytoplasm was displaced. This is similar to the situation in the unperturbed egg, where the subcortical cytoplasm of the vegetal hemisphere rotates some 30 degrees relative to the surface, and the dorsal structures form from the side of the egg away from which the subcortical cytoplasm moved. The displacements elicited by centrifugation probably substitute for the normal displacements brought about by the subcortical rotation. These and other data suggest that the subcortical rotation is a crucial step in the process of axis determination. The subcortical rotation is an autonomous activity of the activated egg, and can displace cytoplasm against gravity. I believe that the subcortical rotation will function normally at microgravity, and I expect that overall development and axis polarity at microgravity will be normal. This will be tested in spaceflight.

Animals↗
PubMed1995

Effects of serotonin precursors on the negative feedback effects of glucocorticoids on hypothalamic-pituitary-adrenal axis function in depression.

In order to investigate the relationships between brain serotonergic turnover and hypothalamic-pituitary-adrenal (HPA) axis function in unipolar depression, the authors measured intact adrenocorticotropic hormone (ACTH) and cortisol levels in baseline conditions and after combined dexamethasone (1 mg PO) and L-5-hydroxytryptophan (L-5-HTP, 200 mg PO) administration in 13 minor, 17 simple major, and 17 melancholic subjects. L-5-HTP significantly enhanced post-DST ACTH and cortisol secretion in major--but not in minor--depressed subjects. Major depressed subjects with or without melancholia exhibited significantly higher post-DST ACTH and cortisol responses to L-5-HTP than minor depressed subjects. L-5-HTP administration converted some major depressed ACTH or cortisol suppressors into nonsuppressors. L-5-HTP stimulated ACTH or cortisol secretion to the same extent in major depressed HPA-axis suppressors and nonsuppressors. It is concluded that L-5-HTP loading may augment ACTH and, consequently, cortisol escape from suppression by dexamethasone in major but not in minor depressed subjects. The findings show that serotonergic mechanisms modulate the negative feedback of glucocorticoids on central HPA-axis regulation. It is hypothesized that the higher L-5-HTP-induced post-DST HPA-axis hormone responses in major depression reflect upregulated 5-HT2 receptor-driven breakthrough secretion of pituitary ACTH from suppression by dexamethasone.

Adrenocorticotropic Hormone↗
PubMed1996

Gender differences in the effect of prenatal alcohol exposure on the hypothalamic-pituitary-adrenal axis response to immune signals.

Immature (3 week old) rat offspring of alcohol (E)-fed dams show a blunted ACTH response to immune signals such as interleukin-1 beta (IL-1 beta) and endotoxin (LPS). In contrast, mature offspring respond to physical stresses with an exaggerated activation of their hypothalamic-pituitary-adrenal (HPA) axis. The present work was aimed at determining if there was a differential influence of prenatal E exposure on the HPA axis responses to various stressors or if, alternatively, sexual maturation modified these responses. When administered IL-1 beta at 5 weeks age, E-treated intact male offspring released less ACTH, compared to control (C) or pair-fed (PF) animals. However, they showed an augmented response to LPS and a local inflammatory process induced by turpentine injection. At this same age, intact E females secreted significantly more ACTH in response to IL-1 beta, LPS and turpentine, than C or PF offspring. By 9 weeks of age, both E males and E females exhibited larger (p < .05) ACTH responses to all three immune stimuli. In order to determine whether sex steroids modulate the influence of E in females, ovariectomy was done prior to puberty. This treatment decreased the difference in the ACTH released by E and C rats in response to IL-1 beta, LPS and turpentine. These results show that while immature rats exposed to E prenatally released less ACTH in response to cytokines than C or PF animals did, this response was qualitatively reversed after puberty. At that time, the larger amounts of ACTH secreted by E offspring, compared to the other groups, were reminiscent of the hyperactive response of the HPA axis when these offspring were exposed to physical stress. Interestingly, removal of circulating ovarian steroids prevented the influence of E from being exerted. This suggests the presence of a functional relationship between the pathways influenced by prenatal E and those influenced by female sex steroids, that are important in regulating the activity of the HPA axis.

Acute-Phase Reaction↗
PubMed1994

Uniform irradiation of the craniospinal axis with a penumbra modifier and an asymmetric collimator.

PURPOSE: A technique is described that uses an independent, asymmetric collimator and a penumbra modifier to uniformly administer radiation over the craniospinal axis. METHOD AND MATERIALS: An isocenter is used at the junction of the cranial and the upper spinal fields. These fields are defined by a single isocenter at spinal cord depth and an independent, asymmetric collimator. From the isocenter, the cranial and upper spinal fields are extended 1 cm inferiorly and superiorly, respectively. A modifier provides a 2-cm wide penumbra at the central axis of the beam (overlapping region) and is attached to a wedge tray in an accessory slot. This modifier allows the fields to be matched so a uniform dose is delivered over the isocenter and junction. Dose distribution was measured with an anthropomorphic head-and-neck wax phantom that included the seventh cervical vertebrae. A film was placed in a coronal cut at the spinal cord level. RESULTS: The administered dose varied less than 10% through the craniospinal axis. Reproducibility with portal films has been very good. Advantages include dose homogeneity, easy reproducibility, and decreased setup time. CONCLUSION: This single-field isocentric technique allows more uniform irradiation of the craniospinal axis than do previously described techniques.

Head and Neck Neoplasms↗
PubMedDate not supplied

In-plane flow velocity quantification along the phase encoding axis in MRI.

In-plane flow quantification in MRI offers the potential for assessing vessel patency, and both volume flow rate and flow velocity. These techniques will have definite future impact on MR angiography. The method used in this paper employs motion artifact suppression technique (MAST) gradients to refocus spins travelling along any of the three imaging axes while encoding the velocity component along the phase encoding axis. This method has several advantages over in-plane flow quantification along the read axis. Primarily, flow voids due to complete spin dephasing can be eliminated (or reduced), wider velocity limits can be measured, and gradients can be designed which are sensitive to only velocity along the phase axis with no additional effect from higher order derivatives, or motion along the read axis. Flow phantom studies, carried out on 19 mm inside diameter glass tubes, have produced accurate results for flow rates ranging from 0.6 gallons per minute (GPM) to 2.5 GPM, corresponding to a mean velocity range from 13.2 cm/sec to 55.3 cm/sec. Reynolds numbers varied from 2,700 to 11,500. Errors were less than or equal to 8% over the range of flow rates studied.

Blood Flow Velocity↗
PubMed1995

Axis formation in zebrafish.

Recent advances in our understanding of axis formation and patterning in zebrafish relate the developmental mode of this aspiring genetic model organism to higher vertebrates. The effect of UV irradiation and lithium treatment, as well as detailed early lineage analyses, have shed some light on dorsoventral axis formation. However, the molecular mechanism of axis formation, as well as the identity of a fish Nieuwkoop center, are still open issues. A Vg1 homolog is expressed in zebrafish, and activin as well as the mouse nodal gene product have been demonstrated to induce mesoderm and ectopic axes, respectively, in zebrafish. The zebrafish organizer is defined by the expression domains of goosecoid, axial, and lim1. The cyclops gene is involved in maintaining goosecoid expression in axial mesoderm of the head. Large mutagenesis screens provide the basis for a genetic analysis of axis formation.

Animals↗
PubMed2004

The triglyceride-high-density lipoprotein axis: an important target of therapy?

Coronary heart disease is the single largest cause of morbidity and mortality in the United States. The link between elevated low-density lipoprotein cholesterol (LDL-C) levels and coronary heart disease (CHD) has been clearly established. However, triglycerides (TG) are increasingly believed to be independently associated with CHD, while high-density lipoprotein cholesterol (HDL-C) is inversely associated with CHD risk. High TG and low HDL often occur together, often with normal levels of LDL-C, and can be described as abnormalities of the TG-HDL axis. This lipid abnormality is a fundamental characteristic of patients with the metabolic syndrome, a condition strongly associated with the development of both type 2 diabetes and CHD. Patients with high TG and low HDL-C should be aggressively treated with therapeutic lifestyle changes. For high-risk patients, lipid-modifying therapy that specifically addresses the TG-HDL axis should also be considered. Current pharmacologic treatment options for such patients include statins, fibrates, niacin, fish oils, and combinations thereof. Several new pharmacologic approaches to treating the TG-HDL axis are currently being investigated. More clinical trial data is needed to test the hypothesis that pharmacologic therapy targeting the TG-HDL axis reduces atherosclerosis and cardiovascular events.

Cholesterol, HDL↗
PubMed2005

Effects of surgical stress on brain prostaglandin E2 production and on the pituitary-adrenal axis: attenuation by preemptive analgesia and by central amygdala lesion.

Surgical stress is the combined result of tissue injury, anesthesia, and postoperative pain. It is characterized by elevated levels of adrenocorticotropin (ACTH), corticosterone (CS), and elevated levels of prostaglandin E2 (PGE2) in the periphery and in the spinal cord. The present study examined the effects of perioperative pain management in rats undergoing laparotomy on serum levels of ACTH, CS, and on the production of PGE2 in several brain regions, including the amygdala. The amygdala is known to modulate the pituitary-adrenal axis response to stress. We, therefore, also examined the effects of bilateral lesions in the central amygdala (CeA) on laparotomy-induced activation of the pituitary-adrenal axis in rats. In the first experiment, rats either underwent laparotomy or were not operated upon. Half the rats received preemptive analgesia extended postoperatively, the other received saline. ACTH, CS serum levels, and ex vivo brain production of PGE2 were determined. In the second experiment, rats underwent bilateral lesions of the CeA. Ten days later, rats underwent laparotomy, and ACTH and CS serum levels were determined. Laparotomy significantly increased amygdala PGE2 production, and CS and ACTH serum levels. This elevation was markedly attenuated by perioperative analgesia. Bilateral CeA lesions also attenuated the pituitary-adrenal response to surgical stress. The present findings suggest that the amygdala plays a regulatory role in mediating the neuroendocrine response to surgical stress. Effective perioperative analgesia attenuated the surgery-induced activation of pituitary-adrenal axis and PGE2 elevation. The diminished elevation of PGE2 may suggest a mechanism by which pain relief mitigates pituitary-adrenal axis activation.

Adrenal Cortex Hormones↗
PubMed2006

Effect of subdiaphragmatic vagotomy on the noradrenergic and HPA axis activation induced by intraperitoneal interleukin-1 administration in rats.

The vagus nerve is thought to participate in signal transduction from the immune system to the CNS. The role of the vagus in the physiological, behavioral and neurochemical responses to intraperitoneally (ip) injected interleukin-1beta (IL-1beta) was studied using awake subdiaphragmatically vagotomized rats. The rats were injected ip with saline and IL-1beta (1 microg/rat) in random order. For the next 2-4 h, they were monitored for locomotor activity, body temperature via abdominally implanted telethermometers, hypothalamic norepinephrine (NE) secretion using in vivo microdialysis and blood sampled via intravenous catheters to determine concentrations of ACTH and corticosterone to assess hypothalamo-pituitary-adrenocortical (HPA) axis activation. Saline injections were followed by transient increases in locomotor activity, body temperature, dialysate NE and plasma concentrations of ACTH and corticosterone. These responses were not significantly altered by vagotomy. IL-1beta injections resulted in short-lived increases in shivering and longer decreases in locomotor activity, as well as a delayed modest fever. IL-1beta also induced prolonged elevations of hypothalamic microdialysate NE, as well as plasma ACTH and corticosterone. Similar responses were observed regardless of the order of the saline and IL-1beta injections. Subdiaphragmatic vagotomy prevented the IL-1-induced increases in body temperature and the increase in dialysate NE, and markedly attenuated the increases in plasma ACTH and corticosterone. The results indicate close temporal relationships between the apparent release of NE and the increase in body temperature and the HPA activation. This together with the effects of vagotomy suggests that the activation of NE in turn increases body temperature and activates the HPA axis. However, because IL-1beta induces a limited HPA activation in subdiaphragmatically vagotomized rats, the vagus nerve does not appear to be the only route by which ip IL-1beta can activate the HPA axis. It is suggested that IL-1beta-induced vagal activation of hypothalamic NE is the major mechanism of HPA activation at low doses of IL-1beta. However, IL-1beta can also exert direct effects on IL-1 receptors on cerebral blood vessels, activating cyclooxygenases and hence synthesis of prostaglandins which in turn can affect body temperature, behavior and HPA axis activation.

Adrenocorticotropic Hormone↗
PubMed2004

Rat estrous cycle influences the sexual diergism of HPA axis stimulation by nicotine.

We previously reported that female rats had significantly greater hypothalamic-pituitary-adrenal (HPA) axis responses to cholinergic stimulation by nicotine (NIC) than did male rats. Females in defined estrous cycle stages, however, were not studied because of sample size limitations. We further explored this finding by determining HPA axis responses to two doses of NIC in female rats (N = 101) during different estrous cycle stages, and in males (N = 69). NIC doses were: 0.3 mg/kg, which provided the greatest female-male difference in the earlier study, and 0.5 mg/kg, which stimulated the HPA axis similarly in the two sexes. Plasma AVP, ACTH, and corticosterone were measured. Proestrous and estrous females had higher ACTH responses to NIC (0.3 mg/kg) compared to metestrous and diestrous females, and compared to males. ACTH responses to NIC (0.5 mg/kg) were similar, regardless of estrous cycle stage or sex. Males had higher AVP responses to both NIC doses compared to females in all estrous cycle stages. Corticosterone responses followed the ACTH responses, except that females in all estrous stages started from a higher corticosterone baseline compared to males. These results are similar to our earlier findings across the estrous cycle with non-specific cholinergic stimulation by physostigmine and suggest that the nicotinic system contributes to the differential HPA axis responses to cholinergic challenge across the estrous cycle.

Acetylcholine↗
PubMed2004

Role of noradrenergic projections to the bed nucleus of the stria terminalis in the regulation of the hypothalamic-pituitary-adrenal axis.

The bed nucleus of the stria terminalis (BNST) plays an important role in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis during stress and it is a major extrahypothalamic relay to the paraventricular nucleus of the hypothalamus (PVN) from the amygdala and the hippocampus. In this review, we discuss the anatomical, neurochemical and behavioral evidence that substantiate a role for noradrenergic terminals of the anterior BNST in the regulation of the HPA axis. We propose the hypothesis that BNST noradrenaline (NA) participates in the regulation of the hippocampal inhibitory influence on the HPA axis activation. The observation that NA exerts a tonic inhibitory effect upon glutamatergic transmission in the anterior BNST supports this hypothesis. We also discuss the known mechanisms involved in the regulation of BNST NA extracellular levels and the possible interactions between NA and corticotropin-releasing hormone (CRH), and of CRH with glutamate (GLU) in the regulation of the HPA axis activity exerted by the BNST. The evidence discussed in the present review situates the BNST as a key extrahypothalamic center that relays and integrates limbic and autonomic information related to stress responses suggesting that dysregulation in the functioning of the BNST may underlie the pathophysiology of stress-related psychiatric disorders.

Animals↗
PubMed2006

Changes within the GH/IGF-I/IGFBP axis in critical illness.

Interest in the somatotropic axis, with its complex network of interactions, during critical illness started only a few decades ago. The distinguished neuroendocrine features of prolonged critically ill patients were not differentiated from those during the acute phase until the 1990s. This incomplete understanding of the somatotropic axis has contributed to some disastrous results. Aiming to stimulate the somatotropic axis without a proper preceding neuroendocrine diagnosis should be held obsolete, because recent data indicate that the patient with the best anabolic parameters may not necessarily be the most favored to survive the ICU stay. Moreover, the fascinating link between regulators of carbohydrate metabolism, such as insulin and insulin-like growth factor 1, and the somatotropic axis may lead to future therapeutic possibilities.

Critical Illness↗
PubMed2006

New small-scale cross-axis coil planet centrifuge. The design of the apparatus and its application to counter-current chromatographic separation of proteins with aqueous-aqueous polymer phase systems.

The cross-axis coil planet centrifuge (X-axis CPC) is useful for partitioning macromolecules with aqueous-aqueous polymer phase systems. The floor model we have built with a pair of separation columns had some shortcomings such as requirement of large space, short life of the flow tubes, and difficulty in installing columns. In order to improve the partition efficiency and the utility of counter-current chromatography (CCC), a new small-scale X-axis CPC was designed and fabricated in our laboratory. The down-sizing of the apparatus was done by reducing the scale to about 1/2 of our original model of X-1.5L type with several improvements. Performance of the apparatus was evaluated on protein separation using an aqueous-aqueous polymer phase system composed of polyethylene glycol 1000 and dibasic potassium phosphate with four multilayer coiled columns. A series of experiments revealed that the combination of right- and left-handed coils produced the best partition efficiencies for both lower and upper mobile phases by selecting the revolution direction. The overall results indicate that the head-tail elution mode substantially affects to the peak resolution and stationary phase retention. This new X-axis CPC would be useful for the separation of various kinds of biologically active compounds.

Centrifugation↗
PubMed2004

Ontogeny of the hypothalamo-pituitary-adrenocortical axis in the chicken embryo: a review.

The embryo of the domestic fowl (Gallus domesticus) tenders one distinctive advantage over general mammalian models for investigating the development of the hypothalamo-pituitary-adrenocortical (HPA) axis. This is the relative simplicity with which the embryonic endocrine environment can be influenced without confounding maternal influences. The ease of direct manipulation of the embryonic endocrine system has facilitated analysis of the development and function of the HPA axis in the chick embryo. As the chick embryo develops, functional activation of the adrenal gland is regulated at three different levels: the adrenal gland itself, the anterior pituitary, and the hypothalamus. The adrenal gland appears capable of independent secretion of glucocorticoids from day 8 until shortly after day 14 of embryonic development, at which point the pituitary influences adrenocortical activity. Around the same age, the hypothalamic level of control also begins. The information covered in this review will describe the major steps in the development of the HPA axis in the chicken embryo and show that the chicken has an emblematic HPA neuroendocrine axis.

Adrenal Cortex↗
PubMed2004

Molecular genetic and physiologic background of the growth hormone-IGF-I axis in relation to breeding for growth rate and leanness in pigs.

The GH-IGF-I axis is of major importance for the regulation of body growth and composition, and cellular proliferation and differentiation processes. Selective breeding aiming to improve growth rate and/or body composition is accompanied by changes of the GH-IGF-I axis. Research aiming to elucidate the genetic and physiologic mechanism(s) underlying these changes may best use single-trait selection lines. Two such pig selection lines, one for growth rate and one for high lean content, were used in experiments to investigate the mechanisms of the GH-IGF-I axis change during selection. This contribution reviews the selection-related changes in the GH-IGF-I axis as the consequences of selection for whole body growth rate or body composition and effects on local tissue growth rate. A model explaining the observed effects and consequences for the pressure on the physiology is presented. In short, selection related demand for GH induces GH synthesis until a limit is reached. After that the pulsatile GH plasma profile changes, which may also affect expression profiles of genes regulating body composition.

Animal Husbandry↗
PubMed2006

Changes within the growth hormone/insulin-like growth factor I/IGF binding protein axis during critical illness.

Interest in the somatotropic axis,with its complex network of interactions, during critical illness arose only a few decades ago. Te distinguishing neuroendocrine features of prolonged critical illness were not differentiated from those during the acute phase until the early 1990s. This incomplete understanding of the somatotropic axis contributed to some disastrous results, such as the multicenter growth hormone trial. The goal of stimulating the somatotropic axis without a proper preceding neuroendocrine diagnosis should be held obsolete. Moreover, the fascinating link between regulators of carbohydrate metabolism, such as insulin and insulin-like growth factor I, and the somatotropic axis may lead to future therapeutic possibilities.

Critical Illness↗
PubMed2005

Expression of the endothelin axis in bladder cancer: relationship to clinicopathologic parameters and long-term survival.

OBJECTIVES: Endothelin-1 (ET-1) and its receptors ET(A)R and ET(B)R, referred to as the Endothelin-axis, play an emerging role in cancer. We examined the ET-axis immunohistochemically in invasive bladder cancer. METHODS: Tumor specimens from 157 patients after cystectomy were stained immunohistochemically for ET-1, ET(A)R and ET(B)R. After semiquantitative analysis the staining results were correlated with clinicopathological parameters and survival rates. RESULTS: Overexpression of ET-1, ET(A)R and ET(B)R was identified in 26.8%, 58.8% and 76.9% of cases, respectively. No association with TNM staging and histologic grading was found. However, patients with ET(B)R expression tended to have organ-confined tumors (p=0.16) and no vascular invasion (p=0.09), the latter being statistically significant in the subgroup of G3 tumors (p=0.02). ET(B)R overexpression was associated with favorable disease-free survival (p=0.04). CONCLUSIONS: The ET-axis is overexpressed in bladder cancer, ET(B)R predominating in this entity and being associated with a more favorable prognosis. Further studies are warranted to elucidate the role of the ET-axis as a molecular target in bladder cancer.

Adult↗