Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “AXIS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 649 records · Page 36Linked to original sources
PubMed2001

Assessment of left ventricular long axis contraction can detect early myocardial dysfunction in asymptomatic patients with severe aortic regurgitation.

OBJECTIVE: To identify variables that could be applied at rest to diagnose subclinical ventricular dysfunction in asymptomatic patients with severe aortic regurgitation. DESIGN: Cross sectional study. PATIENTS: Left ventricular long axis contraction was studied using tissue Doppler and M mode echocardiography in 21 patients with no symptoms (New York Heart Association (NYHA) functional class </= 2a) but severe aortic regurgitation (jet area/left ventricular outflow tract area > 40%). MAIN OUTCOME MEASURES: Left ventricular ejection fraction (LVEF) at baseline and peak exercise (Weber protocol), cardiopulmonary function, and left ventricular long axis function at rest (peak systolic velocity and excursion of the mitral annulus). RESULTS: In 11 patients, ejection fraction increased or did not change (from mean (SD) 55 (5)% to 58 (4)%, p < 0.05) (group I); in 10 patients it decreased by > 5% (from 54 (4)% to 42 (5)%, p < 0.001) (group II). Exercise ejection fraction was < 50% in all patients in group II. At rest, there were no differences between the groups in ejection fraction, left ventricular diameter indices, wall stress, and short axis contraction. However, patients in group II had reduced long axis contraction compared with group I: peak systolic velocity 8.6 (0.6) v 11.9 (2.2) cm/s (p < 0.001); excursion 11 (2) v 14 (2) mm (p < 0.01). A resting velocity of < 9.5 cm/s was the best indicator of poor exercise tolerance (sensitivity 90%, specificity 100%). CONCLUSIONS: Markers of reduced long axis contraction may provide simple and reliable indices of subclinical left ventricular dysfunction in asymptomatic patients with severe aortic regurgitation.

Adult↗
PubMed2005

Assessment of regional left ventricular function: accuracy and reproducibility of positioning standard short-axis sections in cardiac MR imaging.

The assessment of regional left ventricular (LV) function with cardiac magnetic resonance (MR) cine techniques requires a standardized section positioning. A simple selective short-axis method for selective positioning of three short-axis sections (basal, midcavity, apical) was tested for its accuracy, compared with accepted criteria, in 21 volunteers (mean age, 32 years +/- 11) and in 23 patients with myocardial infarction (mean age, 56 years +/- 12). Reproducibility of section positioning and of regional LV parameters was tested in the volunteers. Among the six accuracy criteria defined for standard sections, the selective short-axis approach had an average accuracy of 90.9% in volunteers and 87.7% in patients, compared with 92.1% and 90.6%, respectively, for a multisection approach covering the whole LV. There was very good reproducibility of the selected intersection gap (r = 0.89, P < .001) and of measured midcavity end-diastolic diameters in vertical (r = 0.83, P < .001) and horizontal (r = 0.85, P < .001) long-axis orientations. The proposed method produces standardized short-axis section positions that meet the recommendations for cardiac imaging. The study was approved by the local ethics committee, and all subjects gave written informed consent.

Adult↗
PubMed1993

Floating axis does not reduce motion artifacts in a model of left ventricular wall motion in dogs.

Methods of measuring regional wall motion of the left ventricle superimpose end-diastolic and end-systolic images. Differences in dimensions between images are assumed to be due to contraction, but they are also due to motion artifacts. To determine whether the errors caused by motion artifacts are reduced when measured with floating-axis referencing, and whether the measurement method affects these errors, we simulated end-systolic angiograms of a pure contraction (control) and contractions affected by motion artifacts and then measured differences in wall motion between angiograms with hemichord, radial, and trapezoid methods, using floating-axis and fixed-axis referencing. We chose these three methods because they form the basis for other methods, e.g., the center line method. For the simulations, we applied deformation patterns of the left ventricle, computed from the motion of tantalum markers implanted in the endocardiums of six dogs, to end-diastolic angiograms. This marker method measured the myocardial wall motion directly, independent of the angiogram. We found that differences caused by motion artifacts were not significantly reduced when measured with floating-axis referencing in our model. Normalized differences measured by radial and trapezoid methods were not significantly different, but they were significantly smaller than those measured by the hemichord method. We conclude that the axis referencing system has no significant effect on errors caused by motion artifacts in regional wall motion in our model. The measurement method, however, does affect these errors, with the radial and trapezoid methods being superior to the hemichord method.

Animals↗
PubMed1999

Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: actions and mechanisms of action.

Glucocorticoids are hormone products of the adrenal gland, which have long been recognized to have a profound impact on immunologic processes. The communication between immune and neuroendocrine systems is, however, bidirectional. The endocrine and immune systems share a common "chemical language," with both systems possessing ligands and receptors of "classical" hormones and immunoregulatory mediators. Studies in the early to mid 1980s demonstrated that monocyte-derived or recombinant interleukin-1 (IL-1) causes secretion of hormones of the hypothalamic-pituitary-adrenal (HPA) axis, establishing that immunoregulators, known as cytokines, play a pivotal role in this bidirectional communication between the immune and neuroendocrine systems. The subsequent 10-15 years have witnessed demonstrations that numerous members of several cytokine families increase the secretory activity of the HPA axis. Because this neuroendocrine action of cytokines is mediated primarily at the level of the central nervous system, studies investigating the mechanisms of HPA activation produced by cytokines take on a more broad significance, with findings relevant to the more fundamental question of how cytokines signal the brain. This article reviews published findings that have documented which cytokines have been shown to influence hormone secretion from the HPA axis, determined under what physiological/pathophysiological circumstances endogenous cytokines regulate HPA axis activity, established the possible sites of cytokine action on HPA axis hormone secretion, and identified the potential neuroanatomic and pharmacological mechanisms by which cytokines signal the neuroendocrine hypothalamus.

Animals↗
PubMed2000

Activation of the hypothalamic-pituitary-adrenal axis in IL-1 beta-converting enzyme-deficient mice.

Interleukin-1beta (IL-1beta) plays a key role in immune, behavioral and neuroendocrine responses to inflammation or infection. IL-1beta could also be involved in the response of the hypothalamic-pituitary-adrenal (HPA) axis during stress. Mature IL-1beta derives from a 31-kD precursor (pro-IL-1beta) that is processed by IL-1beta-converting enzyme (ICE). Mice in which the ICE gene has been nullated by homologous recombination were used to investigate the role of IL-1beta in the HPA axis response. Plasma levels of corticosterone and adrenocorticotropic hormone (ACTH) in response to an intraperitoneal injection of 5 microg lipopolysaccharide (LPS) were similar in ICE-deficient mice and wild-type (WT) controls. In contrast, plasma ACTH response to restraint or to 200 ng of rat recombinant IL-1beta (rrIL-1beta) was higher in ICE-deficient mice as compared to WT animals. This hyperreactivity of the HPA axis in ICE knockout mice appears not to be related to the production of plasma IL-1beta or IL-6, which was similar to that of WT mice after rrIL-1beta injection. After lipopolysaccharide, ICE-deficient mice exhibited a smaller increase in plasma-immunoreactive IL-1beta and IL-6 as compared to WT controls. After restraint stress neither increase in plasma IL-1beta nor IL-6 was observed. The mechanisms responsible for the increased reactivity of the HPA axis in ICE-deficient mice may result from a higher sensitivity of the HPA axis to inflammatory cytokines or to cleavage products of pro-IL-1beta processed by non-ICE proteases.

Adrenocorticotropic Hormone↗
PubMed1999

Effect of exogenous nitric oxide and inhibitors of nitric oxide synthase on the hypothalamic pituitary adrenal axis responses to neural stimuli.

It has been shown that the hypothalamic-pituitary-adrenal (HPA) axis responses to immune-derived stimuli in particular can be modulated by nitric oxide (NO). In the present study we examined the effect of endogenous and exogenous NO on the HPA axis responses to neural stimuli which are not related to immune functions. Intracerebroventricular injection of NOR-3, a donor of NO, had no effect on basal HPA axis activity but significantly attenuated the secretion of median eminence (ME) CRH-41 as well as the serum ACTH and corticosterone (CS) in response to acute photic stimulation in a dose-dependent manner. Intracerebroventricular administration of N-omega-nitro-L-arginine methyl ester (L-NAME), a general NOS inhibitor, significantly enhanced ACTH and CS responses to this stress but did not change the basal levels of these hormones. On the other hand, i.c.v. injection of aminoguanidine, an inhibitor of inducible NO synthase (NOS) but not of neuronal NOS, did not affect the HPA axis responses to photic stimulation. These results suggest that: (1) NO is involved in modulation of the HPA axis responses to neural stimuli which are not dependent on immune factors, (2) the effect of NO is mediated by inhibition of hypothalamic ME CRH-41 secretion, and (3) this effect is probably mediated by neuronal NOS and not by inducible NOS.

Adrenocorticotropic Hormone↗
PubMed2000

Acute-stress-induced facilitation of the hypothalamic-pituitary-adrenal axis.

It has been hypothesized that the hypothalamic-pituitary-adrenal (HPA) axis responds to a stressor by secreting facilitatory and inhibitory factors. During a stressor, the relative magnitude of secretion of these factors determines the responsiveness of the HPA axis to a subsequent stressor. Previous studies have suggested that corticosterone (B) secreted during the first stressor is an inhibitory factor. We hypothesized that the transient removal of the inhibitory factor, B, during the first stressor would result in the secretion of only facilitatory factors. This would cause the HPA axis to exist in a state of hyperresponsiveness, and to hypersecrete corticotropin (ACTH) and B in response to a second stressor. Therefore, our primary objective was to demonstrate stress-induced facilitation of the HPA axis response to a subsequent stressor. Male Sprague-Dawley rats were subjected to a 1-hour physical immobilization stressor (IMM) or administered a single dose of ACTH on day 1. B response during these treatments was markedly but transiently attenuated with an 100 mg/kg i.p. dose of aminoglutethimide (AG). Twenty-four hours later, rats were subjected to an intraperitoneal saline injection stressor. B and ACTH levels were measured 15 min after the injection stressor. Rats treated with AG plus IMM on day 1 hypersecreted B and ACTH after the injection stressor on day 2. These results suggest that immobilization stress induces facilitation of both pituitary and adrenal responses. Exogenous administration of ACTH- to AG-pretreated rats on day 1, in lieu of immobilization stress, did not affect the responsiveness of the HPA axis on day 2. This suggests that ACTH secreted during the first stressor does not play an important role in acute-stress-induced facilitation.

Acute Disease↗
PubMed2001

Hypothalamo-pituitary-adrenal axis sensitization after chronic salt loading.

Hypothalamic parvocellular vasopressin (VP) and corticotropin-releasing hormone (CRH) in the paraventricular nucleus (PVN) are major secretagogues of corticotropin (ACTH), and central plasticity including their alteration is closely related to hypothalamic-pituitary-adrenal (HPA) axis modulation. Chronic hyperosmotic stress caused by 2% salt loading has been known to alter VP and CRH expression. We recently reported that rehydration, a recovery stage from salt loading, induced a prolonged increase in parvocellular VP mRNA expression and suggested that rehydration can modulate HPA axis function without obvious external stress. In the present study, we examined hypothalamic VP and CRH mRNA expression and their responsiveness to acute immobilization stress in control, salt-loaded and rehydrated animals, in order to clarify the precise mechanism of HPA axis regulation during rehydration. The results were further compared with plasma corticosterone and ACTH levels. Plasma corticosterone decreased during salt loading, whereas it increased during rehydration at 1 week. Basal ACTH concentration increased in 1-week-rehydrated animals, with enhanced responsiveness to the acute immobilization stress. In the hypothalamic parvocellular PVN, basal CRH mRNA levels also decreased during salt loading and increased during rehydration. Basal VP mRNA was up-regulated during both salt loading and rehydration. VP mRNA responded to additional acute stress during salt loading and rehydration, but CRH mRNA did not. These results indicate that the HPA axis activity of parvocellular neurons is still altered at 1 week of rehydration and that VP plays a dominant role in regulating ACTH release in response to acute stress. This rehydration stage may thus be a good model for analysis of post-stress sensitization of the HPA axis.

Adrenocorticotropic Hormone↗
PubMed2001

Acute effects of purified and UV-inactivated Herpes simplex virus type 1 on the hypothalamo-pituitary-adrenocortical axis.

UNLABELLED: Herpes simplex virus type 1 (HSV-1) is a common cause of viral encephalitis, manifested by neuroendocrine and behavioral changes. We have previously demonstrated that HSV-1 induces marked hypothalamo-pituitary-adrenocortical (HPA) axis activation. In this study we characterized the acute effects of HSV-1 on the HPA axis occurring before viral replication and appearance of clinical signs of encephalitis. Since in previous studies we used crude virus preparations which may contain immune factors produced by the infected cells, we tested here the effects of purified HSV-1 virions. HSV-1 was propagated on Vero cells and virions were purified by centrifugation in sucrose gradients. Inactivation of viral infectivity was achieved by UV-irradiation, which caused a million-fold decrease in virus titer, as determined by plaque assay. Intracerebroventricular (ICV) inoculation of crude or purified virions induced a dose dependent increase in serum corticosterone and corticotropin (ACTH). This effect was maximal within 3.5 h postinfection and lasted for 72 h. ICV inoculation of UV-inactivated purified virions caused a marked increase in serum corticosterone and ACTH at 3.5 h, but in contrast to the effect of the active virus, the hormone levels gradually decreased at 24 h, and returned to basal levels at 72 h postinfection. HSV-1-induced HPA axis activation at 3.5 h was completely abolished by pretreatment with interleukin-1 receptor antagonist, injected ICV. Adrenalectomized rats failed to respond to ICV inoculation of purified HSV-1 by increase in ACTH. In contrast, these rats responded to ICV injection of LPS. IN CONCLUSION: (1) HSV-1 can acutely activate the HPA axis before and independently of any viral replication; (2) HSV-1-induced HPA axis activation depends on a permissive action of circulating glucocorticoids and on host derived brain interleukin-1.

Adrenalectomy↗
PubMedDate not supplied

Treatment-resistant depression and Axis II comorbidity.

BACKGROUND: Researchers of unipolar depression have speculated that personality disturbance is a contributing factor in the development of treatment resistance. The purpose of this study was to compare the prevalence of Axis II disorders between a sample of rigorously defined, treatment-resistant depressed outpatients and a sample of depressed outpatients not having experienced treatment resistance. METHODS: 53 patients with treatment-resistant depression (TRD) and 105 patients with non-treatment-resistant depression (non-TRD) were recruited through respective outpatient clinical trials at the Massachusetts General Hospital's Depression Clinical and Research Program. Diagnosis of Major Depressive Disorder was made using the Structured Clinical Interview for the DSM-III-R, personality disorders were assessed using the Structured Clinical Interview for DSM-III-R Personality Disorders, and antidepressant treatment resistance was defined using the McLean Hospital Antidepressant Treatment Record. Participants from both studies were matched for baseline HAM-D-17 total score and gender. Multiple chi-square analysis was used to compare frequencies of Axis II disorders between TRD and non-TRD patients as well as to compare categorical baseline demographic variables. Unpaired t tests were used to compare baseline demographic and clinical variables measured in a continuous manner. RESULTS: Non-TRD patients had a higher rate of obsessive-compulsive personality disorder than TRD patients, but this difference was not statistically significant after adjusting for multiple comparisons. No other differences were found to be statistically significant. Range of Axis II comorbidity was 0.0-30.2% for TRD patients and 2.9-37.1% for non-TRD patients. CONCLUSIONS: In this sample, treatment resistance in a current major depressive episode was not associated with an increased rate of Axis II disorders. Strengths of this study include the use of structured interview instruments to assess Axis I and II conditions, and having the two study groups matched for gender and baseline severity of depression. Limitations of this study include a modest sample size and reliance on DSM personality constructs.

Adult↗
PubMed2002

Altered control of the hypothalamo-pituitary-adrenal axis in adult male rats exposed perinatally to food deprivation and/or dehydration.

Dehydration, a classic homeostatic stressor in rats, leads to a series of well characterized endocrine responses including stimulation of the hypothalamo-pituitary-adrenal (HPA) axis. In this study, the hypothesis to be tested was that a 50% maternal food restriction (FR50) in late gestation and lactation may have long-term repercussions on HPA axis responsiveness to dehydration in offspring. For this purpose, we studied HPA axis activity in 4-month-old control (C) and perinatally malnourished male rats after a 72-hour water deprivation period. Furthermore, we investigated the long-lasting effects of perinatal maternal malnutrition on the basal activity of the HPA axis. Under basal conditions, rats exposed to perinatal malnutrition showed reduced body weight, enhanced mineralocorticoid receptor (MR) mRNA levels in CA2 and CA3 hippocampal areas, but decreased glucocorticoid receptor (GR) mRNA levels in CA1, CA3 and dentate gyrus (DG) areas. In contrast, the levels of corticotropin-releasing hormone (CRH) and vasopressin (VP) mRNAs in the hypothalamic paraventricular nucleus (PVN) as well as of VP mRNA in the supraoptic nucleus (SON) were unaffected by maternal undernutrition. Expression of proopiomelanocortin (POMC) in the adenohypophysis was significantly enhanced, whereas prohormone convertase-1 (PC1) was not affected. Perinatal malnutrition reduced absolute adrenal weight but did not affect circulating levels of adrenocorticotropin (ACTH), corticosterone and free corticosterone as well as corticosteroid-binding globulin (CBG) binding capacity. Seventy-two hours of dehydration induced a decrease in body weight and CRH mRNA levels in PVN of controls as well as of FR50 rats, but also led to a rise in plasma corticosterone and free corticosterone without changing CBG binding capacity. Dehydration also induced an increase in adenopituitary POMC (C) and PC1 (FR50), PVN and SON VP (C) and GR in CA1 hippocampal area (FR50) mRNA levels and plasma ACTH (C), but a decrease in MR in DG (C) and GR in CA3 and DG (C) mRNA levels. We conclude that maternal food restriction during the perinatal period affects (1) the adult basal activity of the HPA axis with mainly opposite effects on hippocampal MR and GR gene expression and an increase in adenopituitary POMC gene expression, and (2) the responsiveness to water deprivation in adults. In the latter case, the rise in plasma ACTH levels, adenopituitary POMC gene expression, hypothalamic VP gene expression, and the decrease in hippocampal MR gene expression in DG and GR gene expression in CA3 and DG observed in controls are lacking in FR50 rats. In contrast, drastic adenopituitary PC1 gene expression occurred in FR50 rats but not in control animals.

Adrenal Glands↗
PubMed2006

Estrogens and neuroendocrine hypothalamic-pituitary-adrenal axis function.

The function of the HPA axis is subject to regulation by many factors, which achieve relevance under normal and pathological conditions. In the case of aging, this period of life is associated with disturbances of the HPA axis and signs of hippocampal vulnerability. We examined 20-month-old male rats, in which abnormalities of the HPA axis included altered response to stress, reduced effectiveness of the steroid negative feedback and low expression of hippocampal glucocorticoid receptors (GR). Estrogen treatment of aging rats normalized the response to stress, restored the dexamethasone inhibition of the stress response and increased GR density in defined hippocampal areas. Although estrogens could influence the hippocampus of aging animals directly, their effects could be also mediated by estrogen-sensitive forebrain cholinergic neurons projecting to the hippocampus. Additionally, estrogens normalized the deficient granule cell proliferation that aging mice present in the dentate gyrus, and attenuated several markers of hippocampal aging, such as astrocytosis, high lipofucsin content and neuronal loss in the hilus of the dentate gyrus. These effects may be important for the regulation of the HPA axis, in the context that hippocampal function as a whole was normalized by estrogen action. Therefore, estrogens are powerful neuroprotectants in cases of hippocampal dysfunction, and as part of this effect, they contribute to stabilize the function of the HPA axis.

Adrenal Glands↗
PubMed1992

Neurotransmitter-induced hypothalamic-pituitary-adrenal axis responsiveness is defective in inflammatory disease-susceptible Lewis rats: in vivo and in vitro studies suggesting globally defective hypothalamic secretion of corticotropin-releasing hormone.

The susceptibility of female Lewis (LEW/N) rats to the development of streptococcal cell wall (SCW)-induced arthritis and other autoimmune phenomena is associated with the inability of their hypothalamic-pituitary-adrenal (HPA) axis to adequately respond to inflammatory stimuli. In contrast, resistance to the development of SCW-induced arthritis and other inflammatory autoimmune manifestations in histocompatible female Fischer rats (F344/N) is related to their intact HPA axis response to inflammatory mediators. To evaluate the mechanism and the specificity of the HPA axis defect in LEW/N rats, we examined the ability of three major excitatory neurotransmitter systems to activate the HPA axis in both Lewis and Fisher rats. The responsiveness of plasma ACTH and corticosterone to the cholinergic muscarinic receptor agonist arecoline, the alpha 1-adrenergic receptor agonist methoxamine and the serotonin (5-HT) type 2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane were significantly blunted and/or abolished in LEW/N compared to F344/N rats. To localize the HPA axis defect to the hypothalamic CRH neuron, we evaluated the ability of explanted hypothalami from the two strains to secrete immunoreactive CRH in vitro, in response to acetylcholine (ACh), norepinephrine (NE), 5-HT and the 5-HT agonist quipazine. LEW/N hypothalami released less immunoreactive CRH (iCRH) in response to ACh, NE, 5-HT and quipazine than F344/N hypothalami. The dose-response curves of these compounds in the former were shifted to the right and/or abolished, suggesting decreased sensitivity of LEW/N hypothalami to these neurotransmitters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1989

Transient QRS axis shift to the right during right coronary artery and/or left circumflex artery spasms.

The QRS axis was measured in 24 patients during ergonovine malate provocation test (EM test). Of 12 patients with significant spasm of the right coronary artery (RCA) and/or left circumflex artery (LCX), the QRS axis shifted to the right in 7 patients after the EM test (mean 8.2 degrees), and the axis shifted back to the left in 9 patients after nitroglycerin administration (mean -9.1 degrees). The sensitivity of right axis shift for RCA and LCX spasm was 58% and the specificity was 80%. Thus, right axis shift seems to be associated with myocardial ischemia due to RCA and LCX spasm and to be useful for the detection of RCA and/or LCX spasms.

Coronary Vasospasm↗
PubMed2004

Three-dimensional reconstruction of the rabbit atrioventricular conduction axis by combining histological, desmin, and connexin mapping data.

BACKGROUND: The 3D structure of the atrioventricular conduction axis incorporating detailed cellular and molecular composition, especially that relating to gap-junctional proteins, is still unclear, impeding mechanistic understanding of cardiac rhythmic disorders. METHODS AND RESULTS: A 3D model of the rabbit atrioventricular conduction axis was reconstructed by combining histological and immunofluorescence staining on serial sections. The exact cellular boundaries, especially those between transitional cells and atrial myocardium, were demarcated by a dense and irregular desmin-labeling pattern in conductive myocardium. The model demonstrates that the atrioventricular conduction axis is segregated into 2 connecting compartments, 1 predominantly expressing connexin45 (compact node and transitional cells) and the other predominantly coexpressing connexin43 and connexin45 (His bundle, lower nodal cells, and posterior nodal extension). The transitional zone shows unique features of spatial complexity, including a bridging bilayer structure (a deep transitional zone connecting with a superficial atrial-transitional overlay) and asymmetrical continuity (wider atrial-transitional interfaces and shorter atrial-axial distances in the hisian portion than in the ostial portion). In the latter compartment, the His bundle, lower nodal cells, and posterior nodal extension form a continual axis and longitudinal transitional-axial interface. CONCLUSIONS: Key findings of the present study are the demonstration of a distinct anatomical border between transitional and atrial cells, connection between transitional cells and both lower nodal cells and posterior nodal extension, and distinctive connexin expression patterns in different compartments of the rabbit atrioventricular conduction axis. These features, synthesized in a novel 3D model, provide a structural framework for the interpretation of nodal function.

Animals↗
PubMed1979

Left axis deviation: a reassessment.

This report deals with the ramifications of the concept of left axis deviation. In early life, the leftward shift of the frontal plane QRS axis is determined chiefly, if not solely, by the relative weights of the ventricles. Once adult ventricular weight ratios are reached, there is a long period of axis stability, then a gradual leftward drift of the QRS, governed principally by left anterior fascicular conduction. Thus, the normal QRS axis is age-dependent, and left axis deviation must be considered accordingly.

Adult↗
PubMed2005

The RAGE axis in early diabetic retinopathy.

PURPOSE: The receptor for advanced glycation end products (AGEs) has been implicated in the pathogenesis of diabetic complications. This study was conducted to characterize the role of the RAGE axis in a murine model of nonproliferative diabetic retinopathy (NPDR). METHODS: The retinas of hyperglycemic, hyperlipidemic (HGHL, apolipoprotein E(-/-) db/db) mice were examined for the development of early retinal vascular lesions of NPDR and compared to littermates at 6 months of age. Neural function was assessed with electroretinography. Immunohistochemistry, real-time RT-PCR, autofluorescence, and ELISA studies were used to localize and quantify the AGE/RAGE axis. Soluble RAGE, a competitor of cellular RAGE for its ligands, was administered to assess the impact of RAGE blockade. RESULTS: Early inner retinal neuronal dysfunction, manifested by prolonged latencies of the oscillatory potentials and b-wave, was detected in hyperglycemic mice. HGHL mice exhibited accelerated development of acellular capillaries and pericyte ghosts compared with littermate control animals. AGEs were localized primarily to the vitreous cavity and internal limiting membrane (ILM) of the retina, where they were intimately associated with the footplates of RAGE-expressing Müller cells. AGE accumulation measured by ELISA was increased within the retinal extracellular matrix of hyperglycemic mice. AGE fluorescence and upregulation of RAGE transcripts was highest in the retinas of HGHL mice, and attenuation of the RAGE axis with soluble RAGE ameliorated neuronal dysfunction and reduced the development of capillary lesions in these mice. CONCLUSIONS: In early diabetic retinopathy, the RAGE axis, comprising the cellular receptor and its AGE ligands, is amplified within the retina and is accentuated along the vitreoretinal interface. Antagonism of the RAGE axis in NPDR reduces neurovascular perturbations, providing an important therapeutic target for intervention.

Animals↗
PubMed1988

The revision of axis V in DSM-III-R: should symptoms have been included?

The authors studied the relationship of psychological symptoms to clinicians' ratings on DSM-III's axis V. A total of 355 patients received multiaxial assessments and were reinterviewed under blind conditions with the Psychiatric Epidemiology Research Interview, which contains scales to measure aspects of social and occupational functioning and various symptom dimensions. The majority of symptom scales were correlated significantly with axis V ratings. Axis I diagnosis explained 19.0% of the variance in axis V; demographics, 6.5%; and symptoms, 7%. Symptoms had a larger effect, in terms of explained variance, than adaptive functioning variables and tended to detract from the latter's significance. These results have implications for axis V in DSM-III-R and for planning DSM-IV.

Adolescent↗