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At least 955 records · Page 53Linked to original sources
PubMed2002

Post-nodal mesoblast caudalizes the host axis and inhibits cell population growth, and induces new primitive streaks in chick embryos.

One to eight post-nodal fragments (PN) or Hensen's nodes (HN) from full primitive streak stage chick embryos were transplanted onto the area pellucida or area opaca of stage 4 embryos and cultured for 20 h. Thirteen morphological and numerical parameters were affected in the host embryos and analyzed by multiple logistic regression for parametric hierarchy. In the area pellucida, both PN and HN transplants inhibited cell population growth while only PN caudalized the host axis and induced supernumerary primitive streaks expressing the mesoderm-specific gene Brachyury. In the area opaca, neither grafts influenced host axis morphogenesis, but PN inhibited the cell population growth significantly. Tracking [(3)H]TdR labeled grafts showed that PN cells migrated towards the host axis and participated in the formation of supernumerary somites and hearts. When placed near the host axis, PN caudalized it and inhibited cell population growth.

Animals↗
PubMed2003

Medial prefrontal cortex suppression of the hypothalamic-pituitary-adrenal axis response to a physical stressor, systemic delivery of interleukin-1beta.

Previous studies have shown that the medial prefrontal cortex can suppress the hypothalamic-pituitary-adrenal axis response to stress. However, this effect appears to vary with the type of stressor. Furthermore, the absence of direct projections between the medial prefrontal cortex and corticotropin-releasing factor cells at the apex of the hypothalamic-pituitary-adrenal axis suggest that other brain regions must act as a relay when this inhibitory mechanism is activated. In the present study, we first established that electrolytic lesions involving the prelimbic and infralimbic medial prefrontal cortex increased plasma adrenocorticotropic hormone levels seen in response to a physical stressor, the systemic delivery of interleukin-1beta. However, medial prefrontal cortex lesions did not alter plasma adrenocorticotropic hormone levels seen in response to a psychological stressor, noise. To identify brain regions that might mediate the effect of medial prefrontal cortex lesions on hypothalamic-pituitary-adrenal axis responses to systemic interleukin-1beta, we next mapped the effects of similar lesions on interleukin-1beta-induced Fos expression in regions previously shown to regulate the hypothalamic-pituitary-adrenal axis response to this stressor. It was found that medial prefrontal cortex lesions reduced the number of Fos-positive cells in the ventral aspect of the bed nucleus of the stria terminalis. However, the final experiment, which involved combining retrograde tracing with Fos immunolabelling, revealed that bed nucleus of the stria terminalis-projecting medial prefrontal cortex neurons were largely separate from medial prefrontal cortex neurons recruited by systemic interleukin-1beta, an outcome that is difficult to reconcile with a simple medial prefrontal cortex-bed nucleus of the stria terminalis-corticotropin-releasing factor cell control circuit.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Limbs and tail as evolutionarily diverging duplicates of the main body axis.

Contrasting hypotheses have been proposed to explain the pervasive parallels in the patterning of arthropod and vertebrate appendages. These hypotheses either call for a common ancestor already provided with patterned appendages or body outgrowths, or for the recruitment in limb patterning of single genes or genetic cassettes originally used for purposes other than axis patterning. I suggest instead that body appendages such as arthropod and vertebrate limbs and chordate tails are evolutionarily divergent duplicates (paramorphs) of the main body axis, that is, its duplicates, albeit devoid of endodermal component. Thus, vertebrate limbs and arthropod limbs are not historical homologs, but homoplastic features only transitively related to real historical homologs. Thus, the main body axis and the axis of the appendages have distinct but not independent evolutionary histories and may be involved in processes of homeotic co-option producing effects of morphological assimilation. For instance, chordate segmentation may have originated in the posterior appendage (tail) and subsequently extended to the trunk.

Animals↗
PubMedDate not supplied

Radiographic investigation of angular and linear measurements including first metatarsophalangeal joint dorsiflexion and rearfoot to forefoot axis angle.

This study investigated intra- and inter-rater reliability of several radiographic angular and linear parameters using 6 subjects. Using standard weight-bearing radiographs, the following measurements were performed: first metatarsal protrusion distance, hallux abductus, first intermetatarsal, calcaneal inclination and lateral intermetatarsal angles. Measurement of lateral stressed dorsiflexion of the first metatarsophalangeal joint and the rearfoot-to-forefoot-axis angle taken using a composite view were also obtained. All parameters were measured independently by 2 raters, and measurements were repeated on 3 separate occasions at weekly intervals. Intrarater reliability of radiographic measurements ranged between R = 0.65-1.00 for lateral stressed dorsiflexion, and between R = 0.91 and 0.99 for the rearfoot to forefoot axis angle. Inter-rater reliability of radiographic measurements ranged from R = 0.82-0.99. Specifically, lateral stressed dorsiflexion showed R = 0.87 with a mean difference of -1.47 (confidence interval [CI]: -3.42, 0.47), indicating no significant difference ( t = 1.54, P = 0.13). The rearfoot-to-forefoot-axis angle showed R = 0.92 with a mean difference of -0.15 (CI: -1.05, 0.74), indicating no significant difference ( t = 0.35, P = 0.73). The 7 angular and linear measurements chosen demonstrated high inter- and intrarater reliability. These results indicate that weight-bearing radiographic first metatarsophalangeal joint dorsiflexion using the lateral stressed dorsiflexion view, and measurement of the rearfoot-to-forefoot-axis angle using a composite view could be measured reliably within and between raters.

Adult↗
PubMed2000

Comparable effects of inhaled fluticasone propionate and budesonide on the HPA-axis in adult asthmatic patients.

This randomized, double-blind, double-dummy, multicentre cross-over study compared the effects on the hypothalamic-pituitary-adrenal (HPA) axis of fluticasone propionate (750 microg twice daily given via the Diskus) and budesonide (800 microg twice daily given via the Turbuhaler). Two treatment periods of 2 weeks each were preceded by a 2-week run-in period and separated by a 2-week washout period. During run-in and washout, patients received beclomethasone dipropionate (BDP) or budesonide at a constant dose of 1500-1600 microg day(-1). Sixty patients aged 18-75 years with moderate to severe asthma not fully controlled by treatment with 1500-1600 microg day(-1) budesonide or BDP entered run-in and 45 completed the study. HPA axis suppression was assessed by morning serum cortisol (area under the curve from 08.00 to 10.30 hours) and 12-h nocturnal urinary cortisol excretion, measured at the end of run-in (baseline 1), at the end of washout (baseline 2), and at the end of each treatment period. Neither budesonide nor fluticasone produced significant suppression of either parameter compared to baselines. Only a few patients had serum-cortisol and urinary cortisol values below the normal range, before and after treatment. This shows that the patients did not have adrenal suppression before entering the study. The ratio between the AUC serum cortisol measured after fluticasone treatment and after budesonide treatment was 0.99 (95% CI 0.92-1.06), indicating equivalent effects on the HPA axis. This result was achieved after having omitted two patients' results, due to their very sensitive reaction to budesonide, but not to fluticasone. Two exacerbations of acute asthma occurred during budesonide treatment and none during fluticasone treatment. Both treatments were well tolerated. In conclusion, budesonide 1600 microg day(-1) via Turbuhaler and fluticasone propionate 1500 microg day(-1) via Diskus had no clinical effects on the HPA axis in patients with moderate to severe asthma.

Administration, Inhalation↗
PubMed2000

High-frame-rate tissue harmonic imaging enhances anatomic M-mode sections of the left ventricle in short-axis view.

BACKGROUND: High-frame-rate echocardiography (HFRE) and tissue harmonic imaging (THI) may improve image quality, thereby enabling anatomic M-mode sections of left ventricular (LV) wall segments to be visualized in various planes in the short-axis view. OBJECTIVES: The goals of this study were to compare image quality between HFRE and conventional-frame-rate echocardiography (CFRE) and between fundamental imaging (FI) and THI, and to obtain anatomic M-mode values of basal short-axis LV segments from healthy subjects for use in the evaluation of abnormal segments in patients with myocardial infarction (MI). METHODS AND RESULTS: The study included 28 healthy subjects and 15 patients with MI who underwent 2-dimensional echocardiography with an ultrasonographic system equipped with THI and anatomic M-mode. Left ventricular image cineloops at the basal short-axis view that were obtained with 3 combinations of imaging techniques (FI + CFRE, FI + HFRE, and THI + HFRE) were digitized and displayed side-by-side in random order for comparison by blinded readers. M-mode sections were done in 3 planes: anteroseptal-posterior, inferoseptal-lateral, and anterior-inferior basal segments. The THI + HFRE combination showed the best image quality with significant reduction in noise artifacts, resulting in a good signal-to-noise ratio and good tractability of all LV segments by anatomic M-mode. In healthy subjects, significant intersegmental differences existed in the diastolic and systolic thicknesses and in the percent systolic thickening of LV segments. In patients with MI, LV systolic thickening was significantly decreased in abnormal segments. No significant differences were noted in ejection fraction and fractional shortening among the 3 anatomic M-mode planes. CONCLUSION: High-frame-rate tissue harmonic imaging improved image quality, thereby allowing reproducible anatomic M-mode measurements in various planes in the short-axis view and providing a convenient objective evaluation of global and regional LV function.

Adult↗
PubMed2003

Relationship between the axis and degree of high astigmatism and obliquity of palpebral fissure.

PURPOSE: To investigate a possible relationship between the slanting of palpebral fissures and the magnitude and axis of astigmatism in children with astigmatism. METHODS: Cross-sectional study at a referral center of 53 children with astigmatism of more than +1.50 D in at least 1 eye. Visual acuity testing, cycloplegic refraction, slit-lamp biomicroscopy, and ophthalmoscopy were done on every patient. Corneal topography was obtained in 40 cooperative patients. External photographs of the midface were taken in 45 children. The degree of slanting of the palpebral fissures was evaluated based on the photographs. The statistical analysis tool used was repeated measures analysis of variance. Patients in whom photographic analysis was not available were excluded from the part of the statistical analysis dealing with eyelid slant. RESULTS: Palpebral fissure slant (P =.013) and gender (P =.0005) were highly correlated with the obliquity of cylinder axis. There was a possible correlation between gender and eyelid slant (P =.0594), with females having slightly larger degrees of upward palpebral fissure slanting and male more downward slanting of their fissures compared to published angles in an age-matched population. We found a statistically significant correlation between the degree of total astigmatism and a larger abnormal slant (P =.0192) and between the axis and magnitude of corneal astigmatism and abnormal slant (P =.0092). Higher degrees of eyelid slant (> 8 degrees or < -4 degrees ) increased the risk of high cylinder magnitude (> 3.00 D) by an odds ratio of 4.17 (95% CI: 1.03, 19.95). CONCLUSIONS: Children with astigmatism with large degrees of slanting of their palpebral fissures are at higher risk for high astigmatism (> 3.00 D). The axis of the astigmatism is highly correlated with the slanting of the palpebral fissure.

Adolescent↗
PubMed2003

Comparative tests of arbitrary and kinematic transverse horizontal axis recordings of mandibular movements.

STATEMENT OF PROBLEM: The reliability of recording maxillomandibular relationships for articulator programming with a transverse horizontal axis determined arbitrarily with an arbitrary face-bow has not been verified against a kinematically determined and recorded transverse horizontal axis in an in vivo study. PURPOSE: The goal of this study was to determine the measuring accuracy of the Cadiax Compact system in a clinical series of tests and to determine whether there is a clinically significant difference between the 3-dimensional measurements recorded from kinematically and arbitrarily determined transverse horizontal axes. MATERIAL AND METHODS: Thirty subjects (11 women, 19 men; ages 21 to 26) participated in this study. Mandibular movement, the sagittal condylar inclination (SCI) angle, and the transversal condylar inclination (TCI) angle were recorded in each subject with the Cadiax Compact system, by use of first an arbitrarily and second a kinematically determined transverse horizontal axis. A subset of 10 subjects was examined with another computerized axiograph, the Gamma Cadiax system. Measurements were made and recorded twice, on different days under similar circumstances. To compare the systems and measurement methods, the SCI measurements taken at 3- and 5-mm sagittal protrusion and the TCI taken at 3- and 5-mm mediotrusion were used. The lengths and characteristic curvatures of protrusion, opening, and mediotrusion tracings were determined for the evaluation as follows: tracing lengths (<8 mm, 8 to 12 mm, and >12 mm); degree of overlap of the excursive and incursive tracing; and tracing curvature. The intraclass correlation was used to compare angle values at the 95% confidence interval. To assess the track progression, kappa values were calculated. RESULTS: Repetition of the mandibular track inclination angles and the condylar movement pattern was highly reliable (intraclass correlation of >0.8) with the Cadiax Compact system. When the mandibular track inclinations determined kinematically and arbitrarily by the Gamma Cadiax and Cadiax Compact systems were compared, both systems demonstrated high reliability (ICC>0.8). The congruence results of the protrusion tracings from kinematic and arbitrary measurements with the Cadiax Compact system were as follows: strong congruence in quantity, characteristics, and horizontal tracing; only the quality diminished slightly (Kappa 0.46 in the first measurement, which still represented a clear congruence). The opening and mediotrusion tracings demonstrated fair to almost complete congruence in all parameters. CONCLUSION: Within the limitations of this study, the kinematic and arbitrary measurements of the Cadiax Compact system could be reliably used for articulator programming. The results suggest that arbitrarily determined posterior reference points may be comparable to a kinematically determined transverse horizontal axis.

Adult↗
PubMed1995

Molecular aspects of the ontogeny of the pituitary-gonadal axis.

The endocrine function of the mammalian pituitary-gonadal axis begins in utero. This is important particularly for the ontogeny and function of the male reproductive organs, the induction of which is critically dependent on the two fetal testicular hormones, testosterone and anti-müllerian hormone. In contrast, ovarian endocrine activity begins only after birth. The earliest phases of testicular hormone production are probably under autocrine or paracrine regulation, but the dependence on gonadotrophins starts in fetal life. During maturation of the hypothalamic-pituitary-testicular axis, the target organs acquire their responsiveness (viz receptors) before the onset of secretion of the tropic hormonal stimulus. The last link to develop is the feedback regulation, and the whole axis is functional in the developing male rat during the last days of gestation. Although gonadotrophin secretion starts in both sexes simultaneously, the fetal ovary is endocrinologically quiescent--its gonadotrophin responsiveness and endocrine activity begin only after birth. The fetal and postnatal periods of testicular activity have crucial effects on male sexual differentiation, whereas in the female, early sexual development occurs autonomously without influence of ovarian function. The purpose of this review is to elucidate some of the recent findings on the molecular mechanisms involved in the perinatal maturation of the rat hypothalamic-pituitary-gonadal axis.

Androgens↗
PubMed2000

Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning.

The primary neuroendocrine interface, hypothalamus and pituitary, together with adrenals, constitute the major axis responsible for the maintenance of homeostasis and the response to the perturbations in the environment. The gene expression profiling in the human hypothalamus-pituitary-adrenal axis was catalogued by generating a large amount of expressed sequence tags (ESTs), followed by bioinformatics analysis (http://www.chgc.sh.cn/ database). Totally, 25,973 sequences of good quality were obtained from 31,130 clones (83.4%) from cDNA libraries of the hypothalamus, pituitary, and adrenal glands. After eliminating 5,347 sequences corresponding to repetitive elements and mtDNA, 20,626 ESTs could be assembled into 9, 175 clusters (3,979, 3,074, and 4,116 clusters in hypothalamus, pituitary, and adrenal glands, respectively) when overlapping ESTs were integrated. Of these clusters, 2,777 (30.3%) corresponded to known genes, 4,165 (44.8%) to dbESTs, and 2,233 (24.3%) to novel ESTs. The gene expression profiles reflected well the functional characteristics of the three levels in the hypothalamus-pituitary-adrenal axis, because most of the 20 genes with highest expression showed statistical difference in terms of tissue distribution, including a group of tissue-specific functional markers. Meanwhile, some findings were made with regard to the physiology of the axis, and 200 full-length cDNAs of novel genes were cloned and sequenced. All of these data may contribute to the understanding of the neuroendocrine regulation of human life.

Alternative Splicing↗
PubMed1997

Automatic calculation of the medial axis of foot outline and its flexion angles.

As one of the morphological characteristics of human foot, flexion angles of medial axis of foot outline have been proposed in order to improve shoe comfort. Foot outlines were easily obtained by a scriber, whereas calculation of the medial axis and its flexion angles from the foot outline had inter-operator errors and a lack of reproducibility. This is because foot outlines were inputted by a digitizer, and flexion points of the medial axis were determined by eye inspection. An automatic method of calculation was developed for the following purposes: (1) to decrease inter-operator errors caused by manual operation; (2) to improve the reproducibility of the medial axis and its flexion angles; and (3) to save time and trouble in processing a large amount of data. The flexion angle reproducibility of the present method was within 1 degree. The errors in the flexion angles determined by the present method are half those determined by the conventional method. The flexion angles of over 5000 foot outlines that were obtained in 1987 were calculated when the present method was developed. The mean posterior flexion angle of the adults was 8.4 degrees. Since the majority of Japanese feet are outflared, this characteristic should not be ignored in designing/modifying shoe lasts.

Adult↗
PubMed1995

DSM-III-R Axis IV: clinician reliability and comparability to patients' reports of stressor severity.

Stress has long been considered an important precipitant to the development or exacerbation of psychopathology (Selye 1980). However, it has been difficult to reach agreement on how to measure stressors reliably, and whether stressors should be assessed using an objective clinical rating or a subjective appraisal (Mazure and Druss 1995). When the DSM-III multiaxial diagnostic system was derived, Axis IV was designed to provide a mechanism for objectively rating the severity of psychosocial stressors that contributed to the development or exacerbation of psychiatric disorders (Williams 1985). With the continued use of this nosological system, DSM-III-R Axis IV has become the most commonly used assessment of stressors in clinical settings today. The current work focuses on whether DSM-III-R Axis IV can be used reliably by clinicians generating objective ratings, and on whether these objective ratings reflect patients' appraisals of the severity of their psychosocial stressors. Based on this work, options for future use of Axis IV are discussed.

Adaptation, Psychological↗
PubMed1986

The tunica muscularis of human brain arteries: three-dimensional measurements of alignment of the smooth muscle mechanical axis, by polarized light and the universal stage.

The four-axis universal stage, with the polarizing microscope, was assessed for making precise three-dimensional measurements of alignment on muscle cells. The physiological dimensions of the arteries (obtained at autopsy) and the co-alignment of the myofilaments with the long axis of the muscle cells was assured by the fixation of the arteries at normal distending pressure. They were embedded in paraffin wax, either perpendicular to the cutting plane which permitted controlled realignment of the block later, or along with a rectangular block of previously fixed liver parenchyma (providing a cartesian reference). The test for accuracy showed that smooth muscle, when unstained, was measured to within +/- 5 degrees. The same tissue measured after staining by Gomori's silver impregnation, could be repeatedly measured to within 2.4 degrees. The optical axis, parallel to the morphological axis, was not altered by staining. Data from 11 tissue sections revealed that the tunica muscularis is a precisely organized structure, not only with an average alignment which is almost perfectly circumferential, but with a higher degree of alignment among the muscle fibres than has been previously reported. Smooth muscle tissue is abundant and perhaps highly ordered in many structures. The universal stage could be employed to reveal that order.

Aged↗
PubMed2000

Long-axis rotation: the missing link in proximal-to-distal segmental sequencing.

Most assessments of segmental sequencing in throwing, striking or kicking have indicated a proximal-to-distal sequencing of end-point linear speeds, joint angular velocities, segment angular velocities and resultant joint moments. However, the role of long-axis rotations has not been adequately quantified and located in the proximal-to-distal sequence. The timing and importance of upper arm internal-external rotation and pronation-supination in the development of racquet head speed have been examined in the tennis serve and squash forehand drive and considered in relation to conventional concepts of proximal-to-distal sequencing. Both long-axis rotations reached their peak angular speeds late in both strokes, typically after shoulder flexion-extension, shoulder abduction-adduction and elbow extension. These results clarify and confirm the importance of upper limb long-axis rotations in the production of racquet head speed. It appears that traditional proximal-to-distal sequencing concepts are inadequate to describe accurately the complexity of the tennis serve or squash forehand drive. It is essential to consider upper arm and forearm longitudinal axis rotations in explaining the mechanics of these movements and in developing coaching emphases, strength training schedules and injury prevention programmes.

Arm↗
PubMedDate not supplied

Evaluation of accuracy in ankle center location for tibial mechanical axis identification.

Many surgical computer-assisted systems use mechanical axis identification as a reference for their computations. The goal of this study was to compare three methods to determine the location of the distal point of the tibial mechanical axis, based on percutaneous digitization of definite anatomical landmarks. In particular, we evaluated the accuracy of the identified tibial mechanical axis and the repeatability of the obtained results. Tests performed by four surgeons on cadaveric knees showed that the variability in identifying the ankle center using two out of the three methods presented introduced an inaccuracy in the mechanical axis identification of around 1 degrees. This makes their use suitable for computer-assisted systems.

Ankle↗
PubMedDate not supplied

The hypothalamic-pituitary-adrenal axis in the neuroendocrine regulation of food intake and obesity: the role of corticotropin releasing hormone.

The aim of this paper is to review the present knowledge on the role of the hypothalamic-pituitary-adrenal axis in the control of food intake and the pathogenesis of obesity and to discuss, on the basis of available literature, the interactions between other neurosystems and this hormonal axis. Food intake is influenced by a system of physiologic signals and behavioral controls consisting of positive and negative sensory feedback mechanisms. It is regulated by a complex neuroendocrine system consisting of peripheral signals (cortisol, leptin) in constant interplay with central neurosystems such as the cocaine-amfetamine-regulated transcript system. In these neurosystems, corticotropin-releasing hormone, pro-opiomelanocortin, melanin-concentrating hormone and neuropeptide Y are actively involved. The corticotropin-releasing hormone system is widely distributed throughout the brain, but it is particularly abundant in the medial parvocellular division of the paraventricular nucleus. Within the brain corticotropin-releasing hormone with its two receptor types, its binding protein and its closely related peptide urocortin forms a network of neuronal pathways capable of interacting with other circuitries controlling food intake and sympathetically-mediated thermogenesis. A defect in the synthesis and release of corticotropin-releasing hormone has been implicated in the development of obesity in laboratory animals. This condition is alleviated by exogenous corticotropin-releasing hormone treatment. The relationship between the neuropeptide Y system and the hypothalamic-pituitary-adrenal axis is complex and seems to include positive feedback between neuropeptide Y and corticosteroids and negative feedback between corticotropin-releasing hormone and neuropeptide Y. Leptin is involved in the regulation of energy balance by interacting with the hypothalamic-pituitary-adrenal axis. In the past, we have shown by cross-correlation analysis, that under physiological conditions cortisol and plasma leptin levels are related to each other in a time-related negative and positive fashion over 24h.

Adrenal Glands↗
PubMed2005

Modified RV short axis series--a new method for cardiac MRI measurement of right ventricular volumes.

PURPOSE: The current standard image orientation employed in the MRI assessment of right ventricular volumes uses a series of short axis cine acquisitions located with respect to a horizontal long axis view with the first slice placed across the atrio-ventricular valve plane at end diastole. Inherent inaccuracies are encountered with the use of this image orientation due to difficulty in defining the tricuspid valve and the border between atrium and ventricle on the resultant images. Our experience indicates that because the tricuspid valve is usually not in-plane in the slice the atrio-ventricular margin is difficult to distinguish. This leads to inaccuracies in measurements at the base of the RV and miscalculation of the RV volume. The purpose of this study was to assess an alternative method of image orientation aimed at increasing the accuracy of RV volume measurements using current commercially available CMRI sequences. This technique, the modified RV short axis series, is oriented to the outflow tract of the right ventricle. METHOD: We undertook a prospective study of 50 post cardiac transplant patients. A series of LV short axis multi-slice cine acquisition FIESTA images was acquired using the current standard technique. From this data set, LV and RV stroke volumes were derived on an Advantage Windows workstation using planimetry of the endocardial and epicardial borders in end systole and end diastole. Our new technique involved obtaining a set of multi-slice cine acquisition FIESTA images in a plane perpendicular to a line from the centre of the pulmonary valve to the apex of the RV. Planimetry of the RV was then performed and a stroke volume calculated using the same method of analysis. RV stroke volumes obtained from both techniques were compared with LV stroke volumes. Three operators independently derived RV data sets. RESULTS: On the images acquired with the new technique, the tricuspid valve was easier to define leading to more accurate and reproducible planimetry of ventricular borders. RV stroke volumes calculated from the new method showed better agreement with LV stroke volumes than with the current method. These results were consistent across the three operators. CONCLUSIONS: This new method improves visualisation of the tricuspid valve and makes analysis easier and less prone to operator error than the current standard technique for MRI assessment of RV volumes.

Heart Diseases↗
PubMed2000

Interaction among GSK-3, GBP, axin, and APC in Xenopus axis specification.

Glycogen synthase kinase 3 (GSK-3) is a constitutively active kinase that negatively regulates its substrates, one of which is beta-catenin, a downstream effector of the Wnt signaling pathway that is required for dorsal-ventral axis specification in the Xenopus embryo. GSK-3 activity is regulated through the opposing activities of multiple proteins. Axin, GSK-3, and beta-catenin form a complex that promotes the GSK-3-mediated phosphorylation and subsequent degradation of beta-catenin. Adenomatous polyposis coli (APC) joins the complex and downregulates beta-catenin in mammalian cells, but its role in Xenopus is less clear. In contrast, GBP, which is required for axis formation in Xenopus, binds and inhibits GSK-3. We show here that GSK-3 binding protein (GBP) inhibits GSK-3, in part, by preventing Axin from binding GSK-3. Similarly, we present evidence that a dominant-negative GSK-3 mutant, which causes the same effects as GBP, keeps endogenous GSK-3 from binding to Axin. We show that GBP also functions by preventing the GSK-3-mediated phosphorylation of a protein substrate without eliminating its catalytic activity. Finally, we show that the previously demonstrated axis-inducing property of overexpressed APC is attributable to its ability to stabilize cytoplasmic beta-catenin levels, demonstrating that APC is impinging upon the canonical Wnt pathway in this model system. These results contribute to our growing understanding of how GSK-3 regulation in the early embryo leads to regional differences in beta-catenin levels and establishment of the dorsal axis.

Adenomatous Polyposis Coli Protein↗