Biomedical subjects

Yang Xia

Publications and source records attributed to Yang Xia.

33 records · Page 2Linked to original sources

PubMed2004

Antibodies from preeclamptic patients stimulate increased intracellular Ca2+ mobilization through angiotensin receptor activation.

BACKGROUND: Preeclampsia is a serious disorder of pregnancy characterized by hypertension, proteinuria, edema, and coagulation and vascular abnormalities. At the cellular level, abnormalities include increased calcium concentration in platelets, lymphocytes, and erythrocytes. Recent studies have shown that antibodies directed against angiotensin II type I (AT1) receptors are also highly associated with preeclampsia. METHODS AND RESULTS: We tested the hypothesis that AT1 receptor-agonistic antibodies (AT1-AAs) could activate AT1 receptors, leading to an increased intracellular concentration of free calcium and to downstream activation of Ca2+ signaling pathways. Sera of 30 pregnant patients, 16 diagnosed with severe preeclampsia and 14 normotensive, were examined for the presence of IgG capable of stimulating intracellular Ca2+ mobilization. IgG from all preeclamptic patients activated AT1 receptors and increased intracellular free calcium. In contrast, none of the normotensive individuals had IgG capable of activating AT1 receptors. The specific mobilization of intracellular Ca2+ by AT1-AAs was blocked by losartan, an AT1 receptor antagonist, and by a 7-amino-acid peptide that corresponds to a portion of the second extracellular loop of the AT1 receptor. In addition, we have shown that AT1-AA-stimulated mobilization of intracellular Ca2+ results in the activation of the transcription factor, nuclear factor of activated T cells. CONCLUSIONS: These results suggest that maternal antibodies capable of activating AT1 receptors are likely to account for increased intracellular free Ca2+ concentrations and changes in gene expression associated with preeclampsia.

Adult↗

PubMed2004

Significant differences in proton trimethyl ammonium signals between human gastrocnemius and soleus muscle.

PURPOSE: To study the apparent heterogeneous characteristics of trimethyl ammonium (TMA) in healthy human muscles at rest, and to illustrate the importance of establishing the baseline characteristics of proton metabolites in muscles with a West Nile patient. MATERIALS AND METHODS: Point-resolved spectroscopy (PRESS) magnetic resonance spectroscopy imaging (MRSI) with lipid suppression and optional outer-volume presaturation were used to acquire 1H spectra of human muscles at rest at 1.5 Tesla. A total of 28 subjects (27 normal volunteers and 1 patient with West Nile disease) between the ages of 22 and 76 participated in the study. RESULTS: The apparent T2 values of TMA for soleus and gastrocnemius muscles in normal volunteers are 180 +/- 50 and 80 +/- 20 msec, respectively. This difference has profound effects on the apparent spectral pattern of 1H metabolites. The TMA/total creatine (tCr) spectral pattern of the soleus muscle of a West Nile patient resembles that of gastrocnemius muscle of healthy volunteers. CONCLUSION: There are significant differences in the apparent T2 values of TMA between healthy soleus and gastrocnemius muscles at rest. It is important to establish the baseline characteristics of proton metabolites before clinical or physiological studies can be performed.

Adult↗

PubMed2004

Analysis of multi-exponential relaxation data with very short components using linear regularization.

Linear regularization is a common and robust technique for fitting multi-exponential relaxation decay data to obtain a distribution of relaxation times. The regularization algorithms employed by the Uniform-Penalty inversion (UPEN) and CONTIN computer programs have been compared using simulated transverse (T2) relaxation data derived from a typical bimodal distribution observed in cartilage tissue which contain a component shorter than t(0), the time of the first decay sample. We examined the reliability of detecting sub-t(0) relaxation components and the accuracy of statistical estimates of T2 distribution parameters. When the integrated area of the sub-t(0) component relative to that of the total distribution was greater than 0.25, our results indicated a signal-to-noise threshold of about 300 for detecting the presence of the sub-t(0) component with a probability of 0.9 or greater. This threshold was obtained using both the UPEN and CONTIN algorithms. In addition, when using the second-derivative-squared regularizer, UPEN solutions provided statistical estimates of T2 distribution parameters which were substantially free of the biasing effect of the regularizer observed in analagous CONTIN solutions.

Algorithms↗

PubMed2004

The structural adaptations in compressed articular cartilage by microscopic MRI (microMRI) T(2) anisotropy.

OBJECTIVES: To detect structural adaptations of collagen fiber matrix in compressed articular cartilage in individual sub-tissue zones by microscopic magnetic resonance imaging (microMRI) at 23 microm in-depth resolution. DESIGN: Each of the six beagle humeral cartilage specimens was placed in a specially built nonmetallic compression device inside an in-situ rotation device, and was imaged four times at 7T: without and during static compression, and at two orientations: 0 degrees and 55 degrees . Proton intensity images and quantitative T(2) maps were constructed and analyzed. RESULTS: Upon compression at 55 degrees (the magic angle), rather than appearing homogenous, T(2)-weighted intensity images of cartilage showed a distinct laminar appearance and the T(2) profiles exhibited two distinctive peaks. At both 0 degrees and 55 degrees orientations, lower values of T(2) were observed in compressed tissue. A significant correlation was established between changes in tissue T(2) at 55 degrees and a thickness reduction due to compression. At a mean of 20% strain value, modifications in cartilage structure were studied at each histological zone. We found that the percentage of superficial zone was significantly doubled, the percentage of radial zone was significantly decreased by 10%, and no significant change in the transitional zone. CONCLUSIONS: External loading can induce a new kind of laminar appearance at the magic angle. microMRI T(2) anisotropy can be used to analyze the zone-specific alterations in collagen fibril organization in articular cartilage in response to mechanical compression.

Adaptation, Physiological↗

PubMed2004

Spectral pattern of total creatine and trimethyl ammonium in multiple sclerosis.

Fatigue and impairment mobility are frequent problems in multiple sclerosis (MS). Despite its enormous potential, in vivo (1)H MRS of skeletal muscles for MS patients is a largely unexplored field. One fundamental question remains unanswered: whether MS can cause observable proton metabolite changes. High quality two-dimensional in vivo (1)H MRS reveals that the spectral pattern of total creatine (tCr) and trimethyl ammonium (TMA) of soleus muscles of MS patients can be distinctively different from that of healthy volunteers, and in vivo (1)H MRS of skeletal muscles has a potential to become a useful tool in MS study.

Creatine↗

PubMed2003

Transforming growth factor alpha-mediated gastroprotection against stress ulceration in the rat: involvement of capsaicin-sensitive sensory neurons.

Exogenously administered TGF alpha has been shown to protect rodent gastric mucosa against injury caused by acid-dependent and acid-independent injury. The present study examined whether the gastroprotective effects of TGF alpha on stress-induced gastric ulceration in the rat involves activation of capsaicin-sensitive sensory neurons. Fasted male SD rats were subjected to water restraint stress (WRS) for four hours. Thereafter, rats were euthanized; the stomach opened and macroscopic areas of gastric ulceration quantitated (mm(2)). Gastric tissue contents of TGF alpha and the sensory neuropeptide, calcitonin gene-related peptide (CGRP) were determined by radioimmunoassay. Prior to stress rats received TGF alpha 50, 100 or 200 microg/kg by intraperitoneal injection. Sensory denervation was accomplished by high dose capsaicin treatment. WRS caused severe ulceration in the gastric corpus; 46.1 + 6.6 mm(2). Parenteral administration of TGF alpha caused dose-dependent reduction in gastric injury: 34.7 + 4.9 mm(2) with 50 microg/kg (p < 0.05); 25.4 + 3.6 mm(2) with 100 microg/kg (p < 0.001) and 9.4 + 0.8 mm(2) with 200 microg/kg (p < 0.001). The gastroprotective action of TGF alpha (200 microg/kg, i.p.) was abolished by capsaicin-induced sensory denervation. In addition, WRS ulceration was associated with significant reduction in gastric CGRP (-42%) and TGF alpha (-48%) content. Reduction in CGRP content was prevented by TGF alpha pretreatment. We conclude that: 1) TGF alpha caused dose-dependent gastroprotection against WRS ulceration, 2) TGF alpha-mediated gastric mucosal protection was prevented by capsaicin-induced sensory denervation and, 3) stress-induced injury was associated with significant reduction in gastric content of both TGF alpha and CGRP.

Animals↗

PubMed2003

Mammalian target of rapamycin and protein kinase A signaling mediate the cardiac transcriptional response to glutamine.

The addition of glutamine as a major nutrient to cultured neonatal rat cardiomyocytes produced an increase in myocyte size and the organization of actin into myofibrillar arrays. The cellular response was associated with increased abundance of the mRNAs encoding the contractile proteins, alpha-myosin heavy chain and cardiac alpha-actin, and the metabolic enzymes, muscle carnitine palmitoyl transferase I and muscle adenylosuccinate synthetase (ADSS1). Adss1 gene expression was induced approximately 5-fold in glutamine-treated rat neonatal cardiac myocytes. The induction was mediated through the protein kinase A and mammalian target of rapamycin signaling pathways and required a cyclic AMP response element associated with the promoter region of the Adss1 gene. These results highlight glutamine as a major nutrient regulator of cardiac gene expression and identify protein kinase A and mammalian target of rapamycin signaling pathways as mediators of the cardiomyocyte transcriptional response.

Adenylosuccinate Synthase↗

PubMed2003

Imaging the physical and morphological properties of a multi-zone young articular cartilage at microscopic resolution.

PURPOSE: To characterize a number of physical and morphologic properties of young articular cartilage. These properties include the anisotropy of T(2) relaxation, optical retardation, orientation of the collagen fibrils, total thickness of the tissue, number of histologic sub-zones in the tissue, width of individual sub-zones, and correlation between the depths of the local T(2) maxima and the local retardation minima. MATERIALS AND METHODS: Microscopic magnetic resonance imaging (mciro MRI) and polarized light microscopy (PLM) were used to examine three side-by-side specimens from a humeral head of a three-month-old beagle that exhibited a unique topographic heterogeneity from three-zones centrally to multi-zone peripherally. RESULTS: The centrally located specimen showed that the collagen fibrils across the tissue depth have a pattern of the classic three histologic sub-zones (tangential, transitional, and radial). A much more complicated multi-zone structure was found in the specimen located peripherally, with a second transitional zone and a second tangential zone located at the deep part of the tissue. We also showed that the orientation of the collagen fibrils that form the cocoon-shaped territorial matrix surrounding the clusters of chondrocytes can be imaged by our PLM technique. CONCLUSION: The results from the young animal in this report, together with our observations from older animals, demonstrate that MRI and PLM can be used to study the epiphyseal expansion of cartilage in young animals during its growth and subsequent loss in older animals. An illustrative model for the structure of collagen fibrils in a humeral head is suggested as an extension to the classic three-zone model for young articular cartilage.

Animals↗

PubMed2003

Osmotic stress increases cullin-5 (cul-5) mRNA in the rat cerebral cortex, hypothalamus and kidney.

Cullin-5 (cul-5), a member of the cullin gene family, may have a role in proteolysis and cell cycle regulation. Our recent study demonstrated that cul-5 mRNA is ubiquitously expressed in the central nervous system and many peripheral organs. The present study used quantitative realtime polymerase chain reaction to measure changes in cul-5 mRNA expression as a consequence of osmotic stress in vivo. Cul-5 mRNA levels were significantly increased in the rat cerebral cortex, hypothalamus and kidney following 48 h of water deprivation. Water deprivation for a shorter time period (24 h) or rehydration (24 h access to water following 48 h of water deprivation) also elevated kidney cul-5 mRNA levels. Water deprivation did not significantly alter cul-5 mRNA levels in the brainstem, cerebellum, hippocampus, lung or liver. Since cul-5 appears to be linked to proteosome-mediated protein degradation, it may have a role in protein regulation under conditions of osmotic stress.

Animals↗

PubMed2003

Maternal autoantibodies from preeclamptic patients activate angiotensin receptors on human trophoblast cells.

OBJECTIVES: Recent evidence indicates that preeclampsia is associated with the presence of autoantibodies capable of activating the angiotensin II receptor, AT1. We sought to evaluate the role of AT1 agonistic autoantibodies (AT1-AA) in two major features of preeclampsia-increased plasminogen activator inhibitor-1 (PAI-1) production and shallow trophoblast invasion. METHODS: This study included 38 pregnant patients, 20 of whom had severe preeclampsia and 18 normotensive individuals. Immunoglobulin (Ig)G was purified from these individuals, and the presence of AT1-AA was determined based on its ability to stimulate an increase in the contraction rate of cultured rat neonatal cardiac myocytes. Immortalized human trophoblasts were chosen to study PAI-1 production and secretion after treatment with IgG from normotensive and preeclamptic women. An in vitro Matrigel invasion assay was used to test the effect of AT1-AA on the invasive properties of human trophoblasts. Losartan and cyclosporin A were used to determine whether the AT1-AA-induced stimulation of PAI-1 secretion is through the AT1 receptor and the calcineurin-nuclear factor of activated t-cells (NFAT)-dependent pathway. RESULTS: The results show that IgG from 18 of 20 severely preeclamptic women stimulated increased cardiomyocyte contraction rates of 20-40 beats per minute. A significant stimulation of PAI-1 secretion from human trophoblasts was observed with IgG from the same 18 of 20 patients with severe preeclampsia. Of IgG obtained from 18 normotensive pregnant patients, only two showed a relatively low level of biologic activity in the cardiomyocyte contraction and PAI-1 secretion assays. Activation of AT1 receptors by AT1-AA was blocked by losartan (an AT1 receptor antagonist) and by a seven amino acid peptide corresponding to a sequence present on the second extracellular loop of the AT1 receptor. Activation of AT1 receptors by AT1-AA resulted in decreased trophoblast invasiveness as determined by the in vitro Matrigel invasion assay. Additional data indicate that AT1 receptor activation by AT1-AA is followed by the downstream activation of the calcium-dependent calcineurin-NFAT signaling pathway leading to increased PAI-1 gene expression. CONCLUSION: Our findings suggest that maternal autoantibody with the ability to activate AT1 receptors may account for two features of preeclampsia, increased PAI-1 production and shallow trophoblast invasion.

Animals↗

PubMed2003

Mechanisms of transforming growth factor-alpha (TGF-alpha) induced gastroprotection against ethanol in the rat: roles of sensory neurons, sensory neuropeptides, and prostaglandins.

The mechanisms by which transforming growth factor-a (TGP-alpha) protects the stomach against mucosal injury are incompletely understood. The aim of this study was to examine the roles of sensory neurons, sensory neuropeptides and prostaglandins in TGFalpha gastroprotection against ethanol. Fasted rats received TGF-alpha (50 microg/kg, intraperitoneally) prior to orogastric ethanol (75% v/v, 1 ml). Gastric injury was quantitated 30 min after ethanol. Involvement of sensory neurons and the sensory neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP), were examined by capsaicin deafferentation and specific receptor antagonist infusion, respectively. Indomethacin (10 mg, intragastrically) was used to determine the role of prostaglandins in TGF-alpha-mediated gastroprotection. TGF-alpha significantly diminished ethanol-induced gastric lesion area to 5.7 +/- 0.8 mm2 vs 41.1 +/- 5.2 mm2 (p < 0.001). Sensory denervation and CGRP-receptor blockade abolished the TGF-alpha protective effect. In contrast, SP antagonist and indomethacin did not alter TGF-alpha gastroprotection. In conclusion, TGF-alpha-mediated gastroprotection involves sensory neuron activation and CGRP release and this protective effect did not involve substance P or prostaglandin generation.

Analysis of Variance↗

PubMed2002

Angiotensin II inhibits human trophoblast invasion through AT1 receptor activation.

Trophoblast implantation depends, in part, on the controlled production of plasmin from plasminogen, a process regulated by plasminogen activators and plasminogen activator inhibitors. We have determined that angiotensin II (Ang II) stimulates plasminogen activator inhibitor-1 (PAI-1) synthesis and secretion in human trophoblasts in a time- and concentration-dependent manner. Our results indicate that Ang II activates PAI-1 gene expression through the AT1 receptor and involves the calcium-dependent activation of calcineurin and the nuclear translocation of NFAT. Increased PAI-1 synthesis and secretion is associated with reduced trophoblast invasion as judged by an in vitro invasion assay. These studies are the first to link the renin-angiotensin system with the fibrinolytic system to regulate trophoblast invasion.

Angiotensin II↗

PubMed2002

Orientational dependence of T2 relaxation in articular cartilage: A microscopic MRI (microMRI) study.

The experiments reported herein are the first MRI investigations of the orientational dependence of T(2) relaxation in articular cartilage at microscopic resolution over the 360 degrees angular space. For each of six canine cartilage specimens, 48 independent T(2)-weighted proton images were acquired for 12 different specimen orientations. Pixel-wise monoexponential fits of these proton images produced 12 T(2) relaxation images, each with an in-plane pixel resolution of 13.7 microm. Cartilage T(2) as a function of specimen orientation was shown to follow approximately the angular dependence of the nuclear dipole-dipole interaction, with local maxima at approximately 55 degrees, 125 degrees, 235 degrees, and 305 degrees. However, the relative amplitudes of the T(2) maxima deviated somewhat from those expected from the dipolar interaction. The amplitudes of these maxima also varied with tissue depth: the largest amplitudes were found in the radial zone, intermediate amplitudes were found in the superficial zone, and there was a continuous decrease in amplitude approaching the transitional zone from the superficial zone above and the radial zone below. We explain the discrepancy between the observed T(2) anisotropy and the angular dependence of the dipolar interaction by means of a simple model which considers the average of one isotropic and two anisotropic spin populations-the first being associated with "free" water, and the latter two arising from collagen-associated waters. We show that even for the "long" T(2) components, which arise in multiple-compartment studies of collagen-water systems, there appears to be two subpopulations. Each has the same peak value of T(2), but the angular dependence of one is shifted in phase by 90 degrees relative to the other by virtue of the fact that each is associated with groups of mutually perpendicular fibrils.

Animals↗

PubMed2002

Pregnancy-induced changes in renin gene expression in mice.

A puzzling feature of the renin-angiotensin system during pregnancy is the appearance in the maternal circulation of a large increase in the concentration of prorenin and renin. The physiologic role of these changes is not understood. We determined that high levels of renin protein occur in the circulation of pregnant mice, thereby establishing the mouse as a valuable model for understanding gestation-induced changes in the renin-angiotensin system. We used the murine model to show that high levels of renin gene expression occur at the mother-fetus interface, first in maternal decidua and subsequently in placentas. These results were obtained using ICR mice that have 2 related renin genes, Ren1 and Ren2. We also examined renin gene expression in C57Bl/6 mice that have only the Ren1 gene. In these mice, very little renin gene expression was observed in placentas but instead was upregulated in kidneys during pregnancy. In both ICR and C57Bl/6 mice, there is an increase in renin protein in the maternal circulation during pregnancy. However, these mice differ with regard to gestation-induced sites of increased renin gene expression. These studies suggest that mice are a convenient and valuable model for studying renin gene expression during pregnancy.

Animals↗

PubMedDate not supplied

GABAergic mechanisms of gastroprotection in the rat: role of sensory neurons, prostaglandins, and nitric oxide.

gamma-Aminobutyric acid (GABA) is a neurotransmitter found in both the central and the peripheral nervous systems including the gastrointestinal tract. The aims of the present studies were to examine mechanisms by which GABA exerts gastroprotective effects against ethanol- and water-restraint stress (WRS)-induced gastric mucosal injury in the rat. GABA, administered intragastrically (400 mg/kg), induced gastroprotection against ethanol and WRS by activating gastric sensory neurons to release calcitonin gene-related peptide (CGRP) and promote nitric oxide (NO) synthesis and release. Furthermore, these protective effects of GABA were associated with an increase in gastric mucosal blood flow (GMBF) that was dependent on sensory neuron and NO systems. GABA-mediated protection involved GABAA receptor activation and prostaglandin generation. In conclusion, intraluminal GABA protects the stomach against ethanol- and WRS-induced injury by mechanisms which involve sensory neuron/CGRP/NO pathways and increases in GMBF and prostaglandin generation.

Animals↗