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Biomedical subjects

X Yang

Publications and source records attributed to X Yang.

At least 415 records · Page 23Linked to original sources
PubMed2000

Proteases for cell suicide: functions and regulation of caspases.

Caspases are a large family of evolutionarily conserved proteases found from Caenorhabditis elegans to humans. Although the first caspase was identified as a processing enzyme for interleukin-1beta, genetic and biochemical data have converged to reveal that many caspases are key mediators of apoptosis, the intrinsic cell suicide program essential for development and tissue homeostasis. Each caspase is a cysteine aspartase; it employs a nucleophilic cysteine in its active site to cleave aspartic acid peptide bonds within proteins. Caspases are synthesized as inactive precursors termed procaspases; proteolytic processing of procaspase generates the tetrameric active caspase enzyme, composed of two repeating heterotypic subunits. Based on kinetic data, substrate specificity, and procaspase structure, caspases have been conceptually divided into initiators and effectors. Initiator caspases activate effector caspases in response to specific cell death signals, and effector caspases cleave various cellular proteins to trigger apoptosis. Adapter protein-mediated oligomerization of procaspases is now recognized as a universal mechanism of initiator caspase activation and underlies the control of both cell surface death receptor and mitochondrial cytochrome c-Apaf-1 apoptosis pathways. Caspase substrates have bene identified that induce each of the classic features of apoptosis, including membrane blebbing, cell body shrinkage, and DNA fragmentation. Mice deficient for caspase genes have highlighted tissue- and signal-specific pathways for apoptosis and demonstrated an independent function for caspase-1 and -11 in cytokine processing. Dysregulation of caspases features prominently in many human diseases, including cancer, autoimmunity, and neurodegenerative disorders, and increasing evidence shows that altering caspase activity can confer therapeutic benefits.

Animals↗
PubMed2000

Real-time projection MR angiography: feasibility study.

Intraarterial injections of small doses of gadopentetate dimeglumine were combined with a fast spoiled-gradient-echo magnetic resonance (MR) sequence to obtain real-time projection angiographic images of the rabbit aorta and canine coronary arteries. Arterial filling and washout, as well as venous and perfusion phases, were clearly displayed, demonstrating that arterial fluoroscopy in which an MR technique is used is feasible.

Adult↗
PubMed2000

Intravascular MR imaging-guided balloon angioplasty with an MR imaging guide wire: feasibility study in rabbits.

PURPOSE: To develop a technique for intravascular magnetic resonance (MR)-guided balloon angioplasty with use of an MR imaging guide wire. MATERIALS AND METHODS: An MR imaging guide wire (0.6-mm loopless antenna) that could be placed within a balloon catheter was manufactured. The guide wire was expected to function as either an MR receiver probe in real-time MR imaging or a guide wire for use with interventional devices. Laparotomy was performed in eight rabbits, and a dilatable stenosis was created at the upper abdominal aorta. Balloon angioplasty, validated at pre- and postoperative MR aortography with renal contrast enhancement was performed by using a 1.5-T MR unit with a fast spoiled gradient-echo pulse sequence, short repetition and echo times, and a rate of three frames per second. RESULTS: During MR tracking, the entire length of the MR imaging guide wire was always visible as a band of high signal intensity. In all cases, the MR imaging guide wires were passed through the aortic stenoses dilated by means of balloon inflation. Before balloon angioplasty, flow in the aorta distal to the stenosis was decreased, which caused mild contrast enhancement in each kidney. After balloon angioplasty, distal flow was restored, resulting in substantial renal enhancement. CONCLUSION: The MR imaging guide wire is a potential tool for use in endovascular interventional MR imaging.

Angioplasty, Balloon↗
PubMed2000

Acid incubation causes exocytic insertion of NHE3 in OKP cells.

Incubation of opossum kidney clone P (OKP) cells in acid media (pH 6. 8) causes activation of Na(+)/H(+) exchanger 3 (NHE3) at 6, 12, and 24 h. OKP cell NHE3 protein abundance was increased by 45% at 24 h of acid incubation but was unaffected at 3-12 h. By contrast, apical membrane NHE3, measured by surface biotinylation, increased approximately twofold at 6, 12, and 24 h, mirroring the increase in activity. Acid incubation caused a 76% increase in exocytic insertion of NHE3 into the apical membrane but had no effect on endocytic internalization at 6 h. Latrunculin B, an inhibitor of microfilament organization, inhibited the acid-induced increases in apical membrane NHE3, exocytic insertion of NHE3, and NHE3 activity at 6 h. These studies demonstrate two mechanisms for acid-induced increases in NHE3 activity. Beginning at 6 h, there is an increase in apical membrane NHE3 that is due to stimulated exocytic insertion and is required for increased NHE3 activity. At 24 h, there is an additional increase in total cellular NHE3.

Acidosis, Renal Tubular↗
PubMed2000

CYP11B2 expression in rat liver and the effect of spironolactone on hepatic fibrogenesis.

OBJECTIVE: In consideration of the hypothetical possibility that locally produced aldosterone is likely to take an active part in fibrogenesis of the liver, we undertook the present study to investigate the expression of aldosterone synthase gene CYP11B2 in rat liver and the curative effect of spironolactone on fibrosis of the liver. METHODS AND MATERIALS: 160 Wistar rats weighing about 250 g were divided into four groups as follows: model group, spironolactone group, malotilate group and control group. After 2, 4, 6, 8 and 10 weeks, the animals were sacrificed. Morphological examination was based on microscopic and electron microscopic findings. The area of collagen was examined by an Image Analyse System (Leica). By means of reverse transcriptase-polymerase chain reaction and in situ hybridization, the expression of CYP11B2 was detected. RESULTS: The expression of CYP11B2 mRNA, which was localized in the endoplasm of fat-storing cells, was upregulated when fibrogenesis occurred. The grade of fibrosis and the area of collagen in the spironolactone group were less than those in the model group before the 6th week (p < 0.05). After the 6th week, there was no significant difference between the spironolactone group and the model group (p > 0.05). CONCLUSIONS: The expression of CYP11B2 mRNA is upregulated in fibrotic liver. Spironolactone can partly have a fibrogenesis-inhibiting effect in the early stage of CCl(4)-induced hepatic fibrogenesis.

Animals↗
PubMed2000

Nonproteolytic role for the urokinase receptor in cellular migration in vivo.

The urokinase receptor (uPAR) binds and localizes urokinase activity at cellular surfaces, facilitating fibrinolysis and cellular migration at sites of tissue injury. uPAR also participates in cellular signaling and regulates integrin-dependent adhesion and migration in vitro. We now report evidence that uPAR occupancy regulates cellular migration in vivo in the absence of functional urokinase. Recombinant murine KC (1.5 microg), a potent neutrophil chemoattractant, was delivered to the lungs of wild-type, urokinase-deficient or uPAR-deficient mice 18 h after intraperitoneal injection of 200 microg human immunoglobulin G (IgG) or a fusion protein composed of an amino-terminal receptor-binding fragment of urokinase and a human IgG Fc fragment (GFD-Fc). Whole lung lavage for recovery of leukocytes was performed 4 h later. KC treatment resulted in a 100-fold increase in lavage neutrophils. GFD-Fc injection resulted in >50% reduction in neutrophil influx in both wild-type and urokinase-deficient animals but had no effect on uPAR -/- mice. A concomitant reduction in alveolar protein leakage but no change in numbers of circulating neutrophils accompanied this attenuated inflammatory response. The reduction in neutrophil influx induced by GFD-Fc is thus related to uPAR occupancy and yet not due to disruption of uPAR-mediated proteolysis. These observations verify that protease-independent functions of uPAR operate in vivo and identify uPAR as a potential target for regulation of inflammatory processes characterized by neutrophil-mediated injury.

Administration, Intranasal↗
PubMed2000

A calpain-10 gene polymorphism is associated with reduced muscle mRNA levels and insulin resistance.

Previous linkage studies in Mexican-Americans localized a major susceptibility locus for type 2 diabetes, NIDDM1, to chromosome 2q. This evidence for linkage to type 2 diabetes was recently found to be associated with a common G-->A polymorphism (UCSNP-43) within the CAPN10 gene. The at-risk genotype was homozygous for the UCSNP-43 G allele. In the present study among Pima Indians, the UCSNP-43 G/G genotype was not associated with an increased prevalence of type 2 diabetes. However, Pima Indians with normal glucose tolerance, who have a G/G genotype at UCSNP-43, were found to have decreased rates of postabsorptive and insulin-stimulated glucose turnover that appear to result from decreased rates of glucose oxidation. In addition, G/G homozygotes were found to have reduced CAPN10 mRNA expression in their skeletal muscle. A decreased rate of insulin-mediated glucose turnover, or insulin resistance, is one mechanism by which the polymorphism in CAPN10 may increase susceptibility to type 2 diabetes mellitus in older persons.

Adolescent↗
PubMed2000

Early-latency somatosensory evoked potentials elicited by electrical acupuncture after needling acupoint LI-4.

The stimulating methods of prior studies on somatosensory evoked potentials (SEPs) elicited by acupoint stimulus had involved surface electrodes, while the clinical practice of acupuncture is mostly performed by inserting the acupuncture needle inside the body. Clinical observations show that there are often some special sensations when LI-4 is needled. To observe if the SEPs produced by acupoint acupuncture had a distinguishing property, we studied the SEPs elicited by electrical acupuncture after the acupuncture needle was inserted into LI-4 and its control point, and then mapped them with the 128-channel Electric Brain Signal Image system. We also compared this to SEPs by median nerve stimuli. Results showed that the most interesting finding was the marked differences of N1-P1 and N2-P2 amplitude between SEPs at LI-4 (SEP-LI) and its control point (SEP-CP), which were in the opposite direction. Marked differences were also found between latencies and amplitudes of the SEPs elicited by acupuncture and by median nerve stimulus (SEP-M). The differences between SEP-LI and SEP-CP might be due to the additional effects of the activation of nerve endings and muscle spindles in LI-4 to the SEPs formed by the activation of superficial and deep radial nerves during electrical acupuncture. The differences between SEPs to acupoint and median nerve stimuli might be mainly due to the different distances from the stimulated regions to the cerebral cortex, the diversity and the number of activated fibers.

Acupuncture Points↗
PubMed2000

Presenilin-1 regulates neuronal differentiation during neurogenesis.

Mutations in Presenilin-1 (PS1) are a major cause of familial Alzheimer's disease. Our previous studies showed that PS1 is required for murine neural development. Here we report that lack of PS1 leads to premature differentiation of neural progenitor cells, indicating a role for PS1 in a cell fate decision between postmitotic neurons and neural progenitor cells. Neural proliferation and apoptotic cell death during neurogenesis are unaltered in PS1(-/-) mice, suggesting that the reduction in the neural progenitor cells observed in the PS1(-/-) brain is due to premature differentiation of progenitor cells, rather than to increased apoptotic cell death or decreased cell proliferation. In addition, the premature neuronal differentiation in the PS1(-/-) brain is associated with aberrant neuronal migration and disorganization of the laminar architecture of the developing cerebral hemisphere. In the ventricular zone of PS1(-/-) mice, expression of the Notch1 downstream effector gene Hes5 is reduced and expression of the Notch1 ligand Dll1 is elevated, whereas expression of Notch1 is unchanged. The level of Dll1 transcripts is also increased in the presomitic mesoderm of PS1(-/-) embryos, while the level of Notch1 transcripts is unchanged, in contrast to a previous report (Wong et al., 1997, Nature 387, 288-292). These results provide direct evidence that PS1 controls neuronal differentiation in association with the downregulation of Notch signalling during neurogenesis.

Animals↗
PubMed2000

Jumeaux, a novel Drosophila winged-helix family protein, is required for generating asymmetric sibling neuronal cell fates.

The great majority of neurons in the Drosophila embryonic CNS are generated through two successive asymmetric cell divisions; neuroblasts (NBs) divide to produce another NB and a smaller ganglion mother cell (GMC); GMCs divide to generate two sibling neurons which can adopt distinct identities. During the division of the first born GMC from the NB4-2 lineage, GMC4-2a, Inscuteable (Insc) is localised to the apical cortex, Pon/Numb is localised to the basal cortex and two daughters with distinct identities, the RP2 motoneuron and its sibling RP2sib, are born. Resolution of distinct sibling neuronal fates requires correct apical localisation of Insc to facilitate the asymmetric localisation and preferential segregation of Pon/Numb to the basal daughter destined to become RP2. Here we report that jumeaux (jumu), which encodes a new member of the winged-helix family of transcription factors, is required to mediate the asymmetric localisation and segregation of Pon/Numb but is dispensable for Insc apical localisation during the GMC4-2a cell division. In jumu mutants GMC4-2a Pon/Numb asymmetric localisation is defective and both daughter neurons can adopt the RP2 identity. Jumu protein shows nuclear localisation and within the NB4-2 lineage is first detected only after the first neuroblast cell division, in GMC4-2a. Our results suggest that in addition to the correct formation of an apical complex, transcription mediated by Jumu is also necessary to facilitate the correct asymmetric localisation and segregation of Pon/Numb.

Alleles↗
PubMed2000

decapentaplegic is a direct target of dTcf repression in the Drosophila visceral mesoderm.

Drosophila T cell factor (dTcf) mediates transcriptional activation in the presence of Wingless signalling and repression in its absence. Wingless signalling is required for the correct expression of decapentaplegic (dpp), a Transforming Growth Factor (beta) family member, in parasegments 3 and 7 of the Drosophila visceral mesoderm. Here we demonstrate that a dpp enhancer element, which directs expression of a reporter gene in the visceral mesoderm in a pattern indistinguishable from dpp, has two functional dTcf binding sites. Mutations that reduce or eliminate Wingless signalling abolish dpp reporter gene expression in parasegment 3 and reduce it in parasegment 7 while ectopic expression of Wingless signalling components expand reporter gene expression anteriorly in the visceral mesoderm. However, mutation of the dTcf binding sites in the dpp enhancer results in ectopic expression of reporter gene expression throughout the visceral mesoderm, with no diminution of expression in the endogenous sites of expression. These results demonstrate that the primary function of dTcf binding to the dpp enhancer is repression throughout the visceral mesoderm and that activation by Wingless signalling is probably not mediated via these dTcf binding sites to facilitate correct dpp expression in the visceral mesoderm.

Animals↗
PubMed2000

The effects of verapamil SR and bisoprolol on reducing the sympathetic nervous system's activity.

To assess the response of the sympathetic nervous system (SNS) to the handgrip test in essential hypertensive patients and to evaluate the effects of verapamil SR and bisoprolol on the reduction of the SNS's activity. Seventy eight essential hypertensive patients (50 receiving verapamil SR treatment and 28 receiving bisoprolol treatment) took the handgrip test while the SBP, DBP, and HR were measured on three occasions during the test (before test, 3 min after the patients squeezed the handgrip, and 2 min after the handgrip was released). Before and after the patients received Verapamil SR or Bisoprolol treatment, the plasma concentrations of epinephrine(E), norepinephrine (NE), angiotensin-II (AII), aldosterone (ALD), endothelin-1 (ET-1) and renin activity (RA) were measured post-test. 1) In about 70% of the essential hypertensive patients, SNS activity was above normal. Their HR and BP exceeded 20% when responding to stress. 2) In these patients, the baseline plasma concentrations of E, NE, AII, ET-1, ALD, and RA were higher than those whose SNS's activity was normal. 3) After 6 weeks of treatment, all the patients' BPs decreased remarkably. Verapamil SR could reduce the plasma concentrations of NE, AII, and ET-1 and increase RA. Bisoprolol could reduce E and RA. These two antihypertension drugs can both decrease BP and reduce the activity of SNS through different mechanisms.

Adult↗
PubMed2000

In vivo demonstration that human parathyroid hormone 1-38 inhibits the expression of osteoprotegerin in bone with the kinetics of an immediate early gene.

Osteoprotegerin (OPG) is a potent inhibitor of osteoclast formation and function. To elucidate how OPG is regulated in bone, we examined (1) the expression and localization of OPG protein in bone tissue, (2) the effect of human parathyroid hormone 1-38 (hPTH 1-38) on OPG messenger RNA (mRNA) levels in rat femur metaphyseal and diaphyseal bone, and (3) the effect of hPTH(1-38) on expression of OPG mRNA in cultured osteoblast-like cells derived from the metaphysis and diaphysis, and in ROS 17/2.8 osteosarcoma cells. Because PTH has been shown to stimulate osteoblast activity via the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signal transduction pathway we also investigated whether PTH action on OPG in vivo is dependent on activation of cAMP/PKA pathway. Immunohistochemistry was used to evaluate OPG protein expression and Northern blot hybridization was used to analyze OPG mRNA expression both in vivo and in vitro. Immunohistochemistry of OPG protein expression in the rat distal femur metaphysis revealed that it was localized predominantly in preosteoblasts, osteoblasts, lining cells, and the osteoid layer, with occasional immunoreactivity in osteocytes and cells of the bone marrow. Subcutaneous (sc) administration of a single injection of hPTH(1-38) at 80 microg/kg induced a rapid and transient decrease in OPG mRNA expression in both metaphyseal and diaphyseal bone. The decrease in OPG message was evident by 1 h and mRNA levels returned to baseline after 3 h. PTH analog PTH(1-31), which stimulates intracellular cAMP accumulation, inhibited OPG expression, whereas PTH analogs (3-34 and 7-34) that do not stimulate cAMP production had no effect on expression. In contrast to PTH, prostaglandin E2 (PGE2) had no effect on OPG mRNA expression in vivo in the metaphyseal bone cells, under conditions in which PGE2 does promote expression of the c-fos gene. The in vivo effects of hPTH(1-38) on OPG mRNA were confirmed in isolated primary osteoblast cultures derived from either metaphyseal or diaphyseal bone as well as in ROS 17/2.8 osteosarcoma cells. We propose that the rapid and transient decrease in OPG expression may initiate a cascade of events resulting in the differentiation of osteoclast progenitor. Such a spatially and temporally programmed effect of PTH might contribute to bone turnover.

Animals↗
PubMed2000

Structure and function of S-adenosylhomocysteine hydrolase.

In mammals, S-adenosylhomocysteine hydrolase (AdoHcyase) is the only known enzyme to catalyze the breakdown of S-adenosylhomocysteine (AdoHcy) to homocysteine and adenosine. AdoHcy is the product of all adenosylmethionine (AdoMet)-dependent biological transmethylations. These reactions have a wide range of products, and are common in all facets of biometabolism. As a product inhibitor, elevated levels of AdoHcy suppress AdoMet-dependent transmethylations. Thus, AdoHcyase is a regulator of biological transmethylation in general. The three-dimensional structure of AdoHcyase complexed with reduced nicotinamide adenine dinucleotide phosphate (NADH) and the inhibitor (1'R, 2'S, 3'R)-9-(2',3'-dihyroxycyclopenten-1-yl)adenine (DHCeA) was solved by a combination of the crystallographic direct methods program, SnB, to determine the selenium atom substructure and by treating the multiwavelength anomalous diffraction data as a special case of multiple isomorphous replacement. The enzyme architecture resembles that observed for NAD-dependent dehydrogenases, with the catalytic domain and the cofactor-binding domain each containing a modified Rossmann fold. The two domains form a deep active site cleft containing the cofactor and bound inhibitor molecule. A comparison of the inhibitor complex of the human enzyme and the structure of the rat enzyme, solved without inhibitor, suggests that a 17 degrees rigid body movement of the catalytic domain occurs upon inhibitor/substrate binding.

Adenosylhomocysteinase↗
PubMed2000

Color image segmentation based on fuzzy rule-based reasoning applied to colonoscopic images.

A fuzzy color segmentation approach is developed for the analysis of colonoscopic images. The segmentation is made up of two phases: segmentation through histogram space filtering and region merging using fuzzy rule-base reasoning. The first phase involves using a scale-space filter to analyze the hue, saturation, and intensity (HSI) histograms to determine the number of classes and construct a 3-D class grid. The color image is then segmented based on the class grid. In the second phase, region merging based on applying the fuzzy rule-base is employed to guide the combining process of the segmented regions. For fuzzy reasoning, three criteria are evaluated, namely, the edge strength along the boundary, color similarity, and spatial connectivity of adjoining regions. Experimental testing of the proposed method applied on colonoscopic images was conducted, and the results are encouraging.

Colonoscopy↗
PubMed2000

Role of the alpha1 and alpha2 integrin cytoplasmic domains in cell morphology, motility and responsiveness to stimulation by the protein kinase C pathway.

The alpha1beta1 and alpha2beta1 integrins, extracellular matrix receptors for collagens and/or laminins, have similarities in structure and ligand binding. Recent studies suggest that the two receptors mediate distinct post-ligand binding events and are not simply redundant receptors. To discern the mechanisms by which the two receptors differ, we focused on the roles of the cytoplasmic domains of the alpha subunits. We expressed either full-length alpha1 integrin subunit cDNA (X1C1), full-length alpha2 integrin subunit cDNA (X2C2), chimeric cDNA composed of the extracellular and transmembrane domains of alpha2 subunit and the cytoplasmic domain of alpha1 (X2C1), chimeric cDNA composed of the extracellular and transmembrane domains of alpha1 subunit and the cytoplasmic domain of alpha2 (X1C2), alpha1 cDNA truncated after the GFFKR sequence (X1C0) or alpha2 cDNA truncated after the GFFKR sequence (X2C0) in K562 cells. Although the cytoplasmic domains of the alpha1 and alpha2 subunits were not required for adhesion, the extent of adhesion at low substrate density was enhanced by the presence of either the alpha1 or alpha2 cytoplasmic tail. Spreading was also influenced by the presence of an alpha subunit cytoplasmic tail. Activation of the protein kinase C pathway with phorbol dibutyrate-stimulated motility that was dependent upon the presence of the alpha2 cytoplasmic tail. Both the phosphatidylinosotide-3-OH kinase and the mitogen-activated protein kinase pathways were required for phorbol-activated, alpha2-cytoplasmic tail-dependent migration.

Antigens, CD↗
PubMed2000

S100P calcium-binding protein overexpression is associated with immortalization of human breast epithelial cells in vitro and early stages of breast cancer development in vivo.

The mechanism of cell immortalization of human breast epithelial cells leading to neoplastic transformation is not clear. The isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10F, have provided a valuable tool to identify genes involved in this process. Using the technique of differential display, we have identified seven cDNA bands differentially displayed in the MCF-10F cells when compared with the mortal S130 cells from which MCF-10F was originated. One of these bands was isolated and cloned. Sequence analysis revealed 99% homology to the EF-hand calcium-binding protein S100P (Placental). The clone was overexpressed in the immortal cell line MCF-10F when compared to the mortal counterpart S130 or other primary cultures of human breast epithelial cells. In addition, it was highly expressed in chemically transformed breast epithelial cell lines (BP1E and D3. 1), breast cancer cell line T47D, as well as in three invasive ductal carcinomas when compared to their normal adjacent tissue. The S100P protein was localized by immunohistochemistry, using a monoclonal antibody against the same amino acid sequence of the gene cloned, in ductal hyperplasias, in situ and invasive ductal carcinoma, but not in the normal tissues. We concluded that S100P overexpression is an early event that might play an important role in the immortalization of human breast epithelial cells in vitro and tumor progression in vivo.

Base Sequence↗