Biomedical subjects

T Xu

Publications and source records attributed to T Xu.

At least 37 records · Page 2Linked to original sources

PubMed2001

[An application value of detecting K-ras and p53 gene mutation in the stool and pure pancreatic juice for diagnosis of early pancreatic cancer].

OBJECTIVE: To explore new methods for the early diagnosis of pancreatic cancer through detecting of K-ras, p53 mutations in pancreatic juice and stool. METHODS: 201 patients in PUMC Hospital from 1994-2000. 5 and 60-control individuals were enrolled. K-ras point mutations were detected by PCR-RFLP, however p53 mutation was detected by PCR-SSCP. RESULTS: K-ras mutations in pancreatic juice were found in 87.8% (36/41) of pancreatic cancer, 23.5% (4/17) of benign pancreatic disease. Of 261 stools specimens, amplification was successful in 235 (90.0%). K-ras mutation in stool were found in 88.0% (66/75) of pancreatic cancer 51.1% (24/47) of benign pancreatic disease, 19.6% (9/46) of normal individuals. p53 mutation in pancreatic juice were found in 47.4% (18/38), 12.5% (2/16) of benign pancreatic disease, p53 mutation in stool were found in 37.1% (23/62), 19.1% (4/12) of chronic pancreatitis. CONCLUSION: K-ras mutation in pancreatic juice has high sensitivity and specificity, so it can be used as a adjunct in the diagnosis of pancreatic cancer. Detection of K-ras mutation combined with p53 mutation in stool can be helpful to screen for pancreatic carcinoma. Combined with serum CA19-9 detection, it might increase the early diagnostic rate of pancreatic carcinoma.

Adult↗

PubMed2001

Molecular organization of the nodal region is not altered in spontaneously diabetic BB-Wistar rats.

We examined the organization of the molecular components of the nodal region in spontaneously diabetic BB-Wistar rats. Frozen sections and teased fibers from the sciatic nerves were immunostained for nodal (voltage-gated Na(+) channels, ankyrin(G), and ezrin), paranodal (contactin, Caspr, and neurofascin 155 kDa), and juxtaparanodal (Caspr2, the Shaker-type K(+) channels Kv1.1 and Kv1.2, and their associated subunit Kvbeta2) proteins. All of these proteins were properly localized in myelinated fibers from rats that had been diabetic for 15-44 days, compared to age-matched, nondiabetic animals. These results demonstrate that the axonal membrane is not reorganized, so nodal reorganization is not likely to be the cause of nerve conduction slowing in this animal model of acute diabetes.

Animals↗

PubMed2001

Ezrin, radixin, and moesin are components of Schwann cell microvilli.

Ezrin, radixin, and moesin (ERM proteins), as well as the neurofibromatosis 2 (NF2) tumor suppressor merlin/schwannomin, all belong to the protein 4.1 family, yet only merlin is a tumor suppressor in Schwann cells. To gain insight into the possible functions of ERM proteins in Schwann cells, we examined their localization in peripheral nerve, because we have previously shown that merlin is found in paranodes and in Schmidt-Lanterman incisures. All three ERM proteins were highly expressed in the microvilli of myelinating Schwann cells that surround the nodal axolemma as well as in incisures and cytoplasmic puncta in the vicinity of the node. In all of these locations, ERM proteins were colocalized with actin filaments. In contrast, ERM proteins did not surround nodes in the CNS. The colocalization of ERM proteins with actin indicates that they have functions different from those of merlin in myelinating Schwann cells.

Actin Cytoskeleton↗

PubMed2001

Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size.

Tuberous sclerosis complex is a dominant disorder that leads to the development of benign tumors in multiple organs. We have isolated a mutation in the Drosophila homolog of TSC1 (Tsc1). Cells mutant for Tsc1 are dramatically increased in size yet differentiate normally. Organ size is also increased in tissues that contain a majority of mutant cells. Clones of Tsc1 mutant cells in the imaginal discs undergo additional divisions but retain normal ploidy. We also show that the Tsc1 protein binds to Drosophila Tsc2 in vitro. Overexpression of Tsc1 or Tsc2 alone in the wing and eye has no effect, but co-overexpression leads to a decrease in cell size, cell number, and organ size. Genetic epistasis data are consistent with a model that Tsc1 and Tsc2 function together in the insulin signaling pathway.

Animals↗

PubMed2001

Microtubules are involved in glucose-dependent dissociation of the yeast vacuolar [H+]-ATPase in vivo.

The vacuolar [H(+)]-ATPases (V-ATPases) are composed of a peripheral V(1) domain and a membrane-embedded V(0) domain. Reversible dissociation of the V(1) and V(0) domains has been observed in both yeast and insects and has been suggested to represent a general regulatory mechanism for controlling V-ATPase activity in vivo. In yeast, dissociation of the V-ATPase is triggered by glucose depletion, but the signaling pathways that connect V-ATPase dissociation and glucose metabolism have not been identified. We have found that nocodazole, an agent that disrupts microtubules, partially blocked dissociation of the V-ATPase in response to glucose depletion in yeast. By contrast, latrunculin, an agent that disrupts actin filaments, had no effect on glucose-dependent dissociation of the V-ATPase complex. Neither nocodazole nor latrunculin blocked reassembly of the V-ATPase upon re-addition of glucose to the medium. The effect of nocodazole appears to be specifically through disruption of microtubules since glucose-dependent dissociation of the V-ATPase was not blocked by nocodazole in yeast strains bearing a mutation in tubulin that renders it resistant to nocodazole. Because nocodazole has been shown to arrest cells in the G(2) phase of the cell cycle, it was of interest to determine whether nocodazole exerted its effect on dissociation of the V-ATPase through cell cycle arrest. Glucose-dependent dissociation of the V-ATPase was examined in four yeast strains bearing temperature-sensitive mutations that arrest cells in different stages of the cell cycle. Because dissociation of the V-ATPase occurred normally at both the permissive and restrictive temperatures in these mutants, the results suggest that in vivo dissociation is not dependent upon cell cycle phase.

Antineoplastic Agents↗

PubMed2001

Tropical origins for recent North Atlantic climate change.

Evidence is presented that North Atlantic climate change since 1950 is linked to a progressive warming of tropical sea surface temperatures, especially over the Indian and Pacific Oceans. The ocean changes alter the pattern and magnitude of tropical rainfall and atmospheric heating, the atmospheric response to which includes the spatial structure of the North Atlantic Oscillation (NAO). The slow, tropical ocean warming has thus forced a commensurate trend toward one extreme phase of the NAO during the past half-century.

Journal Article↗

PubMed2001

TRM1, a YY1-like suppressor of rbcS-m3 expression in maize mesophyll cells.

The genes rbcS and rbcL encode, respectively, the small and large subunits of the photosynthetic carbon dioxide fixation enzyme ribulose bisphosphate carboxylase/oxygenase. There is a single rbcL gene in each chloroplast chromosome; a family of rbcS genes is located in the nuclear genome. These two genes are not expressed in mesophyll cells but are in adjacent bundle-sheath cells of leaves of the C4 plant Zea mays. Two regions of the maize gene rbcS-m3 are required for suppressing expression in mesophyll cells. One region is just beyond the translation termination site in the 3' region, and the other is several hundred base pairs upstream of the transcription start site. A binding site for a protein with limited homology to the viral, yeast, and mammalian transcription repressor-activator YY1 (Yin-Yang I), has now been identified in the 3' region. A maize gene for a protein with zinc fingers homologous to those of YY1 has been isolated, characterized, and expressed in Escherichia coli. The gene is designated trm1 (transcription repressor-maize 1). The protein TRM1 binds to the YY1-like site and, in addition, TRM1 binds to two sequence regions in the 5' region of the gene that have no homology to the YY1 site. Mutagenesis or deletion of any of these three sequences eliminates repression of rbcS-m3 reporter genes in mesophyll cells.

Amino Acid Sequence↗

PubMed2001

Protein zero is necessary for E-cadherin-mediated adherens junction formation in Schwann cells.

Protein Zero (P0), the major structural protein in the peripheral nervous system (PNS) myelin, acts as a homotypic adhesion molecule and is thought to mediate compaction of adjacent wraps of myelin membrane. E-Cadherin, a calcium-dependent adhesion molecule, is also expressed in myelinating Schwann cells in the PNS and is involved in forming adherens junctions between adjacent loops of membrane at the paranode. To determine the relationship, if any, between P0-mediated and cadherin-mediated adhesion during myelination, we investigated the expression of E-cadherin and its binding partner, beta-catenin, in sciatic nerve of mice lacking P0 (P0(-/-)). We find that in P0(-/-) peripheral myelin neither E-cadherin nor beta-catenin are localized to paranodes, but are instead found in small puncta throughout the Schwann cell. In addition, only occasional, often rudimentary, adherens junctions are formed. Analysis of E-cadherin and beta-catenin expression during nerve development demonstrates that E-cadherin and beta-catenin are localized to the paranodal region after the onset of myelin compaction. Interestingly, axoglial junction formation is normal in P0(-/-) nerve. Taken together, these data demonstrate that P0 is necessary for the formation of adherens junctions but not axoglial junctions in myelinating Schwann cells.

Adherens Junctions↗

PubMed2001

Internodal specializations of myelinated axons in the central nervous system.

We have examined the localization of contactin-associated protein (Caspr), the Shaker-type potassium channels, Kv1.1 and Kv1.2, their associated beta subunit, Kvbeta2, and Caspr2 in the myelinated fibers of the CNS. Caspr is localized to the paranodal axonal membrane, and Kv1.1, Kv1.2, Kvbeta2 and Caspr2 to the juxtaparanodal membrane. In addition to the paranodal staining, an internodal strand of Caspr staining apposes the inner mesaxon of the myelin sheath. Unlike myelinated axons in the peripheral nervous system, there was no internodal strand of Kv1.1, Kv1.2, Kvbeta2, or Caspr2. Thus, the organization of the nodal, paranodal, and juxtaparanodal axonal membrane is similar in the central and peripheral nervous systems, but the lack of Kv1.1/Kv1.2/Kvbeta2/Caspr2 internodal strands indicates that the oligodendrocyte myelin sheaths lack a trans molecular interaction with axons, an interaction that is present in Schwann cell myelin sheaths.

Animals↗

PubMed2001

A study design to investigate the effect of intense Tai Chi in reducing falls among older adults transitioning to frailty.

This paper describes the study design, methodological considerations, and baseline characteristics of a clinical trial to determine if intense (48 weeks, twice per week) Tai Chi practice can reduce the frequency of falls among older adults transitioning to frailty compared to a wellness education program. Twenty facilities will be stratified on socioeconomic status and facility type and randomly assigned to one of the two interventions. Secondary outcome measurements include variables related to function, behavior, and the biomechanics of movement. This study is unique because it represents an effort to offer a novel physical intervention to a large sample of transitional frail adults, a population that has received few formal exercise interventions. In addition to bringing the interventions into facilities, a 1-year follow-up is also included to assess rates of change in outcome measurements.

Accidental Falls↗

PubMed2001

Mechanisms of size control.

The study of organ size control is a discipline of developmental biology that is largely unexplored. Although the size of an organ or organism depends largely on cell numbers and cell size, studies have found that the simple deregulation of cell proliferation or cell growth does not necessarily lead to changes in organ size. Recent genetic screens in Drosophila suggest that mutations that do affect organ size can be classified into three broad categories on the basis of their underlying effects: patterning, proliferation, and growth. Overall, experimental data suggest that organ size might be regulated by a 'total mass checkpoint' mechanism which functions to link the regulation of cell size and cell proliferation. The mechanisms of organ size control could also be critical targets for evolutionary events or disease processes such as tumorigenesis.

Animals↗

PubMed2001

SV2 modulates the size of the readily releasable pool of secretory vesicles.

The exocytosis of neurotransmitters is regulated by calcium and is plastic - features that suggest specialized regulation of the basic membrane trafficking process. Here we show that Synaptic Vesicle Protein 2 (SV2), a protein specific to neurons and endocrine cells, is required to maintain a pool of vesicles available for calcium-stimulated exocytosis. Direct measures of exocytosis in adrenal chromaffin cells showed that the calcium-induced exocytotic burst, which operationally defines the readily releasable pool of vesicles, was significantly reduced in mice lacking SV2A. Burst kinetics were normal in cells from SV2A knockout animals, however, indicating that SV2 functions before the final events of fusion. Analyses of SDS-resistant SNARE (soluble NSF (N-ethylmaleimide-sensitive fusion) attachment protein receptor) complexes in brain tissue showed that loss of SV2A was associated with fewer SDS-resistant complexes. Our observations indicate that SV2 may modulate the formation of protein complexes required for fusion and therefore the progression of vesicles to a fusion-competent state.

Adrenal Medulla↗

PubMed2001

Effects of protracted nicotine exposure and withdrawal on the expression and phosphorylation of the CREB gene transcription factor in rat brain.

Addiction to nicotine may result in molecular adaptations in the neurocircuitry of specific brain structures via changes in the cyclic AMP-responsive element binding protein (CREB)-dependent gene transcription program. We therefore investigated the effects of chronic nicotine exposure and its withdrawal on CREB and phosphorylated CREB (p-CREB) protein levels in the rat brain. We report here that chronic nicotine exposure (1-h withdrawal) had no effect on the expression of CREB and p-CREB in the rat cortex and amygdala. On the other hand, decreases in the expression of CREB protein and phosphorylation of CREB occur in the cingulate gyrus, and in the parietal and the piriform but not in the frontal cortex during nicotine withdrawal (18 h) after nicotine exposure. It was also observed that CREB and p-CREB protein levels were significantly decreased in the medial and basolateral, but not in the central amygdala during nicotine withdrawal (18 h) after chronic nicotine exposure. Furthermore, it was found that nicotine withdrawal (18 h) after chronic nicotine exposure leads to decreased CRE-DNA binding without modulating cAMP-dependent protein kinase A activity in the cortex and the amygdala of rats. In addition, chronic nicotine treatment produced anxiolytic effects whereas nicotine withdrawal (18 h) produced anxiety in rats as measured by the elevated plus-maze test. These results provide the first evidence that decreased CREB activity and/or expression in specific cortical and amygdaloid brain structures may be involved in the underlying molecular mechanisms of nicotine dependence.

Amygdala↗

PubMed2001

Anticandida activity is retained in P-113, a 12-amino-acid fragment of histatin 5.

Through the analysis of a series of 25 peptides composed of various portions of the histatin 5 sequence, we have identified P-113, a 12-amino-acid fragment of histatin 5, as the smallest fragment that retains anticandidal activity comparable to that of the parent compound. Amidation of the P-113 C terminus increased the anticandidal activity of P-113 approximately twofold. The three histidine residues could be exchanged for three hydrophobic residues, with the fragment retaining anticandidal activity. However, the change of two or more of the five basic (lysine and arginine) residues to uncharged residues resulted in a substantial loss of anticandidal activity. A synthetic D-amino-acid analogue, P-113D, was as active against Candida albicans as the L-amino-acid form. In vitro MIC tests in low-ionic-strength medium showed that P-113 has potent activity against Candida albicans, Candida glabrata, Candida parapsilosis, and Candida tropicalis. These results identify P-113 as a potential antimicrobial agent in the treatment of oral candidiasis.

Amino Acid Sequence↗

PubMed2001

Cell cycle progression and cell division are sensitive to hypoxia in Drosophila melanogaster embryos.

We and others recently demonstrated that Drosophila melanogaster embryos arrest development and embryonic cells cease dividing when they are deprived of O2. To further characterize the behavior of these embryos in response to O2 deprivation and to define the O2-sensitive checkpoints in the cell cycle, embryos undergoing nuclear cycles 3-13 were subjected to O2 deprivation and examined by confocal microscopy under control, hypoxic, and reoxygenation conditions. In vivo, real-time analysis of embryos carrying green fluorescent protein-kinesin demonstrated that cells arrest at two major points of the cell cycle, either at the interphase (before DNA duplication) or at metaphase, depending on the cell cycle phase at which O2 deprivation was induced. Immunoblot analysis of embryos whose cell divisions are synchronized by inducible String (cdc25 homolog) demonstrated that cyclin B was degraded during low O2 conditions in interphase-arrested embryos but not in those arrested in metaphase. Embryos resumed cell cycle activity within ~20 min of reoxygenation, with very little apparent change in cell cycle kinetics. We conclude that there are specific points during the embryonic cell cycle that are sensitive to the O2 level in D. melanogaster. Given the fact that O2 deprivation also influences the growth and development of other species, we suggest that similar hypoxia-sensitive cell cycle checkpoints may also exist in mammalian cells.

Animals↗

PubMed2001

Mutation in pre-mRNA adenosine deaminase markedly attenuates neuronal tolerance to O2 deprivation in Drosophila melanogaster.

O2 deprivation can produce many devastating clinical conditions such as myocardial infarct and stroke. The molecular mechanisms underlying the inherent tissue susceptibility or tolerance to O2 lack are, however, not well defined. Since the fruit fly, Drosophila melanogaster, is extraordinarily tolerant to O2 deprivation, we have performed a genetic screen in the Drosophila to search for loss-of-function mutants that are sensitive to low O2. Here we report on the genetic and molecular characterization of one of the genes identified from this screen, named hypnos-2. This gene encodes a Drosophila pre-mRNA adenosine deaminase (dADAR) and is expressed almost exclusively in the adult central nervous system. Disruption of the dADAR gene results in totally unedited sodium (Para), calcium (Dmca1A), and chloride (DrosGluCl-alpha) channels, a very prolonged recovery from anoxic stupor, a vulnerability to heat shock and increased O2 demands, and neuronal degeneration in aged flies. These data clearly demonstrate that, through the editing of ion channels as targets, dADAR, for which there are mammalian homologues, is essential for adaptation to altered environmental stresses such as O2 deprivation and for the prevention of premature neuronal degeneration.

Adenosine Deaminase↗

PubMed2001

[The effects of iron compounds on SO2 and NO emissions in coal combustion process].

The effects of ferric/ferrous chlorides and ferric oxide on emissions in Tongchuan coal combustion process were experimentally investigated using thermogravimetric analyzer. The results show that all iron compounds used in the experiments, namely FeCl3, FeCl2 and Fe2O3 can change the emissions of SO2 and NO, but with different mechanisms and different magnitudes. FeCl3 plays the roles of both a catalyst and an absorbent in the conversions from coal-S to SO2 and from coal-N to NO. Due to the catalysis the activation energy required for the formation of SO2 and NO is reduced, the rates of the reactions leading to SO2 and NO increased. The catalysis is concerned with the forms of coal sulfur. Due to the absorption FeCl3 reacts with SO2 to produce FeSO4 [symbol: see text] Fe2(SO4)3. In addition FeCl3 can decrease the emissions of CO, i.e., the combustion characteristics can be changed. The effects of FeCl2 on the emissions of SO2, NO and CO are similar to those of FeCl3, but weaker. Fe2O3 can also decrease the SO2 and NO emissions to some extent, but has negligible influence on CO emission.

Catalysis↗

PubMed2001

[Inferring landmark displacements from changes in cephalometric angles].

OBJECTIVE: To investigate the appropriateness of using changes in angular measurements to reflect the actually profile changes. METHODS: The sample consists of 48 growing malocclusion patients, contained 24 Class I and 24 Class II subjects, treated by an experienced orthodontist using Edgewise technique. Landmark and superimpositional data were extracted from the previously prepared numerical database. Three pairs of angular and linear measures were computed by the Craniofacial Software Package. RESULTS: Although the associations between all three angular measures and their corresponding linear measures are statistically significant at the 0.001 level, the disagreement between these three pairs of measures are 10.4%, 22.9% and 37.5% respectively in this sample. CONCLUSIONS: The direction of displacement of anterior facial landmarks during growth and treatment cannot reliably be inferred merely from changes in cephalometric Angles.

Cephalometry↗