Biomedical subjects

T Xu

Publications and source records attributed to T Xu.

At least 91 records · Page 5Linked to original sources

PubMed1999

[Evaluation of Wits appraisal with superimposition method].

OBJECTIVE: To compare the conventional Wits appraisal with superimposed Wits appraisal in evaluation of sagittal jaw relationship change between pre and post orthodontic treatment. METHODS: The sample consists of 48-case pre and post treatment lateral head films. Computerized digitizing is used to get the cephalometric landmarks and measure conventional Wits value, superimposed Wits value and ANB angle. The correlation analysis among these three measures was done by SAS statistical package. RESULTS: The change of ANB angle has higher correlation with the change of superimposed Wits than that of the conventional Wits. The r-value is as high as 0.849 (P < 0.001). CONCLUSION: The superimposed Wits appraisal reflects the change of sagittal jaw relationship more objectively than the conventional one.

Cephalometry↗

PubMed1998

The N-termini of the alpha and beta subunits at the top of F1 stabilize the energy-transfer function in the mitochondrial F1Fo ATP synthase.

Limited trypsin digestion of isolated F1 removed 15 and 7 amino acids from the N-termini of the alpha and beta subunits respectively and left other subunits untouched as shown by electrophoresis, immunoblotting and protein sequencing. The cooperativity for ATP hydrolysis by soluble F1 was impaired by trypsin digestion. The Km2 obtained from Eadie-Hofstee plots apparently decreased in trypsin-digested F1 but the affinity for adenosine 5'-[beta,gamma-imido]triphosphate (AdoPP[NH]P) and GTP hydrolysis was not influenced. The inhibition of ATP hydrolysis by ADP was attenuated by trypsin digestion. Trypsin digestion of F1 did not affect its capacity to bind to Fo nor did it alter the sensitivity of ATP hydrolysis in the F1Fo reconstituted system to oligomycin and N,N'-dicyclohexylcarbodiimide. The cleavage of the alpha and beta subunits did, on the other hand impair: (a) the ATP-driven proton pumping in the reconstituted F1Fo complex: (b) the inhibition by F1 of passive proton conduction in Fo; (c) the inhibition of passive proton conduction in Fo by AdoPP[NH]P binding to F1. These results show that the limited cleavage of the N-termini of the alpha and beta subunits, located on the top of F1, results in decoupling of catalysis from proton transport. The possible relationship of these observations with the binding change rotatory model of the F1Fo ATP synthase is discussed.

Adenosine Triphosphate↗

PubMed1998

Positive and negative signals between interacting cells for establishing neural fate.

Specifying multiple cell types from a population of initially equivalent cells is a fundamental process in the development of all multicellular organisms. Neural development in the fruit fly Drosophila melanogaster provides an excellent venue in which to examine mechanisms of cell fate specification. Inhibitory cell-cell interactions mediated by genes of the Notch-Delta signaling pathway govern the selection of neural and epidermal fates among cells with equivalent developmental potential in a process termed lateral inhibition. Recent data on the roles of genes such as Notch, Delta, and kuzbanian warrant a rethinking of the lateral inhibition model. Furthermore, evidence for a positive signaling pathway promoting the neural fate among equivalent cells suggests that this mechanism acts in addition to lateral inhibition to specify cell fate. A balance of opposing signals may be necessary to correctly partition cells of different types from an initially homogeneous population of cells.

Animals↗

PubMed1998

Use of FLP/FRT system to study Drosophila development.

Marked clones in mosaic animals have been used extensively to answer developmental questions in Drosophila. Recently, the use of the FLP/FRT system has allowed for the high-frequency production of mosaic animals for 95% of Drosophila genes. Cell markers have been engineered in this system to label mutant clones in both developing tissues and adult cuticle. Strains carrying these genetically marked FLP/FRT chromosomes have greatly enhanced our ability to study gene function in both germline and somatic Drosophila cells.

Animals↗

PubMed1998

The angiotensin AT1 receptor antagonist CV-11974 regulates cerebral blood flow and brain angiotensin AT1 receptor expression.

We studied cerebral blood flow autoregulation by laser Doppler flowmetry, and expression of brain angiotensin II AT1 receptors by quantitative autoradiography, after administration of an angiotensin AT1 receptor antagonist, CV-11974 (Candesartan, 0.5 or 1.0 mg/kg.day) for two weeks via subcutaneously implanted osmotic pumps in adult normotensive Wistar Kyoto and spontaneously hypertensive male rats (SHR). In SHR, the autoregulation curve was shifted towards higher blood pressures, when compared with that of normotensive Wistar Kyoto rats. Administration of CV-11974 shifted the autoregulation curve toward lower blood pressures in both Wistar Kyoto and SHR, partially normalizing the autoregulation curve in SHR. CV-11974 treatment markedly decreased the expression of AT1 receptors in Wistar Kyoto rats, both in areas outside the blood brain barrier (subfornical organ, 95% decrease) and inside the blood brain barrier (nucleus of the tractus solitarius, 87% decrease, and paraventricular nucleus, 96% decrease). Our results demonstrate that blockade of AT1 receptors tends to normalize the shift to higher pressures in the autoregulation curve of genetically hypertensive rats, and has a profound modulatory role in brain angiotensin II AT1 receptors.

Angiotensin Receptor Antagonists↗

PubMed1998

Cytosolic Ca2+ acts by two separate pathways to modulate the supply of release-competent vesicles in chromaffin cells.

Recovery from depletion of the readily releasable pool of vesicles (RRP) in adrenal chromaffin cells was studied at differing basal [Ca2+]i or following protein kinase C (PKC) activation by phorbol esters. Following depletion, the pool size was estimated at varied times from cell capacitance jumps in response to paired depolarizations. The experimentally observed RRP recovery time course and steady-state size could be predicted from the measured [Ca2+]i signal assuming a Michaelis-Menten-type regulation of the vesicle supply by Ca2+. An elevated recruitment activity was observed at increased [Ca2+]i even when protein kinase C was blocked, but maximum effects could be obtained only after stimulation of PKC by phorbol esters or by prolonged elevations in [Ca2+]i. We suggest that, in chromaffin cells, elevated cytosolic Ca2+ modulates exocytotic plasticity via PKC-dependent and -independent pathways.

Animals↗

PubMed1998

The design, synthesis, and initial evaluation of benzophenone-containing peptides as potential photoaffinity labels of oligosaccharyltransferase.

The benzophenone photophore was incorporated into protected tripeptides and tetrapeptides as photoactivatable probes to study the multimeric enzyme oligosaccharyltransferase (OST). These peptides contain the -Asn-X-Thr- sequon which is required for OST-catalyzed N-glycosylation. Two tripeptides, Bz-Asn-Bpa-Thr-NH2 (3b) and Bz-Asn-Lys[N epsilon-(4-Bz)Bz]-Thr-NH2 (4b), were found to be good OST substrates. They were competitive inhibitors versus standard peptide substrate [14C]Bz-Asn-Leu-Thr-NH2 and their Ki values were determined to be 41 +/- 6 microM and 21 +/- 6 microM, respectively, using synthetic (GlcNAc)2-PP-dolichol.

Benzophenones↗

PubMed1998

Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice.

The resilience and strength of bone is due to the orderly mineralization of a specialized extracellular matrix (ECM) composed of type I collagen (90%) and a host of non-collagenous proteins that are, in general, also found in other tissues. Biglycan (encoded by the gene Bgn) is an ECM proteoglycan that is enriched in bone and other non-skeletal connective tissues. In vitro studies indicate that Bgn may function in connective tissue metabolism by binding to collagen fibrils and TGF-beta (refs 5,6), and may promote neuronal survival. To study the role of Bgn in vivo, we generated Bgn-deficient mice. Although apparently normal at birth, these mice display a phenotype characterized by a reduced growth rate and decreased bone mass due to the absence of Bgn. To our knowledge, this is the first report in which deficiency of a non-collagenous ECM protein leads to a skeletal phenotype that is marked by low bone mass that becomes more obvious with age. These mice may serve as an animal model to study the role of ECM proteins in osteoporosis.

Age Factors↗

PubMed1998

Multiple kinetic components of exocytosis distinguished by neurotoxin sensitivity.

The secretion of synaptic and other vesicles is a complex process involving multiple steps. Many molecular components of the secretory apparatus have been identified, but how they relate to the different stages of vesicle release is not clear. We examined this issue in adrenal chromaffin cells, where capacitance measurements and amperometry allow us to measure vesicle fusion and hormone release simultaneously. Using flash photolysis of caged intracellular calcium to induce exocytosis, we observed three distinct kinetic components to vesicle fusion, of which only two are related to catecholamine release. Intracellular dialysis with botulinum neurotoxin E, D or C1 or tetanus-toxin light chains abolishes the catecholamine-related components, but leaves the third component untouched. Botulinum neurotoxin A, which removes nine amino acids from the carboxy(C)-terminal end of SNAP-25, does not eliminate catecholamine release completely, but slows down both catecholamine-related components. Thus we assign a dual role to SNAP-25 and suggest that its nine C-terminal amino acids are directly involved in coupling the calcium sensor to the final step in exocytosis.

Adenosine Triphosphate↗

PubMed1998

Human metalloprotease-disintegrin Kuzbanian regulates sympathoadrenal cell fate in development and neoplasia.

The development of the sympathetic nervous system involves cell-cell interactions that regulate the fate and migration of progenitor neural cells. Recent evidence shows that focal membrane-bound protease activity is critical for such interactions. The Drosophila kuzbanian (kuz) gene is required in neurogenesis and encodes a highly conserved, membrane-bound metalloprotease- disintegrin closley related to theTNF-alphaconvertingenzyme (TACE). We have characterized the human and mouse kuz homologs and mapped human kuz to chromosome 15q22. During mouse embryonic development Kuz is expressed mainly in the sympathoadrenal and olfactory neural precursors. Once sympathoadrenal cells differentiate into chromaffin cells in the adult adrenal medulla, they no longer express Kuz. However, we found that tumors of sympathoadrenal origin, such as pheochromocytomas and neuroblastomas, overexpress Kuz. Further, transfection of a kuz construct lacking the protease domain, but not the full-length construct, induces neurite formation in PC12 chromaffin tumor cells. Taken together our results suggest a critical role for Kuz in regulation of sympathoadrenal cell fate.

Adrenal Medulla↗

PubMed1998

slimb coordinates wg and dpp expression in the dorsal-ventral and anterior-posterior axes during limb development.

In the Drosophila leg disc, wingless (wg) and decapentaplegic (dpp) are expressed in a ventral-anterior and dorsal-anterior stripe of cells, respectively. This pattern of expression is essential for proper limb development. While the Hedgehog (Hh) pathway regulates dpp and wg expression in the anterior-posterior (A/P) axis, mechanisms specifying their expression in the dorsal-ventral (D/V) axis are not well understood. We present evidence that slimb mutant clones in the disc deregulate wg and dpp expression in the D/V axis. This suggests for the first time that their expression in the D/V axis is actively regulated during imaginal disc development. Furthermore, slimb is unique in that it also deregulates wg and dpp in the A/P axis. The misexpression phenotypes of slimb- clones indicate that the regulation of wg and dpp expression is coordinated in both axes, and that slimb plays an essential role in integrating A/P and D/V signals for proper patterning during development. Our genetic analysis further reveals that slimb intersects the A/P pathway upstream of smoothened (smo).

Amino Acid Sequence↗

PubMed1998

Immortalization and characterization of bone marrow stromal fibroblasts from a patient with a loss of function mutation in the estrogen receptor-alpha gene.

A male patient with abnormal postpubertal bone elongation was shown earlier to have a mutation in both alleles of the estrogen receptor, resulting in a nonfunctional gene. Marrow stromal fibroblasts (MSFs) derived from this patient were called HERKOs (human estrogen receptor knock outs), and in order to obtain continuous HERKO cell lines, they were immortalized using a recombinant adenovirus-origin-minus SV40 virus. MSFs are unique cells because they support hematopoesis and contain a mixed population of precursor cells for bone, cartilage, and fat. Three established cell lines (HERKO2, HERKO4, and HERKO7) were characterized and compared with the heterogeneous population of nonimmortalized HERKOs for their osteogenic potential. We performed Northern analysis of matrix genes implicated in bone development and metabolism and an in vivo bone formation assay by transplanting the cells subcutaneously into immunodeficient mice. All three HERKO lines expressed high amounts of collagen 1A1, osteopontin, osteonectin, fibronectin, decorin, biglycan, and alkaline phosphatase. Except for osteopontin, expression of these genes was slightly lower compared with nonimmortalized HERKOs. In the in vivo bone formation assay, the heterogeneous population of nonimmortalized HERKOs formed bone with high efficiency, while the HERKO lines induced a high-density, bone-like matrix. Finally, all HERKO cell types secreted high levels of insulin-like growth factor I and interleukin-6 into the culture medium relative to cells of normal human subjects. In summary, these lines of HERKO cells retain several of the phenotypic traits of MSFs after immortalization, including matrix and cytokine production, and provide a valuable source of a unique human material for future studies involving estrogen action in bone and bone marrow metabolism.

Adult↗

PubMed1998

[The survey of quality of life among aging population in the rural areas of Guangdong].

In order to investigate the quality of life in 1008 cases of elderly people living in rural areas, Kaipin and Boluo counties in Guangdong Province. Data was collected by cluster stratification and random selection, 96.64% of them were independently managing their activities of daily life with 78.08% lived by themselves. In a self-evaluation questionnaire on health status, 36.31% perceived good, 52.8% moderate and 10.42% bad with 56.05% having had history of chronic illnesses. Arthritis and chronic headache, appeared to take the first and second place 38.8% showed satisfaction about the current medical condition with, 45.7% moderate and 9.1% un-satisfaction. 23.81% of them felt the degree of satisfaction to their life was good, 65.97% moderate and 9.82% poor. Since the proportion of elderly in the rural areas was big, and most elderly could manage their lives in late years because they had engaged in physical labor in the past, the general health condition was bad which led to poor quality of life. It is suggested that more medical care be provided to elderly living in the countryside to improve their quality of life.

Aged↗

PubMed1998

[An experimental study on the capability of laminin receptor antibody and protein kinase C inhibitor to inhibit tumor metastasis in vivo].

OBJECTIVE: To study methods for blocking tumor metastasis. METHODS: Endogenous laminin (LN), protein kinase C (PKC) inhibitor staurosporine (SP), anti-LN receptor (LN-R) were used to act on murine fibrosarcoma cells which were strongly positive for endogenous LN and LN-R, then infused into the caudal veins of 77 C57 mice once, to initiate lung tumor formation. Before infusion, the cells were all measured for surface LN-R quantity with flow cytometry. RESULTS: The positive rate of LN-R on tumor cell surface in the control group, LN group, SP group, anti-LN-R group and anti-LN group being 56.5%, 76.3%, 50.2%, 31.9% and 20.6% respectively. The average volume of the tumors in the lungs of mice being 76 mm3, 110 mm3, 14 mm3, 5 mm3 and 20 mm3 respectively. The rate of tumor embolus formation in lymphatic and blood vessels being 81%, 94%, 36%, 43% and 68% respectively. CONCLUSION: The pathological changes and metastasis in the LN group are more svere than that in control group. But all other groups are less severe than the control group. The level of LN-R on tumor cell surface is positively correlated with tumor volume and rat of tumor embolus formation. The lipositol conduction system in tumor cells is also closely related with size of tumor foci and rate of tumor embolus formation.

Animals↗

PubMed1997

13C- and 15N-labeled peptide substrates as mechanistic probes of oligosaccharyltransferase.

The carboxamide moiety that links the carbohydrate and protein moieties in N-linked glycoproteins has been unambiguously determined to arise intact from asparagine by the use of chemically synthesized Bz-[4-13C, 15N]Asn-Leu-Thr-NH2 as an oligosaccharyltransferase (OST) substrate. Bz-[4-13C]Asn-Leu-Thr-NH2 was also synthesized and used to evaluate a proposed mechanism of OST catalysis similar to that of glutamine-dependent amidotransferases using 15NH4OAc as a potential external nucleophile. Analysis of NMR and MS spectra of the isotopically labeled peptides and the resulting biosynthesized glycopeptides indicates that free 15NH3 is not lost from the doubly labeled substrate during catalysis nor can exogenous 15NH3 intercept any of several postulated enzyme-bound species. These results indicate that OST-catalyzed glycosylation does not follow a mechanism involving the transient generation of exchangeable "NH3". Thus, in contrast to several glutamine-dependent amidotransferases, OST catalysis does not lead to transient scission of the asparagine beta-carboxamide C-N bond. Together with previously published results, these data argue against nucleophilic activation of the asparagine beta-carboxamide moiety being the underlying chemical mechanism for OST-catalyzed glycosylation of peptides.

Carbon Isotopes↗

PubMed1997

Mammalian homologs of seven in absentia regulate DCC via the ubiquitin-proteasome pathway.

DCC (deleted in colorectal cancer) is postulated to function as transmembrane receptor for the axon and cell guidance factor netrin-1. We report here that the DCC cytoplasmic domain binds to proteins encoded by mammalian homologs of the Drosophila seven in absentia (sina) gene, as well as Drosophila Sina. Sina has a critical role in R7 photoreceptor development and shows upward of 85% amino acid identity with its mammalian homologs (termed Siahs), but the function of the Sina/Siah proteins has not been defined. We sought, therefore, to characterize further their interaction with DCC. Immunofluorescence studies suggested the Sina/Siah proteins localized predominantly in the cytoplasm and in association with DCC. DCC was found to be ubiquitinated and the Sina/Siah proteins regulated its expression. Proteasome inhibitors blocked the effects of Sina/Siah on DCC, and the Sina/Siah proteins interacted with ubiquitin-conjugating enzymes (Ubcs). A mutant Siah protein lacking the amino-terminal Ubc-binding sequences complexed with DCC, but did not degrade it. The in vivo interaction between Sina/Siah and DCC was confirmed through studies of transgenic Drosophila lines in which DCC and Sina were ectopically expressed in the eye. Taken together, the data imply that the Sina/Siah proteins regulate DCC and perhaps other proteins via the ubiquitin-proteasome pathway.

Animals↗

PubMed1997

Genetic basis of tolerance to O2 deprivation in Drosophila melanogaster.

The ability to tolerate a low-O2 environment varies widely among species in the animal kingdom. Some animals, such as Drosophila melanogaster, can tolerate anoxia for prolonged periods without apparent tissue injury. To determine the genetic basis of the cellular responses to low O2, we performed a genetic screen in Drosophila to identify loci that are responsible for anoxia resistance. Four X-linked, anoxia-sensitive mutants belonging to three complementation groups were isolated after screening more than 10,000 mutagenized flies. The identified recessive and dominant mutations showed marked delay in recovery from O2 deprivation. In addition, electrophysiologic studies demonstrated that polysynaptic transmission in the central nervous system of the mutant flies was abnormally long during recovery from anoxia. These studies show that anoxic tolerance can be genetically dissected.

Adaptation, Physiological↗

PubMed1997

A case-control study of diet and lung cancer in northeast China.

A case-control study involving interviews with 227 lung-cancer cases and 227 matched hospital controls was conducted in Heilongjiang Province in northeast China to examine the influence of dietary factors on the risk of developing lung cancer. Lung-cancer cases were all incident cases judged to be suitable candidates for tumor removal by surgery. Controls were selected among hospitalized patients with non-neoplastic and non-lung disease. The overall male lung-cancer risks associated with cigarette smoking were similar to those reported in other Chinese studies but quite low compared to risks in Western countries. However, the subjects in this study were relatively young (average age 53.2), had started to smoke on average at a relatively old age (21.3 years), and only smoked an average of 18.7 cigarettes per day. Lung-cancer risk was not strongly associated with any of the nutrients examined, when all cases were compared to all controls. However, the data were suggestive of differences in the relationship of diet to risk among smokers and non-smokers. Cautious interpretation is required because of the wide confidence intervals due to limited sample size. Among the smokers, only higher beta-carotene was associated with estimates suggesting a lowered risk. Among non-smokers, the evidence suggested that increased vegetable consumption might reduce risk, consumption of any fruit might reduce risk but beta-carotene was unrelated to risk. The differences observed in the relationship of diet to lung-cancer risk between Chinese smokers and non-smokers warrant further study.

Case-Control Studies↗