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Biomedical subjects

J Xu

Publications and source records attributed to J Xu.

At least 919 records · Page 51Linked to original sources
PubMed1996

Effects of pinacidil, verapamil, and heart rate on afterdepolarizations in the guinea-pig heart in vivo.

Recently, ionic current simulation in the Luo-Rudy model has elucidated putative mechanisms of afterdepolarizations under various experimental conditions. The present study was aimed at gaining insight into the differential mechanism of different types of afterdepolarizations in the guinea-pig heart in vivo. The effects of pharmacological and heart rate perturbations on early (EADs) and delayed (DADs) afterdepolarizations, induced by either digoxin, CsCl, or BayK 8644 were studied, using mid-myocardial left ventricular monophasic action potential (MAP) recordings. Digoxin insignificantly shortened sinus cycle length (SCL) and CsCl and BayK 8644 differentially prolonged SCL and MAP duration. Digoxin induced phase 3-EADs and DADs and CsCl or BayK 8644 induced phase 2- and phase 3-EADs. Pinacidil shortened MAP duration, suppressed almost all the phase 2-EADs and some of the phase 3-EADs, but not the DADs. In a few cases, DADs were manifested following the abolishment of phase 2-EADs by pinacidil, but this phenomenon did not occur in the presence of hexamethonium. Verapamil prolonged SCL, did not significantly affect phase 2-EADs, but suppressed almost all of the DADs, including those which appeared after pinacidil, and all but one of the phase 3-EADs. The effects of pinacidil and verapamil were independent of the mode of afterdepolarization induction. A pacing-induced heart rate increase, which shortened MAP duration, and vagal stimulation, which prolonged MAP duration, attenuated and enhanced phase 2-EADs, respectively. The amplitude of phase 3-EADs was inversely related to the heart rate. These data, taken together, are consistent with those obtained previously by others in a computer model and recent observations on CsCl-induced EADs in the guinea-pig Purkinje fibers in vitro which have indicated that the mechanism of phase 2-EADs is different from that of DADs and that late phase 3-EADs generated under conditions of Ca2+ overload and DADs share similar properties.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1996

Estimation of the optimal concentrations of residual sugar and cell growth rate for a fed-batch culture of Saccharomyces cerevisiae.

Estimation of the optimal concentrations of residual sugar in medium for a fed-batch culture of Baker's yeast has been studied and practiced. The concentrations, however, depended on different species and targets of the biomass, which was expected to be made. Kinetic changes of the residual phosphate salt in the medium conformed to a logarithmic process until the fourth hour during an 11-h culture. The parabolic method (see ref. 9 later in article) might be qualified to maintain the concentrations of residual sugar around 0.15 g/L. It was demonstrated that cell growth followed a sigmoid process during a fed-batch culture, because the cells consumed the nutrient with two metabolic pathways, one was for cell conversion and another was for non-cell conversion. With the parabolic method, we can estimate kinetics of cell growth and cell growth rate during the culture.

Carbohydrate Metabolism↗
PubMed1996

Immunohistochemical analysis of globulin and complements in blood vessels of placental villi during pregnancy induced hypertension.

The changes of globulin and complements in placental villi blood vessels were immunohistochemically studied in pregnancy induced hypertension patients and normal pregnant patients by a randomized, double-blind approach. The immunostaining of IgG, IgE, C3, C4, and 5-HT was seen in the villous blood vessels and the helicine arteries of pregnancy induced hypertensive placental villi. The strong positive rates were 100%, 90%, 100%, 100% and 90% in serious pregnancy induced hypertensive patients, accompanied by aggregation of mastocytes and vasculopathy of villous blood vessels and the helicine arteries. It is concluded that the immuno-pathological damage took place in the villous blood vessels and helicine arteries, resulting in vasculopathy and villous regressive changes and that the immunological factors were closely related to pregnancy induced hypertension.

Adult↗
PubMed1996

Study of spontaneous combustion coals by GC and GC-MS.

Organic geochemical characteristics of 3 Chinese spontaneous combustion coals have been carried out by means of GC and GC-MS analysis. It has been observed that more compounds with low to medium carbon number, such as terpenoids and others can be found in spontaneous combustion coals than in normal samples.

Journal Article↗
PubMed1996

Protein C inhibitor (PCI).

PCI is a non-specific serpin that inhibits several proteases of the coagulation and fibrinolytic systems as well as plasma- and tissue kallikreins and the sperm protease acrosin. The precise physiological role of PCI has not been defined yet. Heparin stimulates most PCI/protease reactions, but interferes with the tissue kallikrein/PCI-interaction. Thereby heparin not only regulates PCI-activity but also its specificity in systems containing two or more of its target proteases. This effect is not restricted to heparin, but is also seen with other glycosaminoglycans (GAGs) and large, negatively charged molecules. PCI also binds to GAGs present on the surface of epithelial kidney cells, and GAGs isolated from these cells have a similar effect on PCI activity as heparin. Studies analyzing the role of PCI as an acrosin inhibitor revealed that endogenous PCI is immunocytochemically localized to disrupted acrosomal membranes of morphologically abnormal sperms, while intact sperms are negative for PCI-antigen. In a mouse in vitro fertilization model human PCI inhibited sperm/egg binding and decreased the fertilization rate. Northern blotting of human and mouse mRNA using human and mouse PCI-cDNA probes revealed that in the mouse PCI is exclusively synthesized in the genital tract (testis, seminal vesicle, ovary), while in humans PCI is additionally synthesized in many other organs (e.g., liver, pancreas, heart). Therefore PCI might regulate enzymes involved in fertilization (e.g. acrosin) in both species. Other proteases (e.g., tissue kallikrein) are possibly regulated in a species specific manner by different inhibitors.

Animals↗
PubMed1996

Myocardial imaging with a new transpulmonary lipid-fluorocarbon echo contrast agent: experimental studies in pigs.

The development of echo contrast agents that can provide reliable opacification of the myocardium after intravenous injection is an important advancement for the clinical application of contrast echocardiography. In this study, the hemodynamic effects and echocardiographic characteristics of a new lipid-fluorocarbon echo contrast agent, Aerosomes MRX 115 (ImaRx Pharmaceutical Corp., Tucson, Ariz.) were studied in six anesthetized ventilated pigs. Intravenous injection of this new agent in doses ranging from 0.0005 to 0.01 ml/kg produced significant measurable and visible myocardial opacification without any effect on heart rate, systemic pressure, partial pressure of oxygen, or left ventricular systolic function. The two largest doses (0.005 and 0.01 ml/kg), however, resulted in mild reversible increases in mean pulmonary artery pressure of 12 and 16 mm Hg, respectively. In four animals, epicardial images were obtained before and during coronary artery occlusion. Intravenous contrast injection during coronary occlusion permitted delineation of the hypoperfused myocardial segment. This capability may further expand the utility of contrast echocardiography.

Animals↗
PubMed1996

NAB domain is essential for the subunit assembly of both alpha-alpha and alpha-beta complexes of shaker-like potassium channels.

There are at least five subfamilies of Shaker-like K+ channels. The diverse function of K+ channels are thought to be further modulated by hydrophilic beta subunits. Here we report that Kv beta 1 inactivates RCK4 and Shaker B K+ channels of the Kv1 subfamily, but not Shal2 of the Kv4 subfamily. This correlates the subfamily-specific bindings of Kv beta 1 to the cytoplasmic N-terminal domains of Kv1 alpha subunits. We map the Kv beta 1-binding site to a region overlapping NABKv1, a domain that specifies different Kv1 alpha subunits to form heterotetramers. Using chimeric alpha subunits, we demonstrate that NABKv1 is essential for the Kv beta 1-mediated inactivation. These results suggest that Kv beta 1 modulates a subset of K+ channels through the specific assembly of alpha-beta complexes and reveal the dual function of the NAB domain in mediating the assembly of both alpha-alpha and alpha-beta complexes.

Amino Acid Sequence↗
PubMed1996

Graded activation of fibroblast growth factor receptor 3 by mutations causing achondroplasia and thanatophoric dysplasia.

The longitudinal growth of the skeleton arises from the continuous process of endochondral ossification occurring at the ends of growing long bones. Dwarfism results when this process is disrupted, as in the autosomal dominant human skeletal diseases hypochondroplasia (HCH), achondroplasia (ACH) and thanatophoric dysplasia (TD). Interestingly, these disorders display a graded spectrum of phenotypic severity and are the result of distinct missense mutations in the fibroblast growth factor receptor 3 gene (FGFR3). TD, characterized by neonatal lethality and profound dwarfism, is the result of FGFR3 mutations, including an R248C substitution in the extracellular domain or a K650E substitution in the tyrosine kinase (TK) domain. ACH, which is non-lethal and presents less severe dwarfism, results almost exclusively from a G380R substitution in the transmembrane domain. Homozygous achondroplasia resembles the phenotype of TD. In this report the effect of the ACH and TD mutations on the activity and regulation of FGFR3 are analysed. We showed that each of the mutations constitutively activate the receptor, as evidenced by ligand-independent receptor tyrosine phosphorylation and cell proliferation. Moreover, the mutations that are responsible for TD were more strongly activating than the mutation causing ACH, providing a biochemical explanation for the observation that the phenotype of TD is more severe than that of ACH.

3T3 Cells↗
PubMed1996

Extracellular matrix alters PDGF regulation of fibroblast integrins.

Extracellular matrix (ECM) and growth factors are potent regulators of cell phenotype. These biological mediators of cellular responses are potentially interactive and as such could drive cells through progressive phenotypes to create new tissue as in morphogenesis and wound repair. In fact, ECM composition changes during tissue formation accompanied by alterations in cell growth and migration. How alterations in the ECM regulate cell activities is poorly defined. To address this question in wound repair, we cultured normal human dermal skin fibroblasts in relaxed collagen gels, fibronectin-rich cultures or stressed fibrin gels, and stressed collagen gels to model normal dermis, early wound provisional matrix, and late granulation tissue, respectively. Integrin subunits, alpha 2, alpha 3, and alpha 5, that define receptor specificity for collagen and provisional matrix, respectively, were measured at mRNA steady-state level before and after stimulation with platelet-derived growth factor-BB (PDGF-BB), a potent mitogen and chemoattractant for fibroblasts. Fibronectin-rich cultures and fibrin gels supported PDGF-BB induction of alpha 3 and alpha 5 mRNA. In contrast, both stressed and relaxed collagen attenuated these responses while promoting maximal alpha 2 mRNA expression. Posttranscriptional regulation was an important mechanism in this differential response. Together PDGF-BB and collagen gels promoted alpha 2, but not alpha 3 and alpha 5, mRNA stability. Conversely, when fibroblasts were in fibronectin-rich cultures, PDGF-BB promoted alpha 3 and alpha 5, but not alpha 2, mRNA stability. We suggest that ECM alterations during wound healing or any new tissue formation cause cells to respond differently to repeated growth factor stimuli. An ordered progression of cell phenotypes results, ultimately consummating tissue repair or morphogenesis.

Animals↗
PubMed1996

PDGF induction of alpha 2 integrin gene expression is mediated by protein kinase C-zeta.

Platelet-derived growth factor (PDGF) stimulates fibroblasts to move over collagen and contract three-dimensional collagen gels, processes important in wound repair and fibrocontractive diseases. These processes depend on alpha 2 beta 1 integrin ligation of collagen and PDGF induces the expression of this integrin. Several lines of evidence presented here suggest that PKC-zeta plays a role in alpha 2 integrin gene expression. The induction was blocked by chemical inhibitors for protein tyrosine kinases (PTK), genistein, and protein kinase C (PKC), chelerythrine, and bisindolylmaleimide GF 109203X. Cells depleted of phorbol 12-myristate 13-acetate (PMA)-inducible PKCs by chronic treatment with PMA still demonstrated an alpha 2 response to PDGF indicating that a non-PMA-sensitive PKC isoform was required. PDGF induced kinase activity in PKC-zeta immunoprecipitates. Antisense oligonucleotides complementary to 5' end of PKC-zeta mRNA sequences blocked the PDGF-induced increase of alpha 2 mRNA levels up to 70%, indicating PKC-zeta, a non-PMA-sensitive PKC isoform, is a component of the PDGF stimulatory pathway for alpha 2 mRNA synthesis. A 961-base pair (bp) upstream region of alpha 2 gene/CAT construct transfected into human dermal fibroblasts was positively regulated by PDGF as judged by CAT enzymatic levels. Both PTK and PKC inhibitors blocked PDGF-stimulation of the alpha 2 promoter fragment/CAT construct, indicating that the phosphorylation requirement occurred at alpha 2 promoter-directed transcription level. Therefore, we propose that PDGF-stimulatory pathway of alpha 2 integrin gene expression involves multiple cellular protein kinases, one of which is PKC-zeta.

Adult↗
PubMed1996

Chromium(VI) treatment of normal human lung cells results in guanine-specific DNA polymerase arrest, DNA-DNA cross-links and S-phase blockade of cell cycle.

Previous studies have shown that in vitro treatment of a synthetic double-stranded DNA template with chromium(III), or chromium(VI) in the presence of ascorbate, resulted in guanine-specific DNA polymerase arrests that correlated strongly with DNA-DNA cross-linking. In vivo chromium(VI) undergoes a more complicated intracellular cascade of reductive metabolism than is achievable in an in vitro model. Moreover, in living cells, DNA is highly packaged in the form of chromatin which may alter the accessibility of DNA to chromium. A repetitive primer-extension assay was employed to determine whether chromium forms polymerase-arresting lesions in vivo. Normal human lung fibroblasts treated with chromium(VI) exhibited adduct levels of 0.13-0.92 mmol Cr/mol DNA-nucleotides in the total genome (0.26-1.84 Cr adducts/Kbp DNA) and DNA interstrand cross-links. Genomic DNA was isolated and alphoid sequences (1-5% of the genome) were used as a substrate for repetitive primer extension using Taq polymerase. The results showed a dose-dependent, guanine-specific, replication termination, even at low doses resulting in greater than 90% survival. The same treatment resulted in dose-dependent suppression of thymidine incorporation into DNA immediately after treatment. Thymidine incorporation increased during the first 6 h after the 2-h exposure, probably related to the repair of the single strand breaks, but then returned to high suppression levels at 24 h. The chromate treatments inhibited cell growth by specific blocking of the progression of cells through S-phase of the cell cycle. The results confirmed our studies in cell-free systems and taken together they strongly indicate that guanine-guanine DNA interstrand cross-links induced by chromate in living cells is the lesion responsible for blocking DNA replication processivity.

Base Sequence↗
PubMed1996

Characterization of survival motor neuron (SMNT) gene deletions in asymptomatic carriers of spinal muscular atrophy.

Previous reports have established that the telomeric copy of the survival motor neuron (SMNT) gene and the intact copy of the neuronal apoptosis inhibitory protein (NAIP) gene are preferentially deleted in patients with spinal muscular atrophy (SMA). Although deletions or mutations in the SMNT gene are most highly correlated with SMA, it is not clear to what extent NAIP or other genes influence the SMA phenotype, or whether a small fraction of SMA patients actually have functional copies of both SMNT and NAIP. To evaluate further the part of SMNT in the development of SMA, we analyzed 280 asymptomatic SMA family members for the presence or absence of SMNT exons 7 and 8. We report the following observations: (i) 4% of the sample harbored a polymorphic variant of SMNT exon 7 that looks like a homozygous deletion; (ii) approximately 1% of the parents are homozygously deleted for both exons 7 and 8; (iii) one asymptomatic parent lacking both copies of SMNT exons 7 and 8 displays a 'subclinical phenotype' characterized by mild neurogenic pathology; (iv) another asymptomatic parent lacking both SMNT exons showed no signs of motor neuron disorder by clinical and neurodiagnostic analyses. The demonstration of polymorphic variants of exon 7 that masquerade as homozygous nulls, and the identification of SMA parents who harbor two disease alleles, serve as a caution to those conducting prenatal tests with these markers.

Adolescent↗
PubMed1996

Diphtheria antitoxin levels in US blood and plasma donors.

Plasma samples from 500 blood donors were titrated for diphtheria antitoxin (DAT) by the toxin neutralization (TN) test. Only 1.6% of donors had <0.01 IU/mL DAT, the minimum protective level against diphtheria; 15% had levels between 0.01 and <0.1 IU/mL, indicating basic protection, and 83.4% had levels > or =0.1 IU, indicating full protection. Three hundred fifty samples were studied by ELISA for diphtheria toxoid IgG antibodies to assess the utility of the assay as a quick, convenient method for evaluating diphtheria immunity. Although the correlation between TN and ELISA titers for the 350 samples was high (r = .80), there was no correlation (r = .07) for samples with antitoxin titers <0.1 IU/mL, the level of special interest for serosurveys for protection. Titration of 62 immune globulin samples (prepared from 1957 to 1994) showed that DAT levels in Massachusetts blood donors increased concurrently with increased use of tetanus-diphtheria vaccine in the state.

Animals↗
PubMed1996

Assessment of antigenicity and genetic variation of glycoprotein B of murine cytomegalovirus.

An analysis of linear antibody-binding sites of the glycoprotein B (gB) molecule of murine cytomegalovirus (MCMV) and of genetic variation within these regions was performed. To achieve this, a series of overlapping fragments spanning the entire coding sequence of the gB gene of the K181 strain of MCMV was expressed in E. coli as fusion proteins with glutathione S-transferase (GST) using the pGEX expression system. Four antibody-binding regions were mapped to locations spanning amino acid residues 17-79 (BS), 155-278 (BE2), 809-926 (SS) and 347-508 (BB and EE), based on reactivity in Western blot analysis of GST-gB fusion proteins with murine polyclonal antiserum raised against MCMV. Only the antibody-binding region BE2 (155-278) elicited an antiserum that exhibited complement-dependent neutralizing activity, and immunization of mice with the fusion protein BE2 led to moderate but significant reductions in the level of MCMV replication in the spleen. Polyclonal antisera raised against the GST-gB fusion proteins detected purified virion proteins of 105 kDa (anti-BS and anti-BE2) and 52 kDa (anti-SS) and are therefore likely to recognize the N-terminal and C-terminal portions of the gB molecule, respectively. The antibody-binding region within amino acid residues 17-79 was found to be MCMV strain-specific, whereas antibody-binding regions within residues 155-278 and 809-926 were found to be conserved among MCMV field isolates. Comparative sequence analysis of the corresponding regions of MCMV gB revealed a level and extent of sequence of sequence heterogeneity consistent with these findings.

Amino Acid Sequence↗