Biomedical subjects

J Xu

Publications and source records attributed to J Xu.

At least 793 records · Page 44Linked to original sources

PubMed1997

The human delta1261 mutation of the HERG potassium channel results in a truncated protein that contains a subunit interaction domain and decreases the channel expression.

HERG (human eag-related gene) encodes an inward-rectifier potassium channel formed by the assembly of four subunits. Since the truncated HERG protein in patients with long QT syndrome induces a dominant phenotype, that is, cardiac sudden death, the assembly of nonfunctional complexes between wild-type and mutated subunits was implicated in causing the disease. To understand HERG-mediated cardiac sudden death at the molecular level, it is important to determine which regions in the HERG protein participate in subunit interaction. We therefore report the identification of a subunit interaction domain, NAB(HERG), that is localized at the hydrophilic cytoplasmic N terminus and can form a tetramer in the absence of the rest of the HERG protein. Truncated HERG proteins containing NAB(HERG), including one that resulted from the delta1261 human mutation, inhibit the functional expression of the HERG channel in transfected cells. Together, these results support the notion that the expression of HERG in the human heart may be decreased in the presence of the truncated subunit. Such a decrease of potassium channel expression can contribute to the longer QT intervals observed in the patients with the HERG mutation.

Cation Transport Proteins↗

PubMed1997

Follicular dendritic cells specifically express the long CR2/CD21 isoform.

This paper describes an antibody (mAb 7D6) that specifically recognizes human follicular dendritic cells (FDCs). By expression cloning, a cDNA clone encoding for the long human CR2/ CD21 isoform (CD21L) that contains an additional exon (10a) was isolated. We demonstrated that FDCs selectively express CD21L, while B cells selectively express the short CR2/CD21 lacking exon 10a (CD21S). By screening mouse Ltk- cells transfected with the CD21L cDNA, we further showed that the other two anti-human FDC mAbs DRC-1 and KiM4 also recognize CD21L. Thus, CD21L represents the first characterized human FDC-specific molecule, which may confer unique functions of FDCs in germinal center development.

Animals↗

PubMed1997

Tissue-specific regulation by vitamin D3 of a novel protein containing ankyrin-like repeats.

Vitamin D3 is the precursor of the steroid hormone 1,25-dihydroxyvitamin D3 which is involved in the regulation of calcium metabolism, growth and differentiation. We used differential display of mRNA populations from kidney and intestine of vitamin D3-deficient and -replete chicks to determine the steady-state abundance of approximately 5000 mRNAs. One of these sequences, whose differential expression in kidney and down-regulation by vitamin D3 was confirmed by Northern analysis, was used to screen a cDNA library from vitamin D3-deficient chick kidney in order to obtain a full length cDNA. Subcloning and sequencing revealed that this cDNA encodes a novel protein containing ankyrin-like repeats and a C-terminal Fe-S binding region signature. The encoded protein consists of 617 amino acids and contains two sets of four ankyrin-like repeats separated by 146 amino acids. This motif consists of approximately 33 amino acids containing a highly conserved central hydrophobic alpha helix and is abundant in a wide variety of proteins, particularly those participating in the protein-protein or protein-membrane interactions involved in signal transduction, regulation of the cell cycle and control of transcription. Outside of the ankyrin-like domains, no homologies with other proteins in existing data bases were found. Our results have revealed a novel protein containing ankyrin-like repeats tissue-specifically down-regulated by vitamin D3 in the kidney.

Amino Acid Sequence↗

PubMed1997

Recognition of unique carboxyl-terminal motifs by distinct PDZ domains.

The oriented peptide library technique was used to investigate the peptide-binding specificities of nine PDZ domains. Each PDZ domain selected peptides with hydrophobic residues at the carboxyl terminus. Individual PDZ domains selected unique optimal motifs defined primarily by the carboxyl terminal three to seven residues of the peptides. One family of PDZ domains, including those of the Discs Large protein, selected peptides with the consensus motif Glu-(Ser/Thr)-Xxx-(Val/Ile) (where Xxx represents any amino acid) at the carboxyl terminus. In contrast, another family of PDZ domains, including those of LIN-2, p55, and Tiam-1, selected peptides with hydrophobic or aromatic side chains at the carboxyl terminal three residues. On the basis of crystal structures of the PSD-95-3 PDZ domain, the specificities observed with the peptide library can be rationalized.

Amino Acid Sequence↗

PubMed1997

Blockade of CD40 ligand-CD40 interaction impairs CD4+ T cell-mediated alloreactivity by inhibiting mature donor T cell expansion and function after bone marrow transplantation.

Alloreactive T cells require costimulatory signals via CD40 ligand (CD40L). The tissue-destructive properties of allogeneic CD4+ but not CD8+ T cells were inhibited by anti-CD40L mAb. Fewer CD4+ thoracic duct lymphocytes (TDL) were obtained in mAb-treated recipients. Kinetic studies revealed that CD4+ T cell expansion was reduced or delayed which may account, in part, for the partial graft-vs-host disease protective effect of anti-CD40L mAb. TDL were found to have diminished anti-host-specific proliferative responses. The frequency of donor TDL and splenocytes that expressed the Th1 cytokines IL-2, IL-12 p40, and IFN-gamma mRNA was markedly diminished in mAb-treated recipients, demonstrating that Th1-driven alloresponses were susceptible to CD40L targeting. Perforin mRNA-expressing T cells were undetectable in mAb-treated recipients, consistent with reduced in vivo lethality after the adoptive transfer of allogeneic CD4+ T cells. Similar findings were observed in both B cell-replete or -deficient recipients, indicating that allogeneic T cell expansion and priming can be sustained by a non-B cell, CD40+ host cell population. Mice receiving CD40L-deficient allogeneic CD4+ T cells had survival rates comparable to the rates of those given anti-CD40L mAb treatment. Because anti-CD40L mAb also was found to prevent host anti-donor-mediated marrow allograft rejection, in vivo blockade of CD40L-CD40 interactions may provide a highly beneficial approach to improving the outcome of allogeneic bone marrow transplantation.

Animals↗

PubMed1997

Empirical evaluation of genome scans for linkage of a quantitative trait associated with a complex disorder.

Nonparametric sib-pair analysis (Haseman-Elston) was used to search for evidence of linkage between a putative locus for a complex quantitative trait Q1 and genome-wide markers (367 markers from 10 chromosomes) for the first 100 replicates of nuclear family data. The characteristics of the statistically positive linkage results [the magnitude of p-values (p), the number of supporting flanking markers, and the percentage of positive replicates] were compared for true linkage (major and minor genes) and false positive evidence for linkage. Discriminant analysis was used to evaluate which characteristics of these statistically positive linkage results are good indicators to discriminate true linkage from false positive evidence for linkage. Sensitivity and false positive rates of several proposed criteria for linkage, as well as the criteria based on our results were evaluated. The relationship between the map location of the marker with the lowest p-value and the map location of the true underlying gene was also evaluated, which provided useful information for fine mapping and replication studies.

Age Distribution↗

PubMed1997

Extensive DNA deletion associated with severe disease alleles on spinal muscular atrophy homologues.

Spinal muscular atrophy (SMA) is a motor neuron disease presenting with a wide spectrum of phenotypic variations. The primary cause of most, if not all, forms of childhood-onset spinal muscular atrophy appears to be the homozygous loss of the telomeric copy of the survival motor neuron (SMNT) gene. It is interesting that approximately half of all affected patients are likewise homozygous nulls for the neuronal apoptosis inhibitory protein (NAIP) gene and a somewhat lesser fraction for the basal transcription factor, p44 subunit (BTF2p44) gene. It has been proposed that homozygous loss of SMNT is the primary cause of spinal muscular atrophy while the loss of NAIP and perhaps other genes primarily affects the severity of disease manifestation. We explored this hypothesis by evaluating the extent of gene deletions in three multigenerational families with spinal muscular atrophy exhibiting dramatic intrafamilial phenotypic variation. Using somatic cell hybrid lines to sequester individual spinal muscular atrophy homologues, we show that homologues missing several contiguous genes correlate with "severe" disease alleles and homologues missing only SMNT correlate with "mild" disease alleles. These observations support the hypothesis that phenotypic severity among the childhood-onset spinal muscular atrophies is directly correlated with the extent of disease-specific deletions.

Adult↗

PubMed1997

Color Doppler monitoring of changes of utero-placental-fetal circulation in normal pregnancy and intrauterine growth retardation.

The utero-placental-fetal circulation (UPFC) of 150 subjects during second and third trimester was examined by using color Doppler. Of them 89 were normal woman and 58 were patients with intrauterine growth retardation IUGR). Our results showed that UPFC was increased gradually during normal pregnant period. In IUGR patients it was revealed that TAV and Q of UmA, UmV and UtA decreased at 20th week of gestation, especially after 30th week. PI, RI and S/D ratio of UmA were increased, but TAV, Q of UmA and UmV were markly reduced, so was UtA. PI were increased, but the changes of RI, S/D ratio in UtA were not significant. Hemodynamical findings of UmA, UmV and UtA were abnormal in 92.53% of IUGR patients. Only 81.03% present abnormal S/D ratio of UmA (P < 0.01) and the difference was statistically significant. Maternal serum E3, HPL level in IUGR were significantly lower than that of the normal. 6KP level was reduced, TXB2/6KP ratio was significantly increased. TXB2/6KP ratio was markedly related with TAV, Q of UmA, UmV and UtA. Our results suggested that using color doppler ultrasound for examination of hemodynamical changes of UmA, UmV and UtA could revealed UPFC function directly. It is one of the best methods for monitoring IUGR and might be used for early diagnosis of IUGR. The main pathophysiological changes of IUGR were UPFC obstruction and placental disfunction.

Adult↗

PubMed1997

Intravascular ultrasound assessment of regional aortic wall stiffness, distensibility, and compliance in patients with coarctation of the aorta.

BACKGROUND: Impaired aortic pulsatility has been demonstrated by angiography in children and in studies of experimental animals with coarctation of the aorta. OBJECTIVES: The purpose of this study was to assess regional aortic stiffness, distensibility, and compliance before and after balloon dilation in patients with coarctation of the aorta. METHODS AND RESULTS: Intravascular ultrasound examination was performed in 13 pediatric patients with the diagnosis of coarctation of the aorta to yield aortic diameter. Area transverse sections at both systolic and diastolic period were measured at three aortic levels: the proximal, distal, and coarctation segments. Balloon dilation was also performed in eight of 13 patients. By using pressures measured in the same areas, an aortic stiffness index (beta) was calculated as In(Ps/Pd)/(Ds-Dd), where In is natural logarithm, Ps is systolic pressure, Pd is diastolic pressure, Ds is systolic diameter, and Dd is diastolic diameter. Aortic distensibility and an estimation of aortic compliance were also calculated. The beta stiffness index of the coarctation and the proximal segments of the aorta were significantly greater than that of the distal segment of the aorta (p < 0.01). The aortic wall stiffness beta index did not acutely change after successful balloon dilation, but the distensibility and compliance of distal aorta were nonetheless significantly decreased after balloon dilation (p < 0.01, p < 0.05) as a function of changes of pulsatility of flow. CONCLUSIONS: Abnormal proximal aortic stiffness may be a strong contributing factor that promotes the genesis of hypertension in patients with coarctation even after successful repair or balloon angioplasty.

Adolescent↗

PubMed1997

High-pressure infrared and FT-Raman investigation of a dental composite.

Composite resins are often used as filling materials on load-bearing surfaces of teeth. As masticatory stresses can be high, here, we study the effect of pressure on the behaviour of a dental composite. Using a polymerized wafer, the IR and FT-Raman spectra of a zirconia-containing proprietary composite (Z100, 3M, Minneapolis, MN, USA) were recorded. The high-pressure IR spectra were also recorded. Band assignments were made for the main peaks of both organic and inorganic components. Breaks in the pressure dependences (dv/dP) of the organic components were found at 22 kbar. Different pressure dependences for different vibrational modes of inorganic components were also observed. These data suggest that the network structure of the composite is compacted under high pressure and that both the atomic distance and bonding angles in the network are altered.

Biomechanical Phenomena↗

PubMed1997

Vinconate, a cognitive enhancer, and PI turnover-phospholipase C systems in the brain.

The molecular mechanisms for the stimulation of inositol 1-phosphate (IP1) formation by vinconate were investigated using preparations of rat brain. Vinconate (10(-8)-10(-3) M) dose-dependently inhibited the binding of [3H]quinuclidinyl benzilate ([3H]QNB) to muscarinic acetylcholine receptors and its IC50 value for [3H]QNB binding was 1.7 x 10(-5) M. The rightward shift of carbachol displacement curve of [3H]QNB binding by GTP (10(-4) M) was completely abolished by vinconate (10(-5) M). Carbachol (10(-8)-10(-2) M) increased [3H]IP1 formation in a dose-dependent manner and the carbachol-induced [3H]IP1 formation was significantly accentuated by vinconate (10(-5) M). The enhancement of [3H]IP1 accumulation by vinconate was inhibited by approximately 50% in the presence of atropine (10(-5) M), although phentolamine and ketanserin had no effects on the stimulatory effect of vinconate on [3H]IP1 formation. Vinconate showed no alteration in the binding of [3H]guanosine 5'-(beta, gamma-imino) triphosphate ([3H]Gpp(NH)p) to the crude synaptic membranes. The enhancement of phosphatidylinositol 4,5-biphosphate (PIP2)-specific phospholipase C (PLC) activity by GTP was unaffected in the presence of 10(-3) M vinconate, whereas vinconate alone dose-dependently enhanced the activities of both PIP2-specific and cytosolic PLC. These results suggest that vinconate may induce the facilitation of phosphatidylinositide (PI) turnover via the stimulation of muscarinic acetylcholine receptors, the enhancement of coupling between muscarinic acetylcholine receptors and GTP-binding protein, and the direct activations of PIP2-specific and cytosolic PLC.

Animals↗

PubMed1997

Effect of maternally acquired Aujeszky's disease (pseudorabies) virus-specific antibody in pigs on establishment of latency and seroconversion to differential glycoproteins after low dose challenge.

This study investigated whether (1) passively immune pigs could become latently infected after challenge with low doses of wild type pseudorabies virus (PRV) and (2) if seroconversion to PRV could be consistently detected using two commercially available differential diagnostic ELISAs. Three litters of piglets with passively acquired PRV serum neutralizing (SN) antibody (geometric mean titers 47.03 to 95.10) were challenged at 6 to 12 days of age with 236 to 500 TCID50 of Shope strain virus; pigs were vaccinated at 11 weeks of age with a commercially available genetically engineered vaccine (TK- gE- gG- Iowa S62 strain PRV). Vaccination was intended to reduce the risk of reactivation of latent infection resulting in spread of virulent PRV infection to previously uninfected pigs during the experiment. Vaccination at this age also approximated common field practices in infected herds. After 15 weeks, all challenged pigs were seropositive on the PRV glycoprotein (g or gp) E differential ELISA but were seronegative on the gG differential ELISA. All three challenge groups had pigs that were latently infected as evidenced by the detection of PRV DNA by polymerase chain reaction (PCR) assay of their trigeminal ganglia (TG). There was a significant inverse relationship observed for age at challenge and the proportion of PCR positive pigs in the group 15 weeks postchallenge (p = 0.0004). This trend was independent of the passively acquired PRV SN antibody titers at challenge. In this study, passively acquired antibody did not provide protection against establishment of latent infection in piglets after exposure to low doses of virulent PRV. These latent infections were detected serologically by only one of two available differential diagnostic ELISA.

Analysis of Variance↗

PubMed1997

Chronic electrical stimulation of the auditory nerve at high stimulus rates: a physiological and histopathological study.

A major factor associated with recent improvements in the clinical performance of cochlear implant patients has been the development of speech-processing strategies based on high stimulation rates. While these processing strategies show clear clinical advantage, we know little of their long-term safety implications. The present study was designed to evaluate the physiological and histopathological effects of long-term intracochlear electrical stimulation using these high rates. Thirteen normal-hearing adult cats were bilaterally implanted with scala tympani electrode arrays and unilaterally stimulated for periods of up to 2100 h using either two pairs of bipolar or three monopolar stimulating electrodes. Stimuli consisted of short duration (25-50 microseconds/phase) charge-balanced biphasic current pulses presented at 1000 pulses per second (pps) per channel for monopolar stimulation, and 2000 pps/channel for bipolar stimulation. The electrodes were shorted between current pulses to minimize any residual direct current, and the pulse trains were presented using a 50% duty cycle (500 ms on; 500 ms off) in order to simulate speech. Both acoustic (ABR) and electrical (EABR) auditory brainstem responses were recorded periodically during the chronic stimulation program. All cochleas showed an increase in the click-evoked ABR threshold following implant surgery; however, recovery to near-normal levels occurred in approximately half of the stimulated cochleas 1 month post-operatively. The use of frequency-specific stimuli indicated that the most extensive hearing loss generally occurred in the high-frequency basal region of the cochlea (12 and 24 kHz) adjacent to the stimulating electrode. However, thresholds at lower frequencies (2, 4 and 8 kHz), appeared at near-normal levels despite long-term electrode implantation and electrical stimulation. Our longitudinal EABR results showed a statistically significant increase in threshold in nearly 40% of the chronically stimulated electrodes evaluated; however, the gradient of the EABR input/output (I/O) function (evoked potential response amplitude versus stimulus current) generally remained quite stable throughout the chronic stimulation period. Histopathological examination of the cochleas showed no statistically significant difference in ganglion cell densities between cochleas using monopolar and bipolar electrode configurations (P = 0.67), and no evidence of cochlear damage caused by high-rate electrical stimulation when compared with control cochleas. Indeed, there was no statistically significant relationship between spiral ganglion cell density and electrical stimulation (P = 0.459), or between the extent of loss of inner (IHC, P = 0.86) or outer (OHC, P = 0.30) hair cells and electrical stimulation. Spiral ganglion cell loss was, however, influenced by the degree of inflammation (P = 0.016) and electrode insertion trauma. These histopathological findings were consistent with the physiological data. Finally, electrode impedance, measured at completion of the chronic stimulation program, showed close correlation with the degree of tissue response adjacent to the electrode array. These results indicated that chronic intracochlear electrical stimulation, using carefully controlled charge-balanced biphasic current pulses at stimulus rates of up to 2000 pps/channel, does not appear to adversely affect residual auditory nerve elements or the cochlea in general. This study provides an important basis for the safe application of improved speech-processing strategies based on high-rate electrical stimulation.

Action Potentials↗

PubMed1997

Risk factors for human cysticercosis morbidity: a population-based case-control study.

A population-based case-control study to determine social and behavioural risk factors for Taenia solium cysticercosis in humans was carried out in a rural area. Shandong province, China. Forty-eight cases with cysticercosis were ascertained through a prevalence survey conducted among 7281 persons in 1993. For each case, four controls residing in the same village and matched for age and sex were randomly selected. Information regarding demographic, social and behavioural factors was collected during house visits through interviews and direct observation. Risk factors strongly associated with human cysticercosis included poor personal hygiene, being unable to recognize cysticerci-containing meat, poor pig-raising practices and a history of passing tapeworm proglottides. The results indicate that health education in combination with chemotherapy for taeniasis is required for the control of cysticercosis in humans.

Adolescent↗

PubMed1997

Characterization of TSCL, a nonviral retroposon from Arabidopsis thaliana.

We isolated by differential screening a 1.2 kb cDNA from an Arabidopsis thaliana ecotype Columbia cDNA library that is highly expressed in stem and root. In situ hybridization studies on stem sections and root sections showed that the mRNA is expressed in stem sclerenchyma and root cortex, respectively. The isolation and sequence analysis of four other overlapping cDNA clones from two independent A. thaliana cDNA libraries confirmed that these cDNAs lack a significant open reading frame that has recognizable homology to any known proteins. We have obtained from A. thaliana ecotype Columbia three corresponding genomic clones and nucleotide sequence analysis of these clones revealed that we have isolated a retroposon, TSCL, that is flanked by two 13 bp direct repeats, is intronless, and has a poly(A)+ tract at the 3' end. The site of transcription initiation mapped by primer extension analysis lies 48 bp downstream from an external TATA box. Results from Southern blot analysis suggest that TSCL occurs as a single-copy insert in the genomes of A. thaliana ecotype Columbia (Col-0) and Col-2 but is absent in the genomes of Brassica napus. Brassica juncea and A. thaliana ecotypes Be-0, Oy-0 and Ler-0. This suggests that Col-0 and Col-2 are phylogenetically more closely related to each other than to Be-0, Oy-0 and Ler-0, and that the Laibach Landsberg seeds Redei received, from which ecotypes Col-0, Col-2 and Ler-0 originated, were heterogeneous for TSCL.

Amino Acid Sequence↗

PubMed1997

Recollective and automatic uses of memory.

Three cued-recall experiments examined the effects of learning conditions and set size on recollective and automatic uses of memory. Words were studied under different conditions and had either small or large preexisting associative sets. Results based on the process-dissociation procedure showed that learning conditions and set size influenced recollective uses of memory, whereas only set size influenced automatic uses. Other results indicated that process-dissociation and direct-indirect test procedures produce similar results. The findings suggest that the relative contributions of recently acquired information and preexisting information depend on how memory is being used. Recollective uses of memory are affected by the nature of recent study and by what such study activates in long-term memory. In contrast, automatic uses of memory are more affected by what the test cue automatically activates than by what has been learned during recent study.

Automatism↗

PubMed1997

Usefulness of detection of minimal residual disease by 'hypermetaphase' fluorescent in situ hybridization after allogeneic BMT for chronic myelogenous leukemia.

Hypermetaphase FISH (HMF), a molecular cytogenetic procedure combining the long term mitotic arrest of bone marrow cultures with detection of a specific chromosomal rearrangement by fluorescence in situ hybridization (FISH), has recently been shown to be effective in determining the frequency of Philadelphia chromosome positive (Ph+) cells in the bone marrow of chronic myelogenous leukemia (CML) patients undergoing treatment. By combining the probe for the Ph chromosome with one for the detection of the X chromosome, we used HMF to monitor the presence of malignant cells within the emerging host cell population in the marrow of a CML patient that had undergone sex-mismatched allogeneic bone marrow transplantation. In successive studies, we detected 0.5% and 1.75% Ph+ cells, respectively, confirmed by Western blot analysis for p210 protein. These readings occurred concordantly with a repopulation of host-derived diploid female cells. Standard G-band cytogenetic analyses did not detect any Ph+ cells at these time points. Intervention with donor lymphocyte infusion reinduced complete remission. This experience indicates that HMF is useful to identify low levels of repopulation by Ph+ cells in the marrow post-BMT at a stage when intervention is most efficacious.

ABO Blood-Group System↗

PubMed1997

Unscheduled apoptosis during acute inflammatory lung injury.

Apoptosis is a mode of cell death currently thought to occur in the absence of inflammation. In contrast, inflammation follows unscheduled events such as acute tissue injury which results in necrosis, not apoptosis. We examined the relevance of this paradigm in three distinct models of acute lung injury; hyperoxia, oleic acid, and bacterial pneumonia. In every case, it was found that apoptosis is actually a prominent component of the acute and inflammatory phase of injury. Moreover, using strains of mice that are differentially sensitive to hyperoxic lung injury we observed that the percent of apoptotic cells was well correlated with the severity of lung injury. These observations suggest that apoptosis may be one of the biological consequences during acute injury and the failure to remove these apoptotic cells may also contribute to the inflammatory response.

Journal Article↗