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Biomedical subjects

X Liu

Publications and source records attributed to X Liu.

At least 1,009 records · Page 56Linked to original sources
PubMed1998

Chronic study on the neuronal excitability of the cochlear nuclei of the cat following electrical stimulation.

To examine the safety of auditory brainstem prosthesis, the cat cochlear nuclei were implanted and stimulated chronically with bipolar surface electrodes using charge-balanced biphasic current pulses at rates of 250 pulses/s. The stimulation was continuous 16 h/day for up to 12 weeks. The electrically-evoked auditory brainstem response (EABR) was used to monitor neuronal excitability of the cochlear nuclei following the chronic electrical stimulation. The body weight, respiration, and body temperature of the cats were monitored throughout the experiment. The amplitudes and latencies of the EABR waves were measured fortnightly and compared before, during and after the electrical stimulation. The results showed that the respiration, body weight and body temperature of the cats remained within normal limits during the chronic stimulation. During the stimulation, no change was found in the EABR waveform, but a decreased threshold and wider dynamic range were observed after the stimulation. There was no significant change in the amplitudes and latencies of the EABR waves after stimulation. The present findings suggest that chronic bipolar electrical stimulation with surface electrodes at rates of 250 pulses/s is safe for neuronal excitability of the cochlear nuclei in the cat.

Animals↗
PubMed1998

Acute study on the efficacy and safety of an auditory brainstem prosthesis.

Patients with profound binaural sensorineural hearing loss can be treated with cochlear implantation. In recent years, patients who have lost the integrity of the auditory nerve between the spiral ganglion and the cochlear nucleus in the brainstem, and cannot benefit from a cochlear implant, have reported auditory sensations following direct stimulation of the cochlear nucleus with an auditory brainstem prosthesis. To examine the safety and efficacy of such a prosthesis, the cochlear nuclei of guinea-pigs were acutely implanted and stimulated unilaterally with bipolar surface electrodes using the parameters of human implants. The activation of the central auditory pathway by the prosthesis was demonstrated using the 2-deoxyglucose technique. There was broad 2-deoxyglucose labelling in the ipsilateral cochlear nucleus and bilaterally in the inferior colliculi, indicating unusual stimulation of the ipsilateral ascending pathway. Histological examination was performed on all cochlear nuclei. The volumes of cochlear nuclei and the neuron sizes and density in the cochlear nuclei were analysed with three-dimensional reconstruction techniques, and comparisons were made between the stimulated and unstimulated sides. No histological difference, either by direct visual observation or by statistical comparisons, was observed between the stimulated cochlear nuclei and the control sides. These results suggest that in the acute case the auditory brainstem prostheses can safely and effectively activate the auditory pathway in guinea-pigs.

Acoustic Stimulation↗
PubMed1998

Random expression of human immunodeficiency virus-1 (HIV-1) p17 (epitopes) on the surface of the HIV-1-infected cell.

Twenty monoclonal antibodies (MAbs) were obtained by immunizing Balb/c mice with recombinant p17 (rp17) of HIV-1. Epitope specificity of each MAb was determined using six peptides that cover the entire region of p17. We found that each MAb reacts with only one of the peptides, residues 12-29, 30-52, 53-87, and 87-115 (P12-29, P30-52, P53-87, P87-115) of p17 with the exception of one MAb. Three kinds of MAbs that recognize P30-52, P87-115, and a conformational epitope, suppressed the infectivity of HIV-1 (JMH-1) when they added in the culture of MT-4 cells infected by HIV-1 within 24 h of the infection.

Anti-HIV Agents↗
PubMed1998

The effect of education on mortality among older Taiwanese and its pathways.

The present research examines the impact of education on the mortality of older Taiwanese during a 4-year interval from April 1989 to April 1993. Data used for this study come from the Taiwan Survey of Health & Living Status of the Elderly (1989). The research decomposes the effect of education into the direct effect and the indirect effects by means of health status, health behaviors, and social relationships. We have shown that, of the total effect of educational attainment on the mortality of older Taiwanese, about 83% represents indirect influences by means of the 3 mediating factors, particularly health status. On the other hand, the magnitude of the direct effect, which might reflect influences of additional intervening variables on old-age mortality, is low and not statistically significant. The results demonstrate that the apparent strong effect of education on mortality among older Taiwanese can be accounted for parsimoniously through 3 major pathways.

Aged↗
PubMed1998

Interleukin-10 attenuates experimental fetal growth restriction and demise.

Premature labor, fetal demise, and fetal growth restriction are accompanied by indices of inflammation or infection of the uteroplacental unit. To understand whether these events are causally related, we established an animal model of fetal demise and growth restriction and evaluated the potential utility of the anti-inflammatory cytokine interleukin-10 (IL-10). We administered low-dose endotoxin (lipopolysaccharide, or LPS, 100 microg/kg, i.p.) to third trimester rats (gestational days 14-20). Control rats received normal saline. A third group received IL-10 (100 microg/kg; s.c.) concomitantly with LPS for 7 prenatal days. Cytokine gene expression (IL-10 and TNF-alpha) was evaluated by RT-PCR and tissue levels (TNF-alpha) were determined by ELISA. Apoptosis was evaluated by TdT-mediated dUTP nick end labeling immunohistochemistry, and nitric oxide (NO) levels were quantified by microelectrode electrochemical detection in explants in culture media. LPS exposure resulted in 43% fetal demise and reduced the size of the surviving fetuses. Placental weight was not altered by LPS. IL-10 attenuated the LPS-induced fetal death rate (to 22%) and growth restriction (P<0.05). In normal rats, IL-10 did not affect fetus size or the incidence of resorptions, although placental size was marginally smaller. Increased uterine TNF-alpha content and NO release and apoptosis of uterine epithelia and muscularis were hallmarks of the LPS model. All were normalized by IL-10. IL-10 may represent a new therapeutic option for the treatment of a variety of perinatal complications. Benefit may result from the suppression of TNF-alpha- and NO-mediated cell death.

Animals↗
PubMed1998

Effect of mechanical strain on expression of Na+,K+-ATPase alpha subunits in rat aortic smooth muscle cells.

This article reviews related studies from the authors' laboratory, which focus on the regulation of vascular Na+,K+-ATPase in hypertension. Earlier studies, including the authors', suggested that Na-pump activity in cardiovascular tissues is subject to regulation during hypertension; most of these studies report a stimulation of the vascular enzyme during established stages of hypertension. To test hypothesis that in vascular smooth muscle, strain resulting from elevated pressure may be a signal initiating a cascade of events leading to increased expression of Na+,K+-ATPase, the authors used cell culture and the Flexercell Strain Unit to apply cyclical stretch to rat aortic smooth muscle cells (ASMC) for several days. These studies demonstrated that mechanical strain induces the upregulation of both the alpha-1 and alpha-2 subunits of Na+,K+-ATPase. Mechanisms underlying these changes appear to involve a transient increase in intracellular sodium entering the cell through stretch-activated channels. Calcium entering the cell via L-type channels did not affect stretch-induced upregulation of the alpha isoforms. In addition, protein kinase C inhibition resulted in inhibition of the Na-pump during stretch, but not under nonstretch conditions. The authors conclude that the stretch component of vascular pressure upregulates the Na+,K+-ATPase catalytic subunits. Intracellular sodium may be a signal for this regulation. In addition, phosphorylation by PKC may be important in stretch-induced short-term regulation of the vascular Na-pump.

Animals↗
PubMed1998

The effects of pentobarbital on blood-brain barrier disruption caused by intracarotid injection of hyperosmolar mannitol in rats.

UNLABELLED: This study was performed to evaluate both the effects of pentobarbital on disruption of the blood-brain barrier (BBB) by hyperosmolar mannitol and the relationship between its effect on blood pressure and the integrity of the BBB. Under isoflurane anesthesia, rats in the control group were infused with 25% mannitol into the internal carotid artery before measuring the transfer coefficient (Ki) of 14C alpha-aminoisobutyric acid. Ten minutes before the administration of mannitol, rats received an infusion of pentobarbital: 20 mg/kg in the small-dose group and 50 mg/kg in the large-dose group. In another group of animals (hydralazine group), hydralazine was administered to maintain the mean arterial blood pressure (MAP) at 65 mm Hg during the experimental period. The MAP of the control group (113 +/- 14 mm Hg) was significantly higher (P < 0.002) than that of the small-dose pentobarbital group (78 +/- 13 mm Hg) or the large-dose pentobarbital group (68 +/- 14 mm Hg). In the control group, the Ki of the cortex ipsilateral to the mannitol injection was increased to 4.5 times that of the contralateral cortex (14.5 +/- 7.7 vs 3.2 +/- 0.6 microL x g(-1) x min(-1); P < 0.002). The Ki of the ipsilateral cortex of the small-dose pentobarbital group was 9.7 +/- 5.6 microL x g(-1) x min(-1). The Ki of the ipsilateral cortex of the large-dose pentobarbital group was 5.5 +/- 2.9 microL x g(-1) x min(-1), and lower (-9.0 microL x g(-1) x min(-1)) than that of the control animals (P < 0.05). There was no significant difference in the Ki of the contralateral cortex among any of the three groups of animals. At the same MAP, the Ki of the ipsilateral cortex of the large-dose pentobarbital group was lower (-4.3 microL x g(-1) x min(-1)) than that of the hydralazine group (9.8 +/- 4.6 microL x g(-1) x min(-1)) (P < 0.05). Pentobarbital attenuated the BBB disruption induced by hyperosmolar mannitol. This may be attributed, at least in part, to the blood pressure effect of pentobarbital. IMPLICATIONS: When the blood-brain barrier (BBB) was disrupted by a hyperosmolar solution, pentobarbital attenuated the degree of leakage of the BBB. Systemic hypotension caused by pentobarbital played a significant role in decreasing the leakage. Our study suggests that when the BBB is disrupted, pentobarbital may be effective in protecting the BBB. Furthermore, systemic blood pressure plays an important role in determining the degree of disruption.

Aminoisobutyric Acids↗
PubMed1998

Loss of resistance to a highly immunogenic tumor with age corresponds to the decline of CD8 T cell activity.

A number of ultraviolet light-induced tumors that do not grow progressively in 3- or 9-month-old animals grow progressively in animals starting at approximately 15 months of age. We investigated the immune response to one such tumor, 6130, in young and old mice to determine in nature of this breakdown in immune protection with age. The 6130 tumor cells that grow progressively in 22-month-old animals still retain sensitivity of cytotoxic T lymphocytes (CTLs) generated against the highly immunogenic "6130-A" antigen and consequently are still immunologically rejected when transplanted into 3- and 9-month-old animals, but not in mice older than 15 months. Investigation of the CD8+ CTL response found that in animals 3-12 months old, primary and secondary tumor-specific CTL responses to 6130 can be generated in vivo and in vitro. On the other hand, the CD8+ CTL responses to 6130 seen in animals 15 months of age or older were significantly depressed or absent. These results indicate that a decline in antigen-specific CD8+ CTL is the major cause of increased susceptibility to 6130 tumor growth in older animals.

Aging↗
PubMed1998

Study on Haemophilus influenzae type b diseases in China: the past, present and future.

Meningitis caused by Haemophilus influenzae type b (Hib) is a common and serious disease for which there now are WHO-certified vaccines that are recommended for universal infant immunization in North America and European countries. If these vaccines are to be recommended in Asia, it is necessary to know the incidence, age distribution and clinical outcome of Hib meningitis and other systemic infections in this region. Data on Hib disease in China are scanty. Hib meningitis was common during the 1950s in China, accounting for up to 16% of all of pyogenic meningitis (up to 38% of cases were caused by unknown pathogens), despite severe epidemics of meningococcal meningitis during that period. Since 1989 we have conducted hospital- and community-based etiologic and epidemiologic studies of bacterial meningitis. Hib accounts for 30 to 50% of bacterial meningitis in China. The incidence of Hib meningitis in Hefei City was 10.4 per 100000 children <5 years, a result relatively lower than in the West but higher than the rate of 2.7 found in a retrospective study in Hong Kong. Pneumonia is the primary cause of death for Chinese children. From 1991 to 1993 the average mortality of children<5 years because of pneumonia was 1563.2 per 100000. To achieve the goal of reducing the death rate of children by one-third by the year 2000, greater efforts should be made to reduce the mortality of children with pneumonia. Our preliminary study showed that about one-fourth to one-third of cases of pneumonia in Chinese children might be caused by Hib. Therefore Hib vaccination for infants and children in China might be an effective and valuable procedure to achieve the goal.

Child, Preschool↗
PubMed1998

Lack of association between a polymorphism in the promoter region of the dopamine-2 receptor gene and clozapine response.

Dopamine receptors are strong candidates for involvement in schizophrenia and are targeted by a wide variety of antipsychotics. We hypothesized that genetic variation in these neurotransmitter receptors may influence clinical response to clozapine, an antipsychotic which displays high affinity for dopamine D2 receptors in the limbic system. To test this hypothesis, we studied a functional polymorphism in the promoter region of the D2 receptor gene (-141C Ins/Del) in a sample of 151 clozapine treated patients of British origin. In addition, the influence of this polymorphism on antipsychotic response in general was investigated on a sample of 146 Han Chinese schizophrenic patients treated with a variety of antipsychotics. No association was found between this polymorphism and clinical response in either of the two samples suggesting that genetic variation in D2 receptors does not play a major role in determining clinical response to antipsychotic treatment.

Antipsychotic Agents↗
PubMed1998

Carnitine deprivation adversely affects cardiovascular response to bacterial endotoxin (LPS) in the anesthetized neonatal pig.

Sepsis and endotoxemia are important stressors for the neonate. Newborn infants receiving total parenteral nutrition are routinely deprived of carnitine. To investigate whether carnitine deprivation affects the neonate's ability to respond to endotoxin, 19 newborn piglets received parenteral nutrition for 2-3 weeks that was either carnitine free (CARN-) or supplemented (CARN+) with L-carnitine (400 mg/L). Cardiovascular performance, i.e., heart rate; blood pressure (BP); cardiac output (CO); systemic vascular resistance (SVR), and metabolic response, i.e., plasma glucose; lactate; tumor necrosis factor alpha; tissue nitric oxide; and urinary nitrites, were studied serially in anesthetized piglets for 3 h after endotoxin (lipopolysaccharide (LPS), 250 microg/kg intravenous bolus) or vehicle administration. Plasma and tissue carnitine values were lower in CARN- than in CARN+ piglets. Prior to LPS, no differences were found for most parameters (excepting lower diastolic BP and SVR in CARN- animals). Systolic, diastolic, and mean BP fell after LPS but recovered by the end of the experiment. Nadirs were lower in CARN- than in CARN+ piglets. CO tended to be higher in CARN- than in CARN+ animals and fell after LPS. SVR fell after LPS and was lower in CARN- than in CARN+ piglets. LPS-treated animals transiently increased urinary flow. By all measures (plasma tumor necrosis factor alpha, glucose and lactate, tissue nitric oxide, and urinary nitrite excretion), LPS provocation was similar for both groups. Chronologically, BP changes were more closely related to SVR than to CO. Our findings suggest that carnitine deprivation diminishes tissue carnitine concentrations and adversely affects cardiovascular response to LPS, in part mediated by the peripheral vasculature.

Anesthesia↗
PubMed1998

Synthesis and antibacterial evaluation of novel water-soluble organic peroxides.

A set of new water-soluble organic peroxides has been synthesized and evaluated for in vitro antibacterial activity as part of an effort to develop new antibacterial agents for the treatment of acne vulgaris. The water solubility of these new dialkyl peroxides and peroxyesters was achieved by incorporating either a quaternary ammonium group or a polyethylene glycol moiety. These peroxides are effective against both gram-positive and gram-negative bacteria and have a prolonged activity compared to that of benzoyl peroxide and other peroxide-type antiseptic agents. Among them 4-[[(tert-butylperoxy)carbonyl]benzyl]triethylammonium chloride and [10-(tert-butylperoxy)decyl]trimethylammonium bromide have the broadest antimicrobial spectrums. We have shown that the oxidizing properties of the dioxy group of these compounds are responsible for their antibacterial activities.

Anti-Bacterial Agents↗
PubMed1998

Regulation of porin-mediated outer membrane permeability by nutrient limitation in Escherichia coli.

OmpF and OmpC porins were differentially regulated by nutrient limitation and growth rate in glucose- or nitrogen-limited chemostat cultures of Escherichia coli. Transcriptional and translational ompF fusions showed a sharp peak of expression under glucose limitation at D = 0.3 h-1, with lower amounts at lower and higher growth rates. The peak of OmpR-dependent transcriptional stimulation of ompF under glucose limitation in minimal salts media was about 20-fold above nutrient excess levels and 3-fold higher than that achieved with low osmolarity. Analysis of outer membrane protein levels and results of growth competition experiments with porin mutants were consistent with the enhanced role of OmpF under glucose limitation, but not N limitation. In contrast, OmpC was the major porin under N limitation but was increasingly expressed under glucose limitation at very low growth rates approaching starvation, when OmpF was downregulated. In summary, outer membrane permeability under N-limited, sugar-rich conditions is largely based on OmpC, whereas porin activity is a complex, highly sensitive function of OmpF, OmpC, and LamB glycoporin expression under different levels of glucose limitation. Indeed, the OmpF level was more responsive to nutrient limitation than to medium osmolarity and suggested a significant additional layer of control over the porin-regulatory network.

Bacterial Proteins↗
PubMed1998

Catabolite regulation of the Bacillus subtilis ctaBCDEF gene cluster.

Bacillus subtilis cytochrome c oxidase caa3 is encoded by the ctaCDEF genes at the ctaABCDEF locus, with the ctaBCDEF genes organized as an operon-like unit. A dyad symmetry sequence and a catabolite response element homolog can be recognized in the 240-bp intercistronic region between ctaB and ctaC. ctaB'-lacZ and ctaBCD'-lacZ transcriptional fusions integrated at the native locus were used to study catabolite effects on transcription of the ctaB and ctaCDEF genes. In Schaeffer's medium lacking glucose, ctaBCD'-lacZ was expressed at a very low level during the exponential phase, and expression increased about 30-fold 2 h after entry into the stationary phase. In the presence of 0.5% glucose, ctaBCD'-lacZ expression was totally repressed. In contrast to ctaBCD'-lacZ, ctaB'-lacZ was constitutively expressed regardless of carbon source. The ctaCDEF genes were separated from ctaB by insertion of plasmids carrying selectable markers in such a way that the ctaCDEF and ctaB transcription units remained intact. Enzymatic assays of caa3 with these constructs, showed that ctaCDEF was not expressed independently of ctaB. Also, when a 'ctaB-ctaC'-lacZ fusion (containing the ctaB-ctaC intercistronic region) was placed at a remote nonessential locus, beta-galactosidase activity could not be detected. The absence of a promoter in the ctaB-ctaC intercistronic space also was indicated by the inability to detect ctaC-specific transcripts with RNase protection assays, primer extension, and rapid amplification of 5' cDNA ends. Direct mRNA measurements showed that, in the presence of 0.5% glucose, ctaBCDEF transcripts terminated at the 3' end of the putative stem-loop structure and the distal portion was down-regulated. A possible mechanism for ctaCDEF gene regulation is suggested. Catabolite repression of ctaBCD'-lacZ was partly dependent on CcpA but was independent of HPr. The expression of ctaBCDEF also appears to require the strC, ctaA, and resD-resE gene products.

Bacillus subtilis↗
PubMed1998

The rubella virus nonstructural protease requires divalent cations for activity and functions in trans.

The rubella virus (RUB) nonstructural (NS) protease is a papain-like cysteine protease (PCP) located in the NS-protein open reading frame (NSP-ORF) that cleaves the NSP-ORF translation product at a single site to produce two products, P150 (the N-terminal product) and P90 (the C-terminal product). The RUB NS protease was found not to function following translation in vitro in a standard rabbit reticulocyte lysate system, although all of the other viral PCPs do so. However, in the presence of divalent cations such as Zn2+, Cd2+, and Co2+, the RUB NS protease functioned efficiently, indicating that these cations are required either as direct cofactors in catalytic activity or for correct acquisition of three-dimensional conformation of the protease. Since other viral and cell PCPs do not require cations for activity and the RUB NS protease contains a putative zinc binding motif, the latter possibility is more likely. Previous in vivo expression studies of the RUB NS protease failed to demonstrate trans cleavage activity (J.-P. Chen et al., J. Virol. 70:4707-4713, 1996). To study whether trans cleavage could be detected in vitro, a protease catalytic site mutant and a mutant in which the C-terminal 31 amino acids of P90 were deleted were independently introduced into plasmid constructs that express the complete NSP-ORF. Cotranslation of these mutants in vitro yielded both the native and the mutated forms of P90, indicating that the protease present in the mutated construct cleaved the catalytic-site mutant precursor. Thus, RUB NS protease can function in trans.

Cadmium↗
PubMed1998

Protective CD4+ and CD8+ T cells against influenza virus induced by vaccination with nucleoprotein DNA.

DNA vaccination is an effective means of eliciting both humoral and cellular immunity, including cytotoxic T lymphocytes (CTL). Using an influenza virus model, we previously demonstrated that injection of DNA encoding influenza virus nucleoprotein (NP) induced major histocompatibility complex class I-restricted CTL and cross-strain protection from lethal virus challenge in mice (J. B. Ulmer et al., Science 259:1745-1749, 1993). In the present study, we have characterized in more detail the cellular immune responses induced by NP DNA, which included robust lymphoproliferation and Th1-type cytokine secretion (high levels of gamma interferon and interleukin-2 [IL-2], with little IL-4 or IL-10) in response to antigen-specific restimulation of splenocytes in vitro. These responses were mediated by CD4+ T cells, as shown by in vitro depletion of T-cell subsets. Taken together, these results indicate that immunization with NP DNA primes both cytolytic CD8+ T cells and cytokine-secreting CD4+ T cells. Further, we demonstrate by adoptive transfer and in vivo depletion of T-cell subsets that both of these types of T cells act as effectors in protective immunity against influenza virus challenge conferred by NP DNA.

Animals↗