Biomedical subjects

X Chen

Publications and source records attributed to X Chen.

At least 1,099 records · Page 61Linked to original sources

PubMed1997

Resting load and modulation of the myofilament Ca2+ sensitivity in rabbit cerebral arteries.

The effect of preload on myofilament Ca2+ sensitivity was examined using alpha-toxin permeabilization and fura-2 fluorometry in rabbit cerebral arteries. The [Ca2+]i-force curves shifted leftward at a high preload, with a decrease in median effective concentration of Ca2+ in the permeabilized artery. In the fura-2-loaded artery, the preload modulated the force without affecting [Ca2+]i levels during K+ depolarization, and a high preload moved the [Ca2+]i-force curve upward and to the left. It is thus concluded that the preload regulates the Ca2+ sensitivity of the myofilament and, therefore, may play a role in the regulation of cerebral arterial tonus and blood flow.

Actin Cytoskeleton↗

PubMed1997

Role of the Fas/Fas ligand pathway in apoptotic cell death induced by the human T cell lymphotropic virus type I Tax transactivator.

Two distinct human diseases have been described in association with human T cell lymphotropic virus type I (HTLV-I) infection: adult T cell leukaemia and tropical spastic paraparesis/HTLV-I-associated myelopathy. Although comprehensive understanding of specific mechanisms underlying pathogenesis of either disease has not yet been achieved, the viral regulatory protein Tax is believed to play a significant role. Previous studies demonstrated the potential of Tax to transform host cells. Here, it is shown that the Tax transactivator has in addition the potential to induce T cell death by apoptosis. Using an inducible system (Jurkat cell line JPX-9), significant apoptotic cell death upon Tax expression was observed. In an attempt to detect the cellular genes mediating this effect, it was found that induction of Tax was associated with marked upregulation of the Fas ligand (FasL) gene. Tax-induced apoptosis was inhibited when the Fas/FasL pathway was interrupted by YVAD-cmk, the inhibitor of ICE-like proteases. Transient expression experiments provided additional support for the putative role of endogenous FasL in Tax-induced apoptosis. Upon cotransfection with Tax-expressing plasmid, the transcriptional activity of the FasL promoter was found to be significantly upregulated in Jurkat cells and several other cell lines, as measured by reporter gene expression. Furthermore, cotransfection using different Tax mutants demonstrated that both CREB and NF-kappaB activation domains of Tax protein were required for the transactivation to take effect.

Adult↗

PubMed1997

Phylogeny and potential transmission routes of midgut-associated endosymbionts of tsetse (Diptera:Glossinidae).

Many tsetse species (Diptera: Glossinidae) harbour two morphologically different intracellular endosymbiotic microorganisms associated with gut tissue: primary (P) and secondary (S) endosymbionts. The P-endosymbionts of tsetse (Wigglesworthia glossinidia) are sequestered in specialized epithelial cells, bacteriocytes, which form a structure (bacteriome) in the anterior portion of the gut. Phylogenetic characterization of P-endsymbionts from the three subgenera of genus Glossina has shown that these organisms constitute a distinct lineage within the gamma-subdivision of Proteobacteria and have evolved concordantly with their insect host species, suggesting an evolutionarily ancient association for this symbiosis. The S-endosymbiont is a smaller (1-2 micron) gram-negative rod and is harboured in midgut epithelial cells. Its phylogenetic characterization from Glossina morsitans morsitans had shown that it is a member of the family Enterobacteriaceae within the gamma-3 subdivision of the Proteobacteria, closely related to enteric bacteria. Some tsetse species harbour a third bacterium in their reproductive tissue, which was shown phylogenetically to belong to to the Wolbachia pipientis assemblage of microorganisms. Here, we show that S-endosymbionts from five tsetse species, representing all three subgenera, form a cluster of closely related microorganisms, based on their almost identical 16S rRNA gene sequences. The high similarity provides strong evidence of recent independent acquisition of S-endosymbionts by individual tsetse species, unlike Wigglesworthia which displays concordant evolution with host insect species. A PCR-based assay and restriction fragment length polymorphism (RFLP) analysis was developed to localize the S-endosymbionts and Wigglesworthia in ovary, egg, milk-gland and spermatheca tissues in order to investigate the potential routes for the vertical transmission of these symbionts to the intrauterine larvae. Only S-endosymbionts were found to infect milk gland tissue, suggesting that milk gland secretions represent a route of transmission for these symbionts into the developing larva. The ovary tissue was found to harbour only Wolbachia, confirming its transovarial transmission, whereas the mode of transmission of Wigglesworthia remains unknown.

Animals↗

PubMed1997

Extracts of Ginkgo biloba and ginsenosides exert cerebral vasorelaxation via a nitric oxide pathway.

1. Extracts from the leaves of Ginkgo biloba (EGb) and ginsenosides (GS) have been reported to be effective at increasing vascular relaxation. In the present study, the actions of EGb and GS on the vascular functions of porcine basilar arteries were investigated in vitro using tissue bath techniques. 2. Both EGb and GS relaxed the basilar artery in a concentration-dependent and partly endothelium-dependent manner. However, EGb appeared to be more potent than GS. Relaxation induced by transmural nerve stimulation (TNS) was significantly enhanced by EGb (7.5, 15 and 30 micrograms/mL) and GS (20, 40 and 80 micrograms/mL) in both endothelium-intact and -denuded basilar arteries. Enhanced TNS-induced relaxations were abolished by 0.3 mmol/L N-L-arginine. 3. The present study demonstrates that nitric oxide plays a primary role in TNS-induced relaxation as well as in EGb- and GS-enhanced relaxation within the cerebral vasculature. In addition, our data support the potential of these compounds as therapeutic strategies in cerebral ischaemia and other related vascular dysfunctions.

Animals↗

PubMed1997

Predictors of tooth loss over 10 years in adult and elderly Chinese.

This study describes the incidence of tooth loss over a 10-year period in a population of rural Chinese, initially aged between 20 and 80 years. Among the 587 persons who participated in a baseline examination in 1984, 440 persons were available for a follow-up study in 1994. A total of 31 persons, mainly aged 50+ years at baseline, had become completely edentulous. Between 45% and 96% of the persons lost at least one tooth, and the average number of teeth lost ranged between 1.0 and 7.2. The distribution of the number of teeth lost was skew, indicating that a minor group of subjects had a substantially higher risk of tooth loss than the majority. Logistic regression analysis identified six significant predictors of tooth loss among those who remained dentate: age, a high number of teeth with dentinal caries lesions, a high number of teeth with caries lesions of any type, presence of teeth with attachment loss > or = 7 mm, presence of mobile teeth, and a low percentage of sites with subgingival calculus deposits. At the subject level, caries variables and periodontal disease variables seemed equally important predictors of the incidence of tooth loss over 10 years, but at the tooth level caries was a predominant cause of tooth loss in all age groups.

Adult↗

PubMed1997

Predictors of destructive periodontal disease incidence and progression in adult and elderly Chinese.

This study describes some predictors of new and progressing destructive periodontal disease over a 10-year period in rural Chinese. A total of 398 persons aged 20-80 years, who had participated in a baseline survey of tooth mortality, dental caries and periodontal conditions and were still dentate 10 years later, were reexamined for the same parameters as assessed at baseline. Three different threshold values were used to define new and progressing destructive periodontal disease. Irrespective of the threshold used, most persons experienced new disease. Progressing disease was very prevalent when a 2+ mm disease definition was used, but occurred less frequently at the higher threshold levels. The logistic regression models for 2+ and 3+ mm disease were essentially similar, and showed that women, persons with 104 sites or more, and persons with 0-5% sites with 4+ mm attachment levels had a lower risk of disease progression as well as of new disease than did men, persons with few sites and persons with 6% sites or more with attachment levels 4+ mm. The variables sex, number of sites present, percentage of sites with 4+ mm attachment levels, and presence of mobile teeth were predictive for new disease using a 4+ mm definition. Age, percentage of sites with 4+ mm attachment levels and percentage of sites with 4+ mm pockets were predictive for progressing disease using the 4+ mm disease definition.

Adult↗

PubMed1997

Photochemical and photobiological studies of a furonaphthopyranone as a benzo-spaced psoralen analog in cell-free and cellular DNA.

Photobiological activities of the benzo-spaced psoralen analog furonaphthopyranone 3 have been investigated in cell-free and cellular DNA. The molecular geometry parameters of 3 suggest that it should not form interstrand crosslinks with DNA. With cell-free DNA no evidence for crosslinking but also not for monoadduct formation was obtained; rather, the unnatural furocoumarin 3 induces oxidative DNA modifications under near-UVA irradiation. The enzymatic assay of the photosensitized damage in cell-free PM2 DNA revealed the significant formation of lesions sensitive to formamidopyrimidine DNA glycosylase (Fpg protein). In the photooxidation of calf thymus DNA by the furonaphthopyranone 3, 0.29 +/- 0.02% 8-oxo-7,8-dihydroguanine (8-oxoGua) was observed. With 2'-deoxyguanosine (dGuo), the guanidine-releasing photooxidation products oxazolone and oxoimidazolidine were formed predominately, while 8-oxodGuo and 4-HO-8-oxodGuo were obtained in minor amounts. The lack of a significant D2O effect in the photooxidation of DNA and dGuo reveals that singlet oxygen (type II process) plays a minor role; control experiments with tert-butanol and mannitol confirm the absence of hydroxyl radicals as oxidizing species. The furonaphthopyranone 3 (Ered = -1.93 +/- 0.03V) should act in its singlet-excited state as electron acceptor for the photooxidation of dGuo (delta GET ca -6 kcal/mol), which corroborates photoinduced electron transfer (type I) as a major DNA-oxidizing mechanism. A comet assay in Chinese hamster ovary (CHO) AS52 cells demonstrated that the psoralen analog 3 damages cellular DNA upon near-UVA irradiation; however, no photosensitized mutagenicity was observed in CHO AS52 cell cultures.

Animals↗

PubMed1997

Radiation force on a spherical object in the field of a focused cylindrical transducer.

An exact solution of the radiation force on a spherical object, when positioned on the acoustic axis of a cylindrical transducer, is provided. The solution is valid for any type of sphere of any size. The radiation force function allows the calibration of high-frequency focused ultrasound fields from radiation force measurements and expands the utility of the elastic sphere radiometer developed by Dunn et al. [Acustica 38, 58-61 (1977)]. Numeral results reveal an oscillatory behavior of the radiation force function for small spheres near the transducer surface and this behavior may present an opportunity for particle sorting based on the mechanical properties of the particle and other types of manipulation.

Humans↗

PubMed1997

Discontinuous plus-strand DNA synthesis in human immunodeficiency virus type 1-infected cells and in a partially reconstituted cell-free system.

Human immunodeficiency virus type 1 (HIV-1) replication requires conversion of viral RNA to double-stranded DNA. To better understand the molecular mechanisms of this process, we examined viral DNA synthesis in a simple cell-free system that uses the activities of HIV-1 reverse transcriptase to convert regions of single-stranded HIV-1 RNA to double-stranded DNA in a single incubation. This system recapitulated several of the required intermediate steps of viral DNA synthesis: RNA-templated minus-strand polymerization, preferential plus-strand initiation at the central and 3' HIV-1 polypurine tracts, and DNA-templated plus-strand polymerization. Secondary sites of plus-strand initiation were also observed at low frequency both in the cell-free system and in cultured virus. Direct comparison of viral and cell-free products revealed differences in the precision and selectivity of plus-strand initiation, suggesting that the cell-free system lacks one or more essential replication components. These studies provide clues about mechanisms of plus-strand initiation and serve as a starting point for the development of more complex multicomponent cell-free systems.

Binding Sites↗

PubMed1997

p53 is phosphorylated by CDK7-cyclin H in a p36MAT1-dependent manner.

The tumor suppressor protein p53 acts as a transcriptional activator that can mediate cellular responses to DNA damage by inducing apoptosis and cell cycle arrest. p53 is a nuclear phosphoprotein, and phosphorylation has been proposed to be a means by which the activity of p53 is regulated. The cyclin-dependent kinase (CDK)-activating kinase (CAK) was originally identified as a cellular kinase required for the activation of a CDK-cyclin complex, and CAK is comprised of three subunits: CDK7, cyclin H, and p36MAT1. CAK is part of the transcription factor IIH multiprotein complex, which is required for RNA polymerase II transcription and nucleotide excision repair. Because of the similarities between p53 and CAK in their involvement in the cell cycle, transcription, and repair, we investigated whether p53 could act as a substrate for phosphorylation by CAK. While CDK7-cyclin H is sufficient for phosphorylation of CDK2, we show that p36MAT1 is required for efficient phosphorylation of p53 by CDK7-cyclin H, suggesting that p36MAT1 can act as a substrate specificity-determining factor for CDK7-cyclin H. We have mapped a major site of phosphorylation by CAK to Ser-33 of p53 and have demonstrated as well that p53 is phosphorylated at this site in vivo. Both wild-type and tumor-derived mutant p53 proteins are efficiently phosphorylated by CAK. Furthermore, we show that p36 and p53 can interact both in vitro and in vivo. These studies reveal a potential mechanism for coupling the regulation of p53 with DNA repair and the basal transcriptional machinery.

Amino Acid Sequence↗

PubMed1997

Comparative evaluation of within-cultivar variation of rice (Oryza sativa L.) using microsatellite and RFLP markers.

The objective of this study was to determine an efficient way of detecting within-cultivar variation in rice varieties obtained from national and international germplasm collections. Seventy-one rice cultivars were evaluated for within-cultivar variation using a combination of phenotypic, RFLP, and microsatellite or simple sequence length polymorphism (SSLP). Variation between individuals within and accession and between duplicate accessions within a cultivar was detected even in cultivars that had been purified by phenotypic evaluation. Landrace cultivars were more heterogeneous and displayed a larger number of both RFLP and SSLP alleles than did modern cultivars. Microsatellite markers detected a greater number of alleles and were able to discriminate between even closely related individuals more efficiently than RFLPs. Some microsatellite markers were more informative than others for assessing genetic diversity. Single markers revealed 5.6-61.1% of the total variation detected by the 10 SSLP markers. Some marker combinations were complementary, providing more information than others. Several combinations of 4 SSLP markers detected as much as 94% of the total within-cultivar variation detected by the 10 SSLP markers. These results suggest that the use of four well-chosen microsatellites would be an efficient method for evaluating the heterogeneity of rice accessions.

Gene Frequency↗

PubMed1997

Autoreceptor-induced inhibition of neuropeptide Y release from PC-12 cells is mediated by Y2 receptors.

Pheochromocytoma (PC)-12 cells express Y1, Y2, and Y3 neuropeptide Y (NPY) receptors when differentiated with nerve growth factor (NGF). The present work evaluated NGF-differentiated PC-12 cells as a model system to study modulation of NPY release by NPY autoreceptors. We demonstrated that both K+ and nicotine stimulated concomitant release of NPY and dopamine from differentiated PC-12 cells. We also showed in this study that NPY release from PC-12 cells was attenuated in a concentration-dependent manner by peptide YY (PYY)-(13-36), a selective agonist for the Y2 type of NPY receptors. This result demonstrated that NPY release could be modulated by NPY autoreceptors of the Y2 subtype. The inhibitory action of PYY-(13-36) may be mediated at least in part by inhibition of N-type Ca2+ channels, because PYY-(13-36) could not produce further inhibitory effects in the presence of a maximum effective concentration of omega-conotoxin, an N-type Ca2+-channel blocker. The inhibition by PYY-(13-36) could be blocked by pretreatment of cells with pertussis toxin, suggesting that an inhibitory GTP-binding protein was involved. Furthermore, the function of NPY autoreceptors could be modulated by other receptors such as beta-adrenergic and ATP receptors. The evoked release of NPY was also attenuated by ATP and adenosine, which have been shown to be colocalized and coreleased with NPY from sympathetic nerve terminals. These results suggest that PC-12 cells differentiated with NGF may be an ideal model to study regulatory mechanisms of NPY release and that autoreceptor-mediated regulation of NPY release appears to act through the Y2 subtype of the NPY receptor.

Animals↗

PubMed1997

Differential ventral septal vasopressin release is associated with sexual dimorphism in PGE2 fever.

The vasopressinergic innervation of the ventral septal area (VSA) has been shown to be implicated in antipyresis. Because this system is less well developed in female rats, we hypothesized that female rats would display exaggerated febrile responses. We therefore examined the temperature responses of conscious and urethan-anesthetized rats of both sexes to centrally administered prostaglandin E2 (PGE2) and correlated these responses with the release and action of endogenous arginine vasopressin (AVP) in the VSA. Both conscious [25 ng/5 microliters PGE2 intracerebroventricularly (i.c.v.)] and anesthetized (VSA microdialyzed, 50 ng/5 microliters PGE2 i.c.v.) female rats had higher fevers than did males. Infusion of an AVP V1a receptor antagonist {1 nmol [d(CH2)5Tyr(Me)]AVP} plus PGE2 gave rise to higher fevers in males but not in females. Measurements of AVP in microdialysates of the VSA showed that the release of endogenous AVP was increased in response to PGE2 in males only. Baseline AVP release in both sexes was similar. The results suggest that there is a sex-related difference in PGE2 fever, which may be accounted for by the differential AVP release in the VSA.

Animals↗

PubMed1997

Targeting deletion of angiotensin type 1B receptor gene in the mouse.

We null mutated the mouse angiotensin type 1B (AT1B) receptor gene (Agtr1b) by gene targeting. To identify the specific cell types carrying high Agtr1b gene transcriptional activities, the AT1B coding exon was replaced with a reporter gene, lacZ. In 6- to 8-wk-old Agtr1b -/- mice, high AT1B transcriptional activity was observed in adrenal zona glomerulosa cells and the testis, including mature and immature spermatic cells, whereas low activity was detected homogeneously in anterior pituitary cells and choroidal plexus vessel walls. A similar pattern was observed in Agtr1b +/- mice with less intensity. Microscopically, the anterior pituitary, heart, adrenal, zona glomerulosa, kidney, and the testis of Agtr1b -/- mice were intact and were indistinguishable from those of Agtr1b +/+ mice. Systemic blood pressure was comparable in Agtr1b -/- and Agtr1b +/+ mice. Moreover, plasma aldosterone level was comparable between the two mouse groups. No compensatory enhancement of AT1A mRNA was found in the kidney and adrenal gland of Agtr1b -/- mice. The observed absence of the abnormal phenotypes in Agtr1b -/- mice, which have been described for homozygous angiotensinogen null mutant mice, indicates that 1) AT1A receptors can take over the role of AT1B receptors in Agtr1b -/- mice or 2) functionally significant non-AT1, non-AT2 receptor(s) may exist for the action of angiotensin.

Aldosterone↗

PubMed1997

Parameters influencing the efficiency of the thymidine kinase/ganciclovir strategy in human glioblastoma cell lines.

The gene therapy strategy using the hsv1-thymidine kinase gene (TK) and ganciclovir (GCV) injections that has been used for treating human glioblastomas has not been as effective as expected after the first animal experiments. A better understanding of the different steps involved in this treatment, like gene transfer, gene expression, and sensitivity of the recipient cells is needed. Therefore, we studied 7 human glioblastoma cell lines (U87, U118, U251, SNB19, SNB75, SF295, SF539) for their sensitivity to the TK/GCV system. We also studied their in vitro bystander effect and their in vitro transfectability using LipofectAMINE as a transfection enhancer. According to this in vitro analysis, most of the glioblastoma cell lines should be sensitive to the TK/GCV system, but there is a significant need for agents to increase transfection efficiency.

Animals↗

PubMed1997

Genetic association of the low-density lipoprotein receptor-related protein gene (LRP), an apolipoprotein E receptor, with late-onset Alzheimer's disease.

The presence of the APOE epsilon 4 allele encoding apolipoprotein E4 (apoE4) is the major genetic risk factor for late-onset Alzheimer's disease (AD). However, the molecular and cellular mechanisms by which APOE epsilon 4 renders AD risk are unclear. In this report, we present genetic evidence that an apoE receptor, LRP, may be associated with the expression of late-onset AD. Using a biallelic genetic marker in exon 3 of LRP, late-onset AD cases markedly differed from the control subjects in the distribution of LRP genotypes, and this difference was highly accentuated among AD cases with positive family history of senile dementia. Furthermore, the numbers of neutritic plaques were significantly altered as a consequence of different LRP genotypes in postmortem AD cases. Taken together, our results implicate the pathophysiology of LRP in the expression of late-onset AD.

Age of Onset↗

PubMed1997

Effects of apolipoprotein E on dementia and aging in the Shanghai Survey of Dementia.

We investigated the status of the apolipoprotein E allele in 538 participants in the incidence phase of the ongoing Shanghai Survey of Dementia, including 103 demented subjects, 72 with mild cognitive impairment and 363 cognitively normal. The apo E epsilon 4 allele was present in 10.2% of control subjects and the allelic frequency did not change between ages 60 to 96 years. The apo E epsilon 4 allelic frequency was increased both in those wiht Alzheimer's disease (AD) (25.4%) and those with vascular dementia (VaD) (22.2%), but not in those with other dementing illnesses or the cognitively impaired. All of the subjects homozygous for apo E epsilon 4 were demented, three were diagnosed as having AD, and three met NINDS/AIREN criteria for VaD. The increased apo E epsilon 4 allelic frequency in clinically diagnosed VaD patients suggests that some of the infarcts are secondary to congophilic angiopathy. The adjusted odds ratio of developing AD in this community-derived study for persons with at least one apo E epsilon 4 allele was 4.1 (95% CI: 2.2, 7.7). Thus, the apo E epsilon 4 risk of developing AD in this Chinese cohort is similar to that in western community studies.

Age Factors↗

PubMed1997

A 10-year study of the progression of destructive periodontal disease in adult and elderly Chinese.

This study describes the progression of destructive periodontal disease among Chinese aged 20 to 80 with limited access to dental health facilities and minimal traditions for oral hygiene procedures. These individuals were followed for 10 years to determine whether the rates for progression of periodontal disease were markedly different than for populations with more access to oral health care. At baseline, participants had been examined for tooth mobility, plaque, calculus, gingival conditions, attachment levels, and probing depths on 4 sites of each tooth present. These probing depth and attachment level recordings were repeated at follow-up, although third molars were excluded from examination. A total of 398 persons remained dentate at follow-up. The analysis demonstrated that virtually all subjects experienced > or = 2 mm attachment loss over the 10-year period, and frequently in a large proportion of the sites present. Attachment loss > or = 3 mm was also widespread, but the distribution of persons according to the extent of > or = 3 mm attachment loss was positively skewed in all age groups. Positive skewness was even more pronounced when attachment loss of > or = 4 mm was considered. Some types of teeth, such as mandibular incisors and maxillary molars, had higher progression rates than did, for example, maxillary incisors. The mean individual attachment loss rates did not differ significantly between age groups, and were remarkably similar to those reported for populations whose access to and tradition for oral health care is widespread.

Adult↗