Biomedical subjects

L Chen

Publications and source records attributed to L Chen.

At least 523 records · Page 29Linked to original sources

PubMed1999

Apolipoprotein E genotype and its pathological correlation in Chinese Alzheimer's disease with late onset.

In this study, we attempted to find a relationship between apoliprotein E (ApoE) genotypes and Alzheimer's disease (AD) pathology in different areas of the brain in Chinese. We also studied the borderline group of possible AD (Poss). There were 34 definite or probable AD (Ad), 18 Poss, and 123 brains from age-matched normal subjects (N). ApoE genotype was determined by nested polymerase chain reaction on genomic DNA extracted from archival paraffin-embedded materials. Hippocampus (including entorhinal cortex), amygdala, superior temporal lobe, middle frontal gyrus, and inferior parietal lobule of the brains of Ad and Poss were examined with beta amyloid (A beta) immunostaining, and the same regions plus medial occipital lobe were examined with tau immunostaining. The percentage of plaque area stained for A beta in each brain region was obtained by an image analyzer, and the average number of neurofibrillary tangles stained for tau was counted with an eyepiece graticule. ApoE epsilon4 frequency was increased in both Ad (22.1%, chi2, df = 1, P = .00005), and Poss (33.3%, P = .000005) compared with N (5.3%). A beta load was significantly increased in the neocortex in Ad examined with at least 1 copy of epsilon4 compared with subjects without epsilon4 (Mann-Whitney, P = .014). The same trend, though not statistically significant, occurred in Poss (P = .15). Tau expression was associated with ApoE epsilon4 in neither Ad nor Poss. Poss is genetically and histologically similar to Ad, although the overall A beta load is significantly increased in the latter. These findings support the recent Consensus Report's findings that all Alzheimer-type pathology may be significant.

Age of Onset↗

PubMed1999

Histological study of normal and tumor-bearing liver treated with focused ultrasound.

The purpose of this investigation was to study the tissue damage (including blood vessels) on both normal and tumor-bearing experimental livers and the course of liver repair after focused ultrasound (FUS) treatment using histological evaluation. A series of experiments were carried out in vivo. Tissue was treated using arrays of ultrasound exposures with a frequency of 1.7 MHz, in situ spatially averaged focal intensity (I(SAL) in situ) of 212-266 W/cm2 (corresponding to in situ spatial peak intensity of 382-479 W/cm2), 5-10 s exposure duration and 1.5-3.0 mm exposure separation. Tissue specimens were examined using both light and electron microscopy. The damage to the blood vessel walls was studied. The results showed the existence of indirect tissue damage in both normal and tumor tissue that is outside of the treatment volume, due to disruption of the major blood vessels supplying the adjacent area. Evidence for liver regeneration was found 2 months after FUS treatment.

Animals↗

PubMed1999

Serotonergic modulation of astrocytic activity in the hamster suprachiasmatic nucleus.

The present study was undertaken to explore the effects of central serotonin receptor activation on the expression of glial fibrillary acidic protein in the suprachiasmatic nucleus of Syrian hamsters. Immunoblot and immunohistochemical procedures were used to examine the effects of systemic application of the serotonin-1A and serotonin-7 receptor agonist, (+/-)-2-dipropyl-amino-8-hydroxyl-1,2,3,4-tetrahydronaphthalene hydrobromide (8-OH-DPAT; 3.75 mg/kg) on the contents and distribution of glial fibrillary acidic protein in the suprachiasmatic nucleus. Administration of 8-OH-DPAT at midday caused a significant reduction in immunoreactive glial fibrillary acidic protein content within 1 h of injection, compared to vehicle controls. This effect was not evident 3 h after drug injection. Treatment with 8-OH-DPAT during the late dark phase had little effect on glial fibrillary acidic protein content. The 8-OH-DPAT-induced reduction in glial fibrillary acidic protein content seen at midday was blocked partially by pretreatment with the serotonin-2 and serotonin-7 receptor antagonist, ritanserin, and more substantially by pretreatment with the serotonin-1A receptor antagonist, NAN-190. Treatment with 8-OH-DPAT also caused a significant redistribution of immunoreactive glial fibrillary acidic protein, such that the dense mesh-like appearance seen in vehicle controls was significantly reduced. The 8-OH-DPAT treatment also significantly decreased expression of polysialic acid, a cell-surface molecule associated with neural plasticity. Immunoblot assessments of glial fibrillary acidic protein contents 2 h before and 1 h after lights off revealed a significant time-of-day difference in glial fibrillary acidic protein expression, with lowest levels occurring at the latter time-point, associated with maximal endogenous serotonin release in the suprachiasmatic nucleus. Collectively, these results indicate that acute plastic changes in glial fibrillary acidic protein-related astrocytic activity in the suprachiasmatic nucleus can be induced in response to serotonin-7 or serotonin-1A receptor activation in a phase-dependent manner. It is interesting to speculate that circadian reorganizations in astrocytic activity could be regulated by the daily rhythm in serotonin release in the suprachiasmatic nucleus.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1999

The commissure of probst as a source of GABAergic inhibition.

Whole-cell patch-clamp recordings were made from neurons in the rat's dorsal nucleus of the lateral lemniscus (DNLL) in a brain slice preparation. Planes of section were chosen to preserve the integrity of fibers in the commissure of Probst (CP) and postsynaptic responses were evoked by electrical stimulation along its length. Results showed that the crossed projection to the DNLL through the CP is mainly, if not exclusively, inhibitory in the rat. Inhibitory postsynaptic responses (IPSPs) evoked by stimulation of the CP were blocked by the gamma-aminobutyric acid (GABA)(A) receptor antagonist bicuculline, but were unaffected by the glycine receptor antagonist strychnine, supporting the conclusion that the crossed inhibitory projection to DNLL from the contralateral DNLL is GABAergic. Stimulation of the CP close to the DNLL frequently evoked excitatory postsynaptic responses as well as IPSPs, but stimulation near the midline evoked IPSPs only. Thus, the excitatory responses probably originated from a pathway other than the projection to the DNLL from the contralateral DNLL through the CP.

Animals↗

PubMed1999

Diet modification affects DNA oxidative damage in healthy humans.

DNA 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a promising biomarker for oxidative damage. We assessed its responsiveness to diet in 32 nonsmoking, healthy subjects (12 male, 20 female) aged 31+/-7.6 years. They consumed two liquid formula diets (Ensures) as the sole source of nutrition for 10-d in a randomized crossover design, with 5-d control solid food diets as washout before each liquid diet period. Reformulated Ensure (Re-En) had a vitamin E/ PUFA of 3.5 compared to standard Ensure (En) of 1.1. We hypothesized that subjects would have lower leukocyte 8-OHdG/deoxyguanosine (dG) ratios while consuming Re-En compared to En. But 8-OHdG/dG ratios did not change with the consumption of either Re-En or En. The mean ratios of 8-OHdG/dG after 10 days of Re-En and En consumption were (2.12+/-0.68)x10(-5) and (2.16+/-0.63)x10(-5), respectively. However, there was a 22% decrease in 8-OHdG/dG by the end of the study and a significant downward trend of leukocyte 8-OHdG among all subjects throughout all nutrient-rich diet phases as the study progressed (Test for trend: p = .04; paired t-test: p = .07). Because all the experimental diets provided antioxidant nutrients at higher quantities than typically consumed by a U.S. age-matched population, this study adds to the few in vivo studies that show a decrease in DNA damage in healthy nonsmoking subjects through dietary intervention.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1999

Identification of distinct signalling pathways for somatostatin receptors SSTR1 and SSTR2 as revealed by microphysiometry.

Somatostatin receptors (SSTRs) are known to mediate diverse cellular responses. Most target cell express more than one SSTR isoform, making it difficult to define the signalling pathway used by individual receptor subtypes. Thus, we have expressed SSTR1 or SSTR2 in rat pituitary F4C1 cells which lack endogenous SSTRs. Using a silicon-based biosensor system, the Cytosensor microphysiometer, which measures the extracellular acidification rate (ECAR) in real time, we have studied the responses to SS mediated by either SSTR1 or SSTR2. In control F4C1 cells, SS had no effect on the basal ECAR. In transfected cells expressing only SSTR1, SS caused a unique decrease in ECAR in a concentration-dependent manner. Receptor-mediated decreases in ECAR have not been reported previously. In F4C1 cells expressing only SSTR2, SS induced a bidirectional ECAR response, a rapid increase followed by a decrease below basal. Two SS analogues, MK678 and CH275, induced characteristic ECAR responses with the expected receptor selectivities for SSTR1 or SSTR2. Pretreatment of F4C1 cells with pertussis toxin abolished the decreases in ECAR mediated by both SSTR1 and SSTR2, but only partially reduced the increase in ECAR mediated by SSTR2. The decrease in ECAR did not depend on a decrease in intracellular cAMP. The ECAR responses to SS were modestly attenuated by methylisobutylamiloride (MIA), an inhibitor of the ubiquitous Na(+)-H+ exchanger NHE1. Removal of extracellular Na+ greatly inhibited the ECAR responses to SS, demonstrating a role for both amiloride-sensitive and -insensitive Na(+)-dependent acid transport mechanisms in SS-induced extracellular acidification. In conclusion, we have identified and characterized different signalling pathways for SSTR1 and SSTR2 in pituitary cells as measured by microphysiometry.

Animals↗

PubMed1999

Mimotopes of cytolytic T lymphocytes in cancer immunotherapy.

Rapid identification of the cytolytic T lymphocyte (CTL) epitopes that are presented by cancer cells will provide the basis for manipulation of tumor immunity but remains a major challenge in the field. By screening randomly synthesized peptide libraries, mimotopes for tumor-reactive CTLs can be readily constructed and they may be functionally equal to or potentially more potent than natural peptides in stimulating CTL responses; therefore, the peptide library approach provides great promise for design of cancer vaccines and adoptive tumor immunotherapy.

Animals↗

PubMed1999

Use of propofol for office-based anesthesia: effect of nitrous oxide on recovery profile.

STUDY OBJECTIVE: To evaluate the effect of nitrous oxide (N2O) on the recovery profile and the incidence of postoperative nausea and vomiting (PONV) after office-based surgery performed under propofol anesthesia. DESIGN: Prospective, randomized, single-blind study. SETTING: Office-based surgical center. PATIENTS: 69 ASA physical status I, II, and III healthy, consenting outpatients undergoing superficial surgical procedures lasting 15 to 45 minutes. INTERVENTIONS: After a standard propofol induction (1.5 mg.kg-1 i.v.), anesthesia was initially maintained with propofol, 100 micrograms.kg-1.min-1 i.v., in combination with either air or N2O 65% in oxygen. The propofol infusion rate was subsequently varied to maintain an adequate depth of anesthesia. All patients received local anesthetic infiltration prior to the surgical incision, as well as during the operation. No prophylactic antiemetics were administered. MEASUREMENTS AND MAIN RESULTS: Recovery times and the incidences of PONV were recorded during the first 24 hours after surgery. Early and late recovery variables were similar in the two treatment groups; however, 65% N2O produced a 19% decrease in the propofol maintenance dosage requirement. One patient (3%) experienced nausea prior to discharge in the propofol-N2O group, and two patients (6%) experienced nausea at home in the propofol alone group. None of the patients vomited or received antiemetic medication during the 24 hours postdischarge period. Ninety-seven percent of patients receiving propofol alone and all of the patients in the propofol-N2O group were "very satisfied" with their anesthetic experience. CONCLUSIONS: In outpatients undergoing office-based surgical procedures with propofol anesthesia, administration of 65% N2O decreased the anesthetic requirement without increasing PONV. Therefore, use of a propofol-N2O combination may be a cost-effective alternative to propofol alone for office-based anesthesia.

Ambulatory Surgical Procedures↗

PubMed1999

Combinatorial gene regulation by eukaryotic transcription factors.

Recent structure determinations of high order complexes of eukaryotic transcription factors bound to DNA have revealed that residues from their DNA-binding domains are involved in protein-protein interactions between distinct factors. Protein-protein interactions between transactivation domains and coactivators have also been characterized in a number of recently determined structures. These studies support the combinatorial mechanism of transcription regulation in eukaryotic cells and multicellular organisms.

Binding Sites↗

PubMed1999

Synthesis and biodistribution of R- and S-isomers of [18F]-fluoropropranolol, a lipophilic ligand for the beta-adrenergic receptor.

The S and R isomers of [18F]-fluoropropranolol (1-[1-fluoro-2-isopropylamino]-3-naphthalen-1-yloxy-propan-2 -ol) have been prepared by reductive alkylation of the appropriate aminoalcohols. The radiosynthesis provides a reasonable yield (approximately 25%) to give products of 99% enantiomeric excess and specific activities of 1-3 Ci/micromol. The dissociation constants for the beta2 adrenergic receptor are 0.5 and 2.5 nM for the S and the R isomers, respectively. The biodistribution data in rats show that uptake and egress of the tracer is rapid but that the result of blocking studies and the difference between the R and the S isomers suggest receptor-mediated uptake in receptor-rich tissue.

Algorithms↗

PubMed1999

Semi-quantitative reverse-transcriptase polymerase chain reaction: an approach for the measurement of target gene expression in human brain.

Polymerase chain reaction (PCR) is a very powerful tool for qualitative evaluation of nucleic acids due to its high efficiency and convenience. Together with the reverse transcription (RT) reaction, the PCR method has been widely applied to the quantitative measurement of DNA and RNA messages. Since RT-PCR is much more sensitive than all of the traditional methods for quantification of mRNA, including Northern blot, ribonuclease protection, RNA blot, and solution hybridization assays, it is the method of choice for quantitative analyses of low abundance mRNA messages. However, because of the exponential nature of the PCR amplification, RT-PCR quantitation may be problematic, giving false estimates of the abundance of the target messages. By using the constitutively expressed 'housekeeping' gene cyclophilin as a reference gene to normalize mRNA levels, and by taking data from the exponential phase of the PCR amplification, we have developed a rapid and reliable semi-quantitative measurement of the relative abundance of dopamine transporter (DAT) mRNA. The semi-quantitative PCR method has been applied to illustrate its use for the measurement of DAT mRNA in post mortem human brain.

Adult↗

PubMed1999

Attention-sensitive visual event-related potentials elicited by kinetic forms.

Previous event-related potential (ERP) studies have shown that selectively attending to a relevant stimulus feature was associated with selection negativity (SN) components. The present study aimed at investigating the ERP indices of attentional selection based on forms defined by motion (kinetic forms). ERPs were recorded from subjects who attended selectively to sequentially presented kinetic forms of bars in one visual field and detected occasional tilted bar targets. Two kinds of kinetic forms were used as the visual stimuli in separate experiments. The main findings were that spatial attention enhanced the amplitude of early ERP components 1 and N1 as well as the late component N2. Topographic maps of voltage and low resolution electromagnetic tomography (LORETA) of the dN2 wave (difference waveform between N2 under attended condition and N2 under unattended condition) suggested an origin in the right occipitotemporal cortex. According to its timing and morphology, the dN2 wave was considered to be an endogenous ERP (like the SN) and was interpreted as reflecting attentional facilitation of the processing of forms defined by motion primarily involving the right occipitotemporal areas.

Adult↗

PubMed1999

Direct evidence of gonadotropin-releasing hormone (GnRH)-stimulated nitric oxide production in the L beta T-2 clonal gonadotropes.

An immortal cell line (L beta T-2) with characteristics of gonadotropes, such as LH-containing secretory granules, and LH release responsiveness to GnRH, was used to investigate the effect of GnRH stimulation on nitric oxide (NO) production. RT-PCR analysis showed that mouse nNOS mRNA was expressed in cultured L beta T-2 cells. L beta T-2 cells were treated with the calcium ionophore, A23187, and NO levels were measured as nitrite using the Griess assay. The data clearly showed that NO production was increased dose-dependently by A23187 treatment (0-10(-5) M). Next, changes in the intracellular concentration of ionized calcium ([Ca2+]i) in L beta T-2 cells induced by GnRH were analyzed by quantitative fluorescence microscopy, and [Ca2+]i was found to be increased markedly by GnRH treatment. In fact, exposure of L beta T-2 cells to increasing concentrations of GnRH from 0 to 10(-6) M was found to enhance NO production in a dose dependent manner, with maximal augmentation at 10(-6) M. However, the stimulation of NO production by GnRH at this concentration was significantly attenuated by pretreatment with NG-nitro-L-arginine methyl ester hydrochloride (L-NAME), a NO synthase inhibitor. Taken together, the present results suggest that GnRH treatment results in increased NO production in L beta T-2 clonal gonadotropes, and intracellular calcium augmentation produced by GnRH may be participate in this process. Our findings also indicate that the L beta T-2 cell line is a useful tool for in vitro studies of the autocrine and paracrine roles of NO in the anterior pituitary gland.

Animals↗

PubMed1999

Modulation of brain activities by hierarchical processing: a high-density ERP study.

The present study investigated how attention to global or local levels of hierarchical patterns modulates brain activities by recording high-density event-related brain potentials (ERPs) evoked by hierarchical stimuli. 120-channel recordings of ERPs were obtained from subjects while they detected targets at global or local levels of hierarchical stimuli displayed in the left or the right visual field. We found that attention to local stimulus features enhanced posterior P1 and N2 components, with the N2 enhancement showing a left hemisphere predominance regardless of stimulus positions. Difference was also seen in the distribution of the frontal P2. Reaction times were slowed when global and local levels of stimuli were incompatible, and an interference effect was observed on anterior N2 amplitudes and latencies. Three-dimensional current distributions showed common sources over the posterior cortex between 80-230 ms and a contralateral frontal source between 300-400 ms for global and local conditions. However, an additional ipsilateral frontal focus between 230-350 ms was found specially for local processing. The results corroborate the findings of previous ERP studies, and suggest that the frontal lobe is particularly important for the selective processing of local parts of a global structure.

Adult↗

PubMed1999

Parallel and competitive processes in hierarchical analysis: perceptual grouping and encoding of closure.

The role of perceptual grouping and the encoding of closure of local elements in the processing of hierarchical patterns was studied. Experiments 1 and 2 showed a global advantage over the local level for 2 tasks involving the discrimination of orientation and closure, but there was a local advantage for the closure discrimination task relative to the orientation discrimination task. Experiment 3 showed a local precedence effect for the closure discrimination task when local element grouping was weakened by embedding the stimuli from Experiment 1 in a background made up of cross patterns. Experiments 4A and 4B found that dissimilarity of closure between the local elements of hierarchical stimuli and the background figures could facilitate the grouping of closed local elements and enhanced the perception of global structure. Experiment 5 showed that the advantage for detecting the closure of local elements in hierarchical analysis also held under divided- and selective-attention conditions. Results are consistent with the idea that grouping between local elements takes place in parallel and competes with the computation of closure of local elements in determining the selection between global and local levels of hierarchical patterns for response.

Adult↗

PubMed1999

Bilateral lesions of the interpositus nucleus completely prevent eyeblink conditioning in Purkinje cell-degeneration mutant mice.

The authors have previously demonstrated that Purkinje cell-degeneration (pcd) mutant mice are impaired in eyeblink conditioning (L. Chen et al., 1996a). The present study addresses the following 3 questions: (a) whether pcd mice perceive the conditioned and unconditioned stimuli as well as the wild-type mice, (b) whether pcd mice have a normal sensitization level, and (c) whether the residual learning in pcd mice is cerebellum-dependent. Results indicated that the pcd mice exhibited normal tone-induced responses in the cochlear nucleus and normal sensitivity to heat-induced pain. They showed a similar level of sensitization as the wild-type mice and were completely unable to learn conditioned eyeblinks after bilateral lesions aimed at the anterior interpositus nucleus. Thus, pcd mice are partially impaired in eyeblink conditioning because of a deficiency in learning mechanisms, and the residual learning in the pcd mice is mediated by the cerebellar nuclei.

Animals↗

PubMed1999

Minor groove RNA triplex in the crystal structure of a ribosomal frameshifting viral pseudoknot.

Many viruses regulate translation of polycistronic mRNA using a -1 ribosomal frameshift induced by an RNA pseudoknot. A pseudoknot has two stems that form a quasi-continuous helix and two connecting loops. A 1.6 A crystal structure of the beet western yellow virus (BWYV) pseudoknot reveals rotation and a bend at the junction of the two stems. A loop base is inserted in the major groove of one stem with quadruple-base interactions. The second loop forms a new minor-groove triplex motif with the other stem, involving 2'-OH and triple-base interactions, as well as sodium ion coordination. Overall, the number of hydrogen bonds stabilizing the tertiary interactions exceeds the number involved in Watson-Crick base pairs. This structure will aid mechanistic analyses of ribosomal frameshifting.

Crystallography, X-Ray↗

PubMed1999

B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion.

The B7 family members B7-1 and B7-2 interact with CD28 and constitute an essential T-cell co-stimulatory pathway in the initiation of antigen-specific humoral and cell-mediated immune response. Here, we describe a third member of the B7 family, called B7-H1 that does not bind CD28, cytotoxic T-lymphocyte A4 or ICOS (inducible co-stimulator). Ligation of B7-H1 co-stimulated T-cell responses to polyclonal stimuli and allogeneic antigens, and preferentially stimulated the production of interleukin-10. Interleukin-2, although produced in small amounts, was required for the effect of B7-H1 co-stimulation. Our studies thus define a previously unknown co-stimulatory molecule that may be involved in the negative regulation of cell-mediated immune responses.

Amino Acid Sequence↗