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R Chen

Publications and source records attributed to R Chen.

At least 91 records · Page 5Linked to original sources
PubMed2001

3-acetylpyridine reduces tongue protrusion force but does not abolish lick rhythm in the rat.

Data from other laboratories suggest that neurons in the inferior olivary nucleus (IO) may play a role in the modulation of rhythmic tongue movements in rats. Because of its known harmful effects on neurons of the IO, it was suspected that administration of the neurotoxin 3-acetylpyridine (3AP) would affect subsequent tongue dynamics during rat licking. In the present study, the task of licking water from a force-transducing disk was investigated in water-restricted rats that received systemic administration of 3AP (12.5, 25, and 50 mg/kg). After recovery from the acute toxic effects of 3AP, tongue dynamics were assessed by measuring lick force, lick rhythm, variability of timing within bursts of licking, and number of licks per 2-min session. At 50 mg/kg, 3AP resulted in: (1) reduced lick force; (2) reduced number of licks; and (3) increased variance in the timing within bursts. Lick rhythm was not significantly affected by any dose of 3AP. All 3AP treatment groups and the vehicle control group displayed slowing of lick rhythm after harmaline challenge. Compared to vehicle controls, rats receiving lower and mid-range doses of 3AP displayed indistinguishable lick behaviors, with one exception--when the lick task was made incrementally more difficult by extending the distance required to make contact with the lick-disk, rats that had received 25 mg/kg 3AP persevered at the task more than all other rats. The various changes in lick dynamics may be due to the detrimental effects of 3AP at the IO, and possibly at the hypoglossal nucleus and other sites.

Animals↗
PubMed2001

Roles of angiotensin II type 2 receptor stimulation associated with selective angiotensin II type 1 receptor blockade with valsartan in the improvement of inflammation-induced vascular injury.

BACKGROUND: To investigate the effect of angiotensin (Ang) II type 1 receptor (AT(1)) blocker on vascular remodeling and explore the possibility of the involvement of Ang II type 2 receptor (AT(2)) stimulation in this process, we examined the effects of the selective AT(1) blocker valsartan on the vascular injury in wild-type (Agtr2+) and AT(2)-null (Agtr2-) mice. METHODS AND RESULTS: Neointima formation and the proliferation of vascular smooth muscle cells (VSMCs) induced by cuff placement on the femoral artery were greater in Agtr2- mice than those in Agtr2+ mice. Treatment of mice with valsartan at a dose of 1 mg. kg(-1). d(-1), which did not influence systolic blood pressure, significantly decreased neointima formation and the proliferation of VSMCs, whereas the valsartan was less effective in Agtr2- mice. Moreover, cuff placement increased the expression of monocyte chemoattractant protein-1 (MCP-1); inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1beta; and infiltration of CD45-positive leukocytes and macrophages in the injured arteries and further enhanced them in Agtr2- mice, suggesting the antagonistic effects of AT(1) and AT(2) for vascular inflammation. Valsartan attenuated the expression of MCP-1, TNF-alpha, IL-6, IL-1beta, and infiltration of leukocytes and macrophages in the injured arteries; however, these effects of valsartan were less prominent in Agtr2- mice. CONCLUSIONS: These results suggest that the stimulation of the AT(2) receptor after AT(1) blockade is important in the improvement of the inflammatory vascular injury.

Angiotensin I↗
PubMed2001

Pooled umbilical cord blood as a possible universal donor for marrow reconstitution and use in nuclear accidents.

Human umbilical cord blood has been shown to be an effective source of stem cells for marrow reconstitution in pediatric patients. Unfortunately, the quantity of stem cells obtained from an individual donor can be quite limited in both the total volume and the numbers of stem cells per ml of cord blood. HLA matching further limits the availability, but recent publications indicate close matching may be unnecessary. Therefore, if cord blood from different donors can be combined, larger numbers of stem cells can be available for clinical use provided pooling does not produce a negative effect. Storage of single cord blood specimens at 4 degrees C for 10-21 days in gas permeable bags produced an apparent increase in the percentage of immature cells (CD34, CD117, GPA) and mitotic activity (S+G2/M cells) over day 1. With similar storage of pooled specimens there was a further increase in the number of immature colonies cultured, CD34, CD117, GPA, S+G2/M cells. In addition, nucleated red blood cells increased over the mean values obtained from single cord blood samples. Our previous studies have indicated that large numbers of human mononuclear cells are necessary to reconstitute an irradiated animal model. By combining multiple samples of human cord blood, adequate numbers of stem cells could be pooled for use in adults and would provide cells for megadose therapy, including those patients that had accidentally received lethal irradiation.

Bone Marrow Transplantation↗
PubMed2001

Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study.

BACKGROUND: A generally held belief is that cholesterol concentrations should be kept low to lessen the risk of cardiovascular disease. However, studies of the relation between serum cholesterol and all-cause mortality in elderly people have shown contrasting results. To investigate these discrepancies, we did a longitudinal assessment of changes in both lipid and serum cholesterol concentrations over 20 years, and compared them with mortality. METHODS: Lipid and serum cholesterol concentrations were measured in 3572 Japanese/American men (aged 71-93 years) as part of the Honolulu Heart Program. We compared changes in these concentrations over 20 years with all-cause mortality using three different Cox proportional hazards models. FINDINGS: Mean cholesterol fell significantly with increasing age. Age-adjusted mortality rates were 68.3, 48.9, 41.1, and 43.3 for the first to fourth quartiles of cholesterol concentrations, respectively. Relative risks for mortality were 0.72 (95% CI 0.60-0.87), 0.60 (0.49-0.74), and 0.65 (0.53-0.80), in the second, third, and fourth quartiles, respectively, with quartile 1 as reference. A Cox proportional hazard model assessed changes in cholesterol concentrations between examinations three and four. Only the group with low cholesterol concentration at both examinations had a significant association with mortality (risk ratio 1.64, 95% CI 1.13-2.36). INTERPRETATION: We have been unable to explain our results. These data cast doubt on the scientific justification for lowering cholesterol to very low concentrations (<4.65 mmol/L) in elderly people.

Aged↗
PubMed2001

Simultaneous measurement of six cytokines in a single sample of human tears using microparticle-based flow cytometry: allergics vs. non-allergics.

Tears play an essential role in maintaining corneal and conjunctival integrity by providing a tightly regulated, optimal extracellular environment critical to its numerous functions, which include anti-microbial defense, wound healing and inflammatory responses such as allergies. Elevated levels of inflammatory cytokines have been reported in tears from various ocular disease states. Characterization of tear cytokines has been limited by the small volume (microliter amounts) attainable. This limitation was addressed with the newly developed Becton Dickinson Cytometric Bead Array (CBA), which combines the principles of the "sandwich" immunoassay with the capability of flow cytometry for simultaneous measurement of the characteristics of multiple particles. This technique allows determination of six human cytokine (IFNgamma, TNFalpha, IL-2, IL-4, IL-5, IL-10) concentrations simultaneously in a single tear sample. Tears were collected from the inferior fornix of non-allergic (n=7) and allergic (n=9) donors. Each tear sample or cytokine standard was incubated with a mixture of capture Ab-bead reagent and detector Ab-phycoerythrin (PE) reagent, and analyzed using flow cytometry. All six cytokines were detectable in both non-allergic and allergic tears. Tears from allergic donors contained significantly less IL-10 (p=0.035), and had significant increases in the ratios of TNFalpha/IFNgamma, IL-5/IFNgamma and IL-5/IL-10 (p=0.0008, 0.0124 and 0.011, respectively). The small volume required (5-10 microl/test) by the Cytometric Bead Array allows measurement of all six cytokines from a single collection of tears. This decreases collection time, minimizing the confounding effect of stimulation on cytokine concentration in tears, as well as allowing calculation of cytokine ratios.

Adult↗
PubMed2001

Regulation of Akt/PKB activation by tyrosine phosphorylation.

Activation of Akt/PKB by growth factors requires multiple phosphorylation events. Phosphorylation of Thr(308) and Ser(473) of Akt by its upstream kinase(s) or autophosphorylation is critical for optimal activation of its kinase activity. Here, we present evidence that tyrosine phosphorylation is required for Akt activation. Epidermal growth factor treatment induces tyrosine phosphorylation of Akt in COS1 and PC3M cells, which is abrogated by PP2, a selective inhibitor for Src family tyrosine kinases. Elevated Akt activity is observed in v-Src transformed NIH3T3 cells, which is accompanied with increased tyrosine phosphorylation of Akt. Akt activity induced by growth factors is significantly reduced in SYF cells lacking Src, Yes, and Fyn, which can be restored by introducing c-Src, but not the kinase-inactive Src, back to these cells. Furthermore, we have identified two tyrosine residues near the activation loop of Akt that are important for its activation. Substitution of these residues with phenylalanine abolishes Akt kinase activity stimulated by growth factors. These two YF mutants fail to block Forkhead transcription factor activity in 293 cells and are unable to prevent apoptosis induced by matrix detachment. Our data suggest that, in addition to phosphorylation of Thr(308) and Ser(473), tyrosine phosphorylation of Akt may be essential for its biological function.

Amino Acid Sequence↗
PubMed2001

A force-plate actometer for quantitating rodent behaviors: illustrative data on locomotion, rotation, spatial patterning, stereotypies, and tremor.

This report describes a new kind of actometer for recording the behavior of rodents or other small animals. The instrument, a force-plate actometer, uses a stiff, low-mass horizontal plate coupled to four supporting force transducers positioned at the corners of the plate. When an animal moves on the plate, its movements are sensed by the transducers whose signals are processed by computer to yield measurements of a wide range of behaviors or behavioral attributes, such as locomotor activity, rotation around the center, whole-body tremor, and amphetamine-induced stereotypies. Spatial resolution is less than 1 mm, and temporal resolution is 0.02 s. Sample data were presented comparing the locomotor activity of CD-1, BALB/c, and C57BL/6 mice before and after treatment with D-amphetamine sulfate. Rotational behavior was recorded in an amphetamine-treated rat that had sustained a unilateral 6-hydroxydopamine-induced lesion of the nigrostriatal system. In the C57BL/6 mouse, harmaline-induced tremor was quantified. With rats as subjects, the force-plate actometer was used to quantify amphetamine-induced stereotypies, to demonstrate the development of sensitization to amphetamine's effects, and to quantitate the consistent 11-12 Hz rhythmicities that underlie the sterotypies. The performance of the force-plate actometer was compared with that of a variety of instruments reported in the literature on behavioral instrumentation. Finally, potential applications in neuroscience research other than those illustrated in this report were discussed.

Amphetamine↗
PubMed2001

Observation-execution matching system for speech: a magnetic stimulation study.

Observation of limb movements in human subjects resulted in increased motor-evoked potential (MEP) amplitude elicited by magnetic stimulation of motor cortex in the muscles involved in that movement, suggesting that an observation-execution matching (OEM) system exists in humans. We investigated whether the OEM system is activated by speech gestures presented in the visual and auditory modalities. We found that visual observation of speech movement enhanced MEP amplitude specifically in muscles involved in production of the observed speech. In contrast, listening to the sound did not produce MEP enhancement. The findings suggest that the OEM system may be modality specific. It may be involved in action recognition in the visual modality, but is not responsible for perception of simple items of sound.

Acoustic Stimulation↗
PubMed2001

Effects of internal globus pallidus stimulation on motor cortex excitability.

BACKGROUND: Deep brain stimulation is a promising treatment for PD, but its physiologic effects and mechanisms of action remain poorly understood. Magnetic stimulation studies have revealed abnormalities in several different excitatory and inhibitory circuits in the motor cortex in PD. METHODS: The physiologic effects of internal globus pallidus (GPi) stimulation in seven patients with PD and seven age-matched healthy volunteers were studied. The stimulators were set at the optimal parameters (ON), at half the optimal amplitude (Half-Amp), or switched off (OFF) in random order. Patients were taking their usual medications. Magnetic stimulation was applied to the motor cortex, and motor evoked potentials (MEP) were recorded from the contralateral first dorsal interosseous muscle. Several excitatory and inhibitory pathways that have been found to be abnormal in PD were tested. RESULTS: The motor threshold (MT), MEP recruitment curve (stimulus intensities from 100 to 150% of MT), short and long interval intracortical inhibition, and intracortical facilitation were similar in the three stimulator conditions tested both at rest and during voluntary contraction. The silent period (SP) was longer in the OFF and Half-Amp conditions than in normal control subjects. In the stimulator ON condition, the SP was significantly reduced compared with the OFF condition and became similar to that in normal control subjects. CONCLUSIONS: GPi stimulation while on dopaminergic medications reduced the SP following magnetic stimulation but did not change corticospinal excitability or other measures of intracortical inhibition and facilitation. The reduction of SP may be related to the antidyskinetic and levodopa-blocking effects of ventral GPi stimulation.

Aged↗
PubMed2001

Genomic sequence and expression analyses of human chromatin assembly factor 1 p150 gene.

Chromatin assembly factor-1 (CAF-1) plays essential roles in eukaryotic chromatin assembly during DNA replication (Smith and Stillman, 1989. Cell 58, 15-25), (Krude, 1999. Eur. J. Biochem. 263, 1-5). Its p150 subunit, involved in interaction with histone H3 and H4, is critical to the CAF-1 nucleosome assembly activity. In this study, we sequenced a 96-kb genomic DNA region that includes a 42.8-kb CAF-1 p150 subunit gene (CHAF1A), and a 41.1-kb EEN gene. A scripted bioinformatics analysis pipeline (research agent) has been set up to annotate the BAC sequence with a set of integrated algorithms. The CAF-1 p150 subunit gene contains 15 exons and 14 introns. The promoter region is characterized by deletional analyses, revealing a potential repressor. Tissue-correlated alternative splicing forms of the transcript was initially identified by EST clustering analysis, then confirmed by RT-PCR which resulted more splicing forms than computational prediction.

3T3 Cells↗
PubMed2001

Beta-alanine-based dendritic beta-peptides: dendrimers possessing unusually strong binding ability towards protic solvents and their self-assembly into nanoscale aggregates through hydrogen-bond interactions.

A series of poly(beta-alanine) dendrimers 1-4 with Boc-carbamate as the surface functionality, beta-alanine as the dendritic branch, 3,5-diaminobenzoic acid as the branching agent, and 1,2diaminoethane as the interior core has been synthesized by a solution-phase peptide-coupling method. The structural identities and purities of the products have been fully characterized by spectroscopic and chromatographic methods. 1H NMR studies on the dendrimers indicated that the Boc-carbamate surface groups exist as a mixture of syn and anti rotamers in solution, and that the dendrimers adopt an open structure in polar solvents; this allows the free interaction of the interior core functionality with solvent molecules. Due to the cooperative effect of a large number of carbamate and amide groups, the dendrimers exhibit an unusually strong binding ability towards protic solvents and behave as H-bond sponges. As a result, the H/D exchange rates of the N-H protons are significantly enhanced in such dendritic structures, as compared to those of nondendritic carbamates and amides. These dendritic peptide dendrimers also exhibit a strong tendency to form nanoscopic aggregates in nonpolar or polar aprotic solvents through intermolecular H-bond interactions.

Hydrogen Bonding↗
PubMed2001

Association of dietary antioxidants and waist circumference with pulmonary function and airway obstruction.

Dietary antioxidants, waist circumference, and pulmonary function were measured in the Fourth Scottish MONICA cross-sectional survey of 865 men and 971 women aged 25-64 years. Waist circumference was inversely related to forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), even after adjustment for age, height, weight, working status, energy intake, and smoking variables in a multiple linear regression model (men: beta = -0.017 for FEV1 l/cm, p < 0.01 and beta = -0.008 for FVC, p = 0.04; women: beta = -0.009 for FEV1, p < 0.01 and beta = -0.007 for FVC, p = 0.01). After additional adjustment for waist circumference, estimated vitamin C and beta-carotene intakes were positively associated with lung function in men (vitamin C: beta = 0.102 for FEV1 l/mg/day, p = 0.03; beta-carotene: beta = 0.073 for FVC l/g/day, p = 0.02). Retinol and vitamin E were not significantly related to lung function for either sex. A case-control study of airway obstruction showed that waist circumference was significantly associated, while vitamin C could be protective. The study suggests that adequate intake of antioxidants and avoidance of increasing girth could help to preserve lung function.

Adult↗
PubMed2001

Interactions between two different inhibitory systems in the human motor cortex.

Intracortical inhibition in the human motor cortex has been previously demonstrated using paired-pulse transcranial magnetic stimulation (TMS) protocols at short intervals (1-6 ms; short interval intracortical inhibition, SICI) with a subthreshold conditioning pulse preceding a suprathreshold test pulse, and at long intervals (50-200 ms; long interval intracortical inhibition, LICI) with suprathreshold conditioning and test pulses. We investigated whether different circuits mediate these inhibitory phenomena and how they interact. In nine healthy volunteers, we applied TMS to the motor cortex and recorded motor evoked potentials from the first dorsal interosseous muscle. With increasing test pulse strength, LICI decreases but SICI tends to increase. There was no correlation between the degree of SICI and LICI. We tested the interactions between SICI and LICI. SICI was reduced or eliminated in the presence of LICI. Loss of SICI was seen even with a conditioning stimulus too weak to induce significant LICI. Our findings demonstrate that different cell populations mediate SICI and LICI. The results are consistent with the hypothesis that LICI inhibits SICI through presynaptic GABAB receptors. Testing of SICI in the presence of LICI may be a non-invasive way of evaluating inhibitory interactions in the human motor cortex.

Adult↗
PubMed2001

Glycophosphatidylinositol-anchored protein deficiency as a marker of mutator phenotypes in cancer.

Phosphatidylinositol glycan-A (PIGA) is a gene that encodes an element required for the first step in glycosylphosphatidylinositol (GPI) anchor assembly. Because PIGA is X-located, a single mutation is sufficient to abolish cell surface GPI-anchored protein expression. In this study, we investigated whether mutation of the PIGA gene could be exploited to identify mutator (Mut) phenotypes in cancer. We examined eight Mut colon cancer lines and four non-Mut colon cancers as controls. In every case, flow cytometric analyses of cells sorted for low fluorescence after staining for GPI-linked CD59 and CD55 revealed negative peaks in the Mut lines but not in the controls. Single cell cloning of purged and sorted GPI-anchor- HCT116 cells and sequencing of the PIGA gene in each clone uniformly showed mutations. Pretreatment of the Mut lines with anti-CD55 or anti-CD59 antibodies and complement or with the GPI-anchor-reactive bacterial toxin aerolysin enriched for the GPI-anchor- populations. Expansion of purged GPI-anchor+ cells in the Mut lines and analyses using aerolysin in conjunction with flow cytometry yielded PIGA gene mutation frequencies of 10(-5) to 10(-4), values similar to the mutation frequencies of the hprt gene. This novel approach allows for the detection of as yet undescribed repair or replication defects and in addition to its considerably greater ease of use than existing techniques and in principle would not require the production of cell lines.

Biomarkers↗
PubMed2001

Measles-mumps-rubella and other measles-containing vaccines do not increase the risk for inflammatory bowel disease: a case-control study from the Vaccine Safety Datalink project.

CONTEXT: A link between measles virus-containing vaccines and inflammatory bowel disease (IBD) has been suggested by recent studies. OBJECTIVE: To address whether receipt or timing of measles-containing vaccine (MCV) increases risk for IBD. DESIGN: A case-control study. SETTING: Four large health maintenance organizations (HMOs) that are part of the Centers for Disease Control and Prevention's Vaccine Safety Datalink project. PATIENTS OR OTHER PARTICIPANTS: A total of 155 persons with codes from International Classification of Diseases, Ninth Revision specific for IBD, born between 1958 and 1989 and enrolled from birth to the onset of disease, were identified. Up to 5 controls were matched by sex, HMO, and birth year. INTERVENTION: None. MAIN OUTCOME MEASURES: Risk for IBD, Crohn's disease, and ulcerative colitis. RESULTS: Past vaccination was not associated with an increased risk for Crohn's disease (odds ratio [OR] for measles-mumps-rubella vaccine [MMR], 0.4; 95% confidence interval [CI], 0.08-2.0), ulcerative colitis (OR, 0.8; 95% CI, 0.18-3.56), or IBD (OR, 0.59; 95% CI, 0.21-1.68). Risk for IBD was not increased among children vaccinated who were younger than 12 months (OR for MMR, 0.61; 95% CI, 0.15-2.45) or aged 12 to 18 months (OR, 0.86; 95% CI, 0.28-2.59) relative to unvaccinated children. Children vaccinated with MMR who were older than 18 months were at significantly decreased risk for IBD (OR, 0.16; 95% CI, 0.04-0.68). Neither past vaccination nor age at vaccination with other MCV was associated with increased risk for Crohn's disease, ulcerative colitis, or IBD. Risk for Crohn's disease, ulcerative colitis, or IBD was not elevated in the time immediately following vaccination with either vaccine. CONCLUSIONS: Vaccination with MMR or other MCV, or the timing of vaccination early in life, did not increase the risk for IBD.

Adolescent↗
PubMed2001

Lewy bodies and parkinsonism in families with parkin mutations.

Previous work has established that compound mutations and homozygous loss of function of the parkin gene cause early-onset, autosomal recessive parkinsonism. Classically, this disease has been associated with loss of dopaminergic neurons in the substantia nigra pars compacta and locus ceruleus, without Lewy body pathology. We have sequenced the parkin gene of 38 patients with early-onset Parkinson's disease (<41 years). Two probands with mutations were followed up. Clinical evaluation of their families was performed, blinded to both genetic and pathological findings. Chromosome 6q25.2-27 haplotype analysis was carried out independently of the trait; parkin gene expression was examined at both the RNA and protein levels. Haplotype analysis of these families revealed a common chromosome 6, with a novel 40 bp exon 3 deletion that cosegregated with disease. In the proband of the smaller kindred, an exon 7 R275W substitution was identified in addition to the exon 3 deletion; RNA analysis demonstrated that the mutations were on alternate transcripts. However, Lewy body pathology typical of idiopathic Parkinson's disease was found at autopsy in the proband from the smaller kindred. These data suggest that compound heterozygous parkin mutations and loss of parkin protein may lead to early-onset parkinsonism with Lewy body pathology, while a hemizygous mutation may confer increased susceptibility to typical Parkinson's disease.

Adult↗