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Biomedical subjects

R Chen

Publications and source records attributed to R Chen.

At least 235 records · Page 13Linked to original sources

ARG1 (altered response to gravity) encodes a DnaJ-like protein that potentially interacts with the cytoskeleton.

Gravitropism allows plant organs to direct their growth at a specific angle from the gravity vector, promoting upward growth for shoots and downward growth for roots. Little is known about the mechanisms underlying gravitropic signal transduction. We found that mutations in the ARG1 locus of Arabidopsis thaliana alter root and hypocotyl gravitropism without affecting phototropism, root growth responses to phytohormones or inhibitors of auxin transport, or starch accumulation. The positional cloning of ARG1 revealed a DnaJ-like protein containing a coiled-coil region homologous to coiled coils found in cytoskeleton-interacting proteins. These data suggest that ARG1 participates in a gravity-signaling process involving the cytoskeleton. A combination of Northern blot studies and analysis of ARG1-GUS fusion-reporter expression in transgenic plants demonstrated that ARG1 is expressed in all organs. Ubiquitous ARG1 expression in Arabidopsis and the identification of an ortholog in Caenorhabditis elegans suggest that ARG1 is involved in other essential processes.

Amino Acid Sequence↗

Adeno-associated virus-mediated gene transfer to the brain: duration and modulation of expression.

Adeno-associated virus (AAV) is a promising vector for central nervous system (CNS) gene transfer, but a number of issues must be addressed if AAV is to be used for widespread delivery throughout the CNS. Our aim was to test the effect of dose, route of delivery, and hydroxyurea treatment on brain expression of beta-galactosidase activity after cerebral inoculation with an rAAV-lacZ vector (rAAV-beta-gal). We also wished to test whether an immune response appeared against the vector and the transgene product. We found in BALB/c mice that beta-Gal expression increased during the first 2 months after inoculation, then decreased slightly by 4 months, and continued out to 6, 12, and 15 months in single animals. Cerebral injection produced localized beta-Gal expression that did not diffuse to other regions despite a fivefold increase in injection volume. Intraventricular injection resulted in negligible transduction. Antibodies to AAV capsid protein and beta-Gal appeared at low levels at 2 and 4 months, but correlated poorly with beta-Gal expression and did not prevent readministration of rAAV-beta-gal. Hydroxyurea treatment did not result in increased transduction in vivo. We conclude that our study confirms rAAV vectors as having considerable potential for CNS gene transfer; however, several important problems must be addressed if this vector system is to be used for long-term transduction of the entire brain. Sustained, regulatable expression will be needed if rAAV is to be used in the treatment of chronic CNS disease. The difficulty in delivering AAV to diverse regions of the brain is an important problem that must be overcome if these vectors are to be used for anything beyond localized transduction.

Animals↗

Monoclonal antibody-based ELISAs for part-per-billion determination of polycyclic aromatic hydrocarbons: effects of haptens and formats on sensitivity and specificity.

As a first step toward developing sensitive enzyme-linked immunosorbent assays (ELISAs) for multianalyte detection of polycyclic aromatic hydrocarbons (PAHs), haptens with different lengths of carboxylic acid spacers at various positions were derived from naphthalene, fluorene, anthracene, phenanthrene, pyrene, fluoranthene, chrysene, and benzo[a]pyrene (BaP). These haptens were coupled with bovine serum albumin (BSA) to form competitor conjugates. All of these haptens were recognized to different extents by monoclonal antibodies (MAbs) 4D5 and 10C10 originally derived by Gomes and Santella (Chem. Res. Toxicol. 1990, 3, 307-310). The most sensitive indirect ELISAs were obtained by coating wells with the least competitive conjugates. Direct ELISAs using horseradish peroxidase conjugates of pyrene and BaP were less sensitive. The MAbs bound BaP with spacers at either C1 or C6. The cross-reactivity profiles of the eight PAHs were different with each PAH-BSA conjugate used as coating antigen. The ELISA results for BaP closely correlated with those by gas chromatography (GC), but the detection limit of the ELISA was approximately 150-fold more sensitive than that of GC, with 2-600 nM spike recoveries of 80-127% from human urine and canal and tap water.

Antibodies, Monoclonal↗

Quality of HMO vaccination databases used to monitor childhood vaccine safety. Vaccine Safety DataLink Team.

The availability of large, population-based, automated, medical care databases provides unique opportunities for monitoring the safety of childhood vaccines. The authors assessed the quality of automated vaccination databases by comparing them with vaccinations documented in paper-based medical records at three large US West Coast health maintenance organizations (HMOs) participating in the Vaccine Safety DataLink (VSD) study, a Centers for Disease Control and Prevention collaborative study of childhood vaccine safety. The authors randomly selected 1% or 2% samples of VSD study populations (n = 1,224-2,577) for data quality analyses. Agreement between automated and abstracted vaccinations required identical triads of child identification number, vaccination date, and vaccine type. Separate analyses were conducted for each HMO and for each vaccine type administered between 1991 and 1995. Agreement was measured by three matching proportions: 1) the proportion of automated vaccinations present in the abstracted source, 2) the proportion of abstracted vaccinations present in the automated source, and 3) the proportion of vaccinations from either source present in both sources. Overall, for common childhood vaccines, proportion 1 ranged from 83% to 99%, proportion 2 ranged from 82% to 98%, and proportion 3 ranged from 70% to 97%. Lack of automated data was the most frequent type of discrepancy, followed by date mismatches and vaccine type mismatches. Vaccination exposure classification errors in the range reported here were found by mathematical modeling to only modestly bias measured medical outcome rate ratios toward the null hypothesis. The results of the data quality analyses support the usefulness of vaccination exposure data derived from these automated HMO vaccination databases.

Abstracting and Indexing↗

A meta-analysis of epidemiological studies in depression of older people in the People's Republic of China.

BACKGROUND: There has been little information about depression in Chinese elderly people. In order to investigate whether or not there is an excess of depression among the Chinese elderly, we have performed a meta-analysis of the published epidemiological studies. METHODS: Papers published in the literature from The People's Republic of China included in the Chinese medical databases were obtained. Some additional papers collected from other sources were also included. The fixed/random effects model and Poisson model were employed for data analysis. RESULTS: There were 10 cross-sectional studies (23 samples divided according to men/women and urban/rural subjects) giving sufficient prevalence data on depression (13 565 subjects) or depressive mood (8476 subjects). The pooled prevalence of depression was 3.86% (95%CI 3.37-4.42%), while that of depressive mood was 14.81% (14.20-15.64%). The risk of depression in the rural communities (5.07%, 3.61-7.13%) was higher than in the urban (2.61%, 2.22-3.08%). The same trends were observed for depressive mood. The patterns of risk factors were similar to those in western countries. CONCLUSIONS: Chinese tradition and culture may be explanatory factors for the low prevalence, provided the methodological issues have not seriously biased the results.

Aged↗

Effect of muscle activity immediately after botulinum toxin injection for writer's cramp.

Animal and human studies have shown that nerve stimulation enhances some effects of botulinum toxin (btx A) injection. Voluntary muscle activity might work similarly and would focus the effect of an injection into the active muscles. We studied the effects of exercise immediately after btx A injection in eight patients with writer's cramp with established response to btx A over two injection cycles with a single-blinded, randomized, crossover design. Immediately after the first study injection, they were randomly assigned to write continuously for 30 min or have their hand and forearm immobilized for 30 min. Following the second injection, they were assigned the alternate condition. Patients were assessed just before each injection, and at 2 weeks, 6 weeks, and 3 months post-injection. Assessment included objective strength testing, self-reported rating of benefit and weakness, and blinded evaluation of videotapes and writing samples of the patients writing a standard passage. Strength testing showed that the maximum weakness occurred at 2 weeks post-injection, but the benefit was maximum at 6 weeks post-injection. The "write" condition resulted in greater reduction in strength than the "rest" condition. Btx A treatment led to improvement in self-reported ratings, writer's cramp rating scale scores by blinded raters, and reduction in writing time, but the differences between the "write" and "rest" conditions were not significant. We conclude that voluntary muscle activity immediately after btx A injection leads to greater reduction in muscle strength. Our findings raise the possibility that voluntary muscle activation may allow reduction of btx A doses and favorably alter the balance of benefit and side effects of btx A injections.

Adult↗

An open trial of clozapine for dystonia.

Pharmacologic treatment of severe dystonia is often unsatisfactory. The atypical antipsychotic medication clozapine appears to improve tardive dystonia associated with conventional neuroleptic use. We studied the efficacy of clozapine for severe dystonia in five patients in an open trial. The patient cohort included four with generalized dystonia and one with Meige syndrome. All patients were evaluated at baseline and at least weekly while on medication with subjective assessment of response by the patient and physician rating using the Burke-Fahn-Marsden Evaluation Scale for Dystonia. All five subjects had significant improvement detected by the Burke-Fahn-Marsden Evaluation Scale as well as subjective improvement while on clozapine. Side effects, such as sedation and orthostatic hypotension, developed in all patients but was only treatment-limiting in one subject who developed persistent symptomatic orthostatic hypotension and tachycardia. Two of the four remaining patients continued clozapine after completion of the study; an additional patient was uncertain if the benefit outweighed the side effects. One patient discontinued treatment because of difficulty obtaining the FDA-required weekly white blood cell counts for patients on clozapine. We conclude that clozapine appears to be effective for generalized and refractory focal dystonia although its use may be limited by the side effects and need for hematologic monitoring.

Adult↗

Purification and stabilization of a monomeric isocitrate dehydrogenase from Corynebacterium glutamicum.

Monomeric isocitrate dehydrogenase was expressed in Corynebacterium glutamicum cells harboring pEK-icdES1, a plasmid carrying the gene for the enzyme. Two- to three-fold higher expression levels of the recombinant enzyme were observed in such cells when grown in fermentors, compared to those grown in shaker incubators. The enzyme was purified to homogeneity by ammonium sulfate fractionation, Sephadex G-150 gel filtration, FPLC Mono Q anion-exchange chromatography, and affinity gel chromatography. Approximately 4 mg of 98% pure recombinant enzyme was obtained per liter of bacterial culture. Our results also include optimum buffer conditions for purification and storage of the enzyme.

Chromatography, Affinity↗

Mechanism of the silent period following transcranial magnetic stimulation. Evidence from epidural recordings.

We investigated the nature of the silent period (SP) following transcranial magnetic stimulation by recording corticospinal volleys in a patient with implanted cervical epidural electrodes. Single suprathreshold test stimuli and paired stimuli at interstimulus intervals (ISIs) of 50-200 ms were delivered while the subject maintained a constant background contraction. The silent period duration from a single test stimulus was 357+/-62 ms. The test motor-evoked potentials were markedly reduced at all the ISIs tested. The I (indirect) waves induced by the test stimulus were largely unchanged at an ISI of 50 ms, suggesting that there was little change in motor cortex excitability. However, the corticospinal volleys, especially the late I waves, were substantially reduced at ISIs of 100 ms, 150 ms, and 200 ms. Our findings suggest that the early part of the SP is mainly due to spinal mechanisms, while the late part of the SP is related to reduced motor cortex excitability.

Accidents, Traffic↗

Modulation of motor cortex excitability by median nerve and digit stimulation.

We investigated the time course of changes in motor cortex excitability after median nerve and digit stimulation. Although previous studies showed periods of increased and decreased corticospinal excitability following nerve stimulation, changes in cortical excitability beyond 200 ms after peripheral nerve stimulation have not been reported. Magnetoencephalographic studies have shown an increase in the 20-Hz rolandic rhythm from 200 to 1000 ms after median nerve stimulation. We tested the hypothesis that this increase is associated with reduced motor cortex excitability. The right or left median nerve was stimulated and transcranial magnetic stimulation (TMS) was applied to left motor cortex at different conditioning-test (C-T) intervals. Motor-evoked potentials (MEPs) were recorded from the right abductor pollicis brevis (APB), first dorsal interosseous (FDI), and extensor carpi radialis (ECR) muscles. Right median nerve stimulation reduced test MEP amplitude at C-T intervals from 400 to 1000 ms for APB, at C-T intervals from 200 to 1000 ms for FDI, and at C-T intervals of 200 and 600 ms for ECR, but had no effect on FDI F-wave amplitude at a C-T interval of 200 ms. Left median nerve (ipsilateral to TMS) stimulation resulted in less inhibition than right median nerve stimulation, but test MEP amplitude was significantly reduced at a C-T interval of 200 ms for all three muscles. Digit stimulation also reduced test MEP amplitude at C-T intervals of 200-600 ms. The time course for decreased motor cortex excitability following median nerve stimulation corresponds well to rebound of the 20-Hz cortical rhythm and supports the hypothesis that this increased power represents cortical deactivation.

Adult↗

Simultaneous bilateral laser in situ keratomileusis: safety and efficacy.

OBJECTIVE: To compare the safety and efficacy of simultaneous bilateral to sequential bilateral laser in situ keratomileusis (LASIK) surgery for the correction of myopia. DESIGN: Retrospective, nonrandomized, comparative trial. PARTICIPANTS: A total of 2142 consecutive simultaneous and sequential bilateral myopic LASIK surgery eyes operated from March 1996 through June 1998 for the correction of myopia were reviewed. INTERVENTION: Two surgeons (HVG and JAV) performed myopic LASIK using the Nidek EC-5000 excimer laser and either the Chiron Automated Corneal Shaper or the Bausch & Lomb Hansatome microkeratome. MAIN OUTCOME MEASURES: The incidence of intra- or perioperative complications for sequential and simultaneous bilateral LASIK for myopia was recorded. Refractive and visual outcomes at 3 to 6 months postoperative were analyzed. Deviations from targeted spherical equivalent (SE), uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), and retreatment rates are reported. RESULTS: Laser in situ keratomileusis was performed on the first eye of 1853 patients scheduled for simultaneous bilateral myopic LASIK. Of these, 28 (1.5%) first eyes had intraoperative or perioperative complications. The second eye surgery was cancelled in 11 cases, and 1842 second eyes completed simultaneous surgery; 13 (0.7%) intraoperative or perioperative complications occurred. Of these 41 complications in simultaneous cases, 1 eye lost 1 line of BCVA at 6 months follow-up. Two hundred eighty-nine patients were scheduled for sequential bilateral myopic LASIK. Five (1.8%) first eyes of the sequential cases had intraoperative complications compared with four (1.4%) sequential second eyes. There was no loss of BCVA in any sequential bilateral case with complications at a minimum at 6 months follow-up. There was no statistically significant difference between intra- and perioperative complication rates comparing simultaneous to sequential bilateral LASIK. Three to 6 months postoperative visual and refractive data were reviewed; except when comparing simultaneous first eye postoperative SE to sequential first eye, there was no statistically significant difference in refractive or visual outcomes, including deviation from targeted SE, UCVA, BCVA, and retreatment rates. CONCLUSION: Simultaneous bilateral LASIK is as safe and effective as sequential surgery. Simultaneous bilateral LASIK may offer several benefits to the patient.

Adult↗

Root gravitropism: a complex response to a simple stimulus?

Roots avoid depleting their immediate environment of essential nutrients by continuous growth. Root growth is directed by environmental cues, including gravity. Gravity sensing occurs mainly in the columella cells of the root cap. Upon reorientation within the gravity field, the root-cap amyloplasts sediment, generating a physiological signal that promotes the development of a curvature at the root elongation zones. Recent molecular genetic studies in Arabidopsis have allowed the identification of genes that play important roles in root gravitropism. Among them, the ARG1 gene encodes a DnaJ-like protein involved in gravity signal transduction, whereas the AUX1 and AGR1 genes encode proteins involved in polar auxin transport. These studies have important implications for understanding the intra- and inter-cellular signaling processes that underlie root gravitropism.

Arabidopsis↗

Cortical reflex myoclonus studied with cortical electrodes.

OBJECTIVE: To study the mechanism of cortical reflex myoclonus. METHODS: A patient with stimulus sensitive myoclonus of the left foot had an array of subdural electrodes placed over the right sensorimotor cortex. RESULTS: Stimulation through one of the electrodes (contact 13) facilitated leg muscles with the shortest latency and was presumed to lie over the motor cortex. Tibial nerve stimulation evoked a potential with the shortest latency 1 cm further posteriorly (contacts 11-12). These contacts were presumed to lie over the sensory cortex. The potential at 11-12 was followed by a much larger potential that reversed polarity at contact 13. Back averaging from spontaneous myoclonic jerks showed a cortical premovement potential which reversed polarity at contact 13. The threshold for the motor evoked potential in leg muscles evoked by transcranial magnetic stimulation was lower on the affected side. Electrical stimulation through contact 13 produced cortical potentials that could be recorded at adjacent contacts. The combination of a positive potential followed by a negative potential recurred at approximately 35-40 ms intervals, each positive potential generating a myoclonic jerk. Additional waves resembling I waves accompanied only the first positive potential. Surgical removal of the cortex under electrode 13 abolished the myoclonus. CONCLUSIONS: The myoclonic jerks arose in the motor cortex. We postulate that there is increased excitability or synchronization of the cortical neurons at that site. The spontaneous, peripherally induced and recurrent cortical potentials and myoclonic jerks can occur without participation of the circuitry of the presumed I waves.

Aged↗

The time course of changes in motor cortex excitability associated with voluntary movement.

The excitability of the motor cortex is modulated before and after voluntary movements. Transcranial magnetic stimulation studies showed increased corticospinal excitability from about 80 and 100 ms before EMG onset for simple reaction time and self-paced movements, respectively. Following voluntary movements, there are two phases of increased corticospinal excitability from 0 to approximately 100 ms and from approximately 100 to 160 ms after EMG offset. The first phase may correspond to the frontal peak of motor potential in movement-related cortical potentials studies and the movement-evoked magnetic field I (MEFI) in magnetoencephalographic (MEG) studies, and likely represents a time when decreasing output from the motor cortex falls below that required for activation of spinal motoneurons, but is still above resting levels. The second phase of increased corticospinal excitability may be due to peripheral proprioceptive inputs or may be centrally programmed representing a subthreshold, second agonist burst. This may correspond to the MEFII in MEG studies. Corticospinal excitability was reduced below baseline levels from about 500 to 1,000 ms after EMG offset, similar to the timing of increase in the power (event-related synchronization, ERS) of motor cortical rhythm. Similarly, motor cortex excitability is reduced at the time of ERS of motor cortical rhythm following median nerve stimulation. These findings support the hypothesis that ERS represents an inactive, idling state of the cortex. The time course of cortical activation is abnormal in movement disorders such as Parkinson's disease and dystonia, reflecting abnormalities in both movement preparation and in cortical excitability following movement.

Electroencephalography↗

Prevalence of overweight and central adiposity is associated with percentage of indigenous ancestry among native Hawaiians.

OBJECTIVE: To assess the relationship of percentage of indigenous ancestry with body mass index (BMI) and waist to hip ratio (WHR) among Native Hawaiians. DESIGN: A cross-sectional, observational study among 567 rural native Hawaiian men and women, aged 30 or older, enrolled between 1993-96. MEASUREMENTS: Ancestry was assessed by self-report, and was verified with a brief genealogical interview. Anthropometric measurements, as well as dietary and physical activity histories were also obtained. RESULTS: Percentage Hawaiian ancestry was significantly associated with increased body mass index (BMI), waist to hip ratio (WHR), and age. The association between percentage Hawaiian ancestry and both anthropometric measures persisted after adjusting for age, leisure time physical activity and total dietary energy intake. CONCLUSION: Obesity and central adiposity were highly prevalent among Hawaiians participating in this study. The association between BMI and WHR with percentage Hawaiian ancestry, unexplained by differences in diet and physical activity, suggests genetic factors play an important role in the high prevalence of obesity observed among Native Hawaiians.

Adipose Tissue↗

Purification and characterization of trichomaglin--a novel ribosome-inactivating protein with abortifacient activity.

Trichomaglin, a novel ribosome-inactivating protein, has been isolated from root tuber of a plant Maganlin (Trichosanthes Lepiniate, Cucurbitaceae). The isolation and purification procedure included ammonium sulfate precipitation, Sephadex G-75 chromatography and CM-Sephadex C-50 chromatography. The protein was identified to be homogeneous by SDS-PAGE and FPLC analysis. Its molecular weight is 24,673 dalton and isoelectric point is 5.8, determined by electrospray ionization mass spectroscopy and isoelectric focusing gel electrophoresis respectively. Trichomaglin can inhibit protein synthesis in rabbit reticulocyte lysate with ID50 of 10.1 nM. When rat ribosome was incubated with trichomaglin, a diagnostic RNA fragment appeared on polyacrylamide gel after ribosomal RNAs were treated with acidic aniline. It was concluded that trichomaglin is an RNA N-glycosidase. In addition, it has been verified to be an abortifacient protein.

Abortifacient Agents, Nonsteroidal↗