Biomedical subjects

R Chen

Publications and source records attributed to R Chen.

At least 307 records · Page 17Linked to original sources

PubMed1998

Comparative clinical study of inhaled beclomethasone dipropionate and triamcinolone acetonide in persistent asthma.

UNLABELLED: At this time, no placebo-controlled studies in the clinical literature compare the efficacy and safety of the most widely prescribed oral inhaled corticosteroids when dosed at their recommended daily doses. This study compared the efficacy and safety of beclomethasone dipropionate (BDP) 336 microg/day administered by metered dose inhaler (MDI) alone, and triamcinolone acetonide (TA) 800 microg/day by MDI with a built-in tube extender in adults with persistent asthma. METHODS: This 56-day, randomized, double-blind, double-dummy, placebo-controlled, multicenter trial was conducted in 328 adults with mild to moderately severe asthma (FEV1 50% to 90% of predicted while maintained on inhaled corticosteroids). Patients were seen at a baseline visit and on study days 28 and 56. Efficacy variables included pulmonary function tests, physician and patient assessments of asthma condition, and use of rescue medication. RESULTS: Statistically significant improvements from baseline in most efficacy measures were demonstrated for both active treatments versus placebo, and with the following exception were the same between active treatments: mean increase in FEV1 in the beclomethasone dipropionate group was statistically significantly greater than in the triamcinolone acetonide group on day 28. Throughout the study, BDP was statistically superior to TA with respect to mean change from baseline in total asthma symptom scores and for 3 of 8 weeks in reducing the mean average weekly use of rescue albuterol (the two active treatments were comparable for this variable at all other time points). Beclomethasone dipropionate and TA were comparable in safety. CONCLUSION: In adult patients with mild to moderately severe persistent asthma, treatment with BDP consistently conferred greater improvement from baseline in mean FEV1 than TA. This difference achieved statistical significance after 28 days of therapy but was not maintained to endpoint. Decreases in overall asthma symptom scores and in the use of rescue albuterol were statistically significantly greater for the BDP group compared with the TA group. Based on these findings, we conclude that BDP is at least as effective as TA in the treatment of persistent asthma in adults, and judged by some measures, may be superior.

Administration, Inhalation↗

PubMed1998

Electrophysiological studies in the critical care unit: investigating polyneuropathies.

Polyneuropathies frequently contribute to ventilator dependency and prolonged stay in the intensive care unit. As clinical examination is often limited in critically ill patients, electrophysiological studies are invaluable in establishing the diagnosis of neuropathy, determining its pathophysiology, severity and in following the patients' progression. Guillain-Barré syndrome (GBS) developing before intensive care unit admission and critical illness polyneuropathy (CIP) developing as a complication of sepsis and multiorgan failure are the commonest causes of neuropathy. Electrophysiological findings in CIP are that of an axonal neuropathy whereas the findings in GBS are usually consistent with a demyelinating neuropathy. Axonal GBS can be distinguished from CIP by the preceding illnesses, slow nerve conduction velocity in some cases, lack of spontaneous activity on the initial needle electromyographic study and cerebrospinal fluid findings.

Critical Illness↗

PubMed1998

Interaction of DNA-binding proteins with the 5'-flanking region of a cytokinin-responsive cucumber hydroxypyruvate reductase gene.

Transcription of the cucumber hpr-A gene is responsive to cytokinin and light. To investigate the molecular basis for transcriptional regulation by cytokinin, we have identified DNA sequences and proteins that may be involved in the regulation of hpr-A gene expression. Transient expression assays in etiolated cucumber cotyledons indicate that the 315 bp fragment (-382 to -67) contains sequences necessary for cytokinin responsiveness of the luciferase reporter gene. Band shift assays detected cytokinin-enhanced and -reduced protein binding sites in a 97 bp fragment (-382 to -285) upstream of the hpr-A gene. DNase I footprinting identified two protein-protected sites, a 15 bp sequence, 5'-AAATGACGAAAATGC-3', that contains an as-1 TGACG motif found in other plant promoters, and a 13 bp sequence, 5'-AAGATTGATTGAG-3', of unknown function. Two-dimensional band shift analysis of the cytokinin-responsive DNA protein complex revealed the presence of six DNA protein interactions. Band shift assays showed that cytokinin and light have different effects on the interaction of nuclear proteins to the 97 bp fragment of the hpr-A gene. These data suggest that cytokinin and light do not share identical signal transduction pathways in regulating hpr-A gene expression.

Alcohol Oxidoreductases↗

PubMed1998

A meta-analysis of painting exposure and cancer mortality.

To assess risks of cancer mortality among workers exposed to paints, published papers referring to painters and mortality with standardized mortality ratios (SMR) were meta-analyzed in fixed and random effect models. The SMR for all sites of cancer was significantly raised (111.4; 95% CI: 105.8-117.4). The highest risks of cancer death were from leukemia (187; 95% CI: 114.5-306.7) and from liver cancer (143.6; 95% CI: 117.6-175.4). The SMRs for esophagus and stomach cancer were 132.7 (95% CI: 112.1-157.2) and 120.3 (95% CI: 111.3-130.0), respectively. The risks of bladder cancer (130.4; 95% CI: 113.8-149.5) and lung cancer (129.1; 95% CI: 119.2-139.8) were also raised. The findings provide evidence of an association between work as a painter and risk of cancer, although the confounding effects of smoking and alcohol cannot be entirely excluded, especially with respect to liver cancer since deaths from cirrhosis were also increased. The excess deaths from leukemia could have been from exposure to benzene mixed with other organic solvents, while that from lung cancer may be from exposure to particles containing lead chromate and to asbestos in the paint trade. The high risks of cirrhosis and liver cancer need to be examined further as to possible interactions between organic solvents and alcohol.

Female↗

PubMed1998

Clinical correlates of hypertensive end-stage renal disease.

Although there has been much discussion regarding the etiology of hypertensive renal disease, clinical characteristics of this condition have not been thoroughly studied. The purpose of this investigation was to identify clinical correlates of hypertensive end-stage renal disease (ESRD) in a population of patients older than 50 years and to compare these clinical findings with those in a group of ESRD patients with certain known disorders (established diagnoses). Data regarding demographics, cause of ESRD, educational level, presence of diabetes mellitus, angina, myocardial infarction, and peripheral vascular disease were obtained from the Southeastern Kidney Council for patients starting renal replacement therapy between January 1, 1990, and August 1, 1996. Clinical characteristics were compared for white and black patients. Demographic variables and comorbid conditions were compared between groups with general linear regression or logistic regression contrast techniques. A logistic regression model was formed with hypertensive ESRD or established diagnoses as the outcome variable and comorbid and socioeconomic variables as the independent variables. Hypertensive ESRD was diagnosed in 24% of white and 38% of black patients, while established diagnoses were present in 17% of white and 7% of black ESRD patients. The most common established diagnoses were polycystic kidney disease, specified glomerulonephritis, and nephrolithiasis or obstruction. In a logistic regression model, white patients were found more likely to be classified as having hypertensive ESRD if they were older, suffered from angina and other forms of atherosclerosis, smoked, and were less educated. White patients with hypertensive ESRD were more than 2.4 times as likely to suffer from angina as patients with established diagnoses. For black patients, the presence of peripheral vascular disease and female gender were associated with an increased chance of being diagnosed as having hypertensive ESRD. The results of this investigation show that there is a strong association between atherosclerosis and hypertensive ESRD in older white patients. In black patients, the association between atherosclerosis and hypertensive ESRD was also present, but not as strong. The unique association of hypertensive ESRD with atherosclerosis suggests that atherosclerosis is a risk factor for chronic renal failure and that a primary renal microvascular disorder may lead to both hypertension and progressive renal insufficiency.

Age Factors↗

PubMed1998

Pyruvate prevents hydrogen peroxide-induced apoptosis.

Studies were carried out to investigate the protective effects of pyruvate, a key glycolytic intermediate and alpha-keto-monocarboxylate, against oxidative stress-induced apoptosis. Oxidative stress was induced by treating mouse thymocytes with 25 microM hydrogen peroxide for 15 min at 37 degrees C under 5% CO2 in air. Pre- and post-treatment of cells with 10 mM pyruvate inhibited morphological changes, internucleosomal DNA fragmentation, and translocation of phosphatidylserine to the plasma membrane surface, which are characteristic features of apoptosis. L-lactate (10 mM) and acetate (10 mM) were ineffective in inhibiting apoptosis and appeared to be toxic to the cells under similar conditions. The results suggest that pyruvate has therapeutic potential for use in the treatment of oxidative stress-induced disorders associated with increased apoptosis.

Acetates↗

PubMed1998

Comparison of inactivation and conformational changes of native and apo yeast alcohol dehydrogenase during thermal denaturation.

The conformational changes of native and apo yeast alcohol dehydrogenase during thermal denaturation have been followed by fluorescence emission and circular dichroism spectra. A comparison of inactivation and conformational changes during thermal denaturation shows that for the native enzyme and for the apo-I YADH which has the conformational zinc removed, the extent of inactivation was larger than the extent of conformational changes at the same temperature. This result supported the suggestion by Tsou (Trends Biochem. Sci. 1986, 11, 427-429: Science 1993, 262, 380-381) that the enzyme active site is more flexible. The results also show that apo-I YADH without the conformational zinc was more easily inactivated with increasing incubation temperature, indicating that the stability of the apo-I YADH decreased. Kinetic analysis suggest that the substrate does not provide any protective effect during thermal inactivation of native and apo-I YADH.

Alcohol Dehydrogenase↗

PubMed1998

The role of the human motor cortex in the control of complex and simple finger movement sequences.

We evaluated the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) at different stimulus intensities on finger sequences of varying complexity. Eighteen subjects played unimanual finger sequences of different complexity on an electronic piano. For each finger sequence, 16 notes were played to the 2 Hz beat of a metronome. After the first four notes, rTMS was applied to the scalp location overlying the hand motor representation for approximately 2 s. Accuracy and timing errors were analysed. Stimulation over the M1 had a differential effect on sequences of different complexity. Stimulus intensities capable of disrupting the performance of a complex sequence did not affect simple sequences. To disrupt simple sequences, the stimulus strength had to be augmented. This effect was characteristic of the contralateral M1 position (five other scalp locations were also stimulated). It is argued that the differential effect of rTMS on simple and complex sequences is probably due to interference with M1 function. Interference with the lateral premotor cortex (PMC) may play an additional role. The particular relevance of the M1 is supported by results in a patient with PMC stroke. The present findings suggest that the human M1 plays a greater role in the performance of complex than of simple finger movement sequences. One possible explanation could be that the human M1 is not only an executive motor area but can also contribute to movement sequence organization.

Acoustic Stimulation↗

PubMed1998

Relative fitness of three organophosphate-resistant strains of Culex pipiens pallens (Diptera: Culicidae).

Effects of dipterex, temephos, and chlorpyrifos resistance on the relative fitness of Culex pipiens pallens (L.) were evaluated by examining developmental and reproductive characteristics. Age-specific life tables of Dip-R- (dipterex), Tmo-R- (temephos), and Chl-R- (chlorpyrifos) resistant strains were compared with the susceptible strain to determine relative fitness based on population trend indices (I). The 3 organophosphate-resistant strains possessed reproductive and developmental disadvantages involving fecundity and survival relative compared with the susceptible strain, with relative fitness values of 0.465, 0.520, and 0.501, respectively. These results are discussed in relation to the reversal from resistance to susceptibility in natural populations of mosquitoes.

Animals↗

PubMed1998

Positron emission tomography [15O]water studies with short interscan interval for single-subject and group analysis: influence of background subtraction.

Use of short interscan interval [15O]water positron emission tomography (PET) studies reduces the overall study duration and may allow an increased number of scans for single-subject analysis of unique cases (e.g., stroke). The purpose of this study was to examine how subtraction of residual radioactivity from the previous injection (corrected scan) compared to nonsubtraction (uncorrected scan) in a PET short interscan interval (6 minutes) study affects single-subject and group data analysis using a motor activation task. Two currently widely used analytic strategies, Worsley's method and the SPM technique, were applied. Excellent agreement between activation maps obtained from corrected and uncorrected data sets was obtained both in single-subject analyses performed on data sets from the six normal subjects and three stroke (subcortical infarct) patients, and in group analysis (six normal subjects) within a particular statistical method. The corrected and uncorrected data were very similar in the (1) number of activated brain regions; (2) size of clusters of activated brain voxels; (3) Talairach coordinates of the activated region; and (4) t or Z value of the peak intensity for every significantly activated motor brain structure (both for large activations such as in motor cortex and small activations such as in putamen and thalamus). [15O]Water PET data obtained with a short interscan interval (6 minutes) produce similar results whether or not the background is subtracted. Thus, if injection dose and timing are constant, one can achieve the advantage of a short interscan interval without the added complexity of correcting for background radioactivity.

Adult↗

PubMed1998

Studies of neuroplasticity with transcranial magnetic stimulation.

In recent years, there has been increasing interest in studies of brain plasticity. Although still loosely defined, this term describes the ability of the brain to change. Cortical plasticity encompasses a wide variety of phenomena and mechanisms, including modifications in cortical properties such as strength of internal connections, representational patterns, or neuronal modifications, either morphological or functional (Donoghue et al., 1996). We focus on the description of different ways in which transcranial magnetic stimulation (TMS) can be used to study patterns of reorganization and some of the mechanisms involved in these changes. Correlation between TMS and neuroimaging studies in humans and animal studies addressing similar questions is discussed. It is important to identify in each situation whether plasticity plays a beneficial role or is maladaptive in terms of functional compensation. The understanding of patterns, mechanisms, and functional relevance of cortical plasticity will hopefully lead to the design of effective strategies to enhance plasticity when it is beneficial and to down-regulate it when it is maladaptive. An example of a possible strategy, using TMS, is discussed.

Blindness↗

PubMed1998

Nodule parenchyma-specific expression of the sesbania rostrata early nodulin gene SrEnod2 is mediated by its 3' untranslated region

The early nodulin Enod2 gene encodes a putative hydroxyproline-rich cell wall protein and is expressed exclusively in the nodule parenchyma cell layer. The latter finding suggests that the Enod2 protein may contribute to the special morphological features of the nodule parenchyma and to the creation of an oxygen diffusion barrier. The Enod2 gene of the stem-nodulating legume Sesbania rostrata (SrEnod2) is induced specifically in roots by the plant hormone cytokinin, and this induction occurs at a post-transcriptional level. Here, we characterize the cis determinant(s) in the SrEnod2 locus responsible for nodule parenchyma-specific expression and show that the 3' untranslated region (UTR) of the SrEnod2 gene is both required and sufficient for directing chimeric reporter gene expression in the nodule parenchyma of transgenic Lotus corniculatus plants. Moreover, we show that the SrEnod2 3' UTR does not act as a tissue-specific enhancer element. By conducting a detailed deletion analysis of the 5' and 3' SrEnod2 regions, we delimited the minimal promoter of the SrEnod2 gene, and it appears that the 5' flanking sequences are not essential for nodule parenchyma-specific expression. This finding is in contrast with the report that the 5' upstream region of the soybean Enod2 gene directs nodule parenchyma-specific expression, indicating that different mechanisms may be involved in regulating the expression of these two genes. We definitively demonstrate that the cis element(s) for tissue-specific expression is located within the 3' UTR of a plant nuclear gene.

Journal Article↗

PubMed1998

Intracortical inhibition and facilitation in different representations of the human motor cortex.

Intracortical inhibition and facilitation in different representations of the human motor cortex. J. Neurophysiol. 80: 2870-2881, 1998. Intracortical inhibition (ICI) and intracortical facilitation (ICF) of the human motor cortex can be studied with paired transcranial magnetic stimulation (TMS). Plastic changes and some neurological disorders in humans are associated with changes in ICI and ICF. Although well characterized in the hand representation, it is not known if ICI and ICF vary across different body part representations. Therefore we studied ICI and ICF in different motor representations of the human motor cortex. The target muscles were rectus abdominus (RA), biceps brachii (BB), abductor pollicis brevis (APB), quadriceps femoris (QF), and abductor hallucis (AH). For each muscle, we measured the rest and active motor thresholds (MTs), the motor-evoked potential (MEP) stimulus-response curve (MEP recruitment), ICI, and ICF. The effects of different interstimulus intervals (ISIs) were studied with a conditioning stimulus (CS) intensity of 80% active MT. The effects of different CS intensities were studied at ISI of 2 ms for ICI and ISI of 15 ms for ICF. MT was lowest for APB, followed by BB, AH, and QF, and was highest for RA. Except for BB, MEP recruitment was generally steeper for muscles with lower MT. ICI and ICF were present in all the motor representations tested. The stimulus intensity necessary to elicit ICI was consistently lower than that required to elicit ICF, suggesting that they are mediated by separate mechanisms. Despite wide differences in MT and MEP recruitment, the absolute CS intensities (expressed as percentage of the stimulator's output) required to elicit ICI and ICF appear unrelated to MT and MEP recruitment in the different muscles tested. These findings suggest that the intracortical mechanisms for inhibition and facilitation in different motor representations are not related to the strength of corticospinal projections.

Action Potentials↗

PubMed1998

Appropriate regulation of human renin gene expression and secretion in 45-kb human renin transgenic mice.

To create physiological models of the human renin-angiotensin system in transgenic animals, the component genes should be expressed in the correct tissues and cells and respond appropriately to physiological stimuli. We recently showed that mice carrying a 45-kb human renin genomic fragment, containing approximately 25 kb 5'-flanking DNA and 6 kb 3'-flanking DNA, express the transgene in a highly cell- and tissue-specific pattern. More importantly, in contrast to previous models, human renin in the circulating plasma of these mice is derived exclusively from the kidneys. In the present study, we tested the responses of both human and mouse renal renin expression and secretion of the 45-kb hREN transgenic mice to a variety of physiological and pharmacological stimuli. A sodium-deficient diet, angiotensin-converting enzyme inhibition, and beta1-adrenergic stimulation each increased both human and mouse plasma renin concentration significantly, whereas elevated blood pressure and/or increased plasma angiotensin II levels suppressed them. Human and mouse renal renin mRNA levels changed similarly but to a lesser degree. These studies demonstrate that human renin synthesis and secretion respond appropriately in 45-kb hREN mice to physiological stimuli. This most likely results from appropriate cell-specific expression of the transgene conferred by the extended transgene flanking sequences.

Animals↗

PubMed1998

Calreticulin: an intracellular Ca++-binding protein abundantly expressed and regulated by androgen in prostatic epithelial cells.

Calreticulin was identified in a screen for androgen-response genes in the rat ventral prostate. Northern blot and Western blot analyses in the rat model showed that both calreticulin messenger RNA and protein are down-regulated by castration and up-regulated by androgen replacement in the prostate. Northern blot analysis showed that calreticulin expression level in the prostate is much higher than that in seminal vesicles, heart, brain, muscle, kidney, and liver. The regulation of calreticulin expression by androgen is only observed in the prostate and seminal vesicles, two male secondary sex organs. The induction of calreticulin by androgen in prostate organ culture partially resists protein synthesis inhibition, suggesting that calreticulin is a direct androgen-response gene. In situ hybridization and immunohistochemistry studies showed that calreticulin is an intracellular protein in prostatic epithelial cells. Because calreticulin is a major intracellular Ca++-binding protein with 1 high-affinity and 25 low-affinity Ca binding sites, our observations suggest that calreticulin is a promising candidate that mediates androgen regulation of intracellular Ca++ levels and/or signals in prostatic epithelial cells. The expression of calreticulin is also regulated by androgen in the mouse and human prostate, suggesting that androgen regulation and function of calreticulin in the prostate are conserved evolutionarily.

Androgens↗

PubMed1998

Phenytoin does not influence postexercise facilitation of motor evoked potentials.

Postexercise facilitation of motor evoked potentials (MEPs) elicited to transcranial magnetic stimulation occurs after brief, nonfatiguing muscle activation. This phenomenon may be related to post-tetanic potentiation or long-term potentiation (LTP) observed in animal studies. Phenytoin reduces post-tetanic potentiation but does not block LTP. We studied the effects of phenytoin on postexercise MEP facilitation and its decay over time. Phenytoin did not result in either significant change in postexercise MEP facilitation nor significant change in the decay of facilitation. We conclude that postexercise MEP facilitation is unlikely to be secondary to post-tetanic potentiation.

Adult↗

PubMed1998

Dextromethorphan decreases the excitability of the human motor cortex.

OBJECTIVE: To assess the acute effects of dextromethorphan (DM) on human motor cortical excitability. BACKGROUND: DM, a noncompetitive N-methyl-D-aspartate receptor antagonist, has recently attracted clinical interest for its potential as a neuroprotective agent in various models of excitotoxicity. We were interested in learning whether this drug can modulate the excitability of the motor cortex in healthy subjects. METHODS: The effects of DM on the excitability of the normal human motor cortex were studied in eight healthy volunteers by means of focal transcranial magnetic stimulation before and 1.5, 4, 6.5, and 24 hours after a single oral dose of 150 mg DM. Motor evoked potentials (MEPs) were recorded from the relaxed abductor digiti minimi muscle. Measures of motor cortical excitability were motor threshold, MEP recruitment, duration of the cortical silent period, and intracortical inhibition and facilitation. In addition, the authors explored spinal and neuromuscular excitability by means of F waves, duration of the peripheral silent period, and maximum M wave. RESULTS: Intracortical inhibition increased temporarily, intracortical facilitation decreased, and the cortical silent period lengthened slightly. Motor threshold, MEP recruitment, and spinal and peripheral motor excitability were not affected significantly. CONCLUSIONS: Our findings suggest that DM can exert a significant suppression of the excitatory drive in the normal human cortex, which may be relevant for its potential therapeutic use in excitotoxicity-related neurologic disease. Furthermore, the noninvasive technique described may prove useful in preclinical studies to assess the effects on motor cortical excitability induced by new modulators of glutamatergic transmission currently under development.

Adult↗

PubMed1998

Botulinum toxin type F for treatment of dystonia: long-term experience.

The authors analyzed retrospectively the results of open-labeled botulinum toxin type F (BTXF) treatment for 1 year or longer in 18 BTXA-resistant patients. All patients except one primary nonresponder to BTXA improved initially with BTXF. Most patients continued to respond to BTXF for 1 year or longer, but four patients became resistant to BTXF. BTXF-resistant patients received a higher dose per treatment and a higher cumulative dose than BTXF-responsive patients. BTXF can be used for long-term treatment of dystonia. It seems prudent to limit BTX doses of all serotypes to the lowest necessary for clinical efficacy.

Adult↗