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Biomedical subjects

R S Chen

Publications and source records attributed to R S Chen.

At least 19 recordsLinked to original sources

Genetic and DAT imaging studies of familial parkinsonism in a Taiwanese cohort.

We here summarize the results of genetic investigations on a series of 82 parkinsonian patients from 60 families in Taiwan. We found 13 parkin patients in 7 families (12%), 2 PINK1 sibs from 1 family, and 1 LRRK2 patient from 1 family with I2012T mutation. We also identified SCA2 in 8 patients from 5 families (8%) and SCA3 in 3 patients from 1 family, all presenting with parkinsonian phenotype. In the available patients with parkin, PINK1, SCA2 and SCA3, the dopamine transporter (DAT) scan revealed that the reduction of uptake was primarily observed in the bilateral putamen, basically sharing a similar pattern with that in idiopathic Parkinson's disease. We concluded that the genetic causes contributed to about 25% of our series of familial parkinsonism. The parkin mutations and SCA2 were the most frequent genetic causes in our series with Chinese ethnicity. The results of DAT scan indicated that bilateral putamen was essentially involved in various genetically-caused familial parkinsonism.

Adult↗

Environmental risk factors of young onset Parkinson's disease: a case-control study.

While the cause of Parkinson's disease (PD) remains unknown, recent evidence suggests certain environmental factors, such as well water drinking, herbicides and pesticides exposure, and neurotoxins, may trigger the chain of oxidative reactions culminating in the death of dopaminergic neurons in substantia nigra to cause parkinsonism. Most studies to date focused on PD with old age onset. However, there is a peculiar group of parkinsonian patients, the young onset Parkinson's disease (YOPD), in whom the age of onset is before 40. It is intriguing to know whether earlier exposure to the putative neurotoxin(s) may contribute to the earlier onset. We therefore conducted this case-control study in which 60 PD patients, 30 YOPD patients and the same number of age- and sex-matched young controls were included. Using logistic regression, we found well water drinking and head injury were risk factors for the development of YOPD. When YOPD patients were compared with PD, we found head injury and exercise were the significant predictors. Keeping all other variables constant, head injury was a risk factor and exercise appeared to be a protective factor. We conclude early exposure to well water drinking and head trauma may trigger and expedite the appearance of parkinsonian features, but such acceleration may be prevented through regular exercise.

Adult↗

Using a computerized patient database to evaluate guideline adherence and measure patterns of care for major depression.

This study examined the translation of recommendations from the Agency for Health Care Policy and Research (AHCPR) guidelines for major depression into measures derived from a computerized database to assess guideline conformance and patterns of care for major depression. Patients (n = 208) were identified who were hospitalized for major depression and had two or more outpatient mental health appointments within 6 months of discharge from an academically affiliated Veterans Affairs Medical Center. Measures were based on AHCPR guideline recommendations or developed independently. Conformance could be measured for three guideline recommendations. Of patients on single-agent antidepressant therapy, 87% received dosages within the recommended range. Sixty-nine percent received the recommended number of follow-up visits. Specific condition-related treatment interventions were identified in 32% of patients with concurrent alcoholism. Dual diagnoses of depression and drug or alcohol abuse were not deterrents to prescribing benzodiazepines. Despite its limitations, computerized database analyses provided efficient measures of guideline adherence.

Adult↗

Multimethod assessment of psychopathology among DSM-IV subtypes of children with attention-deficit/hyperactivity disorder: self-, parent, and teacher reports.

Using data based on self-, parent, and teacher reports, we assessed various aspects of psychopathology in a large sample of control children and those with ADHD. Confirmatory factor analysis was employed to extract response bias from latent constructs of aggression, anxiety, attention problems, depression, conduct disorder, and hyperactivity. These latent constructs were then entered into logistic regression equations to predict membership in control versus ADHD groups, and to discriminate between ADHD subtypes. Results of the regression equations showed that higher levels of attention problems and aggression were the best predictors of membership in the ADHD group relative to controls. Logistic regression also indicated that a higher degree of aggression was the only significant predictor of membership in the ADHD-Combined group compared to the ADHD-Inattentive group. However, when comorbid diagnoses of Oppositional Defiant Disorder and Conduct Disorder were controlled for in the logistic regression, greater hyperactivity rather than aggression was the sole variable with which to distinguish the ADHD-Combined from the ADHD-Inattentive subtype. Results are discussed in the context of the DSM-IV ADHD nosology and the role of instrument and source bias in the diagnosis of ADHD.

Aggression↗

Temporal stride and force analysis of cane-assisted gait in people with hemiplegic stroke.

OBJECTIVE: To understand the underlying biomechanics of temporal stride and force in people with hemiplegic stroke during cane-assisted walking. DESIGN: Three forceplates, 6 cameras, and an instrumented cane were integrated to analyze the cane-assisted gait of people with hemiplegic stroke. Temporal-stride parameters, and peak vertical, anterior (propulsive), posterior (braking), and lateral shear forces, as well as propulsive-breaking impulses were analyzed. SETTING: Chang Gung Memorial Hospital, Medical Center, Taiwan. PARTICIPANTS: Twenty people with hemiplegic stroke. MAIN OUTCOME MEASURES: Temporal-stride and force parameters. RESULTS: All patients walked at a relatively slow speed, ranging from 4.2 to 35.8cm/s. The triple and double support occupied most of the gait cycle (GC), whereas the single support occupied only 10% of GC. The applied vertical, propulsive, braking, and lateral shear forces on either foot and the cane were 89.7% to 97.6%, 2.2% to 4.8%, 2.9% to 3.9%, and 5.5% to 6.7% body weight (BW), respectively. Patients applied less than 25% BW of peak vertical forces on the cane. They applied greater peak propulsive forces and impulses on the sound foot, while applying greater peak braking forces and impulses on the affected foot and cane. CONCLUSIONS: The cane provided support and a braking function for people with hemiplegic stroke. People with stroke walking with cane assistance rely mostly on the sound limb for propulsion, while using the affected limb and cane for braking. Data provided could be useful in assessing the nature of cane assistance and in planning therapeutic strategies for people with stroke.

Adult↗

Supracondylar extension fracture of the humerus in children. Manipulative reduction, immobilisation and fixation using a U-shaped plaster slab with the elbow in full extension.

We present a method of manipulative reduction, immobilisation and fixation using a U-shaped plaster with the elbow in extension for extension-type supracondylar fractures of the humerus in children. When the elbow is in full extension, both the extensor and the flexor muscles are neutralised during manipulative reduction and the carrying angle can be easily assessed thus preventing cubitus varus, the most common complication. In order to evaluate the efficiency of this method, we compared the clinical results of the new method with those of conventional treatment. In a group of 95 children who sustained an extension-type supracondylar fracture of the humerus, 49 were treated by the new method and 46 by the conventional method, reduction and immobilisation in a plaster slab with the elbow in flexion. Reduction and immobilisation were easily achieved and reliably maintained by one manipulation for all the children treated by the new method. In 12 children treated by the conventional method, the initial reduction failed and in seven secondary displacement of the distal fragment occurred during the period of immobilisation in plaster. All required a second or third manipulation. Of the 46 children, 28 (60.9%) had developed cubitus varus at a mean follow-up of 4.6 years when treated by the conventional method. None of the children treated by the new method developed cubitus varus. The mean score, according to the Hospital for Special Surgery (HSS) elbow scoring system, was 91 points using the new method and 78 with the conventional method. The results were statistically significant with regard to the incidence of cubitus varus and the elbow score (p < 0.01) suggesting that the new method is reliable and gives a satisfactory outcome.

Adolescent↗

Thrombin-stimulated growth, clustering, and collagen lattice contraction of human gingival fibroblasts is associated with its protease activity.

BACKGROUND: Thrombin is a serine protease produced following gingival tissue injury or inflammation. It regulates the functional behavior of injury-neighboring cells via the activation of specific protease-activated receptors (PAR). Thrombin's role in gingival tissue healing and inflammatory response processes is not yet well understood. METHODS: We investigated the effects of thrombin on gingival fibroblast (GF) growth [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay], collagen lattice contraction, and associated morphological changes. RESULTS: Thrombin (>1 U/ml), but not thrombin receptor (PAR-1) agonist peptide (SFLLRN, single letter amino acid code, abbreviated as TRAP, 1 to 50 microg/ml), stimulated the growth and clustering of cultured human GF in vitro. Growth-stimulatory effects of thrombin were inhibited by D-Phe-Pro-ArgCH2Cl (PPACK), a serine protease inhibitor. By contrast, trypsin (>10 microg/ml), a PAR-2 activator, suppressed the growth of GF. Thrombin (>0.2 U/ml) and TRAP (10 to 25 microg/ml), but not trypsin, prostaglandin E2 (0.01 to 0.5 microg/ml), or bovine serum albumin (BSA) (1 to 80 microg/ml), induced the GF-populated collagen lattice contraction within 30 to 60 minutes of exposure. The thrombin-induced collagen lattice contraction was inhibited by PPACK (20 microg/ml) and an actin filament polymerization inhibitor, cytochalasin B (1 microg/ml). The collagen lattice contraction induced by TRAP was also inhibited by cytochalasin B, but not by PPACK. Using a reverse-transcriptase polymerase chain reaction (RT-PCR), the expression of PAR-1, and to a lesser extent PAR-3, was observed for human GF, although little PAR-2 and PAR-4 expression was noted. CONCLUSIONS: These results indicate that thrombin is important in periodontal wound healing and inflammatory processes by promoting the growth and contraction of GF. The stimulatory effects of thrombin are associated with its protease activation of thrombin receptors.

Amino Acid Chloromethyl Ketones↗

Posteroventral pallidotomy for advanced Parkinson's disease.

BACKGROUND: Provoked by the limitations and late complications of levodopa therapy, the advances in stereotactic surgery, and better understanding of the pathophysiology of the basal ganglia, the role of pallidotomy in the treatment of advanced Parkinson's disease (PD) has been revived. METHODS: We included 11 patients with advanced PD, who had a good response to levodopa but had late complications of motor fluctuation and severe dyskinesia. The internal globus pallidus was identified with computed tomography prior to posteroventral pallidotomy and it was reaffirmed by microelectrode recording during surgery. Clinical evaluations were carried out in both the "on" and "off" motor periods at baseline and at 1 week, 3 months, 6 months and 1 year postoperatively. Repeated measures ANOVA followed by multiple comparisons were used for statistical analysis. RESULTS: Dyskinesia improved bilaterally but only significantly in the contralateral limbs. This benefit was sustained up to 1 year. Parkinsonism, particularly contralateral tremor and rigidity, improved in the "off" motor period but not in the "on" motor period. The average Unified Parkinson's Disease Rating Scale motor score was reduced 36% at 3 months and 26% at 1 year in the "off" motor period. Both of the mean Hoehn and Yahr staging and Schwab and England activities of daily living score improved in "off" motor period. Improvement in parkinsonism, however, did not reach a significant level. Mild dysarthria and unstable gait were observed temporarily in 2 patients. Mild weakness in the contralateral limbs was found in 1 patient. CONCLUSIONS: Unilateral pallidotomy guided by microelectrode recording is helpful for severe levodopa-induced dyskinesia in advanced PD. Contralateral parkinsonian disabilities also improve in the "off" motor period.

Adult↗

Specificity and efficiency of Cre-mediated recombination in Emx1-Cre knock-in mice.

Emx1 is a mouse homologue of the Drosophila homeobox gene empty spiracles and its expression is restricted to the neurons in the developing and adult cerebral cortex and hippocampus. We reported previously the creation of a line of transgenic mice in which the cre gene was placed directly downstream of the putative Emx1 promoter using ES cell technology. We showed that Cre protein was present in the cerebral cortex of the transgenic mice and was able to mediate loxP-specific recombination in vitro. In the present study, the specificity and efficiency of the cre-mediated recombination were determined using three independent lines of reporter mice and a combination of histochemical staining, neuronal culture, and Southern detection of the genomic DNA. Our results showed that the recombination was highly efficient in all three lines of reporter mice tested and confirmed that the deletion was restricted to the neurons in the cerebral cortex and hippocampus. Furthermore, we have determined that the recombination efficiency in the cerebral cortex was 91%. Our results suggest that Emx1 is not expressed in every neuron in the developing and adult cerebral cortex. This line of cre mice should contribute to the studies of cortical development and plasticity.

Animals↗

The coevolution of cell senescence and diploid sexual reproduction in unicellular organisms.

In this paper, we investigate the coevolution of diploid sexual reproduction and cell senescence (i.e., cell aging). We use probability analysis, computer simulation, and exact numerical computation to analyze the impacts of deleterious recessive mutations on sexual and asexual reproduction. The main conclusion is that, without cell senescence, the evolutionary advantages of sexual reproduction cannot be realized in unicellular organisms that reproduce both sexually and asexually. Also, cell senescence is found to be useful in the maintenance of sexual reproduction. This result suggests that diploid sexual reproduction was unlikely to establish itself as a widespread reproduction mechanism without the complementary process of cell senescence.

Biological Evolution↗

Facilitation of immune function, healing of pressure ulcers, and nutritional status in spinal cord injury patients.

Multiple communicative pathways among nervous, endocrine, and immune systems facilitate physiological immunoregulation. Spinal cord injury (SCI) patients had strikingly decreased natural and adaptive immune responses by 2 weeks post injury. While NK-cell function was decreased, plasma ACTH and urine-free cortisol levels were increased. T cell function and activation were both diminished. With rehabilitation therapy, NK and T function increased; without rehabilitation, NK levels remained depressed. When rehabilitation ceased, NK function decreased. Cervical SCI patients had less NK and T function than thoracic injury patients. SCI patients also had reduced levels of cellular adhesion molecules (CAMs) that participate in immune function and wound healing. SCI patients with pressure ulcers were compared to those without pressure ulcers. LFA-1, VLA-4, and other surface markers were decreased on the lymphocytes of all SCI patients. SCI patients with pressure ulcers had lower CAM levels than did patients without pressure ulcers. Nutritional status was determined by zinc, albumin, and prealbumin levels. SCI patients had decreased albumin levels. Those with pressure ulcers had decreased prealbumin levels and zinc levels.

Adrenocorticotropic Hormone↗

A new method for protein domain recognition.

A fuzzy cluster method is presented to recognize protein domains. This algorithm can identify domains globally. A protein structure set was used to test the algorithm. Among 219 proteins, 66.7% yielded results that agreed with the reference definitions, 30.6% showed minor differences, and only 2.7% (six proteins) showed major differences with the reference. The new method is more than 20 times fast than previous algorithms.

Cluster Analysis↗

Cost per millimeter of mercury lowering is a measure of economic value for antihypertensive agents.

The use of pharmacoeconomic analyses to evaluate the appropriateness of treatment regimens is increasing rapidly. Trials that study the efficacy of antihypertensive agents do not often measure long-term cardiovascular morbidity and mortality, so complementary methods are needed to evaluate the cost-effectiveness of these agents. One method is to compare agents on the basis of their costs and blood pressure-lowering efficacy, producing a ratio of cost per millimeter of mercury lowering, or cost/mm Hg. This provides a simple, transparent method with which to evaluate the cost-effectiveness of antihypertensive agents. It also allows the cost-effectiveness of a blood pressure treatment to be assessed in terms of ambulatory blood pressure data. The use of cost/mm Hg requires assumptions that tolerability of agents is comparable and that blood pressure lowering is a valid surrogate for cardiovascular risk reduction. Given the emergence of new treatments that have differences in blood pressure efficacy, cost/mm Hg is likely to become increasingly used as an indicator of economic value.

Antihypertensive Agents↗

Review of immune function, healing of pressure ulcers, and nutritional status in patients with spinal cord injury.

The immune, neural, and endocrine systems do not act autonomously; rather, multiple communicative pathways exist among the nervous, endocrine, and immune systems that facilitate physiological immunoregulation. Patients with spinal cord injury (SCI) have decreased natural and adaptive immune responses by 2 weeks after injury. In patients with SCI, adrenocorticotropic hormone (ACTH) and urine-free cortisol levels were increased while zinc and albumin levels were decreased, respectively. In addition, the surface markers alpha 2, alpha 3, alpha 4, CD11a, CD11b, CD18, CD54, and CD8 found on lymphocytes and alpha 3, alpha 4, CD11a, CD18, and CD8 surface markers found on granulocytes were also decreased in the patient population. Finally, the adhesion molecules binding ability in the SCI group was also decreased when compared with a control group. Overall, the investigation showed that patients with SCI have a decreased immune function, especially succeeding the SCI injury, an impaired nutrition status, and a decreased number of adhesion molecules, all of which contribute to delayed wound healing.

Adult↗

Using a computer database to monitor compliance with pharmacotherapeutic guidelines for schizophrenia.

OBJECTIVE: The study examined whether prescription data from a computerized database could be used to measure conformance with treatment recommendations of the Schizophrenia Patient Outcomes Research Team (PORT). METHODS: Records of an academically affiliated Veterans Affairs medical center were reviewed to identify patients who were hospitalized for schizophrenia and later seen for at least two outpatient visits in the six months after discharge (N=353). RESULTS: Conformance with only three of the 18 PORT pharmacotherapeutic recommendations could be measured with the available data. In regard to the recommendation to use antipsychotics other than clozapine as first-line treatments in acute episodes, 77 percent of the sample filled a prescription for an antipsychotic during the acute episode. Of these, only 6 percent received an antipsychotic regimen that included clozapine. In regard to the PORT recommendation on dosage during acute symptom episodes, 42 percent of the patients on conventional antipsychotics received dosages below the recommended range, 5 percent were above the range, and 53 percent were within it. In contrast, of the 53 patients who received clozapine or risperidone, 87 percent received prescriptions within the recommended dosage range. As for the recommendation to offer a trial of clozapine to patients who do not respond to adequate trials of two different classes of conventional drugs, 10 percent of patients who were switched from conventional regimens to clozapine were receiving dosages of conventional medications below the recommended range. CONCLUSIONS: Patient prescription data can provide preliminary measures to cost-effectively assess conformance with treatment. However, the approach has several limitations, and complementary analyses would enhance its usefulness.

Aged↗

Assessing growth patterns--routine but sometimes overlooked.

We performed a retrospective chart review for 149 randomly selected well-child encounters to evaluate the frequency with which clinicians plot growth measurements and document growth abnormalities during health maintenance visits. Providers failed to plot at least one measurement of height, weight, and/or head circumference in 31 of 149 encounters (21%, 95% CI = 14.5% to 27.5%). Growth abnormalities in size, velocity, and/or disproportion were not documented in 22 of 40 relevant encounters (55%, 95% CI = 40% to 70%). Overall, 52 of 149 encounters (35%) were associated with an unplotted measurement and/or an undocumented growth abnormality. We feel that both documentation and assessment of growth represent potential areas for quality improvement.

Ambulatory Care Facilities↗

[Construction, expression and activity test of a reshaping single-chain antibody against human CD3].

Monoclonal antibody (McAb) against human CD3 can adjust human body's immune statement in various ways, so that its clinical potential is highly regarded. In order to overcome the immunogenecity related to the murine McAb, this research effort was focused on constructing a reshaping single-chain antibody(scFv) against human CD3 employing antibody engineering. First, the CDRs of the murine McAb against human CD3 OKT3 was transplanted into the light-chain framework regions (FRs) of human McAb LS1 and the heavy-chain FRs of human McAb Nd respectively, spatial conformation was predicted by computer analysis. Then some particular residues were replaced in FRs basing on the result of conformational prediction to draw out the amino acid sequences of the reshaped VL and VH. The genes were chemically synthesize and inserted into an expression vector pROH80 to construct the reshaping scFv. Inducing the expression of reshaping scFv, the products are mainly as inclusion bodies. The reshaping scFv was expressed in another vector pALM. The inclusion bodies were denatured and then renatured by gel filtration. The renatured products were purified by immobilized metal affinity chromatograph (IMAC). Finally, the antigen-binding activily of the reshaping scFv against human CD3 was testified by the Compelitire in hibilory fluorescenceactivated cell sorting (FACS). The competitive inhibition rate is 18%.

Amino Acid Sequence↗