Biomedical subjects

J G Chen

Publications and source records attributed to J G Chen.

At least 19 recordsLinked to original sources

PubMed2001

Oxygen-containing functional groups on single-wall carbon nanotubes: NEXAFS and vibrational spectroscopic studies.

Single-walled nanotubes (SWNTs) produced by plasma laser vaporization (PLV) and containing oxidized surface functional groups have been studied for the first time with NEXAFS. Comparisons are made to SWNTs made by catalytic synthesis over Fe particles in high-pressure CO, called HiPco material. The results indicate that the acid purification and cutting of single-walled nanotubes with either HNO3/H2SO4 or H2O2/H2SO4 mixtures produces the oxidized groups (O/C = 5.5-6.7%), which exhibit both pi*(CO) and sigma*(CO) C K-edge NEXAFS resonances. This indicates that both carbonyl (C=O) and ether C-O-C functionalities are present. Upon heating in a vacuum to 500-600 K, the pi*(CO) resonances are observed to decrease in intensity; on heating to 1073 K, the sigma*(CO) resonances disappear as the C-O-C functional groups are decomposed. Raman spectral measurements indicate that the basic tubular structure of the SWNTs is not perturbed by heating to 1073 K, based on the invariance of the ring breathing modes upon heating. The NEXAFS studies agree well with infrared studies which show that carboxylic acid groups are thermally destroyed first, followed by the more difficult destruction of ether and quinone groups. Single-walled nanotubes produced by the HiPco process, and not treated with oxidizing acids, exhibit an O/C ratio of 1.9% and do not exhibit either pi*(CO) or sigma*(CO) resonances at the detection limit of NEXAFS. It is shown that heating (to 1073 K) of the PLV-SWNTs containing the functional groups produces C K-edge NEXAFS spectra very similar to those seen for the HiPco material. The NEXAFS spectra are calibrated against spectra measured for a number of fused-ring aromatic hydrocarbon molecules containing various types of oxidized functional groups present on the oxidized SWNTs.

Anthracenes↗

PubMed2001

Treatment of isolated systolic hypertension is most effective in older patients with high-risk profile.

BACKGROUND: Although present guidelines suggest that treatment of hypertension is more effective in patients with multiple risk factors and higher risk of cardiovascular events, this hypothesis was never verified in older patients with systolic hypertension. METHODS AND RESULTS: Using data from the Systolic Hypertension in the Elderly Program, we calculated the global cardiovascular risk score according to the American Heart Association Multiple Risk Factor Assessment Equation in 4,189 participants free of cardiovascular disease (CVD) and in 264 participants with CVD at baseline. In the placebo group, rates of cardiovascular events over 4.5 years were progressively higher according to higher quartiles of CVD risk. The protection conferred by treatment was similar across quartiles of risk. However, the numbers needed to treat (NNTs) to prevent one cardiovascular event were progressively smaller according to higher cardiovascular risk quartiles. In participants with baseline CVD, the NNTs to prevent one cardiovascular event were similar to those estimated for CVD-free participants in the highest-risk quartile. CONCLUSIONS: Treatment of systolic hypertension is most effective in older patients who, because of additional risk factors or prevalent CVD, are at higher risk of developing a cardiovascular event. These patients are prime candidates for antihypertensive treatment.

Age Factors↗

PubMed2001

Modulation of cell proliferation by heterotrimeric G protein in Arabidopsis.

The alpha subunit of a prototypical heterotrimeric GTP-binding protein (G protein), which is encoded by a single gene (GPA1) in Arabidopsis, is a modulator of plant cell proliferation. gpa1 null mutants have reduced cell division in aerial tissues throughout development. Inducible overexpression of GPA1 in Arabidopsis confers inducible ectopic cell division. GPA1 overexpression in synchronized BY-2 cells causes premature advance of the nuclear cycle and the premature appearance of a division wall. Results from loss of function and ectopic expression and activation of GPA1 indicate that this subunit is a positive modulator of cell division in plants.

2,4-Dichlorophenoxyacetic Acid↗

PubMed2001

A lithium-induced conformational change in serotonin transporter alters cocaine binding, ion conductance, and reactivity of Cys-109.

Inactivation of serotonin transporter (SERT) expressed in HeLa cells by [2-(trimethylammonium)ethyl]methanethiosulfonate (MTSET) occurred much more readily when Na(+) in the reaction medium was replaced with Li(+). This did not result from a protective effect of Na(+) but rather from a Li(+)-specific increase in the reactivity of Cys-109 in the first external loop of the transporter. Li(+) alone of the alkali cations caused this increase in reactivity. Replacing Na(+) with N-methyl-d-glucamine (NMDG(+)) did not reduce the affinity of cocaine for SERT, as measured by displacement of a high affinity cocaine analog, but replacement of Na(+) with Li(+) led to a 2-fold increase in the K(D) for cocaine. The addition of either cocaine or serotonin (5-HT) protected SERT against MTSET inactivation. When SERT was expressed in Xenopus oocytes, inward currents were elicited by superfusing the cell with 5-HT (in the presence of Na(+)) or by replacing Na(+) with Li(+) but not NMDG(+). MTSET treatment of oocytes in Li(+) but not in Na(+) decreased both 5-HT and Li(+) induced currents, although 5-HT-induced currents were inhibited to a greater extent. Na(+) antagonized the effects of Li(+) on both inactivation and current. These results are consistent with Li(+) inducing a conformational change that exposes Cys-109, decreases cocaine affinity, and increases the uncoupled inward current.

Animals↗

PubMed2001

Investigation of pharmaceutical high-performance liquid chromatography assay bias using experimental design.

This article presents a systematic approach to investigate, document, and eliminate pharmaceutical HPLC assay bias using experimental design. This is the first article to describe the application of experimental design in the area of assay bias. It is found that both formulation and analytical variables can contribute to pharmaceutical HPLC assay bias using model compounds and formulations.

Chromatography, High Pressure Liquid↗

PubMed2001

Primary study of vascular endothelial growth factor immunohistochemical staining in the diagnosis of early acute myocardial ischemia.

The expression of vascular endothelial growth factor (VEGF) in the model of rat early acute myocardial ischemia was studied by Strept-Avidin-Biotin-Peroxidase Complex (SABC) immunohistochemical staining. After ligating the anterior descending branch of the left coronary artery, an initial rapid (30min) positive expression of VEGF in myocardial ischemic areas was observed, the intensity of positive expression of VEGF increased with the continuation of myocardial ischemia. After 5h infarction, the strongly positive myocytes of SABC-VEGF staining were predominantly limited to perimyocardial infarction areas. No positive expression of VEGF was found in the control group. These findings suggested that SABC-VEGF method could give a sensitive, specific, simple and objective morphologic evidence to the diagnosis of sudden cardiac death caused by acute early myocardial ischemia.

Animals↗

PubMed2001

ABP1 is required for organized cell elongation and division in Arabidopsis embryogenesis.

To directly address the function of a putative auxin receptor designated ABP1, a reverse genetic approach was taken to identify and characterize ABP1 mutant alleles in Arabidopsis. A homozygous null mutation in ABP1 confers embryo lethality. Null mutant embryos develop normally until the early stages of the globular embryo but are unable to make the transition to a bilaterally symmetrical structure because cells fail to elongate. Cell division was also aberrant both in the suspensor and embryo proper. Antisense suppression of ABP1 in tobacco cells causes slow proliferation and eliminates auxin-induced cell elongation and reduces cell division. The complete lack of auxin-inducible elongation in individual cells confirms the results observed in embryos, indicates a cell autonomous function, and, taken together with biochemical evidence that ABP1 binds auxins, suggests that ABP1 mediates auxin-induced cell elongation and, directly or indirectly, cell division.

Alleles↗

PubMed2001

Implications of a utility model for ultraviolet exposure behavior.

Over the past several decades, the incidence of skin cancer has reached epidemic proportions. Despite numerous efforts to increase public awareness of the risks associated with solar radiation, people continue to sunbathe, use indoor tanning facilities, avoid photoprotective clothing, and fail to use sunscreen. We propose using an economic model, the utility model, to better understand how to reduce tanning behaviors. This model has been widely applied in financial decision-making as well as in analysis of risk-taking behaviors such as smoking. The model takes into account both the current perceived benefits of tanning and the future long-term risks. People tend to discount the future; they tend to weigh current benefits more heavily than future risks. As predicted by the model, past prevention efforts that have focused on long-term benefits gained by sun-protective behavior have been largely ineffective. In the current social environment, we cannot expect tanning reduction measures based solely on health education to be very effective. Only by changing public perceptions of a tan will efforts to decrease ultraviolet exposure behavior likely be successful.

Decision Making↗

PubMed2001

Admission base deficit in pediatric trauma: a study using the National Trauma Data Bank.

BACKGROUND: The base deficit, an important indicator of physiologic derangement after severe injury in adults, has not been specifically examined in the pediatric trauma population. The purpose of this study was to assess the ability of the admission base deficit to predict injury severity and outcome in the pediatric trauma population. METHODS: The study group included all patients in the National Trauma Data Bank over a 2-year period aged 0 to 12 years with a base deficit (0 to -30 mEq/L) recorded from the emergency department. Age, presence of a severe closed head injury, and base deficit were analyzed with respect to mortality and other indicators of injury severity. RESULTS: A total of 515 patients constituted the study group. Base deficit less than -4 mEq/L (p < 0.001) and the presence of a closed head injury (odds ratio, 3.8; p < 0.05) were predictors of mortality. For the group, an admission base deficit of -8 mEq/L corresponded to a probability of mortality of 25%. Significant correlations were found between base deficit and emergency department systolic blood pressure, Injury Severity Score, and Revised Trauma Score. There was no relationship between age and mortality. CONCLUSION: In injured children, the admission base deficit reflects injury severity and predicts mortality. The probability of mortality increases precipitously in children with a base deficit less than -8 mEq/L, and should alert the clinician to the presence of potentially lethal injuries or uncompensated shock.

Child↗

PubMed2001

[Production and cytogenetics of intergeneric hybrids between Ogura CMS Brassica campestris var. purpuraria and Raphanus sativus].

Crosses between Ogura CMS Brassica campestris var. purpuraria (AA, 2n = 20) and Raphanus sativus (RR, 2n = 18) were made and many intergeneric hybrids were produced. The F1 seedlings did not show chlorosis at low temperature. When red Raphanus sativus varieties were used as male parent, the leaf petiole and leaf vein of F1 plants were purple, and when white Raphanus sativus varieties were used as male parent, the leaf petiole and leaf vein of F1 plants were not purple. All the F1 plants had white flowers and normal honey glands. Male gametes of the F1 were highly sterile and female gametes of the F1 were partly fertile. Cytological studies indicated that chromosome number of the F1 was 2n = 19 as expected, the mean chromosome pairing pattern was 15.53 I + 1.34 II + 0.25 III + 0.01 IV. Most chromosomes exsistet as univalents, but there also exsisted some bivalents, trivalents and even tetravalents, suggesting that chromosome set A was partly homologous with chromosome set R.

Brassica↗

PubMed2000

Permeation and gating residues in serotonin transporter.

The third transmembrane domain (TM3) of serotonin transporter (SERT) contains two isoleucine residues previously proposed to be involved in binding and transport of serotonin. When Ile-172 was replaced with cysteine, SERT became sensitive to inactivation by externally added [2-(trimethylammonium)ethyl]methanethio-sulfonate (MTSET). The disulfide product of this inactivation was not sensitive to reduction by externally added sulfhydryl compounds, but apparently reacted with intracellular reducing agents to spontaneously regenerate active SERT. The apparent accessibility of this residue to both external and cytoplasmic reagents is consistent with its localization near a serotonin binding site that is alternately exposed to both internal and external media. In another SERT mutant, I179C, transport also was inactivated by MTSET but substrate binding was resistant. External substrate bound to the inactivated I179C and enhanced its reactivation by free thiols. In norepinephrine transporter (NET), cysteine replacement of Ile-155 (corresponding to SERT Ile-179) also rendered the transporter sensitive to MTSET inactivation. In NET I155C, cocaine enhanced this inactivation, and the substrate, dopamine, apparently protected against inactivation. The characteristics of this protection suggest that dopamine was transported, converting NET to a form in which Ile-155 was occluded. The results support the proposal that TM3 of SERT and NET constitute part of the substrate permeation pathway, and that Ile-172 in SERT resides close to the substrate binding site. They also suggest that Ile-179 in SERT (and Ile-155 in NET) is in a conformationally sensitive part of TM3, which may act as part of an external gate.

Allosteric Regulation↗

PubMed2000

Magnetic resonance spectroscopy in Alzheimer's disease: focus on N-acetylaspartate.

This paper reviews published post-mortem brain and in-vivo proton magnetic resonance spectroscopy (1H-MRS) studies in Alzheimer's disease (AD) and focuses on the emerging role of N-acetylaspartate (NAA) as a prognostic marker of neuronal function. Post-mortem brain studies have reported significantly lower NAA levels in AD brains than in control brains, and some have correlated the low levels with neuropathological findings (i.e. amyloid plaques and neurofibrillary tangles). Similarly, almost all published in-vivo studies have reported lower NAA levels in AD patients compared to elderly controls. While some studies have found changes in metabolite levels that were considered useful for the diagnosis of AD, most have found that 1H-MRS provided little or no advantages over other, more common diagnostic tools. Instead, recent studies in AD and other neuropsychiatric disorders suggest that NAA may be more useful as a prognostic marker for monitoring neurodegeneration, stabilization, or improvement, and for evaluating therapeutic response to novel drugs.

Aged↗

PubMed2000

Degradation of a fluoropyridinyl drug in capsule formulation: degradant identification, proposed degradation mechanism, and formulation optimization.

The purpose of this paper was to investigate the degradation chemistry of a fluoropyridinyl drug candidate in capsule formulation and to optimize the formulation based on a proposed degradation mechanism. Small developmental batches of capsules were made by tituration of drug substance and excipients using a mortar and pestle, followed by manual encapsulation. Degradants were identified by LC-MS/MS and LC-photodiode array detector (PDA) and were monitored by LC-ultraviolet detector (UVD) during stability studies. It was found that the drug could undergo a nucleophilic substitution reaction in which hydroxyl groups replace the fluorine substituents on the pyridine rings. The initial degradation rate is independent of the drug concentration but dependent on the temperature, the pH of the microenvironment, and the excipient type. On the basis of these experimental results, a nucleophilic substitution reaction mechanism for the degradation was proposed and a successful capsule formulation was developed.

Anthracenes↗

PubMed2000

Crystallization and preliminary X-ray analysis of the auxin receptor ABP1.

Auxin-binding protein (ABP1) is an important receptor for the plant hormone auxin that is involved with many growth and developmental responses in plants. The maize ABP1 gene has been expressed in insect cells, purified and crystallized. Type II crystals are monoclinic, with two glycosylated homodimers in the asymmetric unit, and diffract to 1.9 A using synchrotron radiation.

Crystallization↗

PubMed1999

An integrated logistics support system for training crew medical officers in advanced cardiac life support management.

The purpose of this paper is to present an approach for the development of an integrated logistics support system for training space flight crew medical officers in advanced cardiac life support (ACLS). The most practical approach to deal with this problem has been determined to be the training of one or more of the crew members on the mission as crew medical officers (CMO's). If this approach is taken, there are a number of problems that must be addressed. The basic approach presented in this paper is to develop a performance quality index for ACLS tasks and use this index to monitor and control the performance of crew members throughout their tenure as CMO's. The control tool of the system is based on an integrated learning and forgetting model used to forecast CMO performance level at a given point during flight training. The model represents an aid for trainers in determining a training regime and maintaining the performance standards. A performance evaluator and trainer is also developed to help in the establishment of trainee performance level during training or retraining. All of these tools were evaluated using either expert opinion questionnaires or experimental results. In conclusion, the results presented provide the tools required for an integrated logistics support system for training ACLS personnel.

Aerospace Medicine↗

PubMed1999

The gatekeeper model is inefficient for the delivery of dermatologic services.

BACKGROUND: Gatekeeper-paradigm managed care systems may discourage the use of dermatologists in the management of skin conditions by limiting direct access. This may limit the quality of care patients with skin disorders receive and may be an inefficient use of medical resources. OBJECTIVE: The purpose of this study was to determine the likelihood that patients with dermatologic conditions who see a primary care provider will be referred to a dermatologist. METHODS: Data on the disposition of outpatient visits to primary care physicians for one and only one dermatologic diagnosis were obtained from the 1990-1994 National Ambulatory Medical Care Survey. These data were used in an econometric model to estimate the likelihood of referral to a dermatologist for an episode of care. RESULTS: Of all visits for a single dermatologic diagnosis, 39% were to primary care physicians. The disposition of referral was more common for these dermatology-related visits than for all office visits to primary care physicians (5.8% vs 4.5%, P < .001). The most frequent diagnoses associated with referral were common dermatologic problems, not rare disorders. The number of visits per episode of care was highly dependent on the assumptions of the analysis, resulting in estimate ranges for referral rates per episode between 6.8% and 18.5% for pediatricians, 8.2% and 23% for family and general practitioners, and 16.6% and 46.5% for internists. CONCLUSION: The relative difficulty for primary care providers of managing skin problems is reflected by their frequent need to refer patients with common skin problems and by the greater likelihood of referral for skin disorders than for other medical conditions. The high rates of referral per episode of care supports the cost-effectiveness of direct access to dermatologists.

Costs and Cost Analysis↗

PubMed1999

[Effect of endothelin-1 injected into rostral ventrolateral medulla on cardiovascular responses in cats].

AIM: To study the effect of endothelin-1 (ET-1) in the rostral ventrolateral medulla (rVLM) on cardiovascular responses in cats. METHODS: The stereotatic technique and microinjection method were used. RESULTS: ET-1 (4 mumol.L-1 0.5 microL) microinjected into rVLM induced mean arterial pressure (MAP) increasing (3.7 +/- 1.3) kPa, heart rate (HR) accelerating (29 +/- 7) beats.min-1, and renal nerve activity (RNA) intensifying 45% +/- 10%. The effects were dose-dependent. Before and after bilateral vagotomy, there was no significant difference in the reaction of MAP, HR, and RNA. After intravenous injection with phentolamine (5 mg.kg-1, alpha-blocker), ET-1 did not induce significant change of MAP. ET-1 raised the content of peripheral plasma argipressin (Arg) from (12.4 +/- 6.5) to (70.3 +/- 24.2) ng.L-1 with radioimmunoassay, and showed a correlation with MAP changes. ET-1 induced heart rhythm disorder (HRhD) in acute myocardiac ischemia, the occur time of HRhD was (4.8 +/- 2.9) min, and the score was 4.4 +/- 1.6, and it was significantly different from control. CONCLUSION: ET-1 microinjected into rVLM could involve with control regulation of cardiovascular and sympathetic nerve activity.

Animals↗

PubMed1998

Determination of external loop topology in the serotonin transporter by site-directed chemical labeling.

The transmembrane topology of the serotonin transporter (SERT) has been examined by measuring the reactivity of selected lysine and cysteine residues with extracellular reagents. An impermeant biotinylating reagent, sulfosuccinimidyl 2-(biotinamido)ethyl-1, 3-dithiopropionate (NHS-SS-biotin), was shown to label SERT transiently expressed in cultured cells. Replacement of four lysine residues that were predicted to lie in external hydrophilic loops (eK-less) largely prevented the biotinylation reaction. Likewise, the cysteine-specific biotinylation reagent N-biotinylaminoethylmethanethiosulfonate (MTSEA-biotin) labeled wild type SERT but not a mutant in which Cys-109, predicted to lie in the first external loop, was replaced with alanine. These two mutant transporters reacted with the biotinylating reagents in digitonin-permeabilized cells, demonstrating that the abundant lysine and cysteine residues predicted to lie in intracellular hydrophilic domains were reactive but not accessible in intact cells. Mutants containing a single external lysine at positions 111, 194, 243, 319, 399, 490, and 571 reacted more readily with NHS-SS-biotin than did the eK-less mutant. Similarly, mutants with a single cysteine at positions 109, 310, 406, 489, and 564 reacted more readily with MTSEA-biotin than did the C109A mutant. All of these mutants were active and therefore likely to be folded correctly. These results support the original transmembrane topology and argue against an alternative topology proposed recently for the related glycine and gamma-aminobutyric acid transporters.

Biotin↗