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Biomedical subjects

K Chen

Publications and source records attributed to K Chen.

At least 19 recordsLinked to original sources
PubMed2006

Flux through a hole from a shaken granular medium.

We have measured the flux of grains from a hole in the bottom of a shaken container of grains. We find that the peak velocity of the vibration, v max, controls the flux, i.e., the flux is nearly independent of the frequency and acceleration amplitude for a given value of v max. The flux decreases with increasing peak velocity and then becomes almost constant for the largest values of v max. The data at low peak velocity can be quantitatively described by a simple model, but the crossover to nearly constant flux at larger peak velocity suggests a regime in which the granular density near the container bottom is independent of the energy input to the system.

Journal Article↗
PubMed2006

Granular materials: packing grains by thermal cycling.

A long-standing problem in managing the behaviour of a collection of solid grains concerns the nature of the grain packing, a property that is typically controlled by how the grains are poured or shaken. Here we show that a systematic and controllable increase in granular packing can be induced by simply raising and then lowering the temperature, without the input of mechanical energy. This thermal processing may have important practical implications for the handling and storage of granular materials.

Journal Article↗
PubMed2006

Variations in the detection of ZAP-70 in chronic lymphocytic leukemia: Comparison with IgV(H) mutation analysis.

Lack of immunoglobulin heavy chain genes (IgV(H)) mutation in patients with chronic lymphocytic leukemia (CLL) is associated with rapid disease progression and shorter survival. The zeta-chain (T-cell receptor) associated protein kinase 70 kDa (ZAP-70) has been reported to be a surrogate marker for IgV(H) mutation status, and its expression in leukemic cells correlates with unmutated IgV(H). However, ZAP-70 detection by flow cytometry varies significantly dependant on the antibodies used, the method of performing the assay, and the condition of the cells in the specimen. The clinical value of ZAP-70 testing when samples are shipped under poorly controlled conditions is not known. Furthermore, testing in a research environment may differ from testing in a routine clinical laboratory. We validated an assay for ZAP-70 by comparing results with clinical outcome and the mutation status of the IgV(H). Using stored samples, we show significant correlation between ZAP-70 expression and clinical outcome as well as IgV(H) mutation at a cut-off point of 15%. While positive samples (>15% positivity) remain positive when kept in the laboratory environment for 48 h after initial testing, results obtained from samples from CLL patients tested after shipping at room temperature for routine testing showed no correlation with IgV(H) mutation status when 15% cut-off was used. In these samples, cut-point of 10% correlated with the IgV(H) mutation (P = 0.0001). This data suggests that although ZAP-70 positivity correlates with IgV(H) mutation status and survival, variations in sample handling and preparation may influence results. We show that IgV(H) mutation results, unlike ZAP-70 remain correlated with CD38 expression and beta-2 microglobulin in shipped samples, and ZAP-70 testing should not be used as the sole criterion for stratifying patients for therapy.

ADP-ribosyl Cyclase 1↗
PubMed2006

Successful dieters have increased neural activity in cortical areas involved in the control of behavior.

OBJECTIVE: To investigate whether dietary restraint, a landmark of successful dieting, is associated with specific patterns of brain responses to the sensory experience of food and meal consumption. DESIGN AND SUBJECTS: Cross-sectional study of the brain's response to the sensory experience of food and meal consumption in nine successful dieters (age: 38+/-7 years, body fat (%): 28+/-3) and 20 non-dieters (age: 31+/-9 years, body fat (%): 33+/-9), all women. MEASUREMENTS: Changes in brain activity in response to the sensory experience of food and meal consumption were assessed by using positron emission tomography and (15)O water as a radiotracer. Body fatness was assessed by dual X-ray absorptiometry. Subjective ratings of hunger and fullness were measured by visual analogue scale. Dietary restraint, disinhibition and hunger were assessed by the Three Factor Eating Questionnaire. RESULTS: Successful dieters had a significantly higher level of dietary restraint compared to non-dieters. In response to meal consumption, successful dieters had a greater activation in the dorsal prefrontal cortex (DPFC), dorsal striatum and anterior cerebellar lobe as compared to non-dieters. In response to the same stimulation, the orbitofrontal cortex (OFC) was significantly more activated in non-dieters as compared to successful dieters. Dietary restraint was positively correlated with the response in the DPFC and negatively with the response in the OFC. The responses in the DPFC and OFC were negatively intercorrelated. CONCLUSION: Cortical areas involved in controlling inappropriate behavioral responses, such as the DPFC, are particularly activated in successful dieters in response to meal consumption. The association between the degree of dietary restraint and the coordinated neural changes in the DPFC and OFC raises the possibility that cognitive control of food intake is achieved by modulating neural circuits controlling food reward.

Adult↗
PubMed2006

An approach of encoding for prediction of splice sites using SVM.

In splice sites prediction, the accuracy is lower than 90% though the sequences adjacent to the splice sites have a high conservation. In order to improve the prediction accuracy, much attention has been paid to the improvement of the performance of the algorithms used, and few used for solving the fundamental issues, namely, nucleotide encoding. In this paper, a predictor is constructed to predict the true and false splice sites for higher eukaryotes based on support vector machines (SVM). Four types of encoding, which were mono-nucleotide (MN) encoding, MN with frequency difference between the true sites and false sites (FDTF) encoding, Pair-wise nucleotides (PN) encoding and PN with FDTF encoding, were applied to generate the input for the SVM. The results showed that PN with FDTF encoding as input to SVM led to the most reliable recognition of splice sites and the accuracy for the prediction of true donor sites and false sites were 96.3%, 93.7%, respectively, and the accuracy for predicting of true acceptor sites and false sites were 94.0%, 93.2%, respectively.

Algorithms↗
PubMed2005

Activation of brain regions vulnerable to Alzheimer's disease: the effect of mild cognitive impairment.

This study examined the functionality of the medial temporal lobe (MTL) and posterior cingulate (PC) in mild cognitive impairment amnestic type (MCI), a syndrome that puts patients at greater risk for developing Alzheimer disease (AD). Functional MRI (fMRI) was used to identify regions normally active during encoding of novel items and recognition of previously learned items in a reference group of 77 healthy young and middle-aged adults. The pattern of activation in this group guided further comparisons between 14 MCI subjects and 14 age-matched controls. The MCI patients exhibited less activity in the PC during recognition of previously learned items, and in the right hippocampus during encoding of novel items, despite comparable task performance to the controls. Reduced fMRI signal change in the MTL supports prior studies implicating the hippocampus for encoding new information. Reduced signal change in the PC converges with recent research on its role in recognition in normal adults as well as metabolic decline in people with genetic or cognitive risk for AD. Our results suggest that a change in function in the PC may account, in part, for memory recollection failure in AD.

Aged↗
PubMed2005

Human health risk assessment of organochlorines associated with fish consumption in a coastal city in China.

Food consumption is an important route of human exposure to organochlorines (OCs). In order to assess the potential health risks associated with these contaminants due to fish consumption, five species of fish were collected from a local market in Zhoushan City, an island in the East China Sea. Dioxin-like compounds, such as polychlorinated dibenzo-p-dioxins/ dibenzofurans, in the fish samples were screened by H4IIE-luc cell bioassay, and the concentrations of specific organochlorines were measured by gas chromatograph-electron capture detector (GC-ECD). The bioassay results indicated that concentrations of dioxin-like compounds in the fish samples were below detection limit (0.64 pg/mL). The concentrations of OC pesticides and PCBs ranged from 0.67 to 13 and 0.24 to 1.4 ng/g wet wt., respectively. Significantly, concentrations of p,p'-DDE in fish meat were comparatively high (average 3.9 ng/g wet wt.) compared with the other OC pesticides. The daily fish consumption, based on a dietary survey conducted among 160 local healthy residents, was determined to be 105 g/person. The relevant cancer benchmark concentrations of HCB, dieldrin, chlordane, DDTs and PCBs were 0.36, 0.04, 1.6, 1.7, and 0.29 ng/kg per day, respectively, based on the local diet. The hazard ratios (HRs), based on non-cancer endpoints were all less than 1.0, while the HRs based on cancer were greater than 1.0 for certain contaminants based on the 95th centile concentration in fish tissue.

Adult↗
PubMed2005

Patient satisfaction with antihypertensive therapy.

The objective of the study was to assess factors associated with treatment satisfaction among patients receiving antihypertensive therapy. A weighted cross-sectional online survey was conducted with hypertensive patients participating in a chronic disease panel in the US. Patients on monotherapy with medications from the following classes were identified: ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta blockers (BBs), calcium channel blockers (CCBs), and diuretics. The control group included patients without treatment. Pairwise comparisons between groups were conducted for factors that may affect patients' satisfaction. The study population had a mean age of 54.7+/-14.2 years and was 56.7% female. Participants with blood pressure (BP) controlled to JNC 7 guidelines were more satisfied with their medication than those with uncontrolled BP (90.3 vs 71.5%, P<0.05). Patients who had not experienced adverse events had higher satisfaction than patients experiencing adverse events (90.9 vs 75.8%, P<0.05). The most frequently self-reported adverse events were frequent urination, sexual dysfunction, and fatigue ranging from 7.0 to 9.6% across classes. The adverse event rates differed by class and were lowest among the ARBs. Patients on ARBs were the most likely to have switched from a previous antihypertensive class as compared to other classes (57.1% ARBs vs 49.8% ACEIs, 38.7% diuretics, 36.3% CCBs, and 31.7% BBs). Physician recommendation was the most common reason for switching. In conclusion, the ability to effectively treat hypertension depends upon a patient's satisfaction with antihypertensive therapy, which may be improved by achieving BP control and minimizing the occurrence of adverse events.

Adult↗
PubMed2005

Oral retinoids for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomized controlled trials.

BACKGROUND: The increased incidence of skin cancers after solid organ transplantation is well recognized. Skin cancers developing in transplant recipients are more aggressive in behaviour. Therapeutic options to reduce and/or delay the development of cutaneous neoplasms are therefore of interest. OBJECTIVES: The objective of this review was to summarize the available medical literature from randomized controlled trials on the use of oral retinoids as a preventive agent for skin cancers in the solid organ transplant population. METHODS: Three electronic databases were searched for relevant trials: MEDLINE (1966-October 2003), EMBASE (1980-week 44, 2003) and the Cochrane Controlled Trials Register (third quarter 2003). Randomized or quasi-randomized controlled clinical trials on subjects of any age or ethnic background who had received a solid organ transplant (cardiac, renal, liver, etc.) were evaluated. All titles and abstracts found by the search strategy were independently reviewed by two researchers for inclusion into the review. RESULTS: Eighty-one abstracts were identified through the electronic databases for consideration. Review of the abstracts identified three eligible trials. One cross-over trial involving 23 subjects treated with acitretin 25 mg daily for 12 months reported 46 squamous cell carcinomas (SCCs) developing in six subjects during acitretin treatment vs. 65 SCCs developing in 15 subjects during the drug-free period. Another trial involving 44 subjects treated with acitretin 30 mg daily or placebo for 6 months reported two of 19 subjects developing two SCCs in the treatment group vs. nine of 19 subjects developing 18 new skin cancers (15 SCCs, one Bowen's disease, two basal cell carcinomas) in the placebo group. One dose comparison trial involving 26 renal transplant recipients treated with acitretin did not find a significant difference in numbers of skin cancers developing at the doses examined. The major limitation to the use of acitretin was poor tolerance due to adverse events. Headaches, rash, musculoskeletal symptoms and hyperlipidaemia were the most common causes of withdrawal from treatment. No alterations in renal or liver function were detected during the periods of treatment or follow-up. CONCLUSIONS: The available data from a small number of randomized controlled trials suggest that acitretin may have a role in the management of solid organ transplant recipients with skin cancers. Tolerability of the drug is a major factor limiting its use. Appropriate selection of patients may help improve the risk-benefit ratio.

Acitretin↗
PubMed2005

Tissue microarray analysis of multiple gene expression in intestinal metaplasia, dysplasia and carcinoma of the stomach.

AIMS: To study multiple gene expression patterns and their roles in the process of gastric carcinogenesis. METHODS AND RESULTS: Using a high-throughput tissue microarray technique, 169 specimens from gastric carcinomas, precursor lesions and normal mucosa were immunostained on a series of tissue chips for p53, p21(WAF1/CIP1) cyclin E, Bcl-2, c-met and mucin 5AC expression. The overexpression of p53 was observed in 10.7% of low-grade dysplasia (LGD), 38.1% of high-grade dysplasia (HGD) and 39.6% of intestinal type gastric carcinoma (IGC). Expression of p21(WAF1/CIP1) was found in 47.6% of incomplete intestinal metaplasia (IM), 36.7% of dysplasia (Dys) and 29.5% of IGC. The overexpression of cyclin E was more frequently present in carcinomas than in Dys (P < 0.05); moreover, high-level expression (> 25% in extent) of cyclin E was observed only among IGC. Abnormal Bcl-2 expression was present in 81.0% of incomplete IM, 69.4% of Dys and 22.9% of IGC. Along with progression of the lesion, the expression of c-met increased; in contrast, mucin 5AC decreased gradually. CONCLUSIONS: The specific expression pattern in incomplete IM was mucin 5AC+/Bcl-2+/p53-/cyclin E-, while mucin 5AC-/cyclin E+ was specific for IGC. p53 was useful for distinguishing LGD from HGD. High-level expression of cyclin E might be an indicator for malignant transformation of dysplasia.

Cell Cycle Proteins↗
PubMed2005

Relationship of P450 2C9 genetic polymorphisms in Chinese and the pharmacokinetics of tolbutamide.

AIM: To study the relationship between P450 2C9 genetic polymorphisms and the pharmacokinetics of tolbutamide in Chinese subjects. METHODS: P450 2C9 genotype was determined by oligonucleotide microarray. Using tolbutamide as a probe of P450 2C9 activity, P450 2C9 phenotype in 20 healthy individuals expressing the P450 2C9*1/*1, *1/*3 and *3/*3 genotypes were evaluated. After administration of 500 mg tolbutamide, plasma and urine samples were collected from each subject over a 24-h period. The tolbutamide and its metabolites' concentrations in human plasma and urine were determined by solid-phase extraction and HPLC. RESULTS: Tolbutamide AUC0-->infinity increased by 20 and 116%, and T(1/2) increased by 60 and 813%, respectively, in subjects expressing the P4502C9*1/*3 and *3/*3 genotypes compared with *1/*1 subjects. Reductions in tolbutamide oral clearance (68 and 11%) and formation clearance (39 and 3%) were detected in the *1/*3 and *3/*3 individuals, respectively, compared with */*1 subjects. CONCLUSION: The P450 2C9 activity was significantly reduced in *1 heterozygotes compared with *1 homozygotes, and the metabolism of tolbutamide was more severely impaired in *3/*3 individuals compared with those expressing *1/*3. Using tolbutamide as a P450 2C9 probe, P450 2C9 genotype was the major determinant of P450 2C9 phenotype.

Adolescent↗
PubMed2005

Effect of progesterone on calcium activated potassium currents and intracellular calcium in guinea pig colon myocytes.

AIMS: To study the effects of progesterone on contractile activity of smooth muscle strips and on ion currents and intracellular Ca2+ ([Ca2+]i) intensity in single colonic myocytes in guinea pig proximal colons. METHODS: Strips and single cells were dissected from female guinea pig proximal colon. Contraction of strips through an isotonic transducer was assessed and the responsible currents to progesterone were recorded with EPC-9 amplifier in nystatin perforated whole-cell configuration. Detection of [Ca2+]i fluorescence loading fura-2 acetoxymethylester (fura-2/AM) was measured with confocal microscope. RESULTS: Progesterone significantly inhibited contraction of guinea pig colon strips in a dose-dependent pattern. Inhibitory concentration 50 (IC50) of progesterone in longitudinal strips and circular strips was, respectively, 9.7 microM and 1.0 nM. Iberiotoxin (IbTX) partially blocked inhibition of progesterone in both oriented smooth muscle strips. Ca2+ activated K+ (K(Ca)) channel currents recorded by depolarizing pulse protocol were enhanced by progesterone to 138% +/- 13% (n = 9, p < 0.01), and to 143% +/- 12% (n = 8, p < 0.01) when perfused with 10 mcM onapristone. Progesterone reduced L-Ca2+ currents to 67% +/- 6% (n = 7, p < 0.01) and had no effect with 5 microM nicardipine in bath solution. [Ca2+]i fluorescence was reduced by progesterone to 75% +/- 12% (n = 8, p < 0.01). CONCLUSION: Progesterone decreases the contraction of colonic smooth muscles by enhancing K(Ca) currents and reducing Ca2+ influx.

Animals↗
PubMed2004

The nongenotropic synthetic ligand 4-estren-3alpha17beta-diol is a high-affinity genotropic androgen receptor agonist.

The nongenotropic ligand estren (Science 298:843-846, 2002) was evaluated for its transcriptional activity mediated by the human androgen receptor (AR). Our results show that estren can bind, translocate, transactivate, and regulate two known target genes of AR in androgen-responsive cell lines. Estren binds recombinant AR with 10-fold higher affinity than either estrogen receptor (ER)-alpha or ERbeta. Estren-bound AR can translocate AR to the nucleus and stimulate the androgen response element-luciferase reporter activity with an efficacy similar to that of androgen. Estren also increased the expression of prostate-specific antigen (PSA) in a dose-dependent manner in human LnCaP cells. Using chromatin immunoprecipitation analysis, we show that the estren-bound AR coimmunoprecipitates with a region of the PSA gene promoter. Therefore, cotreatment with an AR antagonist, bicalutamide, blocked the estren-induced increase in PSA expression. In contrast, phosphoinositol 3-kinase inhibitor wortmannin, or extracellular signal-regulated kinase inhibitor 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophynyltio)butadiene (U0126), and ER antagonist ICI-182780 failed to block the effects of estren. In vivo analysis of estren's action on male-orchidectomized ICR mice revealed estren's AR agonist actions on the levator ani and seminal vesicle target tissues. Taken together, our results reveal the hitherto unidentified genotropic action of estren mediated by AR in androgen-responsive cells and tissues.

Androgens↗
PubMed2004

Improving the diffuse optical imaging spatial resolution of the cerebral hemodynamic response to brain activation in humans.

We compare two geometries of sources and detectors for optimizing the diffuse optical imaging resolution of brain activation in humans. Because of limitations in the instruments' dynamic range, most diffuse optical brain activation images have used only nonoverlapping measurements. We demonstrate theoretically and with a human experiment that a simple geometry of sources and detectors can provide overlapping measurements within the limitation of instrumentation dynamic range and produce an image resolution and localization accuracy that is twofold better.

Adult↗