Biomedical subjects

V Chen

Publications and source records attributed to V Chen.

At least 19 recordsLinked to original sources

PubMed2006

Mail and phone interventions for weight loss in a managed-care setting: weigh-to-be 2-year outcomes.

OBJECTIVE: Evaluate effectiveness of weight-loss interventions in a managed care setting. METHODS: Three-arm randomized clinical trial: usual care, mail, and phone intervention. Participants were 1801 overweight managed care organization (MCO) members. Measures included baseline height, weight at baseline and 24 months, self-reported weight at 18 months. Intervention and participation in other weight-related programs was monitored across 24 months. RESULTS: Weight losses were 2.2, 2.4, and 1.9 kg at 18 months in the mail, phone, and usual care groups, respectively. Mail and phone group weight changes were not significantly different from usual care (P<0.35). Weight losses at 24 months did not differ by condition (0.7 kg mail, 1.0 kg phone, and 0.6 kg usual care, P=0.55). Despite treatment availability over 24 months, participation diminished after 6 months. Participation was a significant predictor of outcomes in the mail and phone groups at 18 months and the mail group at 24 months. Cost-effectiveness of phone counseling was $132 per 1 kg of weight loss with mail and usual care achieving similar cost-efficiency of $72 per 1 kg of weight loss. CONCLUSION: Although mail- and phone-based weight-loss programs are a reasonably efficient way to deliver weight-loss services, additional work is needed to enhance their short- and long-term efficacy.

Adult↗

PubMed2005

The relationship between critical flux and fibre movement induced by bubbling in a submerged hollow fibre system.

Bubbling has been used to enhance various processes. In this paper we deal with the effect of bubbling on submerged hollow fibre membranes, where bubbling is applied to prevent severe membrane fouling. Previous work with submerged hollow fibres has observed that significant fibre movement can be induced by bubbling and that there is a qualitative relationship between fibre movement and filtration performance. Therefore, the aim of the present research has been to analyse the link between bubbling, fibre movement and critical flux, identified as the flux at which the transmembrane pressure (TMP) starts to rise. Tests were performed on vertical isolated fibres with a model feed of yeast suspension. The fibres were subject to steady bubbling from below. The parameters of interest were the fibre characteristics, such as tightness, diameter and length, as well as feed concentration. The results confirmed that the critical fluxes are affected by the fibre characteristics and feed concentration. Higher critical flux values can be achieved by using loose fibres, smaller diameters and longer fibres. The enhancement is partially linked to fibre movement and this is confirmed by improved performance when fibres are subject to mechanical movement in the absence of bubbling.

Bioreactors↗

PubMed2004

The photocatalytic degradation of reactive black 5 using TiO2/UV in an annular photoreactor.

The textile effluent is a major industrial polluter because it is highly colored, containing about 15% unfixed dyes as well as high levels of salts that can potentially be discharged into the environment. Photocatalytic oxidation using an thin gap annular UV reactor with TiO2 was used to break down the colour of a synthetic effluent ranging up to 400 ppm in dye concentration of Reactive Black 5 and up to 80 g/L in NaCl. Results show that the reaction kinetics was dominated by the TiO2 loading, the initial dye concentration, and the dissolved oxygen concentration; with the other parameters showing less significant effects. High rates of decolorization were found, with a linear fit to the Langmuir-Hinshelwood equation yielding a reaction rate constant (k) of 2.45 ppm/min, and an adsorption equilibrium constant (K) of 0.048 ppm(-1) based on color removal. The presence of the combination of high dissolved oxygen (15 ppm) and sodium chloride (up to 80 g/L) was found to enhance the decolorization and mineralization rates of the reactive dye. However, pH was found to not significantly affect the degradation rate. Since textile effluent is strongly alkaline, this result is significant, as no solution neutralisation is required and direct treatment of the effluent is possible.

Catalysis↗

PubMed2003

Cholinergic interneurons of the nucleus accumbens and dorsal striatum are activated by the self-administration of cocaine.

The nucleus accumbens, a major component of the ventral striatum, and the dorsal striatum are primary targets of the mesolimbic dopamine pathway, which is a pathway that plays a critical role in reward and addiction. The shell compartment of the nucleus accumbens and the ventromedial striatum, in particular, receive extensive afferent projections from the ventral tegmental area, which is the major afferent source of the mesolimbic pathway [Prog Brain Res 99 (1993) 209; J Neurosci 7 (1987) 3915]. The present study focused on striatal cholinergic interneurons as potential key neurons involved in the neural basis of drug reinforcement. The main finding of this study is that cholinergic interneurons located in the shell compartment of the nucleus accumbens and the ventromedial striatum were activated, as measured by Fos labeling, following a 1 h session of the self-administration of cocaine in rats. A direct correlation existed between the percent of cholinergic interneurons that were activated and the amount of cocaine that was self-administered. The greatest amount of administered cocaine (approximately 10 mg/kg) resulted in the activation of approximately 80% of the cholinergic neurons. No such correlation existed in the group of animals that self-administered saline. In addition, activation was not found in the core compartment of the nucleus accumbens or the dorsolateral striatum, which receive extensive innervation from the substantia nigra and thus are more closely tied to the motor effects of the drug. In conclusion, cocaine-driven neuronal activation was specific to the shell compartment of the nucleus accumbens (R(2)=0.9365) and the ventromedial striatum (R(2)=0.9059). These findings demonstrate that cholinergic interneurons are involved in the initial stage of cocaine intake and that these neurons are located in areas of the nucleus accumbens and dorsal striatum that are more closely tied to the rewarding and hedonic effects rather than the motor effects of cocaine intake.

Anesthetics, Local↗

PubMed2003

Social exchange of cigarettes by youth.

OBJECTIVE: This study seeks to determine the magnitude, nature, and correlates of social exchange of cigarettes among youth who smoke. DESIGN: Cross sectional survey. SETTING: Schools in 29 Minnesota communities. PARTICIPANTS: All students in grades 8, 9, and 10 (ages 13-16 years) in each participating school. The parent/child response rate for the survey was 90%. Analyses included 4124 respondents who smoked at least one cigarette in the month before the survey. OUTCOME MEASURES: Social exchange scale, consisting of 16 items assessing aspects of social provision and acquisition of cigarettes. RESULTS: Almost 90% of youth in this study had obtained a cigarette from, and about 75% of them had provided cigarettes to, another teen in the prior month. Daily smokers provided to more teens and provided more often than those who smoked less than daily. Daily smokers also reported having more social sources, both teens and adults, than lighter smokers, and were more likely to have both bought from and sold cigarettes to other teens (p < 0.0001 for all comparisons between daily and less than daily smokers). In a multivariate analysis, social exchange was associated with grade, whether siblings and friends smoke, level of smoking, age of smoking initiation, parental influences and community norms about teen smoking, and buying cigarettes. CONCLUSIONS: Social provision and acquisition of cigarettes among teens are widespread, reciprocal behaviours. Parental and community expectations about smoking influence social exchange, possibly by providing opportunities or barriers for social smoking. Commercial and social availability are not mutually exclusive; rather social exchange extends the reach of commercial sources.

Adolescent↗

PubMed2001

Limits of detection of regional differences in vasodilated flow in viable myocardium by first-pass magnetic resonance perfusion imaging.

BACKGROUND: Perfusion imaging techniques intended to identify regional limitations in coronary flow reserve in viable myocardium need to identify 2-fold differences in regional flow during coronary vasodilation consistently. This study evaluated the suitability of current first-pass magnetic resonance approaches for evaluating such differences, which are 1 to 2 orders of magnitude less than in myocardial infarction. METHODS AND RESULTS: Graded regional differences in vasodilated flow were produced in chronically instrumented dogs with either left circumflex (LCx) infusion of adenosine or partial LCx occlusion during global coronary vasodilation. First-pass myocardial signal intensity-time curves were obtained after right atrial injection of gadoteridol (0.025 mmol/kg) with an MRI inversion recovery true-FISP sequence. The area under the initial portion of the LCx curve was compared with that of a curve from a remote area of the ventricle. Relative LCx and remote flows were assessed simultaneously with microspheres. The ratio of LCx and remote MRI curve areas and the ratio of LCx and remote microsphere concentrations were highly correlated and linearly related over a 5-fold range of flow differences (y=0.96 x+/-0.07, P<0.0001, r(2)=0.87). The 95% confidence limits for individual MRI measurements were +/-35%. Regional differences of >/=2-fold were consistently apparent in unprocessed MR images. CONCLUSIONS: Clinically relevant regional reductions in vasodilated flow in viable myocardium can be detected with 95% confidence over the range of 1 to 5 times resting flow. This suggests that MRI can identify and quantify limitations in perfusion reserve that are expected to be produced by stenoses of >/=70%.

Animals↗

PubMed2001

Direct evidence for the existence of Miltenberger antigen.

The Miltenberger (Mi) subsystem, which originally consisted of four phenotypes, now has 11 phenotypes. The antigens of this subsystem belong to the MNS blood group system. The Mia antigen has been reported to be present on red blood cells with several Miltenberger phenotypes, namely: Mi.I, Mi.II, Mi.III, Mi.IV, Mi.VI and Mi.X. However, the existence of the Mia antigen as a separate entity has been in question and difficult to prove with polyclonal reagents. We report the first monoclonal anti-Mia (GAMA210), whose epitope is TNDKHKRD or QTNDMHKR, and thereby confirm the existence of the Mia antigen.

Animals↗

PubMed2001

Occult mucosal injuries with radiofrequency ablation of the palate.

OBJECTIVE: To determine the true incidence of mucosal injury after radiofrequency ablation of the palate (RFAP) for snoring and mild obstructive sleep apnea, and to evaluate the consequences of this injury. STUDY DESIGN AND SETTING: A prospective, nonrandomized analysis of RFAP was undertaken at Stanford University Hospital. Endoscopic examinations of the nasal surface of the palate and of the posterior pharyngeal wall were performed to supplement the routine oral cavity examinations in the postoperative period. Visual analog scales of pain were completed by the patients. Twenty-three patients underwent a total of 54 RFAP procedures using the Somnus system at the recommended level of energy (600 J in the midline palate, and 300 J to each lateral palate). RESULTS: Fourteen of the 23 first stage procedures were associated with a total of 16 mucosal injuries representing an incidence of 60.9%. Mucosal injury at the 1st stage prompted a reduction in energy at the 2nd stage to 500 J in the midline and 250 J laterally; there were 4 injuries among 19 2nd stage procedures (21.1%). The overall incidence of mucosal injury, including stage 3 and 4 procedures, was therefore 42.6%; 37% of these were "occult" (only visualized endoscopically). CONCLUSIONS AND SIGNIFICANCE: RFAP, although intended to be mucosa-sparing, is nevertheless associated with a high incidence of mucosal injuries, many of which are occult. The occurrence of these mucosal ulcers is usually associated with only a trivial degree of increased pain postoperatively.

Catheter Ablation↗

PubMed2001

Novel roles of kallistatin, a specific tissue kallikrein inhibitor, in vascular remodeling.

We have purified, cloned and characterized kallistatin, a tissue kallikrein-binding protein (KBP) in humans and rodents. Kallistatin is a unique serine proteinase inhibitor (serpin) with Phe-Phe residues at the P2 and P1 positions. Structural and functional analysis of kallistatin by site-directed mutagenesis and protein engineering indicate that wild-type kallistatin is selective for tissue kallikrein. Kallistatin is expressed and localized in endothelial and smooth muscle cells of blood vessels and has multiple roles in vascular function independent of the tissue kallikrein-kinin system. First, kallistatin induces vasorelaxation of isolated aortic rings and reduces renal perfusion pressure in isolated rat kidneys. Transgenic mice overexpressing rat kallistatin are hypotensive, and adenovirus-mediated gene delivery of human kallistatin attenuates blood pressure rise in spontaneously hypertensive rats. Second, kallistatin stimulates the proliferation and migration of vascular smooth muscle cells in vitro and neointima formation in balloon-injured rat arteries. Third, kallistatin inhibits the proliferation, migration and adhesion of endothelial cells in vitro and angiogenesis in the rat model of hindlimb ischemia. These results demonstrate novel roles of kallistatin in blood pressure regulation and vascular remodeling.

Animals↗

PubMed2001

Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors.

Pemetrexed disodium (ALIMTA), "pemetrexed") is a novel, multi-targeted antifolate that has demonstrated promising clinical activity in a wide variety of solid tumors, including non-small cell lung, breast, mesothelioma, colorectal, pancreatic, gastric, bladder, cervix, and head and neck. Pemetrexed inhibits multiple folate-dependent enzymes involved in both purine and pyrimidine synthesis including thymidylate synthase, dihydrofolate reductase, glycinamide ribonucleotide formyltransferase, and aminoimidazole carboxamide ribonucleotide formyltransferase. As a single agent, pemetrexed exhibits a moderate toxicity profile at a dose of 500 mg/m(2) by 10-minute infusion once every 21 days with myelosuppression being the dose-limiting toxicity. Folic acid added to the diet in preclinical studies reduced toxicities while maintaining antitumor activity. Based on this observation and clinical toxicities, folic acid and vitamin B(12) dietary supplementation has been recently introduced into all ongoing trials. Studies combining pemetrexed with other active chemotherapeutic agents demonstrate that these combination therapies may become important treatment regimens in a variety of cancer types. Currently, pemetrexed phase III trials are ongoing in mesothelioma and non-small cell lung cancer with future trials planned to explore this unique multitargeted antifolate.

Clinical Trials as Topic↗

PubMed2000

Treatment regimens including the multitargeted antifolate LY231514 in human tumor xenografts.

The scheduling of antifolate antitumor agents, including the new multitargeted autofolate LY231514 (MTA), with 5-fluorouracil was explored in the human MX-1 breast carcinoma and human H460 and Calu-6 non-small cell lung carcinoma xenografts to assess antitumor activity and toxicity (body weight loss). Administration of the antifolate (methotrexate, MTA, or LY309887) 6 h prior to administration of 5-fluorouracil resulted in additive growth delay of the MX-1 tumor when the antifolate was methotrexate or LY309887 and greater-than-additive tumor growth delay (TGD) when the antifolate was MTA. In the H460 tumor, the most effective regimens were a 14-day course of MTA or LY309887 along with 5-fluorouracil administered on the final 5 days. In addition, the simultaneous combination of MTA administered daily for 5 days for 2 weeks with administration of gemcitabine resulted in greater-than-additive H460 TGD. MTA was additive with fractionated radiation therapy in the H460 tumor when the drug was administered prior to each radiation fraction. MTA administered along with paclitaxel produced greater-than-additive H460 TGD and additive responses along with vinorelbine and carboplatin. In the Calu-6 non-small cell lung carcinoma xenograft, MTA administered in combination with cisplatin or oxaliplatin was highly effective, whereas MTA administered in combination with cyclophosphamide, gemcitabine, or doxorubicin produced additive responses. Administration of MTA along with paclitaxel or doxorubicin resulted in additive MX-1 TGD. Thus, MTA appears to be especially effective in combination therapies including 5-fluorouracil or an antitumor platinum complex.

Animals↗

PubMed1999

Circadian rhythm of motor restlessness and sensory symptoms in the idiopathic restless legs syndrome.

STUDY OBJECTIVES: To determine if motor restlessness in the Restless Legs Syndrome (RLS) shows a circadian rhythm with maximum at night, as previously found for subjective discomfort and periodic limb movements (PLMs), and to correlate RLS peak intensity with the core temperature cycle. DESIGN: Subjects underwent two days of normally timed wakefulness and sleep followed by a night and subsequent day of sleep deprivation. Activity was standardized through modified suggested immobilization tests (mSITs). SETTING: The study was conducted in a laboratory environment with a bedroom equipped for polysomnography during sleep and the mSITs. PATIENTS: Nine patients (mean age 59.8+/-11.3 years [range: 33-72]; 4 males, 5 females) with clinically severe idiopathic RLS. INTERVENTIONS: Patients were monitored with continuous ambulatory activity and core temperature recording. The mSITs were performed every three hours while subjects were awake. During the mSITs, subjective discomfort was measured every 15 minutes while motor restlessness was assessed through activity monitoring. MEASUREMENTS AND RESULTS: Subjective discomfort and motor restlessness increased from a trough in the morning to a maximum at night in the hours following midnight. Peak intensity was found on the falling phase of the core temperature cycle, whose circadian rhythm appeared to be within the normal range for age. CONCLUSIONS: An independent circadian factor modulates the intensity of RLS, which seems to peak on the falling phase of the core temperature cycle. Therefore, the diagnostic criteria that RLS occurs with rest and during the night have independent bases. Furthermore, RLS may be partially controlled by some process or substance whose level varies with the normal circadian rhythm.

Adult↗

PubMed1999

Human exonuclease 1 functionally complements its yeast homologues in DNA recombination, RNA primer removal, and mutation avoidance.

Yeast exonuclease 1 (Exo1) is induced during meiosis and plays an important role in DNA homologous recombination and mismatch correction pathways. The human homolog, an 803-amino acid protein, shares 55% similarity to the yeast Exo1. In this report, we show that the enzyme functionally complements Saccharomyces cerevisiae Exo1 in recombination of direct repeat DNA fragments, UV resistance, and mutation avoidance by in vivo assays. Furthermore, the human enzyme suppresses the conditional lethality of a rad27Delta mutant, symptomatic of defective RNA primer removal. The purified recombinant enzyme not only displays 5'-3' double strand DNA exonuclease activity, but also shows an RNase H activity. This result indicates a back-up function of exonuclease 1 to flap endonuclease-1 in RNA primer removal during lagging strand DNA synthesis.

Cell Division↗

PubMed1999

Streptococcal meningitis: effect of CSF filtration on inflammation and neuronal damage.

The effect of CSF filtration on inflammation and neuronal damage was studied in experimental Streptococcus pneumoniae meningitis. New Zealand white rabbits received either antibiotic therapy alone (ceftriaxone i.v., 20 mg/kg bolus, 10 mg/kg maintenance dose; n = 10) or ceftriaxone plus CSF filtration (n = 11) 12 h after intracisternal infection. Immediately after the onset of antibiotic therapy 300 microliters cisternal CSF was removed, passed through a miniaturized CSF-1 filter at a constant flow of 20 microliters/min, and then reinjected. This procedure was repeated six times at intervals of 20 min. Antibiosis plus CSF filtration caused a transient reduction in CSF bacterial titers and leukocyte counts compared with antibiosis alone (P = 0.04 and 0.02 5 h after initiation of therapy). CSF lipoteichoic acid concentrations were not reduced. The concentration of neuron-specific enolase in CSF and the density of apoptotic neurons in the dentate gyrus were almost equal 12 h after the onset of treatment. Adjuvant CSF filtration accelerated the elimination of viable bacteria from CSF in comparison to antibiotic treatment alone. Parameters of neuronal destruction, however, were not reduced.

Animals↗

PubMed1999

Correction of chromosomal point mutations in human cells with bifunctional oligonucleotides.

A sequence-specific genomic delivery system for the correction of chromosomal mutations was designed by incorporating two different binding domains into a single-stranded oligonucleotide. A repair domain (RD) contained the native sequence of the target region. A third strand-forming domain (TFD) was designed to form a triplex by Hoogsteen interactions. The design was based upon the premise that the RD will rapidly form a heteroduplex that is anchored synergistically by the TFD. Deoxyoligonucleotides were designed to form triplexes in the human adenosine deaminase (ADA) and p53 genes adjacent to known point mutations. Transfection of ADA-deficient human lymphocytes corrected the mutant sequence in 1-2% of cells. Neither the RD or TFD individually corrected the mutation. Transfection of p53 mutant human glioblastoma cells corrected the mutation and induced apoptosis in 7.5% of cells.

Adenosine Deaminase↗

PubMed1999

Intravenous granulocyte colony-stimulating factor increases the release of tumour necrosis factor and interleukin-1beta into the cerebrospinal fluid, but does not inhibit the growth of Streptococcus pneumoniae in experimental meningitis.

Granulocyte colony-stimulating factor (G-CSF) possesses an antimicrobial effect in several animal models of infection. To evaluate a possible effect of G-CSF on the course of pneumococcal meningitis, rabbits infected intracisternally (i.c.) with Streptococcus pneumoniae type 3 (n = 7) received 50 microgram/kg of rhG-CSF intravenously (i.v.) 1 h prior to infection. Seven infected animals served as controls. Uninfected rabbits received 10 microgram of G-CSF (n = 3), 2 microgram G-CSF (n = 3) or saline (n = 3) i.c. G-CSF injected i.c. did not produce cerebrospinal fluid (CSF) leucocytosis. Compared with the control group, i.v. G-CSF given prior to i.c. infection increased the percentage of granulocytes in blood 6 h and 12 h after infection. Twelve hours after infection, CSF tumour necrosis factor (TNF) activity and CSF interleukin (IL)-1beta concentrations were significantly higher in G-CSF-treated animals. G-CSF did not decrease bacterial growth in the subarachnoid space and the CSF leucocyte densities were not influenced. At 24 h after infection, G-CSF did not reduce the CSF concentrations of neurone-specific enolase and the density of apoptotic neurones in the dentate gyrus of the hippocampus. In conclusion, i.v. G-CSF increased the concentration of pro-inflammatory cytokines in the CSF but did not decrease the growth of Streptococcus pneumoniae in the subarachnoid space.

Animals↗

PubMed1999

ATP and phosphate reciprocally affect subunit association of human recombinant High Km 5'-nucleotidase. Role for the C-terminal polyglutamic acid tract in subunit association and catalytic activity.

IMP-specific, High Km 5'-nucleotidase (EC 3.1.3.5) is an ubiquitous enzyme, the activity of which is highly regulated by substrate, ATP, and inorganic phosphate. The cDNA encoding this enzyme has recently been cloned and found to contain a unique stretch of nine glutamic and four aspartic acid residues at the C-terminus. To study the effects of this acidic tail, and of ATP and inorganic phosphate on enzyme function, we generated several structural modifications of the 5'-nucleotidase cDNA, expressed the corresponding proteins in Escherichia coli and compared their molecular and kinetic properties. As with the enzyme purified from human placenta, all recombinant proteins were activated by ATP and inhibited by inorganic phosphate. Although the S0.5-values were higher, the specific activities of the purified protein variants (except that truncated at the C-terminus) were similar. The molecular mass of the full-length enzyme subunit has been estimated at 57.3 kDa and the molecular mass of the native protein, as determined by gel-filtration chromatography, was estimated to be 195 kDa. Increasing the concentration of NaCl to 0.3 M promoted oligomerization of the protein and the formation of aggregates of 332 kDa. ATP induced further oligomerization to 715 kDa, while inorganic phosphate reduced the estimated molecular mass to 226 kDa. In contrast to the truncation of 30 amino acids at the N-terminus, which did not alter enzyme properties, the removal of the polyglutamic/aspartic acid tail of 13 residues at the C-terminus caused profound kinetic and structural changes, including a 29-fold decrease in specific activity and a significant increase in the sensitivity to inhibition by inorganic phosphate in the presence of AMP. Structurally, there was a dramatic loss of the ability to form oligomers at physiological salt concentration which was only partially restored by the addition of NaCl or ATP. These data suggest an important function of the polyglutamic acid tract in the process of association and dissociation of 5'-nucleotidase subunits.

5'-Nucleotidase↗

PubMed1999

Pulmonary disorders: ventilation-perfusion MR imaging with animal models.

PURPOSE: To demonstrate the capability of magnetic resonance (MR) imaging to assess alteration in regional pulmonary ventilation and perfusion with animal models of airway obstruction and pulmonary embolism. MATERIALS AND METHODS: Airway obstruction was created by inflating a 5-F balloon catheter into a secondary bronchus. Pulmonary emboli were created by injecting thrombi into the inferior vena cava. Regional pulmonary ventilation was assessed with 100% oxygen as a T1 contrast agent. Regional pulmonary perfusion was assessed with a two-dimensional fast low-angle shot, or FLASH, sequence with short repetition and echo times after intravenous administration of gadopentetate dimeglumine. RESULTS: Matched ventilation and perfusion abnormalities were identified in all animals with airway obstruction. MR perfusion defects without ventilation abnormalities were seen in all animals with pulmonary emboli. CONCLUSION: Ventilation and perfusion MR imaging are able to provide regional pulmonary functional information with high spatial and temporal resolution. The ability of MR imaging to assess both the magnitude and regional distribution of pulmonary functional impairment could have an important effect on the evaluation of lung disease.

Airway Obstruction↗