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Biomedical subjects

L Chen

Publications and source records attributed to L Chen.

At least 217 records · Page 12Linked to original sources

Contrast-enhanced harmonic color Doppler for left ventricular opacification: improved endocardial border definition compared to tissue harmonic imaging and optimization of methodologyin patients with suboptimal echocardiograms.

OBJECTIVES: This study compared the efficacy of contrast-enhanced harmonic color Doppler (C-HCD) and tissue harmonic imaging (THI) for left ventricular endocardial border delineation and explored the optimal methodology of C-HCD in patients with suboptimal echocardiograms. BACKGROUND: The value of C-HCD in improving endocardium remains unknown. Effects of harmonic velocity-encoded color Doppler (HVD) and harmonic power Doppler (HPD) as well as contrast administration and image acquisition modalities on left ventricular opacification (LVO) have not been established. METHODS: One hundred (50 HVD, 50 HPD) patients with suboptimal echocardiograms during conventional fundamental echocardiography were studied with THI and C-HCD using Levovist. Each patient underwent different random contrast administration and image acquisition modalities. Endocardial border definition score index (EBDI), blooming artifacts, contrast destruction, and salvage of suboptimal echocardiograms were calculated in each patient after contrast enhancement. RESULTS: EBDI improved from 2.05 +/- 0.61 in THI to 2.73 +/- 0.48 in HVD, and 1.98 +/- 0.73 in THI to 2.69 +/- 0.51 in HPD (both P < 0.001). The conversion of a nondiagnostic image from fundamental echocardiography to an optimal diagnostic image was 33 (33%) patients in THI compared to 77 (77%) patients in C-HCD (P < 0.001). Blooming artifacts were seen more commonly in HVD than HPD, intermittent than continuous image acquisition, and bolus than infusion administration (all P < 0.001). There was less contrast destruction in intermittent compared with continuous image acquisition (P < 0.001). Contrast destruction was similar in HVD and HPD, bolus and infusion injection of contrast. The highest salvage rate of a nondiagnostic image from THI to an optimal diagnostic image was 45.5% and 42.4% in HPD mode, with intermittent image acquisition during bolus and infusion contrast administrations. CONCLUSIONS: C-HCD seems more effective in demonstrating improved endocardial border definition compared to THI. HPD has less blooming artifacts compared with HCD. The optimal method for LVO was to use HPD with intermittent image acquisition during bolus or infusion administration of Levovist.

Adolescent↗

Clinical applications of contrast echocardiography.

BACKGROUND: Contrast media, used in conjunction with newly developed echocardiographic techniques, can currently be used in several clinical settings: (1) the study of myocardial perfusion, (2) delineation of the endocardial border in technically difficult echocardiographic examinations, and (3) enhancement of low-intensity blood flow, especially coronary blood flow, to study coronary flow reserve. METHODS: Published studies were reviewed to identify the advantages of associating contrast perfusion with classic or new echocardiographic and ultrasonographic imaging techniques in the study of myocardial perfusion and coronary artery flow. RESULTS: Several studies demonstrated the usefulness of contrast echocardiography, even in patients with a bad acoustic window, in evaluating opacification of the left ventricle or in enhancing echocardiographic color Doppler studies of coronary flow and coronary flow reserve. Preliminary results of transthoracic echocardiographic studies of myocardial perfusion are described. CONCLUSIONS: The clinical applications of contrast echocardiography are effective in exploiting examinations that provide poor diagnostic information (ventricular cavity opacification) or in obtaining new physiopathologic data (microvascular opacification/perfusion and coronary flow reserve). The evaluation of coronary flow reserve by contrast-enhanced transthoracic Doppler ultrasonography is an attractive new diagnostic modality that points the way toward important new clinical applications of contrast echocardiography. This technique is useful in evaluating the severity of coronary artery disease of the left anterior descending coronary artery and in all clinical conditions in which the effects of therapeutic interventions aimed at improving coronary flow reserve need to be monitored.

Blood Flow Velocity↗

Comparing methods to identify general internal medicine clinic patients with chronic heart failure.

OBJECTIVES: Identification of patients with left ventricular systolic dysfunction is the first step in identifying which patients may benefit from clinical practice guidelines. The purpose of this study was to develop and validate a computerized tool using clinical information that is commonly available to identify patients with left ventricular systolic dysfunction (LVSD). METHODS: We performed a cross-sectional study of patients seen in a Department of Veterans Affairs General Internal Medicine Clinic who had echocardiography or radionuclide ventriculography performed as part of their clinical care. RESULTS: We identified 2246 subjects who had at least one cardiac imaging study. A total of 778 (34.6%) subjects met study criteria for LVSD. Subjects with LVSD were slightly older than subjects without LVSD (70 years vs 68 years, P =.00002) but were similar with regard to sex and race. Subjects with LVSD were more likely to have prescriptions for angiotensin-converting enzyme (ACE) inhibitors, carvedilol, digoxin, loop diuretics, hydralazine, nitrates, and angiotensin II receptor antagonists. Of the variables included in the final predictive model, ACE inhibitors, loop diuretics, and digoxin exerted the greatest predictive power. Discriminant analysis demonstrated that models containing pharmacy information were consistently more accurate (75% accurate [65% sensitivity, 81% specificity]) than those models that contained only International Classification of Diseases, 9th revision (ICD-9), codes, including ICD-9 codes for congestive heart failure (72% accurate [80% sensitivity, 68% specificity]). CONCLUSIONS: We demonstrated that an automated, computer-driven algorithm identifying LVSD permits simple, rapid, and timely identification of patients with congestive heart failure by use of only routinely collected data. Future research is needed to develop accurate electronic identification of heart failure and other common chronic conditions.

Aged↗

Improving clinical management for consumers with co-existing mental health and substance use disorders: an integrated approach.

Using Quality Improvement project methodology, complex organisational and clinical practice change was brought about to improve services for people with co-existing mental health and alcohol and drug misuse. The project describes local uptake and adaptation of national and state policy to achieve change that is sustainable within existing resources. Emphasis on engagement of staff and consumers and carers throughout the change was an essential component. The project has implications for the introduction of changes in response to other national policy directives.

Diagnosis, Dual (Psychiatry)↗

Human corneal epithelial extracellular matrix perlecan serves as a site for Pseudomonas aeruginosa binding.

PURPOSE: Previous data has shown that basement membrane associated perlecan serves as a binding site for Pseudomonas aeruginosa in the wounded mouse cornea. The current study determined whether it also provides a binding site for Pseudomonas aeruginosa in transformed human corneal epithelium. METHODS: Bacterial adherence to transformed human corneal epithelial cells grown in normal or in media containing various inhibitors of glycosaminoglycan synthesis was tested. Bacterial binding was similarly tested in wild-type and in mutant Chinese hamster ovary cell lines naturally deficient in glycosaminoglycan synthesis. Transformed human corneal epithelial extracellular matrix also was tested before and after treatment with anti-proteoglycan monoclonal antibodies or heparinase III before bacterial inoculation. Scanning electron microscopy was used to quantitate adherent bacteria. Intact transformed human corneal epithelial cells or extracellular matrix, the latter either treated or not treated with heparinase III or chondroitin ABC lyase were stained to localize perlecan. RESULTS: Examination of the binding of bacteria to transformed human corneal epithelial cells (normal media vs with inhibitors) and Chinese hamster ovary cell lines suggested that bacterial binding was not associated with the surface of either cell type. In contrast, anti-perlecan antibody, as well as heparinase III decreased the binding of bacteria to corneal extracellular matrix. Fluorescence staining localized perlecan to the extracellular matrix beneath the corneal epithelial cells. CONCLUSIONS: Perlecan localized to the extracellular matrix but not the apical surface of transformed human corneal epithelial cells, provides a binding site for Pseudomonas aeruginosa.

Animals↗

Disturbed expression of Fas/FasL on CD4(+) and CD8(+)T cells in Behcet's disease, Vogt-Koyanagi-Harada syndrome, and idiopathic anterior uveitis.

AIMS: To evaluate the expression of Fas/FasL antigen on peripheral blood T lymphocytes in patients with Behcet's disease, Vogt-Koyanagi-Harada (VKH) syndrome, and idiopathic anterior uveitis. METHODS: The expression of Fas and FasL on peripheral blood T lymphocytes was determined using flow cytometry in 26 patients with Behcet's disease (BD), 17 patients with VKH syndrome, 25 patients with idiopathic anterior uveitis, and 43 healthy individuals (controls). RESULTS: A higher proportion of CD4(+) T cells expressing Fas was noted in patients with Behcet's disease (25.70 +/- 7.32%), VKH syndrome (19.60 +/- 11.02%), and idiopathic anterior uveitis (20.81+/- 7.40%) compared with controls (14.02 +/- 6.30%). The expression of Fas on CD8(+) cells from patients with Behcet's disease (9.47 +/- 6.97%) and VKH syndrome (6.84+/- 5.5%) was also higher than that seen in controls (3.47+/- 2.75%). There was no difference in FasL expression on T cells between patients and controls except that a lower expression of FasL on CD8(+) T cells was noted in patients with idiopathic anterior uveitis. CONCLUSION: A disturbed expression of Fas and FasL on T cells is present in patients with Behcet's disease, VKH syndrome, and idiopathic anterior uveitis, which may be involved in the perpetuation and recurrence of uveitis.

Adult↗

A study of equivalent source techniques for high-resolution EEG imaging.

High-resolution EEG imaging has been an important topic in recent EEG research, and much work has been done on the two equivalent source imaging techniques: the equivalent distributed dipole-layer source imaging technique (EST) and the equivalent multipole source imaging technique (SAT). In this paper we first develop a forward density formula for a spherical equivalent distributed dipole layer of an arbitrary dipole in a three-concentric-sphere head model. It is clarified using the derived forward formula that the equivalent dipole-layer source and equivalent multipole source are interrelated in theory. Finally, simulation comparisons are conducted, the results of which suggest that EST has a higher spatial resolution than SAT when both of them are implemented by a truncated singular value decomposition algorithm. This is due to the different singularities of the inversion equations involved in the two techniques. An empirical VEP data study also shows that EST is better than SAT in providing higher spatial resolution EEG imaging.

Cerebral Cortex↗

Short-Term and medium-term effects of spinal cord tract transections on soleus H-reflex in freely moving rats.

Spinal cord function is normally influenced by descending activity from supraspinal structures. When injury removes or distorts this influence, function changes and spasticity and other disabling problems eventually appear. Understanding how descending activity affects spinal cord function could lead to new means for inducing, guiding, and assessing recovery after injury. In this study, we investigated the short-term and medium-term effects of spinal cord bilateral dorsal column (DC), unilateral (ipsilateral) lateral column (LC), bilateral dorsal column ascending tract (DA), or bilateral dorsal column corticospinal tract (CST) transection at vertebral level T8-T9 on the soleus H-reflex in freely moving rats. Data were collected continuously for 10-20 days before and for 20-155 days after bilateral DC (13 rats), DA (10 rats), CST (eight rats), or ipsilateral LC (seven rats) transection. Histological examination showed that transections were 98(+/- 3 SD)% complete for DC rats, 80(+/- 20)% complete for LC rats, 91(+/- 13 SD)% complete for DA rats, and 95(+/-13)% complete for CST rats. LC, CST, and DA transections produced an immediate (i.e., first-day) increase in H-reflex amplitude. LC transection also produced a small decrease in background activity in the first few posttransection days. Other than this small decrease, none of the transections produced evidence for the phenomenon of spinal shock. For all transections, all measures returned to or neared pretransection values within 2 weeks. DA and LC transections were associated with modest increase in H-reflex amplitude 1-3 months after transection. These medium-term effects must be taken into account when assessing transection effects on operant conditioning of the H-reflex. At the same time, the results are consistent with other evidence that, while H-reflex rate dependence and H-reflex operant conditioning are sensitive measures of spinal cord injury, the H-reflex itself is not.

Animals↗

Interaction with mLin-7 alters the targeting of endocytosed transmembrane proteins in mammalian epithelial cells.

To investigate the targeting mechanism for proteins bound to the mammalian Lin-7 (mLin-7) PDZ domain, we created receptor protein chimeras composed of the carboxyl-terminal amino acids of LET-23 fused to truncated nerve growth factor receptor/P75. mLin-7 bound to the chimera with a wild-type LET-23 carboxyl-terminal tail (P75t-Let23WT), but not a mutant tail (P75t-Let23MUT). In Madin-Darby canine kidney (MDCK) cells, P75t-Let23WT localized to the basolateral plasma membrane domain, whereas P75t-Let23MUT remained apical. Furthermore, mutant mLin-7 constructs acted as dominant interfering proteins and inhibited the basolateral localization of P75t-Let23WT. The mechanisms for this differential localization were examined further, and, initially, we found that P75t-Let23WT and P75t-Let23MUT were delivered equally to the apical and basolateral plasma membrane domains. Although basolateral retention of P75t-Let23WT, but not P75t-Let23MUT, was observed, the greatest difference in receptor localization was seen in the rapid trafficking of P75t-Let23WT to the basolateral plasma membrane domain after endocytosis, whereas P75t-Let23MUT was degraded in lysosomes, indicating that mLin-7 binding can alter the fate of endocytosed proteins. Altogether, these data support a model for basolateral protein targeting in mammalian epithelial cells dependent on protein-protein interactions with mLin-7, and also suggest a dynamic role for mLin-7 in endosomal sorting.

Animals↗

Phase 1 drug interaction study of suramin and warfarin in patients with prostate cancer.

Potential interaction between suramin and warfarin was evaluated when coadministered to patients with cancer. Thirteen men with advanced hormone-refractory prostate cancer were initially stabilized with warfarin to a prothrombin time (PT) of 2 +/- 0.2 International Normalized Ratio (INR) during a lead-in period of 4 weeks. A baseline daily warfarin dose was established, and treatment with suramin plus hydrocortisone was then started. The effect of suramin on the anticoagulant activity of warfarin was assessed in each patient by comparing his baseline warfarin dose with average daily doses required to maintain the same INR level over each of the initial 6 weeks of a 12-week course of suramin treatment. The average daily dose of warfarin required to maintain PT at 2 +/- 0.2 INR decreased from a baseline value of 4.2 to between 3.4 and 4.0 during the 6 weeks of suramin plus warfarin treatment. Despite failing to demonstrate equivalence applying a 90% confidence interval approach, required reductions in warfarin dose were clinically minor and the combination was well tolerated. Based on these results, the eligibility criteria for a large ongoing randomized study were amended to allow entry of men receiving warfarin therapy. This interaction study, together with experience gained in a larger trial setting, has confirmed that warfarin and suramin can be safely coadministered, provided that coagulation status is appropriately monitored.

Anti-Inflammatory Agents↗

The antinociceptive effect of the combination of spinal morphine with systemic morphine or buprenorphine.

UNLABELLED: We sought to analyze the mode of interaction of spinal morphine with systemic morphine or buprenorphine, administered in a wide range of antinociceptive doses. The study was performed on Sprague-Dawley rats by using a plantar stimulation test and isobolographic and fractional analyses of drug interaction. The isobolographic and fractional analyses demonstrated that intrathecal morphine interacted with subcutaneous morphine in a synergistic manner while producing a 50% or 75% antinociceptive effect. The sum of D(75) fractions was more than that for 50% antinociception, suggesting a less dramatic interaction. The combination with a maximal relative dose of systemic morphine (0.66:1) showed a maximal degree of supraadditivity. The interaction between spinal morphine and systemic buprenorphine was similar to that of morphine/morphine, although the supra-additivity was not as pronounced. For the doses that produced a 50% antinociceptive effect, a synergistic interaction was observed only for the combination with a morphine/buprenorphine ratio of 1.33:1. When the relative amount of intrathecal morphine was decreased or increased, the effect became additive. At the doses that produced 75% antinociception, both combinations of morphine and buprenorphine demonstrated supraadditive interaction. IMPLICATIONS: Spinal morphine interacts with systemic morphine or buprenorphine in asupraadditive manner. This mode of interaction most probably results from the simultaneous activation of spinal and supraspinal antinociceptive systems. Supraspinal structures played a more important role in the antinociceptive effect of experimental combinations than structures of the spinal cord.

Algorithms↗

Pulmonary vasoconstriction during regional nitric oxide inhalation: evidence of a blood-borne regulator of nitric oxide synthase activity.

BACKGROUND: Inhaled nitric oxide (INO) is thought to cause selective pulmonary vasodilation of ventilated areas. The authors previously showed that INO to a hyperoxic lung increases the perfusion to this lung by redistribution of blood flow, but only if the opposite lung is hypoxic, indicating a more complex mechanism of action for NO. The authors hypothesized that regional hypoxia increases NO production and that INO to hyperoxic lung regions (HL) can inhibit this production by distant effect. METHODS: Nitric oxide concentration was measured in exhaled air (NO(E)), NO synthase (NOS) activity in lung tissue, and regional pulmonary blood flow in anesthetized pigs with regional left lower lobar (LLL) hypoxia (fraction of inspired oxygen [FIO2] = 0.05), with and without INO to HL (FIO2 = 0.8), and during cross-circulation of blood from pigs with and without INO. RESULTS: Left lower lobar hypoxia increased exhaled NO from the LLL (NO(E)LLL) from a mean (SD) of 1.3 (0.6) to 2.2 (0.9) parts per billion (ppb) (P < 0.001), and Ca2+-dependent NOS activity was higher in hypoxic than in hyperoxic lung tissue (197 [86] vs. 162 [96] pmol x g(-1) x min(-1), P < 0.05). INO to HL decreased the Ca2+-dependent NOS activity in hypoxic tissue to 49 [56] pmol x g(-1) x min(-1) (P < 0.01), and NO(E)LLL to 2.0 [0.8] ppb (P < 0.05). When open-chest pigs with LLL hypoxia received blood from closed-chest pigs with INO, NO(E)LLL decreased from 2.0 (0.6) to 1.5 (0.4) ppb (P < 0.001), and the Ca2+-dependent NOS activity in hypoxic tissue decreased from 152 (55) to 98 (34) pmol x g(-1) x min(-1) (P = 0.07). Pulmonary vascular resistance increased by 32 (21)% (P < 0.05), but more so in hypoxic (P < 0.01) than in hyperoxic (P < 0.05) lung regions, resulting in a further redistribution (P < 0.05) of pulmonary blood flow away from hypoxic to hyperoxic lung regions. CONCLUSIONS: Inhaled nitric oxide downregulates endogenous NO production in other, predominantly hypoxic, lung regions. This distant effect is blood-mediated and causes vasoconstriction in lung regions that do not receive INO.

Administration, Inhalation↗

ANT1, an aromatic and neutral amino acid transporter in Arabidopsis.

A new amino acid transporter was identified from the Arabidopsis expressed sequence tag cDNAs by expressing the cDNA in a yeast amino acid transport mutant. Transport analysis of the expressed protein in yeast showed that it transports aromatic and neutral amino acids, as well as arginine. This transporter (ANT1, aromatic and neutral transporter) also transports indole-3-acetic acid and 2,4-dichlorophenoxyacetic acid. The cDNA is 1.6 kb in length with an open reading frame that codes for a protein with 432 amino acids and a calculated molecular mass of 50 kD. Hydropathy analysis showed ANT1 is an integral membrane protein with 11 putative membrane-spanning domains. Southern analysis and a BLAST search of the Arabidopsis genome database suggests that ANT1 is part of a small gene family containing at least five members. Phylogenetic comparisons with other known amino acid transporters in plants suggests that ANT1 represents a new class of amino acid transporter. RNA gel-blot analysis showed that this transporter is expressed in all organs with highest abundance in flowers and cauline leaves.

Amino Acid Transport Systems, Neutral↗

EMF1, a novel protein involved in the control of shoot architecture and flowering in Arabidopsis.

Shoot architecture and flowering time in angiosperms depend on the balanced expression of a large number of flowering time and flower meristem identity genes. Loss-of-function mutations in the Arabidopsis EMBRYONIC FLOWER (EMF) genes cause Arabidopsis to eliminate rosette shoot growth and transform the apical meristem from indeterminate to determinate growth by producing a single terminal flower on all nodes. We have identified the EMF1 gene by positional cloning. The deduced polypeptide has no homology with any protein of known function except a putative protein in the rice genome with which EMF1 shares common motifs that include nuclear localization signals, P-loop, and LXXLL elements. Alteration of EMF1 expression in transgenic plants caused progressive changes in flowering time, shoot determinacy, and inflorescence architecture. EMF1 and its related sequence may belong to a new class of proteins that function as transcriptional regulators of phase transition during shoot development.

Amino Acid Sequence↗

EMBRYONIC FLOWER2, a novel polycomb group protein homolog, mediates shoot development and flowering in Arabidopsis.

In higher plants, developmental phase changes are regulated by a complex gene network. Loss-of-function mutations in the EMBRYONIC FLOWER genes (EMF1 and EMF2) cause Arabidopsis to flower directly, bypassing vegetative shoot growth. This phenotype suggests that the EMF genes play a major role in repression of the reproductive program. Positional cloning of EMF2 revealed that it encodes a zinc finger protein similar to FERTILIZATION-INDEPENDENT SEED2 and VERNALIZATION2 of Arabidopsis. These genes are characterized as structural homologs of Suppressor of zeste 12 [Su(z)12], a novel Polycomb group gene currently identified in Drosophila. In situ hybridization studies have demonstrated that EMF2 RNA is found in developing embryos, in both the vegetative and the reproductive shoot meristems, and in lateral organ primordia. Transgenic suppression of EMF2 produced a spectrum of early-flowering phenotypes, including emf2 mutant-like phenotype. This result confirms the role of EMF2 in phase transitions by repressing reproductive development.

Arabidopsis↗

Crystallization of agGST1-6, a recombinant glutathione S-transferase from a DDT-resistant strain of Anopheles gambiae.

Glutathione S-transferases (GSTs) belong to a family of detoxification enzymes that conjugate glutathione to various xenobiotics, thus facilitating their expulsion from the cell. GST activity is elevated in many insecticide-resistant insects, including the DDT-resistant malaria vector Anopheles gambiae. Crystals of the recombinant form of a GST from A. gambiae, agGST1-6, have been grown in at least five different crystal forms, with a broad range of diffraction resolution limits. A complete 2.0 A data set has been collected on a C-centered orthorhombic crystal form with unit-cell parameters a = 99.0, b = 199.4, c = 89.6 A. A search for heavy-atom derivatives has been initiated, along with phase-determination efforts by molecular replacement.

Animals↗

Crystallization and preliminary X-ray diffraction analysis of protein L-isoaspartyl O-methyltransferase from wheat germ.

Wheat-germ protein L-isoaspartyl O-methyltransferase (WPIMT) can initiate the conversion of L-isoaspartyl residues in a protein or peptide, which accumulate during the aging process in wheat-germ seeds, to normal L-aspartyl groups. The recombinant protein of WPIMT was overexpressed in Escherichia coli and purified to homogeneity. The protein was crystallized in the presence of S-adenosine-L-homocysteine using 2-methyl-2,4-pentanediol. Preliminary X-ray analysis indicated a tetragonal space group P4(1)2(1)2 or P4(3)2(1)2, with unit-cell parameters a = b = 77.3, c = 152.9 A for cryofrozen crystals at 90 K. The crystals diffracted to 3.3 A and contain two molecules per asymmetric unit.

Cloning, Molecular↗