Biomedical subjects
R Lee
Publications and source records attributed to R Lee.
Cortical scarring as a variable in the assessment of donor kidney biopsy specimens.
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Increased insulin sensitivity in Gsalpha knockout mice.
The stimulatory guanine nucleotide-binding protein (G(s)) is required for hormone-stimulated cAMP generation. Gnas, the gene encoding the G(s) alpha-subunit, is imprinted, and targeted disruption of this gene in mice leads to distinct phenotypes in heterozygotes depending on whether the maternal (m-/+) or paternal (+/p-) allele is mutated. Notably, m-/+ mice become obese, whereas +/p- mice are thinner than normal. In this study we show that despite these opposite changes in energy metabolism, both m-/+ and +/p- mice have greater sensitivity to insulin, with low to normal fasting glucose levels, low fasting insulin levels, improved glucose tolerance, and exaggerated hypoglycemic response to administered insulin. The combination of increased insulin sensitivity with obesity in m-/+ mice is unusual, because obesity is typically associated with insulin resistance. In skeletal muscles isolated from both m-/+ and +/p- mice, the basal rate of 2-deoxyglucose uptake was normal, whereas the rate of 2-deoxyglucose uptake in response to maximal insulin stimulation was significantly increased. The similar changes in muscle sensitivity to insulin in m-/+ and +/p- mice may reflect the fact that muscle G(s)alpha expression is reduced by approximately 50% in both groups of mice. GLUT4 expression is unaffected in muscles from +/p- mice. Increased responsiveness to insulin is therefore the result of altered insulin signaling and/or GLUT4 translocation. This is the first direct demonstration in a genetically altered in vivo model that G(s)-coupled pathways negatively regulate insulin signaling.
Protein analysis of an individual Caenorhabditis elegans single-cell embryo by capillary electrophoresis.
We present a simple one-dimensional electrophoretic map of the expressed proteins in a Caenorhabditis elegans embryo. The embryo was taken from an adult nematode, injected into a 50-microm I.D. capillary, and lysed. The proteins were fluorescently labeled and then separated by capillary electrophoresis and detected by laser-induced fluorescence. Over 20 components were resolved in the 22-min separation. The dynamic range was outstanding for this separation, noise in the baseline was less than 0.01% the amplitude of the largest component.
Nuclear factor-kappaB and cell survival: IAPs call for support.
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Kidney transplantation for end-stage renal failure in liver transplant recipients with hepatitis C viral infection.
BACKGROUND: End-stage renal failure after successful liver transplantation (LTx) has been described in up to 5% of patients. Kidney transplantation (KTx) has been the treatment of choice in these cases. However, in recipients infected with hepatitis C virus (HCV), the augmentation of immunosuppression after KTx may result in an increased viral load. This, in turn, may adversely affect the liver allograft. METHOD: The present study retrospectively examined the outcome in 17 patients (3 females and 14 males, mean age 51.1+/-11.3 years) who received KTx after LTx. The mean interval from LTx to KTx was 57.6+/-32.1 months. The mean follow-up was 41.7+/-20.5 months after KTx, and 99.6+/-37.7 months after LTx. Sixteen of the 17 patients received tacrolimus-based immunosuppression at the time of KTx. RESULTS: During the follow-up period, one patient underwent combined liver and kidney retransplantation 3.7 years after KTx and 12.7 years after LTx. She subsequently died secondary to primary nonfunction. Four other patients died, two of lung cancer, one of pancreatitis/sepsis, and one of severe depression leading to noncompliance. A total of 29 episodes of biopsy-proven acute renal allograft rejection (1.7 episodes/ patient) were encountered and treated with steroids. Seven patients experienced a rise in liver function tests during the period of increased steroid dosage. Four patients received no treatment, and their liver function returned to baseline. The remaining three were treated with interferon. Overall 1- and 3-year actuarial patient and liver allograft survival was 88% and 71% (after renal transplantation); corresponding 1- and 3-year actuarial graft survival was 88% and 61%. Twelve patients are alive with normal liver function. One patient is on dialysis, because of renal allograft loss to noncompliance. CONCLUSION: In this series, LTx recipients with HCV infection were able to undergo KTx with a reasonable degree of success. KTx should be offered for end-stage renal failure after LTx, even in the presence of HCV infection, to individuals with stable liver function and no signs of liver failure.
gamma-Tocopherol metabolism and its relationship with alpha-tocopherol in humans: a stable isotope supplementation study.
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A family of 12 human genes containing oxysterol-binding domains.
Oxysterol-binding proteins (OSBPs) have been described in a wide range of eukaryotes, and are often found to be part of a multi-gene family. We have used bioinformatics and data mining as a starting point for identifying new family members in humans based on the presence of the OSBP signature EQVSHHPP. In addition to OSBP and the recently reported OSBP2, we have found 10 other genes encoding oxysterol-binding domains. Here, we report cDNA and deduced peptide sequences of the previously unknown OSBPs and compare the peptides and genes. All of the genes encode a pleckstrin homology domain, except OSBPL2. However, two of the peptides, OSBPL2 and OSBPL1A, consist of the OSBP domain only. A second OSBPL1 transcript (OSBPL1B) contains 15 additional upstream exons, with a deduced peptide containing a pleckstrin homology domain. Cladistic analysis divides the human OSBP genes into five groups, whose members share similarities in sequence and gene structure; RT-PCR analysis indicates that expression patterns among group members vary widely.
Immunorestitution diseases in patients not infected with HIV.
The aim of this study was to assess the clinical spectrum of immunorestitution disease (IRD) in hospitalized patients over a 12-month period. In nine of 18 patients who presented with clinical deterioration during reduction or cessation of immunosuppressants (n = 6) or bone marrow engraftment (n = 3), IRD cases included the following infections: scabies infestation (n = 1); gastric strongyloidiasis (n = 1); hepatosplenic candidiasis (n = 1); methicillin-resistant Staphylococcus aureus abscess formation (n = 2); polyomavirus-related hemorrhagic cystitis (n = 3); and influenza A pneumonitis (n = 1). Immunopathological damage during withdrawal of immunosuppression is an incidental way to uncover an asymptomatic infectious disease. Serial monitoring of hematological and clinical profiles is essential in making a diagnosis of IRD.
Dielectric resonances and B(1) field inhomogeneity in UHFMRI: computational analysis and experimental findings.
B(1) Field inhomogeneity and the relative effects of dielectric resonances are analyzed within the context of ultra high field MRI. This is accomplished by calculating the electromagnetic fields inside spherical phantoms and within a human head model in the presence and absence of an RF coil. These calculations are then compared to gradient echo and RARE images, respectively. For the spherical phantoms, plane incident wave analyses are initially presented followed by full wave finite difference time domain (FDTD) calculations. The FDTD methods are then utilized to examine the electromagnetic interactions between the TEM resonator and an anatomically detailed human head model. The results at 340 MHz reveal that dielectric resonances are most strongly excited in objects similar in size to the human head when the conducting medium has a high dielectric constant and a low conductivity. It is concluded that in clinical UFHMRI, the most important determinants of B(1) field homogeneity consist of 1) the RF coil design, 2) the interaction between the RF coil, the excitation source and the sample, and finally 3) the geometry and electrical properties of the sample.
Effect of RF coil excitation on field inhomogeneity at ultra high fields: a field optimized TEM resonator.
In this work, computational methods were utilized to optimize the field produced by the transverse electromagnetic (TEM) resonator in the presence of the human head at 8 Tesla. Optimization was achieved through the use of the classical finite difference time domain (FDTD) method and a TEM resonator loaded with an anatomically detailed human head model with a resolution of 2 mm x 2 mm x 2 mm. The head model was developed from 3D MR images. To account for the electromagnetic interactions between the coil and the tissue, the coil and the head were treated as a single system at all the steps of the model including, numerical tuning and excitation. In addition to 2, 3, 4, 6, and 10-port excitations, an antenna array concept was utilized by driving all the possible ports (24) of a 24-strut TEM resonator. The results show that significant improvement in the circularly polarized component of the transverse magnetic field could be obtained when using multiple ports and variable phase and fixed magnitude, or variable phase and variable magnitude excitations.
N-cadherin regulates target specificity in the Drosophila visual system.
Using visual behavioral screens in Drosophila, we identified multiple alleles of N-cadherin. Removal of N-cadherin selectively from photoreceptor neurons (R cells) causes deficits in specific visual behaviors that correlate with disruptions in R cell connectivity. These defects include disruptions in the pattern of neuronal connections made by all three classes of R cells (R1-R6, R7, and R8). N-cadherin is expressed in both R cell axons and their targets. By inducing mitotic recombination in a subclass of eye progenitors, we generated mutant R7 axons surrounded by largely wild-type R cell axons and a wild-type target. R7 axons lacking N-cadherin mistarget to the R8 recipient layer. We consider the implications of these findings in the context of the proposed role for cadherins in target specificity.
Cryoablation of ventricular tachycardia guided by return cycle mapping after entrainment.
BACKGROUND: Although the implantable cardioverter-defibrillator effectively prevents sudden cardiac death, patients are still prone to recurrence of ventricular tachyarrhythmias. Electrophysiologically guided surgery is the most effective modality in abolishing ventricular tachycardia, having a lower recurrence rate than pharmacologic therapy or catheter ablation. Return cycle mapping after entrainment has been shown to localize the central common pathway, which is the target region for ablation, without pacing at the pathway or recording the potentials from the pathway. METHODS: To determine the accuracy and usefulness of return cycle mapping in surgery for ventricular tachycardia, we cryoablated 8 morphologies of ventricular tachycardia induced in postinfarction dogs with the guidance of return cycle mapping. The ventricular tachycardia was entrained from 3 to 5 different epicardial sites at a paced cycle length 10 to 20 ms shorter than the ventricular tachycardia cycle length and the epicardium was mapped with 61 unipolar electrodes during cessation of entrainment to construct return cycle maps. The return cycle was determined by subtracting the first activation time from the second activation time after the last stimulus in each electrode location, and the maps were then displayed on a computer. RESULTS: The total analysis process was completed within 3 minutes by means of a computer with custom-made programs. The activation map during ventricular tachycardia did not localize the central common pathway in any morphology of ventricular tachycardia, because the pattern of activation was concentric and diastolic potentials were not recorded. Cryoablation of the region where the isotemporal lines of the return cycle equal to the ventricular tachycardia cycle length intersected resulted in termination of ventricular tachycardia in all morphologies. The intersection was 26 +/- 9 mm from the earliest activation site. Epicardial mapping with 253 electrodes during cryothermia showed that the region localized by return cycle mapping was the central common pathway sandwiched between the lines of conduction block and that the cryolesion connected the lines of block, blocked the rotating wave front, and resulted in termination of the ventricular tachycardia. CONCLUSION: Return cycle mapping provides an accurate and rapid means of localizing the central common pathway without the need for recording potentials from the pathway or pacing at the pathway in ablation for ventricular tachycardia.
Analysis of B1 field profiles and SAR values for multi-strut transverse electromagnetic RF coils in high field MRI applications.
In this work, the B1 field homogeneity and specific absorption rate (SAR) values were evaluated for three high-frequency (340 MHz) radio frequency coils designed for use in human magnetic resonance imaging at 8 tesla. Eight-, 16-, and 24-strut transverse electromagnetic (TEM) resonators were examined both experimentally and with the finite difference time domain numerical method. It was observed that increasing the number of TEM elements acted to lower the maximal achievable frequency of the coil and to increase the experimental complexities associated with tuning and matching. In addition, it is demonstrated from experiment and numerical analysis that the circularly polarized component of the B1 (B1+) field homogeneity in the head improved most from 8- to 16-strut coils. Numerical analysis revealed little difference in terms of SAR distribution between these coils; however, stronger tissue/coil coupling and consequently higher SAR peak values were obtained for the 8-strut case.
B1 field homogeneity and SAR calculations for the birdcage coil.
The finite-difference time-domain (FDTD) method is used to model a birdcage resonator. All the coil components, including the wires, lumped capacitors and the source, are geometrically modelled together. As such, the coupling effects within the birdcage, including the interactions of coil, source and human head, are accurately computed. A study of the transverse magnetic (B1) field homogeneity and the specific absorption rate (SAR) is presented on an anatomically detailed human head model at 64 and 200 MHz representing 1.5 and 4.7 T MRI systems respectively. Unlike that at 64 MHz, the B1 field distribution is found to be inhomogeneous at 200 MHz. Also, high local SAR values are observed in the tissue near the source due to the coupling between the source and the head at 200 MHz.
Factor V Leiden: a clinical review.
Factor V Leiden is the most prevalent genetic thrombophilia in people of European descent. Since its discovery, much clinical information has been gathered regarding the distribution and prevalence of the genetic mutation, the mechanism of thrombophilia, and its association with clinical thromboembolic events. Although its association with venous thromboembolism is clear, the role of Factor V Leiden in other disease states is not clear. A review of the literature regarding the mechanism of hypercoagulability, genetic versus functional diagnostic tests, screening issues, relationship to arterial thromboses, pregnancy and pregnancy complications, and treatment are discussed.
Immigrant nurses' experience of racism.
PURPOSE: To document and describe the experiences of immigrant nurses of colour who have filed grievances concerning their employers' discriminatory practices; and to solicit their views of existing policies and recommendations for equity in professional life. DESIGN AND METHODS: In this descriptive, exploratory study nine immigrant nurses of colour in Ontario, Canada, were interviewed between 1997 and 1998. Data were collected through face-to-face interviews and in focus groups. The discourse theory and methods of van Dijk and Essed were used to analyse the qualitative data. FINDINGS: Recurring themes were: (a) being marginalized and acknowledging and naming the racist experiences; (b) experiencing physical stress and emotional pain; (c) strategizing to cope and survive; (d) recommending policy changes. CONCLUSIONS: All nurses interviewed had experienced reprisals as a result of complaining or filing grievances and unfairness was encountered in the redress process itself. Participants recommended policy initiatives to ensure equity and fair practices in the nursing profession.