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Biomedical subjects

J K Anderson

Publications and source records attributed to J K Anderson.

At least 19 recordsLinked to original sources

Observation of velocity-independent electron transport in the reversed field pinch.

Confinement of runaway electrons has been observed for the first time in a reversed field pinch during improved-confinement plasmas in the Madison Symmetric Torus. Energy-resolved hard-x-ray flux measurements have been used to determine the velocity dependence of the electron diffusion coefficient, utilizing computational solutions of the Fokker-Planck transport equation. With improved-confinement, the fast electron diffusivity drops by 2 orders of magnitude and is independent of velocity. This suggests a change in the transport mechanism away from stochastic magnetic field diffusion.

Journal Article↗

Electron heat transport measured in a stochastic magnetic field.

New profile measurements have allowed the electron thermal diffusivity profile to be estimated from power balance in the Madison Symmetric Torus where magnetic islands overlap and field lines are stochastic. The measurements show that (1) the electron energy transport is conductive not convective, (2) the measured thermal diffusivities are in good agreement with numerical simulations of stochastic transport, and (3) transport is greatly reduced near the reversal surface where magnetic diffusion is small.

Journal Article↗

Core electrostatic fluctuations and particle transport in a reversed-field pinch.

Potential and electron-density fluctuation profiles, phi(r) and ñ(e)(r)/n(e), are measured for the first time in the core of a reversed-field pinch using a heavy ion beam probe. It is found that the fluctuations are broadband and correlated with the core resonant m/n=1/6 tearing mode. The electrostatic-fluctuation-induced particle transport in the core of standard RFP plasmas, estimated from measured <ñ(e)phi>, is small compared to the total particle flux. Measurements of fluctuations and estimates of fluctuation induced particle transport in improved confinement RFP discharges are also presented.

Journal Article↗

Measurement of the current-density profile and plasma dynamics in the reversed-field pinch.

First measurements of the current-density profile in the core of a high-temperature reversed-field pinch are presented. The current-density profile is observed to peak during the sawtooth cycle and broaden promptly at the crash. This change in profile can be linked to magnetic relaxation and the dynamo which is predicted to drive antiparallel current in the plasma core. For high-confinement discharges, the dynamo is suppressed and the current-density profile is observed to strongly peak.

Journal Article↗

A prospective, randomized clinical trial of universal WBC reduction.

BACKGROUND: Recipient exposure to allogeneic donor WBCs results in transfusion complications for selected populations of recipients. Whether or not WBC reduction should be universally applied is highly controversial. STUDY DESIGN AND METHODS: In a general hospital, a randomized, controlled clinical trial of conversion to universal WBC reduction was conducted. Patients (11%) with established medical indications for WBC-reduced blood were not eligible. All other patients who required transfusion were assigned at random to receive either unmodified blood components or stored WBC-reduced RBCs and platelets. Analysis for each patient was restricted to the first hospitalization. RESULTS: All eligible patients (n = 2780) were enrolled. Three specified primary outcome measures were not different between the two groups: 1) in-hospital mortality (8.5% control; 9.0% WBC-reduced; OR, 0.94 [95% CI, 0.72-1.22]; p = 0.64); 2) hospital length of stay (LOS) after transfusion (median number of days, 6.4 for control and 6.3 for WBC-reduced; p = 0.21); and 3) total hospital costs (median, $19,500 for control and $19,200 for WBC-reduced, p = 0.24). Secondary outcomes (intensive care LOS, postoperative LOS, antibiotic usage, and readmission rate) were not different between the two groups. Subgroup analysis based on patient age, sex, amount of blood transfused, or category of surgical procedure showed no effect of WBC reduction. Patients who received WBC-reduced blood had a lower incidence of febrile reactions (p = 0.06). CONCLUSION: A beneficial effect of conversion from selective to universal WBC reduction was not demonstrated.

Adolescent↗

Reduced edge instability and improved confinement in the MST reversed-field pinch.

Improved confinement has been achieved in the MST through control of the poloidal electric field, but it is now known that the improvement has been limited by bursts of an edge-resonant instability. Through refined poloidal electric field control, plus control of the toroidal electric field, we have suppressed these bursts. This has led to a total beta of 15% and a reversed-field-pinch-record estimated energy confinement time of 10 ms, a tenfold increase over the standard value which for the first time substantially exceeds the confinement scaling that has characterized most reversed-field-pinch plasmas.

Journal Article↗

Long-term follow-up of living kidney donors: quality of life after donation.

The University of Minnesota has been a strong advocate of living donor kidney transplants. The benefits for living donor recipients have been well documented. The relative low risk of physical complications during donation has also been well documented. Less well understood is the psychosocial risk to donors. Most published reports have indicated an improved sense of well-being and a boost in self-esteem for living kidney donors. However, there have been some reports of depression and disrupted family relationships after donation, even suicide after a recipient's death. To determine the quality of life of our donors, we sent a questionnaire to 979 who had donated a kidney between August 1, 1984, and December 31, 1996. Of the 60% who responded, the vast majority had an excellent quality of life. As a group, they scored higher than the national norm on the SF-36, a standardized quality of life health questionnaire. However, 4% were dissatisfied and regretted the decision to donate. Further, 4% found the experience extremely stressful and 8% very stressful. We used multivariate analysis to identify risk factors for this poor psychosocial outcome and found that relatives other than first degree (odds ratio=3.5, P=0.06) and donors whose recipient died within 1 year of transplant (odds ratio=3.3, P=0.014) were more likely to say they would not donate again if it were possible. Further, donors who had perioperative complications (odds ratio=3.5, P=0.007) and female donors (odds ratio=1.8, P=0.1) were more likely to find the overall experience more stressful. Overall, the results of this study are overwhelmingly positive and have encouraged us to continue living donor kidney transplants.

Adolescent↗

Plateletpheresis in 90- to 110-pound donors using the CS-3000 blood cell separator.

BACKGROUND: Increases in the use of single-donor apheresis components have increased the need for platelet donors. In the United States, persons must weigh 110 pounds or more to qualify as blood donors, and the same weight limitation has been placed on apheresis donors. Because automated plateletpheresis with some instruments differs considerably from whole-blood donation with respect to the volume of blood removed from the donor, the feasibility of using persons weighing between 90 and 110 pounds as platelet donors was evaluated by the use of the CS-3000 blood cell separator. STUDY DESIGN AND METHODS: The study was performed using female subjects who met all usual donor requirements except for minimum weight. The standard platelet collection procedure of the instrument was used, except that the blood processing rate was manually selected so as to optimize the blood withdrawal and return rate in individuals. Vital signs were recorded before and after donation as were signs or symptoms of any type of donor reaction. RESULTS: Twenty-six of 28 women completed the donation procedure; in two instances, collection was terminated prematurely because of an inability to maintain adequate venous access. An average of 4.5 x 10(11) platelets were collected during a mean donation time of 110 minutes. All donors tolerated the procedure well, and no serious adverse reactions were seen. Because of the administration of priming solution and anticoagulant during apheresis, there was a net positive fluid balance following the procedure, in spite of the removal of approximately 220 mL of platelet concentrate. CONCLUSION: These preliminary studies suggest that 90- to 110-pound persons may serve as plateletpheresis donors. Additional studies are needed to more fully document the safety and efficacy of this approach. The use of lower-weight donors may significantly increase the number of persons available to provide single-donor platelet components.

Blood Donors↗

A prospective, randomized study of the use of platelet concentrates irradiated with ultraviolet-B light in patients with hematologic malignancy.

BACKGROUND: Irradiation of platelet concentrates (PCs) with ultraviolet-B (UVB) light inactivates the contaminating white cells and might be an alternative to filtration for the prevention of alloimmunization to HLA antigens and subsequent refractoriness to further platelet transfusions in multiply transfused patients with bone marrow failure. STUDY DESIGN AND METHODS: Patients with hematologic malignancy, mainly acute myeloid leukemia, were prospectively assigned in a random manner to receive either UVB-irradiated or control, nonirradiated PCs. All patients were given red cells that were white cell reduced by filtration. Transfusion efficacy and alloimmunization were assessed by means of corrected count increments, requirement for red cells and PCs, and measurement of lymphocyte-reactive antibodies. RESULTS: UVB-irradiated PCs had a clinical efficacy similar to controls as judged by corrected count increments at 1 to 6 and 12 to 24 hours and by the median requirement for red cell and platelet transfusions. Alloimmunization determined by measurements of lymphocyte-reactive antibodies using both conventional and antiglobulin-augmented lymphocytotoxicity techniques was not abolished in recipients of UVB-irradiated PCs (4/30, 13%) but was less than that in controls (5/20, 25%; p = NS). The mean number of platelet transfusion episodes prior to the occurrence of alloimmunization was greater in the control group (27 vs. 10; p = 0.017). CONCLUSION: In this trial, UVB irradiation did not diminish the clinical efficacy of platelet transfusions. There was a small but nonsignificant reduction alloimmunization, but no difference in refractoriness of the two groups was observed. Larger prospective randomized studies are required to confirm these findings and to compare UVB irradiation with white cell reduction.

Adolescent↗

Cloning and molecular analysis of the Salmonella enterica ansP gene, encoding an L-asparagine permease.

A gene (ansP), which encodes an L-asparagine permease, has been isolated from a cosmid library of Salmonella enterica during screening for recombinant clones which encode L-asparaginase. Nucleotide sequence analysis reveals that the gene product is a polypeptide of 497 amino acid residues, containing 12 putative transmembrane segments. The calculated molecular mass is 54 kDa, although maxicell analysis by SDS-PAGE gave an apparent molecular mass of 37 kDa. Comparison of the deduced amino acid sequence with sequence databases showed significant homology with a family of basic and aromatic amino acid permeases. Strains containing the cloned ansP gene demonstrated a many-fold increase in L-asparagine uptake in comparison with control strains.

Amino Acid Sequence↗

Human stomach class IV alcohol dehydrogenase: molecular genetic analysis.

A partial human stomach alcohol dehydrogenase (ADH) encoding cDNA has been isolated, cloned, and sequenced, which contains 222 nucleotides encoding amino acid residues 227-299 of the ADH subunit. The amino acid sequence deduced from this cDNA was highly homologous with the rat stomach class IV ADH sequence recently reported (81.1% sequence identity). Homology with other human ADH classes was also observed: class I, 58.1% sequence identity; class II, 39.2% sequence identity; class III, 55.4% sequence identity; and class V, 50.0% sequence identity. These results support a proposal that the isolated cDNA encodes a partial sequence for human stomach class IV ADH. This sequence retains val294 for all other human ADH classes reported, as compared with an ala294 at this position reported for rat class IV ADH. This ala residue may contribute to the very high Km values with ethanol for the latter enzyme. In addition, three substitutions are reported for key residues in the coenzyme binding site: 251, gln/ser; 260, gly/asn; and 261, gly/asn, which may contribute to the weak coenzyme binding properties reported for human class IV ADH.

Alcohol Dehydrogenase↗

Chlorpyrifos oxon binds directly to muscarinic receptors and inhibits cAMP accumulation in rat striatum.

Although the acute effects of organophosphorus esters are generally ascribed to inhibition of acetylcholinesterase, work in this laboratory and others indicates that organophosphorus insecticides also interact directly with cholinergic receptors. The current study verifies that the insecticide O,O-diethyl O-3,5,6-trichloro-2-pyridinyl phosphorothionate (chlorpyrifos) and its oxon metabolite inhibits acetylcholinesterase (AChE). The metabolite inhibits rat brain AChE three orders of magnitude more rapidly than chlorpyrifos. In addition to their ability to inhibit AChE, these compounds were shown to interact directly with muscarinic receptors of rat striatum. The oxon metabolite bound at low concentrations to muscarinic receptors labeled by the muscarinic agonist [3H] cis-methyldioxolane; chlorpyrifos oxon bound with an IC50 value of 22.1 +/- 3.6 nM. The receptors bound by chlorpyrifos oxon account for approximately 30% of muscarinic receptors of the striatum and are of the m2 subtype. The binding of chlorpyrifos oxon to the m2 receptor results in a covalent modification of the receptor that does not interfere with the ability of the receptor to interact with the agonist carbachol. This receptor modification may be responsible for the inhibition of adenylate cyclase activity by chlorpyrifos oxon. The oxon inhibited adenylate cyclase with an IC50 of 155 +/- 78 nM. The inhibition of adenylate cyclase activity was not blocked by atropine and was additive to that produced by carbachol. The altering of postreceptor signal transduction by chlorpyrifos oxon may interfere with normal cellular signaling, thereby disturbing neurological function. Direct interaction of chlorpyrifos oxon with muscarinic receptors and associated signal transduction is a potential mechanism of neurotoxicity that is independent of AChE inhibition.

Adenylyl Cyclase Inhibitors↗

Role of N-terminal domain of histidine-rich glycoprotein in modulation of macrophage Fc gamma receptor-mediated phagocytosis.

A brief exposure of murine peritoneal inflammatory macrophages to plasma histidine-rich glycoprotein (HRG; 77,000-81,000 MW) for 1-2 hr increased Fc gamma receptor (Fc gamma R) expression and phagocytic function in these cells. However, a continual culture of the cells without the presence of HRG for the next 18-48 hr resulted in down-regulation of Fc gamma R expression and phagocytic function. Similarly, HRG decreased Fc gamma RII expression in less differentiated human THP-1 monocytic cells during treatment for 18 hr, as determined by cellular ELISA and metabolic labelling. The molecular mechanism by which HRG regulates Fc gamma R expression is unknown. However, at a relatively high concentration (> 1 microgram/ml), HRG altered the cellular metabolism by increasing cellular protein synthesis but reducing protein secretion. These observations suggest a likely mechanism for the HRG-mediated reduction of Fc gamma R expression. A degraded HRG (40,000 MW) which possessed an identical N-terminal sequence as that of the native HRG was capable of decreasing macrophage Fc gamma R expression and phagocytosis. The results indicate that the functional domain of HRG responsible for binding to macrophages is localized to the N-terminal half.

Animals↗

Effects of a protective foam on scrubbing and gloving.

OBJECTIVE: To test the effects of a skin protectant on surgical scrub and glove integrity. DESIGN: Forty-nine healthy adult volunteers were assigned (12 subjects per group) to apply a protective foam (DermaMed; Benchmark Enterprises, Salt Lake City, Utah) in conjunction with surgical scrub in one of the following formulations: 70% isopropyl alcohol, a liquid detergent base containing 4% chlorhexidine gluconate, a liquid detergent base containing 7.5% povidone-iodine, or a nonantimicrobial liquid soap (control). According to a standard protocol, subjects performed a surgical scrub on 3 days (every other day). Foam was applied after surgical scrub on day 1 and before surgical scrub on day 3. No foam was applied on day 2. Subjects were gloved for 2 hours after surgical scrub. SETTING: Laboratory setting. RESULTS: On all test days, there were significant differences in bacterial reduction by products (chlorhexidine gluconate or alcohol > povidone-iodine > control). When controlling for baseline counts and products used, there were no significant differences in colony-forming unit counts on hands with or without foam immediately after scrubbing or at 2 hours after scrub on gloved or ungloved hands, nor were there differences in glove leakage rates when foam was on hands. CONCLUSIONS: Such protectants can be used without detrimental effects to scrub effectiveness or glove integrity.

1-Propanol↗

Enhanced calmodulin binding concurrent with increased kinase-dependent phosphorylation of cytoskeletal proteins following a single subcutaneous injection of diisopropyl phosphorofluoridate in hens.

Diisopropyl phosphorofluoridate (DFP) produces Type I organophosphorus compound-induced delayed neurotoxicity (OPIDN) in adult female chickens. We have proposed that calcium/calmodulin protein kinase II (CaM kinase II) plays a role in the development of OPIDN by increasing the phosphorylation of cytoskeletal proteins. We investigated in vivo the effects of treatment of DFP on CaM kinase II-dependent phosphorylation. In isolated brain supernatants from DFP-treated hens, calmodulin binding increased concurrent with increases in CaM kinase II-dependent autophosphorylation and phosphorylation of cytoskeleton proteins. There were no changes in the relative amounts of the enzyme based on immunobinding studies of antibodies to the CaM kinase II. In the absence of any exogenously added substrate. CaM kinase II and microtubule associated protein-2 (MAP-2) exhibited substantially increased phosphorylation, 833 and 275%, respectively, over brain supernatants from untreated hens. Moreover, isolated brain supernatants from treated hens with exogenously added cytoskeletal proteins and myelin basic protein (MBP) exhibited significant increases in phosphorylation over control, 233, 332 and 60%, for MAP-2, tubulin, and MBP, respectively. 125I-Calmodulin binding studies revealed a 136% increase in calmodulin binding to CaM kinase II in treated hens when compared to control groups. The data suggest that in vivo DFP treatment increases the percentage of unphosphorylated, active CaM kinase II resulting in increased calmodulin binding and subsequent enhanced phosphorylation of cytoskeletal proteins that leads to their aggregation and the production of axonal degeneration.

Animals↗

Regulation of complement functional efficiency by histidine-rich glycoprotein.

The modulation of complement functional efficiency by serum histidine-rich glycoprotein (HRG) was investigated. Addition of exogenous HRG to prewarmed diluted serum, followed immediately by sensitized sheep erythrocytes (EA), resulted in enhanced hemolysis. However, when HRG was incubated with diluted serum for 10 minutes at 37 degrees C, inhibition of hemolysis occurred. The biphasic modulation of complement function was also obtained with the complement alternative pathway when HRG was added to diluted serum for hemolysis of rabbit erythrocytes. Partial reduction of complement functional activity was shown when serum was absorbed by an HRG-Sepharose 6MB column. Western blot analysis showed that complement C8, C9, factor D, and S-protein in diluted serum were bound by nylon membrane-immobilized HRG. However, by immunoprecipitation of relatively undiluted serum with anti-HRG IgG beads, HRG was found to coprecipitate with S-protein and plasminogen, which suggested that HRG may complex with these proteins in serum. In functional tests, HRG inhibited C8 hemolytic activity, probably by preventing C8 binding to EAC1-7 cells. HRG also enhanced polymerization of purified C9 as well as the generation of a 45-Kd C9 fragment. Such an effect was even more pronounced in the presence of divalent cations with the reaction mixtures of C9 and HRG. Partial dimerization of C9 was shown when exogenous HRG was added to normal serum. In contrast, polymerization of serum C9 was inhibited by exogenous HRG during poly I:C activation of serum or incubation under low ionic strength conditions. HRG was further shown to inhibit factor D-mediated cleavage of factor B when bound by cobra venom factor. The molecular basis by which HRG regulates serum complement function is not clear. Hypothetically, the tandem repetitions of a consensus histidine-rich penta-peptide sequence in HRG may provide a highly charged area that interacts with complement components.

Animals↗

Anomalous phosphorylated neurofilament aggregations in central and peripheral axons of hens treated with tri-ortho-cresyl phosphate (TOCP).

Previous biochemical studies demonstrated a dramatic increase in phosphorylation of cytoskeletal proteins that occurs early in organophosphorus ester-induced delayed neurotoxicity (OPIDN). In this report we present immunohistochemical evidence that there is anomalous aggregation of phosphorylated neurofilaments within central and peripheral axons following organophosphate exposure. The morphology, location, and time of appearance of these aggregations are consistent with the hypothesis that the aberrant phosphorylation of cytoskeletal elements is an antecedent to the focal axonal swelling and degeneration characteristic of OPIDN.

Animals↗