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Biomedical subjects

K W Anderson

Publications and source records attributed to K W Anderson.

At least 37 records · Page 2Linked to original sources

Effect of endotoxin on lipid order and motion in erythrocyte membranes.

Electron paramagnetic resonance employing a lipid-specific spin label has been used to investigate the molecular effects of endotoxin on the physical state of bilayer lipids in rat erythrocyte membranes. When added at a concentration as low as 40 micrograms/ml to whole blood (plasma plus leukocytes present), decreased membrane lipid motion was found in subsequently washed and spin-labeled intact erythrocytes (P < 0.02). However, if endotoxin were added to washed, plasma plus leukocyte-free intact erythrocytes, no change in the motion of the spin label was found, suggesting that plasma-soluble substances and/or leukocytes are required to produce the change in the physical state of lipids. The decreased lipid motion found in these studies is discussed with reference to the known decreased deformability of endotoxin-treated red cells and to the pathogenesis of sepsis.

Animals↗

The etiology of psychiatric symptoms in patients with systemic lupus erythematosus.

The purpose of this review was to explore the probable etiologies of psychiatric problems in patients with SLE. Although instances of psychosis generally are attributed to disease pathophysiology, the precise mechanism for this problem remains speculative. The etiology of non-psychotic psychiatric complaints is even less clear. Overall, it is likely that psychiatric complaints in patients with SLE are attributable to numerous factors including acquired brain dysfunction, organ system dysfunction, iatrogenic effects of corticosteroid treatment, learning history, psychosocial stressors, and current coping strategies. Additional research is needed to explore the bi-directional, synergistic, and dynamic interactions among diverse physiological and psychological variables as they impact an individual's psychiatric status.

Adrenal Cortex Hormones↗

In vitro studies of deformation and adhesion properties of transformed cells.

The micropipet aspiration technique and the parallel-plate flow chamber were used to investigate the deformation and detachment properties, respectively, of normal and transformed rat fibroblasts. The normal Cloned Rat Embryo Fibroblasts (CREF) cell line was transfected with the T24 ras oncogene to produce the transformed cell line CREF T24. The CREF T24 cell line was transfected with a Kirsten ras revertant gene (K-rev 1a suppressor) to produce the CT24HKB1 cells, which have the same morphological characteristics as the cells in the CREF line. The cells utilized in this investigation were derived from the parent cell line CREF, the only differences being the presence or absence of the T24 ras oncogene and the Kirsten ras revertant gene. The detachment and deformation properties, therefore, could be related to the metastatic phenotype of the cell rather than inherent differences between disparate cell lines. Results indicated that transfecting the CREF cell line with the ras oncogene greatly modified the detachment and deformation properties. The CREF T24 cells were more easily detached from normal cells and were 50% more deformable. Both CREF and CT24HKB1 showed similar detachment properties. Based on these results, it is speculated that K-rev 1a reversed ras-induced membrane alterations in these cells. Preliminary investigations have demonstrated that both CREF and CREF T24 cells in different phases of the cell cycle differed in morphological characteristics. However, the majority of the cells within a given cell line showed similar deformation characteristics. Current investigations are focusing on characterization of both detachment and deformation properties of these cells as a function of the cell cycle using synchronization techniques.

Animals↗

Maternal alcohol use during breast-feeding and infant mental and motor development at one year.

The detrimental effects of maternal drinking during pregnancy on fetal health have been documented. The consequences for infants of maternal drinking during breast-feeding are unknown, but research in animals suggests that the infant could be affected by exposure to alcohol through the mother's milk. In a study of 400 infants born to members of a health maintenance organization, we investigated the relation of the mother's use of alcohol during breast-feeding to the infant's development at one year of age. Mental development, as measured by the Bayley Mental Development Index (MDI), was unrelated to maternal drinking during breast-feeding. However, motor development, as measured by the Psychomotor Development Index (PDI), was significantly lower in infants exposed regularly to alcohol in breast milk (after alcohol exposure during gestation was controlled for), with a dose-response relation (P for linear trend, 0.006). The infants of breast-feeding mothers who had at least one drink daily had a mean PDI score of 98, whereas the infants exposed to less alcohol in breast milk had a mean PDI score of 103 (95 percent confidence interval for the difference of the two means, 1.2 to 9.8). The effect was more pronounced when mothers who supplemented breast-feeding with formula were excluded from the analysis. The association persisted even after we controlled for more than 100 potentially confounding variables, including smoking and other drug use during pregnancy and in the postpartum period. We conclude that ethanol ingested through breast milk has a slight but significant detrimental effect on motor development, but not mental development, in breast-fed infants.

Adult↗

Solubilization and separation of Ca2+-ATPase from the Ca2+-ryanodine receptor complex.

Heavy sarcoplasmic reticulum (SR) preparations of rabbit skeletal muscle, which are enriched in Ca2+-release vesicles from the terminal cisternae (TC) and [3H]ryanodine receptor density, exhibit 60% of the Ca2+-ATPase activity, 58% of the EP level, and 30% of the steady state Ca2+ loading compared to membrane vesicles from the longitudinal SR. The Ca2+-ATPase of TC SR is solubilized and separated from the Ca2+-ryanodine receptor complex in the insoluble fraction on treatment with the detergent C12E9. However, a 50% decrease in receptor density is observed upon removal of the Ca2+-ATPase, suggesting a significant contribution of this protein to maintaining optimal receptor complex density.

Animals↗

Inhibition of skeletal muscle sarcoplasmic reticulum CaATPase activity by calmidazolium.

Calmidazolium, a lipophilic cation and putative calmodulin-specific antagonist, inhibited potently the calcium ATPase of sarcoplasmic reticulum (SR) vesicles isolated from skeletal muscle. Based on steady-state measurements of catalytic activity over a range of MgATP, calmidazolium, and SR protein concentrations, the calculated values of the inhibition constant (KI) and binding stoichiometry were 0.06 microM and 770 nmol/mg protein, respectively. SR CaATPase inhibition apparently is not a general property of lipophilic cations since the hydrophobic anion tetraphenylboron inhibited catalysis, whereas its cationic analog, tetraphenylarsonium, did not. Enzyme inhibition by calmidazolium was noncompetitive with respect to the substrates Ca2+ and MgATP. In the presence of other SR CaATPase inhibitors, calmidazolium was competitive with respect to quercetin and noncompetitive with respect to trifluoperazine and propranolol. While calmidazolium inhibited enzyme phosphorylation by MgATP, catalysis was more sensitive to the inhibitor. Binding of calmidazolium to SR membranes produced morphological changes seen by electron microscopy as membrane thickening and loss of resolution of surface detail. Our results show that calmidazolium is a high-affinity, noncompetitive inhibitor of skeletal SR CaATPase activity, and they suggest that this inhibition is based on binding to the membrane phospholipids rather than specific antagonism of enzyme activation by calmodulin.

Adenosine Triphosphate↗

Analysis of S-35 labeled WR-2721 and its metabolites in biological fluids.

Studies with WR-2721 and related compounds have been hindered by the lack of a suitable assay for the drug and its major metabolites. We have developed a chromatographic method which requires no derivatization for the separation and detection of WR-2721, the free thiol, its symmetrical disulfide and other mixed disulfides. Our procedure involves ion-pairing for separation of ionizable compounds by causing polar molecules to become more lipophilic and hence separable using reverse phase HPLC. Detection is based upon liquid scintillation counting of S-35 incorporated during the synthesis of the parent compound. This method requires no pre-column preparation of samples and, by detecting the S-35 label, eliminates the chance that a coeluting species could interfere with detection, as might occur with post-column derivatization. Chromatography was done using a 10 micron C8RP column and 35% MeOH/65% 0.0113M NaH2PO4, 0.005 M hexanesulfonate, pH 5.9, flowing at 1 ml/min. Half-minute fractions were collected into scintillation vials for counting. Retention volumes for the various compounds were: column breakthrough (3.5 ml), WR-2721 (4.5 ml), WR-1065 (9 ml), and WR-33278 (24 ml). This analytical technique employing radiotracers can be used to study radioprotective mechanisms by time dependent measurements of the tissue distribution and chemical form of labeled drug. Such chemical information can then be correlated with biological measures of radiation protection.

Amifostine↗

Alterations in the structure of the ribose moiety of ATP reduce its effectiveness as a substrate for the sarcoplasmic reticulum ATPase.

The substrate specificity of the calcium ATPase of isolated sarcoplasmic reticulum vesicles was examined using a series of ribose-modified ATP analogs. Steady state hydrolytic rate measurements using analogs modified at the 2'- and 3'-positions demonstrate that both hydroxyl groups contribute to substrate specificity and high catalytic activity. The 3'-hydroxyl is especially significant in this regard since all analogs modified at the 3'-position were slowly hydrolyzed, if at all, and they did not produce the activation at millimolar concentrations characteristically observed with ATP. In contrast, ATP analogs modified only at the 2'-position were more rapidly hydrolyzed (although at rates less than for ATP), and they did produce activation at millimolar concentrations. These results suggest that neither the catalytic (high affinity) nor the regulatory (low affinity) site of the CaATPase tolerates changes in the hydroxyl substituent at the 3'-position of ATP, whereas steady state rates associated with substrate binding at both types of sites are less affected by changes in the 2'-hydroxyl of ATP.

Adenosine Triphosphatases↗

Development of a computerized drug interaction database (MEDICOM) for use in a patient specific environment.

Drug Interactions are a clearly defined problem that we as health professionals must deal with on a day-by-day basis. It is by far the area of health care that demands more attention today and tomorrow than was possible in the past. The amount of reference sources and text material of drug interactions is growing at such a rate that it is almost impossible to recall essential information in a reasonable time frame. If the practitioner is to continue with an uninterrupted work flow and still maintain the best possible service for the patient, an immediate and accurate method is needed in the hands of the user ... a computerized drug interaction database. The community health care standards would be ultimately raised to a level never before attainable and efficiency would continue with full utilization of professional practice. Combine then, drug interaction data with ancillary benefits such as cost containment, third party accounting, inventory control, and a multitude of other operational functions into a computerized database and the end product results in an enhanced, controlled, professional operation.

Computers↗

Computer-assisted eye examination. VI. Identification and correction of errors in the Refractor III system for subjective examination.

A computer-assisted subjective eye examination was administered to 80 patients. They were also examined in the conventional manual way. The results of the computer-assisted examination were compared with those obtained by conventional subjective methods to identify errors of hardware, software, and optometric flow charting and other problems. An 87.5% satisfactory prescription level was found for the distance prescription. The 12.5% unsatisfactory results are accounted for by several kinds of error. The percentage of unsatisfactory refractive results was greater for near than for distance measures because of special flow-chart and software problems, which were subsequently corrected. With implementation of the changes initiated as a result of this investigation, satisfactory refractive results approaching 95% can be expected.

Adolescent↗