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Biomedical subjects

D L Anderson

Publications and source records attributed to D L Anderson.

At least 55 records · Page 3Linked to original sources

Giant fibrovascular polyps of the esophagus.

A 77-yr-old man with chest discomfort and progressive dysphagia was found to have an intraluminal esophageal lesion of remarkable size. A giant fibrovascular polyp (11 x 7 x 3.5 cm) was successfully removed surgically by a transcervical approach. This unusual benign esophageal lesion is discussed in terms of classification and clinical presentation from a historical perspective. Particular attention is focused on the current approach to diagnosis and management. Endoscopic ultrasonography was employed as part of the evaluation.

Aged↗

Cholera toxin inhibits resting human T cell activation via a cAMP-independent pathway.

The catalytic subunit of cholera toxin (CT) can chemically modify the alpha polypeptides of certain G-binding proteins and thus alter their function. In order to study the involvement of CT-sensitive G proteins in T cell activation, we have utilized CT in an in vitro system in which purified, resting human peripheral T cells are activated by anti-CD3 antibodies and rIL-2. Perturbation of the TCR/CD3 molecular complex by anti-CD3 antibodies causes changes in membrane phospholipids and induces a rise in cytoplasmic Ca2+. These events, however, are insufficient to allow progression into cellular proliferation and addition of IL-2 is required. Under these conditions, treatment of cells with a low concentration of CT (2 ng/ml) causes a significant inhibition of the anti-CD3-induced calcium event as well as the anti-CD3 plus IL-2-stimulated proliferation. Under our experimental conditions, inhibition of both proliferation and intracellular Ca2+ elevation by CT requires the involvement of the TCR/CD3 complex. This is supported by the observation that the toxin does not inhibit either the proliferation triggered by ionomycin and PMA or the Ca2+ influx induced by the ionophore. These data suggest that in TCR/CD3-mediated T cell activation CT acts at a point between TCR/CD3 perturbation and the generation of intracellular Ca2+. In view of the ability of CT to activate the alpha subunit of the G protein that stimulates adenyl cyclase (G alpha s), it is possible that the effect of CT on T cells is secondary to intracellular elevation of cAMP. However, measurement of cAMP levels both early after CT addition and at later time points, when proliferation is maximal, reveals lack of cyclic nucleotide accumulation. The presented data are consistent with the interpretation that the CT-mediated inhibition is caused by the modification of a G-binding protein that is either directly or indirectly associated with triggering of T cells via the TCR/CD3 molecular complex. The data also suggest that this protein is not G alpha s and it probably represents an as yet unidentified moiety or one of the several G proteins that have been recently described as regulators of phospholipase C activation.

Antibodies, Monoclonal↗

Phosphorylation of the insulin receptor in permeabilized adipocytes is coupled to a rapid dephosphorylation reaction.

Phosphorylation and dephosphorylation of the insulin receptor were examined in permeabilized rat adipocytes using pulse-chase techniques. Maximum insulin-dependent phosphorylation during a 2-min labeling period with 75 microM [gamma-32P]ATP was attained at 10(-6)-10(-7) M insulin with a small effect at 10(-9) M. The reaction utilized either Mn2+ or Mg2+, but insulin-dependent phosphorylation was 11-fold greater with Mn2+. In the absence of insulin, phosphorylation was 6-fold greater with Mn2+. With either cation, insulin (10(-7) M) was a potent stimulator of receptor phosphorylation with 5- and 8-fold increases above control levels in the presence of Mg2+ and Mn2+, respectively. Phosphorylation of the insulin receptor reached an apparent steady state within 30 s at 37 degrees C under all conditions. By phosphoamino acid analysis, all insulin- and Mn2+-dependent phosphorylation in the 95-kDa subunit of the insulin receptor was phosphotyrosine. A small amount of phosphoserine was detected, but it was not affected by either insulin or Mn2+. Dephosphorylation of the insulin receptor was examined by "chasing" labeled ATP after 2 min with a 40-fold excess of unlabeled ATP. Maximum dephosphorylation was reached in 2 min under all conditions. Insulin had no effect on the dephosphorylation reaction. The labile fraction of Mn2+-dependent phosphoreceptor dephosphorylated to one-half of its initial level in approximately 21 s at 37 degrees C. Vanadate, a potent phosphotyrosine phosphatase inhibitor, inhibited dephosphorylation of this phosphoreceptor by 25%. When vanadate was present during the 2-min labeling period, phosphorylation of control, and insulin-dependent receptor was increased by 50%. In summary, rapid "in vitro" autophosphorylation of the insulin receptor is coupled to an equally rapid dephosphorylation reaction in permeabilized adipocytes. This suggests that phosphorylation of the insulin receptor is a dynamic, rapidly reversible, insulin-dependent response in target cells and is consistent with it being involved in insulin signal transduction and insulin action.

Adipose Tissue↗

Prospective, randomized trial of rapid venous access for patients in hypovolemic shock.

The placement of central venous catheters was studied prospectively in 138 selected adult patients with hypovolemic shock or in whom rapid volume replacement was needed. The patients were randomized into two groups to receive a central vein catheter: one by basilic vein cutdown and the other by percutaneous subclavian vein placement. The groups were analyzed for success rate, time required for insertion, and complications. The techniques were equally successful (87% in the basilic vein group compared with 91% in the subclavian vein group), and their complication rates were similar (10% compared with 12%). The subclavian vein catheter was inserted more quickly (8.3 minutes compared with 14.4 minutes [P = .0001] for the basilic vein group). Percutaneous subclavian vein catheters can be used successfully in patients with hypovolemic shock and can be place quickly with low complication rates.

Catheterization, Central Venous↗

Search for deep slabs in the Northwest Pacific mantle.

A residual sphere is formed by projecting seismic ray travel-time anomalies, relative to a reference Earth model, onto an imaginary sphere around an earthquake. Any dominant slab-like fast band can be determined with spherical harmonic expansion. The technique is useful in detecting trends associated with high-velocity slabs beneath deep earthquakes after deep-mantle and near-receiver effects are removed. Two types of corrections are used. The first uses a tomographic global mantle model; the second uses teleseismic station averages of residuals from many events over a large area centered on the events of interest. Under the Mariana, Izu-Bonin, and Japan trenches, the dominant fast bands are generally consistent with seismicity trends. The results are unstable and differ from the seismicity trend for Kurile events. The predominant fast band for most deep earthquakes under Japan is subhorizontal rather than near vertical. We find little support for the deep slab penetration hypothesis.

Journal Article↗

Colchicine toxicity: a case report.

A 59-year-old male was admitted to the Intensive Care Unit from the Emergency Department approximately 12 hr after the ingestion of 30 to 40 mg of colchicine, TYLENOL with codeine, IMODIUM, DESYREL and ethanol. He suffered severe systemic manifestations and succumbed approximately 36 hr post-ingestion. Although this is a case of a mixed ingestion, the complications seen suggest that colchicine was responsible for the fatality.

Acetaminophen↗

Genetic variation in the blood of llamas, Llama glama, and alpacas, Llama pacos.

Blood samples of llamas and alpacas were typed using haemolytic, electrophoretic and isoelectric focusing procedures to assay polymorphism at 13 loci. Blood group variation was assessed using six antibody specificities produced by allo- and heteroimmunizations. Two red cell factors (A and B) behave as autosomal, codominant alleles at a closed A locus. The other four factors (C, D, E and F) behave as autosomal, dominant traits. Biochemical variation was found for red cell enzymes catalase, phosphogluconate dehydrogenase, glucose phosphate isomerase and for plasma proteins transferrin and post-albumin. No variants were found for haemoglobin, phosphoglucomutase and albumin. Estimates of probability of exclusion were 0.883 for llamas and 0.681 for alpacas, which are adequate initial levels of efficacy for purposes of parentage verification. Preliminary estimate of Nei's genetic distance measure (D) suggests that llamas and alpacas are more likely related as subspecies than as separate species.

Alleles↗

Effect of polyethylene glycol-superoxide dismutase and catalase on endotoxemia in pigs.

We hypothesized that superoxide anion (O2-.) and hydrogen peroxide (H2O2) might be important mediators of endotoxin-induced acute respiratory failure (ARF) in pigs. As specific scavengers of O2-. and H2O2, we infused polyethylene glycol-superoxide dismutase (PEG-SOD; 2,000 IU/kg) and PEG-catalase (CAT; 15,000 IU/kg), respectively. Escherichia coli endotoxin (055-B5) was infused intravenously into anesthetized 10- to 14-wk-old pigs at 5 micrograms/kg the 1st h, followed by 2 micrograms.kg-1.h-1 for 3.5 h. During phase 1 (i.e., 0-2 h) and 2 (i.e., 2-4.5 h), endotoxin decreased cardiac index (CI) and lung dynamic compliance, and increased mean pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), total peripheral resistance (TPR), alveolar-arterial O2 gradient, and hematocrit. Endotoxemia also caused granulocytopenia and increased the postmortem bronchoalveolar lavage fluid (BALF) albumin concentration and wet-to-dry ratio of bloodless lung. During endotoxemia, PEG-SOD failed to significantly alter any measured or calculated parameter. On the other hand, PEG-CAT attenuated the early (i.e., 0-1 h) endotoxin-induced decrease in CI and increases in Ppa, PVR, and TPR, but failed to modify these parameters during phase 2. PEG-CAT also attenuated the endotoxin-induced granulocytopenia and the increased BALF albumin concentration. In the presence of inactivated PEG-CAT, these protective effects were reversed. We conclude that O2-. does not directly contribute to endotoxin-induced lung injury and that H2O2 (or a subsequent metabolite) contributes to the early endotoxin-induced hemodynamic changes, granulocytopenia, and increased permeability of the alveolar-capillary membrane.

Animals↗

Dimethylthiourea attenuates endotoxin-induced acute respiratory failure in pigs.

We hypothesized that toxic O2 radicals might be important mediators of endotoxin-induced acute respiratory failure in pigs. As a relatively specific scavenger of .OH, we infused dimethylthiourea (DMTU, 1 g/kg) before endotoxemia. Escherichia coli endotoxin (055-B5) was infused intravenously into anesthetized 10- to 14-wk-old pigs at 5 micrograms/kg the 1st h, followed by 2 micrograms.kg-1.h-1 for 3.5 h. During phase 1 (i.e., 0-2 h) and phase 2 (i.e., 2-4.5 h), endotoxin decreased cardiac index (CI) and increased mean pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), alveolar-arterial O2 gradient (AaDo2), and hematocrit (Hct). Endotoxemia also caused leukopenia and increased the postmortem bronchoalveolar lavage fluid (BALF) albumin concentration and wet weight-to-dry weight ratio of bloodless lung. Dimethylthiourea did not significantly modify the phase 1 response. However, during phase 2, DMTU attenuated the endotoxin-induced decrease in CI and increases in Ppa, PVR, Hct, AaDo2, lung water, and BALF albumin concentration. In separate groups of endotoxin- and DMTU + endotoxin-treated pigs, lung microvascular hydrostatic pressure was increased to approximately 16 Torr (by fluid overload) to assess alveolar-capillary membrane permeability. Under these conditions, DMTU markedly attenuated the endotoxin-induced increase in alveolar-capillary membrane permeability. Under these conditions, DMTU markedly attenuated the endotoxin-induced induced increase in alveolar-capillary membrane permeability. We conclude that .OH (and possibly H2O2) significantly contributes to endotoxin-induced lung injury in anesthetized pigs.

Acute Disease↗

Depressive symptoms and persistence in treatment for alcohol dependence.

The relationship between alcoholics' depressive symptoms during their preadmission evaluations and persistence in treatment for alcohol dependence is evaluated. Hierarchical multiple regression was used to determine the contribution of Beck Depression Inventory (BDI) scores to the prediction of the criterion: number of continuous days in treatment (up to 120). After several sources of variance were removed (age, race, age X race interaction, number of previous treatments and referral source), BDI score explained 10.8% of the criterion's variance. The full model explained 28.2%. Early withdrawal occurred in association with freedom from measurable affective distress during preadmission evaluation. A model for the prediction of number of continuous days in treatment is presented.

Adult↗

Production of sheep-goat chimeras by inner cell mass transplantation.

Embryos were surgically flushed from goats and sheep on d 6 and 7, respectively, following the first day of estrus (d 0). After enzymatic removal of the zonae pellucidae, inner cell masses were isolated from caprine blastocysts by immunosurgery. The intact inner cell masses were injected into ovine blastocysts with the aid of a micromanipulator. Twenty-two manipulated blastocysts were surgically transferred into 12 ovine recipients. Nine ewes gave birth to a total of 13 young (59% embryo survival). Ten were classified by serum electrophoretic assays or karyotypes as lambs, one as a kid, and two as interspecific chimeras.

Animals↗

Botulism: emotional impact on patient and family.

During the third largest outbreak of botulism reported in the United States, affective responses of patients and their family members were assessed to monitor and compare the emotional distress experienced by the two groups during the initial, acute phase of the life-threatening illness. Ratings of 12 patients and 16 family members indicated that family members were significantly more fearful and depressed than patients during the first week and as fearful and depressed as patients during the second week of hospitalization/treatment. Anxiety and helplessness decreased significantly in both groups by week 2. Results illustrate the impact of catastrophic illness on the entire family system and provide support for the utility of family-oriented, crisis interventions. In future outbreaks of catastrophic illness, the early identification of emotional distress and informational needs and provision of appropriate counselling to family members as well as patients may be clinically indicated and valuable in facilitating the coping process.

Adult↗

Effects of ketanserin on pulmonary hemodynamics, lung mechanics, and gas exchange in endotoxemic pigs.

The effects of ketanserin on pulmonary hemodynamics, lung mechanics, and gas exchange were determined in anesthetized 10- to 14-week-old pigs after they were endotoxemic for 1 or 4.5 hours. Saline solution was given to controls (group 1). Escherichia coli endotoxin (055-B5) was infused IV at a dosage of 5 micrograms/kg for 1 hour (group 2). In group 3, endotoxin was infused at 5 micrograms/kg the first hour plus a continuous infusion of endotoxin at 2 micrograms/kg/hr. Ketanserin, a specific serotonin receptor antagonist, was infused IV (300 micrograms/kg) after pigs were endotoxemic for 1 or 4.5 hours (groups 2 and 3, respectively). At 1 hour of endotoxemia, mean pulmonary artery pressure and pulmonary vascular resistance were increased, and cardiac index was decreased. Ketanserin caused a small attenuation of the increases in mean pulmonary artery pressure and pulmonary vascular resistance, indicating that serotonin may have a small role in the endotoxin response at 1 hour. At 4.5 hours of endotoxemia, mean pulmonary artery pressure, pulmonary vascular resistance, alveolar dead space ventilation, and alveolar-arterial oxygen gradient were increased, and cardiac index and lung dynamic compliance were decreased; ketanserin significantly attenuated the endotoxin-induced changes in cardiac index, mean pulmonary artery pressure, pulmonary vascular resistance, and lung dynamic compliance. Ketanserin also decreased the blood temperature after pigs were endotoxemic for 4.5 hours. However, the endotoxin-induced increases (at 4.5 hours) in alveolar-arterial oxygen gradient and alveolar dead space ventilation were not acutely reversed by ketanserin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Morphogenesis of bacteriophage phi 29 of Bacillus subtilis: prohead restoration for DNA-gp3 packaging and assembly.

The DNA-protein complex DNA-gp3 of phi 29 is efficiently packaged into purified proheads with the aid of plasmid-derived gp16. The filled heads can be assembled to phage by addition of an extract providing the products for neck-tail assembly (Bjornsti et al., J. Virol. 50:766-772, 1984). However, purified proheads lost their competence to package DNA-gp3 upon storage for 2 months at 4 degrees C. Competence was restored by complementation with extracts of certain mutant-infected cells, and these experiments demonstrated that late proteins were not involved; restoration obtained with 4-8-14--infected cells was indistinguishable from that obtained with 7-8-14--infected cells. 2-8-14- and 3-8-14- extracts restored about one-third of the capacity to package exogenous DNA-gp3. A 1-8-14- extracts restored activity to package 20.6% of the DNA-gp3 added, but phage were not produced.

Bacillus subtilis↗

Dexamethasone and indomethacin modify endotoxin-induced respiratory failure in pigs.

We studied the porcine pulmonary response to endotoxemia before and after administration of nonsteroidal antiinflammatory drugs (NSAID, i.e., indomethacin or flunixin meglumine) or dexamethasone (DEX). Escherichia coli endotoxin was infused intravenously into anesthetized 10- to 12-wk old pigs for 4.5 h. In endotoxemic pigs, the phase 1 (i.e., 0-2 h) increases in pulmonary arterial pressure, pulmonary vascular resistance (PVR), and alveolar-arterial O2 gradient and the decreases in cardiac index (CI) and lung dynamic compliance (Cdyn) were blocked by NSAID. Thus phase 1 changes were cyclooxygenase dependent. Furthermore, these effects were blocked or greatly attenuated by DEX. During phase 2 of endotoxemia (i.e., 2-4.5 h), the increased PVR and decreased CI and Cdyn were not blocked by NSAID but were attenuated by DEX, suggesting the presence of cyclooxygenase-independent metabolites. Both NSAID and DEX blocked the endotoxin-induced increases in lung water, bronchoalveolar lavage (BAL) neutrophil, and BAL albumin content. The fall in plasma proteins persisted in NSAID but not DEX-treated pigs. We conclude that endotoxemia in the pig causes severe acute respiratory failure largely mediated by cyclooxygenase and possibly lipoxygenase products of arachidonic acid metabolism.

Animals↗

Effects of flunixin meglumine on cardiopulmonary responses to endotoxin in ponies.

The effects of endotoxemia on cardiopulmonary parameters, before and after cyclooxygenase blockade, were determined in anesthetized ponies spontaneously breathing a mixture of halothane and 100% O2. Escherichia coli endotoxin was infused intravenously at 20 micrograms/kg for 1 h followed by 10 micrograms X kg-1 X h-1 the subsequent 4 h. By 15 min endotoxin increased mean pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), and alveolar dead space ventilation (VDA/VT), and these were followed by a return to base-line values by 30 min. A second increase in PVR occurred by 5 h of endotoxemia. The early increases in Ppa, PVR, and VDA/VT were blocked by flunixin meglumine (FM), a cyclooxygenase inhibitor. Endotoxin decreased central plasma volume by 1 h and cardiac index by 3 h; hematocrit and plasma protein concentration were increased by 0.5 and 1.5 h, respectively, indicating a loss of plasma volume. These changes were also blocked or attenuated by FM. Moreover, in ponies treated with endotoxin + FM, cardiac index increased, indicating the presence of a cardiac-stimulating factor. We conclude that endotoxemia in ponies causes cardiopulmonary dysfunction that is mediated by cyclooxygenase-dependent and possibly cyclooxygenase-independent metabolites.

Animals↗

Pharmacokinetics of digoxin in sheep: limitations of the use of biological half-life for interspecies extrapolation.

After of single IV digoxin injection of 50 micrograms/kg of body weight, the serum digoxin concentrations of 4 sheep were fitted to a 2-compartment open model. The mean value for the elimination half-life was 7.15 hours; for area volume of distribution, 13.8 L/kg; and for total body clearance, 1.36 L/kg/hr. A comparison of this study with previous studies in sheep and cattle revealed that serious misconceptions could arise if one chose to rely upon elimination half-life as the sole descriptor of drug disposition. A more informative characterization was determined to be total body clearance and area volume of distribution.

Animals↗

Bacteriophage phi 29 proteins required for in vitro DNA-gp3 packaging.

In vitro assembly of bacteriophage phi 29 in crude extracts involves efficient packaging of a DNA-protein complex (DNA- gp3 ) into a prohead with the aid of the gene 16 product ( gp16 ) and subsequent assembly of neck and tail proteins ( Bjornsti et al., J. Virol. 41:508-517, 1982; Bjornsti et al., J. Virol. 45:383-396, 1983; Bjornsti et al., Proc. Natl. Acad. Sci. U.S.A. 78:5861-5865, 1981). To define the viral proteins required for the DNA- gp3 encapsidation phase, we purified biologically active proheads and DNA- gp3 and constructed a chimeric plasmid, pUM101 , which contained and expressed gene 16 of phi 29 and no other viral genes. The plasmid-specified gp16 was both necessary and sufficient to package 24% of the DNA- gp3 added to the purified proheads , and the DNA-filled heads so produced were efficiently complemented to infectious phage by the addition of neck and tail proteins. Purified proheads and DNA- gp3 gave linear dose-response curves with slopes of approximately 1; in contrast, a 4-fold dilution of gp16 resulted in a 1,000-fold reduction of phi 29, suggesting a requirement for multiple copies of this protein.

Bacillus subtilis↗