Issues of retirement from leadership in a family business.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
E Johnson
Publications and source records attributed to E Johnson.
Melting and misalignment of solid crystalline krypton inclusions in aluminum.
Explore the source record for details and available documents.
Journal Article↗
Behavioral rehabilitation of functional alexia.
A 10-year-old boy with a functional reading deficit (i.e. functional alexia) was successfully treated with hospital based escape/avoidance procedures. A multiple baseline design was used to evaluate the effectiveness of treatment. Generalization of treatment effects across individuals, settings and time was demonstrated. Extension of these procedures to other functional deficits is discussed.
Behavior Therapy↗
Structure and origins of the HZ2-feline sarcoma virus.
The HZ2-feline sarcoma virus (HZ2-FeSV) is a replication-defective acute transforming feline retrovirus with oncogene homology to Abelson murine leukemia virus (A-MuLV) (P. Besmer, W.D. Hardy,Jr., E. E. Zuckerman, P. J. Bergold, L. Lederman, and H. W. Snyder, Jr. (1983) Nature (London) 303, 825-828). In contrast to A-MuLV which was isolated from a hematopoietic tumor, the HZ2-FeSV derives from a multicentric fibrosarcoma. We have molecularly cloned the HZ2-FeSV provirus from mink HZ2-FeSV nonproducer cells. The molecularly cloned HZ2-FeSV provirus is biologically active upon transfection of NIH 3T3 indicator cells. The genetic structure of the HZ2-FeSV provirus was determined by EM heteroduplex and Southern blot analysis. The HZ2-FeSV has a 6.8 kb-viral genome with the structure: 5' delta gag-abl-delta pol-delta env 3'. The abl insert, which is 1.4 kb, is located 1.9 kb from the 5' end and 3.5 kb from the 3' end of the viral genome. The 5' 1.9 kb in the HZ2-FeSV are colinear with 5' FeLV sequences, and the 3' 3.5 kb are colinear with 3' FeLV sequences, with the exception of a 0.85-kb deletion in the env gene. HZ2-FeSV v-abl and A-MuLV v-abl share 1.2 kb of abl sequences which are known to specify the protein kinase domain of the abl gene product and are necessary for fibroblast transformation in vitro. The DNA from several tumor tissues of cat 3590 from which the HZ2-FeSV was obtained was found to contain several HZ2-FeSV-related proviruses including the HZ2-FeSV. The variant HZ2-FeSVs have indistinguishable 5' gag-abl sequences; however, they differ in 3' sequences which likely do not include any abl sequences. The DNAs from fibrosarcomas obtained by inoculation of kittens with tumor extract were found to contain variant HZ2-FeSV proviruses as well. Taken together these results indicate a role for the HZ2-FeSVs in sarcomagenesis.
Abelson murine leukemia virus↗
Purification of IgM monoclonal antibody from murine ascitic fluid by a two-step column chromatography procedure.
Two IgM monoclonal antibodies (Mabs) were purified from murine ascitic fluid by a two-step procedure involving pseudoligand affinity chromatography on immobilized Cibacron Blue F3GA and gel filtration chromatography on ACA-22. The purified IgM from one ascites sample, H-1, was determined to be homogeneous by sodium dodecyl sulfate-polyacrylamide gel electrophoresis while ascites containing E3.1 IgM Mab, was purified to greater than 95% IgM. The retention of biological activity was confirmed by immunofluorescence staining of peripheral blood lymphocytes.
Acrylamides↗
Multicenter hypothermia survey.
A multicenter survey evaluated the clinical presentation, treatment, and outcome of accidental hypothermia. Data were collected from 13 emergency departments, with 401 of the 428 cases presenting during a two-year study period. Core temperatures ranged from 35 C to 15.6 C (mean, 30.57 C +/- 3.53) with 272 cases (63.6%) less than or equal to 32.2 C. There were no significant differences by age in presenting temperature, rewarming strategies, or mortality. The first hour rewarming rate was significantly (P less than .05) faster in the population less than or equal to 59 years (1.08 +/- 1.39 C/hr) than in those greater than or equal to 60 years (0.75 +/- 1.16 C/hr). Male core temperatures averaged 30.27 +/- 3.44 C versus female temperatures of 31.1 +/- 3.61 C. There were no clinically significant differences in male (N = 296) versus female (N = 132) profiles. High ethanol levels (315 to 800 mg%) did not affect outcome. Nine of 27 (33%) patients who received CPR initiated in the field survived, versus six of 14 (43%) with CPR begun in the ED. The profile of the CPR versus non-CPR population differed significantly (P less than .05) in location (outdoors), initial temperature (24.8 +/- 3.77 C vs 30.94 +/- 3.12 C), third-hour rewarming rate (2.28 +/- 1.53 C vs 1.17 +/- 1.18 C/hr), and numerous laboratory parameters. Tracheal intubation was performed without incident in 117 cases, of which 97 were less than or equal to 32.2 C. There were 73 fatalities (17.1%). Of these, 84.9% (N = 62) were less than or equal to 32.2 C. Predisposing conditions in this group included "serious" illness (30), systemic infection (28), trauma (15), immersion (ten), frostbite (seven), and overdose (two). The initial pulse, hemoglobin, and first-hour rewarming rate was lower in the deceased population, while the potassium, urea nitrogen, creatinine, and phosphorus were elevated. Excluding treatment combinations, outcome with exclusive use of a single rewarming strategy was passive external rewarming, 14 deaths below 32.2 C, 13 above; active external rewarming, six deaths below 32.2 C, two above; active core rewarming, 38 deaths below 32.2 C, none above. Refinements of the American Heart Association's CPR standards in hypothermia and a Hypothermia Survival Index are proposed.
Age Factors↗
Human alveolar macrophages synthesize active complement components C6, C7, and C8 in vitro.
We investigated whether serum-free human alveolar macrophage cultures synthesize active C6, C7, and C8. There was a significant binding of polyclonal anti-human C6 antibodies to agarose beads incubated with unstimulated macrophages for 24 or 48 h. Endotoxin stimulation of the macrophages was necessary for significant binding of polyclonal anti-C7 and anti-C8 antibodies to agarose beads co-cultured for 48 or 96 h. Two monoclonal antibodies (poly C9-MA and MCaE11) specific for a neoantigen of polymerized C9 in the terminal complement complex (TCC), bound to beads mainly incubated with endotoxin stimulated macrophages. The MCaE11 was more sensitive than the poly C9-MA in detecting the C9 neoantigen on beads incubated with the macrophages or human serum diluted 1:16. We thus conclude that human alveolar macrophages synthesize active C6, C7, and C9 that together with C5 and C9, assemble as the TCC on co-cultured agarose beads. Activation of the alternative pathway on the agarose with generation of fixed C3 and C5 convertases is a prerequisite for the subsequent generation of the TCC.
Adult↗
Formation of the membrane attack complex of complement (MAC) on erythrocytes from monocyte-produced terminal complement components.
By using antibodies against C5, C6, C7, C8, and C9, we found that terminal complement components were deposited on IgM-coated sheep erythrocytes (EIgM) kept in serum-free endotoxin-stimulated monocyte cultures for 24 or 48 h. Monoclonal antibodies revealed C9 neoantigens on the EIgM. There was no specific binding of an anti-S protein antibody, which reacts with the SC5b-9 complex, to the EIgM. Controls were native sheep erythrocytes (E) treated similarly which, in contrast to EIgM, do not activate the classical pathway of complement. Cycloheximide (1.0 microgram/ml) in the cell cultures resulted in no specific binding of the anti-C9 antibodies to EIgM. A fraction of the EIgM was lysed during incubation with the monocytes. We conclude that the monocytes secrete C5, C6, C7, C8, and C9, which form the membrane attack complex of complement (C5b-9) on the EIgM.
Animals↗
Successful oral chemotherapy with idarubicin in refractory anaemia with excess blasts.
6 patients with refractory anaemia with excess blasts (RAEB) were treated with a new oral anthracycline, idarubicin. 3 patients achieved complete remission, and the remaining 3 achieved partial remission. These responses were maintained for 8-60 wk, the longer durations being in the patients who achieved complete remission. Treatment was given on an outpatient basis, and all but 1 patient remained at home for most of the disease course. Unwanted effects were mild. It would thus appear that oral idarubicin is an effective treatment for RAEB, in addition to allowing outpatient management. Larger studies are required for further evaluation.
Administration, Oral↗
Human alveolar macrophages and monocytes generate the functional classical pathway of complement in vitro.
Binding of labelled protein to EIgM kept with macrophage or monocyte cultures with 3H-leucine under serum-free conditions, shows that de novo synthesis of protein with affinity to EIgM takes place. We find that monoclonal anti-C3c and anti-C3g antibodies and polyclonal anti-C4 and anti-C5 antibodies bind to such erythrocytes. This demonstrates that C4b, C3b and iC3b are deposited on the EIgM. Additional evidence for complement synthesis is the increase in binding of anti-C4 antibodies to EIgM when the incubation time was increased from 48 to 96 hours. Stimulation of the mononuclear phagocyte cultures with ET was necessary to obtain significant amounts of erythrocyte-bound complement proteins. From these results we conclude that the functional classical pathway of complement is produced in vitro by the monocytes and macrophages.
Cells, Cultured↗
Theophylline steady-state pharmacokinetics: recent concepts and their application in chronotherapy of reactive airway diseases.
With the introduction of sustained-release theophylline formulations for once-daily dosing or for unequally divided twice-daily dosing, comparison with conventional equally divided twice-daily dosing has been focused on nocturnal serum theophylline concentrations (STCs), plateau properties and peak-trough fluctuation. The merits of various steady-state characteristics such as nocturnal excess, plateau time, residual concentration, peak-trough fluctuation, swing and AUC fluctuation are illustrated by 15 data sets from 7 multiple-dose studies, each including either 10-12 healthy volunteers or 12-20 COPD-patients. In all of the studies, STCs were determined at least every 2 hr over a 24-hr period in steady-state. Included in the studies were 7 sustained-release theophylline formulations which were administered either once daily (in the morning or in the evening), or twice daily (either equally divided, or unequally divided with one-third of the dose being given in the morning and two-thirds in the evening.
Circadian Rhythm↗
Steady state pharmacokinetics, metabolism and pharmacodynamics of theophylline in children after unequal twice-daily dosing of a new sustained-release formulation.
This was an open-label study in 19 children aged 9-13 years, weighing 27-44 kg, with bronchial asthma. Twenty-four-hour steady-state concentrations of theophylline and its metabolites 1,3-dimethyl uric acid, 3-methyl xanthine and 1-methyl uric acid were assessed after daily dosing of 600 mg (ca 18 mg/kg/day) of the sustained-release theophylline micro-pellet sprinkle system BY158K, for 4 days. The dosing regimen used was an unequal twice-daily dose of 200 mg in the morning after breakfast and 400 mg in the evening after dinner. Twenty-four-hour peak expiratory flow (PEF) profiles were compared before treatment and at steady-state, along with lung function parameters after bronchial provocation. Mean values +/- SD (n = 16) of the steady-state characteristics were Cmin 6.8 +/- 2.1 mg/l, Cmax 14.5 +/- 4.8 mg/l and Cav 10.5 +/- 2.9 mg/l, the plateau time was 11.7 +/- 4.8 hr and peak-trough fluctuation and swing were 72 +/- 21 and 118 +/- 52%, respectively. There was an excellent reproducibility of theophylline pre-dose levels at corresponding time points of the 24-hr sampling period [r = 0.864 (p less than 0.001)]. Mean values +/- SD of the 24 hr average serum metabolite levels were 0.9 +/- 0.2 mg/1 for 1,3-dimethyl uric acid, 0.6 +/- 0.1 mg/1 for 3-methyl xanthine and 0.4 +/- 0.1 mg/1 for l-methyl uric acid. Lung function (n = 17) following bronchial provocation, improved in 10 children after theophylline treatment of 4 days, remained stable in 2 patients and deteriorated in 5 patients. Serum theophylline profiles and PEF profiles ran largely in parallel over the 24-hr period. Six children exhibited typical theophylline induced side-effects, headache (n = 3), nausea (n = 4), dizziness (n = 1), vomiting (n = 4), sleep disturbances (n = 1), pallor (n = 1) and tremor (n = 1), necessitating in 3 children one dose omission/reduction (n = 2) or subsequent dose reduction (n = 1). It has been shown that a twice daily dosing regimen with unequal doses of anhydrous theophylline (BY158K) is well suited to this population of fast metabolisers. The patients were well protected throughout the day, including the critical early morning hours.
Asthma↗
Plasma endogenous digitalis-like factors in healthy individuals and in dialysis-dependent and kidney transplant patients.
Plasma digitalis-like factors (DLF), dehydroepiandrosterone sulfate (DHEAS) and cortisol were assayed in 20 healthy subjects, 22 dialysis dependent subjects and 30 patients with kidney transplants. DLF were assayed on plasma extracts by digoxin radioimmunoassay (RIA), and by Na,K-ATPase inhibition and [3H]-ouabain displacement using hogbrain Na,K-ATPase. Values for the 3 methods strongly intercorrelated (r = 0.99, p less than .001). Mean values for plasma DLF, assayed by all three methods, were significantly greater in dialysis dependent subjects, than in healthy subjects (p less than .0001). Mean plasma DLF values measured by digoxin RIA in renal transplant recipients, were significantly lower than in dialysis dependent subjects (p less than 0.0001) and higher than in healthy subjects. Plasma DLF values correlated inversely with creatinine clearance (p less than 0.01). Plasma DHEAS levels were significantly lower and contributed substantially less to digoxin antibody reactivity and ouabain displacement in dialysis subjects and in renal transplants compared with healthy subjects. There was no change in plasma immunoreactive DLF, DHEAS or cortisol measured before and after dialysis. DHEAS is a major digoxin like immunoreactive DLF and a minor Na,K-ATPase inhibitor in healthy subjects but makes only a minor contribution to DLF in dialysis and transplant subjects. We found the assays involving Na,K-ATPase inhibition and [3H]-ouabain displacement from Na,K-ATPase to be more sensitive for plasma DLF than the digoxin RIA, but because of the strong correlation between the methods, we suggest the RIA on plasma extracts can be used as a screening procedure.
Adult↗
Treatment of acute bacterial peritonitis: a trial of imipenem/cilastatin against ampicillin-metronidazole-gentamicin.
Imipenem/cilastatin at a dose of 0.5 g six hourly was compared to conventional combination therapy with ampicillin 0.5 g six hourly, metronidazole 0.5 g eight hourly and gentamicin 80 mg eight hourly (with dose adjustment by trough and peak serum levels) in the treatment of severe intra-abdominal infections. All antibiotics were given intravenously. Forty-five patients entered the trial. Of the 19 evaluable patients in the imipenem/cilastatin group, 16 were clinically cured with five microbiological successes and two failures. Of 24 evaluable patients in the combination group, 22 were clinically cured with one microbiological success and one failure. One patient in each group suffered an adverse effect. Patients in the I/C group tended to be older with more women and more severe infections. The origin of peritonitis was similar. I/C did not differ from combination therapy in efficacy or safety and was comparable in cost. However, I/C was easier to administer than combination therapy and there was no need for serum concentration monitoring.
Adolescent↗
Phenomena dependent on O2 transport waiting for ISOTT input.
Explore the source record for details and available documents.
Altitude↗
Synthesis of complement components C5, C6, C7, C8 and C9 in vitro by human monocytes and assembly of the terminal complement complex.
Monocytes cultured under serum-free conditions secreted protein which bound covalently and non-covalently to agarose beads, an activator of the alternative pathway of complement. There was a significantly binding of monoclonal anti-C3c antibodies, polyclonal anti-C5, anti-C6, anti-C7, anti-C8, and anti-C9 antibodies, and of a monoclonal antibody against a neoantigen of polymerized C9 to agarose beads incubated with the monocytes for 24, 48, 72 or 96 h. From these results, we conclude that monocytes produce C5, C6, C7, C8 and C9 that assemble as the terminal complement complex on the surface of the agarose beads. Activation by agarose of the alternative pathway with generation of particle bound C3 and C5 convertases is a prerequisite for the subsequent formation of the terminal complement complex. Whether SC5b-9 or the membrane attack of complement (C5b-9) is formed on the beads will be examined.
Antibodies, Monoclonal↗
Human alveolar macrophages synthesize the functional alternative pathway of complement and active C5 and C9 in vitro.
Attachment of protein to agarose beads cultured with macrophages in protein-free medium containing 3H-leucine, shows that de novo synthesis of protein with affinity to the beads takes place. We also found that monoclonal antibodies against human C3c, C3g, and a C9-neoantigen as well as polyclonal antibodies against human C5 and C9, bound to agarose beads that had been kept with the macrophage cultures. Demonstration of C3 derivatives on the agarose beads shows that the essential complement factors of the alternative pathway are synthesized and have been activated by the beads. Deposition of C5 and the detection of a neoantigen of C9 on the beads, indicates that the whole terminal complement pathway has been formed and activated. We conclude that human alveolar macrophages form in vitro the functional alternative pathway of complement, C5 and C9, and we have indirect evidence for synthesis of C6, C7, and C8.
Antibodies, Monoclonal↗
Phagocytosis of agarose beads by receptors for C3b (CR1) and iC3b (CR3) on human alveolar macrophages cultured on fibronectin in vitro. A scanning electron microscopic study.
We studied the phagocytosis of agarose beads by human alveolar macrophages in terms of the morphology, the receptors involved, and the cellular substrates (plastic or fibronectin) used. Beads coated with C3b (58%) and iC3b (42%) by treatment with serum, were ingested during 45 min by CR1 and CR3 on the macrophages. This ingestion was inhibited 80-90% by the presence of polyclonal F(ab')2 anti-C3 fragments. Since the phagocytosis of both C3b- and iC3b-coated beads was about threefold stronger than for C3b-coated beads (trypsinized serum-treated beads), the results indicate that the CR3 is more phagocytic than the CR1. The phagocytosis of initially complement uncoated beads, which are slowly opsonized with macrophage-produced C3b and iC3b in vitro, was also strongly inhibited (70-80%) by the presence of anti-human C3 F(ab')2 fragments. There was an increased phagocytosis (10-17%) of complement precoated beads by macrophages cultured on the fibronectin substrate versus the plastic substrate. The morphology and rapid phagocytosis of the complement precoated beads was demonstrated by SEM. The general impression was that membranous protrusions stretched towards the beads, which became increasingly enclosed by plasma membrane.
Adult↗