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Biomedical subjects

E Johnson

Publications and source records attributed to E Johnson.

At least 199 records · Page 11Linked to original sources
PubMed1995

A team approach to adverse drug reaction surveillance: success at a tertiary care hospital.

A retrospective adverse drug reaction (ADR) reporting system has been in place at Cedars-Sinai Medical Center for 7 years. Initially, the system identified 300 to 400 ADRs per year. After adding a checklist, that number increased to 750 to 850 per year, an ADR rate of about 2% of total patient admissions. To increase the ADR reporting rate, we initiated a concurrent surveillance program in conjunction with the retrospective system. In the first year of the program, the combined systems identified 1,174 ADRs. In addition, the ADR rate per 100 patient days increased to between 0.5 and 0.7, and the ADR per admission rate increased to 4%. As a result of the more effective ADR surveillance program, the P & T Committee has additional data from which to develop guidelines and educational programs to increase ADR awareness and prevention, and thus, to improve patient outcomes.

Adverse Drug Reaction Reporting Systems↗
PubMed1995

Detection and monitoring of a concomitant atypical myeloproliferative disorder and chronic lymphocytic leukemia by flow-cytometric immunophenotyping.

OBJECTIVE: To illustrate the utility of a broad panel of monoclonal antibodies to detect secondary processes or unexpected characteristics of the primary blood dyscrasia. DESIGN: Case report and discussion. SETTING: Regional academic medical center. PATIENT: A 64-year-old man presenting with an apparent acute myeloid leukemia. INTERVENTIONS: Sequential immunophenotyping with a broad panel of monoclonal antibodies to monitor progression of disease and response to therapy. MAIN OUTCOME MEASURE: Identification and monitoring of the two atypical populations in this patient with correlation to the clinical status of the patient. RESULTS: Identification of an unsuspected mature lymphoid clone and characterization of the evolution of the myelomonocytic clone. CONCLUSION: The evolving mature lymphoid clone may have been overlooked in the context of a predominant atypical myeloproliferative process, particularly if a limited panel of monoclonal antibodies had been used for immunophenotyping. Sequential immunophenotyping was useful in monitoring the progression of each atypical process.

Antigens, CD↗
PubMed1995

Lethal experimental infections of rhesus monkeys by aerosolized Ebola virus.

The potential of aerogenic infection by Ebola virus was established by using a head-only exposure aerosol system. Virus-containing droplets of 0.8-1.2 microns were generated and administered into the respiratory tract of rhesus monkeys via inhalation. Inhalation of viral doses as low as 400 plaque-forming units of virus caused a rapidly fatal disease in 4-5 days. The illness was clinically identical to that reported for parenteral virus inoculation, except for the occurrence of subcutaneous and venipuncture site bleeding and serosanguineous nasal discharge. Immunocytochemistry revealed cell-associated Ebola virus antigens present in airway epithelium, alveolar pneumocytes, and macrophages in the lung and pulmonary lymph nodes; extracellular antigen was present on mucosal surfaces of the nose, oropharynx and airways. Aggregates of characteristic filamentous virus were present within type I pneumocytes, macrophages, and air spaces of the lung by electron microscopy. Demonstration of fatal aerosol transmission of this virus in monkeys reinforces the importance of taking appropriate precautions to prevent its potential aerosol transmission to humans.

Aerosols↗
PubMed1995

Soft tissue sarcoma and non-Hodgkin's lymphoma in workers exposed to phenoxy herbicides, chlorophenols, and dioxins: two nested case-control studies.

We examined the effect of exposure to chemicals present in the production and spraying of phenoxy herbicides or chlorophenols in two nested case-control studies of soft tissue sarcoma and non-Hodgkin's lymphoma. Eleven sarcoma and 32 lymphoma cases occurring within an international cohort were matched for age, sex, and country of residence with 55 and 158 controls, respectively. Exposures to 21 chemicals or mixtures were estimated by three industrial hygienists who were blind to the subject's case-control status. Excess risk of soft tissue sarcoma was associated with exposure to any phenoxy herbicide [odds ratio (OR) = 10.3; 95% confidence interval (CI) = 1.2-91] and to each of the three major classes of phenoxy herbicides (2,4-dichlorophenoxyacetic acid, 2,4,5-trichlorophenoxyacetic acid, and 4-chloro-2-methylphenoxyacetic acid), to any polychlorinated dibenzodioxin or furan (OR = 5.6; 95% CI = 1.1-28), and to 2,3,7,8-tetrachlorodibenzo-p-dioxin (OR = 5.2; 95% CI = 0.85-32). Sarcoma risk was not associated with exposure to raw materials or other process chemicals. In the non-Hodgkin's lymphoma study, associations were generally weaker than those found in the study on sarcoma. These findings indicate that workers exposed to phenoxy herbicides and their contaminants are at a higher risk of soft tissue sarcoma.

Case-Control Studies↗
PubMed1995

Lilly's hands.

Explore the source record for details and available documents.

Adult↗
PubMed1994

A new method for delivering radioactive cytotoxic agents in solid cancers.

PURPOSE: Therapeutic agents such as monoclonal antibodies, radiopharmaceuticals, and radioactive growth factors are limited in effectiveness due to the inability to deposit significant quantities of the agents and for limited periods of time in solid cancer. A new technique based on knowledge of the pathophysiology of solid tumors allows for significant concentration of these agents to accumulate and for a prolonged period of time, thus allowing interaction with the tumor for potentially increased effectiveness. METHODS AND MATERIALS: Three agents have been studied: 131I antiferritin monoclonal antibody, colloidal 32P chromic phosphate, and 131I transferrin. The time required for maximal tumor uptake was determined in vitro in tissue culture and was 10 min, 25 min, and 40 min, respectively. The new method of in vivo tumor infusion consisted of a direct intratumoral injection of macroaggregated albumin (MAA) 10,000 particles, followed by the radioactive agents under study. Tumors were infused in vivo using the new technique and compared to intratumoral infused controls. In the instance of radiolabeled antiferritin antibody, intraperitoneal administration and intratumoral infusion were compared to the new technique. In the other two instances, intratumoral infusion was compared to the new method. RESULTS: In all instances the direct vascular blockade caused by MAA led to greater deposition of the agent under study for at least 24 h. These results were clinically applied with MAA followed by 32P colloidal chromic phosphate and were consistent with the experimental findings. CONCLUSION: A new technique is described that may be carried out in the experimental laboratory and clinic by direct tumor infusion of macroaggregated albumin (MAA), followed by other radioactive agents that will remain localized in solid cancers and will allow for high tumor dose deposition for potentially increased therapeutic efficacy.

Animals↗
PubMed1994

Characterization of the chicken osteopontin-encoding gene.

A genomic clone of the chicken osteopontin-encoding gene (opn) was isolated and found to be organized as follows: an untranslated 5' exon; a signal peptide; a recognition sequence for phosphorylation by casein kinase II; a domain containing a possible O-linkage site for glycosylation; a second casein kinase II phosphorylation site; an exon containing three functional regions, the poly-Asp sequence of seven consecutive Asp residues, the RGD integrin recognition site and a potential N-linkage site for glycosylation; and a large C-terminal exon which also contains a potential N-linkage site for glycosylation. Primer extension analysis demonstrated only one strong transcriptional start point (tsp) in mRNAs prepared from embryonic bone and cultured osteoblasts. Analysis of the 5' flanking region identified a TATA sequence at -31, an inverted CAAT motif at -57, an AP1-recognition sequence at -84 and a putative vitamin-D-response element (VDRE) sequence at -474. Three plasmid constructs containing 963, 561 and 368 bp of 5' flanking sequence of the avian promoter were used to drive expression of bacterial cat. Comparison of the relative promoter activities of these constructs was carried out in MC3T3/E1 cells, a murine osteoblast cell line. All of the constructs showed approximately 20-fold the levels of expression over background activity of the cat gene without a promoter. Each construct also demonstrated a strong induction with phorbol-12-myristyl-13-acetate (PMA). In contrast, dihydroxycholecalciferol [1,25(OH)2D3] had neither a positive nor a negative effect on the 368- and 936-bp constructs, but was stimulatory for the 561-bp construct.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

The effects of membrane physical properties on the fusion of Sendai virus with human erythrocyte ghosts and liposomes. Analysis of kinetics and extent of fusion.

A number of amphiphiles which raise the bilayer to hexagonal phase transition temperature (TH) of phosphatidylethanolamine (PE) have been shown to inhibit viral fusion. In this study we have further evaluated the mechanism of this inhibition. Several anionic amphiphiles, including cholesterol sulfate, a component of mammalian plasma membranes, lower the final extent of Sendai virus fusion with both human erythrocyte ghosts and liposomes composed of PE and 5% of the ganglioside, GD1a. A cationic amphiphile slightly increased the final extent of fusion. The fusion rate constant is not greatly affected by the presence of as much as 20% cholesterol sulfate or other charged amphiphiles. The zwitterionic amphiphile, cholesterol phosphorylcholine has no effect on the final extent of fusion but it lowers the fusion rate constant. This amphiphile is potent in raising TH. The amphiphile cholesterol hemisuccinate (CHEMS) stabilizes the bilayer relative to the hexagonal phase at neutral pH, while at acidic pH the formation of the hexagonal phase is promoted. When CHEMS is added to vesicles of egg PE containing 5% GD1a, the rate of Sendai virus fusion is little affected at neutral pH but the rate is significantly enhanced at pH 5.0. These results demonstrate that viral fusion can be modulated, in part, by the tendency of the membrane to convert to the hexagonal phase.

Animals↗
PubMed1994

Anti-myelin basic protein and anti-proteolipid protein specific forms of multiple sclerosis.

Human myelin basic protein (hMBP) and proteolipid protein (PLP) were used as antigens in a solid-phase radioimmunoassay to determine relative frequencies of anti-MBP and anti-PLP in cerebrospinal fluid (CSF) of optic neuritis and multiple sclerosis (MS) patients. Forty-nine of 55 patients with optic neuritis had increased CSF anti-MBP and the remaining 6 had increased anti-PLP. Of 385 MS patients, MS relapse: 173 of 180 patients had increased anti-MBP, 5 of the remaining 7 patients had elevated anti-PLP, and 2 had neither of these autoantibodies. Progressive MS: 111 of 116 patients had increased anti-MBP in either free and/or bound form, of the remaining 5 patients 4 had increased anti-PLP, and 1 had neither anti-MBP nor anti-PLP. MS remission: 15 of 87 patients had somewhat increased anti-MBP, none had anti-PLP. IgG was purified by affinity chromatography from necropsy central nervous system (CNS) tissue samples of 4 individual patients with clinically definite and neuropathologically confirmed MS. Three of these 4 patients who had increased levels of CSF anti-MBP also had increased anti-MBP titers in CNS tissue-extracted IgG. The fourth patient who had anti-PLP in CSF also had anti-PLP in brain tissue IgG. These autoantibodies were not detected simultaneously in any patient. These results suggest that there are at least two immunologically distinct forms of MS, i.e., a common form highly associated with anti-MBP and more frequent prominent inflammatory characteristics in CSF and CNS, and an infrequent form associated with anti-PLP in CSF and tissue, and less abundant inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Purification and characterization of an acetyl esterase from Aspergillus niger.

Optimized acetyl esterase enzyme production conditions using Aspergillus niger ATCC 10864 in 14-L fermentation jars were determined to be 33 degrees C, 1.5 vvm aeration, and 300 rpm agitation without pH control. The acetyl esterase was purified by precipitation in 60-80% saturation in ammonium sulfate. The pellet was applied directly to a Pharmacia high-load Phenyl Sepharose column for hydrophobic interaction chromatography and purified to homogeneity in two steps. Stability and kinetic characteristics of the acetyl esterase were determined over a pH range of 4.0-7.5 and from 4 to 45 degrees C. At temperatures > 25 degrees C, stability was superior at pH values < 5.0. The temperature activity optimum was 35 degrees C, and the pH optimum was 7.0. The Vmax was determined to be 46,700 U/mg protein, and the Km was 0.023M p-nitrophenyl acetate at pH 6.5 in 0.2M phosphate buffer at 35 degrees C. The mol wt of the enzyme was 35,000 dalton by size-exclusion chromatography and SDS gel electrophoresis. The N-terminal amino acid sequence and the glycosylation composition were also determined.

Acetylesterase↗
PubMed1994

Reduced complement and granulocyte activation with heparin-coated cardiopulmonary bypass.

Plasma concentrations of the complement activation products C3b, iC3b, and C3c; the terminal C5b-9 complement complex; and the granulocyte proteins calprotectin, myeloperoxidase, and lactoferrin were assessed in two groups of patients undergoing aortocoronary bypass procedures. In 10 patients operated on, the bypass circuits were coated by the Carmeda Bio-Active Surface and systemic heparinization was reduced to 1.5 mg/kg; in another 10, the systems were uncoated and the dosage of systemic heparinization was 4 mg/kg. In both groups, significant complement activation was observed after the onset of cardiopulmonary bypass, but the maximum levels of C3b, iC3b, and C3c and the terminal C5b-9 complement complex were significantly lower in the heparin-coated group. In both groups, a significant increase in calprotectin, myeloperoxidase, and lactoferrin release was observed by the end of operation. The maximum myeloperoxidase levels were significantly lower in the heparin-coated group than those in the uncoated group (p = 0.03). There was a correlation of borderline significance between the formation of terminal C5b-9 complement complex and lactoferrin release, as well as between the formation of terminal C5b-9 complement complex and myeloperoxidase release (p = 0.05). The postoperative blood loss did not differ significantly between the two groups. We conclude that coating by end point-attached and functionally active heparin allows a significant reduction in the amount of systemic heparinization, and significantly reduces complement and granulocyte activation.

Aged↗
PubMed1994

Formation of the terminal complement complex on agarose beads: further evidence that vitronectin (complement S-protein) inhibits C9 polymerization.

Vitronectin occupies the metastable binding site of C5b-7, which is unable to insert membranes as part of the complement lytic attack. Some evidence has been presented that vitronectin inhibits also membrane-associated pore formation by inhibiting C9 polymerization in the terminal complement complex (TCC). The authors wished to add to this background by studying the effect of vitronectin on formation of TCC on a carbohydrate surface like agarose beads, an alternative complement pathway activator. Bound TCC was detected by monoclonal and polyclonal antibodies to C9-neoepitopes. Soluble SC5b-7 and TCC (SC5b-9) did not bind to the agarose beads. Using serum or isolated complement factors for the alternative and terminal pathways, the authors found that vitronectin reduced the density of C9-neoepitopes on the beads. As there was no convincing evidence for association of vitronectin with the factors C5b-8 of the agarose-bound TCC, it was concluded that vitronectin bound directly to C9 in TCC and inhibited C9 polymerization within the complex. The authors have shown that TCC can bind to a carbohydrate surface like agarose (an alternating polymer of galactose moieties) in the absence of lipid. These results suggest that vitronectin can limit the lytic effect of membrane-bound TCC by inhibiting C9 polymerization.

Animals↗
PubMed1994

Effect of gamma-interferon on the synthesis of the functional alternative and terminal complement pathways by human umbilical vein endothelial cells in vitro.

The cytokine gamma-interferon (gIFN) has been reported to modulate synthesis by endothelial cells (EC) of alternative pathway complement factors (H, I, and B). However, the net effect of gIFN on the synthesis and expression of the functional alternative and terminal pathways has not yet been reported. EC cultured under serum-free conditions were treated with different concentrations of gIFN and simultaneously co-incubated with agarose beads, which activate the alternative pathway. C3b and the terminal complement complex (TCC) bound to co-incubated beads were measured by radioimmunoassay using anti-human C3c and TCC antibodies. gIFN in concentrations 500-4000 U/ml increasingly reduced the amount of C3b and TCC detected on the beads. The down-regulating effect of gIFN on EC complement biosynthesis may be physiologically relevant by locally controlling complement activation.

Antibody Specificity↗
PubMed1994

Molecular characterization of a newly recognized mouse parvovirus.

Mouse parvovirus (MPV), formerly known as orphan parvovirus, is a newly recognized rodent parvovirus distinct from both serotypes of minute virus of mice (MVM). Restriction analysis of the MPV genome indicated that many restriction sites in the capsid region were different from those of MVM, but most sites in the nonstructural (NS) region of the genome were conserved. MPV resembled MVM in genome size, replication intermediates, and NS proteins. Replication intermediates in infected cells were the same for MPV and MVM, including packaging of the 5-kb minus (V) strand. Furthermore, the MPV NS proteins were the same size as and present at the same ratio as the MVM(i) proteins in infected cells. Cloning and sequencing of the MPV genome revealed a genome organization closely resembling that of MVM, with conservation of open reading frames, promoter sequences, and splice sites. The left terminal hairpin was identical to that of MVM(i), but the right terminus was not conserved. Also, the MPV genome was unique in that it contained 1.8 copies of the terminal repeat sequence rather than the 1 or 2 copies found in other parvoviruses. The predicted amino acid sequence of the NS proteins of MPV and MVM(i) were nearly identical. In contrast, the predicted amino acid sequence of the capsid proteins of MPV was different from sequences of other parvoviruses. These results confirm that MPV is a distinct murine parvovirus and account for the antigenic differences between MPV and MVM.

Amino Acid Sequence↗