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Biomedical subjects

E S Ward

Publications and source records attributed to E S Ward.

85 records · Page 5Linked to original sources
PubMed1987

Cloning and heterologous expression of an insecticidal delta-endotoxin gene from Bacillus thuringiensis var. aizawai IC1 toxic to both lepidoptera and diptera.

Bacillus thuringiensis var. aizawai IC1 synthesises an insecticidal protein delta-endotoxin (130-135 kDa) that is toxic to both lepidopteran and dipteran larvae, and cross-reacts immunologically with certain monospecific lepidopteran toxins. A 166-kb plasmid from this bacterium was found to hybridise with an intragenic probe derived from the clone B. thuringiensis var. sotto lepidopteran-specific delta-endotoxin gene. A strongly hybridising 5.2-kb SstI fragment from var. aizawai plasmid DNA was cloned in pUC18. After subcloning of this DNA in Escherichia coli, recombinants were obtained that synthesised large amounts of a 130-135-kDa protein. The protein was deposited in the cytoplasm as microscopically visible inclusion bodies and lysates of these cells were found to be toxic to both lepidopteran and dipteran larvae by comparison with controls. The structural basis for the dual specificity of this var. aizawai toxin is now amenable to further study.

Bacillus thuringiensis↗
PubMed1987

Aminoglycoside monitoring: use of a pharmacokinetic service versus physician recommendations.

Two patient populations were evaluated regarding the monitoring of aminoglycoside serum concentrations by either a pharmacokinetic service (PKS) or staff physicians. Both groups were evenly matched by demographic characteristics, underlying disease state(s), and indication for aminoglycoside therapy. Patients in the PKS group showed increased incidence of clinical improvement after therapy when compared with the physicians' group; a decreased length of stay and duration of treatment were also observed in this group. Aminoglycoside dosing and monitoring by the PKS provided an estimated average cost savings of $491,00 per patient. The results indicate that the PKS may provide cost savings and benefit in aminoglycoside monitoring for the patient and/or the hospital.

Adolescent↗
PubMed1987

Pharmacy-based computer system for monitoring and reporting drug interactions.

A pharmacy-based computer system for monitoring and reporting drug interactions is described, and physicians' responses to patient management suggestions generated by the system are reported. Using information from a commercially available drug-interaction database, a pharmacist chose 41 potentially interacting drug combinations to include in the pharmacy's automated system. A warning notice appears on the computer screen if one of these drug combinations is prescribed. Pharmacists who encounter these notices while entering medication orders telephone the prescribing physician if the combination represents a Class I interaction (immediate onset, major severity, established documentation); for Class II interactions, which have a delayed onset, a copy of the warning notice and suggestions for patient management are placed in the prescribing physician's mailbox. The system was evaluated during a three-month period in 1985 to determine physicians' responses to the patient management suggestions. A total of 927 patients had 1004 potentially interacting drug combinations prescribed for them. Changes in drug dosage were made in 44% of these instances, and in 75%, patients were monitored for the development of adverse clinical effects. A computerized drug-interaction monitoring system can help increase physicians' awareness of possibly interacting drug combinations and provide them with useful information about the clinical management of patients for whom such drug combinations have been prescribed.

Adolescent↗
PubMed1986

Bacillus thuringiensis var. israelensis delta-endotoxin. Nucleotide sequence and characterization of the transcripts in Bacillus thuringiensis and Escherichia coli.

The nucleotide sequence of a 1408 base-pair DNA fragment encoding the insecticidal 27,340 Mr delta-endotoxin of Bacillus thuringiensis var. israelensis has been determined by analysis of a recombinant plasmid from Escherichia coli. The hydropathy plot of the protein shows it to be highly hydrophobic, consistent with a postulated cytolytic mechanism of action for the toxin. In addition, the delta-endotoxin transcriptional start points that are used in B. thuringiensis and an E. coli recombinant have been determined. In B. thuringiensis var. israelensis, transcription initiates from a single start point, and gene-specific transcripts are not observed before stage II of sporulation. This is the stage at which delta-endotoxin antigen is first detected, indicating that control of expression is primarily at the transcriptional level for this protein. Analysis of gene-specific transcription in E. coli indicates that at least three start points are utilized in this organism. Interestingly, the highest level of delta-endotoxin mRNA is seen during mid-exponential growth of E. coli and the level appears to decrease as the cells enter the stationary phase of growth.

Amino Acid Sequence↗
PubMed1986

Bacillus thuringiensis var. israelensis delta-endotoxin. Cloning and expression of the toxin in sporogenic and asporogenic strains of Bacillus subtilis.

A plasmid-borne gene from Bacillus thuringiensis var. israelensis encoding a 27,340 Mr insecticidal delta-endotoxin has been cloned on a bifunctional multicopy plasmid in a wild-type sporogenic strain and two asporogenic mutants of Bacillus subtilis. The delta-endotoxin gene is expressed at a low level during vegetative growth in all three strains, but the synthesis of the toxin increases markedly during the third hour of stationary phase for both the sporogenic strain and an asporogenic mutant containing the OJ lesion. However, in a stage OA mutant, this increase in delta-endotoxin synthesis is not observed. In both the wild-type sporogenic B. subtilis and the asporogenic OJ strain, phase-bright inclusions, resembling the israelensis crystal in appearance, are visible during late stationary phase. The insoluble inclusions from the B. subtilis transformants, consisting solely of the 27,340 Mr polypeptide, were purified by density gradient centrifugation and found to be extremely toxic to Aedes aegypti larvae. After solubilization in alkaline buffer, this polypeptide was also shown to be haemolytic for human erythrocytes and to lyse Aedes albopictus cells with the same LC50 value as native israelensis delta-endotoxin crystals. During stationary phase, novel mRNA species appear in both the wild-type strain and the OJ mutant, but not in the OA mutant, and these appear to be the major gene-specific transcripts. Transcriptional mapping of delta-endotoxin-specific mRNA has shown that the same region of initiation is used at a relatively low level in all three strains during vegetative growth.

Bacillus subtilis↗
PubMed1984

Cloning and expression in Escherichia coli of the insecticidal delta-endotoxin gene of Bacillus thuringiensis var. israelensis.

Recombinant plasmids containing the mosquitocidal delta-endotoxin gene were constructed by inserting HindIII fragments of the Bacillus thuringiensis var. israelensis 72-75 Md plasmid in to the Escherichia coli vector pUC12. Two recombinants producing the 26 000 Da delta-endotoxin (pIP173 and pIP174) were identified by screening clones in an E. coli in vitro transcription-translation system. Both recombinants were 12.4 kb chimaeric plasmids comprising pUC12 and a common 9.7 kb HindIII fragment of the B. thuringiensis plasmid. The 26 000 Da polypeptide synthesis in vivo from pIP174 transformed into E. coli JM101 was lethal to mosquito larvae and cytotoxic to mosquito cells in vitro. The biological authenticity of the cloned product was further confirmed by demonstrating that the cytotoxicity of the polypeptide was neutralised by antiserum to the authentic delta-endotoxin or by preincubation with excess toxin receptor. Transcription of the recombinant delta-endotoxin gene in E. coli appears to utilise a Bacillus promoter sequence(s) rather than the pUC12 beta-galactosidase promotor.

Aedes↗
PubMed1982

The stability of personality measures in drug abusers during withdrawal.

The present report is of the stability of personality measures within a group of polydrug abusers during withdrawal. The EPQ (Eysenck and Eysenck, 1975) and a questionnaire assessing disturbances of perceptual and cognitive functioning (Reichenstein, 1976) were the instruments employed. Initial assessments were made within 24 hours of admission and were repeated at 4 weeks and 8 weeks after drug withdrawal. Scores on Psychoticism, Neuroticism, and Extraversion showed considerable stability, although the Lie Score decreased across occasions. Mean scores on the Reichenstein Scale were initially elevated but subsequently normalized. The findings suggest that previously reported scores of drug abusers on the EPQ are not an artifact of drug status.

Adolescent↗
PubMedDate not supplied

Sedimentation equilibrium analysis of recombinant mouse FcRn with murine IgG1.

The interaction of mouse IgG1 or IgG1-derived Fc fragment with recombinant, insect cell expressed mouse FcRn has been analyzed using sedimentation equilibrium. This results in a model for the interaction in which the two binding sites for FcRn on Fc or IgG1 have significantly different affinities with macroscopic binding constants of < 130 nM and 6 microM. This data indicates the formation of an asymmetric FcRn:Fc (or IgG1):FcRn complex which is consistent with earlier suggestions that for this form of recombinant FcRn, binding to IgG1 or Fc does not result in a symmetric 2:1 complex in which both binding sites are equivalent.

Animals↗
PubMedDate not supplied

Relative bioavailability of ondansetron 8-mg oral tablets versus two extemporaneous 16-mg suppositories: formulation and gender differences.

STUDY OBJECTIVE: To compare the relative bioavailability of two 16-mg extemporaneously prepared suppository formulations with that of an 8-mg commercially available oral tablet. DESIGN: Prospective, crossover bioavailability study. SETTING: Inpatient clinical research center. SUBJECTS: Sixteen young, nonsmoking, healthy volunteers. INTERVENTIONS: Blood samples were obtained 24 and 48 hours after administration of an 8-mg oral ondansetron tablet and 16-mg suppository, respectively. Two 16-mg suppository formulations were compounded using commercially available Fattibase and Polybase. MEASUREMENTS AND MAIN RESULTS: Ondansetron was well absorbed by both routes of administration. The following pharmacokinetic parameters (mean+/-SEM) were obtained for the 8-mg tablet, 16-mg Fattibase suppository, and 16-mg Polybase suppository, respectively: area under the curve (AUC) in men 154.2+/-21.77, 253.4+/-72.3, 304.8+/-62.2 ng x hr/ml; AUC in women 353.6+/-32.7, 561.6+/-103.6, and 768.7+/-117.9 ng x hr/ml; maximum concentration (Cmax) in men 45.5+/-7.0, 40.6+/-10.4, and 51.2+/-6.7 ng/ml; Cmax in women 51.4+/-.8, 47.1+/-3.9, and 82.9+/-6.6 ng/ml. Times to Cmax (Tmax; mean+/-SEM) for men were 1.5+/-0.3, 4.4+/-0.5, and 2.9+/-0.3 hours; Tmax for women were 1.8+/-0.3, 4.1+/-0.4, and 4.4+/-0.6 hours for the three formulations, respectively. Women had a consistently higher AUC for all three formulations than men (p<0.05). CONCLUSION: With the exception of the 16-mg Polybase formulation in women, the two suppositories closely approximated the pharmacokinetics of the 8-mg oral tablet. These results suggest that gender may be a significant factor in ondansetron's disposition.

Administration, Oral↗