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Biomedical subjects

E Fowler

Publications and source records attributed to E Fowler.

At least 37 records · Page 2Linked to original sources
PubMed1991

Functional duality and structural uniqueness of depressant insect-selective neurotoxins.

Depressant insect-selective neurotoxins derived from scorpion venoms (a) induce in blowfly larvae a short, transient phase of contraction similar to that induced by excitatory neurotoxins followed by a prolonged flaccid paralysis and (b) displace excitatory toxins from their binding sites on insect neuronal membranes. The present study was undertaken in order to examine the basis of these similarities by comparing the primary structures and neuromuscular effects of depressant and excitatory toxins. A new depressant toxin (LqhIT2) was purified from the venom of the Israeli yellow scorpion. The effects of this toxin on a prepupal housefly neuromuscular preparation mimic the effects on the intact animal; i.e., a brief period of repetitive bursts of junction potentials is followed by suppression of their amplitude and finally by a block of neuromuscular transmission. Loose patch clamp recordings indicate that the repetitive activity has a presynaptic origin in the motor nerve and closely resembles the effect of the excitatory toxin AaIT. The final synaptic block is attributed to neuronal membrane depolarization, which results in an increase in spontaneous transmitter release; this effect is not induced by excitatory toxin. The amino acid sequences of three depressant toxins were determined by automatic Edman degradation. The depressant toxins comprise a well-defined family of polypeptides with a high degree of sequence conservation. This group differs considerably in primary structure from the excitatory toxin, with which it shares identical or related binding sites, and from the two groups of scorpion toxins that affect sodium conductance in mammals. The two opposing pharmacological effects of depressant toxins are discussed in light of the above data.

Amino Acid Sequence↗
PubMed1991

Insecticidal effects of an insect-specific neurotoxin expressed by a recombinant baculovirus.

The scorpion Androctonus australis has a peptide (AaIT) which selectively targets the insect sodium channel. This mode of action is similar to that of many widely used chemical insecticides. When Bombyx mori larvae were infected with a recombinant baculovirus carrying a synthetic AaIT gene, the expressed protein was secreted into the hemolymph and caused symptoms consistent with sodium channel blocking, including tremors and feeding cessation at 40 hr p.i. followed by paralysis and death by 60 hr p.i. Larvae infected with control virus died by 96 hr p.i. These results indicate that foreign genes can be used in recombinant baculoviruses to reduce insect feeding damage and increase the rate of insect kill.

Amino Acid Sequence↗
PubMed1991

Development of a recombinant baculovirus expressing an insect-selective neurotoxin: potential for pest control.

Recombinant nuclear polyhedrosis viruses (NPVs) expressing insect-selective toxins, hormones, or enzymes could enhance their insecticidal properties. We have constructed a recombinant, polyhedrin-positive Autographa californica NPV (AcNPV) that is orally infectious and expresses an insect-selective toxin (AaIT), isolated from the scorpion Androctonus australis, under the control of the p10 promoter. Bioassays with the recombinant baculovirus on 2nd instar larvae of Heliothis virescens demonstrated a significant decrease in the time to kill (LT50 88.0 hours) compared to wild-type AcNPV (LT50 125 hours). Production of AaIT was confirmed by western blot analysis of larval hemolymph from infected H. virescens, and bioassays with larvae of Sarcophaga falculata.

Animals↗
PubMed1991

Evaluation of an alginate dressing for pressure ulcers.

Pressure ulcers that secrete moderate to large amounts of fluid often cause leakage from under dressings, odor, staining of clothing, denuding of the skin, and pain. Two highly absorbent dressings derived from seaweed have been introduced into the U.S. market for use in the management of exuding wounds. Severely debilitated patients with full-thickness pressure ulcers were treated for one week to three months with one of these alginate dressings (Kaltostat). The handling and performance characteristics of the dressing are discussed.

Administration, Topical↗
PubMed1990

A scorpion venom neurotoxin paralytic to insects that affects sodium current inactivation: purification, primary structure, and mode of action.

A new toxin, Lqh alpha IT, which caused a unique mode of paralysis of blowfly larvae, was purified from the venom of the scorpion Leiurus quinquestriatus hebraeus, and its structural and pharmacological properties were compared to those of three other groups of neurotoxins found in Buthinae scorpion venoms. Like the excitatory and depressant insect-selective neurotoxins, Lqh alpha IT was highly toxic to insects, but it differed from these toxins in two important characteristics: (a) Lqh alpha IT lacked strict selectivity for insects; it was highly toxic to crustaceans and had a measurable but low toxicity to mice. (b) It did not displace an excitatory insect toxin, 125I-AaIT, from its binding sites in the insect neuronal membrane; this indicates that the binding sites for Lqh alpha IT are different from those shared by the excitatory and depressant toxins. However, in its primary structure and its effect on excitable tissues, Lqh alpha IT strongly resembled the well-characterized alpha scorpion toxins, which affect mammals. The amino acid sequence was identical with alpha toxin sequences in 55%-75% of positions. This degree of similarity is comparable to that seen among the alpha toxins themselves. Voltage- and current-clamp studies showed that Lqh alpha IT caused an extreme prolongation of the action potential in both cockroach giant axon and rat skeletal muscle preparations as a result of the slowing and incomplete inactivation of the sodium currents. These observations indicate that Lqh alpha IT is an alpha toxin which acts on insect sodium channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1989

Dimer structure of a neuropeptide precursor established: consequences for processing.

A prohormone (P1) of locust adipokinetic hormone I (AKH I) is shown here to be a homodimer of a 41 residue subunit called the A-chain. The A-chain, from the N terminal, consists of AKH I (10 amino acids starting with pyroglutamate) followed by a Gly-Lys-Arg processing site and then a 28 residues called the alpha chain containing a single cysteine and a potential Arg-Lys processing site. When processed each molecule of the homodimer precursor yields two copies of AKH I and one alpha chain homodimer. We call the alpha-alpha homodimer product of P1 processing AKH precursor related peptide 1 or APRP 1. The Arg-Lys dibasic pair found within the alpha chain is not cleaved in vivo. Our results show that neuropeptide precursors can be dimers and that dimer products can be synthesized by processing of a preformed dimer precursor rather than by dimerization of independent subunits.

Amino Acid Sequence↗
PubMed1987

Complete, circular papovavirus genomes in the cells of hamsters exposed to a horizontally transmitted lymphomagenic agent.

Contagious lymphomas were produced in a colony of Syrian golden hamsters by an unknown agent that also caused fatal ulcerative bowel disease (UBD) lesions prior to lymphoma development. A low percentage of these animals developed epitheliomas of the skin independently of the UBD or lymphomas. Previous work has shown that the epitheliomas contain numerous hamster papovavirus (HaPV) particles, whereas lymphomas do not. Cells from both kinds of tumors do contain HaPV DNA sequences, however. In this study, Southern blot hybridization showed that complete, circular HaPV genomes were present in these cells. Complete, circular HaPV genomes also were found in the cells of animals with UBD. Electron microscopy revealed the presence of HaPV particles in UBD lesions. These results, together with previous data, indicate that in the hamster, lymphomas contain complete, circular papovavirus genomes in the absence of virus particles, whereas epitheliomas and UBD lesions contain these genomes in the presence of virus particles.

Animals↗
PubMed1985

Purification of biologically active Epstein-Barr virus by affinity chromatography and non-ionic density gradient centrifugation.

Epstein-Barr virus was purified by affinity chromatography on ricin agglutinin Sepharose followed by non-ionic density gradient centrifugation on Nycodenz. The purified virus was highly active in three biological assays: stimulation of immunoglobulin synthesis by B lymphocytes, transformation of B lymphocytes, and superinfection of Raji cells, as well as in an indirect immunofluorescent binding assay. Electron microscopy revealed intact viral particles free of contaminating membranous structures. CsCl density gradient analysis of nick-translated DNA showed material only at the expected viral density with no detectable material at the density of cellular DNA. SDS gel electrophoresis of radioiodinated virus revealed the characteristic viral polypeptides. This method produces highly purified, biologically active virions with an overall recovery of about 30%.

Agglutination Tests↗
PubMed1985

Management of urinary incontinence in Veterans Administration nursing homes.

Nursing Home Care Units in Veterans Administration Medical Centers across the country were surveyed to determine methods of management of urinary incontinence (UI) in the nursing home (NH) setting. Information was obtained from 90 of the VA NHs on demographic aspects of the NH population, prevalence and severity of urinary and fecal incontinence, common problems encountered, and specific strategies and techniques. Written guidelines for bladder training and catheter care from many of the NHs were analyzed. The results of the survey reinforce the need for research designed to improve the care of the incontinent NH patient.

Aged↗
PubMed1985

Papovavirus in epitheliomas appearing on lymphoma-bearing hamsters: lack of association with horizontally transmitted lymphomas of Syrian hamsters.

Several epizootics of lymphoma occurred in a colony of LVG hamsters contaminated with an unusual, horizontally transmitted, subviral, lymphomagenic agent. Hamsters with horizontally transmitted lymphoma, or others housed with these hamsters, occasionally developed epitheliomas bearing an unclassified papovavirus. The possibility that the virus present in the wart-like structures in our hamster colony could activate lymphoma was tested, and a search was conducted for mature virions in passaged epitheliomas and lymphomas. The agent responsible for the skin epitheliomas in our hamster facility was an icosahedral, 36-nm virion compatible with the morphology of a polyomavirus or simian virus 40. Horizontally transmitted lymphoma cells and epitheliomas contained hamster papovavirus (HaPV) DNA sequences detected by dot hybridization; however, such sequences were not found in extracts of lymphomas with oncogenic potential. In contrast to reports by other investigators, infection of hamsters with the papovavirus present in primary epitheliomas produced epitheliomas in good yield but was not reproducibly associated with lymphoma induction. These data confirm the observation that the HaPV is the causative agent of epitheliomas, but they suggest clearly that HaPV is not the agent responsible for lymphomagenesis.

Animals↗