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Biomedical subjects

N E Williams

Publications and source records attributed to N E Williams.

At least 19 recordsLinked to original sources

Profound bradycardia and hypotension following spinal anaesthesia in a patient receiving an ACE inhibitor: an important 'drug' interaction?

An 86-year-old man on whom a transurethral resection of prostate was performed under spinal anaesthesia developed profound bradycardia and hypotension with disturbance of consciousness during transfer to the recovery room. Initial treatment with atropine produced rapid improvement in cardiovascular and cerebral function. A further hypotensive episode (without bradycardia) occurred approximately 1 h later but responded rapidly to methoxamine. The patient made a full recovery during an overnight stay on the High Dependency Unit. Possible mechanisms for this event are discussed, with the proposal that the concomitant administration of captopril and the relative unavailability of Angiotensin II may have significantly contributed to the problem.

Adenocarcinoma↗

Elevation of endogenous nucleophiles in rat lung by cysteine and glutathione esters in vitro.

In this study, we have compared the uptake of L-cysteine (L-CySH), D-cysteine (D-CySH), L-cysteine isopropyl ester (L-CIPE) and D-cysteine isopropyl ester (D-CIPE) in rat lung slices and tracheal sections and determined the effectiveness of glutathione (GSH), GSH isopropyl monoester, GSH isopropyl diester, gamma-glutamylcysteine (gamma-glu-cys) isopropyl monoester and gamma-glu-cys isopropyl diester to elevate and prolong intracellular GSH concentrations in rat lung slices. Lung slices were incubated with 1.0 mM of thiol and the concentrations determined intracellularly and extracellularly with time. Slices incubated with GSH, GSH isopropyl diester and gamma-glu-cys isopropyl diester had cellular GSH concentrations increased by up to 60%, 95% and 58%, respectively, whereas GSH isopropyl monoester and gamma-glu-cys isopropyl monoester did not increase the intracellular GSH concentration. Extracellularly, the GSH concentration had decreased by 15%, GSH isopropyl diester by 27%, gamma-glu-cys isopropyl diester by 66% and both isopropyl monoesters by over 90% at 120 min. Lung slices and tracheal sections incubated with L- or D-CySH at 37 degrees had increased cellular concentrations of L- and D-CySH which ranged between 0.88-1.25 nmol mg(-1) and 1.35-2.25 nmol mg(-1) , respectively. Reducing the incubation temperature to 4 degrees had little effect on the accumulation of D-CySH; however, L-CySH concentrations increased progressively in the trachea and lung to reach 2.73 and 2.63 nmol mg(-1) at 90 min, respectively. Lung slices incubated with L- or D-CIPE had increased L- or D-CySH concentrations up to a max of 13.7 and 11.1 nmol mg(-1) and tracheal sections up to a max of 5.56 and 11.09 nmol mg(-1). In the lung slice medium, L- and D-CIPE levels had decreased by 75.2% and 74.0% at 90 min, respectively, and from the tracheal section medium, L- and D-CIPE concentrations had decreased by 66.7% and 32.7%, respectively. Preincubation of lung slices and tracheal sections with the carboxylesterase inhibitor, bis (p-nitrophenyl) phosphate (BNPP), almost completely prevented the disappearance of L- and D-CIPE extracellularly and greatly reduced the appearance of cellular L- and D-CySH. GSH, GSH isopropyl diester and gamma-glu-cys isopropyl diester elevated and prolonged GSH concentrations in rat lung slices, but GSH isopropyl monoester and gamma-glu-cys isopropyl monoester did not increase GSH levels. The uptake of L-CySH, but not D-CySH, is temperature sensitive in rat lung slices and tracheal sections and carboxylesterases appear to have a major influence on the uptake and metabolism of L- and D-CIPE by rat lung slices and tracheal sections.

Animals↗

Premedication with controlled release diclofenac sodium reduces post-operative pain after minor gynaecological surgery.

The effect of a single pre-operative oral dose of controlled release diclofenac sodium on post-operative pain after minor gynaecological surgery was investigated. Fifty-two women took part in a double-blind controlled study. Pain was assessed by visual analogue scale (VAS), a four-point verbal rating score, and the requirement for post-operative analgesia. Those patients who received diclofenac had significantly less post-operative pain than the placebo group up to 2 h after surgery.

Analgesics, Non-Narcotic↗

HSP70 and HSP90 homologs are associated with tubulin in hetero-oligomeric complexes, cilia and the cortex of Tetrahymena.

We show in the present study that homologs of hsp90 and hsp70 are induced by heat shocks in Tetrahymena and appear to form a high molecular mass complex (approximately 700 kDa) with tubulin. Three members of the hsp70 family (hsp72, 73, and 78) and one member of the hsp90 family (hsp82) have been identified by immunological or by a combination of immunological and sequencing methods. The known components of the 700 kDa complex and the conditions under which it can be recovered suggest that it may be an induced protective assemblage rather than a normal processing intermediate. Immunoblotting and immunofluorescence studies suggest further that large amounts of hsp73 and lesser amounts of hsp82 are associated with mature microtubules in both cilia and the cortex in this cell type. Some site-specific localizations of the identified heat shock proteins were also noted in non-microtubular components of the cell cortex.

Animals↗

Cellular polarity in ciliates: persistence of global polarity in a disorganized mutant of Tetrahymena thermophila that disrupts cytoskeletal organization.

Much of the cell surface on the ciliate Tetrahymena thermophila is covered by a polarized lattice of cytoskeletal structures that are associated with basal bodies of the ciliary rows. Unique structural landmarks, including an oral apparatus and contractile vacuole pores, develop before cell division in localized domains located, respectively, posterior and anterior to the transverse fission zone. All of these structures can be visualized by specific monoclonal antibodies. A single-locus recessive mutation, disorganized-A (disA), primarily affects the striated rootlets of the ciliary-row basal bodies and brings about a severe disorganization in the positioning and orientation of these basal bodies and associated cytoskeletal elements. Nonetheless, the new oral apparatus, contractile vacuole pores, and other unique structures appeared at or near their normal sites along the anteroposterior axis of disA cells, indicating that the positioning of these localized structures is not dependent on the integrity of the ciliary rows. Abnormalities were present in the details of construction of some of the localized structures and in aspects of cell shape that may be influenced by these details. In the main, however, analysis of disA mutant cells indicates that intracellular domains near the cell poles develop independently of the vectorial polarity of the ciliary rows.

Alleles↗

Is Cyclin Zeuthen's "division protein"?

Biochemical evidence is presented for the presence of cyclin in Tetrahymena. Zeuthen previously postulated the existence of a heat-labile "division protein" to explain heat-shock-induced division synchrony in Tetrahymena [(1964) Synchrony in Cell Division and Growth (Zeuthen, E., Ed.), pp. 99-158, Interscience, New York]. We show that cyclin is heat-labile in Tetrahymena and suggest that cyclin may be Zeuthen's division protein. Cyclin and cell cycle control is of interest in Tetrahymena because the division mechanism drives macronuclear amitosis, closed and acentric micronuclear mitosis, and cortical differentiation in this cell type.

Animals↗

Plasma concentrations of bupivacaine after stellate ganglion block using two volumes of 0.25% bupivacaine plain solution.

Plasma concentrations of bupivacaine were measured in patients after stellate ganglion block using either 10 or 20 ml of 0.25% plain solution. The mean peak concentrations were greater in the larger volume group, but this was not statistically significant. From 30 min after injection, there was a significantly greater plasma concentration in the larger volume group. The concentrations approached the limit of detection in the smaller volume group at 2 h after block.

Anesthesia, Local↗

The formation of basal body domains in the membrane skeleton of Tetrahymena.

Differentiated regions within the membrane skeleton are described around basal bodies in the ciliary rows of Tetrahymena. These domains, approximately 1 micron in diameter, are characterized by a relatively dense ultrastructure, the presence of a family of proteins called K antigens (Mr 39-44 x 10(3)) that are recognized by mAb 424A8, and the apparent exclusion of major membrane skeleton proteins that are present in most other regions of the cell (Mr 135, 125 x 10(3]. Mature basal body domains are asymmetric, reflecting the polarity of the cell as a whole. A similar differentiation of the membrane skeleton occurs in the oral apparatus, except here the K antigens surround four clusters of basal bodies (from which this cell takes its name) rather than the individual basal bodies. The development of new basal body domains in the cell cycle is described, with similarities and differences noted between somatic and oral regions of the cell. It is concluded that the capacity of this cell for precise topographic regulation of molecular events in the membrane skeleton makes it a useful model for the study of cortical differentiation in cells generally.

Animals↗

Tetrins: polypeptides that form bundled filaments in Tetrahymena.

The cortex of the ciliated protozoan Tetrahymena contains a number of fibrous elements, including a network of filaments that pervades the feeding organelle of this organism. The cluster of polypeptides (79-89K; K = 10(3) Mr) in Tetrahymena pyriformis GL-C that constitute these filaments has been purified by in vitro assembly after solubilization in 1.0 M KI. Four distinct sets of these polypeptides, designated 'tetrins', have been shown to be distinguishable from each other by immunochemical and biochemical criteria. The smallest filaments reassembled in vitro were 3-4 nm in diameter and these fine filaments were seen to be bundled together into thicker strands of varying diameters, similar to those within the cell. The thicker filament bundles were clearly distinguishable from intermediate filaments, but fine filaments in these bundles were superficially similar to the 2-5 nm filaments described as microtubule-associated proteins in other organisms. The ultrastructure of the tetrin filaments localized within the feeding organelle reveals a substantial presence of these filaments apart from microtubules. In addition, circular dichroism measurements indicate a relatively low alpha-helical content for these filaments and suggest that the tetrins may be substantially different from other fine filament proteins such as the tektins and giardins.

Amino Acids↗

Structure-activity studies of trichothecenes: cytotoxicity of analogues and reaction products derived from T-2 toxin and neosolaniol.

Forty-two analogues and reaction products derived from T-2 toxin or neosolaniol were assayed for their cytotoxicity to cultured mouse lymphoma cells. Structure-activity relationships confirmed the stereospecific nature of the cytotoxic action of T-2. Cytotoxicity was particularly susceptible to changes at C3, C4, C9, and C10 but was relatively unaffected by changes at C8, which appears to represent a region of steric tolerance in the interaction of T-2 with a cellular constituent. The most potent compounds were T-2, diacetoxyscirpenol, and a series of C8 ester analogues 11 and 31-35.

Animals↗

Properties of microtubule-free cortical residues isolated from Paramecium tetraurelia.

We have found that shape-preserving residues devoid of microtubules can be prepared from Paramecium using Triton X-100 at high ionic strength. These residues contain many proteins, including one showing antigenic relationship to chicken alpha-spectrin, and three showing antigenic relationship to Tetrahymena cortical proteins. These antigens have been localized by immunofluorescence microscopy, and the isolated cortical residues have been characterized ultrastructurally. These preparations should be useful in detailed studies of the structure, development and evolutionary relationships of cortical architecture in ciliated protozoa.

Animals↗

Identification and localization of major cortical proteins in the ciliated protozoan, Euplotes eurystomus.

Shape-preserving cortical residues have been isolated from Euplotes eurystomus cells by the application of Triton X-100 at high ionic strength. These integrated structures consist of articulated plates and widely interspersed cages that formerly contained basal bodies associated with the clusters of cilia characteristic of this cell type. Using SDS-PAGE and immunolocalization procedures, we have identified major subunit proteins of both the plates (116, 110 (X10(3] Mr, and the basal body cages (86 X 10(3) Mr). The potential for studies of these proteins in contributing to our understanding of cortical development and evolution in Euplotes is discussed.

Animals↗

Spread of local anaesthetic solutions following sacral extradural (caudal) block: influence of posture.

Extradural sacral (caudal) block was performed in 17 cases (14 patients) of chronic low back pain. In each case 22 ml of a bupivacaine/methylprednisolone solution incorporating a radioopaque dye was injected over a 2-min period. Patients were randomly assigned to receive the injection in the horizontal position or with 15 degrees head-up or head-down tilt applied to the operating table. Results indicate that analgesia is usually more localised than spread of solution determined by x-ray evidence and that higher levels of analgesia are achieved in patients in the head-up position. Possible causes are the differing distribution characteristics of the constituents of the solution and the gravitational effects of posture on cerebrospinal fluid mechanics. Technical problems associated with obesity, congenital abnormalities, vascular uptake of solution, and delayed spread of the injectant due to adhesions are discussed.

Anesthetics, Local↗

Differential effects of neuromuscular blocking agents on suxamethonium-induced fasciculations and myalgia.

The effect of pretreatment with suxamethonium, gallamine or pancuronium on suxamethonium-induced fasciculations and myalgia was studied in a controlled, randomized and double-blind clinical trial. Both fasciculations and myalgia were assessed on a four-point rating scale. There was no significant correlation between fasciculations and postoperative muscle pain at 24, 48 or 72 h, and pretreatment with suxamethonium had no significant effect on fasciculations or myalgia. Gallamine had a more marked effect on fasciculations than pancuronium, and the decrease in the fasciculation score was statistically significant. In contrast, pancuronium had a greater effect on myalgia, and decreased postoperative muscle pain significantly at 24 and 48 h. These differences may reflect the differential activity of gallamine and pancuronium at the neuromuscular junction. Pretreatment had little or no effect on plasma potassium concentrations.

Adolescent↗