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Biomedical subjects

S Thomson

Publications and source records attributed to S Thomson.

At least 55 records · Page 3Linked to original sources
PubMed1995

Inhibition of local nitric oxide synthase increases homeostatic efficiency of tubuloglomerular feedback.

Nephron filtration rate (SNGFR) and proximal tubular reabsorption are coordinated by the processes of tubuloglomerular feedback (TGF) and glomerulotubular balance (GTB). We examined the role of nitric oxide (NO) in TGF and GTB, by delivering the NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA) into late proximal nephrons by micropuncture in Inactin-anesthetized euvolemic rats. First, we determined the dependence of SNGFR on late proximal tubular flow rate (VLP) during orthograde microperfusion of Henle's loop downstream from an obstructing wax block (open-loop microperfusion). Second, we examined the homeostatic efficiency of the TGF-GTB system, (i.e., its ability to stabilize VLP) by perturbing VLP in free-flowing nephrons, while using a noninvasive optical technique to measure flow immediately upstream from the perturbation (closed-loop perturbation). Third, we tested whether L-NMMA could alter the afferent signal to TGF by changing the relationship between VLP and the flow rate (VED) or ionic content (CED) of early distal tubular fluid during open-loop microperfusion. During open-loop microperfusion, L-NMMA decreased SNGFR at VLP between 10 and 40 nl/min but did not alter the relationship between VLP and VED or CED. During closed-loop perturbation, L-NMMA did not affect ambient VLP but increased the homeostatic efficiency of the TGF-GTB system. The combined effects on SNGFR and ambient VLP suggest that L-NMMA reduces proximal reabsorption. However, this could account for only a small fraction of the increase in homeostatic efficiency, the greater share of which must be mediated within the juxtaglomerular apparatus. It appears that juxtaglomerular NO exerts an upward pressure on SNGFR and reduces the efficiency of the TGF-GTB system in stabilizing VLP at ambient flow rates under euvolemic conditions.

Absorption↗
PubMed1994

Retinal topography with the Heidelberg Retina Tomograph.

The Heidelberg Retina Tomograph is a confocal laser scanning microscope designed for in vivo three-dimensional imaging of the posterior segment of the eye. Due to its ability to produce highly accurate and reproducible topographic images, this sophisticated technology can most effectively be applied to the evaluation of topography at and around the optic nerve head. The main application is seen to be the detection and monitoring of change which occurs in glaucoma.

Glaucoma, Open-Angle↗
PubMed1994

Can pulse oximetry detect raised intracompartmental pressure?

Pulse oximetry has been advocated as a simple noninvasive investigation of vascular compromise. Its usefulness in aiding diagnosis of microvascular compromise in a developing compartment syndrome is questioned. This study investigates the reproducibility of pulse oximetry and the effect on arterial haemoglobin saturation of raising limb intracompartmental pressure by compression bandaging. In 32 out of 50 normal subjects there was a difference in percentage saturation between right and left arms, with a 2% difference in 6 people (12%). Percentage saturation fell significantly at average bandage pressures of 80 mmHg (P < 0.0001) and 60 mmHg (P < 0.001). At clinically relevant pressures, the test had a sensitivity of 40.4%. With a greater than 50% risk of a false-negative result, pulse oximetry is not an appropriate additional investigation in the detection of raised intracompartmental pressure.

Adult↗
PubMed1993

cDNA cloning of a new type of subunit of mammalian proteasomes.

The primary structure of a new type of subunit (RN3) of rat proteasomes (multicatalytic proteinase complexes) has been determined from the nucleotide sequence of the cDNA. The cDNA encodes a protein of 232 amino acids but the directly determined N-terminal amino acid sequence suggests that the subunit is post-translationally processed to a M(r) = 24k form. Sequence alignments reveal a similarity of RN3 to other proteasome subunits. It can be designated a B-type proteasomal subunit but is not closely related to the beta subunit of the archaebacterial proteinase or to other members of the B group.

Amino Acid Sequence↗
PubMed1993

IV therapy: a financial feasibility study.

Results of a feasibility study comparing peripheral catheters to midline catheters are summarized. A step-by-step process involving audit studies, cost figures, data collection, calculation parameters, and cost analysis determined the effectiveness of the new technology.

Catheterization, Peripheral↗
PubMed1992

High-level expression of a recombinant antibody from myeloma cells using a glutamine synthetase gene as an amplifiable selectable marker.

We report a method for introducing a glutamine synthetase (GS) selectable marker into myeloma cells in which transfectants are selected by growth in a glutamine-free medium. Vector amplification can subsequently be selected using the specific inhibitor of GS, methionine sulphoximine (MSX). Using this system, DNA sequences encoding a chimeric B72.3 IgG4 antibody were expressed from hCMV-MIE promoters in NSO myeloma cells. A cell line was isolated after a single round of selection for vector amplification which contains approximately 4 copies of the vector, secretes 10-15 pg/cell/day cB72.3 antibody during exponential growth and can accumulate 560 mg/l antibody in a fed-batch air-lift fermentation system. Productivity is stable in the absence of MSX selection.

Animals↗
PubMed1992

Enhanced levels of multicatalytic proteinase mRNAs in Rous sarcoma virus transformed cells.

The multicatalytic proteinase (proteasome; MCP) is a high molecular mass proteinase which is found in all eukaryotic cells. Northern blot analysis of the levels of MCP mRNAs in a Rat-1 fibroblast cell line and in cells transformed with Rous sarcoma virus showed marked increases in the transformed cells. However, the results of immunoblot analysis with anti-MCP antibodies suggested that the MCP protein content of the two cell lines was similar.

Animals↗
PubMed1991

Thermomechanical analysis of frozen aqueous systems.

Thermomechanical Analysis (TMA), using the parallel-plate-rheometer mode of the DuPont 943 TMA, was used to evaluate the softening properties of frozen aqueous carbohydrate model systems. A sample (of fixed dimension) of frozen solution was placed between the parallel plates and cooled to -80 degrees C. The sample was then heated at a linear heating rate of 2 degrees C/min to +15 degrees C. The dimension change was plotted as a function of temperature or time, and an estimate was made of the glass transition point and of the thermal softening behavior of the system. Good agreement was found with previously published glass transition data for similar frozen carbohydrate model systems measured by differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA).

Chemistry Techniques, Analytical↗
PubMed1991

The V3 loops of the HIV-1 and HIV-2 surface glycoproteins contain proteolytic cleavage sites: a possible function in viral fusion?

Located close to the crown of the V3 type-specific neutralization loop of the human immunodeficiency virus type 1 (HIV-1) (IIIB) SU glycoprotein gp120, are several potential sites that should be susceptible to proteolytic cleavage by enzymes of trypsinlike or chymotrypsinlike specificity, or by aspartic proteinases. The linkages potentially sensitive to chymotryptic/aspartic proteinase cleavage are retained also within the equivalent domain of HIV-2 (ROD) gp105. We show that thrombin and tryptase cleave HIV-1 gp120 specifically at the tryptic site (GPGR decreases AFVT), and that cathepsin E, an endosomal aspartic proteinase, cleaves at the chymotrypsinlike site (GPGRAF decreases VT). HIV-2 gp105 is also cut by cathepsin E at a site (QIML decreases MSGH) in its V3 loop. Cleavage of HIV-1 gp120 by thrombin is enhanced by sCD4 binding, but is prevented by transient exposure of gp120 to nonionic detergent. Thrombin treatment of HIV-1 gp120 destroys the binding sites for some neutralizing monoclonal antibodies (MAbs) on the V3 loop, but does not affect the affinity of gp120 for sCD4. Conversely, binding of neutralizing MAbs to the HIV-1 V3 loop prior to addition of thrombin or cathepsin E blocks the cleavage reactions, and the binding of some HIV-positive sera to gp120 blocks thrombin cleavage. Analysis of published sequences suggests that all HIV-1, HIV-2, and simian immunovirus (SIV) isolates contain potential proteolytic cleavage sites at similar positions in their V3 loops or equivalent domains. We suggest that cleavage of the V3 loop by a cell surface or endosomal proteinase occurs during the HIV-cell fusion reaction, and that neutralizing antibodies directed against the V3 loop might act by inhibition of this reaction.

Amino Acid Sequence↗
PubMed1991

Evaluation of a new hydrocolloid occlusive dressing for central catheters used in total parenteral nutrition.

Catheter-related sepsis still remains one of the most frequent and serious complication of total parenteral nutrition. Strategies for preventing contamination of central venous lines have focused on decreasing the number of micro-organisms around the exit site and inhibiting their entry into the catheter wound. This prospective study compares a new occlusive hydrocolloid dressing (Visiband; Convatec Squibb) with that of a polyurethane film dressing for nutritional catheters. Dressings were changed either on day 3 or day 5 after application. Swab smears of the catheter exit site at each dressing change were stained by Gram's method before inoculation onto a blood agar plate, a chocolate agar plate and a MacConkey agar plate. Significantly less colonisation occurred under the former dressing at day 3 and day 5 dressing changes. In addition, the polyurethane film dressing was associated with a significant increase in skin colonisation (P = 0.04) and the number of positive Gram-stain microbes if left unchanged for 5 days (P = 0.0018). Staphylococcus aureus catheter-related sepsis occurred in 1 patient on day 18 in the polyurethane film dressing group. In addition, Candida albicans colonisation was confined to patients with the polyurethane film dressing. While the type of dressing applied to the catheter exit site may influence the incidence of catheter colonisation and infection, it must be emphasised that strict adherence to aseptic technique during catheter insertion and manipulation of the dressing is vital in the prevention of catheter-related sepsis during total parenteral nutrition.

Adult↗
PubMed1991

The hemodynamic effects of S-nitrosocaptopril in anesthetized dogs.

We studied the effects of a unique vasoactive agent, S-nitrosocaptopril (SnoCap), in an anesthetized canine preparation. We have previously demonstrated that this agent manifests the properties of both a direct nitrovasodilator and an angiotensin-converting enzyme inhibitor in vitro. The present investigation was performed to evaluate the effects of SnoCap in vivo. Intravenous administration of SnoCap produced immediate reductions in blood pressure and significantly attenuated the pressor response to angiotensin I. Equieffective doses of SnoCap had a greater duration of action after intravenous bolus administration compared with nitroglycerin (15.3 +/- 2.6 min vs. 3.2 +/- 0.5 min, respectively; P less than .01); importantly, this effect was apparent despite the relatively short plasma half-life of the compound (T1/2 alpha = 0.48 min, T1/2 beta = 5.54 min) and did not appear to be the result of inhibition of angiotensin-converting enzyme. Another unexpected property of SnoCap was that its nitrovasodilator effect was 10- to 30-fold less potent than nitroglycerin when administered as a bolus, but more efficacious when given by continuous infusion. These data support the view that SnoCap is a vasoactive substance with the properties of a nitrovasodilator and an angiotensin-converting enzyme inhibitor, as well as the unique properties of an extended duration of action and greater potency when administered by continuous intravenous infusion than by bolus injection. The clinical utility of this compound in humans and in individuals with specific disease states remains to be demonstrated.

Angiotensin I↗
PubMed1990

Characterization of recombinant gp120 and gp160 from HIV-1: binding to monoclonal antibodies and soluble CD4.

We compared four preparations of recombinant HIV-1 envelope glycoprotein: mammalian (Chinese hamster ovary cells) gp120 (Celltech); baculovirus gp120 from American Biotechnologies Inc. (ABT) and from MicroGeneSys (MGS); and baculovirus gp160 (Institute of Virology, Oxford, UK). Each envelope glycoprotein binds to a neutralizing monoclonal antibody (MAb) directed against the V3 loop, confirming the integrity of this type-specific neutralization epitope. MGS gp120 binds abnormally well to a MAb which recognizes an epitope preferentially exposed on denatured gp120. Consistent with this finding, MGS gp120 binds to soluble CD4 (sCD4) with an affinity 50-100-fold lower than that of Celltech gp120. The affinity of Celltech gp120 from sCD4 is 2.3 nM, indistinguishable from that of gp120 extracted from HIV-1 virions. Baculovirus gp120 (ABT) and gp160 also have a high affinity for sCD4. A significant proportion of anti-gp120 antibodies in HIV-positive human sera recognize epitopes that are dependent on the mammalian glycosylation pattern, and a human HIV-positive serum inhibits the binding of mammalian gp120 to sCD4 five- to 10-fold more potently than it inhibits baculovirus gp120 binding to sCD4.

Acquired Immunodeficiency Syndrome↗
PubMed1989

A bloodspot androstenedione assay suitable for home-monitoring of steroid replacement therapy in congenital adrenal hyperplasia.

A bloodspot assay has been developed using an antiserum raised against androstenedione-3-carboxymethyloxime-bovine serum albumin (AD-3CMO-BSA) conjugate and 125I-AD-3CMO-histamine tracer. The method has a detection limit of 0.6 nmol/L blood and a working range from 0.6 to 40 nmol/L blood. The between-batch precision ranged from 8.4% to 23.3%. Bloodspot androstenedione (AD) concentrations were measured in 50 neonates (26 male, 24 female) and in 95 children (54 male, 41 female) aged 6 months to 18 years. No sex difference in concentrations was found in neonates, in pre-pubertal children up to 8 years of age, in pubertal children (males 8-16 years, females 8-14 years) or post-puberty. Bloodspot AD concentrations ranged from less than 0.6 to 2.7 nmol/L in neonates, less than 0.6 nmol/L in pre-pubertal children, 0.6-2.1 nmol/L in pubertal children and less than 0.6-4.6 nmol/L post-puberty. Daytime bloodspot profiles in 10 children on replacement therapy for congenital adrenal hyperplasia generally showed good correlation between 17 alpha-hydroxyprogesterone and AD concentrations (r = 0.928, P less than 0.001). Bloodspot AD profiles have advantages over 17 alpha-hydroxyprogesterone profiles for the assessment of the adequacy of glucocorticoid replacement therapy.

17-alpha-Hydroxyprogesterone↗