Search PubMed⌕ Search

Biomedical subjects

S Thomson

Publications and source records attributed to S Thomson.

At least 19 recordsLinked to original sources
PubMed2000

Effect of photodynamic therapy on recurrent pituitary adenomas: clinical phase I/II trial--an early report.

Pituitary adenomas, although histologically benign, are not always curable by surgery alone, principally because of dural infiltration, as well as their peculiar anatomical location. Radiotherapy has been employed as an adjuvant therapy to address residual disease with favourable results. This approach is, however, not without side effects, and it cannot be repeated. We are therefore investigating the effectiveness of photodynamic therapy (PDT) on recurrent pituitary adenomas in humans. This study details the protocol applied to 12 patients with recurrent pituitary adenomas, which involved systemic administration of photosensitizer (Photofrin) followed, after a period of 24-48 h, by intraoperative illumination of the tumour bed using 630 nm laser light. The primary end points were visual, endocrine and radiological improvement. The incidence of side effects was also monitored. The longest follow-up is 2 years. Most patients suffering from visual acuity or field defects have shown improvement when followed for 12 months or more. Three patients showed complete recovery of their visual fields. All those who presented with functional adenomas have shown reduction in their hormone levels. Tumour volume, relative to the preoperative size, was 122, 87, 66, 60 and 46% at 4 days, and 3, 6, 18 and 24 months, respectively. One patient developed severe skin photosensitization due to early exposure to direct sunlight and three others displayed minor skin reactions. There was no treatment-related mortality or morbidity. One patient (operated transcranially) developed hemiparesis postoperatively, which recovered completely. We think this is unrelated to the treatment. This prospective study demonstrates that PDT may be safely applied to the pituitary fossa by the trans-sphenoidal route and indicates the need for a randomized, controlled trial in order to establish its therapeutic potential.

Adenoma↗
PubMed2000

Brain attack!--How good is the early management of subarachnoid haemorrhage in accident and emergency departments? South Thames A&E Specialty Sub Committee Audit Group.

OBJECTIVES: The aim of this study was to assess the characteristics and audit the management of patients for whom a diagnosis of subarachnoid haemorrhage was made and who were admitted to a neurosurgical centre from an accident and emergency (A&E) department. The objective was to use the results to make recommendations for improving care in this group of patients. METHODS: Four neurosurgical centres in the South Thames Region provided lists of patients admitted with a diagnosis of subarachnoid haemorrhage during 1997. The medical records and computed tomography of 162 patient episodes from 20 A&E departments were reviewed. The speed of presentation, the provisional diagnosis and the referral patterns were examined. Patient records were audited to investigate what proportion were treated according to established guidelines while in the A&E departments. RESULTS: 63.7% of patients presented to A&E within six hours of ictus and 81.1% within three days. Some 49.2% of patients were seen by a doctor within 30 minutes and 74.7% within one hour. Computed tomography was performed on 18.8% within two hours and only 66.3% within six hours of arrival at the A&E department. Eighteen per cent were treated with nimodipine, 26% with intravenous fluids and 32% were given analgesia before leaving the department. Delays occurred in obtaining computed tomography. CONCLUSIONS: The management of patients who present to A&E departments with subarachnoid haemorrhage is suboptimal. Improved awareness of the disorder, management by senior A&E staff and clear care pathways could help with management.

Emergency Service, Hospital↗
PubMed2000

Adenosine formed by 5'-nucleotidase mediates tubuloglomerular feedback.

Nephron function is stabilized by tubuloglomerular feedback (TGF). TGF operates within the juxtaglomerular apparatus, sensing changes in tubular flow and eliciting compensatory changes in single nephron GFR (SNGFR). The mediator(s) of TGF remains unconfirmed. One theory is that ATP consumed in active transport by the macula densa leads to formation of adenosine, which causes glomerular vasoconstriction. We performed micropuncture in rats to test this hypothesis. Adenosine activity was manipulated by microperfusing nephrons with adenosine A1 receptor blocker, A1-agonist, or 5'-nucleotidase inhibitor. Effects on TGF were characterized by changes in TGF efficiency (the compensation for small perturbations in tubular flow) and by changes in the maximum range over which TGF can cause SNGFR to change. These data were further applied to generate TGF profiles [SNGFR versus late proximal flow (V(LP))]. TGF efficiency was significantly reduced by blocking A1-receptors. TGF efficiency, TGF range, and the slope of the TGF profile (DeltaSNGFR/DeltaV(LP)) were all significantly reduced by blocking 5'-nucleotidase. When adenosine activity was clamped by combining 5'-nucleotidase inhibitor with A1-agonist to determine whether TGF requires adenosine to be present or to fluctuate, the TGF slope was reduced by 83%, indicating that adenosine activity must fluctuate for normal TGF to occur and that adenosine is a mediator of TGF.

5'-Nucleotidase↗
PubMed2000

External quality assessment in the examination of blood films for malarial parasites within Ontario, Canada.

OBJECTIVE: To assess laboratory practice in the examination of blood films for malarial parasites. METHOD: Ontario medical laboratories, licensed by the Ministry of Health, are required to participate in external quality assessment by the Laboratory Proficiency Testing Program, which assesses performance of laboratory assays and also examines the total testing process. Educational strategies are used to improve performance. RESULTS: A 1995 survey indicated shortcomings in detection and identification of malarial parasites in blood films. Consequently, recommendations for the investigation of malarial parasites in blood were issued. In 1996 and 1997, 16 workshops were conducted. A 1997 follow-up external quality assessment survey indicated that problems persist as 27% of laboratories failed to correctly speciate Plasmodium falciparum. Good Practice Guidelines were issued in 1998. CONCLUSION: Further education and assessment are required. Laboratories lacking expertise must establish referral arrangements with more proficient laboratories.

Animals↗
PubMed1999

The nucleosomal response associated with immediate-early gene induction is mediated via alternative MAP kinase cascades: MSK1 as a potential histone H3/HMG-14 kinase.

The nucleosomal response refers to the rapid phosphorylation of histone H3 on serine 10 and HMG-14 on serine 6 that occurs concomitantly with immediate-early (IE) gene induction in response to a wide variety of stimuli. Using antibodies against the phosphorylated residues, we show that H3 and HMG-14 phosphorylation is mediated via different MAP kinase (MAPK) cascades, depending on the stimulus. The nucleosomal response elicited by TPA is ERK-dependent, whereas that elicited by anisomycin is p38 MAPK-dependent. In intact cells, the nucleosomal response can be selectively inhibited using the protein kinase inhibitor H89. MAPK activation and phosphorylation of transcription factors are largely unaffected by H89, whereas induction of IE genes is inhibited and its characteristics markedly altered. MSK1 is considered the most likely kinase to mediate this response because (i) it is activated by both ERK and p38 MAPKs; (ii) it is an extremely efficient kinase for HMG-14 and H3, utilizing the physiologically relevant sites; and (iii) its activity towards H3/HMG-14 is uniquely sensitive to H89 inhibition. Thus, the nucleosomal response is an invariable consequence of ERK and p38 but not JNK/SAPK activation, and MSK1 potentially provides a link to complete the circuit between cell surface and nucleosome.

Animals↗
PubMed1999

MAP kinase-mediated signalling to nucleosomes and immediate-early gene induction.

Extracellular signals are transduced into the nucleus through a variety of signalling mechanisms to elicit changes in patterns of gene expression. This review is focused in the MAP kinase cascades and the part they play in the induction of the immediate-early (IE) genes. We discuss the MAP kinases and their downstream effectors that are known to phosphorylate substrates in the nucleus. In addition to phosphorylating specific transcription factors, MAP kinases and their downstream kinases are implicated in eliciting rapidly targeted alterations in the chromatin environment of specific genes by modulating the phosphorylation and/or acetylation of nucleosomal and chromatin proteins.

Acetylation↗
PubMed1999

Glomerular hyperfiltration in experimental diabetes mellitus: potential role of tubular reabsorption.

An increase in Na+/glucose cotransport upstream to the macula densa might contribute to the increase in single nephron GFR (SNGFR) in early diabetes mellitus by lowering the signal of the tubuloglomerular feedback, i.e., the luminal Na+, Cl-, and K+ concentration sensed by the macula densa. To examine this issue, micropuncture experiments were performed in nephrons with superficial glomeruli of streptozotocin-induced diabetes mellitus in rats. First, in nondiabetic control rats, ambient early distal tubular concentrations of Na+, Cl-, and K+ were about 21, 20, and 1.2 mM, respectively, suggesting collection sites relatively close to the macula densa. Second, glomerular hyperfiltration in diabetic rats was associated with a reduction in ambient early distal tubular concentrations of Na+, Cl-, and K+ by 20 to 28%, reflecting an increase in fractional reabsorption of these ions up to the early distal tubule. Third, in diabetic rats, early proximal tubular application of phlorizin, an inhibitor of Na+/glucose cotransport, elicited (1) a greater reduction in absolute and fractional reabsorption of Na+, Cl-, and K+ up to the early distal tubule, and (2) a greater increase in early distal tubular concentration of these ions, which was associated with a more pronounced reduction in SNGFR. These findings support the concept that stimulation of tubular Na+/glucose cotransport by reducing the tubuloglomerular feedback signal at the macula densa may contribute to glomerular hyperfiltration in diabetic rats. Glomerular hyperfiltration in diabetic rats serves to compensate for the rise in fractional tubular reabsorption to partly restore the electrolyte load to the distal nephron.

Animals↗
PubMed1998

Children's understanding of extended identity.

As adults, we appreciate that judgments of us may reflect our associations with other people. This article examines the development of "extended identity" (G.R. Semin & K. Papadopoulou, 1989) in children between 5 and 11 years. In Experiment 1, children were presented with hypothetical scenarios in which they imagined a close associate had committed a rule violation in a highly public context. Only the older children judged that they would be evaluated negatively through their association with the wrongdoer and that they themselves would feel embarrassment. Given the late appearance of extended identity, Experiment 2 addressed contexts in which the child was responsible for a younger child, so that accountability for the other was explicitly demanded. In such contexts, an appreciation of extended identity appeared earlier than it did in Experiment 1, in which no responsibility for the other was involved.

Child↗
PubMed1998

Luminal signal in tubuloglomerular feedback: what about potassium?

Evidence suggests that a minimal luminal [K+] is required to elicit a full tubuloglomerular feedback (TGF) response, consistent with transmission of the TGF signal across the macula densa (MD) via the Na+-2Cl(-)-K+ cotransporter. Furthermore, it appears that luminal [K+] at the MD is close to the K+ affinity of the Na+-2Cl(-)-K+ cotransporter and changes in response to altering late proximal tubular flow rate (VLP), that is, a maneuver that induces a TGF response. These findings suggest that luminal [K+] (besides [Cl-]) could be rate limiting in TGF. In the thick ascending limb of Henle's loop (TALH), most of the luminal K+ is derived from recycling across the apical tubular membrane. Because changing VLP causes relatively greater alterations in the absolute Na+ and Cl- delivery to Henle's loop than in K+ load, the parallel changes of VLP and luminal [K+] at the MD, despite significant alteration in K+-dependent reabsorption of Na+ and Cl- via the Na+-2Cl(-)-K+ cotransporter, imply a transport-dependent adaptation of K+ recycling in TALH.

Animals↗
PubMed1997

Potential role of luminal potassium in tubuloglomerular feedback.

Transport through the Na+-2Cl(-)-K+ cotransporter in the luminal membrane of macula densa cells is considered critical for tubuloglomerular feedback (TGF). Although various studies could support the importance of luminal Na+ and Cl-, the role of luminal K+ in TGF has not been thoroughly addressed. The study presented here examines this issue in nephrons with superficial glomeruli of anesthetized male Munich-Wistar-Frömter rats. Ambient Na+ concentration in early distal tubular fluid was approximately 22 mM, suggesting collection sites relatively close to the macula densa segment. First, it was found that ambient early distal tubular K+ concentration is approximately 1.3 mM, i.e., close to the K+ affinity of the Na+-2Cl(-)-K+ cotransporter in the thick ascending limb. Second, it was observed that a change in late proximal tubular flow rate, i.e., a maneuver that is known to induce a TGF response, significantly alters early distal tubular K+ concentration. Third, previous experiments failed to show an inhibition in TGF response during retrograde perfusion of the macula densa with K+-free solutions. Because of a potential K+ influx into the lumen between the perfusion site and the macula densa, however, the K+ channel blocker U37883A was added to the K+-free perfusate. TGF response was assessed as the fall in nephron filtration rate in response to retrograde perfusion of the macula densa segment from early distal tubular site. It was observed that luminal U37883A (100 microM) significantly attenuated TGF. Because adding 5 mM KCl to the perfusate restored TGF in the presence of U37883A and because the inhibitory action of U37883A on tubular K+ secretion was confirmed, the effect of U37883A on TGF was most likely caused by inhibition of K+ influx into the perfused segment, which decreased luminal K+ concentration at the macula densa. The present findings support a potential role for luminal K+ in TGF, which is in accordance with a transmission of the TGF signal across the macula densa via Na+-2Cl(-)-K+ cotransporter.

Adamantane↗
PubMed1996

Subpopulations of proteasomes in rat liver nuclei, microsomes and cytosol.

Mammalian proteasomes are composed of 14-17 different types of subunits, some of which, including major-histocompatibility-complex-encoded subunits LMP2 and LMP7, are non-essential and present in variable amounts. We have investigated the distribution of total proteasomes and some individual subunits in rat liver by quantitative immunoblot analysis of purified subcellular fractions (nuclei, mitochondria, microsomes and cytosol). Proteasomes were mainly found in the cytosol but were also present in the purified nuclear and microsomal fractions. In the nuclei, proteasomes were soluble or loosely attached to the chromatin, since they could be easily extracted by treatment with nucleases or high concentrations of salt. In the microsomes, proteasomes were on the outside of the membranes. Further subfractionation of the microsomes showed that the proteasomes in this fraction were associated with the smooth endoplasmic reticulum and with the cis-Golgi but were practically absent from the rough endoplasmic reticulum. Using monospecific antibodies for some proteasomal subunits (C8, C9, LMP2 and Z), the composition of proteasomes in nuclei, microsomes and cytosol was investigated. Although there appear not to be differences in proteasome composition in the alpha subunits (C8 and C9) in the different locations, the relative amounts of some beta subunits varied. Subunit Z was enriched in nuclear proteasomes but low in microsome-associated proteasomes, whereas LMP2, which was relatively low in nuclei, showed a small enrichment in the microsomes. These differences in subunit composition of proteasomes probably reflect differences in the function of proteasomes in distinct cell compartments.

Animals↗
PubMed1996

Processing of N3, a mammalian proteasome beta-type subunit.

Proteasome subunits are encoded by members of the same gene family and can be divided into two groups based on their similarity to the alpha and beta subunits of the simpler proteasome isolated from Thermoplasma acidophilum. RN3 is the beta-type subunit, N3, of rat proteasomes which has been implicated in the peptidylglutamyl-peptide hydrolase activity of the proteinase complex. We have expressed recombinant RN3 protein in Escherichia coli in order to raise subunit-specific polyclonal antibodies. Identification of the position of RN3 on two-dimensional PAGE gels of purified rat liver proteasomes showed a single protein spot of molecular mass 24 kDa and of pI value of about 5. This protein has a free N-terminus, having undergone post-translational processing. After immunoprecipitation from [35S]methionine-labelled human embryo lung L-132 cells using anti-RN3 antibodies, two radiolabelled spots were observed on two-dimensional PAGE gels, one corresponding to the mature N3, the other of molecular mass 28.5 kDa and pI value around 5, which was probably the unprocessed form of N3. However, the latter protein had a higher molecular mass (31 kDa) than was predicted from the sequence of previously cloned cDNA. Therefore rapid amplification of cDNA ends ("RACE') was carried out to determine the full sequence. The lack of detectable RN3 precursor in purified rat liver proteasomes suggests that the processing probably accompanies assembly of the complex. The half-life of the processing was determined to be 31 min in growing L-132 cells. The unprocessed form of N3 was not observed after immunoprecipitation of 35S-labelled complexes with anti-proteasome antibodies. There was no evidence to suggest that unprocessed N3 is found in precursor complexes which have been implicated in the assembly of some other unprocessed beta-type subunits. Interestingly also, the site of cleavage of N3 (ITR decreases TQN) differs significantly from those of other processed animal beta-type proteasome subunits [(H/T)G decreases TT(T/L)], many of which resemble more closely the cleavage site of the Thermoplasma acidophilum beta subunit.

Amino Acid Sequence↗