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Biomedical subjects

S M Chambers

Publications and source records attributed to S M Chambers.

At least 19 recordsLinked to original sources
PubMed2005

The nadir growth hormone after an octreotide test dose predicts the long-term efficacy of somatostatin analogue therapy in acromegaly.

OBJECTIVE: In the treatment of acromegaly, a 'test dose' of octreotide is recommended prior to the use of depot somatostatin analogue (SSA) therapy. However, there remains no consensus regarding the criteria that predict a response to treatment. The ability to select patients who may benefit most from medical therapy is potentially of great value in clinical practice. The aim of the study was to determine the predictive value of both the nadir GH and the mean GH following an octreotide test dose in identifying patients who subsequently achieved disease remission with depot SSA therapy. Remission was defined as a mean GH < 5 mU/l (< 2 microg/l). DESIGN: Retrospective case-control study. PATIENTS: A group of 41 patients with acromegaly underwent an octreotide test dose where GH was measured hourly for a total of 6 h following an injection of octreotide 50 microg subcutaneously. Nadir GH and mean GH following the octreotide test dose were determined. Thirty-three patients were subsequently treated with depot SSA therapy and mean GH and IGF-I levels were determined at follow-up. RESULTS: The nadir GH demonstrated superior predictive power to that of mean GH across a range of GH cut-off values. A nadir GH < 5 mU/l demonstrated 80% sensitivity and 83% specificity in predicting remission with depot SSA therapy. A nadir GH < 10 mU/l demonstrated 100% sensitivity and 56% specificity. CONCLUSIONS: The nadir GH following an octreotide test dose is a useful predictive marker of achieving disease remission with depot SSA therapy used as either a primary or an adjuvant agent.

Acromegaly↗
PubMed2004

Stem cell plasticity: from transdifferentiation to macrophage fusion.

The past 5 years have witnessed an explosion of interest in using adult-derived stem cells for cell and gene therapy. This has been driven by a number of findings, in particular, the possibility that some adult stem cells can differentiate into non-autologous cell types, and also the discovery of multipotential stem cells in adult bone marrow. These discoveries suggested a quasi-alchemical nature of cells derived from adult organs, thus raising new and exciting therapeutic possibilities. Recent data, however, argue against the whole idea of stem cell 'plasticity', and bring into question the therapeutic strategies based upon this concept. Here, we will review the current state of knowledge in the field and discuss some of the clinical implications.

Adult↗
PubMed2000

Measurement of bilirubin partition coefficients in bile salt micelle/aqueous buffer solutions by micellar electrokinetic chromatography.

The partition coefficients for the distribution of bilirubin between aqueous phosphateborate buffer and cholic, taurocholic, taurodeoxycholic, and taurochenodeoxycholic micelles have been measured by micellar electrokinetic chromatography at pH 8.5. Determination of the partition coefficients required that the critical micelle concentration and partial specific volumes be determined for each bile salt. Critical micelle concentrations were slightly higher for the trihydroxy bile salts. Partial specific volumes of the bile salt micelles differed very little from each other, and for each bile salt they were constant over the concentration range studied, which was typically from slightly above the critical micelle concentration to 35 mM. Capacity factors were corrected for the effects of applied voltage by extrapolation of the capacity factor to zero applied volts. The free solution mobility of bilirubin, determined in the absence of bile salt, was also corrected for the effects of applied voltage. Plots of extrapolated capacity factor versus phase ratio yield the partition coefficient as the slope of a linear fit to the data. Partition coefficients for bilirubin were significantly higher for dihydroxy bile salts than for trihydroxy bile salts.

Bile Acids and Salts↗
PubMed2000

Prognosis of alpha-1-antitrypsin deficiency-related liver disease in the era of paediatric liver transplantation.

BACKGROUND/AIM: Alpha-1-antitrypsin deficiency (alpha1ATD) is the commonest metabolic disease leading to liver transplantation (LT) in children. Approximately 10-15% of the PiZZ population develops liver disease. Five percent of them will require LT within the first 4 years of life. This study aimed to investigate the prognosis of the liver disease associated with PiZZ alpha1ATD in the era of liver transplantation and to determine predictors of outcome. METHODS: We reviewed retrospectively the clinical notes of 97 consecutive patients referred from January 1989, when LT became routinely available in our Unit, to July 1998. RESULTS: Of 26 (27%) patients who developed end-stage liver disease, 24 have been transplanted and two are waiting for LT. Twenty-one (81%) of these patients presented with neonatal hepatitis at a median age of 2.1 months. Of 71 (73%) children who have not required LT, 61 (86%) presented with neonatal hepatitis at a median age of 1.6 months. Among infants with neonatal hepatitis who required LT, 18 out of 21 (86%) had jaundice for more than 6 weeks compared with 34 of 61 (56%) who survived without LT (p<0.01). Children requiring LT had higher aspartate aminotransferase (AST) at presentation (p<0.0001) and both higher AST and gamma-glutamyl transferase (GGT) at 6 months (p<0.001), 1-year (p<0.0003) and 5-year (p<0.01) follow up when compared to those who are well without LT. Furthermore, children who developed end-stage liver disease more frequently had severe bile duct reduplication (p<0.01), severe fibrosis (p<0.03) with bridging septa (p<0.02) and established cirrhosis (p<0.04) in the initial liver biopsy. Ninety-five of the 97 children (98%) are currently alive; two died after LT. CONCLUSIONS: The advent of liver transplantation has significantly improved the prognosis of liver disease associated with PiZZ alpha1ATD. Duration of jaundice, severity of histological features and biochemical abnormalities predict outcome at an early stage of the disease.

Child↗
PubMed2000

Mechanism of arsenate resistance in the ericoid mycorrhizal fungus Hymenoscyphus ericae.

Arsenate resistance is exhibited by the ericoid mycorrhizal fungus Hymenoscyphus ericae collected from As-contaminated mine soils. To investigate the mechanism of arsenate resistance, uptake kinetics for arsenate (H(2)AsO(4)(-)), arsenite (H(3)AsO(3)), and phosphate (H(2)PO(4)(-)) were determined in both arsenate-resistant and -non-resistant H. ericae. The uptake kinetics of H(2)AsO(4)(-), H(3)AsO(3), and H(2)PO(4)(-) in both resistant and non-resistant isolates were similar. The presence of 5.0 microM H(2)PO(4)(-) repressed uptake of H(2)AsO(4)(-) and exposure to 0.75 mM H(2)AsO(4)(-) repressed H(2)PO(4)(-) uptake in both H. ericae. Mine site H. ericae demonstrated an enhanced As efflux mechanism in comparison with non-resistant H. ericae and lost approximately 90% of preloaded cellular As (1-h uptake of 0.22 micromol g(-1) dry weight h(-1) H(2)AsO(4)(-)) over a 5-h period in comparison with non-resistant H. ericae, which lost 40% of their total absorbed H(2)AsO(4)(-). As lost from the fungal tissue was in the form of H(3)AsO(3). The results of the present study demonstrate an enhanced H(3)AsO(3) efflux system operating in mine site H. ericae as a mechanism for H(2)AsO(4)(-) resistance. The ecological significance of this mechanism of arsenate resistance is discussed.

Arsenates↗
PubMed1999

Molecular characterization of a new alpha-1-antitrypsin M variant allele, Mwhitstable: implications for DNA-based diagnosis.

The mother and second child from a family, already with one PI ZZ child, were typed PI MZ by isoelectric focusing and unexpectedly as PI ZZ using a commercial alpha-1-antitrypsin genotyping kit. Both methods typed the father and first child as PI MZ and PI ZZ, respectively. DNA sequence analysis identified a 26-base pair (bp) deletion and 2-bp insertion in intron IV of the normal PI*M allele from both the mother and second child. The majority of the binding site for an amplification primer of the genotyping kit was absent in the variant deletion-insertion allele. The apparent PI*Z/PI*Z genotype of the mother and second child therefore arose from amplification of the PI*Z allele alone. Two hundred random DNA samples were subsequently examined and 5 of these were found to be heterozygous for the same deletion-insertion allele. The authors have designated the previously undescribed PI*M allele that harbors this benign polymorphism PI*Mwhitstable. The genotyping kit has been redesigned and revalidated, and its performance is not affected by the presence of the PI*Mwhitstable allele. The Gen Bank accession number for the nucleotide sequence described is AF159454.

Alleles↗
PubMed1998

Multiplex genotyping for cystic fibrosis from filter paper blood spots.

Cystic fibrosis is a common disease of the Caucasian population and is associated with significant early mortality. We present a simple and rapid method for cystic fibrosis genotyping from filter paper blood spots, using a currently available commercial genotyping kit. Using multiplex technology, genotype information on the four most common UK mutations can easily be obtained within a single working day. Used in conjunction with current immunoreactive typsinogen screening protocols, blood spot genotyping offers a method of hastening the diagnosis, and thus treatment, of cystic fibrosis.

Child↗
PubMed1996

Hypothesis: glucagon receptor glycine to serine missense mutation contributes to one in 20 cases of essential hypertension.

1. A missense mutation leading to reduced ligand affinity in the glucagon receptor (GCG-R) has been found recently to be five-fold more common in essential hypertensives than normotensives. The present paper provides additional information on patients that harbour this variant and proposes a possible mechanism by which this may lead to hypertension. 2. The seven hypertensives with the mutation were all female, had a later age of onset of the disease and a slightly higher body mass index. 3. Glucagon is involved in the regulation of fluid and electrolyte excretion. Mutant GCG-R results in reduced ligand affinity and cAMP response which, in the kidney, would reduce the normal natriuretic effect of glucagon. This could lead to enhanced fluid reabsorption, expansion of extracellular fluid volume and hypertension via long-term autoregulation of blood pressure.

Adult↗
PubMed1996

Thyroxine replacement increases central 5-hydroxytryptamine activity and reduces depressive symptoms in hypothyroidism.

Hypothyroidism is associated with both reduced central 5-HT function and an increased incidence of depression. This study tested the hypothesis that the reduced 5-HT function returns to normal with thyroxine replacement therapy. Seven hypothyroid patients were tested before and after adequate thyroxine replacement. Cortisol and prolactin responses to d-fenfluramine, a centrally acting 5-HT-releasing agent, were used as an index of central (hypothalamic) 5-HT responsiveness. 5-HT-mediated cortisol responses were significantly higher after thyroxine replacement. Basal prolactin levels were reduced, but 5-HT-mediated prolactin responses were not significantly higher after treatment, perhaps due to the pre-treatment responses being elevated by the direct stimulatory effects of hypothyroidism itself on pituitary prolactin secretion. Depressive symptomatology improved with thyroxine. TSH levels were positively related to depressive symptomatology, and inversely to cortisol responses. Depressive symptomatology was inversely related to cortisol responses. These findings thus provide further support that central 5-HT neurotransmission is affected by hypothyroidism. They also suggest that the reduction in 5-HT responsiveness is reversible with thyroxine replacement therapy.

Adult↗
PubMed1995

Relationship between early liver graft viability and enzyme activities in effluent preservation solution.

Determination of cellular enzyme activities in washout preservation solution used in hypothermic liver graft storage may allow development of an index that could be clinically valuable in prediction of early post-transplant graft function. In the present study, we collected washed out preservation fluid at the time of graft rinsing from 53 liver recipients. Aspartate aminotransferase and, to a lesser extent, lactate dehydrogenase levels correlated with early postoperative graft viability as assessed by 1-month graft survival and standard biochemical indices of liver function. Those patients with the highest aspartate aminotransferase activity in the washout preservation solution experienced the highest levels of this enzyme postoperatively (area-under-the-curve day 1-3; 1340 vs. 788 IU/L), total bilirubin (area-under-the-curve day 1-5; 901 vs. 538 mumol/L), and rejection frequency (67% vs. 31%) (all P < 0.05), with a significantly lower 1-month graft survival rate compared with patients with low effluent levels (62% vs. 92%, P < 0.05). Two markers of endothelial cell damage, purine nucleoside phosphorylase and a creatine kinase isoenzyme, measured in the fluid did not correlate with early graft viability. It is suggested that assay of aspartate aminotransferase activities in preservation fluid washout samples is a clinically useful indicator of graft viability.

Adult↗
PubMed1981

Estradiol-17 beta dehydrogenase from chicken liver.

NADP+-linked estradiol-17 beta dehydrogenase has been purified 300- to 400-fold from cell-free extracts of chicken liver in a 20 to 30% yield by ammonium sulfate precipitation, ion exchange chromatography, and gel filtration. The enzyme is stable for at least 3 months when stored at -20 degrees C in buffer containing glycerol (50%, v/v). Two forms, with molecular weights of 43,000 and 97,000 are present; these show one major band (Rm = 0.27) and one minor band (Rm = 0.25) on polyacrylamide disc gel electrophoresis. (Rm is defined as the ratio of the distance migrated by the protein band to that of the tracking dye.) The species of lower molecular weight is the more active, with apparent Km values for estradiol-17 beta of 25 and 17.3 microM in the presence and absence, respectively, of bovine serum albumin in the assay medium. The apparent Km for NADP+ is 7.7 microM, and the optimum pH for dehydrogenation is 9.9. The lower molecular weight form has a lambda max at 280 nm, a shoulder at 290 nm, and an A 1% 1 cm of 12.1 at 280 nm. The fluorescence spectrum corresponds to that of a tryptophan-containing protein with lambda max at 288 nm. Isoelectric focusing in gel at pH 5 to 8 shows three major bands of pI 6.9, 6.8, and 6.0. Cross-linking with dimethyl suberimidate followed by electrophoresis reveals five bands. The enzyme is affected by thio reagents and possesses no associated estradiol-sensitive transhydrogenase activity.

17-Hydroxysteroid Dehydrogenases↗
PubMed1979

"Affinity" chromatography of steroid-transforming enzymes with a non-steroidal ligand.

The chromatographic behaviour of an avian oestradiol-17 beta dehydrogenase, the 3(17) beta-hydroxy steroid dehydrogenase from Pseudomonas testosteroni and cortisone reductase from Streptomyces dehydrogenans was studied on columns of p-(phenoxypropoxy)aniline attached to CNBr-activated Sepharose. The ligand was effective in adsorbing the oestradiol dehydrogenase from a partially purified extract of chicken liver, and the cortisone reductase was perferentially retained when mixtures of the three dehydrogenases were applied to columns in 10mM-buffer. Under these conditions the 3(17)beta-hydroxy steroid dehydrogenase was eluted in the front, but was adsorbed in the presence of 3 M-KCl. beta-N-Acetylglucosaminidase present in the liver preparation was not retained by the ligand, whereas lactate dehydrogenase from rabbit muscle was adsorbed in a manner similar to the retention pattern found on affinity chromatography with 2',5'-ADP--Sepharose. The mean overall purification of the oestradiol dehydrogenase was 13-fold, with a mean recovery of 53%. p-(Phenoxypropoxy)aniline offers promise for the purification of steroid-transforming enzymes where elution with substrate or cofactor is not wanted. It is also suggested that the ligand may be of service in the purification of receptors of hormonal steroids.

17-Hydroxysteroid Dehydrogenases↗
PubMed1979

Microsurgical anatomy and dissection of the sphenoid bone, cavernous sinus and sellar region.

The topographic and internal anatomy of the sphenoid bone is reviewed with an emphasis on the relationships important to the transcranial and subcranial surgical approaches to the sphenoid sinus, sella turcica and cavernous sinus. A stepwise method of study and dissection is outlined. The equipment and materials needed for sphenoid bone dissection in the laboratory are reviewed.

Cavernous Sinus↗
PubMed1976

Some evidence for 'speech' as an acoustic feature.

Under conditions of serial recall of auditorily presented lists of digits, recall of the last item has been shown to be adversely affected by the presence of a redundant item following the list. This is known as 'the suffix effect' (Crowder & Morton, 1969). In a series of experiments it is shown that the size of this effect is not influenced by the phonological complexity of the suffix. Non-speech sounds, on the other hand, produce no suffix effect even when the subjects are forced to process them. Certain speech sounds were also found to produce no effect. It is concluded that these sounds lacked properties which are characteristic of speech sounds and so were classified as 'non-speech' and that as a result, these sounds are processed by a separate system from the speech sounds.

Adult↗