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Biomedical subjects

M D Barber

Publications and source records attributed to M D Barber.

15 recordsLinked to original sources
PubMed1999

Relationship of serum levels of interleukin-6, soluble interleukin-6 receptor and tumour necrosis factor receptors to the acute-phase protein response in advanced pancreatic cancer.

The level of the acute-phase response is a major predictor of survival in patients with advanced pancreatic cancer. This study examines the association between the acute-phase protein response, as determined by serum C-reactive protein, and serum levels of interleukin-6, soluble interleukin-6 receptor and the soluble tumour necrosis factor receptors in patients with pancreatic cancer. Thirty-four blood samples were collected from 13 patients with advanced pancreatic cancer. Samples were also collected from six healthy subjects. Levels of C-reactive protein, interleukin-6, soluble interleukin-6 receptor and soluble tumour necrosis factor receptors 55 and 75 were measured by indirect ELISA. Serum levels of C-reactive protein, interleukin-6 and soluble tumour necrosis factor receptors 55 and 75 were significantly higher in cancer patients than in controls. Levels of serum soluble interleukin-6 receptor were not significantly different between the two groups. In cancer patients, a significant positive association was found between the level of the acute-phase protein response and serum levels of interleukin-6, soluble tumour necrosis factor receptor 55 and soluble tumour necrosis factor receptor 75. No association was found between levels of soluble interleukin-6 receptor and any other factor. There is no significant relationship between the level of soluble interleukin-6 receptor and the acute-phase protein response in vivo and the biological role of soluble interleukin-6 receptor in the chronic inflammatory component of cachexia remains unclear.

Acute-Phase Reaction↗
PubMed1998

Biological evaluation of a lipid-mobilizing factor isolated from the urine of cancer patients.

We have previously shown human lipid-mobilizing factor (LMF) to be homologous with the plasma protein Zn-alpha2-glycoprotein in amino acid sequence, electrophoretic mobility, and immunoreactivity. In this study, both LMF and Zn-alpha2-glycoprotein have been shown to stimulate glycerol release from isolated murine epididymal adipocytes with a comparable dose-response profile. Both LMF and Zn-alpha2-glycoprotein caused a stimulation of adenylate cyclase in murine adipocyte plasma membranes in a GTP-dependent process, with maximum stimulation at 0.1 microM GTP and with saturation at protein concentrations of >5 microg/assay. Administration of LMF to exbreeder male mice over a 89-h period produced a decrease in body weight without a change in food and water intake. Body composition analysis showed a 42% reduction in carcass lipid when compared with controls. Treatment of ob/ob mice with human LMF over a 160-h period also produced a decrease in body weight, with a 19% reduction in carcass fat, without a change in body water or nonfat mass. Serum levels of glycerol and 3-hydroxybutyrate were significantly increased, as was oxygen uptake by interscapular brown adipose tissue, providing evidence of increased lipid mobilization and utilization. Human white adipocytes responded to both LMF and isoprenaline to the same extent, although the maximal response was lower than that for murine white adipocytes. These results suggest that LMF not only has the capacity to induce lipid mobilization and catabolism in mice, but it also has the potential to exert similar effects in cachectic cancer patients.

Adenylyl Cyclases↗
PubMed1998

New reference allelic ladders to improve allelic designation in a multiplex STR system.

This paper reports the composition of a new reference allelic ladder mixture for use with a multiplex DNA profiling system consisting of six short tandem repeat loci. The loci included in this mixture are HUMTH01, D21S11, D18S51, D8S1179, HUMVWAF31/A, HUMFIBRA/FGA and an amelogenin sex test. Sequence analysis of individual ladder alleles was carried out and allelic designations made in accordance with the recommendations of the International Society of Forensic Haemogenetics (1992; 1994). A series of rare alleles which increase the range of alleles previously reported were identified. By including some of the rare alleles into the ladder marker system, we have significantly improved the ability to identify new alleles in unknown samples.

Alleles↗
PubMed1997

Recurrent appendicitis.

BACKGROUND: The existence of appendiceal inflammation which resolves spontaneously without surgical intervention has long been controversial. This study was undertaken, therefore, to determine the existence and incidence of recurrent appendicitis. METHODS: The existence of a large database of patients with abdominal pain enabled a retrospective study of the casenotes of the 1084 patients who had an inflammed appendix removed between January 1982 and December 1991 in a Scottish District General Hospital. Sixty consecutive patients who had a normal appendix removed during this period were also studied. RESULTS: Seventy-one patients (6.5 per cent) attended the accident and emergency department 89 times with symptoms and signs compatible with appendicitis which resolved spontaneously between 3 weeks and 12 years before an attendance during which an inflamed appendix was removed. There were significant differences in clinical signs and symptoms (using the Alvarado scoring system) between patients whose symptoms resolved, those with a normal and those with an inflamed appendix. Those who had a normal appendix removed were more likely to be female than those with resolving symptoms (67 versus 42 per cent, P < 0.01). CONCLUSION: Recurrent appendicitis exists and affects at least 6.5 per cent of those who ultimately have an inflamed appendix removed.

Adolescent↗
PubMed1996

Sequence analysis and allelic designation of the two short tandem repeat loci D18S51 and D8S1179.

This paper reports the sequences of eleven D8S1179 and twenty one D18S51 alleles. The D8S1179 alleles ranged in size from 162 bp to 202 bp and increased in size by regular 4 bp increments. They were shown to possess a compound repeat region composed of the tetranucleotides TCTA and TCTG. Alleles at the D18S51 locus ranged in size from 271 bp to 343 bp and possessed a simple repeat region composed of the tetranucleotide AGAA. The majority of alleles increased in size by 4 bp increments corresponding to the addition of one tetranucleotide repeat unit. However, three alleles differed in size by 2 bp from the 4 bp increment as a result of a dinucleotide insertion within the 3' flanking region. These alleles also exhibited an altered 3' flanking sequence in the first four nucleotides following the repeat region. The allelic designations proposed for these loci on the basis of this sequence data are currently being used in a multiplex PCR profiling system employed in a National DNA database in the United Kingdom.

Alleles↗
PubMed1996

Structural variation in the alleles of a short tandem repeat system at the human alpha fibrinogen locus.

This paper reports the sequences of 22 alleles identified at the HumFGA (human alpha fibrinogen) short tandem repeat locus in the British Caucasian and Afro-Caribbean populations. Alleles at the lower end of the observed size range were found to increase in size by 4-bp increments with the repeat unit following the pattern TC(TCTT)n. However, 5 alleles were identified that differed in size by 2 bp from the 4 bp increment as a result of the deletion of a TC dinucleotide, or the addition of a TT dinucleotide, immediately prior to the 1st repeat unit. Alleles at the upper end of the observed size range were found to have a more complex repeat unit structure and also exhibited duplication of both 5' and 3' flanking sequences. A nomenclature for the designation of HumFGA alleles is proposed on the basis of this sequence data.

Base Sequence↗
PubMed1995

Structural variation of novel alleles at the Hum vWA and Hum FES/FPS short tandem repeat loci.

This paper reports the sequences of novel alleles identified during population databasing studies on the short tandem repeat loci HumvWA and HumFES/FPS. Two HumFES/FPS alleles follow the simple repeat pattern (ATTT)7 and (ATTT)15. Sequence variation corresponding to an A to C transversion occurred in the 5' flanking region in two individuals possessing the designated allele 7. Two HumvWA alleles exhibited compound repeat regions comprising TCTA and TCTG repeat units. Sequence analysis confirmed the putative designation of 11 for a 127 base pair allele. However, a 131 base pair allele, putatively designated as 12, exhibited a more complex sequence. Two different types of repeat unit structures were identified which also exhibited sequence variation in the 3' flanking region.

Alleles↗
PubMed1993

Site-directed mutagenesis of yeast phosphoglycerate kinase. Arginines 65, 121 and 168.

In the absence of a structure of the closed form of phosphoglycerate kinase we have modified by site directed mutagenesis several of the residues which, on the basis of the open form structure, are likely to be involved in substrate binding and catalysis. Here we report on the kinetic and anion activation properties of the yeast enzyme modified at positions 65, 121 and 168. In each case an arginine, thought to be involved in the binding of the sugar substrate's non-transferable phosphate group, has been replaced by lysine (same charge) and by methionine (no charge). Km values for 3-phosphoglycerate of all six mutant enzymes are only marginally higher than that of the wild-type enzyme. Removing the charge associated with two of the three arginine residues appears to influence (as judged by the measured Km's) the binding of ATP. Although binding affinity is not necessarily coupled to turnover the substitutions which have the greatest effect on the Km's do correlate with the reduction in enzymes maximum velocity. The one exception to this generalisation is the R65K mutant which, surprisingly, has a significantly higher kcat than the wild-type enzyme. In the open form structure of the pig muscle enzyme each of the three substituted arginines residues are seen to make two hydrogen bonds to the sugar substrate's non-transferable phosphate. From this it might be expected that anion activation would be similarly affected by the substitution of any one of these three residues. Although the interpretation of such effects are complicated by the fact that one of the mutants (R65M) unfolds at low salt concentrations, this appears not to be the case. Replacing Arg121 and Arg168 with methionine reduces the anion activation whereas a lysine in either of these two positions practically destroys the effect. With the substitutions at residue 65 the opposite is observed in that the lysine mutant shows anion activation whereas the methionine mutant does not.

Adenosine Triphosphate↗
PubMed1993

Topographic mapping of human motor cortex with transcranial magnetic stimulation: Homunculus revisited.

The purpose of this study was to non-invasively evaluate the homuncular organization of the motor cortex in man. We used transcranial magnetic stimulation to induce motor evoked potentials (MEP's) in Abductor Pollicis Brevis (APB) and Biceps Brachii (BB) muscles of 10 healthy volunteers. The practicality and accuracy of magnetic stimulation to scalp sites one cm apart was increased by the application to the scalp of a flexible nylon grid with grid size of 1x1 cm. Responsive scalp sites collectively contributed to distinct but overlapping muscle representational areas for the two muscles. The topography of these motor maps along and slightly anterior to the central fissure corresponds to the homuncular configuration as described by Penfield and Boldrey in 1937.

Adult↗