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Biomedical subjects

D A Robertson

Publications and source records attributed to D A Robertson.

At least 19 recordsLinked to original sources
PubMed1992

A cDNA clone for human glucosamine-6-sulphatase reveals differences between arylsulphatases and non-arylsulphatases.

Glucosamine-6-sulphatase is an exo-hydrolase required for the lysosomal degradation of heparan sulphate and keratan sulphate. Deficiency of glucosamine-6-sulphatase activity leads to the lysosomal storage of the glycosaminoglycan, heparan sulphate and the monosaccharide sulphate N-acetylglucosamine 6-sulphate and the autosomal recessive genetic disorder mucopolysaccharidosis type IIID. Glucosamine-6-sulphatase can be classified as a non-arylsulphatase since, relative to arylsulphatase B, it shows negligible activity toward 4-methylumbelliferyl sulphate. We have isolated human cDNA clones and derived amino acid sequence coding for the entire glucosamine-6-sulphatase protein. The predicted sequence has 552 amino acids with a leader peptide of 36 amino acids and contains 13 potential N-glycosylation sites, of which it is likely that 10 are used. Glucosamine-6-sulphatase shows strong sequence similarity to other sulphatases such as the family of arylsulphatases, although the degree of similarity is not as high as that between members of the arylsulphatase family. This pattern of inter- and intra-family similarity delineates regions and amino acid residues that may be critical for sulphatase function and substrate specificity.

Amino Acid Sequence↗
PubMed1992

Effects of morbid obesity on insulin clearance and insulin sensitivity in several aspects of metabolism as assessed by low-dose insulin infusion.

Obesity is associated with impaired insulin action in glucose disposal, but not necessarily in other aspects of intermediary metabolism or insulin clearance. Sixteen morbidly obese and 14 normal-weight subjects (body mass index, 51.2 +/- 11.5 v 22.1 +/- 2.2 kg.m-2; mean +/- SD) were studied with sequential, low-dose, incremental insulin infusion with estimation of glucose turnover. In obese patients, basal plasma insulin was higher (10.5 +/- 3.8 v 2.4 +/- 3.0 mU.L-1, P less than .001) and remained elevated throughout infusion (F = 492, P less than .001), as did C-peptide (F = 22.7, P less than .001). Metabolic clearance rate for insulin (MCRI) at the highest infusion rate was similar (1,048 +/- 425 v 1,018 +/- 357 mL.m-2.min-1, NS). Basal hepatic glucose production in obese subjects was less than in normal-weight subjects (270 +/- 108 v 444 +/- 68 mumol.m-2.min-1, P less than .01), as was the basal metabolic clearance rate for glucose (MCRG, 77 +/- 26 v 108 +/- 31 mL.m-2.min-1, P less than .05). Insulin infusion caused blood glucose to decrease less in the obese patients (1.4 +/- 0.5 v 1.9 +/- 0.5 mmol.L-1, P less than .05); hepatic glucose production was appropriately suppressed in them by hyperinsulinemia, but their insulin-mediated glucose disposal was reduced (1.67 [0.79] v 4.45 [2.13] mL.m-2.min-1/mU.L-1, P less than .01). Concentrations of nonesterified fatty acids (NEFA), glycerol, and ketones were elevated throughout the insulin infusions in obese patients, despite the higher insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Metabolic effects of monomeric insulin analogues of different receptor affinity.

The effects of two monomeric insulin analogues of differing receptor affinities (human insulin = 100%) B9Asp-B27Glu-insulin (18%) and B10Asp-insulin (327%) were each compared with human insulin in two groups of 10 normal men when infused at equimolar low doses (1.0 and 2.0 pmol kg-1 min-1). The metabolic clearance rate under steady state conditions was highest for the analogue with the highest receptor affinity, 26.8 +/- 0.8 (+/- SE) vs 19.8 +/- 0.7 ml kg-1 min-1 for insulin (p less than 0.001), and lowest for the analogue with the lowest receptor affinity, 13.3 +/- 0.8 vs 25.1 +/- 2.0 ml kg-1 min-1 for insulin (p less than 0.001). The apparent plasma half-life was prolonged for the low affinity analogue compared with human insulin (12.6 +/- 0.6 vs 1.9 +/- 0.2 min, p less than 0.001), and significantly shorter for the higher affinity analogue (1.6 +/- 0.1 vs 3.1 +/- 0.4 min, p less than 0.05). The three insulins gave similar falls in blood glucose, non-esterified fatty acids, glycerol, and total ketone bodies over the infusion period. Thirty minutes after the end of the infusion, the rise in blood glucose for the low affinity analogue was significantly less than for human insulin (0.5 +/- 0.2 vs 0.9 +/- 0.1 mmol l-1, p less than 0.05). Despite different receptor affinities, these analogues have similar in vivo effects in normal men, but the time-course of their actions may differ when they are infused intravenously.

Adult↗
PubMed1992

Basal intermediary metabolism in impaired glucose tolerance and morbid obesity.

The effects of impaired glucose tolerance and obesity, in isolation and in combination, on basal (postabsorptive) intermediary metabolism were examined in four groups of subjects (n = 10 for each) matched for age and gender: Group 1: Non-obese healthy controls with normal glucose tolerance (75 g); Group 2: Non-obese subjects with impaired glucose tolerance; Group 3: Morbidly obese subjects with normal glucose tolerance; Group 4: Morbidly obese subjects with impaired glucose tolerance. While there was no significant difference in fasting blood glucose concentrations between the four groups plasma immuno-reactive insulin concentrations were elevated (p < 0.01 or less) in the obese subjects relative to the non-obese subjects within each category of glucose tolerance. Basal immunoreactive insulin concentrations in non-obese subjects with impaired glucose tolerance were also elevated (p < 0.01) relative to the non-obese healthy controls. Concentrations of glycerol (p < 0.01), non-esterified fatty acids (p < 0.01), and total ketone bodies (p < 0.001) were significantly higher in the obese/normal glucose tolerance and obese/impaired glucose tolerance groups relative to their matched non-obese counterparts. Compared with the subjects with normal glucose tolerance, only lactate (p < 0.05) and pyruvate (p < 0.05) concentrations were elevated in the non-obese/impaired glucose tolerance and obese/impaired glucose tolerance groups, respectively. In conclusion, in addition to fasting hyperinsulinaemia the regulation of lipolysis and ketone body metabolism is abnormal in the basal state in morbid obesity. By contrast, despite normal fasting blood glucose concentrations, impaired glucose tolerance is associated with disturbances of other aspects of basal carbohydrate metabolism.

Adult↗
PubMed1991

Prevention of sepsis following endoscopic retrograde cholangiopancreatography.

Ora; ciprofloxacin was studied as a prophylactic antimicrobial agent in high- and low-risk patients undergoing endoscopic retrograde cholangiography. Ciprofloxacin appeared to be effective, good serum levels were attained, and the drug compared favourably on grounds of cost and convenience with a parenterally-administered cephalosporin.

Administration, Oral↗
PubMed1991

Impaired glucose tolerance in obesity is associated with insensitivity to insulin in multiple aspects of metabolism as assessed by a low dose incremental insulin infusion technique.

To determine whether Impaired Glucose Tolerance gives rise to additional defects in insulin action in lipid and ketone metabolism, thirty-two obese subjects were studied by low-dose incremental insulin infusion. Sixteen had Impaired Glucose Tolerance and 16 had normal glucose tolerance. Body mass index was 36.9-80.9 kg m-2 and was similar in each group. In patients with Impaired Glucose Tolerance, plasma insulin was higher in the fasted state (logarithmic mean 14.5 (9.8-21.6) (-SD(-)+SD) vs 9.6 (6.4-14.5) mU l-1, p less than 0.01) and during the infusion (p less than 0.001). The metabolic clearance rate for insulin at the highest infusion rate was lower (14.2 +/- 0.8 (+/- SE) vs 18.9 +/- 2.1 ml kg-1 min-1, p less than 0.05) in these subjects. Basal hepatic glucose production was higher in subjects with Impaired Glucose Tolerance (6.3 +/- 0.4 vs 4.5 +/- 0.6 mol kg-1 min-1, p less than 0.02) and remained elevated during infusion (p less than 0.01). Glucose disposal per unit circulating insulin at the maximal infusion rate was approximately half in subjects with Impaired Glucose Tolerance (0.022 +/- 0.010 vs 0.047 +/- 0.017 ml kg-1 min-1 mU-1 l, p less than 0.01). When simultaneous insulin and metabolite concentrations during the infusion are plotted as dose-response relationships, a difference in relative sensitivity to insulin in Impaired Glucose Tolerance over subjects with normal glucose tolerance is suggested for non-esterified fatty acids 0.72 (95% CI 0.62-0.84) and glycerol 1.85 (1.37-2.49).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Deoxyribonucleic acid amplification and hybridisation in Crohn's disease using a chlamydial plasmid probe.

The possibility that Crohn's disease is caused by infection with Chlamydia trachomatis was examined by probing for chlamydial plasmid deoxyribonucleic acid (DNA) in DNA extracts from Crohn's disease tissue and by means of a serological study. Gut DNA extracts were obtained from 10 patients with Crohn's disease and four control subjects and were probed with a chlamydial plasmid probe after Southern blotting. The polymerase chain reaction was also used to amplify any chlamydial plasmid DNA present in tissue DNA extracts, before Southern blotting and probing. Chlamydial proctitis control specimens were not available: gut DNA extracts mixed with traces of chlamydia plasmid served as positive controls. Using these techniques, no chlamydial plasmid DNA sequences were found in Crohn's disease tissue. An enzyme linked immunosorbent assay for C trachomatis LI was performed on 48 patients with Crohn's disease and 48 control subjects. Seropositivity was present in 14.6% of patients and 29% of control subjects and was not statistically significant (p greater than 0.05). The failure to show chlamydial DNA and the lack of serological response to chlamydia make C trachomatis infection a very unlikely factor in the pathogenesis of Crohn's disease.

Adult↗
PubMed1991

Effect of fasting, self-selected and isocaloric glucose and fat meals and intravenous feeding on plasma zinc concentrations.

This study investigated the effect of fasting, self-selected meals and isocaloric oral glucose and fat meals and intravenous (i.v.) feeding on plasma zinc concentrations in men. Plasma zinc remained stable when volunteers fasted all day, but self-selected meals and 600 kCal of dextrose or fat emulsion caused significantly reduced plasma zinc concentrations [mean (SD) 12.1 (1.4), 12.3 (0.6) and 12.2 (0.7) mumol/L at 1400 h, respectively, compared with a fasting level of 13.9 (1.6) mumol/L at 0800 h, P less than 0.05]. In patients undergoing intravenous hyperalimentation, plasma zinc decreased from 12.0 (1.4) mumol/L at 0800 h to 10.0 (1.1) mumol/L at 1400 h [mean (SD), P less than 0.01]. These data show that both enteral and i.v. feeding cause a decline in plasma zinc and that glucose alone is not responsible for this post-prandial fall since ingestion of isocaloric amounts of glucose or fat have a similar effect.

Circadian Rhythm↗
PubMed1991

Effect of obesity on circulating intermediary metabolite concentrations in the absence of impaired glucose tolerance.

The published literature on the influence of obesity on intermediary metabolite concentrations does not adequately address the potential confounding effects of the increased prevalence of impaired glucose tolerance in obese subjects. In order to remove this, we studied 109 subjects with proven normal glucose tolerance ranging from underweight to grossly obese (range 15.3-80.9 body mass index). All had blood intermediary metabolites, plasma insulin and C-peptide measured after an overnight fast. Thirty-six (18 from each end of the range of body mass index) received a 3-hour oral glucose tolerance test for metabolites and insulin. Fasting plasma insulin was highly significantly associated with body mass index (r = 0.72; P less than 0.001). Concentrations of lipid intermediaries were better associated with body mass index than with fasting plasma insulin: non-esterified fatty acids (r = 0.36; P less than 0.001), glycerol (r = 0.47; P less than 0.001) and ketone bodies (r = 0.45; P less than 0.001). Fasting concentrations of carbohydrate intermediaries were, however, better correlated with fasting plasma insulin: lactate (r = 0.29; P less than 0.01), pyruvate (r = 0.24; P less than 0.01) and alanine (r = 0.36; P less than 0.001). Glucose concentrations were associated with both to a similar degree (r = 0.33, r = 0.32, respectively; P less than 0.001). After oral glucose, exaggerated rises in plasma insulin and blood glucose were observed in obese subjects but a lesser rise was seen for lactate. Non-esterified fatty acids and ketones, although having higher fasting concentrations in obese subjects, fell to similar concentrations in the two groups after glucose whereas blood glycerol did not fall so far in the obese subjects. The results suggest, even if those subjects with impaired glucose tolerance are excluded, insensitivity to insulin in several aspects of intermediary metabolism in obesity the degree of which may vary in different metabolic pathways or tissues.

Adult↗
PubMed1990

Corticosteroid treatment reduces mast cell numbers in inflammatory bowel disease.

Mast cell degranulation in the gut causes mucus secretion, mucosal edema, and increased gut permeability and may be responsible for some of the symptoms and signs of inflammatory bowel disease. We have used a novel monoclonal antibody (AAI) against tryptase expressed exclusively in the granules of mast cells to enumerate mast cells in rectal biopsies in order to study the effect of inflammatory bowel disease and drug treatment upon rectal mast cell numbers. Rectal mast cell numbers are significantly reduced in inflammatory bowel disease patients taking corticosteroids (mean 4.95 cells/mm2) when compared with control patients (10.1, P less than 0.001) and inflammatory bowel disease patients not taking corticosteroids (9.7, P less than 0.001 Wilcoxon rank sum test). The reduction in mast cell counts was independent of the degree of inflammation or architectural distortion. There was a negative correlation between the dose of corticosteroids and mast cell count (r = 0.53, P less than 0.05 Spearman rank correlation), and the mast cell count was reduced within a few days of treatment and remained low throughout steroid therapy. Mucosal mast cell depletion may be an important mechanism of action of corticosteroids in inflammatory bowel disease.

Adrenal Cortex Hormones↗
PubMed1990

Gas in an infected vascular prosthesis. An unusual finding on plain radiographs.

Infection of prosthetic vascular grafts is a potentially serious complication, which may prove difficult to diagnose despite modern imaging techniques. We report a case in which the diagnosis was strikingly obvious on plain radiographs, gas being present within the lumen of the graft. The clinical features and investigation of suspected graft infection are reviewed.

Adult↗
PubMed1990

Metabolic abnormalities in obese patients with impaired glucose tolerance.

It is not clear whether the glucose tolerance test diagnosis of Impaired Glucose Tolerance introduced in the recent revisions of diagnostic criteria is associated with abnormalities of intermediary metabolism other than glucose. Intermediary metabolite concentrations have therefore been studied fasting and in response to oral glucose in 35 patients referred with morbid obesity accompanied by either normal glucose tolerance (18 patients) or Impaired Glucose Tolerance (17 patients). When fasting obese patients with Impaired Glucose Tolerance had significantly higher blood total ketone body concentrations, 0.24 (0.19-0.30) vs 0.14 (0.12-0.16) mmol l-1 (antilog of mean-SE to mean + SE) (p less than 0.05), and lower blood glycerol concentrations, 0.14 +/- 0.01 vs 0.18 +/- 0.01 mmol l-1 (mean +/- SE) (p less than 0.05), than obese patients with normal glucose tolerance. There were no significant differences in fasting insulin, 16 (15-18) vs 14 (12-15) mU l-1, or glucose levels, 5.3 +/- 0.2 vs 5.1 +/- 0.2 mmol l-1. After oral glucose there was an exaggerated rise in glucose, insulin, lactate, and pyruvate in patients with Impaired Glucose Tolerance.

Adult↗
PubMed1990

Spontaneous regression of hepatocellular carcinoma.

A 63 year old white woman presented with abdominal discomfort, anorexia, and weight loss. Investigations showed hepatocellular carcinoma with pulmonary metastases. The primary and secondary tumours resolved without specific treatment.

Carcinoma, Hepatocellular↗
PubMed1990

Bleeding oesophageal varices associated with anabolic steroid use in an athlete.

A 30 year old bodybuilder who had been taking anabolic steroids for 18 months presented with bleeding oesophageal varices. Serious liver disease secondary to anabolic steroids including peliosis hepatis, nodular hyperplasia and malignant change is well recognized. We report what is, to our knowledge, the first case of bleeding oesophageal varices associated with the use of anabolic steroids.

Adult↗
PubMed1990

Growth hormone, insulin and glucose concentrations in bovine fetal and maternal plasmas at several stages of gestation.

For cows on d 137 (n = 6), 180 (n = 8), 226 (n = 9) and 250 (n = 5) of gestation (Exp. 1), concentrations of insulin and glucose were two- to three-fold less (P less than .01) in fetal venous plasma than in uterine arterial plasma. Concentrations of growth hormone, conversely, were 10- to 20-fold greater (P less than .01) in fetal venous than in uterine arterial plasma. Concentrations of insulin and glucose in maternal and fetal plasmas and concentrations of growth hormone in maternal plasma did not vary with stage of gestation. Concentrations of growth hormone in fetal venous plasma, however, were greater on d 226 and 250 than on d 137 and 180. For cows (n = 6) on d 198 of gestation (Exp. 2), concentrations of insulin and glucose in maternal and fetal plasmas and of growth hormone in maternal plasma remained relatively constant in samples collected every 30 min for 3 h. In contrast, growth hormone concentrations in fetal venous plasma were highly variable and appeared to be episodic, with pulses of 10 to 60 ng/ml in amplitude. No significant correlations were found among concentrations of insulin, glucose and growth hormone in fetal venous plasma. When samples were collected every 15 min for 4 h from cows (n = 5) on d 198 of gestation (Exp. 3), episodes of growth hormone in fetal venous plasma were irregular in amplitude and frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗