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Biomedical subjects

N B Roberts

Publications and source records attributed to N B Roberts.

At least 55 records · Page 3Linked to original sources
PubMed1997

Potential of electrospray mass spectrometry for quantifying glycohemoglobin.

An electrospray ionization-mass spectrometric procedure has been developed for determining glycohemoglobin. Whole-blood samples from 78 diabetic and 50 nondiabetic subjects (glycation range 3-15%, as determined by electrospray mass spectrometry) were diluted 500-fold in an acidic denaturing solvent and introduced directly into a mass spectrometer. The resulting mass spectra were then processed to estimate the percentage of glycohemoglobin present in the sample. Total analysis time, including plotting the spectra and computing the percentage of glycation, was approximately 3 min. The imprecision (CV) of the method was < 5.1% for inter- and intrabatch analyses for total glycohemoglobin in the range 3.6-14%. Comparison of the mass spectrometric results with those from established affinity chromatographic procedures showed good overall agreement. The relative glycation of the alpha- and beta-chains was determined directly and was shown to be constant (0.64:1) over the glycation range measured. Only single glucose attachment to both the alpha- and beta-chains was observed.

Chromatography, Affinity↗
PubMed1996

Electrospray mass spectrometric evidence for the occurrence of two major variants in native pig pepsin A.

Native pig pepsin was analysed by negative ion electrospray mass spectrometry in order to rationalize anomalies between the published sequences. Outstanding variations in otherwise identical sequences indicate that amino acid residue 242 is either Asp or Tyr, and in some determinations an additional Ile is inserted at position 230. Mass spectrometric evidence is consistent with the presence, in the native enzyme, of two variants in comparable abundance, with either Asp or Tyr at residue 242. There is no evidence for the additional Ile at position 230.

Animals↗
PubMed1996

Elemental analysis of femoral bone from patients with fractured neck of femur or osteoarthrosis.

The elemental composition of bone has been determined by inductively coupled atomic emission and mass spectrometry to test the hypothesis that changes in major or minor elemental concentrations may contribute to the risk of fracture. Femoral bone was obtained from patients at operation for the treatment of fracture and compared with that of patients with osteoarthrosis and a necropsy control group. The data suggest that there are no major differences in bone elemental composition in patients with fractures compared with the control group. Bone adjacent to joints with osteoarthrosis tends to be less mineralized (per unit trabecular bone volume) than control bone and bone from fracture patients, and has significantly lower concentrations of boron, lead and, zinc. These observations may reflect the more rapid turnover of bone close to the arthritic joint.

Aged↗
PubMed1996

Serial changes in serum vitamin K1, triglyceride, cholesterol, osteocalcin and 25-hydroxyvitamin D3 in patients after hip replacement for fractured neck of femur or osteoarthritis.

Serum vitamin K1 concentrations were measured at presentation (just before surgery) and then at weekly intervals for 3 weeks in two groups of elderly patients requiring either hemiarthroplasty for fractured neck of femur (FON, n = 13) or total hip replacement for osteoarthritis of the hip (OA, n = 16). In comparison with healthy elderly volunteers (n = 25), serum vitamin K1 concentrations were significantly lower in both groups at presentation, and fell significantly within 24 h after surgery to concentrations approaching non-detectable, subsequently returning to pre-operative values within 3 weeks. Serum vitamin K1 tended to be lower in the fracture group both before and after operation, although calculation of a vitamin K1-triglyceride ratio reduced the apparent difference as triglyceride concentrations were lower in the fracture group. Osteocalcin concentrations were similar and fell significantly after operation in both groups, returning to pre-operative levels within 7 days. No differences in the two forms of osteocalcin (carboxylated and undercarboxylated) were observed either before or after operation in either group. 25-Hydroxyvitamin D3 concentrations were not significantly different between the two groups at any time. Vitamin K1 status may be lower than desirable in certain groups of the elderly population, and supplementation should be considered as prophylactic therapy.

Aged↗
PubMed1996

Accumulation of the endogenous L-arginine analogue NG-monomethyl-L-arginine in human end-stage renal failure patients on regular haemodialysis.

We measured plasma levels of L-arginine, its analogue NG-monomethyl-L-arginine (L-NMMA), and related amino acids in normal subjects and uraemic patients (n = 31), before and after haemodialysis. Plasma levels of L-arginine were reduced to less than half of normal values in uraemic subjects compared with controls, and were not affected by haemodialysis. L-NMMA was not detectable in non-uraemic subjects, but markedly elevated in uraemic patients. In parallel, we used human red blood cells as a model to study the effect of L-NMMA upon the transport of L-arginine. L-NMMA trans-stimulated L-arginine transport significantly, confirming that L-arginine and L-NMMA share common transport pathways. Our results suggest altered L-arginine metabolism and the presence of an increased concentration of a NO synthase inhibitor in uraemia. We propose that alterations in plasma L-arginine levels and increased production of L-arginine analogues will alter NO synthesis and may help to explain some pathological changes seen in uraemia.

Adult↗
PubMed1996

Necropsy study of the association between sudden cardiac death, cardiac isoenzymes and contraction band necrosis.

AIMS: To assess whether a quantitative analysis of myocardial contraction bands could aid the postmortem identification of early myocardial infarction, especially if used in conjunction with cardiac isoenzyme activities. METHODS: Sixty four coroner's necropsies were grouped by gross and histological findings into 26 cases of definite non-cardiac death, 12 cases of definite myocardial infarction and 26 cases in which there was occlusive coronary artery atheroma, but no demonstrable evidence of infarction. Using multiple sections of left ventricular myocardium stained with Heidenhain's iron haematoxylin, the number of myocardial cells containing contraction bands per unit area was quantified. The results were analysed statistically using logistic regression, and were then compared and combined with results from the statistical analysis of postmortem cardiac isoenzymes that had recently been undertaken on the same cases. RESULTS: The number of cells containing contraction bands per unit area was higher in cases of definite myocardial infarction compared with those of non-cardiac deaths. In addition, cases of occlusive coronary artery atheroma only could be identified, indicating the presence of early myocardial infarction. The accuracy of this identification could be improved by combining these results with the results from the statistical analysis of postmortem cardiac isoenzymes. CONCLUSION: The quantitative assessment of myocardial contraction band necrosis can provide useful additional information in cases of sudden death, where myocardial infarction is suspected but not identified on routine histological staining. The value of the information obtained is increased when used in conjunction with the postmortem measurement of cardiac isoenzyme activities.

Coronary Artery Disease↗
PubMed1996

The effects of Helicobacter pylori colonization on gastric function and the incidence of portal hypertensive gastropathy in patients with cirrhosis of the liver.

OBJECTIVES: To investigate the prevalence of Helicobacter pylori infection in 50 cirrhotic patients with biopsy-proven cirrhosis with and without portal hypertensive gastropathy and to study whether or not the effects of H. pylori colonization of the stomach on gastric acid and pepsin secretion, serum gastrin and pepsinogen I levels, gastric mucus, and gastric emptying contributed to the development of portal hypertensive gastropathy in cirrhotics. METHODS: All patients underwent an upper GI endoscopy followed by determination of basal and pentagastrin and insulin-stimulated gastric acid and pepsin secretion and serum gastrin and pepsinogen I levels. The gastric biopsies were stained to detect H. pylori infection, portal hypertensive gastropathy, and gastritis. The amount of gastric mucus was estimated by a microanalytical technique. The rate of gastric emptying was assessed by the radionuclide method using a semi-solid meal. RESULTS: Thirty-three (66%) patients had endoscopic evidence of portal hypertensive gastropathy, 10 with the severe (20%) and 23 with mild form (46%). Twenty (40%) patients had histological evidence of H. pylori infection. Eleven out of 33 (33%) patients with endoscopic portal hypertensive gastropathy had microscopic evidence of H. pylori infection. Eighteen out of 20 (90%) patients with chronic active gastritis had concomitant H. pylori colonization. In contrast, the gastric mucosa was histologically normal in 21 of the 30 patients (70%) not infected with H. pylori. Marked hypochlorhydria and reduced pepsin secretion associated with a tendency to hypergastrinemia were observed in cirrhotic patients colonized with H. pylori compared with those without. However, there was no significant difference in serum pepsinogen I concentrations, the ratio of polymeric to degraded gastric mucus, or the rate of gastric emptying between cirrhotics with and without H. pylori colonization of the stomach. Furthermore, these parameters were not significantly different in patients with portal hypertensive gastropathy with and without H. pylori infection. CONCLUSION: These observations suggest that H. pylori infection is unlikely to be involved in the pathogenesis of portal hypertensive gastropathy.

Adolescent↗
PubMed1995

Five human gastric aspartic proteinases: N-terminal amino acid sequences and amino acid composition.

Human pepsin A consists of 4 or more isoenzymes (designated 1, 3a, 3b and 3c) one of which, pepsin 1, contains up to 50% carbohydrate moieties. The amino-acid composition and N-terminal sequence of pepsin 1 and the other isoforms have been determined and compared with data obtained for pepsin 3b and gastricsin (pepsin C or pepsin 5). Pepsins were isolated from penta-gastrin stimulated gastric juice using repetitive chromatography on DEAE-cellulose, or high performance ion-exchange chromatography. Sequencing was performed using automated solid-phase Edman degradation with a microsequence facility. The amino-acid compositions were similar for pepsins 1, 3a, b and c and the N-terminal sequences of pepsins 1, 3a and c, reported for the first time, were shown to be identical with that for pepsin 3b (the main component of pepsin A) although residue 28 was unassigned in pepsin 1. Residue 30 in all four isoenzymes is valine and we cannot confirm reports of major pepsins with leucine in this position. For gastricsin the sequence differed from the pepsin isoenzymes and in position 24 we find pro rather than ala as was first described. These observations suggest that pepsin 1 is identical to 3b or a mixture of 3a, 3b and 3c but not gastricsin. This data supports the hypotheses that the four pepsin isoenzymes are products of the same gene(s) but have undergone varying levels of post translational modification.

Amino Acid Sequence↗
PubMed1995

Production of acute gastric erosions in the cat by individual human pepsins.

1. Differing amounts of human pepsins 1, 3 (pepsin A) and 5 (pepsin C or gastriscin) in aqueous HCl/NaCl at pH 1.3 were placed in Perspex rings on the exposed luminal surface of the perfused cat stomach to test for mucolytic and erosive activity in vivo, with the acid medium in control rings. 2. After incubation at 37 degrees C for 60 or 120 min, the test and control solutions were replaced by the same volume of each test or control solution containing 18 mg of aspirin and incubated for a further 120 min. 3. The number of bleeding points or erosions was counted at 15 min intervals. None was observed with human pepsins 1, 3 and 5 or with pig pepsin A or in the control rings. 4. With aspirin, erosions developed in all ringed areas. Their rate of development with time for pepsin 1 and pig pepsin did not differ from controls. Significantly more erosions developed with human pepsins 3 (5 mg per ring, P < 0.001) and 5 (0.32 mg per ring, P < 0.05). 5. Human pepsins 3 and 5, applied at pH 1.3 to the mucosal surface of the perfused cat stomach, therefore cause erosions when administered with aspirin, but do not produce erosions when given alone. In man, pepsins secreted in increased amount or concentration may therefore be unlikely to cause significant mucosal erosion unless human gastric mucosa is less resistant to pepsins than cat mucosa. Pepsins may perhaps facilitate the action of a second factor, such as aspirin, or infection with Helicobacter pylori.

Acute Disease↗
PubMed1995

Decreased amino acid uptake by erythrocytes during postoperative sepsis.

We describe a patient with postoperative sepsis associated with reduced ability to transport amino acids into erythrocytes. Administration of amino acid infusion showed no effect on plasma or red blood cell concentrations of the amino acids during the sepsis period. However, when the site of sepsis was removed, patient recovery was associated with marked increases of all amino acids, particularly in the red blood cells. The case illustrates the potential of red blood cells as a marker of amino acid utilization and demonstrates the association of sepsis with effects on cellular uptake.

Adult↗
PubMed1994

Routine outpatient L-dopa monitoring in elderly patients with Parkinson's disease.

In an attempt to improve the therapeutic drug management of patients with Parkinson's disease, plasma L-dopa concentrations were measured by high-performance liquid chromatography and related to the post-dose time with reference to an established therapeutic range of 0.3-1.6 mg/l. The response to treatment was also assessed. One hundred and three samples were obtained at morning clinics from 53 elderly patients (mean age 72.5 years) taking an L-dopa/decarboxylase inhibitor combination. L-Dopa concentrations ranged from 0.01 to 3.6 mg/l. Fifty-nine values were within, 39 values were below and five values were above the therapeutic range. Three values were at or below the lower limit of the assay and probably indicated poor compliance. L-Dopa concentration was significantly negatively correlated with post-dose time for the dosage groups of 50 mg (p = 0.04), 100 mg (p = 0.0013), 200-250 mg (p = 0.055) and for the combined data (p = 0.005). Post-dose times were from 35 to 400 min, with the majority greater than 90 min, and it is likely that most of these corresponded to the post-peak phase of L-dopa absorption. There was a tendency for a good response to treatment to occur with values within and above the therapeutic range and for dyskinesia to be more common above the therapeutic range. It was concluded that plasma L-dopa measurement at known post-dose time, 90-360 minutes after the morning dose, can identify non-compliance, patients at risk of dose related side-effects and give useful information about the suitability of the L-dopa dose.

Aged↗