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Biomedical subjects

C J Roberts

Publications and source records attributed to C J Roberts.

At least 19 recordsLinked to original sources
PubMed1995

In vivo inhibition of oestrone sulphatase and dehydroepiandrosterone sulphatase by oestrone-3-O-sulphamate.

Many tumours in endocrine-sensitive tissues, such as the breast and endometrium, are hormone-dependent and the hydrolysis of oestrone sulphate (EIS) to oestrone by oestrone sulphatase (EI-STS) is a major source of oestrogen in such tumours. Oestrone-3-O-sulphamate (EMATE) has been shown to be a potent EI-STS inhibitor in vitro, and in this study its ability to inhibit enzyme activity in vivo was examined. EMATE was initially administered to female rats for 7 days, after which liver EI-STS activity was measured. As EMATE also inhibits a related sulphatase in vitro, dehydroepiandrosterone sulphatase (DHA-STS), its effect on the activity of this enzyme in vivo was also investigated. DHA-STS has a pivotal role in regulating the synthesis of another steroid with potent oestrogenic properties, androstenediol. Administration of EMATE almost completely inhibited liver EI-STS (99%) and DHA-STS (99%) activities and was active when given by the oral or subcutaneous routes. After a single dose of EMATE or following the cessation of multiple doses for 10 days, liver EI-STS activity remained inhibited ( > 95%) for up to 7 and 10 days, respectively. Other compounds, such as 4-hydroxytamoxifen and the "pure" antioestrogen ICI 182,780, which are reported to inhibit EI-STS activity in vitro, did not inhibit activity in vivo. In a preliminary study, EMATE, when injected over a 12-day period, effectively reduced the growth of EIS-stimulated nitrosomethyl-urea-induced mammary tumours in ovariectomised rats and inhibited tumour sulphatase activity in treated animals.

Animals↗
PubMed1995

Scanning tunnelling microscopy studies of beta-amyloid fibril structure and assembly.

Alzheimer's disease is in part characterised by the deposit of beta-amyloid peptide in the form of fibrils in the brain. In this study, the scanning tunnelling microscope (STM) has been used to provide high resolution images of synthetic fibril structure and formation as a function of time. Short fibrils are observed following brief peptide incubation times. At longer incubation periods ribbon like filaments were observed. These results suggest that beta-amyloid self-assembly is an ordered process, with a correlation between time of incubation and length of beta-amyloid filament growth.

Amino Acid Sequence↗
PubMed1995

Development of an ELISA using a universal method of enzyme-labelling drug-specific antibodies. Part I: Detection of dexamethasone in equine urine.

The development, validation, and application of an ELISA for dexamethasone in equine urine is described. The drug-protein conjugate was immobilised in microtitre plate wells and antiserum raised against the same drug-protein conjugate was allowed to compete with sample or standard drug and the immobilised drug-protein conjugate. The proportion of antiserum binding to the immobilised drug-protein conjugate was detected using a biotinylated protein G/extravidin-alkaline phosphatase complex in situ and measurement of the substrate product. The method was used to detect the presence of drug-derived material in unextracted diluted urine after the administration of a single i.m. dose of dexamethasone at approximately 0.04 mg/kg to a thoroughbred horse. Validation of the method was carried out against a radioimmunoassay and GC/MS analysis.

Animals↗
PubMed1995

Carpal malalignment following intra-articular fractures of the distal radius in a working population.

In a review of 52 consecutive intra-articular fractures of the wrist (mean age 41 years), 18 developed one of five carpal malalignment patterns. Seven patients developed a volar intercalated collapse pattern. Although showing some loss of motion and/or grip strength, this group remains relatively pain free on follow-up. Patients who developed dorsal translation (six cases) or a dorsal intercalated collapse pattern (one case) were the most symptomatic, with loss of grip strength, decreased range of motion and pain being prevalent.

Adult↗
PubMed1995

The role of cytokines and sulphatase inhibitors in regulating oestrogen synthesis in breast tumours.

Synthesis of oestrogens within breast tissues makes an important contribution to the high concentrations of oestradiol which are found in breast tumours. The activities of the enzymes involved in oestrogen synthesis, i.e. the aromatase, oestradiol dehydrogenase (E2DH) and oestrone sulphatase (E1-STS), can be stimulated by several growth factors and cytokines. As it is possible that some of these factors may be derived from cells of the immune system (macrophages and lymphocytes), the effects of basic fibroblast growth factor (bFGF) and interleukin-2 (IL-2), which are produced by these cells, on E2DH activity was examined in MCF-7 cells. Treatment of these cells with bFGF resulted in a dose-dependent increase in E2DH reductive activity whereas IL-2 was inactive at the concentration tested. To obtain further evidence that factors produced by macrophages and lymphocytes can modulate the activities of enzymes involved in oestrogen synthesis, conditioned medium was collected from these cells and found to stimulate both E1-STS and E2DH activities. In addition to understanding the control of oestrogen synthesis in breast tumours an inhibitor to block the synthesis of oestrone via the oestrone sulphatase pathway was developed. Oestrone-3-O-sulphamate (EMATE) is a potent, irreversible, inhibitor of E1-STS. A single dose of EMATE (10 mg/kg) inhibited tissue E1-STS activity in rats by more than 95% for up to 7 days, indicating that this compound may have considerable therapeutic potential for the treatment of breast cancer. Evidence is also reviewed that another steroid sulphatase, dehydroepiandrosterone sulphate sulphatase, may have a crucial role in regulating cytokine production and that this may indirectly control tumour oestrogen synthesis.

Breast Neoplasms↗
PubMed1995

The antiemetic effectiveness of droperidol during morphine patient-controlled analgesia.

This prospective, double-blind study examined the antiemetic effectiveness of the addition of droperidol to a morphine solution for use in patient-controlled analgesia in a group of 50 patients undergoing elective lumbar laminectomy. The addition of 20 mg droperidol to 120 mg morphine in 60 ml saline given by a Baxter 'Infusor' patient-controlled analgesia device reduced the incidence of vomiting as compared to the addition of sodium chloride from 42.8% to 12.5% (p = 0.028) and of nausea from 71.4% to 29.2% (p = 0.005). The proportion of patients requiring rescue antiemetic therapy was reduced from 47.6% to 16.7% (p = 0.025) and the time interval to the first use of rescue antiemetic agent was significantly prolonged (p = 0.029). The use of droperidol was associated with an increased degree of sedation during the first 12 h after operation.

Adult↗
PubMed1995

Improving the primary management of emergency surgical admissions: a controlled trial.

The initial screening by senior surgical staff of surgical patients referred for emergency hospital admission should result in improved patient management. The present study was undertaken to determine the effects of this policy. The primary outcome measure was hospital admission rates. The number of operations, diagnostic investigations, initial treatments, deaths, length of stay and bed days per 100 referrals were also measured. The results suggest a 20 per cent reduction in emergency surgical admissions, an important potential benefit to the health service, and to individual patients.

Adult↗
PubMed1994

Stem cell responses in myelosuppressed mice following sequential treatment with recombinant human interleukin 1 (rHuIL-1), recombinant murine interleukin 3 (rMuIL-3) and recombinant human macrophage colony-stimulating factor (rHuM-CSF).

In vivo, recombinant human interleukin 1 alpha (rHuIL-1 alpha) + recombinant human macrophage colony-stimulating factor (rHuM-CSF) (IL-1 + M-CSF) effectively serves as a rescue agent for myelosuppression by enhancing the recovery of hematopoietic stem cell (HSC) subpopulations following treatment with 5-fluorouracil (5-FU). Because in vitro studies have suggested that hematopoietic recovery in 5-FU-treated bone marrow (FUBM) may proceed from a 5-FU resistant, (IL-1 + IL-3 + M-CSF-responsive) high proliferative potential HSC subpopulation of colony forming cells (HPP-CFC), studies were carried out to determine whether the addition of recombinant murine interleukin 3 (rMuIL-3) (IL-3) to either IL-1 or IL-1 + M-CSF would further enhance the recovery of HSC subpopulations in myelosuppressed C57Bl/6 mice. With the exception of the HPP-CFC, IL-3 dampened, rather than enhanced, the accelerated recovery of 8 d and 12 d colony forming units-spleen (8 d and 12 d CFU-S) and the committed macrophage progenitor (CFU-M) associated with in vivo treatment with IL-1 alone. Similarly, IL-3 interfered with the enhanced recovery of those HSC subpopulations in FUBM influenced by the synergistic interaction of IL-1 + M-CSF. This interference, however, was observed only when the rMuIL-3 was administered on day 2 or 3 of a four-day treatment with IL-1 + M-CSF. There was, however, no evidence that IL-3 exerted a negative influence on the restoration of granulocytes in the myelosuppressed animals. Moreover, sequencing studies provided data suggesting that the dampening effects of IL-3 on the synergistic interaction of IL-1 + M-CSF resulted from both an enhanced differentiation of the more primitive HSC subpopulations and a significant, but preferential, mobilization of the more mature 8 d CFU-S and CFU-M to extramedullary organs and that the mobilization of these more mature HSC subpopulations was temporally linked to their generation from the recovering HPP-CFC and 12 d CFU-S subpopulations.

Animals↗
PubMed1994

Characteristics of plasma protein binding of tacrine hydrochloride: a new drug for Alzheimer's disease.

The aim of this study was to characterise the plasma protein binding of tacrine hydrochloride (THA) in vitro. Binding was assessed in the plasma of 11 healthy individuals aged 20 to 27 years using ultrafiltration followed by HPLC assay. At THA concentrations from 10 to 100 ng/ml protein binding ranged from 78.6 to 71.0%. Binding to commercially available human albumin ranged from 41.7 to 38.3% and to human alpha 1-acid glycoprotein from 23.1 to 12.4% over the THA concentrations from 25 to 100 ng/ml. THA binding and total plasma protein, plasma albumin and alpha 1-acid glycoprotein were measured in healthy young subjects (n = 13), healthy elderly individuals (n = 12) and patients hospitalised with acute illnesses (n = 8). There were significant differences between the groups in total plasma protein, plasma albumin and in alpha 1-acid glycoprotein but no differences in the protein binding of THA which remained constant at about 75%. There was no correlation between THA binding and any plasma protein concentration. The THA binding was not high enough to be of major significance clinically or to reduce the validity of total plasma THA measurement in therapeutic monitoring.

Adolescent↗
PubMed1994

Atomic force microscopy and scanning tunnelling microscopy: refining techniques for studying biomolecules.

The scanning tunnelling microscope and the atomic force microscope offer the prospect of real-time, nanometre-scale imaging of biomolecules and biosurfaces under physiological environments. Much effort is therefore being made to establish these techniques as routine biophysical tools. The considerable recent progress that has been made in biotechnological applications is reviewed, highlighting specific examples of the applications of this new and exciting method of analysis.

Biological Products↗
PubMed1994

Compliance with guidelines for choice of radiographic projections: a multicentre study.

A study of compliance with guidelines for choice of radiographic projections was carried out in each of six centres. The study concerned 5851 examinations undertaken by 116 radiographers under the supervision of 29 consultant radiologists. The results showed good compliance between centres for examination of the chest (range 81-93%), abdomen (range 73-100%), thoracic spine (range 82-96%), pelvis/hip (range 78-99%) but not for examination of cervical spine (range 0-85%), paranasal sinus (range 0-100%) and lumbar spine (range 52-84%). The reasons given for these wide variations are discussed and estimates are given for the potential reductions in exposure to the UK population consequent upon national implementation of guidelines such as these.

Decision Making↗
PubMed1993

Abnormal chromosome behavior in Neurospora mutants defective in DNA methylation.

The function and regulation of DNA methylation in eukaryotes remain unclear. Genes affecting methylation were identified in the fungus Neurospora crassa. A mutation in one gene, dim-2, resulted in the loss of all detectable DNA methylation. Abnormal segregation of the methylation defects in crosses led to the discovery that the methylation mutants frequently generate strains with extra chromosomes or chromosomal parts. Starvation for S-adenosylmethionine, the presumed methyl group donor for DNA methylation, also produced aneuploidy. These results suggest that DNA methylation plays a role in the normal control of chromosome behavior.

5-Methylcytosine↗
PubMed1993

Effect of intraoperative inspired gas mixtures on postoperative nocturnal oxygen saturation.

Continuous postoperative nocturnal pulse oximetry was performed in 20 patients undergoing elective cholecystectomy to examine if the composition of anaesthetic gas mixtures affects postoperative gas exchange. The patients were allocated randomly to receive either nitrogen or nitrous oxide during anaesthesia, and oximetry was performed on the night before operation and the first and third nights after operation. Considerable oxygen desaturation was seen in both groups. During the first night after operation the proportion of the night during which oxygen saturation was less than 85% was greater in the nitrogen group than in the nitrous oxide group, but there was no significant difference between the mean overnight saturation values of the two groups.

Adult↗
PubMed1992

Topographical investigations of human ovarian-carcinoma polymorphic epithelial mucin by scanning tunnelling microscopy.

Human polymorphic epithelial mucin is a high-molecular-mass glycoprotein that associates to provide protection to the epithelial-cell surface and may afford the malignant cell a selective advantage for growth. The scanning-tunnelling-microscopy micrographs obtained in the present study identify the purified human ovarian-carcinoma polymorphic epithelial mucin glycoproteins as rod-shaped molecules of mixed length. The dimensions of the individual molecules range from 25 to 45 nm in length and are 3-4 nm in width. The images further suggest that lateral association of the rods occurs.

Animals↗
PubMed1992

Nitrendipine and renal tubular function in human volunteers.

Nine normotensive, water-loaded subjects received 10 mg oral nitrendipine, and eight subjects received placebo in a double-blind randomized manner. Urine and plasma were collected at fixed time points for 1 hour before and for 4 hours after drug administration for biochemical measurements. Glomerular filtration rate was measured by inulin clearance and effective renal blood flow was measured by para-amino hippurate clearance. Absolute sodium excretion increased by 25.9% from 0.27 +/- 0.03 mmol/min to 0.34 +/- 0.02 mmol/min (P = .02), and fractional sodium excretion increased by 32.3% from 18.9 +/- 3.0% to 25.0 +/- 1.9% (P = .03) after nitrendipine, but both were unchanged after placebo. There was no change in inulin clearance, para-amino hippurate clearance, urine volume, or fractional excretion of uric acid, which made an effect on glomerular filtration, renal blood flow, or proximal tubular function an unlikely explanation of the natriuresis. Fractional excretion of magnesium increased after both placebo and nitrendipine administration, from 5.0 +/- 0.6% to 6.8 +/- 0.7% (P = .027) and 5.7 +/- 0.8% to 8.8 +/- 1.0% (P = .006), respectively. Fractional excretion of phosphate also increased after both placebo and nitrendipine, from 9.5 +/- 2.3% to 12.9 +/- 3.9% (P = .05) and 9.7 +/- 1.7% to 14.2 +/- 1.9% (P = .002), respectively. These changes are likely to be due to the effects of the water load rather than due to a drug effect. There was no change in clearance of solute free water, which made a direct effect on the loop of Henle or cortical diluting segment unlikely.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗