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Biomedical subjects

J Gilbert

Publications and source records attributed to J Gilbert.

At least 73 records · Page 4Linked to original sources

The migration of propylene glycol, mono-, di-, and triethylene glycols from regenerated cellulose film into food.

Chocolates, boiled sweets, toffees, cakes and meat pies were wrapped in regenerated cellulose films (with or without coatings) that contained various mixtures of glycol softeners and which had been specially formulated for particular food applications. Samples were unwrapped at intervals (up to the end of the usual maximum shelf-life for the food) and analysed for their glycol content. Analysis involved homogenization of the food in hot water, removal of fats with hexane, precipitation of sugars with calcium hydroxide and analysis of the glycols by capillary gas chromatography with flame ionization detection (GC/FID) after trimethylsilyl (TMS) derivatization. Triethylene glycol was analysed by selected ion monitoring GC/mass spectrometry (GC/MS) as interference problems occurred with the GC/FID approach. The results of the study showed that higher levels of migration occurred for propylene glycol than for triethylene glycol and the presence of a coating reduced the migration of both softeners. Generally, mono- and diethylene glycol levels in the food samples were below 10 mg/kg, although some samples wrapped in polyethylene glycol-softened films contained levels approaching the current statutory limit of 50 mg/kg.

Cellophane

A chemical classification of nonsteroidal antagonists of sex-steroid hormone action.

A highly varied collection of nonsteroids have been reported over the last forty years as being able to exert an antihormonal action versus steroid hormones in vivo. This diversity is partly explained by the manifold molecular targets of these compounds which may be either enzymes or receptors (leading to inhibition of steroid production and action respectively) and by the different possible levels of interference within feedback loops between the central nervous system, pituitary, gonads and other peripheral organs. The present chapter is a chemist's classification of some of these structures often in the absence of detailed biochemical data. Nonsteroid antiestrogens (and estrogens) most often share a common feature with diethylstilbestrol and consequently the effects of structural modifications on biological activities can be studied in a rational manner. This is not the case for non-steroidal antiandrogens that we have only been able to classify into conventional chemical groups. Nor have any true lead compounds nor well-defined chemical classes been identified for nonsteroid antiprogestogens. This is however the only hormonal class where natural products play an important role.

Androgen Antagonists

Analogies and differences in the modulation of progesterone receptor induction and cell proliferation by estrogens and antiestrogens in MCF-7 human breast cancer cells: study with 24 triphenylacrylonitrile derivatives.

Structure-activity relationships in a homogeneous series of 24 triphenylacrylonitrile derivatives were examined with respect to the stimulation of progesterone receptor induction and cell proliferation in MCF-7 cells. In general, triphenylacrylonitrile derivatives were found to be full or partial agonists for both responses; the partial agonists were also able to antagonize the stimulatory action of estradiol. The agonistic activities of these molecules decreased as the size of the lateral side chain increased, but the side-chains correlated with partial agonism of progesterone receptor induction were bulkier than those correlated with partial agonism of cell proliferation. Agonistic and antagonistic effects on both responses were correlated with affinity for the estrogen receptor. Half maximal effects on the two responses occurred at different concentrations (4-fold) of the compounds. It can be concluded that in MCF-7 cells, triphenylacrylonitrile modulation of progesterone receptor induction and cell proliferation are mediated by the estrogen receptor; the two effects, which occur at different concentrations and with slightly different substituents of the compounds, are differentially modulated.

Breast Neoplasms

Binding of steroids to the progestin and glucocorticoid receptors analyzed by correspondence analysis.

The relative binding affinities of over 30 steroids have been measured for the cytosol glucocorticoid receptor (GR) of thymus, liver, and hepatoma tissue culture cells and for progestin, androgen, and mineralocorticoid receptors. The data have been analyzed by correspondence analysis to reveal the singularities among the receptors of different hormonal classes, the similarities in GR of different origins, and the different specificities of the ligands. Additional data on new steroids have been injected into the system as well as results on a further parameter, namely the induction of tyrosine aminotransferase (TAT) activity, to illustrate the power and flexibility of the methodology. The analysis has confirmed previous correlations between GR binding and TAT response but also highlighted the antiglucocorticoid activity of progestins. This method should prove to be a substantial aid to the interpretation of increasingly complex data, in particular with regard to the action of existing and newly synthesized steroids on glucocorticoid systems of differential sensitivity.

Animals

Home intravenous antibiotic treatment in cystic fibrosis.

The prognosis for patients with cystic fibrosis who are colonised with Pseudomonas aeruginosa has improved as a result of the regular use of intravenous antibiotics; however, this necessitates long periods of hospitalisation. Home intravenous antibiotic treatment has potential advantages over hospital treatment. We describe our experience during the first 20 months of using a system of home intravenous antibiotic treatment in which a cystic fibrosis liaison sister has an essential role. Thirteen patients have received 40 courses of treatment. There were highly significant improvements in weight, respiratory function, and white cell count during home treatment. There was no significant difference in weight and forced expiratory volume in one second between the end of home treatment and the end of hospital treatment while forced vital capacity was better after home treatment. All patients preferred home treatment. The advantages of home visits by the cystic fibrosis liaison sister during treatment are emphasised.

Adolescent

Markers for faecal fat estimation in monitoring steatorrhoea in cystic fibrosis.

Polyethylene glycol (PEG) 4000 is one of numerous substances used as non-absorbable markers to correct for variable faecal output when assessing daily faecal losses of nutrients. The introduction of enteric coated micro-encapsulated pancreatic enzyme (EMPE) preparations has greatly improved the control of fat malabsorption in cystic fibrosis and chronic pancreatitis patients. Unfortunately, these enzyme preparations contain significant quantities of PEG 4000 or polyvinyl pyrrolidine (PVP) as components of the enteric coating and thus PEG 4000 cannot be used either as a faecal marker, or in intubation studies, if these enzyme preparations are being used.

Celiac Disease

Brain acetylcholinesterase activity is markedly reduced in dominantly-inherited olivopontocerebellar atrophy.

The activity was measured of the acetylcholine catabolising enzyme acetylcholinesterase (AChE) in brain after necropsy of seven patients from one established pedigree with dominantly-inherited olivopontocerebellar atrophy (OPCA), a cerebellar ataxia disorder in which neuropathological changes are assumed to be primarily restricted to cerebellum, lower brain stem and spinal cord. Mean AChE activity was significantly reduced in cerebral (-51% to 65%) and cerebellar (-47%) cortex with a less severe change (-37%) in the hippocampus. The magnitude of the enzyme reduction in cerebral cortex was equal to or greater than that reported in brain of demented Alzheimer's and Parkinson's disease patients having loss of AChE-containing nucleus basalis cholinergic neurons. It is concluded that the data provide additional biochemical evidence suggesting a cerebral cortical cholinergic denervation in OPCA.

Acetylcholinesterase

The current physical therapy regimens of 108 consecutive patients attending a regional cystic fibrosis unit.

Comprehensive assessment of patients attending the Regional Cystic Fibrosis Unit includes a detailed evaluation of their physical therapy habits and management. The following were analysed during the assessment by the physiotherapist: the frequency of patient contact with a physiotherapist, the techniques used for chest clearance, the exercise habits, the postural drainage equipment used, if any, and the frequency of respiratory cultures. The results were divided into three groups: group 1, 72 patients (66%), were first-referral patients (FR) to our cystic fibrosis unit; group 2, 26 (24%), received all their care at our unit (CFU); group 3, 10 (9%), were attending a local hospital but had had a previous assessment at our unit (PA). For all factors examined the CFU and PA patients had a more effective management than the FR patients cared for by local hospitals, with the conclusion drawn that regular contact with a physiotherapist at a cystic fibrosis unit improves the understanding, compliance, and effectiveness of the patient's treatment programme.

Ambulatory Care Facilities

Ileal pH in cystic fibrosis.

In cystic fibrosis jejunal hyperacidity has an adverse effect on lipid digestion. It is not known whether hyperacidity extends to the ileum. We have studied pH through the whole length of the small bowel in 42 normal and 6 cystic fibrosis subjects by means of pH-sensitive radiotelemetry capsules. In cystic fibrosis subjects the time spent below pH 6.0 was significantly greater during the 1st h in the small bowel than in normal subjects. In the rest of the small bowel the pH remained above 6.0 in both groups. The recordings in the cystic fibrosis group did not show the clear distinction between ileum and colon which is seen in normal subjects. In cystic fibrosis low pH conditions are confined to the proximal small intestine. There is adequate time at optimal pH in the small bowel for dissolution of enzyme supplements and assimilation of nutrients.

Adult

Osteoblasts increase their rate of division and align in response to cyclic, mechanical tension in vitro.

Bone adapts to physical deformation in vivo, yet the mechanism of the adaptive process remains unknown. One reason for this perplexity has been the difficulty in examining the effects of a well-defined deformation regimen on individual bone cells. With the utilization of novel, flexible-bottomed cell culture plates, one can study the effects of cyclic strain on the morphologic and biochemical adaptations of individual osteoblasts in vitro. Avian, calvarial osteoblast-like cells, from passes 2-5, responded to cyclic strain, by increasing their rates of DNA synthesis and cell division during the first 72 h after initiation of a continuous deformation regimen comprised of 3 cycles per min of 0-24% elongation. In addition, within hours after initiation of the deformation regimen, cells oriented 90 degrees to the applied strain field at the periphery of the culture plate in the region of maximum strain and elongation.

Animals

A new probe for the diagnosis of myotonic muscular dystrophy.

Myotonic muscular dystrophy (DM) is the most common muscular dystrophy, affecting adults as well as children. It is inherited as an autosomal dominant trait and is characterized by variable expressivity and late age-of-onset. Linkage studies have established the locus on chromosome 19. In order to identify tightly linked probes for diagnosis as well as to define in detail the DM gene region, chromosome 19 libraries were constructed and screened for restriction fragment length polymorphisms tightly linked to DM. A genomic clone, LDR152 (D19S19), was isolated that is tightly linked to DM; recombination fraction = 0.0 (95% confidence limits 0.0-0.03); lod score, 15.4.

Adult

A quantitative analysis of blood-brain barrier ultrastructure in the aging human.

The unique ultrastructure of brain endothelial cells restricts nonspecific leakage of blood-borne molecules across the blood-brain barrier (bbb). Human barrier ultrastructure has not been studied extensively because of the rapid ultrastructural degeneration that takes place after death. We have obtained living, structurally normal neocortex and underlying white matter at biopsy from patients of various ages, and have quantitated ultrastructural features that are associated with the bbb so that we could characterize human barrier ultrastructure and determine whether it changes with age. We found that gray matter capillaries have thinner walls than white matter capillaries, and that during aging white matter capillary walls became thinner until they approached the dimensions of those in gray matter. Thinning is due to loss of pericytes and thinning of the endothelial cytoplasm. The mitochondrial density was found to be higher in gray matter than in white matter, but this is a consequence of there being a smaller cytoplasmic volume and not more (or larger) mitochondria. The mitochondrial population did not change with age. Presumptive nonspecific permeability routes (endothelial vesicles, junctional gaps) did not change with age; therefore we found no morphological substrate for increased nonspecific bbb permeability in the aging human. The loss of pericytes, however, suggests that the bbb in the elderly may be less able to compensate for transient leaks.

Aging

Studies on the metabolism of deoxynivalenol in the rat.

The metabolism and tissue distribution of [14C]deoxynivalenol have been studied in male PVG rats. Following administration of a single oral 10-mg/kg dose, radioactivity excreted in the urine and faeces accounted, respectively, for 25 and 64% of the administered dose within 96 hr. Less than 0.15% of the dose was detected in the respired air. Very little radioactivity appeared to be retained in any of the tissues examined after 96 hr. HPLC separation of several urinary and faecal metabolites was achieved on a reversed-phase column, using two different elution systems, one at neutral pH and one acidified. Two of the major non-polar HPLC peaks were identified by gas chromatography-mass spectrometry as unchanged deoxynivalenol and 3 alpha,7 alpha,15-trihydroxytrichothec-9,12-dien-8-one.

Animals

Intravenous sedation for cataract surgery.

Fifty-five unpremedicated outpatients scheduled for cataract surgery were randomly allocated to receive either a fixed dose of nalbuphine and methohexitone or fentanyl and diazepam administered in a dose adjusted to produce the required sedative effect. Statistical analysis revealed no difference between groups with regard to immediate side effects, intra-ocular pressure or postoperative nausea or vomiting. Recovery time from administration of the sedative until compliance with simple commands was significantly longer in the nalbuphine/morphine group (89 vs 196 seconds) but this was not felt to be of clinical importance. This combination was better in terms of sedation at the time of insertion of the nerve blocks, lack of recall of insertion of the nerve block, incidence of intra-operative complications, surgeon's assessment of operating conditions and patient acceptability. This fixed dose by weight drug combination for intravenous sedation should be applied widely.

Adolescent