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Biomedical subjects

J Gilbert

Publications and source records attributed to J Gilbert.

At least 163 records · Page 9Linked to original sources
PubMed1989

Down's syndrome individuals begin life with normal levels of brain cholinergic markers.

We measured the activities of the cholinergic marker enzymes choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in autopsied brains of seven infants (age range 3 months to 1 year) with Down's syndrome (DS), a disorder in which virtually all individuals will develop by middle age the neuropathological changes of Alzheimer's disease accompanied by a marked brain cholinergic reduction. When compared with age-matched controls cholinergic enzyme activity was normal in all brain regions of the individuals with infant DS with the exception of above-normal activity in the putamen (ChAT) and the occipital cortex (AChE). Our neurochemical observations suggest that DS individuals begin life with a normal complement of brain cholinergic neurons. This opens the possibility of early therapeutic intervention to prevent the development of brain cholinergic changes in patients with DS.

Acetylcholinesterase↗
PubMed1989

Totally implantable venous access systems in paediatric practice.

Forty seven totally implantable venous access systems have been inserted in 45 patients for the management of malignant disease (n = 29), haematological disorders (n = 5), and cystic fibrosis (n = 11). We report our experience with them and discuss the problems we have encountered during the past three years.

Adolescent↗
PubMed1989

DNA replication and cell cycle control in Xenopus egg extracts.

Aspects of the regulation of DNA replication and mitosis have been studied using a cell-free extract of Xenopus eggs. The extract is characterized by repeated cycles of DNA replication and mitosis, which are accompanied by periodic synthesis and degradation of cyclins as well as fluctuations in the level of Histone H1 kinase activity. DNA replication in this system is dependent upon the formation of a nucleus. However, while nuclear structures are clearly required for initiation, a complete nuclear membrane does not appear to be necessary. Indirect immunofluorescence and DIC microscopy indicate that nuclear reformation from chromosomes occurs asynchronously around individual chromatids. Lamin polymerization, biotin-11-dUTP incorporation and association of polymerases with chromatin occur before membrane formation is complete. S phase nuclei are typified by the co-distribution of both anti-DNA polymerase alpha and anti-PCNA antibodies as discrete spots of fluorescence which align the chromatin. However, as DNA replication is terminated, PCNA fluorescence fades and DNA polymerase alpha dissociates from the chromatin and is redistributed throughout the nucleoplasm. By inhibiting DNA replication with aphidicolin, both DNA polymerase alpha and PCNA remain associated with the chromatin throughout prolonged incubation. Under these conditions mitosis is delayed by up to 70 min, although both the general rate of protein synthesis and more importantly the rate of cyclin synthesis and histone kinase activation are unaffected. Upon nuclear envelope breakdown and lamin dispersal, cyclins degrade; however, no chromosomes are formed, and both PCNA and DNA polymerase alpha remain associated with the chromatin. Also, histone kinase activity is maintained at elevated levels.

Animals↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗