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Biomedical subjects

G Tucker

Publications and source records attributed to G Tucker.

At least 55 records · Page 3Linked to original sources
PubMed1990

Pharmacokinetics of moclobemide after single and multiple oral dosing with 150 milligrams 3 times daily for 15 days.

This study was undertaken to determine the absolute bioavailability and steady-state concentrations of moclobemide after doses of 150 mg. In 14 healthy human volunteers, no differences in tmax, t 1/2 beta, C1/F, Cmax and AUC were found between a single oral dose of 100 mg and one of 150 mg. The mean absolute oral availability was 0.66 and 0.69 respectively. Plasma concentration profiles of moclobemide on repeated dosing with 150 mg 3 times daily for 15 days were essentially superimposable, although the mean concentration was higher than after the single 150 mg dose. This concentration increased over the first week and then remained relatively constant. Mean accumulation factors for moclobemide during the first week were 1.85 for Cmax and 3.0 for AUC. These values were higher than predicted from single-dose characteristics. There was a marked reduction in the variability of AUC and clearance (C1/F) values at steady-state compared with the first dose. Minimum plasma concentrations of the 2 metabolites, Ro 12-5637 and Ro 12-8095, were relatively stable throughout dosing. The exact mechanism of the decrease in systemic and oral clearance of moclobemide with time during multiple oral dosing is not known at present. Either moclobemide inhibits its own clearance or moclobemide metabolism is inhibited by one or more of its metabolites. The findings indicate that, if dosage needs to be adjusted during treatment with moclobemide, the changes should be made carefully and at intervals of not less than 1 week.

Administration, Oral↗
PubMed1989

Carcinoma of the pancreas. Is treatment worthwhile?

A study of 60 patients with adenocarcinoma of the pancreas demonstrates the poor prognosis associated with this disease. Unless patients had localized, resectable tumors, survival was virtually unchanged by any treatment prescribed.

Adenocarcinoma↗
PubMed1988

Adhesion mechanisms in embryogenesis and in cancer invasion and metastasis.

Cell-substratum and cell-cell adhesion mechanisms contribute to the development of animal form. The adhesive status of embryonic cells has been analysed during epithelial-mesenchymal cell interconversion and in cell migrations. Clear-cut examples of the modulation of cell adhesion molecules (CAMs) have been described at critical periods of morphogenesis. In chick embryos the three primary CAMs (N-CAM. L-CAM and N-cadherin) present early in embryogenesis are expressed later in a defined pattern during morphogenesis and histogenesis. The axial mesoderm derived from gastrulating cells expresses increasing amounts of N-cadherin and N-CAM. During metamerization these two adhesion molecules become abundant at somitic cell surfaces. Both CAMs are functional in an in vitro aggregation assay; however, the calcium-dependent adhesion molecule N-cadherin is more sensitive to perturbation by specific antibodies. Neural crest cells which separate from the neural epithelium lose their primary CAMs in a defined time-sequence. Adhesion to fibronectins via specific surface receptors becomes a predominant interaction during the migratory process, while some primary and secondary CAMs are expressed de novo during the ontogeny of the peripheral nervous system. In vitro, different fibronectin functional domains have been identified in the attachment, spreading and migration of neural crest cells. The fibronectin receptors which transduce the adhesive signals play a key role in the control of cell movement. All these results have prompted us to examine whether similar mechanisms operate in carcinoma cell invasion and metastasis. In vitro, rat bladder transitional carcinoma cells convert reversibly into invasive mesenchymal cells. A rapid modulation of adhesive properties is found during the epithelial-mesenchymal carcinoma cell interconversion. The different model systems analysed demonstrate that a limited repertoire of adhesion molecules, expressed in a well-defined spatiotemporal pattern, is involved in tissue formation and in key processes of tumour spread.

Animals↗
PubMed1985

Responses of the pigmented rabbit retina to NMPTP, a chemical inducer of parkinsonism.

The electrophysiological and neurochemical effects of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP), a chemical inducer of Parkinsonism in man and monkeys, on the pigmented rabbit retina were determined under both chronic and acute conditions. The implicit time, the oscillatory potentials, and the amplitude of the b-wave of the rabbit electroretinogram were affected; both dopamine and dihydroxyphenylalanine (DOPA) levels were depressed. Ultrastructural analysis of acute and chronic retinas showed the occurrence of an intranuclear filamentous inclusion in the nucleus of some cells in the inner nuclear and ganglion cell layer of chronic samples. The effects of the neurotoxin NMPTP on the retina suggest that dopaminergic metabolism is impaired, which then affects the components of the electroretinogram attributed to both bipolar and amacrine cells. In addition, the retina may provide a model in which to study the bichemical and pharmacological mechanisms of NMPTP toxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1984

Absence of IgG Fc receptors on varicella-zoster virus-infected cells.

Herpesvirus-infected cells usually express receptors for the Fc portion of immunoglobulin G. Varicella-zoster virus has so far been the sole exception in the family. Both immunehemadsorption and immunofluorescence techniques failed to detect the expression of such receptors. This observation excludes the possibility of false-positive results in serological tests for antibodies to this virus. It is possible that the function of these receptors early in infection is not needed in the subsequent reactivation(s) of the virus. No variation has been shown to occur with different isolates.

Cells, Cultured↗
PubMed1983

Changes in clinical features of coeliac disease in adults in Edinburgh and the Lothians 1960-79.

From 1960 to 1979 there was a threefold increase in the number of cases of coeliac disease diagnosed annually in adults in Edinburgh and the Lothians. Women accounted for 80% of the increase and their mean age at diagnosis was significantly reduced. The ratio of female to male new cases changed from 1.25 in the '60s to 2.5 in the '70s. In the period 1975-9 56 of 102 adults with coeliac disease presented with no gastrointestinal symptoms, including 30 cases diagnosed as a result of minor biochemical or haematological abnormalities, such as red-cell macrocytosis without anaemia. Over the same period, only 13 presented with a typical malabsorption syndrome compared to 24 of 38 (63%) in the years 1960-4. During 1975-9 58 new cases had no anaemia, compared with eight (21%) in the earlier period. Hypoproteinaemia (concentration less than 60 g/l) and hypocalcaemia of less than 2.00 mmol/l (8 mg/100 ml) were also less common. Though a real increase in the incidence of coeliac disease cannot be discounted, these changes are more likely to be the result of greater awareness of the disease and a lowered threshold for investigation.

Adolescent↗
PubMed1983

Interferon induction of (2'-5') oligoisoadenylate synthetase in diploid and trisomy 21 human fibroblasts: relation to dosage of the interferon receptor gene (IRFC).

Trisomy 21 human fibroblasts are more sensitive to human interferon-alpha (IFN-alpha) than are diploid controls, consistent with the location of the gene (IFRC) which codes for the IFN-alpha receptor on chromosome 21. When compared in the antiviral assay, the difference in sensitivity is five- to tenfold, much greater than the 50% difference in IFRC gene dosage. An understanding of the mechanism by which this amplification of gene dosage occurs is relevant to the specific pathology of Down's syndrome and as a model system for studying the pathogenic effects of chromosomal aneuploidy. The enzyme (2'-5') oligoisoadenylate synthetase (2-5A synthetase), which is believed to be central to the interferon-induced antiviral response, is induced 50% more in trisomy 21 fibroblasts than in diploid controls. Thus the amplification in response occurs subsequent to the binding of IFN-alpha to its receptor and the triggering of the first set of intracellular events, the latter exemplified by the induction of 2-5A synthetase. Similar results were obtained with IFN-gamma, consistent with other evidence which indicates that a gene coding for a separate IFN-gamma receptor is also located on chromosome 21.

Diploidy↗
PubMed1983

In vitro migration of avian hemopoietic cells to the thymus: preliminary characterization of a chemotactic mechanism.

Hemopoietic cells differentiating in the thymus have an extrinsic origin; it has been suggested that, in avian embryos, the thymic epithelium can recruit precursor cells at several precisely determined periods by a chemotactic mechanism. We have used a chemotactic chamber (Zigmond, S.H.: J. Cell Biol. 75, 606-616 (1977] to analyse quantitatively the behaviour of hemopoietic precursor cells confronted with thymuses. The embryonic bone marrow was found to be a rich source of precursor cells carrying thymic lymphocyte potentialities. In the Zigmond chamber, precursor cells exhibited a strong chemotactic response to a concentration gradient of substances secreted by attractive thymuses from 7 1/2-day-old chick embryos; the mesonephros from embryo of the same age had no effect. In addition 7 1/2-day-old attractive and 10-day-old refractory chick thymuses induced a net increase of adhesiveness and speed of locomotion. The chemotactic factor secreted by an attractive thymic epithelium was not retained by a 12 kdalton cut-off dialysis membrane, whereas the chemokinetic activity was associated with material of molecular weight higher than 50 kdaltons. Refractory thymuses freed of most of their homopoietic cells became attractive and produced a chemotactic factor of a molecular weight close to 1 kdalton. When introduced into the two separate compartments of the chemotactic chamber, the chemokinetic and the chemotactic activities could complement each other to produce a full response identical to that obtained with attractive thymuses. The two factors, synthesized exclusively by the thymus, were effective on basophilic precursor cells but not on granulocytes. A theoretical model for random cell migration described in the Appendix showed that the standard deviation of the chemotactic index was greatly influenced by the degree of persistence in the direction of movement, the duration and the number of cells recorded. The high values obtained for the standard deviations are fully explained by the persistence in the direction of movement of the basophilic bone marrow cells. In all cases, a clear distinction could be made between a chemokinetic and a chemotactic response. For the first time, a chemotactic mechanism has been demonstrated to control the directed migration of embryonic cells. Our data fully support the hypothesis proposed by Le Douarin (1978, in: Cold Spring Harbor Conferences on Cell Proliferation, pp. 5-31) that the homing of hemopoietic precursor cells into the thymus is controlled by a chemotactic mechanism.

Animals↗
PubMed1981

Echovirus type 7 meningitis in young children.

Clinical and virological features are presented of an epidemic of aseptic meningitis in children caused by echovirus type 7. The majority of patients were younger than 1 year of age. Symptoms varied according to age. The degree of CSF pleocytosis was inversely related to age and was significantly greater in infants 7 months of age and younger than in those older than 7 months. A CSF polymorphonuclear pleocytosis was documented in 66% of the cases. Human placental fibroblast provided a more rapid detection of cytopathic effect and improved final recovery rates when compared with rhesus monkey kidney cells, Vero cells, and human epidermoid (Hep-2) cells. Several possible explanations for the sudden appearance of echovirus type 7 activity are discussed.

Adolescent↗