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Biomedical subjects

J Nelson

Publications and source records attributed to J Nelson.

At least 271 records · Page 15Linked to original sources

Acute tolerance to cocaine in humans.

There is controversy as to whether acute tolerance develops to the principal effects of cocaine in humans. The studies described here demonstrate the phenomenon of acute tolerance to cocaine chronotropic and subjective effects and the rate and extent of tolerance development. Stable plasma cocaine concentrations were produced and then maintained in volunteer cocaine users by administering an intravenous cocaine injection followed by a cocaine infusion designed to compensate for the plasma clearance of cocaine. The euphoric effect (high) intensified to a peak at about 1 hour and then declined toward baseline at 4 hours despite the presence of constant plasma cocaine levels. The chronotropic effect reached a peak within 10 minutes and then declined, with a half-life of 31 +/- 13 (mean +/- SD) minutes toward a plateau at 33% +/- 21% of its peak intensity. Tolerance development was quantified as an exponential process, with a rate constant (tolerance factor) accounting for the progressive alteration of the cocaine concentration-effect relationship.

Adult↗

Clinical findings in 12 patients with MPS IV A (Morquio's disease). Further evidence for heterogeneity. Part I: Clinical and biochemical findings.

Clinical heterogeneity in MPS IV A (Mucopolysaccharidosis IV A, Morquio Disease Type A)has become more clearly identified in recent years. The clinical findings in 12 cases of MPS IV A are described. Clinical presentation was variable, and some cases were only mildly affected. All showed deficiency of N-acetylgalactosamine-6-sulphate sulphatase in fibroblasts, but the patient with the mildest clinical presentation showed a high residual enzyme activity. The urinary glycosaminoglycans (GAGs) were examined on all patients by a two-dimensional electrophoresis technique which proved to be highly reliable and efficient. In particular, no false negative results were obtained, a problem often encountered with routine screening methods. These cases support the division of MPS IV A into three subgroups: the severe "classical" type, an intermediate type and a mild type, all caused by N-acetylgalactosamine-6-sulphate sulphatase deficiency. Residual enzyme activity may be an important prognostic indicator.

Adolescent↗

Clinical findings in 12 patients with MPS IV A (Morquio's disease). Further evidence for heterogeneity. Part II: Dental findings.

Typical dental changes were present in all cases, although they were of variable degree. However, the tooth morphology would appear to be highly specific for MPS IV A, and is not found in MPS IV B (beta-galactosidase deficiency) or the recently delineated MPS IV C (enzyme defect unknown). Thus the dental changes have a very useful diagnostic potential in mild atypical cases of MPS IV A, although they may only be demonstrable radiologically in some such cases.

Adolescent↗

Clinical findings in 12 patients with MPS IV A (Morquio's disease). Further evidence for heterogeneity. Part III: Odontoid dysplasia.

Odontoid dysplasia in the absence or presence of atlanto-axial instability was found in all cases. In general, this correlated well with the overall clinical severity of the condition and illustrates the importance of careful follow-up of these patients. Symptoms or signs of cervical cord compression merit further investigation. Proven compromise of the upper cervical cord is an indication for posterior fusion of the upper cervical spine.

Atlanto-Axial Joint↗

Asymptomatic adult Alexander's disease: entity or nosological misconception?

Two adults were found to have heavy deposits of Rosenthal fibers in the CNS after dying from severe systemic medical illnesses. Previously reported cases of neurologically asymptomatic adult Alexander's disease patients also had complicated systemic disease. We suggest that heavy Rosenthal fiber deposition may occur in the setting of severe medical illness and should not be classified as adult Alexander's disease.

Aged↗

A modified spectrofluorometric assay for DNA using adriamycin.

A spectrofluorometric assay for DNA is described. The changes in the fluorescence of adriamycin when it binds to DNA may be quantitated in terms of the amount of DNA present. The assay is specific and reproducible, being free from interference from RNA, protein, and sample turbidity.

Breast Neoplasms↗

A dual role for calcium in regulation of superoxide generation by stimulated rat alveolar macrophages.

Superoxide production in alveolar macrophages is stimulated by agonists which act through Ca2+-mediated (concanavalin A) and/or protein kinase C (phorbol ester or diacylglycerol analogues) -mediated events. Simultaneous addition of saturating concentrations of concanavalin A and a protein kinase C activator (either phorbol 12-myristate-13-acetate or 1-oleoyl-2-acetyl-sn-glycerol) caused a supra-additive enhancement of the initial rate of O2-. production. This synergism closely correlated with the known time-course of Ca2+ mobilization induced by concanavalin A; however, it occurred under conditions in which protein kinase C activation is reportedly not Ca2+ dependent. Phorbol ester-induced O2-. production was partially inhibited by the Ca2+ ionophore, A23187. Although phorbol ester-stimulated O2-. production initially was enhanced by concanavalin A, the duration of this O2-. production was reduced in comparison to that induced by phorbol ester alone. These results suggest a dual role for intracellular Ca2+ in both stimulatory and inhibitory regulation of O2-. production.

Animals↗

The early development of the eye of the pouch-young of the marsupial Dasyurus hallucatus.

The development of the eye of the pouch-young of the marsupial native cat Dasyurus hallucatus from birth to day 30 is described. Following the staging system used by other authors, the stage of development of the eye at birth is comparable to that of a six-week human embryo, a 33 day rhesus embryo or a 14 day rat embryo. In contrast to eutherian mammals where development progresses from one stage to another at approximately the same rate, in the native cat the rate tends to progressively decrease. All of the neural development of the native cat eye occurs while the young is in the pouch.

Animals↗

The value of computed tomography in patients with mucopolysaccharidosis.

Cranial computed tomography (CT) was performed on 11 cases of mucopolysaccharidosis (MPS) IVA (Morquio syndrome). Our results suggest that although the patients may have normal intelligence CT changes may be seen with increasing age. In two cases white matter low density was found and in a third there was gross dilatation of the ventricles, basal cisterns and subarachnoid space. Nine other patients with various types of mucopolysaccharidosis also had cranial CT performed and in general those types associated with mental retardation showed changes although there was an interesting exception involving a case of MPS IIIA who had a normal CT scan.

Adolescent↗

Recombinant human interferon alpha increases oestrogen receptor expression in human breast cancer cells (ZR-75-1) and sensitizes them to the anti-proliferative effects of tamoxifen.

Exposure of ZR-75-1 human breast cancer cells for 48 h to human recombinant interferon alpha (IFN alpha) resulted in increased expression of oestrogen receptors as measured in a whole cell binding assay. This effect was inversely proportional to dose being significant following treatment with 10-100 IU IFN ml-1 and was only observed at a low initial cell plating density. The extent of the increase in oestrogen receptor levels ranged from 1.2- to 7.2-fold following treatment with 10 IU IFN ml-1. No increase in progesterone receptor expression was observed under the same experimental conditions. Concentrations of IFN which increased oestrogen receptor levels had no effect on cell proliferation. IFN (500 IU ml-1) inhibited cell proliferation and the combination of this treatment with tamoxifen (2 microM) had a greater anti-proliferative effect than either drug alone although there was no evidence of synergism. However, a 5-day pretreatment of cells with IFN (10 IU ml-1) markedly sensitised them to the growth-inhibiting effect of a subsequent 6-day exposure to tamoxifen.

Binding, Competitive↗