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Biomedical subjects

G Sharpe

Publications and source records attributed to G Sharpe.

At least 37 records · Page 2Linked to original sources
PubMed1992

Structure and chromosomal localization of the human 2',3'-cyclic nucleotide 3'-phosphodiesterase gene.

Human brain cDNA clones for the myelin associated enzyme 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) have been isolated and sequenced. The only 5' untranslated region (UTR) sequence found was that of a human CNPII mRNA, with no direct evidence for a CNPI mRNA. Human CNPase cDNAs were used to isolate genomic clones containing the human CNPase gene which is 9 kb long. Four exons were identified, separated by three introns, and the sequence of each exon and intron/exon boundary has been established. The polymerase chain reaction (PCR) was used to detect the presence of the human CNPase gene in DNA from a panel of rodent/human somatic cell hybrids. By this means the human CNPase gene was mapped to chromosome 17. In situ hybridization of a human CNPase genomic clone to metaphase chromosomes further localized this gene to chromosomal band 17q21.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1986

Enhanced basophil histamine release to concanavalin A in allergic rhinitis.

It has been suggested that IgE-dependent basophil histamine release (HR) does not necessarily relate to the amount of cell-bound IgE and, therefore, basophil "releasability" must be considered an important factor in this secretory process. To compare an IgE-dependent basophil HR process in nonatopic subjects and patients with allergic rhinitis, concanavalin A (Con A) was used as a secretagogue to stimulate mediator secretion. In 1.0 mmol/L of calcium-containing buffer, basophil HR to Con A (3.0 mcg/ml) was 50.2 +/- 8.6% in patients with allergic rhinitis and only 10.1 +/- 3.9% in nonatopic subjects. To evaluate whether this enhanced HR might be related to increased membrane influx of calcium, the following strategy was followed. Strontium (3.0 and 10.0 mmol/L) enhances immunologic (IgE) release of basophil histamine. Although the mechanism for strontium enhancement is not established, strontium may pass through the membrane channel more easily than calcium to increase secretion. We reasoned that if the enhanced release of histamine to Con A was related to increased membrane permeability to calcium, stimulation of basophil histamine secretion in the presence of strontium would reduce this difference. In both nonatopic subjects and patients with allergic rhinitis, strontium (3.0 and 10.0 mmol/L) enhanced HR. Enhanced HR with strontium was greater with basophils from normal subjects than from subjects with allergic rhinitis. Whether our observations with strontium indicate that the enhanced histamine releasability to Con A in subjects with allergic rhinitis may, in part, be due to a greater influx of calcium after immunologic stimulation must await characterization of the strontium effect or direct measurements of calcium ion disposition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

The management of severe brittle diabetes with "Infusaid" implantable pumps.

Two severely brittle diabetic patients were treated with "Infusaid" implantable insulin infusion pumps. Both were young females with recurrent ketoacidosis, prolonged or repeated hospital admissions, and subcutaneous insulin resistance. They also had psychological problems, and had seriously interfered with their treatment to induce glycaemic instability. Delivery of insulin from the pumps was intravenous (i.v.) in one patient, and intraperitoneal (i.p.) in the other. Following implantation, there was a marked improvement in glycosylated haemoglobin level (HbA1), fasting blood glucose (BG), daily insulin dose and hospitalizations. The beneficial effect has continued to date (9 months, and 12 months follow-up) with no major problems.

Adult↗
PubMed1985

The effect of procaterol treatment on beta-adrenergic bronchodilation and polymorphonuclear leukocyte responsiveness.

Procaterol is a new and effective beta-adrenergic bronchodilator. To determine if procaterol administration could cause tachyphylaxis, airway and leukocyte beta-adrenergic function were monitored in 10 patients with asthma during two 4-wk, double-blind treatment periods, each preceded by a 2-wk beta-agonist washout. Treatment periods were randomized to placebo or procaterol (2 wk, 0.1 mg/day; 2 wk, 0.2 mg/day). At each 7 biweekly evaluations, the patient's cumulative bronchodilator dose-response to inhaled isoproterenol (0.1 to 0.64%) was measured, and venous blood was collected to quantitate, in vitro, the polymorphonuclear leukocyte (PMN) beta-adrenergic receptor's 125Iodo-cyanopindolol (125I-CYP) ligand binding and the PMN cyclic AMP response to isoproterenol and procaterol. Neither the airway nor leukocyte beta-adrenergic characteristics were changed during placebo treatment. Procaterol treatment reduced (p less than 0.05) the maximal 125I-CYP binding to PMN membranes but only during the initial 2 wk at low dosage. The percent PMN cyclic AMP increase to procaterol (10(-5) M) was also significantly (p less than 0.05) less during active treatment (141 +/- 40%) than during washout (256 +/- 24%) or placebo (257 +/- 32%). In contrast, procaterol treatment did not alter the acute isoproterenol bronchodilation response as measured by either the percent improvement in FEV1 or the dose required to produce 50% maximal bronchodilation. The duration of bronchodilation was not measured. Therefore, although procaterol therapy of asthma is associated with decreased PMN beta-adrenergic function, airway smooth muscle function appears not to be altered.

Adult↗
PubMed1982

Expression of a chemically synthesized human alpha 1 interferon gene.

Cells of Escherichia coli containing a chemically synthesized human alpha 1 interferon (IFN-alpha 1) gene, under control of the lac promoter, make a product with biological properties indistinguishable from those of the natural IFN-alpha 1 [antiviral activity, acid stability, species crossreactivity, inactivation by antisera directed against leukocyte or Namalwa cell interferon, and stimulation of (2'-5')oligoadenylate synthetase activity]. Similar levels of IFN synthesis were obtained when the expression unit (lac promoter plus synthetic IFN-alpha 1 gene) was transplanted into the obligate methylotroph Methylophilus methylotrophus.

2',5'-Oligoadenylate Synthetase↗