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Biomedical subjects

D Jack

Publications and source records attributed to D Jack.

At least 37 records · Page 2Linked to original sources

Evaluation of light transmission and distribution materials for Lunar and Martian bioregenerative life support.

The materials that were selected and evaluated in this study in the context of bioregenerative advanced life support included polymer optical cables, for transmission of photosynthetic photon flux (PPF), and light pipe, woven optical pad and light-emitting fiber (LEF) for PPF distribution. All materials exhibited significant fidelity in transmitting the spectral characteristics of the artificial lluminator's Xenon-Metal Halide lamp. The PPF attenuation values for the polymer cables EL-200, EL-300, EL-400, and EL-500 were not significantly distinguishable from one another nor from that of the fused-silica cable of 0.34 dB/m. With the exception of EL-100 and EL-700, which had significantly lower PPF transmission efficiencies of 54.9%/m and 66.6%/m, respectively, all the other polymer cables had PPF transmission efficiencies of over 85%/m which, except for EL-300, were not significantly different from one another nor from that of the fused-silica cable of 93.2%/m. The highest PPF output efficiency achieved for the 7.1-cm light pipe 14.7%, for its maximum pipe length of 100 cm. At a constant pipe length of 50 cm, the PPF output efficiency of the 10-cm light pipe of 0.71% was significantly lower than that of the 7.1-cm light pipe of 10.54%. The PPF output for the woven optical pad was determined to be 36.3%. The PPF output efficiency for the LEF without the optic fastener was determined to be 27.1%, whereas that for the LEF with the optic fastener was 50.3%, that is, the maximum value of PPF output efficiency in the study. The polymer optical cables, light pipe, woven optical pad, and LEF exhibited significant regularity and symmetry in their PPF output spatial distributions.

Ecological Systems, Closed↗

Simultaneous genotyping for all three known structural mutations in the human mannose-binding lectin gene.

We describe a rapid and simple method for genotyping the three known structural mutations within exon 1 of the mannan-binding lectin (MBL) gene. A PCR-amplifiable synthetic DNA (Universal Heteroduplex Generator) was annealed to genomic PCR product from exon 1 to generate unique DNA heteroduplexes for each mutation. Heteroduplexes were then resolved by non-denaturing polyacrylamide gel electrophoresis. The technique was initially validated with previously typed samples and then applied to previously untyped samples with the results confirmed by DNA sequencing.

Amino Acid Sequence↗

Asthma guidelines.

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Administration, Inhalation↗

Salmeterol, a novel, long-acting beta 2-adrenoceptor agonist: characterization of pharmacological activity in vitro and in vivo.

1. Salmeterol, a novel, long-acting beta-adrenoceptor agonist, has been compared with isoprenaline and salbutamol for activity in vitro on a range of beta-adrenoceptor containing preparations from laboratory animals and man, and in vivo for bronchodilator activity in the conscious guinea-pig. 2. Salmeterol, like isoprenaline and salbutamol, relaxed preparations of both guinea-pig trachea (contracted by prostaglandin (PG)F2alpha or electrical stimulation) and human bronchus (contracted by PGF 2 alpha) in a concentration-related fashion. Salmeterol was of similar potency to isoprenaline and more potent than salbutamol on both airway preparations. 3. Relaxant responses of superfused guinea-pig trachea and human bronchus to isoprenaline and salbutamol declined rapidly when the agonists were washed from the tissues, with complete recovery within 10 min, whereas responses to salmeterol were more persistent. In electrically-stimulated guinea-pig trachea preparations, inhibition by salmeterol persisted for periods of up to 12h, despite continuous superfusion with agonist-free medium. However, these persistent responses were rapidly and fully reversed by the beta-adrenoceptor blocking drug, propranolol (0.1 microM). In further studies on guinea-pig trachea, propranolol caused concentration-related parallel, rightward shifts of salmeterol concentration-effect curves, yielding a pA2 of 9.0. The slope of the Schild plot was 1.02. 4. Another beta-adrenoceptor blocking drug, sotalol (10 microM), also fully and rapidly reversed established submaximal responses to salmeterol in superfused guinea-pig trachea. However, after administration of sotalol was stopped, the antagonism waned, and salmeterol responses were reasserted without the addition of further agonist. 5. In the beta 1-adrenoceptor containing preparation, rat left atria, isoprenaline exhibited potent, concentration-related, positive inotropic activity, whereas salbutamol and salmeterol were at least 2000-5000 fold less potent, and appeared to be partial agonists. At a concentration of 72 microM, salmeterol exhibited weak antagonism of isoprenaline-induced increases in atrial force of contraction. This antagonism was less marked than that caused by salbutamol (42 microM).6. On the guinea-pig isolated gastric fundus strip, a putative beta3-adrenoceptor containing preparation, salbutamol and salmeterol had only modest agonist activity, being 20-30 fold less potent than isoprenaline and the selective ,beta3-adrenoceptor agonist, BRL 35135.7. In conscious guinea-pigs, inhaled salmeterol and salbutamol were approximately equipotent in causing dose-related bronchodilatation. Whereas the duration of action of salbutamol at its threshold-effective dose was less than 90min, the responses to a similarly effective dose of salmeterol were well-maintained for at least 6 h.8. Salmeterol is therefore a potent and selective beta2-adrenoceptor agonist with a remarkably long duration of action in isolated superfused airways smooth muscle. It also causes persistent bronchodilatation in vivo, in the guinea-pig, when administered by the inhaled route.

Adrenergic beta-Agonists↗

Safety by design.

Safety by design for any kind of drug requires it to act selectively on the cells which mediate the desired effect, and affect other cellular functions as little as possible. To illustrate this, the treatment of bronchial asthma was much improved during the past 20 years by the development of inhalation treatment based on drugs such as salbutamol (albuterol), a selective beta 2-adrenoceptor stimulant, and beclomethasone dipropionate, a topical anti-inflammatory steroid, from their parent physiological mediators epinephrine (adrenaline) and hydrocortisone (cortisol). Their development and that of H1- and H2-antagonists from histamine are described. From these and other sources the general conditions for safe, selective drug action and the range of drug effects that may be attained by modifying physiological mediators are deduced. This involves the identification and definition of type 1 and type 2 agonism. This analysis led to the discovery of salmaterol (salmeterol), a new uniquely long acting beta 2-adrenergic bronchodilator, by modification of salbutamol. The development, by modification of serotonin (5-hydroxytryptamine), of ondansetron, a new antiemetic for use in cancer chemotherapy, and sumatriptan, a new type of drug for treating migraine, are also described. All these new drugs are more efficacious and safer than their predecessors.

Animals↗