Molecular and quantitative analysis of helper T cell-replacing factors on the induction of antigen-sensitive B and T lymphocytes.
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Biomedical subjects
Publications and source records attributed to J Shaw.
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1. Spiral strips of human digital arteries have been studied in vitro to investigate whether DL-propranolol, D-propranolol, oxprenolol and labetalol have peripheral vascular effects in man. 2. Labetalol was a potent inhibitor of contractile responses to noradrenaline, but had less effect on responses to 5-hydroxytryptamine and barium chloride. 3. DL-and D-propranolol were equally effective inhibitors of responses to barium chloride. They were only weak antagonists of noradrenaline responses, but stronger, non-competitive antagonists of 5-hydroxytryptamine responses. 4. Oxprenolol was only a weak inhibitor of the responses to both noradrenaline and 5-hydroxytryptamine and had little effect on responses to barium chloride. 5. It is concluded that labetalol has specific alpha-adrenoreceptor-blocking properties, which are probably relevant to its therapeutic action in man. Propranolol has non-specific inhibitory effect on vascular smooth muscle, which might contribute to its hypotensive activity at high concentrations, but oxprenolol has only slight peripheral effects that are probably therapeutically insignificant.
1. Chlorothiazide twice a day plus atenolol, metoprolol, pindolol and propranolol in single daily doses administered to patients with essential hypertension achieved effective control of blood pressure. 2. Each beta-adrenoreceptor-blocking drug was associated with small, but significant, increases in plasma triglyceride concentrations and suppression of fasting immuno-reactive glucagon concentrations.
1 The effect of intravenous aminophylline infusion (6 mg-1 kg in 20 min, then 0.9 mg-1 kg-1 h thereafter) and its interaction with inhaled isoprenaline (800 microgram ex inhaler) on plasma cyclic AMP levels was studied in five normal and five asthmatic subjects. 2 Aminophylline infusion alone did not significantly change plasma cyclic AMP levels in either group. 3 In both groups, the plasma cyclic AMP response to isoprenaline aerosol inhalation was enhanced by aminophylline, although to a lesser degree in the asthmatic subjects. 4 The results provide in vivo evidence consistent with the hypothesis that in man, therapeutic doses of aminophylline may exert their clinical effects by inhibition of cyclic AMP phosphodiesterase.
A conceptually simple and east-to-use technique is described that uses continuous impedance measurements for automated monitoring of microbial growth and metabolism. The method has been applied to a wide range of microorganisms. Optical clarity is not required. The sensitivity and reproducibility of the method are demonstrated. The mechanism whereby microbial growth alters the impedance of the medium is discussed, as well as potential applications of the method to clinical microbiology.
We recently described a factor, costimulator, that is required for the concanavalin A-induced proliferation of CBA mouse thymocytes in vitro (see Reference 1). Using the costimulator dependence of mouse thymocytes as an assay, we have now determined that spleen cells from congenitally athymic (nude) BALB/c mice do not produce costimulator in response to Con A, and spleen cells depleted of Thy 1-positive cells do not respond to it in the presence of Con A. Thus, costimulator both requires thymus-derived (Thy 1+ lymphocytes for its production and has an effect on this type of cell. (However, the costimulator-producing and responsive cells may be different.) Purified costimulator preparations are a source of the required second component for the stimulation of adult, CBA/J thymic lymphocytes by PHA, normally a poor mitogen for these cells. They also enhance the level of DNA synthesis in a mixed leukocyte reaction, and the specific generation of cytotoxic lymphocytes to allogeneic tumor cells in vitro. Costimulator is not H-2 restricted in its effects, and it is produced in mixed leukocyte reactions. Finally, it has been possible to grow normal, primary thymic lymphocytes in culture for about 20 days by adding partially purified costimulator to the cultures.
We have partially purified a lymphokine, costimulator, which is necessary to induce mitogenesis in mouse thymocytes in vitro. Costimulator is released from mouse leukocytes exposed to Con A for 12 to 18 hr. It has been purified more than 100 X by gel exclusion chromatography and isoelectric focusing. Thymocytes from CBA/J mice respond to the mitogenic lectin Con A only if the costimulator concentration is above a certain level. Culturing such cells with Con A at a density below 1 X 10(6) cells/ml produces costimulator concentrations too low for mitogenesis. This system has been developed into a quantitative assay for costimulator, to monitor purification, recovery, and biologic activity in various methods of molecular characterization. The activity is trypsin sensitive, and has a buoyant density characteristic of protein or glycoprotein. However, for a protein, it is relatively heat stable. Its m.w., established by carrying out sedimentation, gel filtration, and buoyant density measurements, is 30,500, and its frictional coefficient is 1.45. Costimulator purified by isoelectric focusing is active at 10(-10) M or lower in tissue culture.
To identify the mode of action of prazosin, its effects on isolated human vascular preparations were studied. Isometric tension was recorded from spiral strips of dorsal metacarpal veins, common palmar digital arteries and uterine, splenic and ileocolic arteries. Prazosin was a potent antagonist of noradrenaline, but not 5-hydroxytryptamine or barium chloride in the metacarpal veins. Higher concentrations of prazosin were necessary to antagonize noradrenaline in the visceral arteries. The digital arteries were resistant to its sympatholytic effect. It is concluded that prazosin acts as an alpha-adrenoceptor antagonist of different potency in various vascular beds. It is postulated that the initial cardiovascular side effects of prazosin are due to venous pooling and that the long term antihypertensive effect is the result of reduced peripheral resistance because of interference with arterial sympathetic tone.
A survey was made of 1,832 patients who attended the Outpatients' Pharmacy of The Royal Melbourne Hospital during a five-day period. We identified 280 patients who did not speak English as their native tongue; of these 257 (90%) answered a series of questions asked by a pharmacist. An interpreter was essential for communication with 73 of the 257, yet only 31 had been previously classified as requiring an interpreter. Sixty-five per cent of the sample had a good knowledge of drug doses, frequency and drug function. Of the remaining 90, 39 were uncertain of the correct dose, 38 could not state the function and 13 knew neither function nor dose. The proportion of poorly informed patients varied significantly between clinics. Although it is routine practice to place cautionary labels on medication containers, only 78% of the patients had knowledge of these special warnings. Many patients were accompanied by friends or children who spoke some English; however, their translations were sometimes inaccurate and misleading. To improve communication with non-English speaking patients, more trained interpreters should be available in the hospital.
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A double-blind placebo-controlled study compared the efficacy of the antimotion sickness drug scopolamine when administered by oral or transdermal routes. A secondary purpose was to extend our bioassay involving fixed-dose combinations of the homergic drugs promethazine and ephedrine. After receiving 12 apparently identical drug-placebo treatments, eight normal male students were exposed to a slow rotation room to stressful accelerations generated by their execution of 40 head movements out of the plane of the room's rotation of 1 rpm and at 1-rpm increments until either symptoms were experienced (just short of frank motion sickness) or the 27-rpm ceiling on the test was reached. Efficacy of a drug was defined in terms of the placeborange and categorized as beneficial, inconsequential, or detrimental. The rank order of drugs with beneficial effects was: 1) promethazine 25 mg plus ephedrine 12.5 mg (86%); 2) scopolamine by mouth (75%); 3) scopolamine transdermally (63%); and 4) promethazine 12.5 mg plus ephedrine 25 mg (29%). The only detrimental effect was with scopolamine given orally. It is concluded that the advantages of the transdermal scopolamine, which include minimal side effects and prolonged effectiveness, deserve full exploitation.