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Biomedical subjects

G Jennings

Publications and source records attributed to G Jennings.

At least 145 records · Page 8Linked to original sources
PubMed1983

Adaptive changes in the concentration of the mitochondrial 'uncoupling' protein in brown adipose tissue of hamsters acclimated at different temperatures.

The effect of acclimation at different temperatures on the activity of interscapular brown adipose tissue has been investigated in the hamster, a hibernator. Between 31 degrees and 4 degrees C the cytochrome oxidase activity of the tissue increased 4- to 5-fold, mitochondrial GDP binding per mg of mitochondrial protein doubled, and the amount of uncoupling protein rose from 1.7% to 5.4% of total mitochondrial protein. It is concluded that there are clear adaptive changes induced by temperature in brown adipose tissue of the hamster, but the changes are limited in comparison with those in the mouse.

Acclimatization↗
PubMed1983

Measurement of rat brown-adipose-tissue mitochondrial uncoupling protein by radioimmunoassay: increased concentration after cold acclimation.

A specific antiserum has been raised against the 32 000-mol.wt. uncoupling protein from the mitochondria of rat brown adipose tissue and a sensitive radioimmunoassay for the protein has been developed. The uncoupling protein is present in large amounts in brown adipose tissue; its concentration is increased substantially by cold acclimation. The protein has not been detected in the liver, heart, or parametrial white adipose tissue of rats.

Adaptation, Physiological↗
PubMed1983

Cardioselectivity of prenalterol and isoproterenol.

We examined the hemodynamic effects and kinetics of prenalterol, a new beta-adrenoceptor agonist, in 10 normal subjects. There is some doubt whether prenalterol is selective for beta 1 adrenoceptors in animals; therefore, we also compared its cardioselectivity with that of the nonselective agonist, isoproterenol, with respect to heart rate (HR) and blood pressure (BP) responses after inhibition of cardiovascular reflexes with atropine, clonidine, and phentolamine. After intravenous (2.5 mg) and oral (10 mg and 100 mg) dosing, t 1/2 beta was 2 to 3 hr. Oral bioavailability averaged 33% and was independent of dose. Oral prenalterol, 10 mg and 100 mg, increased resting HR, systolic BP, and cardiac index by up to 27% but had no significant effects during graded exercise. Prenalterol infusions were calculated to attain steady-state plasma concentrations of 10, 20, and 40 ng/ml. HR and BP effects of the levels (10.8, 23.6, and 47.4 ng/ml) were compared with those of 0.5, 1.5, and 2.5 micrograms isoproterenol. Before autonomic block, prenalterol increased HR by 10 bpm at the highest dose and mean arterial pressure (MAP) by 10 mm Hg. In contrast, HR rose and MAP fell after isoproterenol. After block, at the highest doses of prenalterol and isoproterenol, there was an average rise in HR of 42 and 27 bpm; BP was almost maintained after the former but fell by 33 mm Hg after the latter. Prenalterol is an inotropic drug that has the effects of a full cardioselective beta-adrenoceptor agonist. Its inotropic effects are evident at doses that have little effect on HR because of the modifying effect of cardiovascular reflexes. The hemodynamic effects are most obvious at rest when sympathetic tone is low.

Administration, Oral↗
PubMed1982

A simple semi-automated plaque method for the detection of antibody-forming cell clones in microcultures.

A simple semi-automated method for the assay of large numbers of replicate microcultures for the presence of antibody-forming cell clones is described. The supernatant medium is removed from microcultures by a single sharp flick on inverting the tray. The cultured cells are mixed with 0.05 ml of a plaque-revealing mix containing indicator erythrocytes and complement and then transferred to new flat-bottomed 96-well microculture trays, using a multichannel pipette or 96-channel replicator. The tray is centrifuged, the indicator erythrocytes and cultured cells forming an even monolayer on the bottom surface of the well. Trays are held at 37 degrees C for 1-1 1/2 h to allow plaque development. Using a dissecting microscope, the number of plaques in each well is counted, or in the case of limiting dilution analysis, each well is simply scored as positive or negative. This assay procedure provides a simple, rapid and inexpensive means of assaying large numbers of microculture trays for the detection and enumeration of antibody-forming cell clones. There is no loss in sensitivity compared with the standard hemolytic plaque assay methods. The method is particularly useful for limiting dilution analysis which necessitates the assay of large numbers of replicate cultures for either the presence of absence of a clone of antibody-forming cells.

Animals↗
PubMed1982

An indexing stage for microscopic scanning of microtitre tray wells.

A simple stage has been designed to hold and to move microtitre trays for examination under a low power dissecting microscope. Movement of a ball on a handle from well to well of a reference tray to the left of the stage is mechanically translated into movement from one well to another under the microscope field. Movement can be controlled entirely by touch, and the particular well under the field can be determined from the reference tray position. The flat bottoms of all 96 wells stay in alignment and in focus without further adjustment, enabling rapid scanning of all wells on a tray. The apparatus is particularly useful for the microtitre tray antibody-forming cell plaque assay described by Pike et al. (1982).

Antibody-Producing Cells↗
PubMed1982

Biochemical quantification of sympathetic nervous activity in humans using radiotracer methodology: fallibility of plasma noradrenaline measurements.

We have developed radiotracer techniques for studying noradrenaline kinetics, to assess better sympathetic nervous system function in humans. Tritiated l-noradrenaline was infused intravenously (0.35 microCi/m2/min) to plateau plasma concentration. Noradrenaline plasma clearance was calculated from plasma tritiated noradrenaline concentration at steady state, and the rate of spillover of noradrenaline to plasma derived from plasma noradrenaline specific radioactivity. Mean noradrenaline spillover at rest in 34 normal subjects was 0.33 micrograms/m2/min (range 0.17-0.61 micrograms/m2/min). Predictably, noradrenaline spillover was reduced in patients with subnormal sympathetic nervous system activity, 0.16 +/- 0.09 micrograms/m2/min in eight patients with idiopathic peripheral autonomic insufficiency, and 0.11 +/- 0.07 micrograms/m2/min (mean +/- SD) in six patients with essential hypertension treated with clonidine (0.45 mg daily). Noradrenaline line plasma clearance in normal subjects was 1.32 +/- 0.28 L/m2/min. Clearance fell with age, causing the previously described rise in plasma noradrenaline concentration with aging. Unexpected effects of drugs were encountered, for example chronic beta-adrenergic blockade in patients with essential hypertension reduced noradrenaline clearance. Plasma noradrenaline concentration measurements were not in agreement with noradrenaline release rate values, and do not reliably indicate sympathetic nervous system activity, in instances such as these where noradrenaline clearance is abnormal.

Humans↗
PubMed1982

Antigen-initiated B lymphocyte differentiation. XX. Colony-forming B lymphocytes are not identical with the intermediate, "pre-progenitor" subset of primary or secondary B cells.

The surface immunoglobulin isotype and the cell cycle status of B lymphocyte agar-colony-forming cells (BL-CFC) were studied in order to test a hypothesis, based on their culture behavior, that they represent a mixture of virgin and memory "intermediate" or "pre-progenitor" B cells. If so, BL-CFC would be equivalent to the minor subset of B cells initiating adoptive immune responses. Most BL-CFC were found to be s-IgD+, whereas most progenitors of primary or secondary adoptive responses were s-IgD-. An intense nonspecific stimulus, in the form of horse erythrocytes injected i.p., failed to throw BL-CFC into cell cycle, as judged by hydroxyurea suicide experiments, whereas the progenitors of adoptive responses were thrown into cell cycle. It was concluded that BL-CFC as a whole were not "pre-progenitor" B cells, but more closely resembled the typical "direct progenitor" B cell. Some data derived from unprimed animals, namely, the level of dividing BL-CFC as assessed by hydroxyurea killing and sedimentation velocity distribution, together with the special sensitivity of even nondividing BL-CFC to killing by 3H-TdR, suggested that the agar culture system might select more activated B cells as colony formers.

Animals↗
PubMed1981

Low oral bioavailability of dihydroergotamine and first-pass extraction in patients with orthostatic hypotension.

The relative importance of the effect of absorption and first-pass extraction in bioavailability and clinical effectiveness of oraldihydroergotamine (DHE) was examined in six subjects with orthostatic hypotension. Maximum increases in systolic blood pressure of standing subjects occurred within 15 min of intravenous administration (10 micrograms/kg); after 30 min pressure declined linearly with respect to time over the ensuing 3 hr. Plasma DHE concentrations declined biexponentially with respect to time. Mean plasma half-life was 2.15 hr and plasma clearance averaged 862 ml/min. There was no rise in "standing" systolic blood pressure on oral administration (200 to 600 micrograms/kg). Peak plasma concentrations ranged from less than 0.1 to 2 ng/ml. Apparent oral absorption for DHE ranged from 19.5% to 53.3% while systemic bioavailability varied from less than 0.1% to 1.5%. when glyceryl trinitrate was taken orally with DHE, the bioavailability of the latter increased between 56% and 370% over the 0.1% to 1.5% without any apparent alteration in DHE absorption. Standing systolic blood pressure increased 27% (P less than 0.05) 2 hr after the same doses of DHE with glyceryl trinitrate. These findings suggest that the extent of first-pass extraction by the liver is the prime determinant of DHE bioavailability after oral administration and that factors that alter gastrointestinal and portal vein flow to the liver affect its bioavailability.

Absorption↗
PubMed1981

Effect of propranolol on noradrenaline kinetics in patients with essential hypertension.

1 The rates of noradrenaline spillover to, and removal from, plasma were measured in ten patients with essential hypertension treated with propranolol, to ascertain if long-term administration of this drug reduces sympathetic nervous system tone. 2 The plasma clearance of noradrenaline fell with propranolol, leading to a small rise in the mean plasma noradrenaline concentration. Sympathetic nervous activity in treated patients cannot be reliably gauged from plasma noradrenaline values because these are distorted by the reduction in noradrenaline clearance. 3 There was no consistent effect on noradrenaline spillover rates, which fell in six patients, but rose in the remaining four. The magnitude of the antihypertensive response was unrelated to these changes in noradrenaline release. During propranolol treatment, noradrenaline spillover rates were in every case within the normal range, much higher than in patients treated with the known sympathetic nervous systems suppressant, clonidine. 4 The principal mode of antihypertensive action of propranolol is something often than central suppression of sympathetic tone or pre-synaptic inhibition of noradrenaline release.

Adult↗
PubMed1980

Determination of noradrenaline uptake, spillover to plasma and plasma concentration in patients with essential hypertension.

1. The rates of entry of noradrenaline to plasma and of removal of noradrenaline from plasma, and plasma noradrenaline concentration, were determined in normal subjects and in patients with essential hypertension. Neuronal uptake of noradrenaline was assessed from the plasma tritiated noradrenaline disappearance curve, after infusion to steady state. 2. Noradrenaline disappearance was biexponential. Rapid removal was dependent on neuronal uptake, being slowed if neuronal noradrenaline uptake was reduced, either by desipramine in normal subjects, or in patients with sympathetic nerve dysfunction (autonomic insufficiency). 3. In 10 of 41 hypertensive patients the t 1 1/2 similarly was prolonged, presumptive evidence of a defect in neuronal noradrenaline uptake. Endogenous noradrenaline escaping uptake after release, and spilling over into plasma, and plasma noradrenaline concentration, were increased in these patients. 4. Defective neuronal uptake of noradrenaline, by exposing adrenoreceptors to high local transmitter concentration, may be important in the pathogenesis of essential hypertension in some patients.

Adult↗
PubMed1980

Norepinephrine kinetics in patients with idiopathic autonomic insufficiency.

The rates of norepinephrine release into plasma and removal from plasma were studied in patients with idiopathic peripheral autonomic insufficiency (sympathetic neuronal dysfunction), as it was thought that plasma norepinephrine concentration alone inadequately quantifies the degree of sympathetic nervous underactivity in this disorder. In four patients with autonomic insufficiency, clearance of norepinephrine from the circulation was slowed, 1.69 +/- 0.44 liters/min, compared with 2.80 +/- 0.73 liters/min in 10 normal subjects (P less than 0.05). As a consequence, despite a 60% lower norepinephrine apparent secretion rate, 0.19 +/- 0.12 microgram/m2 per min vs. 0.54 +/- 0.20 microgram/m2 per min, the plasma norepinephrine concentration was near normal. The plasma concentration of neurotransmitter does not provide a valid index of sympathetic nervous tone in this disorder in which removal of norepinephrine from the circulation is slowed.

Dysautonomia, Familial↗
PubMed1979

Comparison of effectiveness of timolol administered once a day and twice a day in the control of blood pressure in essential hypertension.

The effects of a single dose and of two equally divided doses of timolol were compared in a double-blind trial in 15 patients with essential hypertension. The amount of timolol per day remained constant for each patient, but individual patients received different amounts (from 10 mg to 30 mg/day). Timolol combined with a diuretic produced similar lowering of blood pressure in patients who required 10 mg, 20 mg or 30 mg of timolol per day when given either as one dose or in two equal doses. Plasma concentrations of timolol were high enough to be a major contributing factor to the long duration of the hypotensive response.

Adult↗