ABSTRACT
The neutralizing activity and fusion-inhibition activity per unit weight of immunoglobulin were determined for each of a panel of 20 monoclonal antibodies (MAbs) to the fusion (F) protein of respiratory syncytial (RS) virus. Neutralization did not correlate with fusion-inhibiting activity, suggesting that the F protein plays at least two independent, antibody-sensitive roles in viral infection. Antibodies with the highest biological activity against A2, a subgroup A strain of RS virus, neutralized a subgroup B strain (8/60) poorly, suggesting a degree of antigenic variation that may be important in human infection. All but one fusion-inhibiting MAb bound to protein blots and binding was mapped to two areas on overlapping F protein fragments. One MAb with relatively poor fusion-inhibiting activity bound only to fragments C-terminal of amino acid 384, the remainder bound only to fragments containing residues 253 to 289. MAbs directed to the latter site were heterogeneous in neutralizing activity, subgroup specificity and fusion-inhibiting activity. These variations between MAbs could not be accounted for by differences in their binding avidities. We suggest that this binding site is not the complete antibody epitope which probably includes conformation-dependent elements.
Subject(s)
Antibodies, Monoclonal/metabolism , Respiratory Syncytial Viruses/metabolism , Viral Fusion Proteins/metabolism , Animals , Antibodies, Monoclonal/pharmacology , Binding Sites, Antibody , Enzyme-Linked Immunosorbent Assay , Mice , Mice, Inbred BALB C/immunology , Neutralization Tests , Recombinant Fusion Proteins/analysis , Recombinant Fusion Proteins/immunology , Recombinant Fusion Proteins/metabolism , Viral Fusion Proteins/analysis , Viral Fusion Proteins/immunologySubject(s)
Electronics, Medical/standards , European Union , Industry , Equipment Safety , Europe , United KingdomABSTRACT
Dopamine was shown to be effective in releasing glycerol and nonesterified fatty acid from brown fat adipocytes. The response was inhibited by dopamine-antagonists, and by a beta-blocker. This is further evidence that dopamine may be important in the release of energy from brown fat in newborn and cold-adapted animals.
Subject(s)
Adipose Tissue, Brown/metabolism , Dopamine/pharmacology , Fatty Acids, Nonesterified/metabolism , Glycerol/metabolism , Adaptation, Physiological , Adipose Tissue, Brown/drug effects , Adrenergic alpha-Antagonists/pharmacology , Adrenergic beta-Antagonists/pharmacology , Animals , Animals, Newborn , Cold Temperature , Female , In Vitro Techniques , Oxygen Consumption/drug effects , Rats , Rats, Inbred Strains , Receptors, Dopamine/drug effectsABSTRACT
The effect of dopamine upon the oxygen consumption (QO2) of brown fat adipocytes was measured by polarography. The results showed a marked stimulation of QO2 by dopamine, similar to that induced by noradrenaline. The dopamine response could be blocked by haloperidol, butaclamol, propranolol and by high concentrations of tolazoline. These results suggest a role for dopamine in energy release from brown fat.
Subject(s)
Adipose Tissue, Brown/metabolism , Dopamine/pharmacology , Oxygen Consumption/drug effects , Adipose Tissue, Brown/cytology , Adrenergic alpha-Antagonists/pharmacology , Animals , Butaclamol/pharmacology , Fatty Acids, Nonesterified/blood , Female , Glycerol/blood , Haloperidol/pharmacology , In Vitro Techniques , Oxidation-Reduction , Propranolol/pharmacology , Rats , Rats, Inbred StrainsABSTRACT
Oxygen consumption (VO2) was measured in Porton albino rats using a closed circuit apparatus. The groups studied were controls, cold-adapted animals, and those which had accumulated brown adipose tissue as a result of a cafeteria diet with a high energy content. It was possible to show in each group studied a difference in VO2 according to the time of day at which it was measured. This was consistent within each group studied. The diurnal variation shown (higher in the morning than in the afternoon) is characteristic of nocturnal animals. Measurement of VO2 then must be made within the same time-period or integrated over 24 h. Spurious correlations may otherwise occur.
Subject(s)
Circadian Rhythm , Oxygen Consumption , Acclimatization , Adipose Tissue, Brown/metabolism , Animals , Cold Temperature , Female , Rats , Rats, Inbred StrainsABSTRACT
The urinary concentrations of dopamine, noradrenaline and adrenaline were measured by a radioenzymatic method in 212 full-term and premature newborns. The ranges, means and standard deviations from birth to 4 days + are presented. The excretion of dopamine was ten times that of noradrenaline or adrenaline. The absolute concentrations of each catecholamine were reduced as birth weight decreased. The values were increased in babies with fetal distress. Any changes found in hypoglycaemic or jaundiced infants were attributable to prematurity. Very high levels were found in a few infants given tolazoline. We speculate that the role of dopamine production and excretion in the newborn has been underestimated. Dopamine may have an important role to play in the homeostatic mechanisms of the newborn.
Subject(s)
Catecholamines/urine , Infant, Newborn , Creatinine/urine , Dopamine/urine , Epinephrine/urine , Female , Fetal Distress/urine , Gestational Age , Humans , Hyaline Membrane Disease/urine , Hypoglycemia/urine , Jaundice, Neonatal/urine , Male , Norepinephrine/urine , Pregnancy , Respiratory Distress Syndrome, Newborn/urineABSTRACT
We increased the mass of interscapular brown adipose tissue in rats by dietary manipulation ("cafeteria" feeding), cold exposure, or by both. The animals were then used to determine the temperature response of the interscapular brown adipose tissue to dopamine or norepinephrine. These results, and the increase in blood glycerol values, were very similar for either catecholamine. These findings suggest that dopamine may have a role in releasing energy from brown adipose tissue similar to that of norepinephrine in the newborn infant.
Subject(s)
Adipose Tissue, Brown/drug effects , Dopamine/pharmacology , Animals , Body Temperature Regulation/drug effects , Body Weight/drug effects , Female , Norepinephrine/pharmacology , Rats , Rats, Inbred StrainsABSTRACT
The effect of a preparation containing the lymphokine "Interleukin-3" (IL-3) on murine marrow CFUs has been investigated. When marrow cells are incubated for a short period with IL-3 in vitro, the number of spleen colonies that develop upon injection into irradiated recipients is increased. In addition, an increase is seen in the proportion of CFUs killed in vitro by tritiated thymidine. IL-3 does not affect the seeding efficiency of CFUs in the spleen, but appears to act directly on them, not through production of an endogenous marrow stimulator.
Subject(s)
Bone Marrow Cells , Hematopoiesis , Hematopoietic Stem Cells/cytology , Lymphokines/physiology , Animals , Cell Cycle , Colony-Forming Units Assay , Culture Media , Interleukin-3 , Mice , Mice, Nude , Thymidine/metabolismABSTRACT
The effect of nisoldipine (5 micrograms/kg/i.v.) was studied in anesthetized intact dogs. This calcium antagonist increased heart rate by 68%, doubled cardiac output, and increased coronary sinus flow from 62 +/- 10 ml/min to a maximum of 131 +/- 7 ml/min. Mean systemic pressure decreased from 125 +/- 10 mm Hg to a minimum of 115 +/- 2 mm Hg for at least 15 min after the injection. Mean pulmonary artery pressure increased from 12 +/- 2 mm Hg to 18 +/- 4 mm Hg within 2 min of the injection. Left ventricular work (joules/s) doubled and right ventricular work trebled during the first 15 min after injection. Peripheral resistance fell by 57%, total pulmonary resistance by 40%, and coronary vascular resistance by half. Coronary sinus O2 content increased by 50%, and cardiac efficiency (index) increased from 0.2 (control) to a maximum of 0.46, within 2 min after the injection of the drug.
