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Biomedical subjects

M D Adams

Publications and source records attributed to M D Adams.

At least 91 records · Page 5Linked to original sources

Evidence for an intracellular pool of a migration inhibitory factor-associated, activation antigen of human mononuclear phagocytes, Mo3e.

Mo3e is a protease-sensitive Ag (p75,50) selectively expressed by human monocytic cells stimulated in vitro by exposure to various activating factors including PMA. Here, we report the existence of a large intracellular pool of Mo3e Ag in addition to that expressed on the surface of activated U-937 cells. As detected by quantitative immunofluorescence analysis, permeabilization of unstimulated and PMA-stimulated U-937 cells revealed a latent pool of Mo3e Ag that was 75-fold and 9-fold greater, respectively, than the magnitude of Mo3e Ag expressed on the surface. PMA stimulation not only induced an increase in the relative proportion of Mo3e antigen expressed on the surface membrane, but also stimulated a 1.8-fold increase in "total" Mo3e detectable in permeabilized cells. Trypsin treatment of intact PMA-stimulated U-937 cells eliminated surface Mo3e expression but had little measureable effect on the total Mo3e pool. Permeabilization also uncovered a sequestered compartment of Mo3e Ag in I-937 cells, a variant of U-937 that is surface Mo3e negative. Although the PMA-induced surface Mo3e expression of U-937 was abrogated by cycloheximide, the total pool of Mo3e detectable in permeabilized PMA-stimulated cells was only partially reduced; cycloheximide treatment caused no reduction in the intracellular Mo3e compartment of unstimulated U-937 cells. Detergent lysates of PMA-stimulated U-937 cells exhibited undiminished quantities (relative to untrypsinized cells) of p75 and p50 proteins immunoreactive with anti-Mo3e mAb as detected by Western blotting. This trypsin-sequestered intracellular Mo3e Ag may serve as a reservoir for the up-regulated surface expression of Mo3e that occurs as a result of mononuclear phagocyte activation.

Antibodies, Monoclonal↗

The effect of sodium on the fibrillatory potential of ioversol.

The spontaneous ventricular fibrillation (VF) potential of the nonionic contrast media, ioversol (IOV), with and without the addition of sodium was examined during right coronary artery (RCA) injections into anesthetized closed-chest dogs. Protocols included fixed volume (6 mL) and fixed rate (0.4 and 0.6 mL/sec) injections to compare two or more of the following: IOV, IOV + (0.075-0.9% wt/vol) NaCl, and sodium/meglumine diatrizoate (DIA). In these studies, the incidence of VF for IOV alone was either greater that with IOV + NaCl formulations or, if equivalent, the incidence of other arrhythmias was greater with IOV alone than with the sodium formulations. When DIA was included in the comparisons, the incidence of VF was always greater than IOV with or without sodium. There was a sodium-related concentration prolongation in QT interval that, at 0.9% NaCl, approximated that with DIA, even though the incidence of VF for the sodium formulation was 0/15 vs. 6/12 for DIA. Thus, the addition of sodium to IOV appears to reduce the propensity for sponteneous VF in the canine model.

Animals↗

A rat EEG model for evaluating contrast media neurotoxicity.

The electroencephalographic (EEG) effects of intracisternally administered x-ray contrast media were evaluated in rats as a means of assessing neurotoxicity. Rats were ventilated with a mixture of nitrous oxide and oxygen (70/30) sufficient to maintain light anesthesia/analgesia and neuromuscular blockade was induced to prevent movement artifacts. A femoral artery was catheterized for monitoring arterial blood pressure (BP), heart rate, blood gases, and pH. Four 22-gauge stainless steel needle electrodes were inserted underneath the scalp for recording EEG. Approximately 1 hour after the start of EEG recording, test agents were injected via the cisterna magna and rats were placed in a 20 degrees head-down position. EEG and BP were monitored continuously for up to 160 minutes postinjection. Blood gases and pH were monitored periodically. The effects of meglumine iothalamate (IOT), metrizamide (MET), iogulamide (IOG), and ioversol (IOV) were compared at dose levels from 30 to 240 mgI/kg. Normal saline was injected as a control substance and caused no changes in EEG, blood gases, pH, and BP for up to 160 minutes postinjection. IOT (30 mg I/kg) produced profound EEG effects consistent with epileptogenic activity, followed by slowing and subsequent death in 3 of 4 animals. Metrizamide had minimal EEG effects at 30 mg I/kg but at 60 mg I/kg, and 120 mg I/kg produced moderate to severe EEG changes including epileptiform patterns and death in 33% of animals. IOV caused mild EEG abnormalities in 4 of 12 animals at 120 mg I/kg, mild EEG abnormalities in 6 of 11 animals, and moderate EEG abnormalities in 1 of 11 animals at 240 mg I/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Adrenergic receptors in the nucleus tractus solitarii of the rat.

The nucleus tractus solitarii (NTS) is an area of the medulla in which baroreceptor afferent fibers mediating an inhibition of vasoconstriction terminate. The NTS also appears to be a site at which alpha-adrenergic receptors may be involved in blood pressure control. alpha- and beta-adrenergic agonists and antagonists were injected into the NTS via stainless steel cannulae and the effects on blood pressure determined. Norepinephrine (NE) and isoproterenol (ISO) caused dose-related decreases in mean arterial blood pressure (MABP). Phentolamine (PH) and propranolol (PR) caused dose-related increases in MABP. PH pretreatment in the NTS blocked the effects of ISO, but not NE. The effect of increased baroreceptor impulses to the NTS, produced by altering perfusion of the carotid sinus was blocked by propranolol. These results indicate the presence of beta- as well as alpha-receptors in the NTS, and also suggest the existence of presynaptic beta-receptors which facilitate neurotransmission.

Adrenergic beta-Antagonists↗

Biodistribution study of Ethiodized Oil Emulsion 13 for computed tomography of the liver and spleen.

Biodistribution studies were conducted with a new intravenous lipoid contrast material currently undergoing clinical trials in four hospitals. The contrast material selectively opacifies the liver and spleen for computed tomographic examination. The experiments were performed on rats with 125I-labeled ethiodized oil emulsion. The study showed that the liver accumulates nearly 80% of the injected iodine within 15 min of the injection and retains a high concentration over 3 h. The second highest concentration was found in the spleen. More than 99% of the iodine is eliminated from the liver and spleen within 48 h, primarily through the kidneys.

Animals↗

Ioglucomide: a new nonionic myelographic agent. Preclinical studies.

Ioglucomide, a new iodinated nonionic contrast medium directed primarily toward myelographic use, was subjected to an extensive toxicological examination in animals. In the majority of studies, ioglucomide was compared directly with metrizamide. In some respects, including freedom from production of arachnoiditis, ioglucomide and metrizamide were comparable. However, acute toxicity after intravenous injection or instillation into cerebrospinal fluid was significantly less for ioglucomide. Also, in contrast to metrizamide, ioglucomide produced no evidence of any type of convulsive activity after subarachnoid administration. The improved safety of ioglucomide could not be related to osmolality; therefore, the importance of osmolality for nonionic myelographic agent safety is questioned.

Animals↗

A cannabinoid with cardiovascular activity but no overt behavioral effects.

Abnormal-delta8-tetrahydrocannabinol (ABN-delta8-THC) failed to elicit central nervous system and cardiovascular effects in laboratory animals. Abnormal-cannabidiol (ABN-CBD) was also devoid of overt behavioral effects but produced marked hypotension with only slight bradycardia in anesthesized dogs.

Animals↗

Brain 5-hydroxytryptamine correlates of behavior: studies involving spontaneously hypertensive (SHR) and normotensive Wistar rats.

Brain area 5-hydroxytrhptamine (5-HT) turnover and behavioral correlates were compared in spontaneously hypertensive rats (SHR) and normotensive Wistar rats. SHR appeared to have hyperfunctional 5-HT systems as evidenced by the finding that brain area 5-HT turnover times were 53% lower in SHR, with significant changes seen in the limbic forebrain. SHR, while less active upon initial testing of spontaneous motor activity than Wistar rats, did not habituate as readily to the testing procedures as evidenced by higher activity than Wistar rats in repeated testing stiuations. In the light of other data indicating that 5-ht systems are predominantly inhibitory to ongoing behavior, these data suggest that habituation, as determined in this study, is an active process that is retarded in the SHR because of hyperfunctional 5-HT systems. Spontaneous activity of SHR was inhibited less than that of Wistar rats by a conditioned stimulus which is consistent with the observations of others that 5-HT systems tend to suppress responsiveness to external stimuli. While spontaneous activity data suggested that SHR were more emothinal than Wistar rats, the SHR also exhibited a higher avoidance rate in an unsignaled shuttle avoidance procedure which is usually indicative of a lower emotional state.

Animals↗

Tolerance to the cardiovascular effects of delta9-tetrahydrocannabinol in the rat.

1. Daily intraperitoneal injections of delta9-tetrahydrocannabinol (delta9-THC, 10 mg/kg) resulted in tolerance to the effects of the cannabinoid on body weight and body temperature within 1-2 weeks of treatment. 2. Tolerance failed to develop to the suppression of spontaneous motor activity produced by delta9-THC during 28 days of treatment with the cannabinoid (10 mg/kg, i.p. per day). 3. Following treatment with vehicle for 28 days, intravenous administration of delta9-THC in anaesthetized rats produced a transient pressor response followed by a sustained hypotension and bradycardia. 4. Tolerance to the hypotensive and negative chronotropic responses to intravenous delta9-THC was readily apparent in animals which had received daily intraperitoneal injections of delta9-THC (10 mg/kg) for 28 days. 5. Tolerance failed to develop to the pressor actions of intravenous delta9-THC after 28 days of preptreatment. 6. There was no difference in the pressor response to intravenous noradrenaline in vehicle-treated animals (1.0 ml/kg, i.p., per day for 28 days) and delta9-THC-treated animals (10 mg/kg, i.p., per day for 28 days).

Animals↗

Characteristics of histamine disposition in vascular smooth muscle.

This study has examined uptake, efflux and metabolism of 14C-histamine by vascular smooth muscle. 14C space in aortae reached 4.3 +/- 0.14 ml/g (mean +/- SE) after 1 h exposure to 14C-histamine (2 muM) in Tyrode's solution. Aminoguanidine (10(-5) M) and non-radioactive histamine (10(-4) and 10(-3) M) significantly reduced 14C space. Efflux experiments were performed on aortic strips exposed to 14C-histamine for 1 h. The rate of loss of radioactivity was not enhanced by nonradioactive histamine or compound 48/80. It appears that 14C-histamine was not accumulated and bound in mast cells in this tissue. After 1 h exposure to 14C-histamine, labeled material was extracted from tissues for identification of metabolites by paper chromatography. About 40% of the label was 14C-histamine, and the remainder was primarily imidazole acetic acid. After exposure to aminoguanidine, an inhibitor of diamine oxidase, about 80% of the label was 14C-histamine. These data suggest that oxidative deamination is the primary catabolic route for histamine in rabbit aorta.

Animals↗

Vasoconstrictor actions of delta8- and delta9-tetrahydrocannabinol in the rat.

Cardiovascular effects of delta8- and delta9-tetrahydrocannabinol (THC) were studied after systemic intravenous administration and intra-arterial administration into a perfused vascular bed in the urethane-anesthetized rat. Intravenous administration of delta8- and delta9-THC produced dose-related transient increases in blood pressure followed by more prolonged hypotensive responses and bradycardia. Intra-arterial administration of delta8- and delta9-THC into the perfused hindquarters of the rat produced an increase in perfusion pressure indicative of vasoconstriction. The vasoconstrictor response to the cannabinoids corresponded temporally to a similar response produced by i.a. norepinephrine and was in contrast to the more prolonged vasoconstrictor responses produced by vasopressin. Phentolamine, in a dose which reduced the vasoconstrictor effect of norepinephrine by 90%, significantly reduced the response to i.a. delta9-THC while having no effect on the actions of i.a. vasopressin. It was demonstrated that reserpine pretreatment significantly reduced vasoconstrictor actions of i.a. tyramine and delta9-THC but did not alter the responses to norepinephrine. These data suggest that delta8- and delta9-THC have peripheral vasoconstrictor activity in the rat which may be mediated, in part, through a tyramine-like action on adrenergic nerve terminals.

Adrenergic alpha-Antagonists↗