Search PubMed⌕ Search

Biomedical subjects

J L Walker

Publications and source records attributed to J L Walker.

At least 109 records · Page 6Linked to original sources

Pharmacokinetics and tissue residues in channel catfish, Ictalurus punctatus, given intracardiac and intramuscular injections of gentamicin sulfate.

We studied the rate of absorption, distribution and elimination of gentamicin sulfate in the channel catfish, Ictalurus punctatus. It was determined that the plasma half-life of immunoreactive gentamicin was 12 to 15 hours in the catfish and the rate of elimination from fish after intracardiac and intramuscular (im) routes are not significantly different. Compared to mammals, the very extended half-life is probably the result of a greater unionized fraction of drug in the central compartment and increased reabsorption of drug from the alkaline urine of the fish. Tissue levels at the end of one dose experiments approximate what was predicted based on the intracardiac microconstants. A dosage regimen was established on a 24 hr interval that would keep peak plasma concentration between 10-13 micrograms/ml and allow trough concentrations of 3-4 micrograms/ml. Intramuscular gentamicin appears to have a bioavailability of approximately 37%. Finally, a renal lesion was produced by giving gentamicin im at 10 mg/kg every 33 hr for 6 treatments. The lesion was identical to that described for other mammals and was reversible even while medication was continued.

Animals↗

Pharmacological effects of (+/-)-11-deoxy, 16-phenoxy-prostaglandin E1 derivatives in the cardiovascular system.

M&B 28,767 [(+/-)-11-deoxy-16-phenoxy-17,18,19,20-tetranor prostaglandin E1] and a series of close analogues have been compared with U-46619 [(15S)-hydroxy-11 alpha, 9 alpha-(epoxymethano)-prosta-(5Z,13E)-dienoic acid] for prostaglandin endoperoxide-like pharmacological actions in vitro and in vivo. M&B 28,767 caused powerful dose-related contraction of rabbit aorta (EC50: 2.0 microM) and mesenteric artery (EC50: 0.2 microM) strips in vitro, but was less active than U-46619 and/or noradrenaline. M&B 28,767 induced rapid and irreversible aggregation of rat (0.9 times potency of U-46619) and human (0.25 times potency of U-46619) platelets in platelet-rich plasma (PRP) in vitro. Intravenous administration of M&B 28,767 to urethane-allobarbitone anaesthetized rats produced immediate and dose-related thrombocytopoenia (equipotent with U-46619), accompanied in some animals by transient small pressor effects at low doses (1-2 micrograms kg-1) which were not statistically significant and invariably by sharp depressor effects at higher doses (3-10 micrograms kg-1). U-46619 caused moderate, but not dose-related, pressor effects at all doses tested. Considerable variation in potency occurred amongst the thirteen structural analogues of M&B 28,767. Platelet aggregatory activity for those members of the 11-deoxy 16-phenoxy-PGE1 series tested in rat PRP in vitro demonstrated a positive and significant correlation with pro-aggregatory activity in vivo and agonist potency on rabbit aortic strip in vitro.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Interstitial deletion of the short arm of chromosome 5 in a mother and three children.

An interstitial deletion (5) (p13p15.1) was found in a mentally retarded woman and three of her four children. The variable manifestation of this chromosomal defect and the relevance of this particular deletion to the cri du chat syndrome are discussed. To our knowledge the only other reported case of inherited 5p deletion from an affected parent involved the terminal segment of the 5p15.3 band.

Adult↗

Failure to detect abnormal fatty acid profiles in serum lipoproteins in Friedreich's ataxia.

A recent report indicated an association between the spinocerebellar degeneration of Friedreich's ataxia and abnormal fatty acid profiles of the cholesterol ester fraction in both total plasma and high-density lipoprotein. In an effort to substantiate these findings in lipoproteins, we estimated fatty acid profiles of total high-density lipoprotein and the cholesterol esters of high- and low-density lipoproteins. Those profiles in 10 Friedreich's ataxia patients compared well with previously reported normal values and did not differ significantly from results in 10 age-matched controls.

Cholesterol Esters↗

Lipids and lipoproteins in Friedreich's ataxia.

Friedreich's ataxia is an autosomal recessively inherited disease affecting the nervous system with a high incidence of heart involvement. Abnormalities of lipid metabolism are known to be associated with several progressive ataxic conditions. In this study of 46 Friedreich's ataxia patients, serum lipids, fatty acids and lipoproteins were assayed and compared with some earlier findings on Friedreich's ataxia and related disorders. Abnormalities of low and high density lipoproteins suggestive of a major defect have been reported; in the present study the level and chemical composition of high density lipoprotein has been assessed in 20 Friedreich's ataxia patients but previous abnormalities could not be substantiated. Lipid compositional analysis of Friedreich's ataxia central nervous tissue and heart, which has not been previously reported, did not markedly differ from control tissue.

Adult↗

Intracellular chloride activity in quiescent cat papillary muscle.

Intracellular chloride activity (alpha iCl) was measured in quiescent cat papillary muscles with chloride liquid ion-exchanger microelectrodes. Muscles were superfused in bicarbonate-buffered solutions containing a control concentration of chloride (146.1 mM) and either 2.7, 4.4, or 5.4 mM potassium. The resulting mean membrane potentials were -96.2, -86.8, and -80.6 mV, respectively. In contrast, alpha iCl and the chloride equilibrium potential were unchanged by these alterations in external potassium and remained stable at 11 mM and -60 mV for up to 10 h following removal of the tissue from the animal. This value of alpha iCl is approximately 2-4 times greater than that predicted assuming chloride is passively distributed. The upper limit of intracellular interference was estimated from low external chloride superfusion and found to be no greater than 2-3 mM. Prolonged exposure to bicarbonate-free solutions buffered with N-2-hydroxyethyl piperazine-N'-2-ethanesulfonic acid (HEPES) did not reduce the apparent value of alpha iCl, suggesting that intracellular interference from intracellular bicarbonate does not significantly influence the measurement of alpha iCl. These results suggest that chloride can move into cat papillary muscle against an electrochemical gradient.

Animals↗

Interaction of cardiopulmonary and somatic reflexes in humans.

Activation of cardiopulmonary receptors with vagal afferents results predominantly in reflex inhibition of efferent sympathetic activity, whereas activation of somatic receptors reflexly increases sympathetic activity to the heart and circulation. Previous studies in experimental animals indicate that there is an important interaction between these excitatory and inhibitory reflexes in the control of the renal circulation. The purpose of this study was to determine whether there is a similar interaction between somatic and cardiopulmonary reflexes in humans. The activity of the cardiopulmonary receptors was altered (reduced) with lower body negative pressure (-5 mm Hg), which causes a decrease in cardiac filling pressure and a small reflex increase in forearm vascular resistance without accompanying changes in arterial pressure. Activation of somatic receptors by isometric handgrip for 2 min at 10 and 20% of maximum voluntary contraction resulted in reflex vasoconstriction in the nonexercising arm. Lower body negative pressure at -5 mm Hg produced a threefold augmentation in the forearm vasoconstrictor response to isometric handgrip in the nonexercising arm. This increase in resistance was significantly greater (P < 0.05) than the algebraic sum of the increases in resistance resulting from lower body suction alone plus isometric handgrip alone. Furthermore, it occurred despite a greater rise in arterial pressure, which would be expected to decrease forearm vascular resistance through activation of arterial baroreceptors and through passive dilatation of forearm vessels. Thus, removal of the inhibitory influence of cardiopulmonary receptors by pooling blood in the lower extremities enhances the somatic reflex. These data suggest an interaction between cardiopulmonary and somatic reflexes in the control of forearm vascular resistance in man.

Adult↗

Preferential distribution of inhbititory cardiac receptors in left ventricle of the dog.

The purpose of this study was to determine the relative magnitudes of the reflex effects mediated by sensory endings in the left ventricle activated by intracoronary injection of nicotine or veratridine into left anterior descending (LAD) or circumflex (Cx) coronary arteries in the dog. Injection of nicotine or veratridine into the Cx consistently resulted in larger decreases in heart rate, arterial pressure, and in gracilis perfusion pressure than were observed following injection of the same dose into the LAD. Vagotomy abolished the cardioinhibitory and vasodepressor responses to intracoronary nicotine or veratridine. The weight of left ventricle perfused by LAD or Cx was not different (43.5 +/- 1.65 and 44.5 +/- 2.2 g, respectively. These data indicate that chemical activation of sensory endings with vagal afferents in the inferoposterior left ventricle of the dog results in larger cardionhibitor and vasodepressor responses than result from activation of respects in the anterior left ventricle. Further, these data provide strong evidence that these sensory endings which are chemically activated are preferentially distributed to the inferoposterior left ventricle.

Afferent Pathways↗

Preferential distribution of inhibitory cardiac receptors with vagal afferents to the inferoposterior wall of the left ventricle activated during coronary occlusion in the dog.

The purpose of this study was to determine the relative magnitudes of the reflex effects mediated by cardiac receptors during anterior as opposed to inferoposterior ischemia of the left ventricle of the dog. Cessation of perfusion (coronary "occlusion") of the circumflex coronary artery (Cx) in 29 chloralose-anesthetized dogs with common carotids ligated (group I) resulted in significant bradycardia and hypotension, but in no significant change in perfusion pressure in the gracilis muscle perfused at constant flow. Occlusion of the left anterior descending coronary artery (LAD) produced less hypotension, no change in heart rate, and vasoconstriction in the gracilis. After vagotomy and aortic nerve section, no significant change in heart rate or gracilis perfusion pressure was observed during lad or Cx occlusion, and the blood pressure responses to LAD and Cx occlusion were not different. In nine dogs with sinoaortic denervation (group II), brief Cx occlusion resulted in bradycardia, hypotension, and vasodilation in the gracilis muscle. LAD occlusion in group II dogs caused less hypotension and no change in heart rate or gracilis perfusion pressure. After vagotomy, the bradycardia and vasodilation resulting from Cx occlusion were abolished and the blood pressure responses to LAD and Cx occlusion were not different. The weights of left ventricle perfused by each occluded vessel were not different. These data show that left ventricular receptors with vagal afferents which are activated during coronary occlusion and which mediate cardioinhibitory and vasodepressor responses are located mainly in the inferoposterior left ventricle of the dog heart.

Animals↗

Scanning and transmission electron microscopic study of equine infectious anemia virus.

Scanning and transmission electron microscopy were used to study in detail the morphogenesis and replication of equine infectious anemia virus (EIAV) in cultured, persistently infected equine fetal kidney fibroblasts. The EIAV was shown by thin-section electron microscopy to resemble morphologically more closely the members of the genus Lenti-virus in the family Retroviridae than other genera. Scanning electron microscopy demonstrated budding virus on only about 5% of the equine fetal kidney fibroblasts; however, the entire surface of these cells was involved in viral replication. Except where virus budding was observed, EIAV-infected cells were smooth and free of the topographic surface alterations characteristic of cells transformed by type C retroviruses. The morphologic relationship of EIAV and pathologic manifestations of EIAV infection to those of other Retroviridae are discussed.

Cells, Cultured↗