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J W Palmer

Publications and source records attributed to J W Palmer.

10 recordsLinked to original sources
PubMed1992

Developing and implementing a "basic science clerkship" for first-year students.

For over 15 years, human genetics at the University of Illinois College of Medicine at Chicago (UICMC) was taught exclusively through lectures. In 1989-90 the authors revised this course for the graduating class of 1993 in order to incorporate many features found in a clerkship experience, such as oral presentations and the exploration of differential diagnoses through patient cases. In addition to lectures, the revised course consisted of small-group work in concentrated blocks of time, involving both a library research project and problem-based learning, each of which contributed to (1) significant gains in student achievement compared with data from the class of 1992 and (2) extremely favorable assessments from the students and faculty. The format of a basic science clerkship is being adopted by other departments at UICMC. The authors suggest that this format could be used by other medical schools to integrate the basic and clinical sciences.

Clinical Clerkship↗
PubMed1989

Are disturbances in lipid-protein interactions by phospholipase-A2 a predisposing factor in affective illness?

Current theories of affective disorders do not account for many of the biological markers replicated in patient studies. We link many biological findings in a reasonable physiological relationship, compatible with mechanisms of action of pharmacological and electroshock therapies for depression. We propose that excessive phospholipase-A2 (PLA2) activity disrupts membrane fluidity, composition, and therefore, the activity, of membrane-dependent proteins. Similar disruptions in these proteins are documented in depressed patients and can be accounted for by excessive PLA2 activity. This paradigm accounts for disturbances in the activity of Na-K-ATPase, beta2- and alpha2-adrenergic receptors, MAO, norepinephrine and serotonin uptake, and imipramine binding. Disturbances in other membrane-dependent proteins, tyrosine and tryptophan hydroxylase, can explain the biogenic amine hypothesis. Inhibition of glucocorticoid receptor and TRH receptor binding to their respective ligands by PLA2 may explain patient nonsuppression in the Dexamethasone Suppression Test and poor response in the TRH stimulation test. Physiological regulators of PLA2 activity; calcium, cortisol, estrogen, progesterone, and PGE2 are documented abnormalities in some patients with affective disorders and consistent with excessive PLA2 activity. Thus, postpartum depression and premenstrual tension syndrome may be described in the paradigm. The mechanisms of action of tricyclic antidepressants, lithium, electroconvulsive shock, and some novel antimanic agents can be described in terms of alterations of PLA2 activity. Interestingly, ethanol perturbs membrane fluidity and membrane-bound enzymes in a manner similar to excessive PLA2 activity. A hereditary factor predisposing patients to affective disorders may be a gene defect at either PLA2 or in its regulation.

Brain↗
PubMed1987

Hormonal effects on mitochondrial respiration: potential role of endogenous lipolytic activities.

Hormonal effects on heart mitochondrial metabolism are investigated by comparing respiratory rates, Ca2+ uptake capacity, and lipolytic activities of mitochondria isolated from control rats to those of mitochondria isolated from thyroparathyroidectomized animals. Two biochemically and morphologically distinct populations of heart mitochondria are prepared--one derived from the region of the cell directly beneath the sarcolemma (subsarcolemmal mitochondria), the other originally between the myofibrils (interfibrillar mitochondria). Subsarcolemmal mitochondria isolated from normal rat cardiac tissue have both lower respiratory rates and Ca2+ uptake capacity than do interfibrillar mitochondria. However, when these mitochondrial populations are isolated from hearts from thyroparathyroidectomized rats, there is a selective increase in the maximal ability of the subsarcolemmal mitochondria to accumulate Ca2+, which is accompanied by a proportionate increase in their maximal respiratory rates. Neither Ca2+ uptake capacity nor respiratory rates are similarly increased in the interfibrillar mitochondria. Cytochrome contents and mitochondrial protein recoveries are not significantly changed in either of these mitochondrial preparations. The relationship between these selective increases in respiratory properties of the subsarcolemmal mitochondria to endogenous lipolytic activities is also investigated. It was previously demonstrated that, in the absence of Ca2+, both the rate and extent of formation of free fatty acids from endogenous phospholipids is greater in subsarcolemmal than interfibrillar mitochondria (J. W. Palmer et al. (1981) Arch. Biochem. Biophys. 211, 674-682). In this study it is shown that lipolysis is also more sustained in the subsarcolemmal mitochondria when Ca2+ is added. In the subsarcolemmal mitochondria isolated from thyroparathyroidectomized rats, however, the rates of release of stearic acid and oleic acid are reduced in both the presence and absence of Ca2+. In the presence of added Ca2+, the rate of release of arachidonic acid is also decreased compared to control subsarcolemmal mitochondria, suggesting that the expressed activity of Ca2+-activated phospholipase A2 is lower in those mitochondria isolated from the thyroparathyroidectomized animals, in which respiratory rates and Ca2+ uptake capacity are increased.

Animals↗
PubMed1987

Characterization of phospholipase C-mediated phosphatidylinositol degradation in rat heart ventricle.

Phosphoinositide-specific phospholipase C (PI-PLC) activity was investigated in the rat heart ventricle. Incubation of ventricle homogenate or 100,000g supernatant fraction with [3H]myoinositol or [3H]arachidonate-labeled phosphatidylinositol in the presence of Ca2+ resulted in a decrease in phosphatidylinositol with a concomitant increase in water-soluble [3H]inositol phosphate or [3H]diglyceride, respectively. Total overt homogenate PI-PLC activity could be accounted for in the supernatant fraction. Neutral, zwitterionic, cationic, or anionic detergents did not unmask membrane-associated activity. While cytosolic phospholipase C was active against a pure phosphatidylinositol substrate in the presence of Ca2+, no hydrolytic activity was detected when phosphatidylinositol was presented as a component (4-5%) of a mixture of phospholipids. However, addition of deoxycholate to the incubation mixture (pH 6.5, Ca2+ 10(-3) M) containing mixed phospholipids resulted in the exclusive hydrolysis of inositol phospholipids. Ventricular supernatant phospholipase C-mediated phosphatidylinositol degradation has a sharp pH optimum at 5.5 and a specific requirement for Ca2+. Activity is maximal at 1 to 2 X 10(-3) M Ca2+, with inhibition occurring at higher levels. Under optimized conditions phosphatidylinositol is hydrolyzed at a rate of 20-25 nmol/min/mg protein. Multivalent cations inhibit Ca2+-dependent PI-PLC activity while monovalent cations and anions have no effect. There is no apparent selectivity for specific fatty acid moieties on phosphatidylinositol. Soluble PI-PLC is inhibited by sulfhydryl reagents, neomycin, mepacrine, trifluoperazine, and propranolol. Chlorpromazine, dibucaine, and tetracaine exert a biphasic influence, stimulating at lower and inhibiting at higher concentrations.

Animals↗
PubMed1987

Alterations in phospholipid metabolism in the globally ischemic rat heart: emphasis on phosphoinositide specific phospholipase C activity.

The effect of global ischemia on myocardial ventricular membrane phospholipids was evaluated using a modified Langendorff preparation. Isolated rat hearts were perfused at 37 degrees C with oxygenated Krebs Ringer solution or rendered ischemic by cessation of perfusion (10 min to 3 h). Longer periods of ischemia were assessed by incubating preperfused (10 min) intact hearts in non-oxygenated Krebs (37 degrees C) for 6 to 18 h. Ischemia-induced alterations in phosphatidylinositol levels and phosphoinositide-specific phospholipase C (PI PLC) activity were assessed in detail, since inositol phospholipids and PI-PLC play putative roles in the regulation of cell function and Ca2+ homeostasis. Decreases in major membrane phospholipids (phosphatidylcholine, phosphatidylserine, cardiolipin and sphingomyelin) were demonstrated after long ischemic periods (6 to 18 h). While periods of ischemia (3 h or less) induced no change in structural phospholipids, an elevation in lysophosphatidylcholine and free fatty acids was found by 1 h. Notably a significant increase in phosphatidylinositol content and an accompanying decrease in cytosolic PI PLC activity was detected by 30 mins of ischemia. Reduced enzymic activity was not due to altered in vitro activation or deactivation of PI-PLC, to a change in the Ca2+ requirement of the enzyme, or to translocation of the enzyme from the cytosol to a membrane fraction. The isolated rat heart made globally ischemic for 30 mins under conditions described for this investigation shows signs of irreversible injury i.e. increased cell Ca2+ content and inability to initiate and maintain rhythmic contraction upon reperfusion. Therefore, it is possible that altered phosphoinositide metabolism may contribute to the evolution of ischemia-elicited irreversible cell injury.

Animals↗
PubMed1986

Heterogeneous response of subsarcolemmal heart mitochondria to calcium.

The Ca2+ -uptake capacity of two distinct populations of rat heart mitochondria was characterized by monitoring Ca2+ movements directly (using both 45Ca and dual-wavelength spectroscopy) and indirectly (monitoring effects of Ca2+ on respiration, enzyme release, and morphology). Interfibrillar mitochondria accumulated up to 930 nmol/mg protein, whereas the capacity of the subsarcolemmal mitochondria for Ca2+ uptake was limited to 620 nmol/mg protein. In both mitochondrial populations, uptake of the maximal amount of Ca2+ was accompanied by increased proton permeability and subsequent release of the accumulated Ca2+. Even when calcium was taken up and apparently retained by the subsarcolemmal mitochondria, resting respiratory rates increased. Morphological examination of these mitochondria revealed that, although the majority of mitochondria were in the aggregated, energized conformation, a considerable number were disrupted. These damaged mitochondria were probably responsible for the increased resting respiratory rates. No net release of calcium was observed, however, since the intact mitochondria could take up any calcium released by the damaged mitochondria. Morphological disruption of this subset of subsarcolemmal mitochondria was accompanied by release of not only cytochrome c but also of mitochondrial marker enzymes into the extramitochondrial milieu. In contrast, the interfibrillar mitochondria were relatively unaffected in terms of morphology and marker enzyme release, even when their capacity to retain calcium was exceeded.

Animals↗
PubMed1985

Biochemical differences between subsarcolemmal and interfibrillar mitochondria from rat cardiac muscle: effects of procedural manipulations.

Differences in oxidative metabolism between subsarcolemmal and interfibrillar heart mitochondria were investigated. Interfibrillar mitochondria oxidized substrates donating reducing equivalents at Complex I (NADH-CoQ reductase), Complex II (succinate-CoQ reductase), and Complex III (CoQH2-cytochrome c reductase) more rapidly than did subsarcolemmal mitochondria. There was no difference in oxidation of substrates entering the electron transport chain at Complex IV (cytochrome c oxidase). Differences expressed in normal-ionic-strength medium at Complexes II and III but not I were eliminated in low-ionic-strength medium. The concentrations of cytochromes and activities of NADH and cytochrome c oxidase were virtually the same in the two populations. In permeabilized mitochondria, activities of succinate-duroquinone and TMPD plus ascorbate oxidase were significantly lower in the subsarcolemmal mitochondria. Differences in membrane permeability between the populations were suggested by the greater permeability of subsarcolemmal mitochondria to exogenous NADH. The influence of isolation buffers and preparative procedures on the two classes of mitochondria were also examined. Characteristic biochemical and morphological properties of the two populations were unchanged by exposing each to the preparative procedure used to isolate the alternate population; the oxidative performance of the two populations cannot be equalized by experimental manipulation.

Animals↗
PubMed1977

Biochemical properties of subsarcolemmal and interfibrillar mitochondria isolated from rat cardiac muscle.

Two populations of mitochondria were observed upon ultrastructural examination of cardiac muscle tissue, one located directly beneath the sarcolemma (subsarcolemmal mitochondria) and another between the myofibrils (interfibrillar mitochondria). Subsarcolemmal mitochondria were released by treatment of heart muscle with a Polytron tissue processor, while interfibrillar mitochondria were released by nagarse digestion of the remaining tissue. These results were supported by electron microscopy of Polytron-treated heart tissue showing rupture and loss of sarcolemma with release of the underlying mitochondria but with retention of intact mitochondria between the myofibrils. Electron microscopy of the isolated mitochondria indicated that both mitochondrial types maintained their structural integrity throughout the isolation procedure. Specific activities of succinate dehydrogenase and citrate synthase were higher in the interfibrillar mitochondria as compared to the subsarcolemmal mitochondria, while those of carnitine palmitoyltransferase and alpha-glycerophosphate dehydrogenase were nearly the same in both. Interfibrillar mitochondria oxidized all substrates tested approximately 1.5 times faster than did the subsarcolemmal mitochondria. Thus the two mitochondrial types differed not only in their respective locations in the cell, but also in certain biochemical properties.

Animals↗