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Biomedical subjects

P Graf

Publications and source records attributed to P Graf.

At least 91 records · Page 5Linked to original sources

Preserved learning in amnesic patients: perspectives from research on direct priming.

An important source of evidence for preserved learning ability in amnesic patients is provided by the phenomenon of repetition or direct priming: the facilitative effect of an encounter with an item on subsequent processing of the same item. In this article we consider a series of experiments that have attempted to clarify the nature of priming in amnesic patients and normal subjects. The experiments indicate that there may be two varieties of priming, one dependent upon the activation of preexisting memory representations, the other dependent upon newly formed memory representations. We suggest that the former type of priming is preserved even in severely amnesic patients, whereas the latter may be preserved only in mildly-to-moderately amnesic patients. Implications of research on preserved learning for the development of remedial strategies are also discussed.

Adult↗

Hepatic thiol and glutathione efflux under the influence of vasopressin, phenylephrine and adrenaline.

Thiol and glutathione (GSH) efflux across the sinusoidal plasma membrane in isolated perfused rat liver was stimulated by addition of hormones such as vasopressin, phenylephrine and adrenaline, whereas glucagon or dibutyryl cyclic AMP were without effect. Phenylephrine and adrenaline effects were sensitive to prazosin and phentolamine, respectively. The increase in thiol efflux was largely accounted for by an increase in GSH efflux. Thiol efflux and the hormone effects were abolished in GSH-depleted liver. Biliary GSH efflux was diminished upon hormone addition. The newly discovered hormone-dependence of GSH release across the sinusoidal plasma membrane may explain the known loss of GSH during conditions of experimental shock (traumatic or endotoxin) and stress and peripheral inflammation.

Animals↗

Independence of recognition memory and priming effects: a neuropsychological analysis.

In order to examine the relation between recognition memory and priming effects, we have tracked the recovery of recognition memory and word completion ability during the hours after individual treatment given as part of a prescribed course of electroconvulsive therapy (ECT). Recognition memory was tested by a three-alternative, forced-choice method. In the word completion test, the initial letters of previously presented words were given as cues, and subjects were asked to complete each cue to form the first word that came to mind. Patients receiving bilateral ECT markedly improved their recognition memory performance 45 min to 9 hr after treatment. Word completion performance was normal at 45 min after treatment and did not change thereafter. Despite exhibiting normal priming effects, patients prescribed bilateral ECT scored at chance levels on recognition tests given 45 min after treatment. These findings support the view that recognition memory and priming are independent memory processes, and they suggest that the processes that support priming make little if any contribution to recognition memory. The results are considered in terms of neuropsychological evidence from amnesic patients for the existence of multiple memory systems.

Amnesia↗

Priming across modalities and priming across category levels: extending the domain of preserved function in amnesia.

Amnesia is considered to reflect the effects of damage to a specific brain system required for elaboration, consolidation, and conscious recollection. The study of amnesia is therefore a useful approach for establishing dissociations of function and for understanding the normal organization of memory functions. Amnesic patients and two control groups were tested in two studies of priming. In the first experiment, as measured by a word completion test, all groups exhibited significant priming effects that were greater within a modality than across modalities. The amnesic patients exhibited normal priming effects both within and across modalities, despite severe impairment in recall. In the second experiment, all groups exhibited significant and equivalent priming of category exemplars when category labels were presented and subjects were asked to produce the first exemplars that came to mind. The results extend the domain in which preserved priming effects can be observed in amnesia and they suggest that features of priming observed in normal subjects describe a capacity that is independent of the brain system damaged in amnesia.

Adult↗

Implicit and explicit memory for new associations in normal and amnesic subjects.

Two experiments examined whether repetition priming effects on a word completion task are influenced by new associations between unrelated word pairs that were established during a single study trial. On the word completion task, subjects were presented with the initial three letters of the response words from the study list pairs and they completed these fragments with the first words that came to mind. The fragments were shown either with the paired words from the study list (same context) or with other words (different context). Both experiments showed a larger priming effect in the same-context condition than in the different-context condition, but only with a study task that required elaborative processing of the word pairs. This effect was observed with college students and amnesic patients, suggesting that word completion performance is mediated by implicit memory for new associations that is independent of explicit recollection.

Adult↗

A novel biologically active seleno-organic compound--I. Glutathione peroxidase-like activity in vitro and antioxidant capacity of PZ 51 (Ebselen).

a synthetic seleno-organic compound, 2-phenyl-1,2-benzoisoselenazol-3(2H)-one (PZ 51), exhibits GSH peroxidase-like activity in vitro, in contrast to its sulfur analog, PZ 25. In addition, PZ 51 behaves as an antioxidant shown by a temporary protection of rat liver microsomes against ascorbate/ADP-Fe-induced lipid peroxidation, an effect also elicited by PZ 25 but to a smaller extent. This protection against lipid peroxidation is independent of GSH and of P-450 monooxygenase activity.

Animals↗

An inhibitor of mitochondrial respiration which binds to cytochrome b and displaces quinone from the iron-sulfur protein of the cytochrome bc1 complex.

Myxothiazol, an antibiotic from Myxococcus fulvus, which inhibits mitochondrial respiration in the bc1 complex of the respiratory chain, has effects on the redox components of isolated succinate-cytochrome c reductase complex which suggest that it interacts with both cytochrome b and the iron-sulfur protein of the bc1 complex. The inhibitor appears to increase the midpoint potentials of cytochromes b-562 and b-566, as indicated by an increase in their reducibility by the succinate/fumarate couple. It also causes a red shift in the optical spectrum of ferrocytochrome b-566, as reported previously (Becker, W. F., Von Jagow , G., Anke , T., Steglisch , W. (1981) FEBS Lett. 132, 329-333). This red shift is enhanced by Triton X-100, and there is no shift in the spectrum of b-562. These results are consistent with evidence that mutations conferring myxothiazol resistance in yeast map to the mitochondrial gene for cytochrome b ( Thierbach , G., and Michaelis, G. (1982) Mol. Gen. Genet. 186, 501-506). In addition, myxothiazol has effects on reduction of the cytochromes b and c1 by succinate or ubiquinol which are identical to those caused by removal of the iron-sulfur protein from the bc1 complex. It blocks reduction of cytochrome c1 during single and multiple turnovers of the bc1 complex, but does not block reduction of the b cytochromes. In the presence of antimycin, it blocks reduction of both cytochromes b and c1. In contrast to antimycin, myxothiazol inhibits oxidant-induced reduction of both b cytochromes and does not inhibit their oxidation by fumarate. Myxothiazol also inhibits reduction of the iron-sulfur protein by ubiquinol and shifts the gx resonance in the EPR spectrum of the iron-sulfur protein from g = 1.79 to 1.76. It does not affect the midpoint potential of the iron-sulfur protein, but does eliminate the increase in midpoint potential which is caused by inhibitory hydroxyquinones which bind to the iron-sulfur protein. The effects of myxothiazol are consistent with a protonmotive Q cycle pathway of electron transfer in which myxothiazol binds to cytochrome b and displaces quinone from the iron-sulfur protein of the bc1 complex. These results suggest either that a myxothiazol-induced conformational change in cytochrome b is transmitted to a quinone binding site on the iron-sulfur protein, or that there is a quinone binding site which consists of peptide domains from both cytochrome b and iron-sulfur protein.

Animals↗

Hepatic uptake of cadmium and its biliary release as affected by dithioerythritol and glutathione.

Net cadmium uptake in the isolated perfused rat liver was half-maximal at 5 microM, and the maximal rate of uptake was 22 nmoles/min per gram liver wet weight. Uptake was augmented when a permeable thiol, dithioerythritol, was infused, whereas it was restricted when glutathione as a nonpermeable thiol or also when bovine serum albumin were infused. The ratio of extra cadmium taken up versus dithioerythritol added was 1:2. Uptake of cadmium was insensitive to anoxia or to the infusion of cyanide. Biliary cadmium release in the perfused liver was not augmented by dithioerythritol but was rather suppressed, whereas bile flow or the release of added 3H-taurocholate were unaffected.

Animals↗

The information that amnesic patients do not forget.

The performance of three kinds of amnesic patients and control subjects was assessed using four methods for testing memory: free recall, recognition, cued recall, and word completion. Whereas amnesic patients were impaired on free recall, recognition, and cued recall, they were normal on word completion. Moreover, performance on the word-completion test declined at a normal rate reaching chance after about 120 min. The word-completion test resembled the cued-recall test in that the initial letters of previously presented words were given as cues. It differed from cued recall only in the instructions, which directed subjects away from the memory aspects of the test and asked them to complete each three-letter cue with the first word that came to mind. The present results offer an explanation of conflicting findings that have been obtained with amnesic patients on tests of the cued-recall type. The results are considered in terms of a process (activation or procedural learning), which is spared in amnesia and not dependent on the integrity of the damaged brain regions.

Adult↗

Viability of surrounding tissue attached to vein graft.

The technique of grafting skin with an attached subcutaneous vein for vessel-skin defects was investigated in an experimental rabbit study. Vein grafts were not able to nourish the skin immediately after grafting. After 14 days, there was a certain amount of vital, revascularized tissue in the area of the vein graft. Plasmatic circulation and revascularization from the wound bed are apparently responsible for the successful clinical application of this technique.

Angiography↗

[Nailing for alignment combined with the Sarmiento method. An interesting combination in the treatment of unstable diaphyseal fractures of the tibia].

The authors have reviewed 51 cases of unstable fracture of the tibia treated by nailing followed 3 weeks later by bracing using the Sarmiento technique. The results confirmed the basis of Kuntscher nailing with reaming. This combination of two techniques can rival more sophisticated techniques such as locked nailing. Several complications were noted - one sepsis, one non-union, two malunions and one shortening of 2 cms.

Adult↗

Decreased flux through pyruvate dehydrogenase during calcium ion movements induced by vasopressin, alpha-adrenergic agonists and the ionophore A23187 in perfused rat liver.

Vasopressin or alpha-adrenergic agents such as phenylephrine or adrenaline, but not glucagon, elicited an initial decrease in flux through pyruvate dehydrogenase assayed by 14CO2 production from [1-14C]pyruvate in perfused rat liver. This rapid decrease in 14CO2 production was maximal within 1-2 min of exposure, concomitant with a rise in effluent pyruvate concentration: a subsequent return towards initial values in both parameters was completed well before 5 min. This time course was superposed with Ca2+ efflux from perfused liver, maximal (at 116 nmol/min per g wet wt. of liver) at 1-2 min of exposure. The percentage of the active (dephospho) form of pyruvate dehydrogenase was not decreased at 2 min of exposure. The effect on flux through pyruvate dehydrogenase by phenylephrine was abolished by prazosine, phentolamine or phenoxybenzamine. Ionophore A23187 also caused a depression in 14CO2 production from [1-14C]pyruvate and a rise in effluent pyruvate concentration, but this effect was stable for longer times, and it was delayed when Ca2+ was omitted from the perfusion medium. Responses of phenylephrine and A23187 were not additive. The results demonstrate that under the experimental conditions employed in intact perfused liver, the mitochondrial multienzyme system of pyruvate dehydrogenase is sensitive to vasopressin, alpha-adrenergic agents and A23187. The similar time course in Ca2+ efflux may be indicative of the involvement of Ca2+ in mediating this effect.

Adrenergic alpha-Agonists↗

[The risk non-union following closed-focus nailing and reaming. Results of 1059 interventions using the Kunstcher method].

The authors have studied a series of 1059 compound and closed fractures of the diaphysis of long bones treated by intramedullary nailing according to the technique of Kuntscher, to assess the incidence of non-union. Between January 1st 1967 and December 31st 1980, 503 fractures of the tibia, 440 of the femur and 116 of the humerus were so treated in both adolescents and adults. The fractures were mostly sustained in road traffic accidents. The risk of aseptic non-union was small, but occurred more readily when the skin was damaged and when the site of the fracture was at the junction of the lower two quarters of the tibia; the incidence was highest when the technique of nailing was incorrect or when the going was undertaken too late. The incidence of non-union and infection are compared with those of other series using the same closed technique and with reports describing insertion of the nail of the plate by opening the fracture. It is concluded that intramedullary nailing using the Kuntscher technique is the most reliable treatment for this type of injury for routine use in an acute fracture service. In this series the incidence of aseptic non-union was approximately 1%, of infection with non-union less than 0.5% and of early infection with eventual union less than 1.5%.

Adolescent↗

Decreased flux through pyruvate dehydrogenase by thiol oxidation during t-butyl hydroperoxide metabolism in perfused rat liver.

Addition of t-butyl hydroperoxide to isolated perfused rat liver leads to a decreased flux through pyruvate dehydrogenase, shown by a decreased 14CO2 release from [1-14C]pyruvate. The effect is observed at rates of infusion of t-butyl hydroperoxide exceeding 0.7 mumol per min per g liver in normal livers and at significantly lower rates in glutathione-depleted livers. The effect is absent in livers from Se-deficient rats in which the hepatic Se-dependent glutathione peroxidase activity is very low, indicating that reduction of t-butyl hydroperoxide by glutathione peroxidase is a necessary prerequisite for the inhibition. With isolated mitochondria, decreased 14CO2 release from [1-14C]pyruvate during t-butyl hydroperoxide metabolism correlates with decreased GSH and increased GSSG contents, respectively. The addition of various disulfide compounds, including GSSG, inhibits activity of the enzyme in mitochondrial extracts. In both mitochondria and perfused liver, t-butyl hydroperoxide-mediated decrease of pyruvate dehydrogenase flux is relieved by thiol reductants. The active (dephospho)form of pyruvate dehydrogenase as measured in freeze-stopped liver samples is actually increased from 46% to 72% during t-butyl hydroperoxide metabolism. The tissue levels of ATP and ADP and perfusate beta-hydroxybutyrate/acetoacetate ratio are not markedly perturbed by addition of the hydroperoxide (10 min). It is concluded that the decreased flux through pyruvate dehydrogenase during t-butyl hydroperoxide metabolism results from oxidation of critical thiol group(s) of the enzyme complex consequential to a decrease in mitochondrial GSH/GSSG.

Animals↗