Biomedical subjects

R R Malcolm

Publications and source records attributed to R R Malcolm.

5 recordsLinked to original sources

PubMed1991

Glutathione dependent metabolism and detoxification of 4-hydroxy-2-nonenal.

The involvement of glutathione (GSH) dependent processes in the detoxification of 4-hydroxy-2-nonenal (4HNE) was investigated using Chinese hamster fibroblasts and clonogenic cell survival. GSH reacted, in a dose-dependent fashion, with 4HNE in phosphate buffer at pH 6.5, leading to the disappearance of 4HNE. The addition of glutathione transferase activity (GST) facilitated a more rapid disappearance of 4HNE but the reaction was still dependent on the concentration of GSH. When cell cultures were exposed to the reaction mixtures, 4HNE cytotoxicity was also reduced in a manner which was dependent on the concentration of GSH. When 2.16- or 1.08-mM GSH were incubated in phosphate buffer with 1.08-mM 4HNE in the presence or absence of GST, then mixed with media and placed on cells for 1 h, the cytotoxicity associated with exogenous exposure to free 4HNE was abolished. GSH depletion (greater than 90%) using buthionine sulfoximine (BSO) was accomplished in control (HA1) and H2O2-resistant variants derived from HA1. GSH depletion resulted in enhanced cytotoxicity of 4HNE in all cell lines. This BSO-induced sensitization to 4HNE cytotoxicity was accompanied by a significant reduction in the ability of cells to metabolize 4HNE. The magnitude of the sensitization to 4HNE toxicity caused by GSH depletion was similar to the magnitude of the reduction in the ability of cells to metabolize 4HNE. These results support the hypothesis that GSH and GST provide a biologically significant pathway for protection against aldehydic by-products of lipid peroxidation.

Aldehydes↗

PubMed1990

Cytotoxicity and metabolism of 4-hydroxy-2-nonenal and 2-nonenal in H2O2-resistant cell lines. Do aldehydic by-products of lipid peroxidation contribute to oxidative stress?

Toxic aldehydes, such as 4-hydroxy-2-nonenal (4HNE) and 2-nonenal (2NE), formed during lipid peroxidation have been isolated and implicated in the cytotoxic effects of oxidative stress. We have investigated the cytotoxicity and metabolism of 4HNE and 2NE in control (HA-1) cells and in two H2O2-resistant Chinese hamster fibroblast cell lines. The H2O2-resistant cells were found to be significantly more resistant than HA-1 cells to the cytotoxicity of 4HNE, as determined by clonogenic cell survival (dose-modifying factors at 10% isosurvival of 2.0-3.0). The H2O2-resistant cells demonstrated a significant 2-3-fold increase in the amount of 4HNE removed (mol/cell) from culture media containing 72 microM-4HNE when compared with HA-1 cells. The enhanced ability of H2O2-resistant cells to metabolize 4HNE was abolished by heating the cells at 100 degrees C for 45 min. Similar results were obtained with 2NE. Total glutathione and glutathione transferase activity, believed to be involved in cellular detoxification of 4HNE, were found to be significantly increased (2-3-fold) in the resistant cells when compared with the HA-1 cells. These results show that cell lines adapted and/or selected in a highly peroxidative environment are also resistant to the cytotoxicity of aldehydes formed during lipid peroxidation. This resistance appears to be related to increased cellular metabolism of these aldehydes, possibly through the glutathione transferase system. These findings suggest that the formation of aldehydes due to lipid peroxidation may contribute significantly to the mechanisms of oxidant-induced injury and the selective pressure exerted by H2O2-mediated cytotoxicity in culture.

Aldehydes↗

PubMed1990

As-if: the phenomenon of not learning.

In this paper I discuss a clinical problem presented by those patients who, instead of using analysis as an emotional learning experience, invest all their energies in keeping it in a static condition. Using the material of four patients, I illustrate how they have an underlying state of disintegration which is contained in a precarious enclosure. The patients experience great difficulty in facing this situation and preventing further disintegration. I describe a particular type of splitting, which I call 'slicing', by which they achieve an arrest of further disintegrative processes, and for which they need the continuous existence of a useless analysis. I link this situation with Bion's concept of 'minus K'.

Adult↗

PubMed1981

Technical problems in the analysis of a pseudo-compliant patient.

This is a clinical paper which describes the analysis of a defensive narcissistic personality. The emphasis is on studying and illustrating the behaviour in the sessions which I have called that of a pseudo-compliance. This behaviour was aimed at maintaining a splitting between an idealized relationship with the analyst and the projection into external objects of persecuting and painful aspects of this relationship. By appearing to agree with almost everything and listening to almost nothing, the patient felt that she could avoid contact with feelings of dependency that seemed to terrify her.

Adult↗

PubMedDate not supplied

Expiation as a defense.

This paper presents a specific defense mechanisms that leads not only to the stagnation of the analysis but also makes it difficult to terminate analysis. The predominance of what I call "expiation" demands continual punishment of the self and of internal objects in contrast with reparation. It is essential for the patient to maintain the immobilization of the analyst and of the analytic work. This defensive constellation aims at protecting the patient from the pain that comes from the guilt brought from the realization that his good and loved object is the same one that he hates and has attacked. Expiation is to be distinguished from the negative therapeutic reaction as well as from other problems in psychoanalysis. A case is presented. There is also a discussion of the relevant psychopathology and of the technical problems expiation poses, with particular attention to countertransference.

Adult↗