Roy A. Fox

The Use of Goal Attainment Scaling in a Geriatric Care Setting

Goal attainment scaling (GAS) is a measurement approach used extensively in mental health. It accommodates multiple individual patient goals, yet retains mathematical properties allowing comparisons between patients. This study was carried out to investigate the feasibility and measurement properties of GAS in a geriatric care setting.

Endotoxin and macrophage-migration inhibition.

Abstract Endotoxin inhibits the in vitro migration of macrophages. Macrophages which have been stimulated by intraperitoneal oil (Marcol) are more sensitive to the endotoxin than are nonstimulated, normal macrophages. Other factors appear to affect the sensitivity of macrophages and there is great variation between individual animals. This effect is not due to toxicity since the macrophages remain viable. Furthermore, it can be reversed by the addition of polymyxin B. This action appears to be a direct effect on macrophages since it is still evident with viable, enriched populations. The action of endotoxin can be potentiated by exposure of macrophages to lymphocyte supernatants containing migration-inhibition factor. The action is not potentiated by periodate treatment. In this situation the two effects are additive. It is suggested that some of the variability in the migration-inhibition factor assay might be due to contaminating endotoxin. Endotoxin has been found to contaminate most biological materials. The degree of contamination might well influence the level of activation of the macrophage, and thus the responsiveness to migration-inhibition factor. This work supports the concept that the macrophage needs to be at a certain level of activation to respond to migration-inhibition factor. It is clear that the presence of contaminating endotoxin needs to be considered, and prevented, in all work on migration-inhibition factor.

Macrophage migration stimulation factor, migration inhibition factor and the role of suppressor cells in their production.

Abstract Guinea pig lymph node lymphocytes and human peripheral blood lymphocytes when stimulated by specific antigen or mitogen will release factors that affect in vitro macrophage migration. Migration inhibition factor production appears to be under the control of suppressor cells which are T lymphocytes. When suppressor cells are generated by stimulation with Con A for 4 days, migration stimulation factor (M.St.F.) activity is found. In other situations where M.St.F. is found this is thought to be due to increased suppressor cell activity. For example, young adults produce this lymphokine when stimulated with Con A, whereas aged individuals produce MIF. Concanavalin A appears to be the mitogen of choice for M.St.F. production, and phytohemagglutinin for MIF production. The release of this putative factor M.St.F. from suppressor T cells helps to explain some of the difficulties that have existed in studies of macrophage migration inhibition.

A link between helper and suppressor factors and the lymphokines migration inhibition factor and migration stimulation factor

Abstract Spleen and thymus cells from Swiss Webster ICR mice were separated into enriched subpopulations using anti-Lyt-1.2 and anti-Lyt-2.2, and tested for lymphokine production in response to Con A stimulation. The Lyt-1.2 subpopulation, helper cells, produces migration inhibition factor (MIF). The Lyt-2.2 subpopulation, suppressor cells, produces migration stimulation factor, (MStF). This is confirmed in the human system with tμ producing MIF and Tγ, MStF. When MIF-rich supernatants are added to lymphocyte suspensions undergoing transformation in response to phytohemagglutinin (PHA), transformation is significantly increased. This effect is blocked by the addition of 0.1 M l -fucose. In contrast MStF suppresses transformation in response to PHA, and also lowers background counts. It is suggested that MIF is a helper factor, and MStF, a suppressor factor.

The Isolation of Migration Inhibition Factor

Migration inhibition factor (MIF) has been separated from the supernates of tuberculin stimulated lymphocytes and from fetal calf serum by an affinity column of fucosamine bound to agarose beads. A glycoprotein with the characteristics of biologically active MIF and a molecular weight of approximately 50,000 Daltons was obtained by this one stage purification procedure.

The biochemical and biological characterization of macrophage migration inhibition factor isolated from fetal calf serum by affinity chromatography

Abstract Macrophage migration inhibition factor (MIF) has been isolated from fetal calf serum (FCS) by affinity chromatography on fucosamine epsilon amino caproic acid agarose. This material has been radiolabelled and shown to be a glycoprotein with a molecular weight of about 50,000 Daltons. The radiolabelled material elutes with the biologically active moiety on gel filtration with Biogel. The affinity column eluate is fairly homogenous, as demonstrated by SDS polyacrylamide gel electrophoresis. Apart from the biological effect of inhibiting in vitro macrophage migration, we have also documented the inhibition of in vitro spreading onto glass substrate over 1 hour (fast spreading). Thus FCS-MIF has some biochemical and biological features which are similar to other types of MIF and some of which are unique. The study of this readily available material and its interaction with the macrophage allows a closer understanding of macrophage function.

Adhesion and spreading behaviour of human peripheral blood mononuclear cells (PBMC) in vitro.

Abstract While the in vitro adhesion and spreading behaviour of fibroblastic cells have been extensively documented, similar studies on the cells of immunological importance are still lacking. We report here the in vitro adhesion and spreading behaviour of normal human peripheral blood mononuclear cells (PBMC) isolated by the Ficoll-Hypaque technique. Since the presence of serum retarded cell adhesion by 25%, serum-free RPMI-1640 medium was used in these studies. Based on the light and scanning electron microscope studies, glass-immobilized PBMC were classified on the basis of their spreading behaviour as follows: (A) Cells with non-deformable nucleus: I, Cytoplasm non-spread; II, Cytoplasm partially spread; III, Cytoplasm well spread. (B) Cells with deformable nucleus: IV, Nucleus partially spread; cytoplasm well spread; V, Nucleus and cytoplasm well spread. These different cell types occur in the normal human peripheral blood in the relative frequency of 24 ± 3: 27 ± 4: 13 ± 2: 20 ± 5: 16 ± 2 percent. Cell types I–III show the characteristics of lymphocytes and the cells of type V were identified as monocytes, while the nature of cell type IV is not known at present. The immobilized PBMC contained T and B cells as confirmed by sheep erythrocyte (SE) and mouse erythrocyte (ME) rosette formation and surface immunoglobulin. The spreading behaviour of these cells appears to be limited by factors such as available surface membrane area, number and density of adhesion sites, other membrane receptors and the deformability of cell and nuclear membranes. Further characterization of these cell types would aid as a behavioural marker for the subpopulations of lymphocytes and monocytes in health and disease.

Idiopathic gait disorders of the elderly

Changes in mobility are a frequent concomitant of ageing. In a proportion of those presenting with mobility problems no specific diagnosis can be made, and these individuals are stated to be suffering from idiopathic gait disorder of the elderly (IGDE). In order to better describe this entity we examined 15 non-impaired individuals (mean age 77.8 years) and contrasted them to 14 individuals (mean age 80.2 years) suffering from IGDE. Evaluation included detailed physical examination including sensory evaluation, strength testing, upper extremity dexterity testing, and formal gait analysis. There were no significant differences between the two groups with regard to the physical examination, strength testing, or upper extremity function. Both groups were equivalently able to learn a new neuromuscular task involving their upper extremities. There were significant differences with regard to gait parameters between the two groups - IGDE subjects were significantly slower, had a shorter stride, and spent more time in double support. From our study we conclude that: (1) IGDE disproportionately affects lower extremity function with relative sparing of upper extremity function, and (2) IGDE subjects appear to have adequate sensory input, muscle strength, and are able to learn new neuromuscular tasks suggesting that this disorder would be remediable to appropriate therapy.

The Role of Suppressor Cells in the Production of Macrophage Migration Inhibition Factor

The production of migration inhibition factor (MIF) by human peripheral blood lymphocytes and guinea pig lymph node lymphocytes, in response to mitogen, concanavalin A, or antigen, tuberculin, has been studied. Suppressor cells have been depleted by in vitro ageing of cultures for 24 hours, and this has resulted in a significant increase in MIF activity. Reconstitution of the aged lymphocyte population by the addition of fresh lymphocytes results in a suppression of MIF production. When lymphocytes, which have been cultured for 24 hours in the presence of antigen or mitogen to generate suppressor cells, are added to aged cultures MIF production is inhibited. These results suggest that suppressor cells play a regulatory role in the production of MIF.

Migration Inhibition Produced by Sodium Periodate Oxidation of the Macrophage Membrane, and Reversal by Sodium Borohydride

Guinea pig peritoneal exudate cells were harvested 3 to 4 days after the intra‐peritoneal injection of Marcol oil. The washed cells were exposed to various concentrations of sodium periodate in phosphate‐buffered saline (PBS) at pH 7.4 for 10 min at +4°C. The cells were then used in the in vitro migration assay, and migration was consistently inhibited at concentrations from 10−3 to 10−5M. The viability of the macrophages was not affected by this treatment. Sodium borohydride (10−3 to 10−5M) in PBS for 10 min at pH 7.4 reversed the periodate effect. Experiments with purified macrophages showed that sodium periodate has a direct effect on macrophage function rather than an indirect effect via the potentiation of migration inhibition factor. In support of this, the in vitro spreading of macrophages on glass substrate foe 1 h has been shown to be inhibited. This spreading inhibition can also be reversed by treatment with sodium borohydride. These results provide a new approach to understanding the biological significance and role of macrophage migration inhibition.