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Biomedical subjects

C J Elliott

Publications and source records attributed to C J Elliott.

29 records · Page 2Linked to original sources

HLA-DR expression in epidermal keratinocytes after allogeneic bone marrow transplantation. Relationship to histology, rash, marrow purging, and systemic graft-versus-host disease.

HLA-DR expression on epidermal keratinocytes was studied in leukemic recipients of allogeneic marrow in order to clarify its relationship to GVHD, investigate its diagnostic value, and gain insight into the pathogenetic mechanisms. Using frozen-section immunohistological techniques, positive keratinocytes were encountered in a small minority of normal donors and in a few recipients prior to transplantation. In patients receiving marrow unpurged of T lymphocytes, keratinocyte HLA-DR staining was found in the majority of patients with, and in about one third of those without, histological evidence of GVHD. Positivity was strongly related to the presence of a rash and was more likely to be found if the interval between the onset of the rash and biopsy exceeded 24 hr. There was a strong association between the presence of positive cells and the subsequent development of systemic GVHD, indicating that staining for HLA-DR on keratinocytes may be a useful adjunct to conventional morphological analysis in the interpretation of post-transplant skin biopsies. Positivity was not observed in patients who received marrow depleted of T lymphocytes, indicating a crucial role for these cells in stimulating keratinocyte HLA-DR expression. Sequential studies, however, showed that keratinocyte positivity preceded lymphocytic infiltration of the epidermis.

Bone Marrow Transplantation↗

Cutaneous leucocyte composition after human allogeneic bone marrow transplantation: relationship to marrow purging, histology and clinical rash.

Immunohistological and morphometric techniques were used to study the skin after marrow transplantation with particular reference to the relationship of marrow purging, the presence of a clinical rash and histological changes to leucocyte numbers and phenotype. Recipients of T-cell-depleted marrow showed significant reductions in CD2+, CD4+ and CD8+ T-lymphocytes in the first 22 d after transplantation but not after this time. T-cell numbers in recipients of unpurged marrow were similar to those of normal donors, indicating a rapid repopulation by cells from the graft. Langerhans cells (CD1+ dendritic cells) and macrophages, on the other hand, were present in similar numbers in both groups of patients within the first 22 d; the former in low and the latter in normal numbers. Biopsies exhibiting graft versus host disease showed increases in CD2+, CD4+ and CD8+ T-lymphocytes with significant lowering of the CD4:CD8 ratio. A proportion expressed markers of activation and HNK1+ cells and macrophages were also increased. Biopsies exhibiting epidermal basal abnormalities only (changes identical to graft versus host disease but without detectable leucocyte infiltration on conventional microscopy) showed a minor increase in macrophages and HNK1+ cells but no other leucocyte alterations to suggest a pathogenetic link with graft versus host disease. Langerhans cells were reduced in these biopsies, however, when taken more than 22 d post-transplant, suggesting that the epidermal changes are associated with Langerhans cell damage or repopulation. We were unable to identify any significant alteration in leucocytes in patients with strong clinical evidence of graft versus host disease but with histologically unremarkable biopsies. Although it is possible that perivascular increases in T-cells and expression of activation markers precede the characteristic histological picture of graft versus host disease the time scale is probably too short to allow diagnostic value.

Adolescent↗

The histological diagnosis of cutaneous graft versus host disease: relationship of skin changes to marrow purging and other clinical variables.

Punch biopsies of skin were taken from allogeneic marrow recipients routinely before transplantation, at 14-22 and 90-107 d after grafting and in the event of a clinical rash. Three histological appearances were encountered: graft versus host disease (GvHD), epidermal abnormalities, and normal. Graft versus host disease was characterized by epidermal basal vacuolation, spongiosis and individual cell necrosis associated with mononuclear cell infiltration of the upper dermis and lower epidermis, while epidermal abnormalities were identical to GvHD but without the mononuclear cell infiltrate. Graft versus host disease occurred only in patients receiving marrow unpurged of T-cells while epidermal abnormalities occurred with equal frequency in recipients of purged and unpurged marrow and were also noted in a high proportion of pre-transplant biopsies. Patients whose skin biopsies exhibited epidermal abnormalities showed no greater incidence of subsequent clinical or histological GvHD than those with normal biopsies. For these reasons, we conclude that epidermal abnormalities cannot be regarded as a minor manifestation of GvHD as has often been previously assumed. We also conclude that they cannot be regarded as the cause of a rash as, unlike GvHD, the incidence was not significantly different in patients with and without rashes. The cause of epidermal abnormalities is not entirely clear; cytotoxic drugs and irradiation appear to play a part but their occurrence in patients with previously normal post-transplant biopsies suggests that other factors may also be important. Some patients with strong clinical evidence of GvHD had negative biopsies; these should be regarded with caution especially within the first 24 h after the onset of a rash as the diagnostic histological picture may take time to develop. In some cases, GvHD was confined to pilosebaceous units; this seems to represent a minor form of the disease with only a limited capacity for progression. Dysplastic epidermal changes which have previously been attributed to the use of cyclosporin A were found with equal frequency in patients who did not receive this drug and must therefore have some other cause.

Antibodies, Monoclonal↗

Interactions of pattern-generating interneurons controlling feeding in Lymnaea stagnalis.

Intracellular recordings were made from rhythm-generating interneurons in the Lymnaea feeding system. The feeding pattern is a three-phase rhythm of interneuronal activity (N1, N2, N3) corresponding to protraction, rasp, and swallow. We describe the firing pattern and anatomy of the premotor interneurons, each of which fires a predominant burst in only one phase of the feeding rhythm. The rhythm can be driven by steady depolarization of N1 cells. The phase of the rhythm is reset by brief stimulation of N2 or N3 interneurons. N1 neurons excite the N2 interneurons, and these in turn inhibit the N1 cells. This recurrent inhibitory pathway can account for the switch from the N1 phase of the feeding cycles to the N2 phase. The endogenous properties of the N2 interneurons are apparently responsible for the termination of N2 bursts. N3 interneurons display postinhibitory rebound (PIR), and this probably contributes to their burst after the end of the N2 inhibitory input. N2 and N3 interneurons inhibit the N1 cells. When the N3 burst dies away, activity in N1 cells resumes under the stimulus of depolarizing current. Interactions between interneurons are mainly by discrete, monophasic postsynaptic potentials, that follow 1:1. They have relatively short latency (2-12 ms) and duration (up to 100 ms). The synaptic connections between the three types of premotor interneurons are sufficient to account for the sequence of activity seen during feeding.

Action Potentials↗

Interactions of the slow oscillator interneuron with feeding pattern-generating interneurons in Lymnaea stagnalis.

We have used intracellular recording from groups of interneurons in the feeding system of the pond snail, Lymnaea stagnalis, to examine the connections of a modulatory interneuron, the slow oscillator (SO), with the network of pattern-generating interneurons (N1, N2, and N3). The SO is an interneuron whose axon branches solely within the buccal ganglia. There is only one such cell in each snail. In half the snails the cell body is in the right buccal ganglion and in the other half in the left buccal ganglion. Stimulation of either the SO or one of the N1 pattern-generating interneurons elicits the feeding rhythm, but of all the buccal neurons, only the SO can drive the feeding rhythm at the frequency seen in the intact snail. The SO makes reciprocal excitatory synapses with the N1 interneurons that drive the protraction of the radula. This ensures strong activation of the feeding system. The SO inhibits the N2 interneurons. Postsynaptic potentials evoked by stimulation of the SO facilitate without spike broadening in the SO. The SO is strongly inhibited by N2 and N3 interneurons, which are active during the retraction phase. This gates any excitatory inputs to the SO, probably preventing protraction of the radula while retraction is underway. The results support the idea of a single interneuron capable of driving a hierarchically organized motor system.

Action Potentials↗

Queensland's rural practitioners: background and motivations.

In view of the continuing maldistribution of medical manpower, this study was undertaken in order to delineate the backgrounds and motivating factors influencing choice of practice by rural practitioners in Queensland. Of those doctors in rural practice 38% had spent more than 10 years of their childhood in a rural environment. Interest of work and variety of practice were most consistently designated as attractions of rural practice, while the factor designated as the greatest attraction of rural practice was the variety of practice. The major disadvantages of rural practice were: (i) restricted opportunities for continuing education; (ii) difficulty obtaining adequate locum assistance for holidays and continuing education; and (iii) professional isolation. The prime reasons doctors had for choosing their present practice were the practice conditions (31.3%), and geographical location (20.9%).

Attitude of Health Personnel↗

Workload in rural practice: implications for education and health service structure.

In view of the reported maldistribution of medical manpower in Queensland, this study was undertaken to establish the effects of such a maldistribution on the workload and range of work performed by rural practioners. Rural practitioners were found to have a higher patient contact rate per week, and to perform more surgery and obstetrics than do their city counterparts.

Australia↗