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R Kingston

Publications and source records attributed to R Kingston.

At least 55 records · Page 3Linked to original sources

An investigation of T cell receptor gene rearrangement and expression in organ cultures of normal embryonic thymus and Thy-1+ cells of nude mice.

We have shown that beginning with 14-day mouse embryo thymus, rearrangements of T cell receptor beta-chain genes and transcripts of alpha and beta chains culminating in the generation of T cell receptor-bearing cells can be obtained in organ cultures. We have failed to detect rearranged beta chain genes, and beta chain transcripts or membrane receptors in concanavalin A-activated nude spleen cells, although we cannot exclude the possibility that a minor subpopulation of nude Thy-1+ cells may express T cell receptors. Our results suggest that the thymus is both necessary and sufficient for generation of T cell receptor-bearing cells and that organ culture provides a system for further investigation of the mechanisms involved.

Animals↗

Generation of cells expressing cytoplasmic and/or surface T-cell receptor beta chains during the development of mouse fetal thymus.

We have used a double immunofluorescence technique to identify newly formed cells expressing cytoplasmic and/or surface T-cell receptor beta chains in mouse embryo thymus. In addition, we have localized these cells to the developing thymic cortex by immunoperoxidase labelling of frozen sections. The first positive cells appear in small numbers in the thymus at Day 15 of gestation and express cytoplasmic but not surface beta chains (C beta+). At Day 16 of gestation, cells appear that express small capped areas of surface beta chains as well as cytoplasmic beta chains (C beta+S beta+ cells). Just prior to birth, a cohort of cells appears that express surface beta chains but no cytoplasmic beta chains detectable by the methods employed (S beta+ cells). These results and vincristine mitosis-blocking studies suggest that a proliferating population of cortical thymocytes accumulate cytoplasmic beta chains before giving rise to T cells that express surface beta chains (presumably in association with alpha chains). When a monoclonal antibody to beta chains is present in organ cultures of embryonic thymus, C beta+ thymocytes continue to be generated but there is an absence of S beta+ cells. The latter appear after the cultures are transferred to fresh medium not containing the antibody.

Animals↗

Stromal cell types in the developing thymus of the normal and nude mouse embryo.

The anatomical distribution of various nonlymphoid cell types in the embryonic mouse thymus in vivo and in vitro, as well as in the thymic rudiment of the nude mouse embryo, has been studied. For this purpose a panel of monoclonal antibodies, ER-TR3, 4, 5, 6 and 7, directed to various types of stromal cells of the mouse thymus, was used in combination with immunoperoxidase labeling on frozen sections. It was shown that as early as day 13 in thymic ontogeny distinction of TR4+ cortical epithelial cells and TR5+ medullary epithelial cells is possible. Thus, as far as stromal components are concerned, the thymus at day 13 in ontogeny is already subdivided into cortex and medulla. At day 13, Ia (TR3) was expressed in a focal pattern in the medulla subsequently appearing throughout both cortex and medulla by day 16. The thymic rudiment of the nude mouse embryo differs markedly from the normal embryonic thymus in its lack of demonstrable Ia antigen. Furthermore, TR4 and TR5 were only expressed on occasional epithelial cells lining the cysts of the nude thymus in a mutually exclusive fashion. The majority of stromal cells of the nude thymus, however, is negative for all ER-TR antibodies tested. In addition, we have shown that in organ cultures the organization of the stroma of thymic lobes remains intact, at least for a period of 11 days. Embryonic thymi cultured in the presence of deoxyguanosine, which causes depletion of lymphoid cells, also contain cortical and medullary areas as identified by the presence of TR3,4+ and TR5+ stromal cells. This indicates that the lack of organization in the nude thymus is not simply due to the absence of lymphoid cells.

Animals↗

An epidemiological view of poisoning.

An epidemiological approach to understanding the incidence and control of injuries is essential. Epidemiology facilitates discovery of factors contributing to the occurrence of, in this case, injuries from poisoning. This page reviews those theories relative to agent, host and environment involved in an unintentional poisoning incident. It is through an understanding of each of these factors that the poisoning incident becomes more clearly defined.

Adolescent↗

Characterization of stromal cell populations in the developing thymus of normal and nude mice.

The role of the thymic stromal components in T cell maturation has been investigated by compairing stromal composition in the developing thymus of normal mice with that of nude mice which are unable to support thymopoiesis. Stromal cell populations have been characterized using monoclonal antibody recognizing class II (Ia) major histocompatibility complex antigens, monoclonal antibody A2B5 recognizing GQ gangliosides characteristic of neuroendocrine cells and monoclonal antibody LE.61 recognizing a determinant associated with the tonofilaments of simple epithelia. Using these probes we have shown that the majority population of Ia+, LE.61+ cells is distinct from the A2B5+ stromal population and that both these populations appear early in normal thymus development showing a similar pattern in vivo and in thymus lobes developing in organ culture. In the nude thymic rudiment both Ia and LE.61 labeling are absent supporting previous conclusions on the epithelial nature of the thymic defect in these animals. In contrast, A2B5+ cells are present in the nude thymic rudiment indicating that these cells are unlikely to share the same developmental origin as the Ia+ epithelial population. In functional terms these results suggest that the Ia+ LE.61+ components, deficient in the nude mouse, are essential for normal thymus function and that whatever the function of the A2B5+ population, alone they are not sufficient to support thymocyte development.

Animals↗

Trazodone overdose.

Trazodone did not appear to be a potent respiratory depressant or cardiotoxic or neurotoxic agent in our cases. Further experience is needed to determine a recommended treatment procedure. It is not clear whether the experience with these two cases can be extrapolated to elderly patients, patients with serious physical illnesses, or cases involving larger ingestions. Additional information is required concerning concurrent ingestion of trazodone and alcohol or other CNS-depressant drugs. It would appear that standard treatment including emptying of the stomach, activated charcoal and cathartic, and close observation to monitor and support the respiratory and cardiovascular systems is appropriate. These two case reports suggest that trazodone lacks the serious toxicity encountered with other antidepressant compounds when taken in large overdoses.

Adult↗

Effect of deoxyguanosine on lymphopoiesis in the developing thymus rudiment in vitro: application in the production of chimeric thymus rudiments.

On the basis of reports that deoxyguanosine is selectively toxic for adult T lymphocytes, the usefulness of this compound in the production of lymphocyte-depleted embryonic thymus rudiments in an in vitro organ culture system was investigated. The results showed that a period of exposure to deoxyguanosine causes depletion of the lymphoid cells while the stromal elements continue to survive, with many of the cells showing an epithelial morphology and expression of I region products of the major histocompatibility complex (MHC). When associated with either fetal liver or another thymus fragment as a source of T cell precursors in transfilter experiments, these "empty" thymuses become recolonized, enabling the production of chimeric thymus with stromal and lymphoid cells of different haplotypes. In combination with functional assays, this system offers an entirely in vitro approach to questions relating to the repertoire potential of T cell precursors from different sources and the role of the thymus in tolerance and MHC restriction.

Animals↗

Acute poisoning: management protocol.

Management of the acutely poisoned patient should start with decontamination of the skin and irrigation of the eyes, if necessary, and assessment of cardiorespiratory status, neurologic status, and pupils and eye movement. If a definable toxic syndrome is present, the specific "antidote" should be given. If no such syndrome is apparent and the patient is comatose, 50 ml of 50% glucose and 0.4 mg of naloxone (Narcan) intravenously should be tried. General measures, applicable in either situation, include induction of emesis or lavage and administration of charcoal and cathartics.

Acute Disease↗

Diagnostic yield of gastroscopy in a general surgical unit.

Gastroscopy is the gold standard for investigating upper gastrointestinal complaints. Open access gastroscopy has advantages, but may not always be feasible in a small unit. Our 2-consultant general surgical unit provides gastroscopy on demand for medical and surgical patients. We audited the 499 gastroscopies carried out in our unit in 1997 to assess yield and diagnostic trends. The overall diagnostic yield of 69 per cent was comparable with published data from centres in Ireland and overseas. Diagnostic yield in our series was significantly lower for medical patients (59 per cent) than for surgical patients (72 per cent) (p < 0.05). Yield also varied considerably according to indication for referral. Patients referred with anaemia had a low yield (41 per cent). The indications associated with high yields were haematemesis (95 per cent), dysphagia (91 per cent), and persistent vomiting (85 per cent).

Adolescent↗

Need-based waiting lists for hip and knee arthroplasty.

BACKGROUND: Need-based waiting lists have been shown to offer advantages over traditional time-based waiting lists. This study investigated the effect of their introduction in our orthopaedic practice. METHODS: Each patient on the waiting list for total hip replacement (n = 240) and total knee replacement (n = 98) was invited to attend a dedicated assessment clinic. At the clinic each patient had a joint score (Harris Hip Score or American Knee Society Score) calculated. Patients with the lowest joint scores were moved to the top of the waiting lists. Scores were repeated postoperatively. RESULTS: Validation of the hip replacement and knee replacement waiting lists reduced them by 20% and 11% respectively. The efficiency and transparency of the service were increased. CONCLUSION: Need-based waiting lists are easily introduced and offer significant advantages over time-based waiting lists. We advocate their introduction in other centres.

Arthroplasty, Replacement, Hip↗