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Biomedical subjects

P McCullagh

Publications and source records attributed to P McCullagh.

At least 37 records · Page 2Linked to original sources
PubMed1995

Expression and regulation of anti-thyroid autoimmunity directed against cultivated rat thyrocytes.

Lymph node cells from DA rats that had been exposed in utero to 131I in doses sufficient to interrupt thyroid development, attacked monolayers of normal syngeneic thyrocytes in vitro. Lymph node cells from normal DA rats did not damage syngeneic thyrocyte monolayers. Thyrocytes could be protected from damage provided they had been incubated with lymph node cells from normal syngeneic rats before the introduction of lymph node cells from 131I exposed rats. Spleen cells from both 131I exposed and normal rats attacked syngeneic thyrocytes. It is concluded that normal rats possess cells capable of downregulating anti-thyroid autoimmunity.

Animals↗
PubMed1995

Suppression of anti-thyrocyte autoreactivity by the lymphocytes of normal fetal lambs.

We have devised an experimental strategy to determine whether the developing immune system of normal fetal animals can spontaneously acquire the capacity to inhibit autoimmune responses by its cells as it matures. Whilst the existence of cells with the capacity to exert negative regulation and to curtail autoimmune responses has been demonstrated previously in response to the experimental induction of these responses, the relevance of such regulatory processes to the prevention of overt autoimmunity in normal animals has not been established. We have produced pairs of identical twin fetal lambs by splitting blastocysts and have subsequently deprived one of each pair of exposure to thyroid-specific antigens by surgical thyroidectomy before development of immunological self recognition. Thyroidectomized fetuses developed T lymphocytes autoreactive against self thyrocytes. However, their normal, identical co-twins were found to acquire a class of T lymphocytes with the capacity to block anti-thyrocyte autoreactive cells from the thyroidectomized fetal co-twin. Blocking of anti-thyroid autoreactivity required preliminary contact between these normal T lymphocytes and the target thyrocytes. Substitution of an allograft of fetal thyroid tissue for a fetal lamb's own thyroid gland failed to prevent the development of autoreactivity against autologous thyrocytes by the recipient's lymphocytes. However, the reactivity of those lymphocytes against thyrocytes from the specific allogeneic thyroid donor was markedly curtailed.

Animals↗
PubMed1994

Retarded and excessive development of skin appendages in fetal lambs in response to thyroidectomy before wool follicle appearance.

The impact on wool follicles of development in an athyroid environment was studied in a series of twin fetal lambs by surgically thyroidectomizing one of each pair before the appearance of follicle buds and comparing development of epidermal appendages in it with their development in the normal co-twin. Thyroidectomy was undertaken at 51 to 54 days' gestation, i.e. after approximately one-third of the gestation period. Each treated fetus was then replaced in the uterus, allowing pregnancy to continue. Eight pairs of twins were removed at intervals from 67 to 122 days' gestation and skin samples from the thyroidectomized and the intact twins were compared. Micromorphometric examination of the samples was used to assess quantitatively the effects of thyroid deprivation on wool follicle development. In thyroidectomized fetuses there was a failure of keratinization in primary wool follicles, an absence of secondary follicles, a tendency to excessive follicular branching and sweat gland development, and a paucity of sebaceous gland formation. The density of wool follicles was substantially increased, but the mean cross-sectional area of these follicles was reduced. The effects of very early thyroidectomy imply that the thyroid plays a role in the stimulation and regulation of wool follicle differentiation. To test the reversibility of the effects observed in the skin of thyroidectomized fetuses, grafts from these animals were transplanted to normal, young fetal lambs. Subsequent examination of grafted skin revealed that complete keratinization had occurred but that none of the other abnormal features had been reversed.

Animals↗
PubMed1994

Evaluation of a transgenic mouse model for alpha-1-antitrypsin (AAT) related liver disease.

We have attempted to produce a transgenic mouse model of the neonatal liver disease associated with the human PIZ allele. Analysis of a number of transgenic mouse lines carrying either a normal human PIM gene construct or the mutant Z is reported. Using isoelectric focusing analysis of plasma from transgenic mice, we have shown that the human AAT proteins produced in mice are processed in a similar way to their counterparts in humans. By comparing the level of M and Z mRNA in liver with the levels of M and Z proteins in plasma we have inferred that, as in humans, the mutant protein tends to accumulate within the hepatocyte. Accumulation of Z protein has also been demonstrated by immunocytochemistry. Two of the M transgenic lines produce such high levels of the human protein that it, like the Z protein, accumulates as globules. Histological features of livers from 116 mice of different ages and genotypes were examined: 37 non-transgenic, 62 Z transgenic (23 low expressing and 39 high expressing) and 17 M transgenic mice, all high expressing. Cirrhosis or fibrosis was not seen in any animal and we were unable to find any evidence for neonatal liver disease. Some necrosis was seen in all genotypes and this increased significantly with age with one Z line showing significantly more frequent necrosis than any other group. This line, the highest expressing Z line, was back crossed onto 7 different genetic backgrounds but no major differences between the back crosses with respect to liver disease were observed. The mouse model we have developed is compared with other transgenic Z mouse models; none of these is representative of human neonatal liver disease. Our view is that the transgenic animals generated in these experiments may be most useful for investigating the liver manifestations that almost invariably occur in ZZ adults. Alteration of additional factors other than accumulation of Z protein, for example inactivation of the endogenous mouse genes or some environmental challenge, might produce a mouse model with more relevance to neonatal liver disease.

Animals↗
PubMed1993

Proliferation of reactive and neoplastic human tissue mast cells. An immunohistochemical study using the antibody PC10 (anti-PCNA).

Studies on the proliferative compartment of human tissue mast cells (MCs) and their tumours (mastocytosis) have not been performed. We have used the monoclonal antibody PC10 to study MCs in reactive or hyperplastic states (chronic non-specific lymphadenitis, n = 10; benign and malignant solid tumours, n = 5) and in the various subtypes of mastocytosis (urticaria pigmentosa, n = 22; solitary mastocytoma of the skin, n = 7; systemic mastocytosis; n = 8; malignant mastocytosis, n = 4). The identification of PC10-positive MC nuclei was achieved by double staining. We found no PC10-positive MCs in reactive or hyperplastic states, or in 14 of 22 cases of urticaria pigmentosa. PC10-positive MCs could be identified in all other mastocytosis but mostly in very low numbers. The mean percentages of PC10-positive MCs amounted to 0.5 in eight positive cases of urticaria pigmentosa, 1.2 in mastocytoma, 0.7 in systemic mastocytosis, and 4.0 in malignant mastocytosis. The difference between the latter form of mastocytosis and each of the other subtypes proved to be significant (P < 0.05). The very small proliferative compartment in the cutaneous and systemic variants of mastocytosis is in accord with their favourable prognosis. Most of the patients with systemic mastocytosis in the present study are all alive and well up to 12 years after diagnosis. In contrast, most of the patients with malignant mastocytosis died within 1 year of diagnosis.

Adult↗
PubMed1993

The failure of a combination of thyroid and thymus allografts to prevent the development of autoimmunity in thyroidectomized foetal lambs.

Previous experiments have shown that surgical removal of the thyroid gland from the foetal lamb one third of the way through gestation prevents the development of self tolerance towards thyroid-specific determinants. As a result, self thyroid tissue reintroduced into the foetal lamb after maturation of the immune system is not recognized as self and is subject to autoimmune thyroiditis. Furthermore, the transplantation of a thyroid allograft into a foetal lamb immediately after extirpation of its own gland has been shown not to direct the development of self tolerance to thyroid determinants. In the present experiment, foetal lambs were submitted to removal of the entire thyroid gland and the majority of the thymus gland, at 51-54 days of gestation followed by the immediate implantation of thyroid and thymic allografts. The additional implantation of thymus tissue did not affect the previously observed incapacity of a thyroid allograft to facilitate induction of organ-specific tolerance by the thyroid allograft. It was inferred that any T lymphocytes generated within the thymus graft and tolerant of thyroid-specific determinants had not had the capacity to suppress the activity of autoreactive cells generated in the host's thymus.

Animals↗
PubMed1993

Giant cell lesions complicating fibro-osseous conditions of the jaws.

Three patients who presented with giant cell lesions complicating ossifying fibroma, Paget's disease, and cherubism are reported. The giant cell lesions complicating ossifying fibroma and cherubism were diagnosed as giant cell granuloma (GCG), whereas the lesion complicating Paget's disease demonstrated more aggressive clinical and histologic features. The possible therapeutic and prognostic implications of these findings are discussed.

Adult↗
PubMed1993

Case studies in binary dispersion.

It is common in biomedical studies with binary responses that variability in the observed number of events exceeds binomial variability, a phenomenon known as overdispersion. Failure to make an adjustment to the nominal standard errors can lead to seriously misleading inference for regression analysis. In this note, we examine a series of examples drawn from the literature to see which of two commonly used variance formulas is more adequate for describing overdispersion in applications. Two methods, residual analysis and formal comparison, are introduced. We recommend that both methods be employed in seeking an appropriate variance expression for binary responses. Each of the five data sets exhibits substantial overdispersion, one favoring the beta-binomial form, another favoring a constant overdispersion factor. The remaining three examples exhibit no preference.

Animals↗
PubMed1992

Interaction between inoculated allogeneic lymphocytes and fetal rats.

Interaction between allogeneic lymphocytes and 12-20-day gestation rat fetuses was examined in vitro and in vivo. Intravenous injection of lymphocytes was achieved either by in vitro cannulation of the vitelline vein followed by culture of the whole fetus, or of its organs, or by in utero cannulation of the vitelline vein through the uterine wall. Cytotoxic reactions on the part of the inoculated allogeneic lymphocytes against fetal tissue could not be detected in the young hosts. The fetal spleen, mesentery and intestine appeared to have a specific affinity for adult lymphocytes from the earliest gestational age examined.

Animals↗
PubMed1992

The influence of intravenously introduced allogeneic lymphocytes on fetal rats.

Semi-allogeneic or allogeneic bone marrow cells, or allogeneic spleen cells, were injected in utero into PVG, DA and Fischer rat fetuses at 15-18 days of gestation via the vitelline vein. Prenatal (PVG x DA) F1 bone marrow cell inoculation produced allograft tolerance far more frequently in DA recipients than in PVG recipients. Inoculation of allogeneic or semi-allogeneic spleen cells into rat fetuses failed to induce allograft tolerance but sensitized the recipients. The observation that Fischer recipients could be rendered tolerant to skin allografts by prenatal inoculation of PVG, but not DA, bone marrow cells indicated that variation in susceptibility to tolerance induction among different donor-recipient strain combinations is unlikely to be explicable on the basis of strain differences in developmental maturity of the host immune system.

Animals↗
PubMed1991

The inability of thyroid allografts to induce self-tolerance of organ-specific antigens in foetal lambs.

Foetal lambs in the eighth week of gestation were submitted to thyroidectomy followed by the immediate implantation of a thyroid allograft from a donor of similar age. Excised thyroid glands were transplanted to nude mice and maintained there for approximately 2 months, after which they were re-implanted in the original donor. Some foetuses also received second allografts of thyroid tissue from the original donors at this time. Several weeks later, foetuses were killed to permit histological examination of the original thyroid allografts and of subsequent autografts and allografts. Examination revealed heavy lymphocytic infiltration, interpreted as autoimmune thyroiditis, in reimplanted autografts. Thyroid allografts which had been transferred in the eighth week occasionally showed limited areas of lymphocytic infiltration but their most notable feature was a highly abnormal follicular morphology. Whilst these primary allografts had not been rejected, second thyroid allografts from the same donors were all rapidly destroyed. The failure of foetal lambs which had experienced thyroidectomy and receipt of a thyroid allograft to acquire self-tolerance to thyroid tissue was attributed to the inadequacy of thyroid-specific antigens to achieve this when presented exclusively on allogeneic thyroid cells.

Animals↗
PubMed1990

Developmental modeling effects on the quantitative and qualitative aspects of motor performance.

The purpose of the present experiment was to replicate and extend previous developmental modeling research by examining the qualitative as well as quantitative aspects of motor performance. Eighty females of two age groups (5-0 to 6-6 and 7-6 to 9-0 years) were randomly assigned to conditions within a 2 x 2 x 2 (Age x Model Type x Rehearsal) factorial design. Children received either verbal instructions only (no model) or a visual demonstration with experimenter-given verbal cues (verbal model) of a five-part dance skill sequence. Children were either prompted to verbally rehearse before skill execution or merely asked to reproduce the sequence without prompting. Both quantitative (order) and qualitative (form) performances were assessed. Results revealed a significant age main effect for both order and form performance, with older children performing better than younger children. A model type main effect was also found for both order and form performance. The verbal model condition produced better qualitative performance, whereas the no model condition resulted in better quantitative scores. These results are discussed in terms of differential coding strategies that may influence task components in modeling.

Child↗
PubMed1990

Demonstrations and knowledge of results in motor skill acquisition.

In learning motor skills, different types of information can be utilized to reinforce correct execution of the skill. Over the years, augmented information after the movement (i.e., knowledge of results) has been the most widely studied and has received attention as the most important variable for learning. Recently, however, researchers have begun to focus on modeling or providing information prior to movement as another important aspect of skill learning. The present experiment compared a KR 100% condition with a KR 33% condition, with a final modeling plus KR condition on the acquisition and immediate transfer retention of a timing task. The results showed that all groups reached the same performance level by the end of acquisition. However, over the immediate transfer phase, subjects who had received modeling plus KR during acquisition, increased their errors. Delayed retention produced no significant group effects.

Adult↗
PubMed1990

Curtailment of autoimmunity following parabiosis with a normal partner.

The development of thyroiditis in DA rats that had been exposed to 131I in utero was prevented by parabiosis to normal, syngeneic partners. However, if the normal partner had received sublethal irradiation before parabiosis, thyroid implants placed in either partner were likely to manifest spontaneous thyroiditis.

Animals↗