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Biomedical subjects

J Price

Publications and source records attributed to J Price.

At least 145 records · Page 8Linked to original sources
PubMed1994

Metastasizing neuroblastomas in mice transgenic for simian virus 40 large T (SV40T) under the olfactory marker protein gene promoter.

The olfactory marker protein (OMP) is a M(r) 19,000 polypeptide originally considered a selective marker for differentiated olfactory receptor neurons. In an attempt to induce neoplastic proliferation in the olfactory cells, we made mice transgenic for the simian virus 40 large T-antigen gene linked to the OMP gene promoter. Four independent lines of transgenic mice were established. Despite a high expression of the transgene in the olfactory receptor neurons, no evidence of tumor growth was observed. Instead, starting from an age of 4 months, animals of all four lines presented with highly metastatic tumors originating in the adrenal medullas or sympathetic ganglia. The histological, ultrastructural, and immunohistochemical features of the tumors were identical to those of human infant neuroblastoma. Five independent neuroblastoma cell lines were established from tumors of different transgenic animals. All cell lines constitutively express the endogenous OMP gene. The transgene product, simian virus 40 large T-antigen, associates with the product of the anti-oncogene p53 in these cell lines. This transgene system not only offers a biologically faithful model for investigations on the pathogenesis of neuroblastoma, the most common solid neoplasia of infancy, it also raises intriguing questions about the role of the OMP gene for the differentiation of the sympathetic neurons.

Animals↗
PubMed1994

Inverse expression of two laminin binding proteins, 67LR and galectin-3, correlates with the invasive phenotype of trophoblastic tissue.

Tumor invasion of host tissues and trophoblastic penetration of the endometrium share common biological features. Both processes involve the invasion of basement membranes, an event that is initiated by adhesion of cancer or trophoblast cells to basement membrane components and particularly to laminin. Adhesion to this latter glycoprotein is mediated through a variety of cell surface receptors. We have previously shown that the 67 kD Laminin Receptor (67LR) and a 31 kD Human Laminin Binding Protein, recently renamed galectin-3, are inversely modulated as the invasive phenotype of cancer cells progresses, with up regulation of the former, and down regulation of the latter, respectively. In this study, we examined the expression of these two proteins in 27 human trophoblastic specimens at different gestational ages using Northern and Western blot techniques. Expression of the 67LR increased from 7 weeks to a maximum at 12 weeks, when invasion is maximal, and then decreased. Expression of galectin-3 was inversely modulated by the gestational age, with a minimum expression at 12 weeks. Our data demonstrate that invasive trophoblast displays the same pattern of laminin binding proteins expression than invasive cancer cells, and further demonstrates that invasion of the extracellular matrix by trophoblast and cancer cells share common molecular mechanisms.

Antigens, Differentiation↗
PubMed1994

RXR alpha mutant mice establish a genetic basis for vitamin A signaling in heart morphogenesis.

We have established a targeted loss-of-function mutation in the RXR alpha gene in the mouse germ line that results in embryonic lethality between E13.5 and E16.5 when bred to homozygosity. The major defect responsible for lethality is hypoplastic development of the ventricular chambers of the heart, which is manifest as a grossly thinned ventricular wall with concurrent defects in ventricular septation. This phenotype is identical to a subset of the effects of embryonic vitamin A deficiency and, therefore, establishes RXR alpha as a genetic component of the vitamin A signaling pathway in cardiac morphogenesis. The cardiac outflow tracts and associated vessels, which are populated by derivatives of the neural crest and which are also sensitive to vitamin A deficiency, are normal in homozygous embryos, indicating the genetic independence of ventricular chamber development. Hepatic differentiation was dramatically but transiently retarded yet is histologically and morphologically normal. These results ascribe an essential function for the RXR alpha gene in embryonic development and provide the first evidence of a requirement for RXR in one of its predicted hormone response pathways.

Animals↗
PubMed1994

Extrathymic expression of the intracellular hepatitis B core antigen results in T cell tolerance in transgenic mice.

We previously developed a transgenic (Tg) murine lineage (B10.S-Tg31e), which secretes the hepatitis B e Ag (HBeAg) into the serum at a concentration of 10 ng/ml. This serum concentration was sufficient to render B10.S-Tg31e mice functionally tolerant at the T cell but not B cell level. To determine the tolerogenic potential of an intracellular form of this Ag, namely the hepatitis B core Ag (HBcAg), expressed outside the thymus, the B10.S-Tg10c lineage was developed. In B10.S-Tg10c mice the HBcAg is expressed as an intracellular "self"-Ag predominantly in the liver, and cannot be detected in the serum, the thymus or in nonthymic lymphoid tissue. Despite the liver-specific and intracellular location of this transgenic self-protein, B10-STg10c mice demonstrate a significant degree of HBcAg-specific T cell tolerance at the level of T cell proliferation. Similarly, in vivo anti-HBc antibody production after HBcAg immunization is significantly reduced as compared with non-Tg littermate controls. No spontaneous anti-HBc antibody is produced in B10.S-Tg10c mice, however, adoptive transfer of HBcAg-specific T cells from non-Tg B10.S mice elicits anti-HBc specific "autoantibody" production. Interestingly, antibodies with specificity for the HBeAg as well as the HBcAg are produced. Antibody production in B10.S-Tg10c mice adoptively transferred with T cells indicates that sufficient native HBcAg can gain access to the extracellular compartment to engage HBcAg-specific B cells that are clearly not tolerant in this model. No liver injury was observed as a consequence of HBcAg expression, even in B10.S-Tg10c mice adoptively transferred with HBcAg-specific T cells. Unless HBcAg is unique in this regard, these results suggest that organ-specific, intracellular self-Ag may be released during normal cell turnover in sufficient concentrations to elicit systemic T cell tolerance. B10.S-Tg10c mice also serve as an immunologic model system for chronic infection with the HBeAg-negative mutant of the hepatitis B virus.

Animals↗
PubMed1994

Glial cell lineage and development.

Recent studies on the development of glial cells are making rapid progress in two major directions. While the factors that control gliogenesis during the perinatal period are becoming more clearly characterized, so too is the relationship between gliogenesis and the patterning of the embryonic central nervous system as a whole.

Animals↗
PubMed1994

Mast cell ultrastructure in the adenoids of children with and without secretory otitis media.

This study was designed to compare the differences in morphology of the mast cells from the adenoid in children with otitis media with effusion (OME) and those from children with recurrent tonsillitis. Tissue for electron microscopy was prepared in the standard manner and between three and 10 blocks were examined for each child. All the mast cells with nuclei were photographed and the condition of the granules noted. The number of electron dense granules in each cell was assessed on a scale between zero and 10. Sixteen unselected children with OME were compared with 19 children with recurrent tonsillitis. There were no obvious differences in the degree of degranulation between the two groups although there was more vacuolation than previously described in the normal nose but less than in those patients with perennial allergic rhinitis. Allergy and mast cell reactions do not seem to predispose to OME. It was concluded that the adenoids are not the ideal tissue in which to study normal mast cells.

Adenoids↗
PubMed1994

Influence of motivational and demographic factors on performance in the medical course: a prospective study.

A questionnaire was completed by students entering the University of Queensland (Australia) MB BS course in 1983 and 1984 (n = 399). It contained wide-ranging questions regarding the decision to enter medicine, including how, why and when the decision was reached. Demographic data were also collected. All but two students have now completed their involvement with the course. The most important determinant of qualifying MB BS was geographical, metropolitan students doing so in greatest proportion. High levels of course performance were predicted by father's occupation, and being aware of a widely held attitude, namely that it would be a pity not to enter medicine if able to do so. Several gender differences are noted. Finally, it was noteworthy that the predictive aspects of questionnaire responses did not lessen as students progressed through the course.

Career Choice↗
PubMed1994

The direct clinical examination: an alternative method for the assessment of clinical psychiatry skills in undergraduate medical students.

Because of dissatisfaction with the traditional long case procedure as a method of examining the clinical competence of medical students undertaking a psychiatry term, an alternative 'direct' method whereby two examiners observe the interaction between student and patient has been developed and is described. This method of examining allows the examiners to set and evaluate case-specific tasks. It is demonstrated that the two examiners achieve satisfactory interrater reliability both with respect to the mark awarded and the difficulty the patient presents and that, as one would wish, these two measures do not correlate. Students' opinions regarding the examination were assessed pre- and post-examination using visual analogue scales. The students found the examination stressful but rated the method as an appropriate form of clinical assessment both before and after their examination. The method is seen as having several advantages which must be set against the disadvantage of its being relatively expensive of examiners' time.

Australia↗
PubMed1994

Imaging of the absent cervical pedicle syndrome.

Three cases of congenital absence of a cervical spine pedicle are described. This anomaly comprises a radiological triad of (i) the absent pedicle producing an apparently 'giant' neural foramen; (ii) a dorsally displaced ipsilateral articular mass and lamina with a dysplastic and reversed facet joint; and (iii) deficiency or absence of the ipsilateral transverse process. Recognition of this anomaly is particularly important in the context of acute injury to avoid misdiagnosis as a traumatic facet joint fracture-dislocation. The giant foramen must also be differentiated from expansion due to a neurofibroma. A correct plain radiographic diagnosis is usually possible, but in doubtful cases appearances on computed tomography are pathognomonic. Magnetic resonance imaging, performed in two of the cases, was helpful in elucidating the contents of the giant foramen, but should rarely be necessary in clinical practice.

Adult↗
PubMed1994

Efficacy and side effects of botulinum toxin treatment for blepharospasm and hemifacial spasm.

PURPOSE: To analyse the effectiveness and rate of side effects of botulinum toxin treatment for blepharospasm and hemifacial spasm. METHODS: In a prospective trial, 81 patients with blepharospasm and 70 with hemifacial spasm were treated with botulinum toxin A in the neuroophthalmology clinic at St Vincent's Hospital, Melbourne. Some 989 treatments were given and the mean follow-up time was 28.7 months. RESULTS: The duration of action was longer for patients with hemifacial spasm than for those with blepharospasm (median 12.0 weeks compared with 7.0 weeks, P < 0.0001). There was no change in the duration of effect over time with repeated treatments of the same dose (F = 0.4, P > 0.05). Once an effective dosage was reached, increasing the dose further did not prolong the duration of effect. There were no systemic side effects, but there were a number of local transient side effects. The most significant side effect was ptosis, which occurred in 12% of treatments given to those patients with blepharospasm and hemifacial spasm. CONCLUSION: Botulinum toxin is an effective treatment for blepharospasm and hemifacial spasm, but there are a number of side effects, the most significant being ptosis.

Blepharoptosis↗
PubMed1994

Fetal marrow suppression after maternal chemotherapy for leukaemia.

A preterm baby, whose mother received chemotherapy for acute leukaemia during pregnancy, required intensive care because of profound anaemia and neutropenia. Haemopoietic progenitor cell studies showed fetal marrow suppression. Those caring for such mothers and babies should know the possible serious effects chemotherapy for malignancies can have on a developing fetus. Long term follow up of the baby is imperative.

Acute Disease↗
PubMed1994

Adaptive function of depression: psychotherapeutic implications.

Using the frameworks of attachment and social hierarchy theories, strategies seen in depression and in normal life are better understood. A hierarchial encounter elicits the "Involuntary Subordinate Strategy" ("ISS") in the loser, which terminates the "ISS" and brings the encounter to an end. These are psychophysiological mechanisms deeply rooted in our phylogenetic ancestry. Loss of a love object also elicits ineffective anger or rage which may, in turn, trigger the ISS. A prolonged intense ISS manifests in depression. Factors are examined that prevent "acceptance" of losing, thereby contributing to an escalation of the ISS and culminating in depressive illness. Psychotherapeutic implications include cognitive restructuring to enable the patient to explore options that might turn off the ISS such as "acceptance" (without making negative self-evaluations), changing unrealistic ideals and aspirations, leaving the scene, or becoming more self-assertive. Case examples are given to illustrate these interventions.

Adult↗
PubMed1994

The social competition hypothesis of depression.

Depressive personality and depressive illness are examined from an evolutionary adaptationist standpoint. It is postulated that the depressive state evolved in relation to social competition, as an unconscious, involuntary losing strategy, enabling the individual to accept defeat in ritual agonistic encounters and to accommodate to what would otherwise be unacceptably low social rank.

Cognitive Behavioral Therapy↗