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T Chambers

Publications and source records attributed to T Chambers.

At least 19 recordsLinked to original sources
PubMed2001

Theory and the organic bioethicist.

This article argues for the importance of theoretical reflections that originate from patients' experiences. Traditionally academic philosophers have linked their ability to theorize about the moral basis of medical practice to their role as outside observer. The author contends that recently a new type of reflection has come from within particular patient populations. Drawing upon a distinction created by Antonio Gramsci, it is argued that one can distinguish the theory generated by traditional bioethicists, who are academically trained, from that of "organic" bioethicists, who identify themselves with a particular patient community. The characteristics of this new type of bioethicist that are explored in this article include a close association of memoir and philosophy, an interrelationship of theory and praxis, and an intimate connection between the individual and a particular patient community.

Bioethics↗
PubMed2001

The fiction of bioethics: a precis.

Recently, bioethics has become interested in engaging with narrative, but in this engagement, narrative is usually viewed as a mere helpmate to philosophy. In this precis to his book The Fiction of Bioethics, Tod Chambers argues that narrative theory should not be simply a helpful addition to medical ethics but instead should be thought of as being as vital and important to the discipline as moral theory itself. The reason we need to rethink the relationship of medical ethics to narrative is that ethicists test their ideas by applying them to cases, and cases are a narrative genre. Recognizing the importance that cases have for the way medical ethicists do ethics is essential in order to appreciate the field as a form of applied philosophy. Like other forms of representation, narrative has distinct and defining features, which ethicists, in order to understand the data of their field, must learn to recognize and differentiate. Ethicists need to attend to the way decisions about the discourse of a narrative influences the kind of moral theories judged relevant to it. The author briefly examines six features of narrative discourse that rhetorically condition the way we understand medical ethics cases: filter, reportability, closure, characters, chronotope, and gender.

Bioethics↗
PubMed2001

Efficacy of a cold-adapted, intranasal, equine influenza vaccine: challenge trials.

A randomised, controlled, double-blind, influenza virus, aerosol challenge of horses was undertaken to determine the efficacy of a cold-adapted, temperature sensitive, modified-live virus, intranasal, equine influenza vaccine. Ninety 11-month-old influenza-naïve foals were assigned randomly to 3 groups (20 vaccinates and 10 controls per group) and challenged 5 weeks, 6 and 12 months after a single vaccination. Challenges were performed on Day 0 in a plastic-lined chamber. Between Days 1 and 10, animals were examined daily for evidence of clinical signs of influenza. Nasal swabs for virus isolation were obtained on Day 1 and Days 1 to 8 and blood samples for serology were collected on Days 1, 7 and 14. There was no adverse response to vaccination in any animal. Following challenge at 5 weeks and 6 months, vaccinates had significantly lower clinical scores (P = 0.0001 and 0.005, respectively), experienced smaller increases in rectal temperature (P = 0.0008 and 0.0007, respectively) and shed less virus (P<0.0001 and P = 0.03, respectively) over fewer days (P<0.0001 and P = 0.002, respectively) than did the controls. After the 12 month challenge, rectal temperatures (P = 0.006) as well as the duration (P = 0.03) and concentration of virus shed (P = 0.04) were significantly reduced among vaccinated animals. The results of this study showed that 6 months after a single dose of vaccine the duration and severity of clinical signs were markedly reduced amongst vaccinated animals exposed to a severe live-virus challenge. Appropriate use of this vaccine should lead to a marked reduction in the frequency, severity and duration of outbreaks of equine influenza in North America.

Administration, Intranasal↗
PubMed2000

Transgenic mice reveal novel sites of calcitonin receptor gene expression during development.

To characterize the tissue and developmental-specific transcriptional activity of the human calcitonin receptor (hCTR) gene in vivo, transgenic mice containing a 4.9-kb hCTR promoter/beta-galactosidase (lacZ) construct were generated. Between 8.5 and 10.5 days of development, lacZ-positive cells were observed on the lateral side of cervical and occipital level somites and in the lateral myotome. LacZ-positive cells also appeared to be migrating from the dermomyotome into the adjacent limb buds, suggesting that the hCTR promoter is active in hypaxial muscle progenitors. By 11.5-16 days of development, novel hCTR expression sites were identified that included limb buds, cornea, retina, skin, intercostal muscles, muscles of the limbs, face, and dorsal root ganglion. hCTR promoter activity in a number of these tissues was repressed at adult stages of development. RT-PCR demonstrated endogenous mCTR mRNA in all lacZ-positive tissues assayed. The developmental regulation of hCTR gene expression in the above tissues suggests that CTRs are likely to play an important role in their morphogenesis.

Animals↗
PubMed2000

Multiple promoters regulate human calcitonin receptor gene expression.

To initiate studies on the transcriptional regulation of the human calcitonin receptor (hCTR) gene, a 4.9-kb hCTR promoter fragment was cloned and hCTR transcriptional initiation sites were mapped in human osteoclasts, kidney, and breast cancer cell line T47D. RT-PCR detected additional hCTR transcripts initiating at least 1 kb 5' to the transcripts mapped above, demonstrating that the hCTR gene is regulated by at least two separate promoters (hCTRP1 and hCTRP2). Transcripts initiating from the upstream promoter (hCTRP2) have a novel 5' untranslated region (5' UTR). Transfection of T47D breast cancer cells with hCTR promoter/luciferase deletion constructs demonstrated that the cloned 4.9-kb hCTR promoter fragment contains both hCTRP1 and hCTRP2 promoters. Fine deletion mapping of the more transcriptionally active hCTRP1 promoter demonstrated that only 97 bp of the hCTRP1 5' flanking region is required for the majority of its transcriptional activity.

5' Untranslated Regions↗
PubMed1999

The porcine calcitonin receptor promoter directs expression of a linked reporter gene in a tissue and developmental specific manner in transgenic mice.

We have investigated the transcriptional regulation of the porcine calcitonin (CT) receptor (pCTR) promoter in transgenic mice. A construct containing 2.1 kb pCTR 5' flanking region, fused to a beta-galactosidase (lacZ) gene, was employed for the production of transgenic mice. At 11.5 days of development lacZ expression was observed in the embryonic brain and spinal cord. By 15.5 days post fertilization, lacZ expression was detected in the developing mammary gland, external ear, cartilage primordium of the humerus, and anterior naris (nostril). RT-PCR on RNA from these fetal tissues showed endogenous mouse CTR (mCTR) expression. In neonatal and adult transgenics, lacZ expression was silenced, except in brain, spinal cord, and testis (adults only). Endogenous mCTR gene expression and pCTR promoter activity were corepressed in the same tissues from adult mice. No pCTR promoter activity was detected in the kidney or bone of transgenic animals. This suggests that additional DNA sequences may be required for pCTR promoter activity in these tissues. From these results, we conclude that the pCTR promoter is active only in tissues expressing endogenous mCTR. Many of the these tissues represent previously unknown sites of CTR gene expression. Finally, the developmental regulation of pCTR/mCTR in tissues such as breast and cartilage primordium suggests that CTRs may play a role in the morphogenesis of these tissues.

Aging↗
PubMed1999

Prostaglandin E2 cooperates with TRANCE in osteoclast induction from hemopoietic precursors: synergistic activation of differentiation, cell spreading, and fusion.

It was recently found that osteoblastic cells express TRANCE (tumor necrosis factor-related activation-induced cytokine), a newly identified member of the tumor necrosis factor superfamily, and that expression was increased by calciotropic hormones. Furthermore, soluble recombinant TRANCE induces osteoclast formation and resorption in stroma-free populations of hemopoietic precursor cells. However, overexpression of the decoy receptor osteoprotegerin in vivo shows that there are substantial differences in the sensitivity of different sites to resorption-inhibition, suggesting that either alternative ligands exist or the sensitivity of osteoclasts to TRANCE can be modified by cofactors. We therefore tested the possibility that cofactors might enhance osteoclast formation by TRANCE. We found that the number of tartrate-resistant acid phosphatase-positive and calcitonin receptor-positive cells was increased by a factor of 10 by the presence of PGE2 in the absence of stromal cells. Moreover, although the tartrate-resistant acid phosphatase-positive cells that formed in TRANCE alone were typically mononuclear and poorly spread, the addition of PGE2 induced the formation of large, well spread multinuclear cells. There was an increase in bone resorption that corresponded with the increase in osteoclast number. PGE2 did not synergize with TRANCE for resorption-stimulation in mature cells. 8-Bromo-cAMP showed a similar syngergistic effect on osteoclastic differentiation. Thus, PGE2 appears to stimulate bone resorption through a direct effect on hemopoietic precursors, primarily through a synergistic effect on the ability of TRANCE to induce osteoclastic differentiation.

Acid Phosphatase↗
PubMed1998

Cytoskeletal reorganization induced by retinoic acid treatment of human endometrial adenocarcinoma (RL95-2) cells is correlated with alterations in protein kinase C-alpha.

We have shown previously that treatment of human endometrial adenocarcinoma (RL95-2) cells with either 13-cis or all-trans retinoic acid results in reorganization of actin filaments, indicating reversion to a stationary phenotype. In the present study, we investigated the role of protein kinase C (PKC) in this process. Treatment of cells with PKC inhibitors (staurosporine, bisindolylmaleimide, or G¿6976) resulted in morphological alterations and reorganization of actin filaments similar to retinoic-acid-treated cells. For example, RL95-2 cells treated with staurosporine flattened, exhibited cell surface extensions and some actin filaments. Bisindolylmaleimide-treated cells flattened, and actin filaments reorganized similar to retinoic-acid-treated cells. RL95-2 cells treated with G¿6976, which inhibits only PKC, alpha, beta and gamma, exhibited many cell surface extensions and some actin filament reorganization. We then investigated whether retinoic acid affected the subcellular localization of PKC-alpha. In control cells, PKC-alpha was mainly evident as diffuse cytoplasmic immunostaining, with a small percentage of total PKC-alpha also evident in the plasma membrane. Retinoic acid treatment dramatically altered PKC-alpha localization, since a more distinct cytoplasmic and perinuclear staining pattern was apparent. Western blot analysis confirmed these results, since the amount of cytosolic PKC-alpha increased following retinoic acid treatment. Thus, retinoic-acid-induced endometrial differentiation may be associated with alterations in PKC-alpha localization and signaling.

Adenocarcinoma↗
PubMed1997

A multimodal, second generation, posttraumatic stress disorder rehabilitation program.

Second Generation posttraumatic stress disorder (PTSD) treatment programs were recently proposed as one component of a model of treatment of chronic PTSD. While First Generation PTSD programs emphasized trauma work, Second Generation programs emphasize skills for the present/future ability to adapt within society. The present paper describes a functioning Second Generation PTSD treatment program for Vietnam combat veterans. The guiding principles underlying this multimodal and vocational rehabilitation program are outlined.

Adaptation, Psychological↗
PubMed1997

Questionable ethics--whistle-blowing or tale-telling?

Renal biopsy is a potentially hazardous procedure, generally performed for therapeutic reasons. An open renal biopsy was performed when there appeared to be no accepted clinical indication and its results published in a specialty journal, whose editors declined publication of subsequent correspondence, questioning the ethical propriety of such a procedure. The implications for clinical practice, authors, editors and readers are discussed.

Adolescent↗