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Biomedical subjects

C Mattingly

Publications and source records attributed to C Mattingly.

At least 19 recordsLinked to original sources

Characterization of a newly established human pancreatic carcinoma cell line, UK Pan-1.

BACKGROUND: A highly tumorigenic cell line designated as UK Pan-1 was established in a surgically removed human pancreatic adenocarcinoma and characterized as having many of the genotypic and phenotypic alterations commonly found in pancreatic tumors. METHODS: The cell line was characterized by its morphology, growth rate in monolayer culture and soft agar, tumorigenicity in nude mice, and chromosomal analysis. Furthermore, the status of p53, Ki-ras mutation and transforming growth factor (TGF)-/receptor expression were determined. The characteristics of UK Pan-1 were compared with those of other commonly used pancreatic carcinoma cell lines. RESULTS: Quiescent UK Pan-1 cells could be stimulated to proliferate in growth factor free nutrient media, indicating a growth factor independent phenotype. UK Pan- 1 cells grew in soft agar and rapidly formed tumors in nude mice. This cell line possesses a mutation at codon 12 of the c-Ki-ras-2 gene that is commonly found in pancreatic carcinoma. Fluorescence in situ hybridization showed that two alleles of p53 tumor suppressor gene were present in UK Pan-1. However, sequencing analysis revealed a mutation in one allele at exon 8, codon 273 (G to A; Arg to His). Additional growth assays indicated that the cell line was insensitive to negative growth regulation induced by exogenous TGF-beta. Molecular analysis of the TGF-beta signaling pathway showed that UK Pan-1 did not express appreciable levels of the TGF-beta receptor type I, II, or III mRNAs, but did express DPC4 mRNA. Karyotype analysis revealed an 18q21 deletion indicating a possible loss of heterozygosity for DPC4, as well as other chromosomal deletions and rearrangements. CONCLUSIONS: This study indicates that UK Pan-1 is a highly tumorigenic cell line possessing a molecularly complex pattern of mutations that may be used as a model to further the understanding of the mechanisms responsible for the development of pancreatic carcinoma.

Adenocarcinoma↗

In search of the good: narrative reasoning in clinical practice.

Based on ethnographic work among North American occupational therapists, I compare two forms of everyday clinical talk. One, "chart talk," conforms to normative conceptions of clinical rationality. The second, storytelling, permeates clinical discussions but has no formal status as a vehicle for clinical reasoning. I argue that both modes of discourse provide avenues for reasoning about clinical problems. However, these discourses construct very different clinical objects and different phenomena to reason about. Further, the clinical problems created through storytelling point toward a more radically distinct conception of rationality than the one underlying biomedicine as it is formally conceived. Clinical storytelling is more usefully understood as a mode of Aristotle's "practical rationality" than the technical rationality of modern (enlightenment) conceptions of reasoning.

Adult↗

Metaphor and meaning in a clinical interview.

This study examined the narrative features of 20 life histories gathered from psychiatric patients with the Occupational Performance History Interview. The aim was to identify how narrative features were present in the patient interview responses and to illustrate how such narrative features can be located. We found that the patients organized their interview responses with deep metaphors that served to "emplot," or give meaning to, the life story. This article illustrates how patients used the deep metaphors to both circumscribe and frame possible solutions to the problems in their lives. Deep metaphors are consistent, recurring images of a life story that give coherence to, and aid in, the interpretation of the events of that life. Moreover, we explored how metaphors can be located in patient life histories and their implications for occupational therapy.

Adult↗

In vitro cytolytic activity of lymphocytes from tumor-draining lymph nodes is associated with increased numbers of CD8+ cells and increased cytokine production.

A murine footpad tumor model was used to determine the cytotoxic activity, tumor specificity, phenotypic profile, and cytokine production of stimulated cells from draining lymph nodes (DLN). Popliteal DLN from 5-day-old P-815 footpad tumors were stimulated with 10(-7) M phorbol 12, 13-dibutyrate +5 x 10(-7) M ionomycin for 16 hr and cultured in IL-2 (20 units/ml) for 7 or 14 days without autologous tumor. Most cells in both groups were CD3+ (93% at Day 7, 99% at Day 14); however, the percentage of CD8+ cells increased as the cell population matured in the presence of low-dose IL-2. On Day 7, the phenotypic profile was 62% CD4+ and 29% CD8+, whereas on Day 14 it was 16% CD4+ and 81% CD8+. Similarly, in vitro cytokine production increased with time in culture. After 7 days, the level of tumor necrosis factor-alpha (TNF-alpha) was 220 pg/mL and the interferon-gamma (IF-gamma) production was 150 pg/ml. At Day 14 the TNF level had increased to 500 pg/ml, and IF production had increased to 350 pg/ml. These increases in the CD8+ population and in cytokine production correlated with the increase in the percentage of target cells killed by the DLN cells. Cytolytic activity against P-815 was only 13% on Day 7 but 39% on Day 14. Neither group of effector cells (Day 7 or Day 14) had any cytolytic activity against the syngeneic tumor cell line L-1210, demonstrating the tumor specificity of the DLN cells. We describe a model for generating tumor-specific cytotoxic T-cells that have significant cytokine production, which may account for previously described in vivo activity.

Animals↗

The concept of therapeutic 'emplotment'.

This paper considers the narrative structure of clinical action. I argue that clinical encounters involve clinician and patient in the creation and negotiation of a plot structure within clinical time. This clinical plot gives meaning to particular therapeutic actions by placing them within a larger therapeutic story. No therapeutic plot is completely pre-ordained, however. Improvisation and revision are necessary to its creation. In making a case for the narrative construction of lived time, of narratives that are created before they are told, this paper departs from the predominant mode of narrative analysis within medical anthropology that has focused on narrative discourse. Therapeutic emplotment is concretely considered through an interpretation of a single case, a clinical interaction between an occupational therapist and a head-injured patient.

Anecdotes as Topic↗

Oncology and narrative time.

Oncologists encounter the uncertainty of time horizons in their patients' lives. Although American oncologists are given a cultural mandate to instill hope in the therapeutic narratives they create with patients, uncertainty leads them to expressions of time without horizons or of time with highly foreshortened horizons as they seek to create for patients an experience of immediacy rather than of chronology. The distinctiveness of the American pattern is highlighted through comparison with Japanese exemplar cases and stories of therapeutic practices in oncology. Concepts drawn from narrative analysis of temporality and the construction of the therapeutic plot are employed.

Anecdotes as Topic↗

Volition as narrative: understanding motivation in chronic illness.

This paper expands the current concept of volition in the Model of Human Occupation. The present version views personal causation, values, and interests as traits that determine choices to engage in occupations. Through a detailed investigation of the life histories of two persons with psychiatric disorders, this paper illustrates how volition is embedded in a personal narrative. Two features of narratively organized volition are highlighted: (a) how narrative places decisions and actions within a plot, thus giving them meaning in the context of a whole life, and (b) how the personal narrative motivates the person by serving as a context for choosing and action. Thus, the paper illustrates how persons seek to narrate their lives and live their life narratives.

Chronic Disease↗

The terrible adventure of rehabilitation.

Friendship with patients, caregivers are taught during their professional training, is to be avoided. Yet the capacity for friendship--to be "a person who emerges in her personhood and not simply as a professional"--may be crucial to effective therapy.

Empathy↗

Proliferation-associated nucleolar antigen P120: a prognostic marker in node-negative breast cancer.

BACKGROUND: P120 is a nucleolar proliferation antigen found in rapidly dividing cells and in a variety of malignancies. METHODS: Our purpose was to determine whether P120 expression is a prognostic factor for patients with node-negative breast cancer by testing pathologic material from 90 patients for P120 immunoreactivity, histologic grade, and estrogen receptors. RESULTS: P120 was detected in 52 of the 90 specimens (58%). Node-negative cancer patients with tumors that did not express the P120 antigen had a significantly better overall survival rate than node-negative cancer patients with tumors that did express P120 (92% vs 69%; p = 0.035). Histologic studies indicated that 36 tumors were grade I, 28 were grade II, and 26 were grade III. The presence of P120 correlated significantly with the nuclear grade of the tumor: 73% of grade III tumors, 64% of grade II tumors, and 42% of grade I tumors stained positive for P120 (p = 0.033). The correlation between nuclear grade and overall survival rate was also significant (grade 1, 94%; grade II, 79%; grade III, 58%); (p = 0.003). No significant correlation was found between P120 expression and estrogen receptors. Multivariate analysis shows that P120 expression and histologic grade together are the strongest predictors of survival. CONCLUSIONS: The biologic marker P120 may play an important role in determining which patients with node-negative cancer will benefit most from adjuvant therapy.

Antigens, Neoplasm↗

Incorporation of ethnographic methods in occupational therapy assessment.

Many constructs of interest to occupational therapists can only be studied through qualitative methods. Such constructs include meaning of activity or the illness experience and the context in which these occur. The purpose of this paper is to describe how ethnographic methods used in research can be generalized and applied to clinical practice. Ethnography is compared with other qualitative research approaches and a model clinical ethnographic assessment process is described.

Activities of Daily Living↗

Anthropology, occupational therapy, and action research.

This paper describes the research process and methodology used in the American Occupational Therapy Association/American Occupational Therapy Foundation Clinical Reasoning Study. This study examined the clinical reasoning of occupational therapists through a 2-year ethnography of therapists at one hospital site. The research was innovative in several important respects. One important innovation was a combined ethnographic and action research design that involved collaboration between the research team and those therapists being studied. Therapists who were research subjects became actively involved in examining and reflecting on their own practice through group analysis of videotaped sessions with clients. One outcome of this action research component was that the study served as both a research and a staff development project.

Clinical Competence↗

What is clinical reasoning?

This paper offers a concept of clinical reasoning that differs from many of the traditional definitions of clinical reasoning in occupational therapy and the health professions in general. Here, clinical reasoning in occupational therapy is described as a largely tacit, highly imagistic, and deeply phenomenological mode of thinking. It is argued that clinical reasoning involves more than the ability to offer explicit reasons that justify clinical decisions because it is also based on tacit understanding and habitual knowledge gained through experience. Clinical reasoning also involves more than a simple application of theory, particularly theory as understood in the natural sciences, because complex clinical tasks often require that the therapist improvise a treatment approach that addresses the unique meaning of disability as it relates to a particular patient.

Clinical Competence↗

The narrative nature of clinical reasoning.

Narrative reasoning is a central mode of clinical reasoning in occupational therapy. Therapists reason narratively when they are concerned with disability as an illness experience, that is, with how a physiological condition is affecting a person's life. In this paper, narrative reasoning is contrasted with propositional reasoning, and two kinds of narrative thinking are examined. The first is the use of narrative as a mode of speech that can be contrasted with biomedical discourse, in which disability is framed as physical pathology. The second involves the creation rather than the telling of stories. Therapists try to "emplot" therapeutic encounters with patients, that is, to help create a therapeutic story that becomes a meaningful short story in the larger life story of the patient.

Clinical Competence↗

Coumarin (1,2-benzopyrone) enhances DR and DQ antigen expressions by peripheral blood mononuclear cells in vitro.

Coumarin (1,2-benzopyrone) is a natural substance that appears to have some clinical activity against renal cell carcinoma and malignant melanoma. Preliminary evidence from in vitro and in vivo studies suggests that coumarin possesses immunomodulatory activity. It was reported previously that coumarin therapy resulted in augmented DR antigen expression by peripheral blood monocytes in cancer patients. The purpose of the present study was to examine the effects of coumarin on DR and DQ antigen expression by normal donor peripheral blood mononuclear cells in vitro. Using monoclonal antibody labeling techniques and FACS analysis, it was shown that both DR and DQ antigen expression by peripheral blood mononuclear cells were enhanced over controls after 48 hours of exposure to coumarin. While monocytes normally express these antigens, enhanced expression is consistent with an activated state. These results support the hypothesis that coumarin acts, at least in part, through immune augmentation.

Cells, Cultured↗

Whistleblowing.

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Ethics, Nursing↗