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Biomedical subjects

J W Freeman

Publications and source records attributed to J W Freeman.

At least 73 records · Page 4Linked to original sources

Excess demand and cost relationships among Kentucky nursing homes.

This article examines the influence of excess demand on nursing home costs. Previous work indicates that excess demand, reflected in a pervasive shortage of nursing home beds, constrains market competition and patient care expenditures. According to this view, nursing homes located in underbedded markets can reduce costs and quality with impunity because there is no pressure to compete for residents. Predictions based on the excess demand argument were tested using 1989 data from a sample of 179 Kentucky nursing homes. Overall, the results provide partial support for the excess demand argument. Factors that may counteract the influence of excess demand are considered. Finally, the role of competition in nursing home markets and difficulties associated with making it operational are discussed.

Bed Occupancy↗

Proper focus.

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Attitude of Health Personnel↗

Virtue and longitudinal ethics education in medical school.

This article advances the argument that the inherent virtue/character of the caregiver is an important element in clinical ethical decision making. Virtue should be promoted as an essential component of professional behavior, and specifically emphasized in both medical student education and professional practice.

Bioethics↗

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↗

Easing the edges.

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Communication↗

On consumption.

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Humans↗

Cell cycle regulated expression of nucleolar antigen P120 in normal and transformed human fibroblasts.

Normal and SV40 virus-transformed WI-38 human lung fibroblasts were serum starved and refed, or synchronized by double thymidine block and released from the block. At different time points in the cell cycle, steady state levels of P120 mRNA and P120 protein content of the cells were determined by densitometric scans of Northern and Western blots. At the same time points, [3H]thymidine uptake was measured and flow cytometric analysis performed for DNA content and P120 antigen staining. Levels of P120 protein and P120 mRNA were approximately 4 times greater in non-synchronous, exponentially growing transformed cells than in similarly growing normal cells. Early G1-phase cells, synchronized either with serum deprivation or with metabolic block, contained only a trace amount of P120 protein and mRNA. The P120 gene was transcribed early in G1 and P120 protein synthesis initiated in middle G1. A dramatic increase of P120 protein level occurred in S-phase with a corresponding mRNA peak preceding the P120 protein peak. These results indicate that P120 is overexpressed in transformed WI-38 cells and that P120 is temporally regulated during the cell cycle of both transformed and normal fibroblasts. The dramatic increase in P120 protein expression at the G1 to S boundary suggests that P120 may play a role in the regulation of cell cycle and increased nucleolar activity that is associated with cell proliferation.

Blotting, Western↗

Phorbol dibutyrate and ionomycin improve murine effector cell cytotoxicity.

Simultaneous protein kinase C stimulation with phorbol 12,13-dibutyrate (PDBU) and calcium mobilization with ionomycin (Io) trigger cellular events leading to expression of proliferation-associated genes in human lymphocytes. The effect of a 16-hr exposure to PDBU and Io on the growth and cytotoxic activity of murine splenocytes and tumor-infiltrating lymphocytes (TIL) cocultured with interleukin-2 (IL-2) was studied. PDBU + Io increased the number of cytotoxic effector cells that could be generated in lymphokine-activated killer cells (LAK) cultures (40-fold) and to a lesser extent in TIL (10-fold). DNA synthesis of TIL increased significantly when exposed to PDBU + Io. Also, TIL stimulated with PDBU + Io demonstrated in vitro tumor-specific lytic activity significantly greater than that of control TIL (500 lytic units vs 50). The cell-surface phenotype of TIL treated with PDBU + Io was identical to that of control TIL (> 95% CD-3+, CD-4-, CD-8+). Results of adoptive immunotherapy using splenocytes stimulated by PDBU + Io and cultured in IL-2 were identical to those achieved when standard LAK cultures were used. However, treatment using TIL stimulated by PDBU + Io led to a significant reduction in the number of pulmonary nodules compared to standard TIL. In addition, PDBU + Io-stimulated TIL maintained significant in vivo activity without the need for systemic IL-2 administration. Pharmacologic manipulation of cytotoxic precursor cells is a useful strategy for improving the generation of murine cytotoxic effector cells. By using PDBU + Io, cytotoxic lymphocytes could be generated with improved in vitro and in vivo activity.

Animals↗

Antisense-mediated specific inhibition of P120 protein expression prevents G1- to S-phase transition.

A pentadecadeoxyribonucleotide (5'-AAAGCCCCCCACCAC), complementary to a splice junction site of mRNA for human proliferation-associated nucleolar protein P120, inhibited expression of the P120 gene and the mitogen-induced proliferation of human lymphocytes. The inhibition of P120 gene expression and proliferation was concentration dependent and reached 90% at 200 microM, as measured by [3H]thymidine uptake and by densitometric scanning of Northern (mRNA) and Western (protein) blots of P120. Inhibition was not observed in cells treated with the correspondent nonsense oligomer. P120 antisense oligomer treatment prevented S-phase entry of mitogen-stimulated lymphocytes, as determined by flow cytometric analysis, but did not block G0-G1 transition assessed by morphological blast transformation and induction of [3H]uridine incorporation. Results of this study suggest that P120 expression may be required for the upregulation of nucleolar function necessary for cell proliferation.

Base Sequence↗

Phorbol dibutyrate plus ionomycin improves the generation of cytotoxic T cells from draining lymph nodes of patients with advanced head and neck cancer.

Fifty-one cervical nodes from 19 patients with advanced head and neck cancer were stimulated with phorbol dibutyrate and ionomycin (PDBu + Io) to determine the effect of such stimulation on the generation of cytotoxic T cells and whether this stimulation could bypass the need for autologous tumor stimulation. Lymphocytes stimulated with PDBu + Io demonstrated a sixfold greater in vitro expansion and significantly increased DNA synthesis. Whereas fresh lymphocytes displayed no cytotoxicity, stimulation with PDBu + Io and culture in interleukin-2 (IL-2) led to significant cytotoxicity equivalent to that of lymphocytes stimulated with autologous tumor and IL-2. T cells with the greatest cytotoxicity were generated from patients with nodal metastases. In patients with stage IV tumors, effector cells demonstrating greater lysis of natural killer-resistant targets (Daudi cells) were associated with higher rates of recurrence (50% versus 12%, respectively, p < 0.001). Stimulation with PDBu + Io augments growth and proliferation of lymphocytes from draining lymph nodes and preserves cytotoxicity without the need for autologous tumor. Excluding the need for antigenic stimulation by autologous tumor may prove useful in adoptive immunotherapy procedures.

Antineoplastic Combined Chemotherapy Protocols↗