Biomedical subjects

T Rosengart

Publications and source records attributed to T Rosengart.

5 recordsLinked to original sources

PubMed2000

High-level expression of Egr-1 and Egr-1-inducible genes in mouse and human atherosclerosis.

To understand the mRNA transcript profile in the human atherosclerotic lesion, RNA was prepared from the fibrous cap versus adjacent media of 13 patients undergoing carotid endarterectomy. cDNA expression arrays bearing 588 known genes indicated that lesions express unexpectedly high levels of the early growth response gene, Egr-1 (NGFI-A), a zinc-finger transcription factor that modulates a cluster of stress-responsive genes including PDGF and TGF-beta. Expression of Egr-1 was an average of 5-fold higher in the lesion than in the adjacent media, a result confirmed by RT-PCR, and many Egr-1-inducible genes were also strongly elevated in the lesion. Time-course analyses revealed that Egr-1 was not induced ex vivo. Immunocytochemistry indicated that Egr-1 was expressed prominently in the smooth muscle-actin positive cells, particularly in areas of macrophage infiltration, and in other cell types, including endothelial cells. Induction of atherosclerosis in LDL receptor-null mice by feeding them a high-fat diet resulted in a progressive increase in Egr-1 expression in the aorta. Thus, induction of Egr-1 by atherogenic factors may be a key step in coordinating the cellular events that result in vascular lesions.

Animals↗

PubMed1997

Circumvention of anti-adenovirus neutralizing immunity by administration of an adenoviral vector of an alternate serotype.

Effective gene transfer and expression following repetitive administration of adenoviral (Ad) vectors in experimental animals is limited by anti-Ad neutralizing antibodies. Knowing that anti-Ad humoral immunity is serotype-specific, we hypothesized that anti-Ad neutralizing immunity could be circumvented using Ad vectors of different serotypes (Ad2, Ad5) within the same subgroup (C) to transfer and express beta-glucuronidase (beta glu) in the lung. Sprague-Dawley rats received an intratracheal administration of either Ad2 beta glu or Ad5 beta glu, and, 14 days later, repeat administration of either the same vector or a vector of a different serotype. Analysis of serum and bronchoalveolar lavage fluid following initial vector administration demonstrated systemic and local serotype-specific neutralizing antibodies. For both the Ad2 and Ad5 vectors, beta glu expression 24 hr following the second administration of the same serotype was < 30% of that of naive animals. In contrast, beta glu expression 24 hr following second administration of a different serotype Ad vector was similar to expression at 24 hr of naive animals receiving a single administration (Ad5 beta glu followed by Ad2 beta glu, as well as Ad2 beta glu followed by Ad5 beta glu; p > 0.2 both comparisons). Although the alternative serotype bypassed anti-Ad neutralizing immunity, persistence of expression was reduced compared to that following administration to naive animals. Compatible with this observation, systemic administration of the same vectors to C57B1/6 mice demonstrated induction of cytotoxic T lymphocytes directed against the beta glu transgene, as well as products of the Ad genome. Interestingly, intratracheal administration of vectors with different serotypes and different transgenes to rats resulted in longer expression (but still not normalized) compared to that achieved with vectors of different serotypes but the same transgene. These observations demonstrate that alternate use of Ad vectors from different serotypes within the same subgroup can circumvent anti-Ad humoral immunity to permit effective gene transfer after repeat administration, although the chronicity of expression is limited, likely by cellular immune process directed against both the transgene and viral gene products expressed by the vector.

Adenoviridae↗

PubMed1996

Elective bedside tracheostomy in the intensive care unit.

BACKGROUND: Tracheostomy is a frequently performed procedure, and historically has had a high reported complication rate. This has led some authors to suggest that a tracheostomy should be done only in the operating room (OR). Concerns regarding the hazards of transporting critically ill patients to the OR may inhibit the use of tracheostomy. Bedside tracheostomy in the Intensive Care Unit (ICU) has been shown to be safe, but this concept has not been widely accepted. STUDY DESIGN: We retrospectively reviewed consecutive patients undergoing tracheostomy over a four-year period and compared the safety of elective beside tracheostomy with OR tracheostomy. RESULTS: We studied 536 patients who underwent tracheostomy during the four years, in 470 of whom the procedures were elective. Of these, 66 percent were done at the bedside without an anesthesiologist present. For the 311 patients who underwent bedside tracheostomy, the complication rate was 8.7 percent compared to 9.4 percent of 159 patients undergoing OR tracheostomy (p values were not significant). No deaths were directly associated with tracheostomy procedures, although the overall hospital mortality rate for these patients was 59 percent. CONCLUSIONS: A tracheostomy can safely be performed in an ICU without requiring transport of the patient to the operating suite, thereby eliminating the hazards of transport.

Adolescent↗

PubMed1995

Effect of tumor necrosis factor-alpha on a cell line transformed by a secreted form of human fibroblast growth factor-1 gene and on its parental cell line.

In the present study we characterized the responses of the cell line HST-alpha, stably transformed by a secreted form of human fibroblast growth factor-1 (acidic FGF) gene, and its parental NIH 3T3 cell line to recombinant murine (rMu) TNF-alpha. Treatment of HST-alpha cells with rMu TNF-alpha can significantly reduce the number of foci formed in the in vitro transformation assay. In the presence of the RNA polymerase inhibitor actinomycin-D, the transformed HST-alpha cell is more susceptible to the cytotoxicity of rMu TNF-alpha than is its parental NIH 3T3 cell. The median lethal concentrations (LC50) of rMu TNF-alpha to HST-alpha cell and NIH 3T3 cell were 0.35 ng/ml and 4.56 ng/ml respectively. These results demonstrated that the introduction of a single oncogene or a growth factor gene to a cell can change the cell's response to cytokines.

3T3 Cells↗

PubMedDate not supplied

Cost containment in cardiac surgery: results with a critical pathway for coronary bypass surgery at the New York hospital-Cornell Medical Center.

PURPOSE: A multidisciplinary project was undertaken at The New York Hospital-Cornell Medical Center to develop critical pathways for open-heart surgery to help reduce cost, shorten hospital length of stay (LOS), and streamline patient care. METHODS: A critical pathway for elective coronary artery bypass grafting instituted on March 1, 1995, was developed through a cooperative effort involving surgeons, anesthesiologists, nurses, social workers, physical therapists, nutritionists, and patient case managers. Prospective data collected on consecutive patients forming a critical pathway group (n = 114) over a 6-month period were compared with retrospective data on consecutive patients forming a cohort group (n = 382) who underwent elective coronary artery bypass grafting in 1994. RESULTS: The critical pathway group of patients experienced a significantly shorter total hospital LOS (7.7 +/- 2.3 days vs 11.1 +/- 6 days, p < 0.0001) and shorter intensive care unit LOS (1.5 +/- 0.9 days vs 2.0 +/- 2.8 days, p < 0.0001). Direct costs were computed by use of hospital charges multiplied by the Medicare cost-to-charge ratio. Mean hospital direct cost (ancillary resources) was $1181 lower in the critical pathway group when compared with the control group (p < 0.0001). The postoperative mortality and readmission rates were similar for the two groups of patients. CONCLUSIONS: The ongoing analysis of cost, LOSs, and outcomes has made possible a process of continuous quality improvement on the cardiothoracic service in which further areas for improvement are identified and studied. The use of a critical pathway for elective coronary artery bypass grafting at our institution significantly reduced hospital LOS and direct costs while maintaining the overall quality of patient care.

Coronary Artery Bypass↗