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Biomedical subjects

S Sullivan

Publications and source records attributed to S Sullivan.

At least 37 records · Page 2Linked to original sources
PubMed2000

Phylogenetics of flowering plants based on combined analysis of plastid atpB and rbcL gene sequences.

Following (1) the large-scale molecular phylogeny of seed plants based on plastid rbcL gene sequences (published in 1993 by Chase et al., Ann. Missouri Bot. Gard. 80:528-580) and (2) the 18S nuclear phylogeny of flowering plants (published in 1997 by Soltis et al., Ann. Missouri Bot. Gard. 84:1-49), we present a phylogenetic analysis of flowering plants based on a second plastid gene, atpB, analyzed separately and in combination with rbcL sequences for 357 taxa. Despite some discrepancies, the atpB-based phylogenetic trees were highly congruent with those derived from the analysis of rbcL and 18S rDNA, and the combination of atpB and rbcL DNA sequences (comprising approximately 3000 base pairs) produced increased bootstrap support for many major sets of taxa. The angiosperms are divided into two major groups: noneudicots with inaperturate or uniaperturate pollen (monocots plus Laurales, Magnoliales, Piperales, Ceratophyllales, and Amborellaceae-Nymphaeaceae-Illiciaceae) and the eudicots with triaperturate pollen (particularly asterids and rosids). Based on rbcL alone and atpB/rbcL combined, the noneudicots (excluding Ceratophyllum) are monophyletic, whereas in the atpB trees they form a grade. Ceratophyllum is sister to the rest of angiosperms with rbcL alone and in the combined atpB/rbcL analysis, whereas with atpB alone, Amborellaceae, Nymphaeaceae, and Illiciaceae/Schisandraceae form a grade at the base of the angiosperms. The phylogenetic information at each codon position and the different types of substitutions (observed transitions and transversions in the trees vs. pairwise comparisons) were examined; taking into account their respective consistency and retention indices, we demonstrate that third-codon positions and transitions are the most useful characters in these phylogenetic reconstructions. This study further demonstrates that phylogenetic analysis of large matrices is feasible.

Base Sequence↗
PubMed2000

Optimization of cationic lipid/DNA complexes for systemic gene transfer to tumor lesions.

Intravenous (i.v.) administration of cationic lipid N-[( 1-(2-3-dioleyloxy)propyl)]-N-N-N-trimethylammonium chloride (DOTMA)-based transfection complexes in mice with subcutaneous squamous cell tumors yielded plasmid delivery and expression in tumor lesions. The efficiency of gene transfer in tumors was significantly lower than in the lung. This was consistent with low plasmid levels associated with the tumor, suggesting that plasmid delivery to the tumor site was a limiting factor. Lowering the lipid/DNA charge ratio from 5:1 to 0.8:1 (+/-) did not change DNA levels in tumor but significantly reduced DNA levels in lung. However, expression levels were significantly reduced in both tissues at lower lipid/DNA charge ratios. Complexes prepared from small unilamellar liposomes gave significantly lower expression levels in the lungs but similar expression levels in tumors when compared to complexes prepared from larger unilamellar liposomes. The small liposome complexes were better tolerated than large liposome complexes. Varying the cationic lipid to colipid (cholesterol or DOPE) molar ratio from 4: 1 to 1: 1 significantly reduced expression levels in both tumor and lung. Cationic lipid substitution, using a cholesterol cationic lipid, diethyldiamino-carbamyl-cholesterol instead of DOTMA, produced reduced expression in all other tissues except tumor. Incorporation of PEG into preformed transfection complexes reduced DNA delivery to lung, increased circulation half-life, and enhanced DNA delivery to tumor. In a lung metastatic mouse tumor model, where the accessibility of the i.v. administered transfection complexes to tumor lesions should be less challenging, DOTMA: CHOL complexes (4: 1 lipid to colipid molar ratio, 3: 1 +/- lipid to plasmid charge ratio) were preferentially localized in tumor lesions. These data demonstrate that systemic gene transfer to distal tumor sites by lipid/ DNA complexes may be limited by low plasmid delivery. Modifying the chemical surface properties of transfection complexes enhanced both DNA delivery and expression in tumor and is one approach that may overcome limitations.

Animals↗
PubMed1999

Promoting tobacco cessation in primary care practice.

Promoting tobacco cessation is an important part of the work of clinicians and staff in primary care practice. This article describes the significant public health impact of helping patients quit using tobacco through the use of an effective clinic-based intervention. The most effective strategies are to develop organization commitment, ask every patient about tobacco use at every visit and document it, advise all tobacco users to quit, assess readiness to quit, provide at least brief behavioral counseling, provide follow-up soon after quit date, conduct at least basic evaluations of each component of the process, and assess the quit rate for the practice as a whole.

Ambulatory Care↗
PubMed1999

Remodeling of an acellular collagen graft into a physiologically responsive neovessel.

Surgical treatment of vascular disease has become common, creating the need for a readily available, small-diameter vascular graft. However, the use of synthetic materials is limited to grafts larger than 5-6 mm because of the frequency of occlusion observed with smaller-diameter prosthetics. An alternative to synthetic materials would be a biomaterial that could be used in the design of a tissue-engineered graft. We demonstrate that a small-diameter (4 mm) graft constructed from a collagen biomaterial derived from the submucosa of the small intestine and type I bovine collagen has the potential to integrate into the host tissue and provide a scaffold for remodeling into a functional blood vessel. The results obtained using a rabbit arterial bypass model have shown excellent hemostasis and patency. Furthermore, within three months after implantation, the collagen grafts were remodeled into cellularized vessels that exhibited physiological activity in response to vasoactive agents.

Animals↗
PubMed1999

Systemic inhibition of tumor growth and tumor metastases by intramuscular administration of the endostatin gene.

Tumors require ongoing angiogenesis to support their growth. Inhibition of angiogenesis by production of angiostatic factors should be a viable approach for cancer gene therapy. Endostatin, a potent angiostatic factor, was expressed in mouse muscle and secreted into the bloodstream for up to 2 weeks after a single intramuscular administration of the endostatin gene. The biological activity of the expressed endostatin was demonstrated by its ability to inhibit systemic angiogenesis. Moreover, the sustained production of endostatin by intramuscular gene therapy inhibited both the growth of primary tumors and the development of metastatic lesions. These results demonstrate the potential utility of intramuscular delivery of an antiangiogenic gene for treatment of disseminated cancers.

Animals↗
PubMed1998

Inhibition of eosinophil rolling and recruitment in P-selectin- and intracellular adhesion molecule-1-deficient mice.

To determine the relative in vivo importance of endothelial expressed adhesion molecules to eosinophil rolling, adhesion, and transmigration, we have induced eosinophilic peritonitis using ragweed allergen in P-selectin-deficient, intracellular adhesion molecule-1 (ICAM-1)-deficient and control wild-type mice. Circulating leukocytes visualized by intravital microscopy exhibited reduced rolling and firm adhesion in P-selectin-deficient mice and reduced firm adhesion in ICAM-1-deficient mice. Eosinophils exhibited reduced rolling and firm adhesion to endothelium in P-selectin-deficient mice. Eosinophil recruitment in P-selectin-deficient mice ( approximately 75% inhibition of eosinophil recruitment) and ICAM-1-deficient mice ( approximately 67% inhibition of eosinophil recruitment) was significantly reduced compared with wild-type mice. Eosinophil recruitment was not completely inhibited in P-selectin/ICAM-1 double-mutant mice (eosinophil recruitment inhibited approximately 62%). However, pretreatment of P-selectin/ICAM-1-deficient mice with an anti-vascular cell adhesion molecule (VCAM) antibody induced near complete inhibition of eosinophil recruitment. Overall, these studies show that eosinophil rolling and firm adhesion is significantly reduced in P-selectin-deficient mice and that P-selectin, ICAM-1, and VCAM are important to eosinophil peritoneal recruitment after ragweed challenge.

Animals↗
PubMed1998

Malignant mixed Müllerian tumors of the uterus: a clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 44 cases.

AIM: The authors retrospectively analyzed the prognostic significance of p53, mdm-2, DNA ploidy, S-phase fraction (SPF), and traditional clinical and pathologic factors in patients with malignant mixed Müllerian tumors (MMMT) of the uterus. METHODS: Between 1970 and 1995, 44 uterine tumors were diagnosed as MMMT (21 stage I, 2 stage II, 10 stage III, and 11 stage IV). Thirty-two were homologous type and 12 were heterologous type. DNA flow cytometry and immunohistochemical analysis for p53 and mdm-2 overexpression were performed on paraffin-embedded archival tissue. RESULTS: 68% of the tumors were nondiploid and 61% had an SPF greater than 10%. Sixty-one percent overexpressed p53 and 25% were mdm-2-positive. Furthermore, 91% of the tumors had a mitotic count greater than 10/10 hpf and 95% had high-grade cytologic atypia. Twenty-seven (61%) patients died of tumor and 6 (14%) died of intercurrent disease. Eleven (25%) patients are alive with no evidence of disease. The median follow-up for patients still alive was 59 months (range, 28-178 months). The overall 5-year survival rate was 38%. In a univariate analysis that included stage, histologic type, DNA ploidy, SPF, p53, mdm-2, mitotic index, and age, and with survival as the end point, only stage reached statistically prognostic significance. CONCLUSION: The majority of the tumors had obvious signs of aggressiveness such as high grade, high mitotic count, nondiploid pattern, high SPF, and overexpression of p53. This study found that stage is the most important prognostic factor for survival in MMMTs of the uterus.

Aged↗
PubMed1998

Inhibition of pulmonary eosinophilia in P-selectin- and ICAM-1-deficient mice.

Adhesion molecule expression by pulmonary endothelial cells is considered to play an important role in the recruitment of circulating leukocytes to sites of inflammation in the lung. We have used P-selectin- and intercellular adhesion molecule type 1 (ICAM-1)-deficient mice to determine whether these adhesion molecules are important to pulmonary eosinophil recruitment after allergen challenge. There was a significant inhibition of lung tissue eosinophil recruitment in ICAM-1-deficient mice (approximately 84% inhibition compared to wild-type mice) and P-selectin-deficient mice (approximately 67% inhibition compared to wild-type mice) 3 h after allergen challenge. The number of bronchoalveolar lavage (BAL) eosinophils in P-selectin-deficient and ICAM-1-deficient mice was also significantly reduced compared with wild-type mice. Levels of BAL eosinophil peroxidase (EPO) were significantly lower in ICAM-1-deficient mice (0.21 +/- 0.03 EPO units) compared with wild-type mice (3.34 +/- 0.65 EPO units). There was no significant difference in the degree of inhibition of eosinophil recruitment in ICAM-1-deficient mice at the three time points (3, 12, and 24 h) of study after allergen challenge. However, in P-selectin-deficient mice there was a decline in the degree of inhibition of eosinophil recruitment from 3 h (67% inhibition) and 12 h (72% inhibition) postchallenge, to 24 h postchallenge (38% inhibition), suggesting that other adhesion molecules may be playing a more prominent role than P-selectin at later time points. These studies suggest an important role for ICAM-1 and P-selectin in eosinophil recruitment to the lung after allergen challenge.

Animals↗
PubMed1997

A simple, inexpensive applicator for irradiation of localized areas of the vagina with intracavitary brachytherapy.

PURPOSE: To describe the construction of a simple, inexpensive applicator for irradiation of localized areas of the vagina with intracavitary brachytherapy. METHODS AND MATERIALS: It was desirable to avoid an interstitial implant in an elderly patient with a stage T2 vaginal cancer. The final phase of radiation therapy was delivered with a custom made intracavitary cylinder that allowed the high-dose area to be limited to the portion of the vagina at high risk for residual disease. The applicator was fabricated from a clear cast acrylic (Lucite) rod with dimensions 3.5 cm diameter x 5.0 cm long. The applicator contained 11 parallel grooves, each 1.8 mm deep x 2.2 mm wide, machined along the surface of the cylinder parallel its long axis at 1.0 cm increments. Plastic needles (15 gauge) were inserted into the grooves along the surface of the acrylic cylinder and held in place with heat shrink tubing. The applicator was easily inserted and positioned without anesthesia. Standard low dose rate 192Ir ribbons were inserted into the plastic needles after positioning the applicator in the vagina. RESULTS: Construction of this applicator system requires a few weeks notice and approximately $150. Fabrication of the grooved cylinder is a routine task for a workshop with a milling machine. A step-by-step description of how to construct and use the applicator is provided along with the telephone numbers of commercial vendors to call to order all necessary materials. CONCLUSION: This article describes a simple, inexpensive method for constructing a customized vaginal applicator that can be used to treat a limited area of the vagina with intracavitary brachytherapy.

Aged↗
PubMed1997

Intention-to-treat analysis in randomized trials: who gets counted?

This article discusses the rationale and implications associated with the selection and use of analysis strategies for randomized clinical trials as they relate to protocol deviations. The topics addressed specifically are the conceptual and methodologic approaches and biases of clinical efficacy and effectiveness assessment. Examples are provided that highlight the consequences of different analytic strategies, particularly regarding intention-to-treat analysis. Favored by statisticians intention-to-treat analysis seeks to answer the question, "Is it better to adopt a policy of treatment A if possible, with deviations if necessary, or a policy of treatment B if possible, with deviations if necessary?" This is a relevant question, sometimes more relevant than "Is treatment A better than treatment B?" The authors suggest that different analytic strategies may be more or less appropriate depending on the intended audience.

Drug Therapy↗
PubMed1997

Environmental Awareness, Economic Orientation, and Farming Practices: A Comparison of Organic and Conventional Farmers

/ This study examines similarities and differences between organic and conventional farmers. We explore the factors that underlie farmers' conservation attitudes and behaviors, including demographic and farm characteristics, awareness of and concern for environmental problems associated with agriculture, economic orientation toward farming, and self-reported conservation practices. A series of intensive personal interviews was conducted with 25 farmers in Washtenaw County, Michigan, USA, using both qualitative and quantitative survey methods. The findings indicate that both groups of farmers share a concern for the economic risks associated with farming, although the organic farmers reported a significantly greater concern for long-term sustainability and a greater willingness to incur present risk to gain future benefits. Organic farmers expressed a greater awareness of and concern for environmental problems associated with agriculture. Organic farmers also scored significantly higher on a multifaceted measure of conservation practices, although both groups had a fairly high adoption rate. Implications of these findings are discussed, relative to economic risks of farming, implications for new farmers, effectiveness of conservation education and government programs, and impact of farm size and crop diversity.KEY WORDS: Environmental attitudes; Conservation behaviors; Organic farming; Agricultural sustainability

Journal Article↗