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Biomedical subjects

Michael Rubinstein

Publications and source records attributed to Michael Rubinstein.

11 recordsLinked to original sources
PubMed2006

A physical linkage between cystic fibrosis airway surface dehydration and Pseudomonas aeruginosa biofilms.

A vexing problem in cystic fibrosis (CF) pathogenesis has been to explain the high prevalence of Pseudomonas aeruginosa biofilms in CF airways. We speculated that airway surface liquid (ASL) hyperabsorption generates a concentrated airway mucus that interacts with P. aeruginosa to promote biofilms. To model CF vs. normal airway infections, normal (2.5% solids) and CF-like concentrated (8% solids) mucus were prepared, placed in flat chambers, and infected with an approximately 5 x 10(3) strain PAO1 P. aeruginosa. Although bacteria grew to 10(10) cfu/ml in both mucus concentrations, macrocolony formation was detected only in the CF-like (8% solids) mucus. Biophysical and functional measurements revealed that concentrated mucus exhibited properties that restrict bacterial motility and small molecule diffusion, resulting in high local bacterial densities with high autoinducer concentrations. These properties also rendered secondary forms of antimicrobial defense, e.g., lactoferrin, ineffective in preventing biofilm formation in a CF-like mucus environment. These data link airway surface liquid hyperabsorption to the high incidence of P. aeruginosa biofilms in CF via changes in the hydration-dependent physical-chemical properties of mucus and suggest that the thickened mucus gel model will be useful to develop therapies of P. aeruginosa biofilms in CF airways.

Biofilms↗
PubMed2006

Adsorption-induced scission of carbon-carbon bonds.

Covalent carbon-carbon bonds are hard to break. Their strength is evident in the hardness of diamonds and tensile strength of polymeric fibres; on the single-molecule level, it manifests itself in the need for forces of several nanonewtons to extend and mechanically rupture one bond. Such forces have been generated using extensional flow, ultrasonic irradiation, receding meniscus and by directly stretching a single molecule with nanoprobes. Here we show that simple adsorption of brush-like macromolecules with long side chains on a substrate can induce not only conformational deformations, but also spontaneous rupture of covalent bonds in the macromolecular backbone. We attribute this behaviour to the fact that the attractive interaction between the side chains and the substrate is maximized by the spreading of the side chains, which in turn induces tension along the polymer backbone. Provided the side-chain densities and substrate interaction are sufficiently high, the tension generated will be strong enough to rupture covalent carbon-carbon bonds. We expect similar adsorption-induced backbone scission to occur for all macromolecules with highly branched architectures, such as brushes and dendrimers. This behaviour needs to be considered when designing surface-targeted macromolecules of this type-either to avoid undesired degradation, or to ensure rupture at predetermined macromolecular sites.

Journal Article↗
PubMed2006

Flow-enhanced epitaxial ordering of brush-like macromolecules on graphite.

Long-range orientational order in monolayers of brush-like macromolecules was achieved during spreading of a polymer melt on the surface of highly oriented pyrolytic graphite. The combination of wetting-induced flow and epitaxial adsorption of poly(n-butylacrylate) side chains on graphite led to the formation of large domains of uniaxially oriented rodlike molecules. The domain size varied from ca. 1 to 10 microm which is noticeably larger than the submicrometer-sized mosaic domains typically observed upon adsorption from solution. The increase in the degree of order is attributed to the flow-enhanced diffusion of the macromolecules within spreading monolayers which facilitates the epitaxial alignment of the large macromolecules. The diffusion coefficient was shown to increase linearly with the spreading rate. Even though the ordering occurred during flow, no correlation was observed between the molecular orientation and the flow direction. Thus, the role of the flow was not to induce the molecular orientation but to facilitate the intrinsic ordering process. This finding can inspire and lead to new strategies for constructing large scale ordered structures on surfaces.

Journal Article↗
PubMed2005

Molecular visualization of conformation-triggered flow instability.

A new type of flow fingering instability was observed in monolayer-thick polymer films as they spread on a solid substrate. Tracing the movement of individual molecules by atomic force microscopy enabled us to follow the development of the flow instability on the molecular level and to understand the underlying physical mechanism. The fingering instability was observed to be triggered by conformational changes of brushlike macromolecules in response to the pressure gradient driving the flow.

Journal Article↗
PubMed2004

Molecular motion in a spreading precursor film.

Spreading of a polymer drop on a solid substrate was monitored with molecular resolution. Three characteristic rates, i.e., the spreading rate of the precursor film D(spread)=(3.9+/-0.2)x10(3) nm(2)/s, the flow-induced diffusion rate of molecules within the film D(induced)=1.3+/-0.1 nm(2)/s, and the thermal diffusion coefficient of single molecules D(therm)</=0.10+/-0.03 nm(2)/s, were independently measured. Since D(spread)>>D(induced), the plug flow of polymer chains was identified as the main mass-transport mechanism of spreading with an insignificant contribution from the molecular diffusion.

Journal Article↗
PubMed2003

The cardiac access longitudinal study. A study of access to invasive cardiology among African American and white patients.

OBJECTIVES: We sought to identify factors contributing to racial disparity in the receipt of coronary angiography (CA). BACKGROUND: Numerous studies have demonstrated that African American patients are less likely to receive needed diagnostic and therapeutic coronary procedures than white patients. This report summarizes the methods and findings of a study linking medical records with patient and physician interviews to address racial disparities in the utilization of CA. METHODS: This is a retrospective, cross-sectional study conducted in three urban hospitals in Maryland. A total of 9,275 medical records were reviewed, representing all 7,058 cardiac patients admitted in a two-year period. We identified 2,623 patients who, according to American College of Cardiology guidelines, were candidates for receiving CA. A total of 1,669 patients (721 African Americans and 948 whites) and 74% of their physicians were successfully interviewed. Multivariate and hierarchical multivariate logistic regression were used to construct a model of receipt of CA within one year of the hospitalization. RESULTS: The unadjusted odds of white patients receiving CA was three times greater than the odds for African American patients (odds ratio [OR] 3.0, 95% confidence interval [CI] 2.4 to 3.7). Adjusting for patients' clinical and social characteristics resulted in a 13% reduction in the OR for race. Adjusting for physician and health care system characteristics reduced the OR by 43%, to 1.7 (95% CI 1.3 to 2.4). CONCLUSIONS: Racial disparity in the utilization of CA is a function of differences in the health care system "context" in which African American and white patients obtain care, combined with differences in the specific clinical characteristics of patients.

Adult↗
PubMed2003

Explaining racial differences in receipt of coronary angiography: the role of physician referral and physician specialty.

The authors examine three hypotheses regarding race differences in utilization of coronary angiography (CA): (1) patients with a cardiology consultation are more likely to obtain a referral for CA, (2) African American patients are less likely to have a cardiology consultation, and (3) among patients referred for CA, there is no difference by race in receipt of the procedure. To determine if they obtained a referral for or received CA, 2.623 candidates for CA were followed. Multivariate models were estimated using logistic regression. Cardiology consultation was associated with referral for CA (OR = 5.1, p < .001). White patients had higher odds of cardiology consultation (OR = 2.2, p < .001). The racial disparity was reduced among patients who received a referral (OR = 1.4, p < .05). Researchers must eliminate racial differences in access to specialty care and variation in referral patterns by physician specialty, and efforts must be targeted to those specialties where greater disparities exist.

Black or African American↗
PubMed2002

Polymeric nanogels produced via inverse microemulsion polymerization as potential gene and antisense delivery agents.

Polymeric nanogel vectors were developed for cellular gene and antisense delivery. Inverse microemulsion polymerization was utilized to synthesize biocompatible nanogels with controlled size, morphology, and composition. The chemical composition, size, polydispersity, stability, and swelling behavior of the nanogels were investigated by NMR, light scattering, transmission electron microscopy, and atomic force microscopy. The cell viability, uptake, and physical stability of nanogel-DNA complexes were evaluated under physiological conditions. Monodisperse nonionic and cationic nanogels were produced with controllable sizes ranging from 40 to 200 nm in diameter. The nanogels demonstrated extended stability in aqueous media and exhibited low toxicity in cell culture. Cationic nanogels formed monodisperse complexes with oligonucleotides and showed enhanced oligonucleotide uptake in cell culture. The nanogels synthesized in this study demonstrate potential utility as carriers of oligonucleotides and DNA for antisense and gene delivery.

Acrylates↗
PubMed2002

Physician referral patterns and race differences in receipt of coronary angiography.

OBJECTIVE: This study addresses the following research questions: (1) Is race a predictor of obtaining a referral for coronary angiography (CA) among patients who are appropriate candidates for the procedure? (2) Is there a race disparity in obtaining CA among patients who obtain a referral for the procedure? STUDY SETTING: Three community hospitals in Baltimore, Maryland. STUDY DESIGN: We abstracted hospital records of 7,927 patients from three hospitals to identify 2,653 patients who were candidates for CA. Patients were contacted by telephone to determine if they received a referral for CA. Logistic regression was used to assess whether racial differences in obtaining a referral were affected by adjustment for several potential confounders. A second set of analyses examined race differences in use of the procedure among a subsample of patients that obtained a referral. PRINCIPAL FINDINGS: After controlling for having been hospitalized at a hospital with in-house catheterization facilities, ACC/AHA (American College of Cardiology/American Heart Association) classification, sex, age, and health insurance status, race remained a significant determinant of referral (OR = 3.0, p < .05). Additionally, we found no significant race differences in receipt of the procedure among patients who obtained a referral. CONCLUSIONS: Our results demonstrate that race differences in utilization of CA tend to occur during the process of determining the course of treatment. Once a referral is obtained, African American patients are not less likely than white patients to follow through with the procedure. Thus, future research should seek to better understand the process by which the decision is made to refer or not refer patients.

Black or African American↗