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Biomedical subjects

Barry Stein

Publications and source records attributed to Barry Stein.

At least 19 recordsLinked to original sources
PubMed2006

Morphology of hybrid polystyrene-block-poly(ethylene oxide) micelles: analytical ultracentrifugation and SANS studies.

Morphology and structure of aqueous block copolymer solutions based on polystyrene-block-poly(ethylene oxide) (PS-b-PEO) of two different compositions, a cationic surfactant, cetyl pyridinium chloride (CPC), and either platinic acid (H2PtCl6.6H2O) or Pt nanoparticles were studied using a combination of analytical ultracentrifugation (AUC), transmission electron microscopy (TEM), and small angle neutron scattering (SANS). These studies combining methods contributing supplemental and analogous structural information allowed us to comprehensively characterize the complex hybrid systems and to discover an isotope effect when H2O was replaced with D2O. In particular, TEM shows formation of both micelles and larger aggregates after incorporation of platinic acid, yet the amount of aggregates depends on the H2PtCl6.6H2O concentration. AUC reveals the presence of micelles and micellar clusters in the PS-b-PEO block copolymers solution and even larger (supermicellar) aggregates in hybrids (with CPC). Conversely, SANS applied to D2O solutions of the similar species indicates that micelles are spherical and no other micellar species are found in block copolymer solutions. To reconcile the SANS and AUC data, we carried out AUC examination of the corresponding D2O block copolymer solutions. These measurements demonstrate a pronounced isotope effect on micelle aggregation and micelle size, i.e., no micelle aggregation in D2O solutions, revealing good agreement of AUC and SANS data.

Calorimetry, Differential Scanning↗
PubMed2006

Surveillance for recurrent bladder cancer using a point-of-care proteomic assay.

CONTEXT: At least 50% of patients with a history of bladder cancer have recurrences, so rigorous surveillance is necessary. Cystoscopy is standard but can fail to detect some bladder cancers, so a urine test is frequently part of the evaluation. OBJECTIVE: To investigate whether a point-of-care proteomic test that measures the nuclear matrix protein NMP22 in voided urine could improve detection of recurrence during monitoring of patients with a history of bladder cancer. DESIGN, SETTING, AND PATIENTS: From September 2001 to February 2002, 23 academic, private practice, and hospital facilities in 9 US states prospectively enrolled 668 consecutive patients with a history of bladder cancer in this cross-sectional study. Patients provided a voided urine sample for analysis of NMP22 protein and cytology prior to cystoscopy. MAIN OUTCOME MEASURES: Diagnosis of bladder cancer recurrence, based on cystoscopy with biopsy, was accepted as the reference standard. The performance of the NMP22 test was compared with voided urine cytology as an aid to detection. Testing for the NMP22 tumor marker was conducted in a blinded manner. RESULTS: Bladder cancer was diagnosed in 103 patients. Cystoscopy alone identified 91.3% of the cancers (94/103; 95% confidence interval [CI], 84.1%-95.9%). The combination of cystoscopy with the NMP22 assay detected 99.0% of the malignancies (102/103; 95% CI, 94.7%-100%; P = .005). The NMP22 assay detected 8 of 9 cancers that were not visualized during initial cystoscopy, including 7 that were high-grade. The sensitivity and specificity of the NMP22 test alone were 49.5% (51/103; 95% CI, 39.5%-59.5%) and 87.3% (493/565; 95% CI, 84.2%-89.9%), respectively. Voided cytology detected only 3 of the malignancies missed during initial cystoscopy and did not significantly increase the sensitivity of cystoscopy (94.2%; 95% CI, 87.7%-97.8%; P = .08). CONCLUSION: The noninvasive point-of-care assay for elevated urinary NMP22 protein can increase the ability to detect recurrent bladder cancer, with test results available during the patient visit.

Adult↗
PubMed2006

Laparoscopy for colectomy accelerates restoration of bowel function when using patient controlled analgesia.

PURPOSE: A standardized care plan incorporating patient-controlled analgesia with iv morphine and a non-accelerated feeding schedule following colectomy was used to compare return of bowel function and hospital discharge times following surgery done by laparoscopy or laparotomy METHODS: Thirty-eight patients were assigned to undergo either laparoscopic or laparotomy colon resection. Postoperative analgesia was achieved with patient-controlled analgesia with iv morphine. General anesthesia and perioperative care were standardized, and a traditional surgical and nursing care program was implemented. Gastrointestinal function (time from surgery to return of passage of flatus and presence of bowel movements), pain intensity (visual analogue scale) at rest, on coughing and on mobilization, amount of morphine used, and criteria for discharge and length of hospital stay were recorded. RESULTS: Bowel movements resumed earlier in the laparoscopic group (P < 0.05), but not passage of flatus. No significant relationship was found between the amount of morphine used and return of bowel function. Cumulative morphine consumption during the first two postoperative days was similar in both groups. Where a trend towards lower postoperative visual analogue scale scores was observed in the laparoscopic group, visual analogue scale scores on coughing were lower in the laparoscopic vs laparotomy group only during the first 24 hr (P < 0.05). Length of hospital stay was significantly shorter in the laparoscopic group (P < 0.05), although times to meet discharge criteria were similar in both groups. CONCLUSIONS: When patient-controlled analgesia with morphine and a traditional perioperative program are used, a laparoscopic approach to colon surgery promotes earlier restoration of bowel function and more rapid hospital discharge in comparison to resection by laparotomy.

Aged↗
PubMed2006

Toremifene for the prevention of prostate cancer in men with high grade prostatic intraepithelial neoplasia: results of a double-blind, placebo controlled, phase IIB clinical trial.

PURPOSE: A randomized, double-blind, dose finding, placebo controlled, parallel group clinical study was done to determine the incidence of prostate cancer in men with high grade prostatic intraepithelial neoplasia treated with toremifene. MATERIALS AND METHODS: A total of 514 patients with high grade prostatic intraepithelial neoplasia and no evidence of prostate cancer on screening biopsy were randomized to 20, 40 or 60 mg toremifene, or placebo daily for 12 months. Patients underwent re-biopsy at 6 and 12 months. RESULTS: The number of evaluable patients, that is those with 1 on study biopsy who were compliant, was 447. The cumulative risk of prostate cancer was decreased in patients on 20 mg toremifene compared with placebo (24.4% vs 31.2%, p <0.05). The annualized rate of prevention was 6.8 cancers per 100 men treated. In patients with no biopsy evidence of cancer at baseline and 6 months, the 12-month incidence of prostate cancer was decreased by 48.2% with 20 mg toremifene compared with placebo (9.1% vs 17.4%, p <0.05). The 20 mg dose was most effective but cumulative and 12-month incidences of prostate cancer were lower for each toremifene dose vs placebo with a cumulative risk of 29.2% and 28.1%, and a 12-month incidence of 14.3% and 13.0% for 40 and 60 mg, respectively. Gleason scores were similar across treatments. The overall incidence of drug related and serious adverse events did not differ between any of the toremifene groups and the placebo group. CONCLUSIONS: Toremifene decreased the incidence of prostate cancer by 1 year and had a tolerability profile comparable to that of placebo in a high risk population.

Adult↗
PubMed2006

Nanoparticle-templated assembly of viral protein cages.

Self-assembly of regular protein surfaces around nanoparticle templates provides a new class of hybrid biomaterials with potential applications in medical imaging and in bioanalytical sensing. We report here the first example of efficiently self-assembled virus-like particles (VLPs) having a brome mosaic virus protein coat and a functionalized gold core. The present study indicates that functionalized gold particles can initiate VLP assembly by mimicking the electrostatic behavior of the nucleic acid component of the native virus. These VLP constructs are symmetric, with the protein stoichiometry and packaging properties indicating similarity to the icosahedral packing of the capsid. Moreover, a pH-induced swelling transition of the VLPs is observed, in direct analogy to the native virus.

Biomimetic Materials↗
PubMed2006

Quantum dot encapsulation in viral capsids.

Incorporation of CdSe/ZnS semiconductor quantum dots (QDs) into viral particles provides a new paradigm for the design of intracellular microscopic probes and vectors. Several strategies for the incorporation of QDs into viral capsids were explored; those functionalized with poly(ethylene glycol) (PEG) can be self-assembled into viral particles with minimal release of photoreaction products and enhanced stability against prolonged irradiation.

Capsid↗
PubMed2006

The effect of lectins on Cryptosporidium parvum oocyst in vitro attachment to host cells.

The influence of lectins on Cryptosporidium parvum oocyst agglutination and on attachment to both fixed Madin Darby Canine Kidney (MDCK) cells and fixed HCT-8 (human colorectal epithelial) cells was examined. Oocyst cell wall characteristics were examined by transmission electron microscopy. Lectin-free oocysts were shown to adhere equally to both MDCK cells and HCT-8 cells. In MDCK cells, the addition of 1-25 microg/ml Codium fragile lectin, 10 microg/ml Maclura pomifera lectin, 10 microg/ml Helix pomatia lectin, and 10-200 microg/ml Artocarpus integrifolia lectin significantly increased attachment to at least 1 of the cell cultures as compared to oocysts incubated without any lectin. The lectin-enhanced attachment was reversed by co-incubation of lectin treated-oocysts with 250 mM of each specific sugar (for a given lectin). In agglutination assays, concentrations as low as 0.5 microg/ml of C. fragile, M. pomifera, and A. integrifolia lectin agglutinated oocysts within 60 min. Finally, in TEM samples, colloidal gold conjugated-lectins from A. integrifolia, C. fragile, H. pomatia, and M. pomifera attached to oocysts, and this could be competitively inhibited by a lectin-specific sugar. This suggests that C. parvum oocysts are highly reactive to N-acetyl galactosamine-binding lectins and that the presence of N-acetyl-galactosamine containing molecules on oocysts can potentially help in oocyst attachment to host cells.

Agglutination↗
PubMed2005

Metalated diblock and triblock poly(ethylene oxide)-block-poly(4-vinylpyridine) copolymers: understanding of micelle and bulk structure.

The paper provides new insights into the structure of Pt-containing diblock and triblock copolymers based on poly(ethylene oxide) (PEO) and poly(4-vinylpyridine) (P4VP), using a combination of atomic force microscopy (AFM), X-ray diffraction (XRD), transmission electron microscopy (TEM), and anomalous small-angle X-ray scattering (ASAXS). Parallel studies using methods contributing supplemental structural information allowed us to comprehensively characterize sophisticated polymer systems during metalation and to exclude possible ambiguity of the data interpretation of each of the methods. AFM and TEM make available the determination of sizes of the micelles and of the Pt-containing micelle cores, respectively, while a combination of XRD, TEM, and ASAXS reveals Pt-nanoparticle size distributions and locations along with the structural information about the polymer matrix. In addition, for the first time, ASAXS revealed the organization of Pt-nanoparticle-filled diblock and triblock copolymers in the bulk. The nanoparticle characteristics are mainly determined by the type of block copolymer system in which they are found: larger particles (2.0-3.0 nm) are formed in triblock copolymer micelles, while smaller ones (1.5-2.5 nm) are found in diblock copolymer micelles. This can be explained by facilitated intermicellar exchange in triblock copolymer systems. For both systems, Pt nanoparticles have narrow particle size distributions as a result of a strong interaction between the nanoparticle surface and the P4VP units inside the micelle cores. The pH of the medium mainly influences the particle location rather than the particle size. A structural model of Pt-nanoparticle clustering in the diblock PEO-b-P4VP and triblock P4VP-b-PEO-b-P4VP copolymers in the bulk was constructed ab initio from the ASAXS data. This model reveals that nearly spherical micellar cores of about 10 nm in diameter (filled with Pt nanoparticles) aggregate forming slightly oblate hollow bodies with an outer diameter of about 40 nm.

Micelles↗
PubMed2005

Transformations of poly(methoxy hexa(ethylene glycol) methacrylate)-b-(2-(diethylamino)ethyl methacrylate) block copolymer micelles upon metalation.

Micelle transformations upon metalation (i.e., incorporation of metal compounds and metal nanoparticle formation) in poly(methoxy hexa(ethylene glycol) methacrylate)-block-poly((2-(diethylamino)ethyl methacrylate)), PHEGMA-b-PDEAEMA, solutions have been studied using transmission electron microscopy (TEM) and photon correlation spectroscopy (PCS). Three different methods for the formation of metalated micelles are compared: (A) dissolution of the block copolymers in pure water followed by incorporation of platinic acid (H(2)PtCl(6).6H(2)O), (B) micellization in acidic molecular solutions of block copolymers induced by interaction of the protonated amino groups with the PtCl(6)(2)(-) ions, and (C) incorporation of metal species in pH-induced micelles. The latter method leads to well-defined metalated micelles of 22-25 nm diameter containing nanoparticles with diameters of 1.3-1.5 nm. No nanoparticle aggregation is observed. Good agreement is obtained for the sizes of the platinic acid-containing micelles assessed by TEM and PCS.

Light↗
PubMed2005

Core-shell nanostructures from single poly(N-vinylcaprolactam) macromolecules: stabilization and visualization.

Formation of core-shell poly(N-vinylcaprolactam) (PVCL) single-molecule nanostructures due to interaction of PVCL with metal ions was studied using transmission electron microscopy, 13C NMR, and light scattering. This study demonstrates that addition of CoCl2 to PVCL in its globular conformation yields unimolecular core-shell polymer particles with the core decorated with Co(II) ions. The crucial condition for formation of well-defined unimolecular nanostructures is the presence of stable globular aggregates in aqueous solution. Moreover, the metal ions should have a sufficiently high coordination number (higher than 2) to provide a cross-linking and stabilization of the core.

Caprolactam↗
PubMed2005

Diel infection of a cyanobacterium by a contractile bacteriophage.

Light was found to strongly influence the infection of a freshwater cyanobacterium (Synechococcus elongatus PCC 7942) by a contractile DNA phage named AS-1. Phage progeny production was correlated with the amount of light in the laboratory and occurred in a diel pattern under natural light. At least one effect of light on AS-1 infection is at the level of adsorption.

Adsorption↗
PubMed2005

Packaging of gold particles in viral capsids.

In-vitro self-assembly conditions known to result in generating infectious virions have been used in vitro to reassemble bromovirus capsid proteins around negatively charged gold nanoparticles cores. We discuss here the optical properties (elastic light scattering) and the influence of the core size and of the functional moiety on the resulting virus-like particles. Our results indicate that the formation of a closed shell, as opposed to an amorphous protein coat, does occur and that the shell/core interactions can be tuned using different coatings on the nanoparticle core. Such studies may lead to real-time monitoring of viral traffic on the scale of a single virus, as well as to the possibility of chemical sensing along the intracellular and intercellular viral pathways and contribute to a better understanding of the virus transport and cellular compartmentalization.

Bromovirus↗
PubMed2004

Functional polymer colloids with ordered interior.

Polymer colloids with internal ordering were synthesized using hydrolytic condensation of octadecyl-dimethyl(3-trimethoxysilylpropyl)ammonium chloride (ODMACl) and a mixture of ODMACl and the trisodium salt of the triacetic acid N-(trimethoxysilylpropyl)ethylenediamine (TANED). The structure and morphology of these colloids were studied with small-angle X-ray scattering, transmission electron microscopy, nuclear magnetic resonance, sedimentation in ultracentrifuge; and other methods. When polymer colloids are obtained from a single precursor (ODMACl), their local structure, molecular weight characteristics, and morphology strongly depend on the reaction conditions, while lamellar ordering remains nearly unaffected. Use of a mixture of cationic and anionic silanes (ODMACl and TANED) as precursors in hydrolytic condensation results in novel zwitterionic copolymer colloids with two-dimensional hexagonal packing. Interaction of the ODMACl quaternary ammonium groups with the three carboxy groups of TANED leads to replacement of sodium and chloride ions and formation of gegenions, resulting in a molar ratio ODMACl:TANED = 3:1 (each TANED molecule contains three carboxy groups). Due to their ordered interior, polyODMACl (PODMACl) and PODMACl-TANED colloids can be used as templates for controlled positioning of nanoparticles within these colloids. For example, lamellar ordering controls Pt nanoparticle formation within PODMACl colloids providing Pt nanoparticle alignment within the lamellar structure. Loading of PODMACl-TANED colloids with iron salts followed by pH increase results in the formation of iron oxide nanoparticles located within PODMACl-TANED cylinders.

Journal Article↗
PubMed2003

Gold nanoparticles as spectroscopic enhancers for in vitro studies on single viruses.

Gold particles with diameters between 2.5 and 4.5 nm have been introduced in the inner cavity of an icosahedral brome mosaic virus. The optical properties of single gold-marked virions have been tested in-vitro with respect to the characteristic plasmon polariton resonance. The shift in the plasmon polariton resonance of a single Au particle encapsulated in a virus with respect to a free particle in solution indicates a close interaction between the basic residues on the inner wall of the capsid and the negative surface charge of the particle. Incorporation of a pair of Au particles, approximately 4 nm diameter, is shown to be a frequent event. In this case, the dependence of the two-particle surface plasmon spectrum on the interparticle distance and the strong particle/capsid wall interaction suggest that, in the future, it will be possible to use encapsulated Au particles to track changes in the viral capsid volume in real-time and in a physiological environment.

Bromovirus↗
PubMed2002

A multiinstitutional, concurrent chemoradiation trial of strontium-89, estramustine, and vinblastine for hormone refractory prostate carcinoma involving bone.

BACKGROUND: Estramustine phosphate (EMP) and vinblastine have radiosensitizing properties and significant activity against hormone refractory prostate carcinoma. Strontium-89 is a palliative agent that acts as a selective radiation source for bone metastasis. The combination of EMP, vinblastine, and strontium-89 was developed to exploit the potential for radiosynergy. PATIENTS AND METHODS Forty-four patients at the Brown Oncology Group affiliated hospitals were treated with oral EMP 600 mg/m2 daily on Weeks 1-4 and 7-10, vinblastine 4 mg/m2 intravenously once each week on Weeks 1-4 and 7-10, and strontium-89 2.2 MBq/kg on Day 1. Courses were repeated every 12 weeks. Response assessment was based on a change in the serum prostate specific antigen (PSA) levels, correlated with change in measurable disease and bone scan appearance. RESULTS: A greater than or equal to 50% decline in PSA for at least 6 weeks was observed in 21 patients (48%, 95% confidence interval, 33-62%). Median duration of response was 23 weeks (range, 6-70.8 weeks). The median survival was 13 months with 1- and 2-year survival rates of 55% and 25%, respectively. After completion of protocol therapy, a retrospective review showed that only nine patients received subsequent palliative external beam radiation after progression. CONCLUSIONS: The addition of strontium-89 to the regimen of EMP and vinblastine can be delivered safely and in repeated doses, provides effective palliation, and may decrease the need for future radiation therapy. A randomized trial is necessary to quantify these effects.

Administration, Oral↗
PubMed2002

Nipple connective tissue and its development: insights from the K14-PTHrP mouse.

Parathyroid hormone-related protein (PTHrP) regulates a wide variety of developmental processes. Keratin 14 (K14) promoter-mediated overexpression of PTHrP in the epidermis during development converts the entire murine ventral skin to hairless nipple-like skin. In this report, we characterize the morphology and processes that influence the development of nipple connective tissue. The connective tissue of the nipple displayed increased levels of proteoglycans, and collagen bundles with atypical morphology, as well as increased numbers of mast cells, capillaries, nerve fibers and dermal melanocytes. The unique characteristics of nipple connective tissue were not present until mice reach 3-4 weeks of age. The adult male K14-PTHrP mouse has a less dramatic ventral skin phenotype, and does not manifest a nipple-like dermis. Ovariectomy or orchiedectomy prior to sexual maturity had no impact on the ventral skin of the male or female K14-PTHrP mice, but exposure to androgens in utero repressed many of the nipple-like characteristics in the ventral skin of the female K14-PTHrP mice.

Animals↗