Rectification in donor-acceptor molecular junctions.

We perform density functional theory (DFT) calculations on molecular junctions consisting of a single molecule between two Au(111) electrodes. The molecules consist of an alkane or aryl bridge connecting acceptor, donor or thiol endgroups in various combinations. The molecular geometries are optimized and wavefunctions and eigenstates of the junction calculated using the DFT method, and then the electron transport properties for the junction are calculated within the non-equilibrium Green's function (NEGF) formalism. The current-voltage or i(V) characteristics for the various molecules are then compared. Rectification is observed for these molecules, particularly for the donor-bridge-acceptor case where the bridge is an alkane, with rectification being in the same direction as the original findings of Aviram and Ratner (1974 Chem. Phys. Lett. 29 277-83), at least for relatively large negative and positive applied bias. However, at smaller bias rectification is in the opposite direction and is attributed to the lowest unoccupied orbital associated with the acceptor group.

Theoretical study of ethynylbenzene adsorption on Au(111) and implications for a new class of self-assembled monolayer.

Density functional calculations of the adsorption of ethynylbenzene on the Au(111) surface show that, after cleavage of the C-H bond, the terminal carbon makes a strong covalent bond to the surface. The bond energy is shown to be about 70 kcal.mol(-1) with the fcc hollow site being most stable and the molecule oriented perpendicular to the surface. Adsorption without elimination of hydrogen is also possible via a hydrogen 1,2 shift to form a vinylidene surface-bound species, or opening of the C-C triple bond and adsorption through the two carbon atoms in a flat conformation. The reaction energy for formation of the surface-bound vinylidene is estimated to be 5 kcal.mol(-1) exothermic relative to the isolated ethynylbenzene and gold substrate.

Enzyme-replacement therapy in mucopolysaccharidosis I.

BACKGROUND: Mucopolysaccharidosis I is a lysosomal storage disease caused by a deficiency of the enzyme alpha-L-iduronidase. We evaluated the effect of enzyme-replacement therapy with recombinant human alpha-L-iduronidase in patients with this disorder. METHODS: We treated 10 patients with mucopolysaccharidosis I (age, 5 to 22 years) with recombinant human alpha-L-iduronidase at a dose of 125,000 U per kilogram of body weight given intravenously once weekly for 52 weeks. The patients were evaluated at base line and at 6, 12, 26, and 52 weeks by detailed clinical examinations, magnetic resonance imaging of the abdomen and brain, echocardiography, range-of-motion measurements, polysomnography, clinical laboratory evaluations, measurements of leukocyte alpha-L-iduronidase activity, and urinary glycosaminoglycan excretion. RESULTS: Hepatosplenomegaly decreased significantly in all patients, and the size of the liver was normal for body weight and age in eight patients by 26 weeks. The rate of growth in height and weight increased by a mean of 85 and 131 percent, respectively, in the six prepubertal patients. The mean maximal range of motion of shoulder flexion and elbow extension increased significantly. The number of episodes of apnea and hypopnea during sleep decreased 61 percent. New York Heart Association functional class improved by one or two classes in all patients. Urinary glycosaminoglycan excretion decreased after 3 to 4 weeks of treatment; the mean reduction was 63 percent of base-line values. Five patients had transient urticaria during infusions. Serum antibodies to alpha-L-iduronidase were detected in four patients. CONCLUSIONS: In patients with mucopolysaccharidosis I, treatment with recombinant human alpha-L-iduronidase reduces lysosomal storage in the liver and ameliorates some clinical manifestations of the disease.

Comparison of different lymphoma cell purging modalities: An experimental study with K422 lymphoma cells.

Blood-derived autografts from patients with non-Hodgkin's lymphoma (NHL) are frequently contaminated with clonogenic lymphoma cells. In order to obtain a more efficient lymphoma cell depletion from the transplants we compared the efficiency of different purging techniques: B-cell-directed depletion, CD34+ selection by immunomagnetic beads (IMB selection) or by immunoadsorption with a biotin-avidin column (BAC selection). Furthermore, two combination approaches were investigated: IMB selection after B-cell depletion as well as BAC selection after B-cell depletion. To assess purging efficiency, fluorescence-tagged (PKH26) K422 follicular NHL cells were admixed to the respective samples of leukapheresis products. BAC selection following B-cell depletion compared to BAC selection alone showed no significant differences in CD34+ purity (77 +/- 12. 5% vs. 70.7 +/- 5.4%) (mean +/- SE) or CD34+ recovery (35.3 +/- 8.5% vs. 32.8 +/- 10.4%), but a significantly (p < 0.005) higher lymphoma cell purging efficiency (log 4.32 +/- 0.15 vs. log 2.92 +/- 0.19). IMB selection following B-cell depletion and IMB selection alone resulted in a CD34+ purity of 40.8 +/- 8.7% and 64.7 +/- 7.9%, a CD34+ recovery of 47.2 +/- 8.3% and 26.5 +/- 6.5% and a lymphoma cell purging efficiency of log 3.68 +/- 0.16 and log 3.48 +/- 0.21, respectively. Lymphoma cell purging efficiency after either CD34 selection method alone as well as after either double purging method was significantly higher (p < 0.0005 and p < 0.00005, respectively) compared to B-cell depletion alone (log 1.44 +/- 0.23). Our results argue for the combination of different purging modalities to achieve a maximal lymphoma cell depletion.

Clinical evidence for hepatitis B transmission resulting from corneal transplantation.

PURPOSE: Two cases of hepatitis B virus (HBV) infection after penetrating keratoplasty are presented. METHODS: An extensive clinical and serologic investigation of these two transplant recipients was performed. In addition, the medical histories, autopsy reports, and specimens of blood from the two deceased corneal tissue donors were retrieved and studied. RESULTS: Serum from both donors was positive for hepatitis B surface antigen; the clinical history and serologic testing of both recipients strongly suggest that the HBV infection in each case was acquired from donor corneal tissue. CONCLUSION: To our knowledge, these are the first documented cases of HBV infection after corneal transplantation. Eye banks should continue to screen donors for HBV.

Retroviral transfer of the multidrug resistance-1 gene into lineage-committed and primitive hemopoietic cells.

Transfer of the multidrug resistance-1 (MDR1) gene to hemopoietic cells for myeloprotection against cytostatic agents is a new and rapidly developing field in "cancer gene therapy." Before clinical application, safety and efficacy criteria need to be met. The retroviral producer cell lines and the retroviral supernatant need to be tested for replication-competent retrovirus and contamination with adventitious agents. The cell source needs to contain sufficient hemopoietic cells with repopulating ability. We used CD34(+)-selected mobilized peripheral blood progenitor cells (PBPC) for MDR1 transductions in order to obtain a favorable vector to target cell ratio. An analysis of 249 patients who had undergone PBPC harvesting revealed that primarily solid tumor and non-Hodgkin's lymphoma patients are eligible for CD34+ selection. They can be expected to retain sufficient CD34+ cells for rapid and sustained engraftment after myeloablative therapy if the CD34+ cell loss (approximately 50%) during the procedure is taken into account. Clinical MDR1 gene therapy protocols focus on these two patient groups. Next we characterized MDR1 gene transfer into lineage-committed and primitive hemopoietic cells. Provirus-specific polymerase chain reactions showed a high efficiency gene transfer into colony-forming-units granulocyte-macrophage and long-term culture cells. The level of the conferred P-glycoprotein expression was estimated by fluorescence-activated cell sorting analysis to be up to 3 log above mock-transduced controls. The cobblestone area forming cell assay, which is a stroma-dependent long-term culture assay measuring frequencies of stem cell subsets in a limiting-dilution set-up, allowed demonstration of sustained expression of the MDR1 gene in the progeny of primitive hemopoietic cells. This is a favorable basis for a clinical MDR1 gene therapy trial.

Successful medical management of Acanthamoeba keratitis.

Seven patients with documented Acanthamoeba keratitis were treated with prolonged and intensive triple antiamoebic therapy consisting of topical neomycin-polymyxin B-gramicidin, propamidine isethionate 0.1%, and miconazole nitrate 1%. Additionally, five patients were treated with topical corticosteroids. Six of seven patients were cured of Acanthamoeba keratitis with medical therapy alone, one patient required therapeutic penetrating keratoplasty to eradicate the infection. Two patients underwent penetrating keratoplasty to improve their vision after medical therapy. Our series differs from previous reports in that triple antiamoebic therapy was used in all seven patients and was successful in both early and advanced cases of Acanthamoeba keratitis. Prolonged and intensive topical therapy with these three antiamoebic drugs may be an effective mode of therapy for Acanthamoeba keratitis.

Keratitis and contact lens wear: a review.

The most feared complications of contact lens wear are keratitis and infectious corneal ulceration. This article first defines terms for the clinical practitioner, and then describes and illustrates clinical presentation and management.

Intraocular lens damage associated with posterior capsulotomy: a comparison of intraocular lens designs and four different Nd:YAG laser instruments.

A comparison of intraocular lens damage associated with four different Nd:YAG laser instruments was performed using polarized light, scanning electron microscopy, and a qualitative measurement of optical resolution. Five intraocular lens designs, each of which provided a different separation between the intraocular lens and a model of the posterior capsule, were tested with each laser instrument. There was no statistically significant difference in the frequency of lens pitting caused by each laser. Intraocular lenses designed with a theoretical separation of 0.25 mm or more between the lens and the posterior capsule sustained no damage with any of the laser instruments used in this study.

The problems and benefits of associating academic medical centers with health-maintenance organizations.

The growth of prepaid medical-care programs has caused the leaders of a number of academic medical centers to begin to have an increased interest in affiliating with or sponsoring centers in prepaid programs -- otherwise known as health-maintenance organizations (HMOs)--is motivated by a number of potential benefits. An HMO may provide an academic medical center with an additional source of patients for teaching and research; generate additional revenue; increase resources for education in primary care; increase the exposure of students, residents, and faculty to the characteristics of prepaid medical practice; and improve the delivery of health services locally. Issues of importance to the academic medical center include the pros and cons of sponsorship of, as opposed to affiliation with, an HMO and the additional costs attributable to medical education in the HMO setting. Problems may arise between HMOs and medical centers as a result of disparate styles of practice, the high cost of clinical services at the medical center, and the differing perspectives of HMO and medical-center policy makers.