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Biomedical subjects

Bin Chen

Publications and source records attributed to Bin Chen.

At least 163 records · Page 9Linked to original sources

Photoinduced intramolecular electron transfer and triplet energy transfer in a steroid-linked norbornadiene-carbazole dyad.

Bichromophoric compound 3 beta-((2-(methoxycarbonyl)bicyclo[2.2.1]hepta-2,5-diene-3-yl)carboxy)androst-5-en-17 beta-yl-[2-(N-carbazolyl)acetate] (NBD-S-CZ) was synthesized and its photochemistry was examined by fluorescence quenching, flash photolysis, and chemically induced dynamic nuclear polarization (CIDNP) methods. Fluorescence quenching measurements show that intramolecular electron transfer from the singlet excited state of the carbazole to the norbornadiene group in NBD-S-CZ occurs with an efficiency (Phi SET) of about 14 % and rate constant (kSET) of about 1.6 x 10(7) s-1. Phosphorescence and flash photolysis studies reveal that intramolecular triplet energy transfer and electron transfer from the triplet carbazole to the norbornadiene group proceed with an efficiency (TET + TT) of about 52 % and rate constant (kTET + kTT) of about 3.3 x 10(5) s-1. Upon selective excitation of the carbazole chromophore, nuclear polarization is detected for protons of the norbornadiene group (emission) and its quadricyclane isomer (enhanced absorption); this suggests that the isomerization of the norbornadiene group to the quadricyclane proceeds by a radical-ion pair recombination mechanism in addition to intramolecular triplet sensitization. The long-distance intramolecular triplet energy transfer and electron transfers starting both from the singlet and triplet excited states are proposed to proceed by a through-bond mechanism.

Androstenes↗

A tandem metal carbene cyclization-cycloaddition approach to the pseudolaric acids.

An approach toward the synthesis of the antifungal and cytotoxic pseudolaric acids based on the tandem metal carbene cyclization-cycloaddition reaction is described. Using this strategy, the advanced intermediate 3a bearing three of the four stereocenters of the target molecules has been synthesized. The substrate-controlled diastereoselectivity of the tandem carbene cyclization-cycloaddition was preferential for the undesired diastereomer, but reagent control through the use of Hashimoto's chiral rhodium catalyst Rh(2)(S-BPTV)(4) reversed the selectivity in favor of 3a. Ring opening of the oxabicyclic nucleus to give a hydroxycycloheptene has been demonstrated in a model study.

Antifungal Agents↗

Nanosized particles of organically modified silica as microreactors to enhance the regioselectivity in the photocycloaddition of 9-substituted anthracenes.

[reaction: see text] Nanosized particles of modified silica with 3-ammoniumpropyl residue have been prepared and successfully used as microreactors to control the regioselectivity of the photocycloaddition of five 9-substituted anthracences [AnCH(2)N(+)(CH(3))(3)Br(-) (1), AnCH(2)COO(-)Na(+) (2), AnCH(2)CH(2)COOH (3), AnCH(2)OH (4), AnCH(3) (5), where An = 9-anthryl]. While the photocycloaddition of the five substrates in methanol mainly gave rise to their head-to-tail (h-t) photocyclomers, irradiation of 1-4 incorporated in the suspension of the modified silica in methanol almost exclusively yielded the head-to-head (h-h) photocyclomers with high quantum yields.

Journal Article↗

Simulating the nucleation of water/ethanol and water/n-nonane mixtures: mutual enhancement and two-pathway mechanism.

A combination of the aggregation-volume-bias and configurational-bias Monte Carlo algorithms and the umbrella sampling technique was applied to investigate two different binary vapor-liquid nucleation systems: water/ethanol and water/n-nonane. The simulations are able to reproduce the different nonideal nucleation behavior observed experimentally for these two systems, i.e., the mutual enhancement of nucleation rates for water/ethanol mixtures and the two-pathway nucleation for water/n-nonane mixtures. Structural analysis provides microscopic explanations for the observed nucleation behavior. In particular, the simulations show a large and size-dependent surface enrichment of ethanol in the water/ethanol droplets, which confirms the previous experimental interpretation for this system. The immiscibility observed even for small water/n-nonane clusters causes the two-pathway nucleation mechanism.

Journal Article↗

Photodynamic therapy with verteporfin in the radiation-induced fibrosarcoma-1 tumor causes enhanced radiation sensitivity.

Photodynamic therapy (PDT) with verteporfin (lipid form of benzoporphyrin derivative,benzoporphyrin derivative monoacid ring A) was used to treat radiation-induced fibrosarcoma tumors before X-ray treatment. When verteporfin was injected 3 h before light irradiation, the tumor partial pressure of oxygen (pO(2)) rose from a pretreatment value of 2.8 +/- 1 to 15.2 +/- 6.9 mm Hg immediately after light application was complete (P = 0.048). When the optical irradiation was given 15 min after verteporfin injection, the tumor pO(2) decreased slightly after treatment [i.e., 6.8 +/- 1.6 mm Hg (pretreatment) versus 4.1 +/- 0.3 mm Hg (posttreatment)], whereas control tumor pO(2) did not change significantly. In vitro study of the cellular oxygen consumption rate before and after PDT treatment indicated that the consumption rate decreased linearly with delivered optical dose and quantitatively matched the loss of cell viability as measured by a mitochondrial tetrazolium assay. Doppler measurements show that red cell flux is still patent immediately after treatment, indicating that oxygen should still be delivered to the tumor. Computational simulations of the oxygen supply from the vessels and the consumption from mitochondrial activity confirmed that if oxygen consumption is decreased in the presence of unhindered blood flow, the tumor oxygenation should rise, and the hypoxic fraction of the tumor should decrease. Combination treatments with PDT delivered (100 J/cm(2) optical dose, with 1 mg/kg benzoporphyrin derivative monoacid ring A injected 3 h before treatment) after radiation treatment (10 Gy from 300 keV source) were compared with PDT delivered simultaneously with radiation. Tumor regrowth assay showed that the delays to reach double the tumor volume for PDT alone and radiation alone were 2.7 +/- 1.6 and 3.2 +/- 1.7 days, respectively. When radiation was given before PDT, the delay was 5.4 +/- 1.4 days, and when PDT was given at the same time as radiation, the delay was 8.1 +/- 1.5 days. This observation indicates that the combined effect in the latter case was greater than additive (P = 0.049).

Animals↗

Novel espin actin-bundling proteins are localized to Purkinje cell dendritic spines and bind the Src homology 3 adapter protein insulin receptor substrate p53.

We identified a group of actin-binding-bundling proteins that are expressed in cerebellar Purkinje cells (PCs) but are not detected in other neurons of the CNS. These proteins are novel isoforms of the actin-bundling protein espin that arise through the use of a unique site for transcriptional initiation and differential splicing. Light and electron microscopic localization studies demonstrated that these espin isoforms are enriched in the dendritic spines of PCs. They were detected in the head and neck and in association with the postsynaptic density (PSD) of dendritic spines in synaptic contact with parallel or climbing fibers. They were also highly enriched in PSD fractions isolated from cerebellum. The PC espins efficiently bound and bundled actin filaments in vitro, and these activities were not inhibited by Ca2+. When expressed in transfected neuronal cell lines, the PC espins colocalized with actin filaments and elicited the formation of coarse cytoplasmic actin bundles. The insulin receptor substrate p53 (IRSp53), an Src homology 3 (SH3) adapter protein and regulator of the actin cytoskeleton, was identified as an espin-binding protein in yeast two-hybrid screens. Cotransfection studies and pull-down assays showed that this interaction was direct and required the N-terminal proline-rich peptide of the PC espins. Thus, the PC espins exhibit the properties of modular actin-bundling proteins with the potential to influence the organization and dynamics of the actin cytoskeleton in PC dendritic spines and to participate in multiprotein complexes involving SH3 domain-containing proteins, such as IRSp53.

Actin Cytoskeleton↗

Stable transfection of an estrogen receptor beta cDNA isoform into MDA-MB-231 breast cancer cells.

We previously reported stable transfection of estrogen receptor alpha (ERalpha) into the ER-negative MDA-MB-231 cells (S30) as a tool to examine the mechanism of action of estrogen and antiestrogens [J. Natl. Cancer Inst. 84 (1992) 580]. To examine the mechanism of ERbeta action directly, we have similarly created ERbeta stable transfectants in MDA-MB-231 cells. MDA-MB-231 cells were stably transfected with ERbeta cDNA and clones were screened by estrogen response element (ERE)-luciferase assay and ERbeta mRNA expression was quantified by real-time RT-PCR. Three stable MDA-MB-231/ERbeta clones were compared with S30 cells with respect to their growth properties, ability to activate ERE- and activating protein-1 (AP-1) luciferase reporter constructs, and the ability to activate the endogenous ER-regulated transforming growth factor alpha (TGFalpha) gene. ERbeta6 and ERbeta27 clones express 300-400-fold and the ERbeta41 clone express 1600-fold higher ERbeta mRNA levels compared with untransfected MDA-MB-231 cells. Unlike S30 cells, 17beta-estradiol (E2) does not inhibit ERbeta41 cell growth. ERE-luciferase activity is induced six-fold by E2 whereas neither 4-hydroxytamoxifen (4-OHT) nor ICI 182, 780 activated an AP-1-luciferase reporter. TGFalpha mRNA is induced in response to E2, but not in response to 4-OHT. MDA-MB-231/ERbeta clones exhibit distinct characteristics from S30 cells including growth properties and the ability to induce TGFalpha gene expression. Furthermore, ERbeta, at least in the context of the MDA-MB-231 cellular milieu, does not enhance AP-1 activity in the presence of antiestrogens. In summary, the availability of both ERalpha and ERbeta stable breast cancer cell lines now allows us to compare and contrast the long-term consequences of individual signal transduction pathways.

Breast Neoplasms↗

Supramolecular systems as microreactors: control of product selectivity in organic phototransformation.

This Account reviews the developments in microreactor-controlled selectivity in organic phototransformation. Photocycloaddition of alpha,omega-diaryl compounds with long flexible chains within Y-type zeolite and low-density polyethylene films leads to formation of intramolecular cyclomers to the exclusion of intermolecular products. ZSM-5 zeolite, Nafion membranes, and vesicles as hosts direct photosensitized oxidation of alkenes selectively toward either the energy-transfer-mediated or the electron-transfer-mediated products. Zeolites, Nafion membranes, and microemulsions as microreactors remarkably control chemo-, regio-, and stereoselectivity in the photochemical reaction of phenyl phenylacetates, photocycloaddition of anthracenes, and photocyclization of azobenzene and stilbazole.

Journal Article↗

Two new alkaloids from Miliusa cuneata.

Two new isoquinoline alkaloids, 2,10-dimethoxy-3,11-dihydroxy-5,6-dihydroprotoberberine (1) and 1,9-dihydroxy-2,11 -dimethoxy-4,5-dihydro-7-oxoaporphine (2), together with thirteen known alkaloids, were isolated from the ethanolic extracts of the stem and leaves of Miliusa cuneata (Graib). Their structures were elucidated predominantly by spectral evidence.

Annonaceae↗

Sample size determination based on rank tests in clinical trials.

The problem of sample size determination based on three commonly used non-parametric rank based tests, namely, one-sample Wilcoxon's rank sum test, two-sample's Wilcoxon's rank sum test, and the rank-based test for independence is studied. Explicit formulas for variabilities of the test statistics under the alternative hypotheses are derived. Consequently, close forms of power functions of these test statistics are obtained for sample size determination utilizing the concept of higher order polynominal equations. Simulation studies were performed to evaluate the finite samples performance of the derived sample size formulas. The results indicates that the derived methods work well with moderate sample size.

Clinical Trials as Topic↗

A model for the modulation of microvessel permeability by junction strands.

To investigate the effect of junction strands on microvessel permeability, we extend the previous analytical model developed by Fu et al. (1994, J. Biomech. Eng., 116, pp. 502-513), for the interendothelial cleft to include multiple junction strands in the cleft and an interface between the surface glycocalyx layer and the cleft entrance. Based on the electron microscopic observations by Adamson et al. (1998, Am. J. Physiol., 274(43), pp. H1885-H1894), that elevation of intracellular cAMP levels would increase number of tight junction strands, this two-junction-strand and two-pore model can successfully account for the experimental data for the decreased permeability to water, small and intermediate-sized solutes by cAMP.

Animals↗

Quantitative analysis of retinal ganglion cell (RGC) loss in aging DBA/2NNia glaucomatous mice: comparison with RGC loss in aging C57/BL6 mice.

PURPOSE: To quantify the extent and pattern of retinal ganglion cell (RGC) loss in the DBA2/NNia glaucomatous mouse strain as a function of age and compare it with ganglion cell loss in a nonglaucomatous strain. METHODS: All the ganglion cells in retinas of DBA/2NNia and C57/BL6 mice of various ages (five eyes per age group in 3-month intervals from 3 to 18 months of age) were counted. A novel counting method that does not rely on sampling and that uses retrograde labeling of RGCs with Fluorogold (Fluorochrome; Englewood, CO) was used. RGC loss in the glaucomatous DBA/2NNia mouse strain was contrasted to RGC loss in C57 mice at the same ages. The total number of Fluorogold-labeled cells per retina was compared within and among the two strains as a function of age. In addition, RGC density maps were constructed for each retina, and the range of densities for each age group was compared within and among the two strains. IOP in awake, nonsedated DBA/2NNia mice was measured with a rebound tonometer. RESULTS: RGC loss started between 12 and 15 months of age in C57 mice and led to an approximate 46% reduction by 18 months of age. The rate of loss was best approximated by a second-order polynomial curve. In comparison, DBA/2NNia mice also began showing RGC loss at approximately 12 months of age, but it proceeded at a much faster rate, with approximately 64% of their RGCs dying by the 15th month of age but little additional loss thereafter. RGC loss in the DBA animals had a focal pattern that appeared more patchy and showed greater variability than the age-related loss in C57 mice, which was more diffuse. IOP and total retinal area in DBA/2NNia mice began to increase at approximately 6 months of age. IOP normalized after the 12th month of age. CONCLUSIONS: Age-related RGC loss of up to 50% can occur in the C57 mouse by 18 months of age. The loss does not proceed linearly with age, as is often assumed, and differs both in extent and locational pattern from pathologic RGC loss secondary to glaucoma in DBA/2NNia mouse retinas.

Aging↗

Potentiation of photodynamic therapy with hypericin by mitomycin C in the radiation-induced fibrosarcoma-1 mouse tumor model.

Hypericin, a polycyclic quinone obtained from plants of the genus Hypericum, has been shown to be a promising photosensitizer. We investigated the combination of hypericin-photodynamic therapy (PDT) and a bioreductive drug mitomycin C (MMC) in the present study. The radiation-induced fibrosarcoma-1 tumors were exposed to laser light (120 J/cm2 at 595 nm) 24 h after an intravenous injection of hypericin (1 mg/kg). Hypericin-PDT alone significantly decreased tumor perfusion and oxygen tension as demonstrated by India ink staining technique and OxyLite pO2 measurement, respectively. The in vivo-in vitro cell-survival assay revealed about 60% direct tumor cell killing immediately after PDT. No significant delayed tumor cell death was observed after PDT, which suggests that vascular damage does not contribute significantly to the overall tumor cell death. Injection of a 2.5 mg/kg dose of MMC 20 min before light application significantly decreased tumor cell survival and delayed tumor growth compared with PDT or MMC alone. No greater skin reaction was observed after the combination of MMC and PDT than after PDT alone. Our study demonstrates that combining hypericin-PDT with MMC can be effective in enhancing tumor response with little side effect.

Animals↗

Blood flow dynamics after photodynamic therapy with verteporfin in the RIF-1 tumor.

In the present study, the effects of photodynamic therapy (PDT) with verteporfin on tumor blood flow and tumor regrowth were compared as verteporfin distributed in different compartments within the RIF-1 tumor. Tissue distribution of verteporfin was examined by fluorescence microscopy, and blood flow measurements were taken with a laser Doppler system. It was found that, at 15 min after drug administration, when verteporfin was mainly confined within the vasculature, PDT induced a complete arrest of blood flow by 6 h after treatment. PDT treatment at a longer drug-light interval (3 h), which allowed the drug to diffuse to the tumor interstitium, caused significantly less flow decrease, only to 50% of the initial flow in 6 h. A histological study and Hoechst 33342 staining of functional tumor vasculature confirmed the primary vascular damage and the decrease in tumor perfusion. The regrowth rate of tumors treated with 15-min interval PDT was 64% of that of the control group. However, when tumors were treated with 3-h interval PDT, the regrowth rate was not significantly different from that of the control, indicating that only the 15-min interval PDT caused serious damage to the tumor vascular bed. These results support the hypothesis that temporal pharmacokinetic changes in the distribution of the photosensitizer between the tumor parenchyma and blood vessels can significantly alter the tumor target of PDT.

Animals↗

Analyses of the tumour suppressor ING1 expression and gene mutation in human basal cell carcinoma.

The incidence of basal cell carcinoma is the highest among all human malignancies. Epidemiological evidence indicates that ultraviolet radiation is the primary environmental cause for the pathogenesis of basal cell carcinoma. However, the genetic changes caused by ultraviolet radiation that lead to basal cell carcinoma formation remain unclear. We and others have demonstrated that the ING1 (inhibitor of growth 1) tumour suppressor plays an important role in cellular stress response to ultraviolet irradiation, such as DNA repair and apoptosis. This study was designed to investigate whether ING1 is overexpressed and/or mutated in human basal cell carcinoma. Immunohistochemistry, single-strand conformation polymorphism, and DNA sequencing were used to determine the expression and mutational status of the ING1 gene in 54 basal cell carcinoma biopsies. Immunohistochemical staining demonstrated that ING1 is overexpressed in 25% (6/24) human basal cell carcinomas. Single-strand conformation polymorphism and DNA sequencing revealed that only 1 in 54 (1.8%) basal cell carcinoma primaries contained a missense mutation in the ING1 gene. The mutation is located in exon 2 and could thus potentially interfere with the structure of every ING1 isoforms and the functions of the PHD zinc finger motif. Our data indicate that overexpression and mutation of the ING1 gene are infrequent in human basal cell carcinoma.

Adult↗

[Surgical treatment of acute embolism of the upper extremity].

OBJECTIVE: To study the methods of surgical treatment and the prognosis of acute embolism of the upper extremity. METHODS: Balloon catheter embolectomy through the brachial artery was performed in 18 patients with acute embolism of the upper extremity. RESULTS: Both the pulse of the radial and ulnar artery could be palpated in 8 patients, either the pulse of the radial or ulner artery could be palpated in 9 patients. The temperature of the upper extremity was increased in the patient whose embolectomy was performed in the 6th day after onset of the illness. Three patients died postoperatively. CONCLUSIONS: Embolectomy through the brachial artery is an effective method to treat acute embolism of the upper extremity. Elderly and heart and pulmonary diseases are the high risk factors for postoperative death.

Acute Disease↗

Comparison of hexamethylhypericin and tetrabromohypericin to hypericin for their in vivo efficacy as PDT tools.

The present study was performed to evaluate the PDT efficacy, the singlet oxygen yield, and the plasma binding profile of the natural photosensitizer hypericin and two hypericin derivatives, hexamethylhypericin and tetrabromohypericin. All compounds exhibited an excellent 1O2 quantum yield, as documented by TEMP spin trapping experiments. The efficacy of PDT with the different compounds using a P388 lymphoma tumour model was clearly dependent on the interval between drug administration and light irradiation of the tumours. The most effective PDT treatment time was obtained with hypericin (5 mg/kg) using a 30-min drug-light interval, whereas a 24-h interval was optimal for a similar dose of tetrabromohypericin. No significant difference in survival between control animals and animals treated with PDT using tetrabromohypericin (5 mg/kg) was noted when a 30-min, 2- or 6-h interval was used. PDT with hexamethylhypericin (5 mg/kg) using different drug-light intervals was unable to prolong the life span of the tumour-bearing mice. In contrast, a dose of 20 mg/kg hexamethylhypericin, especially when administered 30 min prior to light exposure, produced a profound local reduction of tumour mass and a concomitant significant increase in survival time. The binding of the hypericins to human plasma was evaluated using density-gradient ultracentrifugation. It was found that tetrabromohypericin exhibits an affinity for plasma constituents almost similar to hypericin, in contrast to the more hydrophilic hexamethylhypericin that mainly binds to heavy proteins (e.g. albumin). Since the latter compound showed an efficacy profile similar to hypericin, no correlation could be found between the optimal drug-light interval and the plasma protein binding of the compounds.

Animals↗