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Biomedical subjects

B Li

Publications and source records attributed to B Li.

At least 793 records · Page 44Linked to original sources

Transcallosal circuitry revealed by blocking and disinhibiting callosal input in the cat.

The purpose of this study was to obtain quantitative measures of the influence of callosal input to cells at the area 17/18 border region where transcallosal axons terminate most densely. Single-cell recordings were performed at the area 17/18 border region of the right hemisphere, while gamma-aminobutyric acid (GABA) or its antagonist, bicuculline, were applied to the transcallosal projecting regions of the left hemisphere to either block or overactivate the cells which projected to the neurons at the recording site. The results showed that visually evoked responses of the cells at the area 17/18 border were affected by administration of GABA or bicuculline to the contralateral hemisphere. Blockade of transcallosal input by application of GABA in the left hemisphere diminished the visually evoked responses of 51% of the neurons in the right hemisphere, and led to an increase in response magnitude for 17% of the neurons. Disinhibition of transcallosal input by application of bicuculline increased the evoked activity of 40% of the neurons and diminished the response magnitude of 20% of the neurons in the right hemisphere. GABA and bicuculline failed to show antagonistic effects on some cells. Thirty-two percent of the cells were affected by only one type of drug administration, and 13% of the cells showed either an increase or a decrease in responses after both GABA and then bicuculline administration. This study demonstrated complex interactions between neurons connected by the transcallosal pathway. A model of the transcallosal circuitry was proposed to explain the results.

Animals↗

Application of visual basic in high-throughput mass spectrometry-directed purification of combinatorial libraries.

We present an approach to customize the sample submission process for high-throughput purification (HTP) of combinatorial parallel libraries using preparative liquid chromatography electrospray ionization mass spectrometry. In this study, Visual Basic and Visual Basic for Applications programs were developed using Microsoft Visual Basic 6 and Microsoft Excel 2000, respectively. These programs are subsequently applied for the seamless electronic submission and handling of data for HTP. Functions were incorporated into these programs where medicinal chemists can perform on-line verification of the purification status and on-line retrieval of postpurification data. The application of these user friendly and cost effective programs in our HTP technology has greatly increased our work efficiency by reducing paper work and manual manipulation of data.

Combinatorial Chemistry Techniques↗

Selectin ligands promote ultrasound contrast agent adhesion under shear flow.

Contrast-enhanced ultrasound imaging has shown promise in the field of molecular imaging. This technique relies upon the adhesion of ultrasound contrast agent (UCA) to targeted molecular markers of disease. This is accomplished by coating the surface of the contrast agent with a ligand that specifically binds to the intended molecular marker. Most UCA particles remain in the blood space, and their retention is influenced by the forces imposed by blood flow. For a UCA bound to a molecular target on the vascular endothelium, blood flow imposes a dislodging force that counteracts retention. Additionally, contrast agent adhesion to the molecular marker requires rapid binding kinetics, especially in rapid blood flow. The ability of a ligand:target bond complex to mediate fast adhesion and withstand dislodging force is necessary for efficient ultrasound-based molecular imaging. In the current study, we describe a flow-based adhesion assay which, combined with a novel automated tracking algorithm, enables quick determination of the ability of a targeting ligand to mediate effective contrast agent adhesion. This system was used to explore the adhesion of UCA targeted to the proinflammatory endothelial protein P-selectin via four targeting ligands, which revealed several interesting adhesive behaviors. Contrast agents targeted with glycoconjugate ligands modeled on P-selectin glycoprotein ligand 1 exhibited primarily unstable or transient adhesion, while UCA targeted with an anti-P-selectin monoclonal antibody exhibited primarily firm adhesion, although the efficiency with which these agents were recruited to the target surface was relatively low.

Adhesiveness↗

Direct synthesis and identification of benzo[a]pyrene diol epoxide-deoxyguanosine binding sites in modified oligodeoxynucleotides.

Adducts derived from the reaction of the benzo[a]pyrene metabolite model compound (+)-anti-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene [(+)-BPDE] with the single-stranded oligodeoxynucleotide 5'-d(TATGCGTAT) were obtained according to direct synthesis techniques described earlier [Cosman, M., Ibanez, V., Geacintov, N. E., and Harvey, R. G. (1990) Carcinogenesis 11, 1667-1672]. Four major adducts, involving trans and cis addition (trans/cis adduct ratio approximately 4.5) of (+)-BPDE to the exocyclic amino groups of guanines G4 and G6 (the numbers denote the positions of the guanines counted from the 5'-side) were obtained. These adducts can be separated from one another by reverse-phase high-performance liquid chromatography methods. The site of BPDE binding on either G4 or G6 can be determined from the electrophoresis band patterns on 20% polyacrylamide gels of the BPDE-modified oligonucleotides subjected to the G+A and G Maxam-Gilbert strand cleavage reactions [Maxam, A. M., and Gilbert, W. (1980) Methods. Enzymol. 65, 499-560]. The electrophoresis gel band patterns are different for unmodified DNA and the two different BPDE-modified oligonucleotides because (1) the strand cleavage fragments bearing BPDE residues migrate slower than the corresponding fragments derived from the unmodified oligonucleotide and (2) strand cleavage tends to be inhibited on the 5'-sides of BPDE-modified guanines in the G+A, but not the G reaction.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

Laser pulse-induced photochemical strand cleavage of site-specifically and covalently modified (+)-anti-benzo[a]pyrene diol epoxide-oligonucleotide adducts.

The specificity of the laser pulse-induced photocleavage method [Boles, T. C., and Hogan, M. E. (1986) Biochemistry 25, 3039] for detecting the sites of covalent binding of benzo[a]pyrene diol epoxide in DNA was investigated using site-specifically modified oligonucleotide duplexes d(CTCACAT[G*]TACACTCT).d(GAGAGTGTACATGTGA), where [G*] is the adducted guanine residue (+)-trans-anti-BPDE-N2-dG (anti-BPDE = 7 beta,8 alpha- dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene). The appropriate oligonucleotide strands were 32P-end-labeled, and the duplexes were irradiated with a pulse train of 355 nm Nd:YAG laser pulses (approximately 300 mW/cm2). The products of the photocleavage reaction were analyzed by denaturing gel electrophoresis. The major observed products included the intact oligonucleotide strand that had lost the BPDE residue, and shorter oligonucleotide fragments arising from strand scission at the BPDE-modified guanine residue and at nearby flanking bases. Photocleavage at the BPDE-modified G is dominant (approximately 50 +/- 5% of the sum of all of the shorter oligonucleotide fragments), and cleavage extends to at least 4 bases on the 5'-side, and 7 bases on the 3'-side of the BPDE-modified G residue; the probability of cleavage diminishes with increasing distance from the modified G residue. On the unmodified complementary strand, nonspecific strand cleavage is also observed, but the probability of cleavage is > or = 20 times smaller than at the BPDE-modified G residue on the modified strand. The photocleavage method thus preferentially causes strand scission at the sites of BPDE modification, but the occurrence of strand cleavage with lower probabilities at neighboring sites is also significant.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

Base sequence-dependent bends in site-specific benzo[a]pyrene diol epoxide-modified oligonucleotide duplexes.

The site specifically modified oligonucleotides 5'-d(TCCTCCTG1G2CCTCTC) (I) and 5'-d(CTATG1G2G3TATC) (II) were synthesized with single modified guanine residues at positions G1, G2, or G3, derived from the covalent binding reaction of 7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene ((+)-anti-BPDE) with the exocyclic amino groups of the guanine residues. In denaturing 20% polyacrylamide gels, the electrophoretic mobilities of the (+)-anti-BPDE-modified oligonucleotides I and II are slower than the mobilities of the respective unmodified oligonucleotides and independent of the positions of the BPDE-modified guanines. However, in the double-stranded forms in native 8% polyacrylamide gels, the electrophoretic mobilities of the duplexes with lesions at G2 or G3 are remarkably slower (reductions in mobilities up to approximately 40%) than to duplexes with lesions at G1 and are attributed to physical bends or flexible hinge joints at the sites of the BPDE lesions. These sequence-dependent mobility effects occur whenever the BPDE-modified guanine residues with (+)-trans-stereochemistry are flanked by unmodified G's on the 5'-side. These retarded electrophoretic mobilities are attributed to bending induced by steric hindrance effects involving the bulky 5'-flanking guanines and the pyrenyl residues that are known to point into the 5'-direction relative to the modified G [Cosman, M., et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 1914-1918]. These anomalous electrophoretic mobility effects are not observed in the case of (-)-anti-BPDE-modified sequences I with trans-(-)-anti-BPDE-N2-dG adduct stereochemistry.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

Global methylation profiling of lung cancer identifies novel methylated genes.

Epigenetic changes, including DNA methylation, are a common finding in cancer. In lung cancers methylation of cytosine residues may affect tumor initiation and progression in several ways, including the silencing of tumor suppressor genes through promoter methylation and by providing the targets for adduct formation of polycyclic aromatic hydrocarbons present in combustion products of cigarette smoke. Although the importance of aberrant DNA methylation is well established, the extent of DNA methylation in lung cancers has never been determined. Restriction landmark genomic scanning (RLGS) is a highly reproducible two-dimensional gel electrophoresis that allows the determination of the methylation status of up to 2000 promoter sequences in a single gel. We selected 1184 CpG islands for RLGS analysis and determined their methylation status in 16 primary non-small cell lung cancers. Some tumors did not show methylation whereas others showed up to 5.3% methylation in all CpG islands of the profile. Cloning of 21 methylated loci identified 11 genes and 6 ESTs. We demonstrate that methylation is part of the silencing process of BMP3B in primary tumors and lung cancer cell lines.

Aged↗

Association of air pollution with hospital outpatient visits in Beijing.

Data collected at a community-based hospital in Beijing, China, were analyzed in an assessment of the association of air pollution with daily outpatient visits. Total suspended particle (TSP) measurements were available for 210 d (mean, 388 micrograms/m3; maximum, 1,255 micrograms/m3), and sulfur dioxide (SO2) measurements were available for 2 d (mean, 119 micrograms/m3; maximum, 478 micrograms/m3). The average number of daily hospital outpatient visits was 1,386; approximately 8.5% of these visits were to the surgery department, 7.9% were to the pediatrics department, and 20.6% were to the internal medicine department. A large increase in nonsurgery outpatient visits was observed in association with increases in both SO2 and TSP in linear regression models, after adjusting for temperature, humidity, season, and day of the week. The estimated effects (in which the most polluted days were compared with the least polluted days) on nonsurgery outpatient visits were increases of 20% (SE = 5%) and 17% (SE = 4%) in association with increases in SO2 and TSP, respectively. In a department-specific analysis, the association was found to be 1.5- to 2.0-fold stronger for pediatrics and internal medicine visits than for other types of visits. The separate associations of SO2 and TSP with internal medicine visits remained statistically significant when both SO2 and TSP were considered simultaneously and when adjustment was made for surgery visits. SO2 and TSP were found to be significant, independent predictors of internal medicine visits in both winter and summer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Selective fluorescence of zymogen granules of pancreatic acinar cells stained with hematoxylin and eosin.

Following staining with hematoxylin and eosin Y, paraffin sections of mouse pancreas were examined by transmitted light, epifluorescence and confocal laser scanning microscopy. Light microscopy revealed that the nuclei of pancreatic acinar cells were located basally, while the apices of the cells appeared eosinophilic, although the secretory granules were difficult to visualize. Under violet-blue light excitation, the zymogen granules at the apices of the acinar cells showed strong yellowish fluorescence; the other part of the cytoplasm was only faintly fluorescent and the nuclei and the supporting tissues were nonfluorescent. Confocal laser scanning microscopy resulted in clear pictures of the zymogen granules and their distribution within the cell. The fluorescent emission of zymogen granules was certainly the result of eosin Y staining, because hematoxylin is not a fluorochrome and the zymogen granules are not autofluorescent. Staining with eosin Y alone, however, did not result in clear fluorescent images of zymogen granules or any other cellular structures. Our observation shows that the fluorescence emission of eosin Y allows easy and precise recognition of zymogen granules of pancreatic cells.

Animals↗

Seasonal home range changes of the Sichuan snub-nosed monkey (Rhinopithecus roxellana) in the Qinling Mountains of China.

The seasonal changes in home range and habitat use of the Sichuan snub-nosed monkey, Rhinopithecus roxellana, have been studied by radio tracking and direct observation in the Qinling Mountains of China. The home range size was 14.1 km(2) in spring, 9.5 km(2) in summer, 12.1 km(2) in autumn and 12.3 km(2) in winter; the total area used was 22.5 km(2). The area of the home range is closely correlated with the distribution and abundance of food resources. Seasonal change in the home range area is correlated with the phenology of the vegetation. An unusually large home range is a unique characteristic of this monkey.

Animals↗

Effect of pneumatic suction ring placement on intraocular pressure in cats.

PURPOSE: To determine the effect of placing a pneumatic suction ring on intraocular pressure (IOP) in the cat and to design an improved method to generate a stable elevation of IOP. METHODS: A pneumatic suction ring was applied to the eye in cats while the IOP was monitored. Three groups of animals (10 per group) were used. A vacuum pressure of 450 mbar was applied in one step to eyes of group 1 (anesthetized) and to group 2 (euthanized) cats. In group 3 (anesthetized) cats, an initial vacuum pressure of 250 mbar was applied, followed by a vacuum of slowly increasing pressure at a rate of 5 mbar/min for a total of 40 min to 450 mbar. RESULTS: After the one-step application of a vacuum (450 mbar) to the eyes of anesthetized cats (group 1), IOP peaked within the first minute from a basal value of 25 +/- 2 mm Hg (mean +/- SD) to 90 +/- 7 mm Hg. It then rapidly decreased to 69 +/- 2 mm Hg 5 min later and continued to decrease to 39 +/- 4 mm Hg 40 min later. This sharp peak and decline of IOP were also observed in eyes of euthanized cats (group 2). The basal IOP of these eyes was 8 +/- 1 mm Hg. It rose to 18 +/- 2 mm Hg immediately after the application of vacuum pressure (450 mbar) and returned to the basal level 5 min later. In contrast, the eyes of group 3 receiving an initial vacuum of 250 mbar followed by a 5 mbar/min vacuum increment exhibited a rapid increase in IOP and a very stable plateau (mean IOP = 62-68 mm Hg), lasting the whole study period (40 min). CONCLUSION: IOP after a one-step application of a vacuum via a pneumatic suction ring is self-adjusting and declines rapidly over time. This decline in IOP can be overcome by a supplementary increment in vacuum pressure.

Animals↗

Dielectric properties of human glioma and surrounding tissue.

Dielectric properties of human glioma and surrounding tissue from five patients were measured. Experiments were performed at frequencies of 5-500 MHz at 24 +/- 0.5 degrees C using a Network Analyser and a coaxial line capacitive sensor. The permittivity and conductivity of tumours were 30% higher than that of the surrounding tissues due to their higher water content. The characteristic of less differentiation in tumours clearly was reflected in the dielectric properties, namely a smaller parameter for the relaxation time distribution of the tumour's dielectric relaxation. With the dielectric data, the power absorption ratios of tumour to surrounding tissue were calculated for four representative electromagnetic (EM) irradiation cases. The calculation shows that power absorption ratios are strongly dependent on the incident direction of the EM wave and optimum frequency. To improve therapeutic efficiency, it is appropriate to have the electric field vector (E) parallel to the interface of tumour/surrounding tissue at optimum frequencies around 100 MHz, and the case of E perpendicular to the interface must be avoided in applications of EM hyperthermia for brain tumours.

Adult↗

A pilot study of intracavitary hyperthermia combined with radiation in the treatment of oesophageal carcinoma.

Twenty-five patients with primary squamous cell carcinoma of the oesophagus were treated with intracavitary hyperthermia combined with external beam radiation and intraluminal radiation at Nanjing Jinling Hospital, China. External beam radiation was given with a 6-MV X-ray; 1.8-2.0 Gy per fraction and five fractions per week; this brought the total dose to 60 Gy. Two weeks later, hyperthermia was applied with 915 MHz microwave intracavitary applicators, which were designed at the City of Hope. Temperature measurements were obtained while moving fibreoptic temperature sensors at 1.0 cm intervals in each of the six peripheral channels of the applicator. Hyperthermia was applied for 1 h before and after the intraluminal radiation. Intraluminal radiation was provided by low dose-rate iridium-192 ribbons in the same intracavitary applicator, giving 30 Gy at 0.75 cm from the applicator surface. The 3-month post-treatment responses showing complete response, partial response, no change and progressive disease were 60% (15/25), 24% (6/25), 8% (2/25) and 8% (2/25) respectively. The median follow-up time was 17 months (range 4-29 months). The 1- and 2-year overall survival rates were 72% (18/25) and 32% (8/25) respectively, and disease-free survival rates were 47 and 30% respectively. The median overall survival and disease-free survival periods were 17 and 10 months respectively. Fourteen patients had local recurrence (either at the primary site or in the lymph node) or had local progression, and five developed metastases. The median duration of the onset of local recurrence or of local progression was 9.5 months (range 0-20 months); the median of distant metastases was 8 months (range 2-16 months). Seventeen patients died. Of these, 15 died of cancer: six with local recurrence alone, four with local progression primary cancer alone, three with distant metastases alone, and two with both local and distant failure. Two patients with complete response of the primary disease died of other diseases. The toxicity was mild. According to the mucous reaction scoring criteria of the Radiation Therapy Oncology Group, the acute toxicity grades I, II, III and IV were 0% (0/25), 20% (5/25), 48% (12/25) and 32% (8/25) respectively. The major late complication was a mild oesophagus fibrosis and difficult swallowing. No serious side effects (grade IV), fistulas or perforations were seen. These results indicate that this method is safe and feasible for treating oesophageal carcinoma.

Combined Modality Therapy↗

An empirical model of hyperopic shift with corticosteroid modulation and refractive power prediction after photorefractive keratectomy.

Data from a selected sample of 158 patients who received excimer laser photorefractive keratectomy (PRK) in our center and obtained a desirable refractive outcome at 6-months were analyzed retrospectively to establish an empirical model of refractive power after PRK. This model, generated by a computer-assisted regression program, is presented as a multivariate non-linear quadratic equation. Since the coefficients of each variable (attempted correction and postoperative days) are statistically significant, the estimated influence of the variables on the postoperative refraction from this regression model is reliable and consistent. Therefore, this model has been used to direct the use of corticosteroids for modulating post-PRK refraction. The predictability of this model has also been corroborated by separate data from 1-year follow up of PRK recipients. The recipients whose refraction at 6 months agree with the calculation from this model have obtained an excellent outcome; while those whose refractive outcome deviates from this model have gotten undesirable results.

Computer Simulation↗