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Biomedical subjects

S Han

Publications and source records attributed to S Han.

At least 235 records · Page 13Linked to original sources

No-react detoxification process: a superior anticalcification method for bioprostheses.

BACKGROUND: Glutaraldehyde pretreatment of bioprosthetic heart valves is the major pathogenic factor in their calcific degeneration. This comparative study investigates the merit of the No-React aldehyde detoxification process as an alternative modifier of xenograft tissues. METHODS: Glutaraldehyde- and No-React-pretreated porcine aortic valve cusps were implanted subcutaneously in 6-week-old rats (n = 20). At 3, 6, and 14 weeks, randomly selected animals were sacrificed and the explants underwent mineral and morphologic analyses. Glutaraldehyde- and No-React-treated bovine pericardium and porcine aortic valve cusp were incubated in fibroblast cell culture plates. Cell viability was observed under reversed microscope at 6, 24, 48, and 96 hours. Erythrosin B dye exclusion test was used to validate percent cell death. RESULTS: Pretreatment with No-React significantly inhibited calcification of aortic cusp subcutaneous implants throughout the 14-week period (mean tissue Ca2+ content = 1.3 +/- 0.7 micrograms/mg at 14 weeks.) Glutaraldehyde-treated cusps underwent protracted calcification (Ca2+ content = 190.6 +/- 89.5 micrograms/mg; p < 0.01). Morphologic findings correlated with mineral analyses. One-hundred percent of fibroblast cells survived in the presence of No-React-treated tissue, with a growth pattern indistinguishable from control cell culture (ie, in the presence of no tissue). The cells incubated with glutaraldehyde-treated tissue showed signs of nonviability by 6 hours, with 100% cell death by 48 hours. Dye exclusion tests validated these findings. CONCLUSIONS: The No-React detoxification process completely abolishes the cytotoxicity of the xenograft tissue and inhibits calcific degeneration.

Animals↗

Weight loss alters organ concentrations and contents of lead and some essential divalent metals in rats previously exposed to lead.

The loss of adipose tissue during energy restriction may be accompanied by a loss of lean body mass, including bone mass. Because most of the body lead burden is in the skeleton, we studied the effects of weight loss on the concentrations of lead in bone, blood and several organs in rats with prior but not current lead exposure. Concentrations of the essential divalent metals calcium, copper, iron, magnesium and zinc were also determined for comparison with lead. Lead-exposed rats (n = 25) were randomly assigned to one of three treatment groups: weight maintenance (WM), moderate weight loss (MWL) or substantial weight loss (SWL). For the two last-named groups, food intake was restricted for 4 wk to 70 and 40% of that of the WM group. Lead concentrations did not differ significantly (ANOVA, P > 0.05) among the three groups for blood, brain and bone. Significantly higher liver lead concentrations were observed in the SWL rats than in the WM and MWL groups. In general, organ concentrations of calcium, copper, magnesium and zinc were either lower or did not differ in the groups losing weight compared with the WM group. In contrast, organ Iron concentrations of the SWL group were higher than those of the other groups except in brain where there were no significant differences. The total liver content of lead was highest in the SWL group, but the lead content of other organs did not differ among the treatment groups. The contents of calcium, copper, magnesium and zinc generally were lower in the MWL and SWL groups than in the WM group in the liver and some of the other organs. The results demonstrate that weight loss can increase the quantity and concentration of lead in the liver, even in the absence of continued lead exposure. The data also demonstrate considerable differences among organ divalent metals in response to weight loss.

Analysis of Variance↗

Classification of cardiac arrhythmias using fuzzy ARTMAP.

We have investigated the QRS complex, extracted from electrocardiogram (ECG) data, using fuzzy adaptive resonance theory mapping (ARTMAP) to classify cardiac arrhythmias. Two different conditions have been analyzed: normal and abnormal premature ventricular contraction (PVC). Based on MIT/BIH database annotations, cardiac beats for normal and abnormal QRS complexes were extracted from this database, scaled, and Hamming windowed, after bandpass filtering, to yield a sequence of 100 samples for each ORS segment. From each of these sequences, two linear predictive coding (LPC) coefficients were generated using Burg's maximum entropy method. The two LPC coefficients, along with the mean-square value of the QRS complex segment, were utilized as features for each condition to train and test a fuzzy ARTMAP neural network for classification of normal and abnormal PVC conditions. The test results show that the fuzzy ARTMAP neural network can classify cardiac arrhythmias with greater than 99% specificity and 97% sensitivity.

Algorithms↗

The effect of ultrasonically determined anisotropy on longitudinal fracture of cortical bone.

This study examines the effects of density and microstructural anisotropy on longitudinal crack propagation in compact bone. Bovine cortical bone samples were demineralized by acid, producing specimens with a wide range of bone density. Ultrasound velocity was measured in the radial and longitudinal directions of each specimen using a pulse transmission technique. A proposed microstructural anisotropy parameter based on these ultrasound velocities was introduced and evaluated. The critical stress intensity factors K(IC) of these specimens were determined by mechanical fracture toughness tests. A linear regression study demonstrated that assessment of fracture toughness was precisely achieved by the combined effect of density and microstructural anisotropy of compact bone (r2 = 0.951, p < 0.0001).

Animals↗

Processing of global and local properties--an analysis with event-related brain potentials.

The different processing of global and local properties of compound visual stimuli was studied with event-related brain potentials (ERPs) in the present experiment. It was found that, compared with the identification of global properties, the discrimination of local properties elicited longer RTs, lower accuracies, increased amplitudes of PI, decreased amplitudes of N1, and longer latencies of N2 and P3. The conflict of global and local properties increased the amplitudes of P2, decreased the amplitudes of P3, and prolonged latencies of N2 and P3. These results indicated that the advantage of global processing occurs at an early perceptual stage, and the attentional mechanisms for global and local processing may be different.

Adolescent↗

[The establishment of a three dimensional PCR screening system and quality evaluation of human YAC library].

In order to screen out YAC clones in the CEPH YAC library related to a definite gene, DNA fragment or locus, we need to establish a screening system. This paper includes the establishment of this system and the evaluation of its feasibility. According to the experiments, we suggest that it is better to screen the Mega YAC part of the library at first and put five culture plates as a group. Meanwhile, FISH experiments to assess the quality of CEPH YAC library and the first generation physical map of human genome, Were conducted FISH experiments on 26 YAC clones were carried out. There were 13 clones that were chimeric (about 50%), 6 clones that were mapped by mistake (about 23%). So, there were only 9 clones that were mapped correctly and were not chimeric (about 35%).

Chromosomes, Artificial, Yeast↗

[The laboratory study on biofragmentable anastomosis rings (BAR) in gastrointestinal tract reconstruction].

To study and investigate the feasibility of biofragmentable anastomosis ring (BAR) for gastrointestinal (GI) tract reconstruction, we performed gastroenterostomy in 34 dogs. BAR anastomoses were performed with proper outer diameter and gape size in small bowel in 8 cases, in large bowel in 11 cases, in esophagus in 12 cases, in esophago-intestinal in 2 cases, in gastrojejunum in 1 cases. The postoperative serial X-ray examinations showed that BAR maintained good integration two weeks postoperation. The ring disintegrated into several small fragments that passed out of the body in feces from the 14th postoperative day after surgery. All of the dogs were killed on the 28th operative day and autopsied. The anastomosis site had smooth serosa and scar membrane in gross and were substituted by regenerative fibrous tissue. The specimen barim-air double contrast X-ray revealed that GI tract was coherent without leakage and stenosis. Therefor, the authors recognized that BAR can be recommended as a safe technique in GI operation.

Anastomosis, Surgical↗

In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. IV. Affinity-dependent, antigen-driven B cell apoptosis in germinal centers as a mechanism for maintaining self-tolerance.

Germinal centers (GCs) are the sites of antigen-driven V(D)J gene hypermutation and selection necessary for the generation of high affinity memory B lymphocytes. Despite the antigen dependence of this reaction, injection of soluble antigen during an established primary immune response induces massive apoptotic death in GC B cells, but not in clonally related populations of nonfollicular B lymphoblasts and plasmacytes. Cell death in GCs occurs predominantly among light zone centrocytes, is antigen specific, and peaks within 4-8 h after injection. Antigen-induced programmed death does not involve cellular interactions mediated by CD40 ligand (CD40L) or Fas; disruption of GCs by antibody specific for CD40L was not driven by apoptosis and C57BL/6.lpr mice, though unable to express the Fas death trigger, remained fully susceptible to soluble antigen. Single injections of antigen did not significantly decrease GC numbers or average size, but repeated injections during an 18-h period resulted in fewer and substantially smaller GCs. As cell loss appeared most extensive in the light zone, decreased GC cellularity after prolonged exposure to soluble antigen implies that the Ig- centroblasts of the dark zone may require replenishment from light zone cells that have survived antigenic selection. GC cell death is avidity-dependent; oligovalent antigen induced relatively little apoptosis and GC B cells that survived long exposures to multivalent antigen expressed atypical VDJ rearrangements unlikely to encode high affinity antibody. Antigen-induced apoptotic death in GCs may represent a mechanism for the peripheral deletion of autoreactive B cell mutants much as the combinatorial repertoire of immature B lymphocytes is censored in the bone marrow.

Amino Acid Sequence↗

Crystal structure of the biphenyl-cleaving extradiol dioxygenase from a PCB-degrading pseudomonad.

Polychlorinated biphenyls (PCBs) typify a class of stable aromatic pollutants that are targeted by bioremediation strategies. In the aerobic degradation of biphenyl by bacteria, the key step of ring cleavage is catalyzed by an Fe(II)-dependent extradiol dioxygenase. The crystal structure of 2,3-dihydroxybiphenyl 1,2-dioxygenase from a PCB-degrading strain of Pseudomonas cepacia has been determined at 1.9 angstrom resolution. The monomer comprises amino- and carboxyl-terminal domains. Structural homology between and within the domains reveals evolutionary relationships within the extradiol dioxygenase family. The iron atom has five ligands in square pyramidal geometry: one glutamate and two histidine side chains, and two water molecules.

Amino Acid Sequence↗

Cellular interaction in germinal centers. Roles of CD40 ligand and B7-2 in established germinal centers.

Costimulatory interactions between T and B lymphocytes are crucial for T cell activation and B cell proliferation and differentiation. We have compared the roles of CD40L and B7-2 in the initiation and maturation of humoral immunity by administering anti-CD40 ligand (L) or anti-B7-2 Ab during the early (days -1 to 3) or late (days 6-10) phases of primary responses to thymus-dependent (Td) and -independent (Ti) Ags. Germinal center (GC) formation in response to a Td Ag was inhibited completely by the early administration of anti-CD40L or anti-B7-2 Abs. Later in the response, established GCs remained sensitive to anti-CD40L but were resistant to treatment with anti-B7-2. However, Ig hypermutation was reduced dramatically in GCs of anti-B7-2-treated mice and humoral memory was impaired. Early administration of anti-CD40L reduced serum Ab levels to approximately 10% of controls, whereas early treatment with anti-B7-2 reduced Ab production by only 50%. Later treatments with either Ab had no effect on Ab production. Response to a type II Ti Ag was more resistant than Td responses to interruption of costimulatory interactions. Our findings suggest that the costimulatory roles of CD40:CD40L and B7-2:CD28/CTLA-4 differ in the GC; administration of anti-CD40L abrogates an established GC reaction, whereas Ab to B7-2 suppresses Ig hypermutation and entry into the B cell memory compartment. Once B cells have entered the differentiation pathway to Ab production, neither CD40L nor B7-2 is necessary for their continued differentiation and persistence.

Animals↗

In vivo and in vitro replication consequences of stereoisomeric benzo[a]pyrene-7,8-dihydrodiol 9,10-epoxide adducts on adenine N6 at the second position of N-ras codon 61.

Benzo[a]pyrene-7,8-dihydrodiol 9,10-epoxide (BPDE), a metabolite of the widespread environmental pollutant benzo[a]pyrene, is a mutagenic in both bacterial and mammalian systems. Toward understanding the mutagenic effects of different stereoisomers of BPDE at specific sites in DNA, six stereochemically defined BPDE adducts were constructed on adenine N6 at position 2 of the human N-ras 61 codon within an 11-base oligonucleotide fragment. Both the nonadducted and BPDE-adducted N-ras 61 11-mers were inserted into a unique EcoRI site in single-stranded M13mp7L2 DNA and utilized for in vivo studies. The ligation efficiencies of BPDE-adducted 11-mers into the single-stranded vector were determined by Southern hybridization and confirmed by electron microscopy. Repair-deficient AB2480 E. coli cells were transformed with adducted and non-adducted DNA samples. The resultant plaque-forming abilities were used to evaluate the replication competence of the various BPDE adducts with respect to the nonadducted 11-mer. Point mutations due to aberrant replication at the adducted site were identified by the technique of differential DNA hybridization. All of the six BPDE adducts examined were mutagenic in vivo, generating exclusively A-->G mutations at frequencies ranging from 0.26 to 1.20%. In vitro replication studies using these BPDE-adducted 11-mers involved primer extension assays with Klenow fragment. All of the BPDE-modified templates demonstrated distinct blockage at the adducted site and/or 1 base 3' to the adducted site, allowing essentially no translesion synthesis to form fully extended polymerization products in vitro.

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

Retinoid absorption from simple and mixed micelles in the rat intestine.

The absorption of three retinoid analogs etretinate (ET), acitretin (ETA), and motretinid (MOE) from two distinct micellar systems was studied in the rat intestine. Each of the three drugs was loaded into simple micelles consisting of 10 mM sodium taurocholate (NaTC) and mixed micelles consisting of 10 mM egg phosphatidylcholine (PC) and 10 mM NaTC. Following perfusion through the jejunum segments, both the fraction of drug disappearing from the segment and the permeability of the drug from the lumen into the gut wall (Peff) was greater with the mixed micelles as compared to the simple micelles. Perfusion flow rate had an influence on the Peff for ET and ETA. Similar trends as for the jejunum were seen in the ileum perfusions. The simultaneous uptake of PC and NaTC during the retinoid perfusions was monitored. There appeared to be a correlation between the Peff values for PC and that of the retinoids. The viability of the in-situ perfusion system was confirmed histologically. There is evidence to indicate that the permeability of the intestine is sensitive to subtle differences in the chemical structure of the retinoids.

Animals↗

The genotoxicity of substituted nitrobenzenes and the quantitative structure-activity relationship studies.

The genotoxicity of 22 substituted nitrobenzenes was evaluated by the chromosome aberrations test in cultured human peripheral lymphocytes. 18 of 22 compounds exhibit genotoxic activities. A quantitative structure-activity relationship model was established to correlate the genotoxicity of substituted nitrobenzenes and the characteristics of the substituents on the benzene ring.

Cell Count↗

Dietary calcium and lead interact to modify maternal blood pressure, erythropoiesis, and fetal and neonatal growth in rats during pregnancy and lactation.

We studied the effects of dietary calcium and lead exposure on lead toxicity, fetal and neonatal growth, erythropoiesis and blood pressure during pregnancy and lactation in rats. Pregnant Sprague-Dawley rats (n = 43) were randomly assigned to one of six treatment groups of 7-8 rats each. Half of the rats were fed diets of low (0.1%), normal (0.5%) or high (2.5%) calcium as calcium carbonate and exposed to 250 mg/L of lead in their drinking water for the duration of the pregnancy and for 1 wk of lactation. Three control groups were fed the same diets without lead exposure. Pups were studied at 1 d and 1 wk of age. Maternal and fetal blood and organ samples from the groups fed the low calcium diet had the highest lead concentrations, whereas the lowest lead concentrations were found in the groups fed the high calcium diet. Dam and pup hemoglobin concentrations, hematocrits, and body weights and lengths were reduced by lead exposure and by the high calcium diet. The latter also reduced organ iron concentrations and prevented lead-induced increases in free erythrocyte protoporphyrin. Dam systolic blood pressures during the third trimester of gestation were significantly higher in rats exposed to lead and fed the low calcium diet than in rats in the other five treatment groups. The results demonstrate that dietary calcium and lead exposure interact in rats to influence maternal blood pressure, erythropoiesis, and fetal and neonatal growth during pregnancy and lactation.

Animals↗

Sensitivity of a mixed field dosimetry algorithm to uncertainties in thermoluminescent element readings.

An error analysis of the effects of the algorithms used to resolve the deep and shallow dose components for mixed fields from multi-element thermoluminescent (TLD) badge systems was undertaken for a commonly used system. Errors were introduced independently into each of the four element readings for a badge, and the effects on the calculated dose equivalents were observed. A normal random number generator was then utilized to introduce simultaneous variations in the element readings for different uncertainties. The Department of Energy Laboratory Accreditation Program radiation fields were investigated. Problems arising from the discontinuous nature of the algorithm were encountered for a number of radiation sources for which the algorithm misidentified the radiation field. Mixed fields of low energy photons and betas were found to present particular difficulties for the algorithm. The study demonstrates the importance of small fluctuations in the TLD element's response in a multi-element approach.

Algorithms↗